FN Thomson Reuters Web of Science™ VR 1.0 PT J AU James, CA Winkelstein, JA Holtzman, NA Hadley, DW AF James, CA Winkelstein, JA Holtzman, NA Hadley, DW TI How does the mode of inheritance of a genetic condition influence families? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 14 BP 164 EP 164 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700015 ER PT J AU Chan, K Puck, JM AF Chan, K Puck, JM TI Developing population based newborn screening for severe combined immunodeficiency. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Genet & Mol Branch, NIH, Bethesda, MD USA. Yale Epi & Pub Hlth, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 28 BP 167 EP 167 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700030 ER PT J AU Friderici, KH Zhu, M Yang, T Wei, S DeWan, AT Belyantseva, I Morell, RJ Elfenbein, JL Fisher, RA Leal, SM Smith, RJH AF Friderici, KH Zhu, M Yang, T Wei, S DeWan, AT Belyantseva, I Morell, RJ Elfenbein, JL Fisher, RA Leal, SM Smith, RJH TI Mutations in the gamma actin gene (ACTG1) cause dominant progressive deafness (DFNA20/26). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Michigan State Univ, Dept Micro & Mol Gen Peds & Hum Dev Audio Speech, E Lansing, MI 48824 USA. Univ Iowa, Dept Otol, Iowa City, IA USA. Baylor Coll Med, Dept Mol & Hum Gen, Houston, TX USA. NIDCD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 43 BP 170 EP 170 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700043 ER PT J AU Wooding, S Kim, UK Larsen, J Bamshad, MJ Jorde, LB Drayna, D AF Wooding, S Kim, UK Larsen, J Bamshad, MJ Jorde, LB Drayna, D TI Natural selection and molecular evolution in PTC, a bitter taste receptor. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Utah, Salt Lake City, UT USA. NIDCD, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 44 BP 170 EP 170 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700045 ER PT J AU Shianna, KV Hullinger, H Strand, MK Marchuk, DA AF Shianna, KV Hullinger, H Strand, MK Marchuk, DA TI Functional analysis of yeast and human NADH kinase in Saccharomyces cerevisiae: implications for mitochondrial genome stability and neurodegenerative disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA. NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 90 BP 179 EP 179 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700091 ER PT J AU Holmans, P Myers, A Hardy, J Goate, A Williams, J Owen, M AF Holmans, P Myers, A Hardy, J Goate, A Williams, J Owen, M TI Evidence of interaction between susceptibility loci on chromosomes 1, 10 and 12 in late-onset Alzheimers disease (LOAD). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Washington Univ, Sch Med, St Louis, MO USA. Univ Wales Coll Cardiff, Coll Med, Cardiff CF1 3NS, S Glam, Wales. MRC, Biostat Unit, Inst Publ Hlth, Cambridge CB2 2BW, England. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RI Myers, Amanda/B-1796-2010; Holmans, Peter/F-4518-2015 OI Myers, Amanda/0000-0002-3100-9396; Holmans, Peter/0000-0003-0870-9412 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 112 BP 184 EP 184 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700114 ER PT J AU Singleton, A Farrer, M Johnson, J Singleton, A Hague, S Kachergus, J Hulihan, M Peuralinna, T Dutra, A Lincoln, S Crawley, A Hanson, M Cookson, M Muenter, M Baptista, M Miller, D Blancato, J Hardy, J Gwinn-Hardy, K AF Singleton, A Farrer, M Johnson, J Singleton, A Hague, S Kachergus, J Hulihan, M Peuralinna, T Dutra, A Lincoln, S Crawley, A Hanson, M Cookson, M Muenter, M Baptista, M Miller, D Blancato, J Hardy, J Gwinn-Hardy, K TI Triplication of the normal alpha synuclein gene is a cause of hereditary Parkinson's disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA. Mayo Clin, Dept Neurosci, Genet Neurodegenerat Lab, Jacksonville, FL USA. NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. NHGRI, Cytogenet & Confocal Microscopy Core, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, Cell Biol & Gene Express Sect, Bethesda, MD 20892 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. RI Johnson, Janel/A-7136-2010; Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 113 BP 184 EP 184 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700113 ER PT J AU Scott, LJ Sparks, AB Mohlke, KL Hinds, DA Li, M Ballinger, DG Chines, PS Tuomilehto, J Bergman, RN Frazer, KA Watanabe, RM Collins, FS Cox, DR Boehnke, M AF Scott, LJ Sparks, AB Mohlke, KL Hinds, DA Li, M Ballinger, DG Chines, PS Tuomilehto, J Bergman, RN Frazer, KA Watanabe, RM Collins, FS Cox, DR Boehnke, M TI Pool-based association scan for type 2 diabetes using 49,419 SNPs in a 92.2 Mb region on chromosome 6. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Michigan, Ann Arbor, MI 48109 USA. Perlegen Sci, Mt View, CA USA. NHGRI, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 121 BP 186 EP 186 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700122 ER PT J AU Pollin, TI Agarwala, R Schaffer, AA Shuldiner, AR Mitchell, BD O'Connell, JR AF Pollin, TI Agarwala, R Schaffer, AA Shuldiner, AR Mitchell, BD O'Connell, JR TI Investigations of male founder structure and the Y chromosome in the Old Order Amish. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Maryland, Baltimore, MD 21201 USA. NIH, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD USA. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 128 BP 187 EP 187 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700130 ER PT J AU Atwood, LD Heard-Costa, NL Cupples, LA Fox, CS Jaquish, CE Willson, PWF D'Agostino, RB AF Atwood, LD Heard-Costa, NL Cupples, LA Fox, CS Jaquish, CE Willson, PWF D'Agostino, RB TI Sex and age dependent effects of chromosomal regions linked to body mass index across 28 years of the Framingham Heart Study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 166 BP 195 EP 195 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700169 ER PT J AU McCallion, AS Portnoy, ME Grice, E Cashuk, C Emison, E Green, ED Chakravarti, A AF McCallion, AS Portnoy, ME Grice, E Cashuk, C Emison, E Green, ED Chakravarti, A TI A common mutation in the RET gene in all forms of Hirschsprung disease (HSCR). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Gen Med, Baltimore, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 168 BP 195 EP 195 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700170 ER PT J AU Correa-Cerro, LS Wassif, CA Kratz, L Kelly, RI Porter, FD AF Correa-Cerro, LS Wassif, CA Kratz, L Kelly, RI Porter, FD TI Development, characterization, and treatment of a hypomorphic SLOS mouse model. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, NIH, Bethesda, MD USA. Kennedy Krieger Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 190 BP 199 EP 199 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700191 ER PT J AU Tessitore, A Martin, MD Mann, L Ingrassia, A Sano, R Proia, R Ma, Y Hendershot, LM d'Azzo, A AF Tessitore, A Martin, MD Mann, L Ingrassia, A Sano, R Proia, R Ma, Y Hendershot, LM d'Azzo, A TI G(M1)-gangliosidemediated ER stress response causes neuronal death in G(M1)-gangliosidosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 186 BP 199 EP 199 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700189 ER PT J AU Huizing, M Dorward, H Helip-Wooley, A Gahl, WA AF Huizing, M Dorward, H Helip-Wooley, A Gahl, WA TI Understanding Hermansky-Pudlak syndrome by visualizing intracellular trafficking patterns. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 191 BP 200 EP 200 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700192 ER PT J AU Kirschner, L Grinberg, A Westphal, H Stratakis, CA AF Kirschner, L Grinberg, A Westphal, H Stratakis, CA TI Deletion of the Carney Complex Gene PRKAR1A leads to immortalization of primary mouse embryonic fibroblast cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Ohio State Univ, Dept Human Canc Genet, Columbus, OH 43210 USA. NICHD, LMGD, NIH, Bethesda, MD USA. NICHD, SGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 200 BP 201 EP 201 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700201 ER PT J AU Griffin, KJ Kirschner, L Stergiopoulos, S Lenherr, S Claflin, E Matyakhina, L Bauer, A Carney, JA Stratakis, CA AF Griffin, KJ Kirschner, L Stergiopoulos, S Lenherr, S Claflin, E Matyakhina, L Bauer, A Carney, JA Stratakis, CA TI A transgenic mouse model for studies of cyclic-AMP-dependent PKA function. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, SEGEN, DEB, NIH, Bethesda, MD USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. WRAMC, Washington, DC USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 201 BP 202 EP 202 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700202 ER PT J AU Li, W Zhang, Q Oiso, N Novak, EK Gautum, R O'Brien, EP Tinsley, CL Blake, DJ Spritz, RA Copeland, NG Jenkins, NA Amato, D Roe, BA Starcevic, M Dell'Angelica, EC Elliott, RW Mishra, V Kingsmore, SF Paylor, R Swank, RT AF Li, W Zhang, Q Oiso, N Novak, EK Gautum, R O'Brien, EP Tinsley, CL Blake, DJ Spritz, RA Copeland, NG Jenkins, NA Amato, D Roe, BA Starcevic, M Dell'Angelica, EC Elliott, RW Mishra, V Kingsmore, SF Paylor, R Swank, RT TI Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutations in dysbindin a new member of the biogenesis of lysosome-related organelles complex 1 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Roswell Pk Canc Inst, Dept Cell & Mol Biol, Buffalo, NY 14263 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Oxford, Oxford OX1 2JD, England. NCI, Frederick, MD 21701 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Oklahoma, Norman, OK 73019 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Florida, Gainesville, FL 32611 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 219 BP 205 EP 205 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700218 ER PT J AU Scacheri, PC Rozenblatt-Rosen, O Caplen, N Wolfsberg, T Meyerson, M Collins, FS AF Scacheri, PC Rozenblatt-Rosen, O Caplen, N Wolfsberg, T Meyerson, M Collins, FS TI WARNING: siRNAs can induce off-target effects in mammalian cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 230 BP 207 EP 207 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700231 ER PT J AU Crawford, G Holt, I Tai, D Green, E Wolfsberg, T Collins, F AF Crawford, G Holt, I Tai, D Green, E Wolfsberg, T Collins, F TI Generation of a genome-wide library of regulatory sequences through the use of a novel DNAse hypersensitive site cloning procedure SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Gaithersburg, MD USA. NIH, Intramural Sequencing Ctr, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 232 BP 208 EP 208 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700234 ER PT J AU Mohlke, KL Silander, K Peck, EC Scott, LJ Hollstein, PE Skol, AD Li, C Chinas, PS Valle, TT Bergman, RN Tuomilehto, J Watanabe, RM Boehnke, M Collins, FS AF Mohlke, KL Silander, K Peck, EC Scott, LJ Hollstein, PE Skol, AD Li, C Chinas, PS Valle, TT Bergman, RN Tuomilehto, J Watanabe, RM Boehnke, M Collins, FS TI Common non-coding SNPs near the Hepatocyte Nuclear Factor-4 Alpha gene are associated with type 2 diabetes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Michigan, Ann Arbor, MI 48109 USA. NHGRI, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. Univ So Calif, Los Angeles, CA 90089 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 241 BP 210 EP 210 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700242 ER PT J AU Edison, R Muenke, M AF Edison, R Muenke, M TI Congenital anomalies following gestational statin exposure. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIH, Med Genet Branch, DHHS, NHGRI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 251 BP 212 EP 212 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700252 ER PT J AU McDonald-McGinn, DM DeBerardinis, R Bartlett, S Whitaker, L Jacobs, I Gripp, K Stolle, C Wilkie, AOM Muenke, M Zackai, EH AF McDonald-McGinn, DM DeBerardinis, R Bartlett, S Whitaker, L Jacobs, I Gripp, K Stolle, C Wilkie, AOM Muenke, M Zackai, EH TI Molecular characterization of Pfeiffer syndrome: Implications for prognosis and genetic counseling. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Penn, Sch Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Alfred I Dupont Inst, Wilmington, DE 19899 USA. Weatherall Inst Mol Med, Oxford, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 253 BP 212 EP 212 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700253 ER PT J AU Schulze, TG Zhang, K Chen, YS Akula, N Sun, F McMahon, FJ AF Schulze, TG Zhang, K Chen, YS Akula, N Sun, F McMahon, FJ TI Defining haplotype blocks in the human genome: The impact of methods, parameters and allele frequencies. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ So Calif, Dept Biol Sci & Math, Los Angeles, CA USA. RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 268 BP 215 EP 215 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700270 ER PT J AU Zhao, H Pfeiffer, R Gail, M AF Zhao, H Pfeiffer, R Gail, M TI How useful are the tagging SNPs for identifying complex disease genes? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Yale Univ, Sch Med, New Haven, CT USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 273 BP 216 EP 216 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700273 ER PT J AU Kim, G Park, S Park, S Kim, C AF Kim, G Park, S Park, S Kim, C TI Genomic imbalances in Schwann cells of neuroblastic tumors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 53rd Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CA SP Amer Soc Human Genet C1 Wayne State Univ, Hutzel Hosp, NICHHD, Dept Obster & Gynecol,Perinatol Res Branch, Detroit, MI 48202 USA. Ewha Womans Univ, Coll Med, Dept Anat, Seoul, South Korea. Korea Univ, Coll Med, Inst Human Genet, Seoul 136701, South Korea. Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 SU S MA 286 BP 219 EP 219 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700289 ER PT J AU Kang, Y Kim, G Uhm, K Cho, S Park, S AF Kang, Y Kim, G Uhm, K Cho, S Park, S TI Induction and expression of cyclin D3 in Korean hepatocellular carcinoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Korea Univ, Coll Med, Inst Human Genet, Dept Anat, Seoul 136701, South Korea. Wayne State Univ, Hutzel Hosp, NICHHD, Dept Obster & Gynecol,Perinatol Res Branch, Detroit, MI 48202 USA. Hallym Univ, Coll Med, Dept Pathol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 305 BP 222 EP 222 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700305 ER PT J AU Kirsch, I Roschke, A Tonon, G Gehlhaus, K Mctyre, N Bussey, K Lababidi, S Scudiero, D Weinstein, J AF Kirsch, I Roschke, A Tonon, G Gehlhaus, K Mctyre, N Bussey, K Lababidi, S Scudiero, D Weinstein, J TI Karotypic complexity of the "NCI-60" drug-screening panel. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Natl Canc Inst, Genet Branch, Bethesda, MD USA. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 303 BP 222 EP 222 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700304 ER PT J AU Matyakhina, LD McWhinney, S Bei, TA Stergiopoulos, S Carney, JA Eng, C Stratakis, CA AF Matyakhina, LD McWhinney, S Bei, TA Stergiopoulos, S Carney, JA Eng, C Stratakis, CA TI Identifying the genes for paraganglioma, gastric stromal tumors (GST), and pulmonary chondroma (Carney triad/dyad): the SDHC gene and its locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, DEB, NIH, Bethesda, MD USA. OSU, Columbus, OH USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 308 BP 222 EP 222 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700309 ER PT J AU Jia, L Gerhard, D Grouse, L Greenhut, S AF Jia, L Gerhard, D Grouse, L Greenhut, S TI CGAP and MGC - two comprehensive genomic resources for the scientific research community. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Off Canc Genom, NIH, Bethesda, MD 20892 USA. NIH, CGAP Team, Bethesda, MD 20892 USA. NIH, MGC Project Teams, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 342 BP 228 EP 228 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700343 ER PT J AU Schaffer, AA Desper, R Khan, J AF Schaffer, AA Desper, R Khan, J TI Tumor classification using phylogenetic methods on expression data. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCBI, DHHS, NIH, Bethesda, MD USA. NCI, DHHS, NIH, Gaithersburg, MD USA. RI Schaffer, Alejandro/F-2902-2012; Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 343 BP 229 EP 229 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700344 ER PT J AU Goldstein, AM AF Goldstein, AM TI Familial melanoma, pancreatic cancer and germline CDKN2A mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Genet Epidemiol Branch, DCEG, DHHS,NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 352 BP 230 EP 230 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700354 ER PT J AU Goldin, LR Pfeiffer, RM Gail, MH Mellemkjaer, L Olsen, JH Hemminki, K AF Goldin, LR Pfeiffer, RM Gail, MH Mellemkjaer, L Olsen, JH Hemminki, K TI Familial aggregation of lymphoproliferative tumors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, DCEG, Gen Epidemiol Br, Bethesda, MD 20892 USA. NCI, DCEG, Biostat Br, Bethesda, MD USA. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. Karolinska Inst, Novum, Dept Biosci, Stockholm, Sweden. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 355 BP 231 EP 231 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700356 ER PT J AU Marroni, F Aretini, P Bailey-Wilson, JE Bevilacquaa, G Parmigiani, G Presciuttini, S AF Marroni, F Aretini, P Bailey-Wilson, JE Bevilacquaa, G Parmigiani, G Presciuttini, S CA Italian Consortium Hereditary Brea TI Unbiased estimation of breast and ovarian cancer penetrances in BRCA1/2 mutation carriers using genetic-test results. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Pisa, Dept Biomed, Pisa, Italy. Univ Pisa, Dept Oncol, Pisa, Italy. NHGRI, NIH, Baltimore, MD USA. JHU, Dept Biostat, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 378 BP 234 EP 234 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700379 ER PT J AU Kennedy, AL Scacheri, PC Munasinghe, J Schimel, D Crabtree, JS Collins, FS AF Kennedy, AL Scacheri, PC Munasinghe, J Schimel, D Crabtree, JS Collins, FS TI Noninvasive imaging of pancreatic neuroendocrine tumors in MEN1-knockout mice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 389 BP 236 EP 236 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700388 ER PT J AU Moslehi, R DiGiovanna, J Goldstein, A Khan, S Tucker, P Kraemer, K AF Moslehi, R DiGiovanna, J Goldstein, A Khan, S Tucker, P Kraemer, K TI Cancer risk in xeroderma pigmentosum homozygotes and heterozygotes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Brown Med Sch, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 385 BP 236 EP 236 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700386 ER PT J AU Robinson-White, AJ Leitner, W He, L Olson, D Stratakis, CA AF Robinson-White, AJ Leitner, W He, L Olson, D Stratakis, CA TI The protein kinase A (PKA) regulatory subunit RI alpha (PRKARIA) alters MAP kinase and cell cycle entry in transformed B-lymphocytes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, UGEN, DEB, NIH, Bethesda, MD USA. NCI, DB, NIH, Bethesda, MD USA. NIAMHS, IRP, AB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 411 BP 240 EP 240 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700411 ER PT J AU Baser, ME Wallace, AJ Olschwang, S Bijlsma, E Papi, L Parry, DM Rouleau, GA Evans, DGR AF Baser, ME Wallace, AJ Olschwang, S Bijlsma, E Papi, L Parry, DM Rouleau, GA Evans, DGR TI The distribution of constitutional NF2 mutations: results from an international NF2 database SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. Fdn Jean Dausset, CEPH, INSERM, U434, Paris, France. Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. Univ Florence, Dept Clin Physiopathol, Florence, Italy. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. McGill Univ, Neurosci Res Ctr, Montreal, PQ, Canada. RI Olschwang, Sylviane/G-2716-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 424 BP 242 EP 242 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700426 ER PT J AU Gerhard, DS Strausberg, RL Riggins, GJ Schaefer, CF Wagner, L Jongeneel, V Simpson, A AF Gerhard, DS Strausberg, RL Riggins, GJ Schaefer, CF Wagner, L Jongeneel, V Simpson, A TI Towards the definition of the cancer transcriptome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Off Canc Genom, NIH, Bethesda, MD USA. Duke Univ, Durham, NC USA. NCI, Ctr Bioinformat, Bethesda, MD 20892 USA. NCBI, NIH, Bethesda, MD USA. Ludwig Inst Canc Res, Louisanne, Switzerland. Ludwig Inst, New York, NY USA. 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NCI, Occupat Epidemiol Branch, Dept Canc Epidemiol & Genet, NIH, Bethesda, MD USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Gaithersburg, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 453 BP 247 EP 247 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700453 ER PT J AU Shan, Z Tracy, P Wiest, J AF Shan, Z Tracy, P Wiest, J TI Identifying novel homozygous deletions by microsatellite analysis and characterization of a putative tumor suppressor gene, TSG-9, on chromosome 9p in human lung cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, CCR, Bethesda, MD 20892 USA. 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PD NOV PY 2003 VL 73 IS 5 MA 475 BP 251 EP 251 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700476 ER PT J AU Casey, G Lindor, N Papadopoulas, N Moskow, J Jenkins, R Thibodeau, S Gallinger, S Bapat, B Hopper, J Jass, J Young, J Buzin, C Song, W Baron, J Steelman, S Wen-Fong, C Estaki, B Sommer, S Seminara, D Haile, R AF Casey, G Lindor, N Papadopoulas, N Moskow, J Jenkins, R Thibodeau, S Gallinger, S Bapat, B Hopper, J Jass, J Young, J Buzin, C Song, W Baron, J Steelman, S Wen-Fong, C Estaki, B Sommer, S Seminara, D Haile, R TI Conversion technology increases the sensitivity of genetic testing in hereditary non-polyposis colorectal cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. GMP Genet, Waltham, MA USA. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Melbourne, Melbourne, Vic, Australia. Evergreen Ctr, Lebanon, NH USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NCI, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 485 BP 252 EP 252 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700484 ER PT J AU Baysal, BE DeLoia, JA Goodman, MT Willett-Brozick, JE Watson, P Birrer, MJ Gallion, HH AF Baysal, BE DeLoia, JA Goodman, MT Willett-Brozick, JE Watson, P Birrer, MJ Gallion, HH TI Analysis of CHEK2 for ovarian cancer susceptibility. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. Creighton Univ, Omaha, NE 68178 USA. NCI, Mol Mech Sect, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 493 BP 254 EP 254 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700494 ER PT J AU He, H Roschke, A Yonescu, R Hatchwell, E Ried, T Kirsch, I AF He, H Roschke, A Yonescu, R Hatchwell, E Ried, T Kirsch, I TI Genome-wide analysis of genetic alterations in tumor cell lines by Ccap BAC microarray. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, CCR, Genet Branch, Bethesda, MD 20892 USA. Cold Spring Harbor Lab, Genome Res Ctr, Woodbury, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 497 BP 254 EP 254 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700496 ER PT J AU Pereira, LHM Sigurdson, AJ Doody, MM Pineda, MA Alexander, BH Greene, MH Struewing, JP AF Pereira, LHM Sigurdson, AJ Doody, MM Pineda, MA Alexander, BH Greene, MH Struewing, JP TI CHEK2 : 1100delC mutation and elevated breast cancer risk SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Lab Populat Genet, DHHS, NIH, Bethesda, MD USA. NCI, Radiat Epidemiol Branch, DHHS, NIH, Bethesda, MD USA. NCI, Clin Genet Branch, DHHS, NIH, Bethesda, MD USA. Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 507 BP 256 EP 256 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700507 ER PT J AU Olson, LE Baxter, LL Carlson, EJ Epstein, CJ Reeves, RH AF Olson, LE Baxter, LL Carlson, EJ Epstein, CJ Reeves, RH TI Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Johns Hopkins Sch Med, Dept Physiol, Baltimore, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 557 BP 265 EP 265 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700559 ER PT J AU McBride, K Lewin, M Pignatelli, R Fernbach, SD Schliekelman, P Combes, A Menesses, A Lam, W Bezold, LI Kaplan, N Towbin, JA Belmont, JW AF McBride, K Lewin, M Pignatelli, R Fernbach, SD Schliekelman, P Combes, A Menesses, A Lam, W Bezold, LI Kaplan, N Towbin, JA Belmont, JW TI Inheritance analysis of congenital left ventricular outflow tract obstruction (LVOTO) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Baylor Coll Med, Dept Pediat, Div Cardiol, Houston, TX 77030 USA. Univ Georgia, Dept Stat, Athens, GA 30602 USA. NIEHS, Environm Dis & Med Program, Biostat Branch, Res Triangle Pk, NC 27709 USA. OI McBride, Kim/0000-0002-8407-8942 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 579 BP 269 EP 269 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700582 ER PT J AU Dugan, RE Bawle, E Kalche, K Rozelle, A Gilbert, AD Romero, R Johnson, A AF Dugan, RE Bawle, E Kalche, K Rozelle, A Gilbert, AD Romero, R Johnson, A TI FGFR2 and severe anomalies: phenotype-genotype correlation SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Wayne State Univ, Detroit, MI USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. NIH, Perninatal Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 651 BP 281 EP 281 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700654 ER PT J AU Leung, MYK Baxendale, V Leschek, E Wu, SM Fichman, K Chan, WY Rennert, OM AF Leung, MYK Baxendale, V Leschek, E Wu, SM Fichman, K Chan, WY Rennert, OM TI A novel polymorphic site at the mutation hot-spot(TM VI)of the luteinizing hormone receptor in a patient with familial male-limited precocious puberty. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, NIH, LCG, Bethesda, MD USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. Kaiser Permanente, Dept Pediat, San Rafael, CA USA. Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. Georgetown Univ, Dept Cell Biol, Washington, DC 20057 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 733 BP 294 EP 294 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700734 ER PT J AU Parry, DM Jackson, A Wallace, AJ Kluwe, L Mautner, VF Ramsden, RT Evans, DGR Baser, ME AF Parry, DM Jackson, A Wallace, AJ Kluwe, L Mautner, VF Ramsden, RT Evans, DGR Baser, ME TI Evaluation of genotype-phenotype correlations for vestibular schwannoma rowth rates in neurofibromatosis 2 (NF2). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ Manchester, Div Imaging Sci & Biomed Engn, Manchester, Lancs, England. St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. Univ Hosp Eppendorf, Dept Neurosurg, Hamburg, Germany. Klinikum Nord Ochsenzoll, Dept Neurol, Hamburg, Germany. Manchester Royal Infirm, Dept Otolaryngol, Manchester M13 9WL, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 731 BP 294 EP 294 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700733 ER PT J AU Bendavid, C Haddad, B Muenke, M AF Bendavid, C Haddad, B Muenke, M TI A strategy for detecting submicroscopic deletions in patients with holoprosencephaly using FISH. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NHGRI, Med Genet Branch, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 843 BP 314 EP 314 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700844 ER PT J AU Vlangos, CN Blancato, J Wilson, M Smith, ACM Elsea, SH AF Vlangos, CN Blancato, J Wilson, M Smith, ACM Elsea, SH TI Commercial FISH probes for Smith-Magenis syndrome do not contain the RAI1 gene and fail to diagnose all cases. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Dept Clin Genet, Westmead, NSW, Australia. Georgetown Univ, Inst Mol & Human Genet, Washington, DC USA. Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. Michigan State Univ, Grad Program Genet, E Lansing, MI 48824 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 874 BP 319 EP 319 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700877 ER PT J AU Gropman, AL Howell, BW AF Gropman, AL Howell, BW TI Molecular and biochemical analysis of oligophrenin, a RhoGAP, in fibroblasts. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIH, Neurogenet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 891 BP 322 EP 322 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700894 ER PT J AU Duncan, WC Gropman, A Morse, R Krasnewich, D Smith, ACM AF Duncan, WC Gropman, A Morse, R Krasnewich, D Smith, ACM TI Good babies sleeping poorly: Insufficient sleep in infants with Smith-Magenis syndrome (SMS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, MGB, NIH, HHS, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. NIMH, Bethesda, MD 20892 USA. RI SMITH, ANN C.M./C-1122-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 896 BP 323 EP 323 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700897 ER PT J AU Lin, T Sandusky, SB Xue, H Fishbein, K Spencer, R Rao, M Francomano, CA AF Lin, T Sandusky, SB Xue, H Fishbein, K Spencer, R Rao, M Francomano, CA TI Tissue specific FGFR3 transgenic mouse models for Thanatophoric Dysplasia Type II SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 899 BP 323 EP 323 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700901 ER PT J AU Cui, C Hashimoto, T Durmowicz, M Ottolenghi, C Griggs, B Srivastava, AK Schlessinger, D AF Cui, C Hashimoto, T Durmowicz, M Ottolenghi, C Griggs, B Srivastava, AK Schlessinger, D TI EDA-A1 transgene-induced guard hair formation and sebaceous gland hyperplasia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 922 BP 327 EP 327 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700922 ER PT J AU Vong, QP Wu, SM Dym, M Rennert, OM Chan, WY AF Vong, QP Wu, SM Dym, M Rennert, OM Chan, WY TI Dby expression and germ cell development. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. Georgetown Univ, Dept Cell Biol, Washington, DC 20057 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 931 BP 328 EP 328 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700932 ER PT J AU Lindhurst, MJ Blake, T Chen, A Liu, PP Biesecker, LG AF Lindhurst, MJ Blake, T Chen, A Liu, PP Biesecker, LG TI Animal models for Amish lethal microcephaly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 934 BP 329 EP 329 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700934 ER PT J AU Ottolenghi, C Uda, M Herrera, L Garcia, E Forabosco, A Schlessinger, D Crisponi, L Deiana, M Pilia, G AF Ottolenghi, C Uda, M Herrera, L Garcia, E Forabosco, A Schlessinger, D Crisponi, L Deiana, M Pilia, G TI Microarray and functional analyses of primordial follicle formation and the etiology of premature ovarian failure. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Modena, Dept Mother & Child Hlth, I-41100 Modena, Italy. Univ Cagliari, Osped Reg Microcitemie, Dipartimento Sci Biomed & Biotecnol, Cagliari, Italy. CNR, Inst Ric Talassemie & Anemie Mediterranee, Cagliari, Italy. NIA, Genet Lab, GRC, NIH,IRP, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 936 BP 329 EP 329 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700935 ER PT J AU Tayebi, N Feng, LX Baxendale, V Wu, SM Pang, ALY Dym, M Chan, WY Rennert, OM AF Tayebi, N Feng, LX Baxendale, V Wu, SM Pang, ALY Dym, M Chan, WY Rennert, OM TI Using sage to confirm a telomerase immortalized spermatogonial cell line as an experimental model. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. Georgetown Univ, Dept Cell Biol, Washington, DC USA. NICHD, Lab Clin Genomic, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 932 BP 329 EP 329 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700933 ER PT J AU Bakalov, VK Cooley, MM Bondy, CA AF Bakalov, VK Cooley, MM Bondy, CA TI Family history of diabetes mellitus (DM) and Turner syndrome (TS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 953 BP 332 EP 332 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700952 ER PT J AU Drgon, T Takahashi, M Walther, D Lin, Z Lin, L Tafti, M Billiard, M Thorpy, M Temple, H Montplaisir, J Mignot, E Uhl, GR AF Drgon, T Takahashi, M Walther, D Lin, Z Lin, L Tafti, M Billiard, M Thorpy, M Temple, H Montplaisir, J Mignot, E Uhl, GR TI Narcolepsy: involvement of imprinted, differentially-methylated promotor haplotypes of vesicular monoamine transporter 2 (VMAT2). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIDA, NIH, Baltimore, MD USA. Stanford Med Ctr, Stanford, CA USA. Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. Montefiore Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 949 BP 332 EP 332 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700950 ER PT J AU Bondy, CA Cooley, M Bakalov, VK Zinn, AR AF Bondy, CA Cooley, M Bakalov, VK Zinn, AR TI The parental origin of the normal X chromosome affects blood pressure in Turner Syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Nat Inst Child Hlth, NIH, Bethesda, MD USA. Univ Texas, SW Med Ctr, McDermott Ctr, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 960 BP 333 EP 333 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599700961 ER PT J AU Antonellis, A Lee-Lin, SQ Baxter, LL Wolfsberg, TG Program, NCS Pavan, WJ Green, ED AF Antonellis, A Lee-Lin, SQ Baxter, LL Wolfsberg, TG Program, NCS Pavan, WJ Green, ED TI Multi-species comparative sequence analysis of the WS4/CMT1/Sox10 locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis REs Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH Intramural Sequencing Ctr, NIH, Gaithersburg, MD USA. George Washington Univ, Genet Program, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1057 BP 350 EP 350 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701058 ER PT J AU Hu, X Mazzanti, C Lipsky, RH Goldman, D AF Hu, X Mazzanti, C Lipsky, RH Goldman, D TI Role of a tetranucleotide repeat polymorphism in the first intron of the tyrosine hydroxylase gene in expression and behavioral phenotypes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1086 BP 355 EP 355 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701085 ER PT J AU Peters, JA Kenen, R Giusti, R Loud, J Weissman, N Greene, MH AF Peters, JA Kenen, R Giusti, R Loud, J Weissman, N Greene, MH TI Feasibility and utility of the Colored Eco-Genetic Relational Map(CEGRM) in women at risk for hereditary breast cancer SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Rockville, MD USA. Coll New Jersey, Dept Sociol, Ewing, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1110 BP 360 EP 360 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701113 ER PT J AU Turner, JT Biesecker, BB Leib, JR Biesecker, LG Peters, KF AF Turner, JT Biesecker, BB Leib, JR Biesecker, LG Peters, KF TI Parental coping with Proteus syndrome: A chronic progressive disorder. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1109 BP 360 EP 360 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701110 ER PT J AU Mitchell, J Fomous, C Morrison, S Mucci, D Davenport, S McCray, A AF Mitchell, J Fomous, C Morrison, S Mucci, D Davenport, S McCray, A TI Genetics home reference: a new federal government resource. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Missouri, Columbia, MO 65211 USA. Natl Lib Med, Bethesda, MD USA. Sensory Genet, Bloomington, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1117 BP 361 EP 361 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701117 ER PT J AU Ibay, GP Doan, B Reider, L Dana, D Schlifka, M Hu, H Holmes, T O'Neill, J Bailey-Wilson, JE Stambolian, D AF Ibay, GP Doan, B Reider, L Dana, D Schlifka, M Hu, H Holmes, T O'Neill, J Bailey-Wilson, JE Stambolian, D TI Familial Myopia study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Interited Dis Res Br, NIH, Baltimore, MD USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1141 BP 366 EP 366 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701144 ER PT J AU Jackson, AU Watanabe, RW Scott, LJ Mohlke, KL Silander, K Valle, TT Doheny, K Pugh, E Tuomilehto, J Bergman, RN Collins, FS Boehnke, M AF Jackson, AU Watanabe, RW Scott, LJ Mohlke, KL Silander, K Valle, TT Doheny, K Pugh, E Tuomilehto, J Bergman, RN Collins, FS Boehnke, M TI Evidence for a free fatty acid-related diabetes susceptibility locus on chromosome 22 in Finnish subjects. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ So Calif, Los Angeles, CA 90089 USA. NHGRI, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. Ctr Inherited Dis Res, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1142 BP 366 EP 366 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701142 ER PT J AU Bergen, AW Yeager, M Welch, R Haque, K Ganjei, JK Mazzanti, C Nardi, I Van den Bree, MBM Fichter, M Halmi, K Kaplan, A Strober, M Treasure, J Woodside, B Bulik, CM Bacanu, SA Devlin, B Berretini, W Goldman, D Kaye, WH AF Bergen, AW Yeager, M Welch, R Haque, K Ganjei, JK Mazzanti, C Nardi, I Van den Bree, MBM Fichter, M Halmi, K Kaplan, A Strober, M Treasure, J Woodside, B Bulik, CM Bacanu, SA Devlin, B Berretini, W Goldman, D Kaye, WH TI Association of the DRD2 - 141 indel polymorphism with anorexia nervosa. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Biognosis US Inc, Gaithersburg, MD USA. Univ Pisa, I-56100 Pisa, Italy. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1150 BP 367 EP 367 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701149 ER PT J AU Yeager, M Packer, B Welch, R Bergen, AW Chanock, SJ Hughes, AL AF Yeager, M Packer, B Welch, R Bergen, AW Chanock, SJ Hughes, AL TI Widespread purifying selection at polymorphic sites in human protein-coding loci SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1146 BP 367 EP 367 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701147 ER PT J AU Roy-Gagnon, MH Jee, SH Wilson, AF AF Roy-Gagnon, MH Jee, SH Wilson, AF TI Heritability associated with candidate polymorphisms for cardiovascular risk factors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Genom Sect, IDRB, NIH, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Yonsei Univ, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1171 BP 371 EP 371 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701174 ER PT J AU Kim, UK Larsen, J Drayna, D AF Kim, UK Larsen, J Drayna, D TI Worldwide genetic variation in human bitter taste receptor genes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIDCD, NIH, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1214 BP 378 EP 378 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701214 ER PT J AU Conneely, KN Silander, K Lazaridis, KN Mohlke, KL Scott, LJ Valle, TT Watanabe, RM Buchanan, TA Bergman, RN Tuomilehto, J Collins, F Boehnke, M AF Conneely, KN Silander, K Lazaridis, KN Mohlke, KL Scott, LJ Valle, TT Watanabe, RM Buchanan, TA Bergman, RN Tuomilehto, J Collins, F Boehnke, M TI Variation in the resistin gene is associated with diabetes-related phenotypes in Finns SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Michigan, Ann Arbor, MI 48109 USA. Natl Publ Hlth Inst, Helsinki, Finland. NHGRI, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1244 BP 383 EP 383 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701244 ER PT J AU Oleksyk, TK Thio, CL Truelove, AL Goedert, JJ Donfield, S Thomas, DL O'Brien, SJ Smith, MW AF Oleksyk, TK Thio, CL Truelove, AL Goedert, JJ Donfield, S Thomas, DL O'Brien, SJ Smith, MW TI Genetic linkage and association of single nucleotide polymorphisms in the IL10 region and HCV clearance. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Lab Genomic Divers, Frederick, MD 21701 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NCI, SAIC, Basic Res Program, Frederick, MD USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Rho Inc, Chapel Hill, NC USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. RI Smith, Michael/B-5341-2012; Taras, Oleksyk/J-8805-2013 OI Taras, Oleksyk/0000-0002-8148-3918 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1256 BP 385 EP 385 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701256 ER PT J AU Shrestha, S Strathdee, SA Galai, N Thomas, D Vlahov, D O'Brien, SJ Smith, MW AF Shrestha, S Strathdee, SA Galai, N Thomas, D Vlahov, D O'Brien, SJ Smith, MW TI CCR5 pathway candidate genes susceptible to HIV-infection. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Basic Res Program, Frederick, MD 21701 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. NCI, Lab Genomic Divers, NIH, Frederick, MD 21701 USA. RI Strathdee, Steffanie/B-9042-2009; Smith, Michael/B-5341-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1259 BP 385 EP 385 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701260 ER PT J AU Drake, J Loomer, M Newton-Cheh, C Lochner, A Levy, R Parise, H Schaffner, SF Gabriel, S Larson, M Benjamin, EJ Daly, MJ O'Donnell, CJ Hirschhom, JN AF Drake, J Loomer, M Newton-Cheh, C Lochner, A Levy, R Parise, H Schaffner, SF Gabriel, S Larson, M Benjamin, EJ Daly, MJ O'Donnell, CJ Hirschhom, JN TI Efficacy of haplotype-based association approaches. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Harvard Univ, Childrens Hosp, Boston, MA 02115 USA. MIT, Ctr Genome Res, Cambridge, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. RI Schaffner, Stephen/D-1189-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1267 BP 387 EP 387 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701270 ER PT J AU Nadif, R Jedlicka, A Mintz, M Kauffmann, F Kleeberger, S AF Nadif, R Jedlicka, A Mintz, M Kauffmann, F Kleeberger, S TI Association of CCR5 and CCL5 polymorphisms with coal workers' pneumoconiosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIEHS, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. INSERM, U472, Villejuif, France. RI Nadif, Rachel/R-2876-2016 OI Nadif, Rachel/0000-0003-4938-9339 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1287 BP 390 EP 390 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701289 ER PT J AU Bernig, T Staats, B Yeager, M Taylor, JG Foster, CB Chanock, S AF Bernig, T Staats, B Yeager, M Taylor, JG Foster, CB Chanock, S TI Resequence analysis of the Mannose-binding lectin gene (MBL2) demonstrates substantial genetic diversity with functional implications. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Natl Canc Inst, ATC, Pediat Oncol Branch, Gaithersburg, MD USA. Natl Canc Inst, ATC, Core Genotyping Facil, Gaithersburg, MD USA. Johns Hopkins Univ, Dept Pediat, Div Infect Dis, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1295 BP 391 EP 391 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701296 ER PT J AU Berthier-Schaad, Y Plantinga, L Liu, Y Fink, N Klag, MJ Coresh, J Smith, MW AF Berthier-Schaad, Y Plantinga, L Liu, Y Fink, N Klag, MJ Coresh, J Smith, MW TI IL10 polymorphisms and risk of cardiovascular disease in the CHOICE cohort. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, SAIC, Basic Res Program, Frederick, MD 21701 USA. RI Smith, Michael/B-5341-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1296 BP 392 EP 392 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701297 ER PT J AU Duggal, P Klein, AP Lee, KE Klein, R Bailey-Wilson, J Klein, BK AF Duggal, P Klein, AP Lee, KE Klein, R Bailey-Wilson, J Klein, BK TI Segregation analysis of intraocular pressure in the beaver dam eye study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, IDRB, Stat Genet Sect, NIH, Baltimore, MD USA. Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1348 BP 400 EP 400 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701347 ER PT J AU Seldin, MF Collins-Schramm, HE Chima, B Morii, T Wah, K Figueroa, Y Criswell, LA Hanson, RL Knowler, WC Silva, G Belmont, JW AF Seldin, MF Collins-Schramm, HE Chima, B Morii, T Wah, K Figueroa, Y Criswell, LA Hanson, RL Knowler, WC Silva, G Belmont, JW TI Mexican American ancestry-informative markers: Examination of population structure and marker characteristics in European Americans, Mexican Americans, Amerindians and Asians. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Calif Davis, Rowe Program, Davis, CA 95616 USA. Univ Calif San Francisco, Arthrit Ctr, San Francisco, CA 94143 USA. Natl Inst Hlth, Phoenix, AZ USA. Obras Sociales Hermano Pedro, Antigua, Guatemala. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1345 BP 400 EP 400 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701348 ER PT J AU Johnson, JOM Hanson, MJ Hague, S Singleton, A Crawley, A Ravina, B Hardy, J Gwinn-Hardy, K Singleton, A AF Johnson, JOM Hanson, MJ Hague, S Singleton, A Crawley, A Ravina, B Hardy, J Gwinn-Hardy, K Singleton, A TI Alpha synuclein gene dosage in familial and sporadic Parkinson's disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIA, NIH, Bethesda, MD 20892 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NIH, Neurogenet Lab, Bethesda, MD 20892 USA. RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1364 BP 403 EP 403 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701366 ER PT J AU Leib, JR Gollust, SE Hull, SC Wilfond, BS AF Leib, JR Gollust, SE Hull, SC Wilfond, BS TI Carrier screening panels for Ashkenazi Jews: Is more better? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NINDS, NGB, NIH, Bethesda, MD 20892 USA. NHGRI, MGB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1443 BP 416 EP 416 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701442 ER PT J AU Dean, M Gold, B Van Ness, J Galas, DJ AF Dean, M Gold, B Van Ness, J Galas, DJ TI Surveying genomic deletions and duplications through the generation of oligonucleotide fingerprints using primer-free amplification. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD USA. Keck Grad Inst Appl Life Sci, Claremont, CA 91711 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1455 BP 419 EP 419 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701456 ER PT J AU Yan, D Park, HJ Ouyan, XM Pandya, A Doi, K Erdenetungalag, R Du, LL Nance, WE Griffith, AJ Liu, XZ AF Yan, D Park, HJ Ouyan, XM Pandya, A Doi, K Erdenetungalag, R Du, LL Nance, WE Griffith, AJ Liu, XZ TI Evidence of a founder effect for the 235delC mutation of GJB2 (connexin 26) in East Asians. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Miami, Dept Otolaryngol, Miami, FL 33152 USA. NIDCD, NIH, Rockville, MD USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Dept Otolaryngol & Sensory Organ Surg, Osaka, Japan. Maternal & Child Hlth Res Ctr, Dept Human Genet, Ulaanbaatar, Mongol Peo Rep. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1459 BP 419 EP 419 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701458 ER PT J AU Modi, WS AF Modi, WS TI LAG-1 and LD78-beta chemokine genes are located in a segmental duplication at chromosome 17q12. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1468 BP 421 EP 421 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701471 ER PT J AU Chang, KT Shi, YJ Min, KT AF Chang, KT Shi, YJ Min, KT TI Drosophile model of Down syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1496 BP 425 EP 425 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701497 ER PT J AU Pang, ALY Johnson, W Ravindranath, D Dym, M Rennert, OM Chan, WY AF Pang, ALY Johnson, W Ravindranath, D Dym, M Rennert, OM Chan, WY TI A survey of housekeeping gene expression on during germ cell development. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, Lab Clin Genom, NIH, Washington, DC USA. Georgetown Univ, Dept Cell Biol, Washington, DC USA. Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1520 BP 429 EP 429 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701521 ER PT J AU Mortlock, DP Chandler, RL McDermott, KJ Portnoy, ME AF Mortlock, DP Chandler, RL McDermott, KJ Portnoy, ME TI A mammalian chromosomal rearrangement involving a cis-regulatory element of the Gdf6 gene: implications for duplication-mediated gene evolution and for gene regulatory boundaries SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1525 BP 430 EP 430 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701524 ER PT J AU Rioux, JD Mather, K Schaffner, S Farwell, L Daly, M Patterson, N Cullen, M Carrington, M Bugawari, T Erlich, H Campbell, J Barrett, J Miller, K Thomson, G Lander, ES Walsh, EC AF Rioux, JD Mather, K Schaffner, S Farwell, L Daly, M Patterson, N Cullen, M Carrington, M Bugawari, T Erlich, H Campbell, J Barrett, J Miller, K Thomson, G Lander, ES Walsh, EC TI An integrated haplotype map of the human major histocompatibility complex. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Roche Mol Syst, Dept Human Genet, Alameda, CA USA. NCI, Basic Res Program, SAIC Frederick, Lab Genomic Divers, Frederick, MD 21701 USA. Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. RI Schaffner, Stephen/D-1189-2011 NR 0 TC 0 Z9 0 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1537 BP 432 EP 432 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701536 ER PT J AU Haque, KA Beerman, MB Puri, V Yadavalli, S Crenshaw, AT Welch, RA Yeager, M Packer, BR Garcia-Closas, M Rothman, N Chanock, SJ Bergen, AW AF Haque, KA Beerman, MB Puri, V Yadavalli, S Crenshaw, AT Welch, RA Yeager, M Packer, BR Garcia-Closas, M Rothman, N Chanock, SJ Bergen, AW TI Evaluation of whole genome amplification methods SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Core Genotyping Facil, NIH, Bethesda, MD 20892 USA. NCI, OEB, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. NCI, HREB, DCEG, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick Inc, Core Genotyping Facil, NIH, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1550 BP 434 EP 434 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701551 ER PT J AU Lee, JA Dean, M Gold, B Lupski, JR Inoue, K AF Lee, JA Dean, M Gold, B Lupski, JR Inoue, K TI Genomic architecture involved in PLP1 duplication causing Pelizaeus-Merzbacher disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, Human Genet Sect, Lab Genomic Divers, Frederick, MD 21701 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1562 BP 436 EP 436 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701563 ER PT J AU Flippin, JD Strunnikova, N Hilmer, SC Hoffman, EP Casky, KG AF Flippin, JD Strunnikova, N Hilmer, SC Hoffman, EP Casky, KG TI The effect of vitamin E on gene expression in patients with age-related macular degeneration (AMD) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NEI, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1567 BP 437 EP 437 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701566 ER PT J AU Bernardini, I Ueda, M Phomphutkul, C Krasnewich, D Kleta, R Gahl, WA AF Bernardini, I Ueda, M Phomphutkul, C Krasnewich, D Kleta, R Gahl, WA TI Long-term follow-up of well treated nephropathic cystinosis patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, MGB, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1610 BP 445 EP 445 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701610 ER PT J AU Phornphutkul, C Suwannarat, P Introne, W Bernardini, I Turner, M Heekin, RD Kleta, R Gahl, WA AF Phornphutkul, C Suwannarat, P Introne, W Bernardini, I Turner, M Heekin, RD Kleta, R Gahl, WA TI Making the diagnosis of alkaptonuria: Unusual skin findings in an alkaptonuria patient. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, MGB, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Orthopaed Surg Serv, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1622 BP 447 EP 447 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701622 ER PT J AU Wassif, CA Porter, FD AF Wassif, CA Porter, FD TI Disruption of the 3-beta-hydroxysterol Delta 24-reductase gene: Development and characterization of a murine model of desmosterolosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, HBD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1621 BP 447 EP 447 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701624 ER PT J AU Cabral, WA Makareeva, E Leikin, S Colige, A Letocha, AD Ty, J Yeowell, HN Pals, G Marini, JC AF Cabral, WA Makareeva, E Leikin, S Colige, A Letocha, AD Ty, J Yeowell, HN Pals, G Marini, JC TI Delineating the OI/EDS region of the alpha 1(I) chain and the shared mechanism of OI/ED and EDS VIIA SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, BEMB, NIH, Bethesda, MD USA. NICHD, Sect Phys Biochem, NIH, Bethesda, MD USA. Univ Liege, Lab Connect Tissue Res, Liege, Belgium. Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27710 USA. Vrije Univ Amsterdam, Med Ctr, Dept Human Genet, NL-1081 HV Amsterdam, Netherlands. RI Pals, Gerard/A-5198-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1630 BP 448 EP 448 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701629 ER PT J AU Sparks, S Lalor, M Orvisky, E Huizing, M Krasnewich, D Sun, MS Dalakas, M Gahl, W AF Sparks, S Lalor, M Orvisky, E Huizing, M Krasnewich, D Sun, MS Dalakas, M Gahl, W TI UDP-GlcNAc 2-epimerase activity in hereditary inclusion body myopathy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIMH, NSB, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1626 BP 448 EP 448 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701627 ER PT J AU Goker-Alpan, O Schiffmann, R Lwin, A Sidransky, E AF Goker-Alpan, O Schiffmann, R Lwin, A Sidransky, E TI Do mutations in the glucocerebrosidase gene modify the course of Parkinson disease? Family studies in patients with Gaucher disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIMH, NSB, NIH, Bethesda, MD 20892 USA. NHGRI, MGB, NIH, Bethesda, MD 20892 USA. NINDS, DMNB, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1634 BP 449 EP 449 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701634 ER PT J AU Gunay-Aygun, M Dobbie, A Kleta, R Dorward, H Crow, Y Gahl, WA McClean, P Huizing, M AF Gunay-Aygun, M Dobbie, A Kleta, R Dorward, H Crow, Y Gahl, WA McClean, P Huizing, M TI Clinical and molecular findings in a patient with Griscelli syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Sect Human Biochem Genet, MGB, NIH, Bethesda, MD 20892 USA. St Jamess Univ Hosp, Leeds, W Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1645 BP 451 EP 451 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701648 ER PT J AU Sidransky, E Orvisky, E Lwin, A Stubblefield, B Schiffmann, R Goker-Alpan, O AF Sidransky, E Orvisky, E Lwin, A Stubblefield, B Schiffmann, R Goker-Alpan, O TI Role of genetic modifiers in determining the phenotype in Gaucher disease: A closer-look at the genotype L444P/L444P. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIMH, NSB, NIH, Bethesda, MD 20892 USA. NHGRI, MGB, NIH, Bethesda, MD 20892 USA. NINDS, DMNB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1648 BP 451 EP 451 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701647 ER PT J AU Schiffmann, R Gupta, S AF Schiffmann, R Gupta, S TI Normative data in adult female patients with Fabry disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Natl Inst Neurol, DMNB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1654 BP 452 EP 452 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701653 ER PT J AU Orvisky, E Martin, BM Walker, JM Sidransky, E AF Orvisky, E Martin, BM Walker, JM Sidransky, E TI Substrate specificity and multiple tissue isoforms of glucocerebrosidase in patients with Gaucher disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIMH, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1673 BP 455 EP 455 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701674 ER PT J AU Hess, RA Claassen, DA White, J Gahl, WA Huizing, M AF Hess, RA Claassen, DA White, J Gahl, WA Huizing, M TI Hermansky-Pudlak syndrome type 5 and type 6: Four new patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1676 BP 456 EP 456 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701676 ER PT J AU Kleta, R Morse, RP Alroy, J Orvisky, E Krasnewich, D Wenger, DA Gahl, WA AF Kleta, R Morse, RP Alroy, J Orvisky, E Krasnewich, D Wenger, DA Gahl, WA TI Clinical, biochemical and molecular diagnosis of a free sialic storage disease patient of moderate severity. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Sect Humann Biochem Genet, MGB, NIH, Bethesda, MD 20892 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. New England Med Ctr, Boston, MA 02111 USA. NIMH, NSB, NIH, Bethesda, MD 20892 USA. Jefferson Med Coll, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1677 BP 456 EP 456 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701679 ER PT J AU LaMarca, ME Goker-Alpan, O Orvisky, E Ginns, EI Sidransky, E AF LaMarca, ME Goker-Alpan, O Orvisky, E Ginns, EI Sidransky, E TI Apoptosis in brain in the type 2 Gaucher mouse: neurotoxicity starts in utero. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIMH, Mol Neurogenet Sect, Bethesda, MD 20892 USA. NHGRI, Mol Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1675 BP 456 EP 456 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701678 ER PT J AU Wooley, AH Dorward, H Gahl, WA Huizing, M AF Wooley, AH Dorward, H Gahl, WA Huizing, M TI Localization and clathrin binding of the Hermansky Pudlak syndrome type 3 protein. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1674 BP 456 EP 456 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701675 ER PT J AU Suwannarat, P Bernardini, I Kaiser-Kupfer, M Tsilou, E Rubin, B O'Brien, K Gahl, W AF Suwannarat, P Bernardini, I Kaiser-Kupfer, M Tsilou, E Rubin, B O'Brien, K Gahl, W TI A pilot study of nitisinone in Alkaptonuria. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIH, Sect Human Biochem Genet, Med Genet Branch, Bethesda, MD 20892 USA. NEI, Clin Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1723 BP 464 EP 464 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701726 ER PT J AU Ghosh, M Smith, T Vijaya, R Riazuddin, S Ahmad, ZM Naz, S Kabra, M Menon, PSN Friedman, TB Wilcox, ER AF Ghosh, M Smith, T Vijaya, R Riazuddin, S Ahmad, ZM Naz, S Kabra, M Menon, PSN Friedman, TB Wilcox, ER TI Molecular epidemiology of non-syndromic recessive deafness in the Indian subcontinent: the emerging spectrum. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 AIIMS, Genet Unit, New Delhi, India. NIDCD, Mol Genet Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1735 BP 466 EP 466 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701735 ER PT J AU Justice, CM Marosy, B Novak, S Boyce, P Pettengill, J Doheny, KF Pugh, EW Wilson, AF Miller, NH AF Justice, CM Marosy, B Novak, S Boyce, P Pettengill, J Doheny, KF Pugh, EW Wilson, AF Miller, NH TI Genetic linkage of kyphoscoliosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Genometr Sect, NIH, Baltimore, MD USA. Johns Hopkins Univ, Dept Orthopaed Surg, Baltimore, MD USA. Johns Hopkins Univ, CIDR, IGM, SOM, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1744 BP 467 EP 467 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701745 ER PT J AU Dupuis, J Larson, MG Vasan, RS Massaro, JM Wilson, PWF Lipinska, I Corey, D Vita, JA Keaney, JF Benjamin, EJ AF Dupuis, J Larson, MG Vasan, RS Massaro, JM Wilson, PWF Lipinska, I Corey, D Vita, JA Keaney, JF Benjamin, EJ TI Systemic biomarkers of vascular inflammation in the NHLBI Framingham Heart Study: Genome scan evidence for susceptibility loci on chromosome 1q. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1771 BP 472 EP 472 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701771 ER PT J AU Ziv, M Schiffmann, R Altarescu, G AF Ziv, M Schiffmann, R Altarescu, G TI Endothelial nitric oxide synthase gene polymorphism in Fabry disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NINDS, Dev & Metab Branch, NIH, Bethesda, MD 20892 USA. Shaare Zedek Med Ctr, Genet Unit, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1774 BP 472 EP 472 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701775 ER PT J AU Boyce, P Brown, D Goldstein, J Witmer, D Hayden, D Pettengill, J Tsai, Y Pugh, E Luong, E Nussbaum, R Doheny, K AF Boyce, P Brown, D Goldstein, J Witmer, D Hayden, D Pettengill, J Tsai, Y Pugh, E Luong, E Nussbaum, R Doheny, K TI A flexible software tool for designing and multiplexing SBE SNP assays for detection by MALDI-TOF. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, IDRB, NIH, Bethesda, MD 20892 USA. Univ Waterloo, Waterloo, ON N2L 3G1, Canada. Ctr Inherited Dis Res, JHUSOM, IGM, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1779 BP 473 EP 473 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701778 ER PT J AU Arcos-Burgos, M Castellanos, FX Lopera, F Pineda, D Palacio, JD Rapoport, JL Berg, K Bailey-Wilson, J Muenke, M AF Arcos-Burgos, M Castellanos, FX Lopera, F Pineda, D Palacio, JD Rapoport, JL Berg, K Bailey-Wilson, J Muenke, M TI Genome-wide scan in multigenerational and extended pedigrees segregating ADHD from a genetic isolate. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NYU, Ctr Child Study, New York, NY USA. NIMH, NIH, DHHS, Bethesda, MD 20892 USA. Univ Antioquia, Neurosci Grp, Medellin, Colombia. NHGRI, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1795 BP 476 EP 476 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701795 ER PT J AU Friedrichsen, DM Stanford, JL Isaacs, SD Janer, M Chang, BL Deutsch, K Gillanders, E Kolb, S Wiley, K Badzioch, MD Zheng, SL Walsh, PC Jarvik, GP Hood, L Trent, JM Isaacs, WB Ostrander, EA Xu, J AF Friedrichsen, DM Stanford, JL Isaacs, SD Janer, M Chang, BL Deutsch, K Gillanders, E Kolb, S Wiley, K Badzioch, MD Zheng, SL Walsh, PC Jarvik, GP Hood, L Trent, JM Isaacs, WB Ostrander, EA Xu, J TI Identification of a prostate cancer susceptibility locus in 37 Jewish families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA. NHGRI, NIH, Bethesda, MD 20892 USA. 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PD NOV PY 2003 VL 73 IS 5 MA 1797 BP 476 EP 476 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701796 ER PT J AU Rokman, A Baffoe-Bonnie, A Gillanders, E Gibbs, KD Ikonen, T Jones, MP Gildea, D Freas-Lutz, D Markey, C Matikainen, MP Koivisto, PA Tammela, TLJ Kallioniemi, OP Trent, J Bailey-Wilson, JE Schleutker, J AF Rokman, A Baffoe-Bonnie, A Gillanders, E Gibbs, KD Ikonen, T Jones, MP Gildea, D Freas-Lutz, D Markey, C Matikainen, MP Koivisto, PA Tammela, TLJ Kallioniemi, OP Trent, J Bailey-Wilson, JE Schleutker, J TI Search for Finnish prostate cancer predisposition loci - Fine-mapping of chromosome 3p25-p26 and 11q14. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Translat Genomics Res Inst, Phoenix, AZ 85004 USA. VTT State Technol Res Ctr, Med Biotechnol Grp, Turku, Finland. Tampere Univ Hosp, Dept Clin Genet, Tampere, Finland. Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. Univ Tampere, Div Urol, FIN-33101 Tampere, Finland. NHGRI, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1814 BP 479 EP 479 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701816 ER PT J AU Smaoui, N Li, S Chaabouni, M Mrad, R Kallet, H Maazoul, F Nouiri, E Chaabouni, H Hejtmancik, JF AF Smaoui, N Li, S Chaabouni, M Mrad, R Kallet, H Maazoul, F Nouiri, E Chaabouni, H Hejtmancik, JF TI Genetic study of the Bardet-Biedl syndrome in Tunisia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Ras Jebel Hosp, Dept Pediat, Bizerte, Tunisia. Fac Med, Dept Genet, Tunis, Tunisia. NEI, Dept OGVFB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1824 BP 481 EP 481 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701827 ER PT J AU Belfer, I Phillips, G Taubman, J Max, MB Goldman, D AF Belfer, I Phillips, G Taubman, J Max, MB Goldman, D TI Haplotype architecture of the norepinephrine transporter gene [SLC6A2] in four populations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. NIDCR, Pain & Neurosensory Mech Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1834 BP 482 EP 482 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701835 ER PT J AU Gillanders, E Juo, S Jones, M Markey, C Holland, E Gruis, N Bressac-de-Paillerets, B Goldstein, A Tucker, M Mann, G Bailey-Wilson, J Trent, J AF Gillanders, E Juo, S Jones, M Markey, C Holland, E Gruis, N Bressac-de-Paillerets, B Goldstein, A Tucker, M Mann, G Bailey-Wilson, J Trent, J TI Localization of novel loci involved in ocular and cutaneous melanoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Queensland Inst Med Res Unit, Brisbane, Qld, Australia. Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Sydney, NSW 2006, Australia. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. LUMC, Dept Dermatol, Leiden, Netherlands. LUMC, Ctr Human & Clin Genet, Leiden, Netherlands. Inst Curie, Paris, France. Inst Gustave Rousy, Villejuif, France. Translat Genom Res Inst, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1846 BP 484 EP 484 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701847 ER PT J AU Nowotny, P Li, Y Holmans, P Smemo, S Tacey, K Doil, L Lau, K Catanese, J Garcia, V Myers, A Wavrant-DeVrieze, V Lovestone, S Thal, L Jones, L Williams, J Owen, M Hardy, J Goate, A Grupe, A AF Nowotny, P Li, Y Holmans, P Smemo, S Tacey, K Doil, L Lau, K Catanese, J Garcia, V Myers, A Wavrant-DeVrieze, V Lovestone, S Thal, L Jones, L Williams, J Owen, M Hardy, J Goate, A Grupe, A TI Strong pattern of association with AD in a 210 kb region on chromosome 12. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA. Celera Diagnost, Alameda, CA USA. MRC Biostat Unit, Cambridge, England. NIA, Bethesda, MD USA. UCSD, Dept Neurosci, San Diego, CA USA. Inst Psychiat, Dept Neurosci, London, England. Dept Psychol Med, Cardiff, S Glam, Wales. RI Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; Holmans, Peter/F-4518-2015 OI Myers, Amanda/0000-0002-3100-9396; Holmans, Peter/0000-0003-0870-9412 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1848 BP 485 EP 485 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701851 ER PT J AU Buervenich, S Detera-Wadleigh, SD Akula, N Thomas, CJM Kassem, L Rezvani, A Corona, WR Berrettini, W Byerley, W Coryell, W DePaulo, JR Gershon, ES Kelsoe, J McInnis, MG Murphy, DL Numberger, JI Reich, T Scheftner, W McMahon, FJ AF Buervenich, S Detera-Wadleigh, SD Akula, N Thomas, CJM Kassem, L Rezvani, A Corona, WR Berrettini, W Byerley, W Coryell, W DePaulo, JR Gershon, ES Kelsoe, J McInnis, MG Murphy, DL Numberger, JI Reich, T Scheftner, W McMahon, FJ TI Fine mapping on chromosome 6q in the NIMH genetics initiative bipolar pedigrees. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIMH, Intramural Res Program, Bethesda, MD USA. Indiana Univ, Sch Med, NIMH Gent Initiat Bipolar Disorder, Indianapolis, IN USA. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1882 BP 490 EP 490 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701883 ER PT J AU Doheny, K Boyce, P Witmer, D Hayden, D Pettengill, J Tsai, Y Pugh, E Luong, E Nussbaum, R AF Doheny, K Boyce, P Witmer, D Hayden, D Pettengill, J Tsai, Y Pugh, E Luong, E Nussbaum, R TI Screening validated SNPs for the development of a human genome linkage marker resource. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 JHUSOM, IGM, Ctr Inherited Dis Res, Baltimore, MD USA. NHGRI, IDRB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1880 BP 490 EP 490 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701882 ER PT J AU Pras, E Smaoui, N Hejtmancik, JF AF Pras, E Smaoui, N Hejtmancik, JF TI A nonsense mutation in the I-branching beta-1,6-N-acetylglucosaminyl-transferase (IGnT) gene, causes autosomal recessive congenital cataract SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NEI, OGVFB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1904 BP 494 EP 494 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701906 ER PT J AU Riaz, N Ahmad, J Raza, B Riazuddin, S Cox, N Drayna, D AF Riaz, N Ahmad, J Raza, B Riazuddin, S Cox, N Drayna, D TI Genetic studies of stuttering in inbred Pakistani families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Punjab Univ, CEMB, Lahore, Pakistan. NIDCD, NIH, Rockville, MD USA. Univ Chicago, Dept Human Genet, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1905 BP 494 EP 494 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701904 ER PT J AU Tsai, Y Pugh, EW Boyce, P Doheny, KF Fan, YT Scott, AF St Hansen, M Oliphant, A Loi, H Mei, R Puck, JM AF Tsai, Y Pugh, EW Boyce, P Doheny, KF Fan, YT Scott, AF St Hansen, M Oliphant, A Loi, H Mei, R Puck, JM TI Replication of linkage on 2p for chronic mucocutaneous candidiasis and thyroid disease using two different high-density SNP genome scan technologies. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 JHUSOM, IGM, CIDR, Baltimore, MD USA. Illumina, San Diego, CA USA. Affymetrix Inc, Santa Clara, CA USA. NHGRI, GMBB, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1911 BP 495 EP 495 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701910 ER PT J AU Yang, RX Kelley, MJ McMaster, M Liebsch, NJ Bergen, AW Beerman, M Haque, K Goldstein, AM Parry, DM AF Yang, RX Kelley, MJ McMaster, M Liebsch, NJ Bergen, AW Beerman, M Haque, K Goldstein, AM Parry, DM TI Genetic heterogeneity in familial chordoma SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NCI, DHHS, Dept DCEG, NIH, Rockville, MD USA. Duke Univ, Dept Med, Durham, NC USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. NCI, DHHS, CGF, NIH, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1908 BP 495 EP 495 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701911 ER PT J AU Chen, YS Akula, N Detera-Wadleigh, SD Schulze, TG Thomas, J DePaulo, JR McInnis, MG Cox, NJ McMahon, FJ AF Chen, YS Akula, N Detera-Wadleigh, SD Schulze, TG Thomas, J DePaulo, JR McInnis, MG Cox, NJ McMahon, FJ TI Findings in an independent sample support association between bipolar affective disorder and the G72/G30 locus on chromosome 13q33 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Chicago, Chicago, IL 60637 USA. Natl Inst Mental Hlth Intramural, Res Program, Mood & Anxiety Program,Dept Human & Human Serv, NIH, Bethesda, MD USA. Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, Mannheim, Germany. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. 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PD NOV PY 2003 VL 73 IS 5 MA 1917 BP 496 EP 496 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701916 ER PT J AU Kovac, I Havlik, RJ Foley, D Peila, R Singleton, A Hardy, J Egan, J Taub, D Rodriguez, B Masaki, K Curb, D Fujimoto, W Wilson, AF AF Kovac, I Havlik, RJ Foley, D Peila, R Singleton, A Hardy, J Egan, J Taub, D Rodriguez, B Masaki, K Curb, D Fujimoto, W Wilson, AF TI Additional support for a type 2 diabetes susceptibility locus on chromosome 14 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Dept Genometr, Baltimore, MD USA. NIA, Bethesda, MD 20892 USA. NIA, Baltimore, MD 21224 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ Washington, Seattle, WA 98195 USA. 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Univ Trier, Ctr Psychobiol & Psychosomat Res, Trier, Germany. JHSPH, Dept Epidemiol, Baltimore, MD USA. Univ Penn, Ctr Psychobiol & Psychosomat Res, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. NIA, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1945 BP 501 EP 501 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701945 ER PT J AU Zhou, Z Lipsky, R Goldman, D AF Zhou, Z Lipsky, R Goldman, D TI Detection and characterization of human TPH2 variants. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1968 BP 505 EP 505 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701971 ER PT J AU Cabin, DE Gispert, S Murphy, D Auburger, G Myers, A Nussbaum, RL AF Cabin, DE Gispert, S Murphy, D Auburger, G Myers, A Nussbaum, RL TI Deletion of the endogenous mouse Snca gene markedly exacerbates synucleinopathy in transgenic mice expressing Ala53-> Thr. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. Univ Frankfurt, Inst Expt Neurobiol, D-6000 Frankfurt, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Hosp, Sect Mol Neurogenet, Frankfurt, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 1997 BP 510 EP 510 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599701997 ER PT J AU Ishiguro, H Liu, Q Uhi, GR AF Ishiguro, H Liu, Q Uhi, GR TI Fine-mapping of a Chromosome 7 substance abuse vulnerability locus implicates NrCAM gene regulatory regions. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIDA, Dept Mol Neurobiol, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2005 BP 511 EP 511 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702004 ER PT J AU van der Walt, JM Martin, ER Scott, WK Zhang, F Fujiwara, K Kittappa, R Nance, MA Hubble, JP Koller, WC Pahwa, R Stern, M Hiner, BC Jankovic, J Goetz, CG Small, GW Mastaglia, F Middleton, LT Pericak-Vance, MA Vance, JM AF van der Walt, JM Martin, ER Scott, WK Zhang, F Fujiwara, K Kittappa, R Nance, MA Hubble, JP Koller, WC Pahwa, R Stern, M Hiner, BC Jankovic, J Goetz, CG Small, GW Mastaglia, F Middleton, LT Pericak-Vance, MA Vance, JM TI Association of FGF20 with late-onset Parkinson Disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. NINDS, NIH, Bethesda, MD 20892 USA. RI Scott, William/A-7593-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2015 BP 513 EP 513 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702015 ER PT J AU Lalovic, A Merkens, L Arsenault-Lapierre, G Nowaczyk, M Porter, FD Russell, L Steiner, R Turecki, G AF Lalovic, A Merkens, L Arsenault-Lapierre, G Nowaczyk, M Porter, FD Russell, L Steiner, R Turecki, G TI Serum cholesterol and suicidality in Smith-Lemli-Opitz syndrome heterozygotes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Douglas Hosp, Res Ctr, McGill Grp Suicide Studies, Verdun, PQ H4H 1R3, Canada. Oregon Hlth Sci Univ, Portland, OR 97201 USA. McMaster Univ, Hamilton, ON, Canada. NICHD, Heritable Diorders Branch, NIH, Bethesda, MD USA. Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2052 BP 519 EP 519 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702054 ER PT J AU Bektas, A Taub, D Najjar, S Muller, D Ferrucci, L AF Bektas, A Taub, D Najjar, S Muller, D Ferrucci, L TI Search for association with Klotho allele variation and atherosclerosis in the Baltimore Longitudinal Study on Aging. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2076 BP 523 EP 523 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702078 ER PT J AU Feng, J Shibayama, A Glanzmann, C Yan, J Cook, E Craddock, N Jones, I Goldman, D Heston, L Sommer, S AF Feng, J Shibayama, A Glanzmann, C Yan, J Cook, E Craddock, N Jones, I Goldman, D Heston, L Sommer, S TI MECP2 variants in psychiatric diseases: Possible association with autism. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 City Hosp Natl Med Ctr, Dept Mol Genet, Duarte, CA USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Birmingham, Div Neurosci, Queen Elizabeth Psychiat Hosp, Birmingham, W Midlands, England. NIAAA, NIH, Bethesda, MD USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RI Jones, Ian/B-4925-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2078 BP 523 EP 523 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702079 ER PT J AU Pangilinan, F Swanson, D Weiler, A O'Leary, V Parle-McDermott, A Conley, M Cox, C Frey, T Molloy, A Kirke, P Mills, J Scott, J Brody, L AF Pangilinan, F Swanson, D Weiler, A O'Leary, V Parle-McDermott, A Conley, M Cox, C Frey, T Molloy, A Kirke, P Mills, J Scott, J Brody, L TI Transcobalamin II polymorphisms influence plasma levels of vitamin B12 but are not major risk factors for neural tube defects. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, Dublin, Ireland. Trinity Coll Dublin, Dept Biochem, Dublin, Ireland. NICHHD, Dublin, Ireland. Hlth Res Board, Dublin, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2088 BP 525 EP 525 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702090 ER PT J AU Mineta, M Ishiguro, H Egan, M Taubman, J Kolachana, B Rowe, T Lipsky, R Uhl, GR Weinberger, DR Goldman, D AF Mineta, M Ishiguro, H Egan, M Taubman, J Kolachana, B Rowe, T Lipsky, R Uhl, GR Weinberger, DR Goldman, D TI epsilon-sarcoglycan, a gene in which causes Myoclonus-Dystonia Syndrome, may also contain Schizophrenia vulnerability variants SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIAAA, Lab Neurogenet, NIH, Rockville, MD 20852 USA. NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2100 BP 527 EP 527 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702102 ER PT J AU Gornick, M Addington, AM Sporn, A Gogtay, N Greenstein, D Lenane, M Gochman, P Weinberger, B Rapoport, JL Straub, RE AF Gornick, M Addington, AM Sporn, A Gogtay, N Greenstein, D Lenane, M Gochman, P Weinberger, B Rapoport, JL Straub, RE TI Polymorphisms in dysbindin (DTNBP1, 6p22.3) are associated with intermediate phenotypes measured by the Premorbid Adjustment Scale (PAS) in cases of childhood onset psychosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIMH, NIH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2113 BP 529 EP 529 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702112 ER PT J AU Addington, AM Langefeld, CD Zandi, PP DePaulo, J Numberger, J Reich, T Gershon, E McInnis, MG AF Addington, AM Langefeld, CD Zandi, PP DePaulo, J Numberger, J Reich, T Gershon, E McInnis, MG TI Evidence for gene-gene interaction in susceptibility to bipolar disorder. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD USA. Indiana Univ, Indianapolis, IN 46204 USA. Washington Univ, St Louis, MO USA. Univ Chicago, Chicago, IL 60637 USA. RI McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2118 BP 530 EP 530 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702120 ER PT J AU Lwin, AA Orvisky, E Eblan, M Sidransky, E AF Lwin, AA Orvisky, E Eblan, M Sidransky, E TI Glucocerebrosidase mutations in subjects with Parkinson disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIMH, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Med Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2115 BP 530 EP 530 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702116 ER PT J AU Remmers, E Balow, J Li, W Aksentijevich, I Lee, A Damle, A Chen, W Amos, C Gregersen, P Kastner, D AF Remmers, E Balow, J Li, W Aksentijevich, I Lee, A Damle, A Chen, W Amos, C Gregersen, P Kastner, D TI Possible association of a 14 kb haplotype block from the receptor activator of NF-kappa B (RANK) gene with susceptibility to rheumatoid arthritis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIAMS, Genet & Genom Branch, Bethesda, MD USA. N Shore Long Isl Jewish Res Inst, Manhasset, NY USA. Univ Texas, MD Anderson Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2156 BP 536 EP 536 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702157 ER PT J AU Peck, EC Mohlke, KL Jackson, AU Suh, Y Scott, LJ Tuomilehto, J Bergman, RN Boehnke, M Collins, FS AF Peck, EC Mohlke, KL Jackson, AU Suh, Y Scott, LJ Tuomilehto, J Bergman, RN Boehnke, M Collins, FS CA FUSION Study Grp TI Assessing the role of the mitochondrial genome in type 2 diabetes mellitus and related traits in Finns. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Natl Publ Hlth Inst, Helsinki, Finland. Univ So Calif, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2164 BP 538 EP 538 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702167 ER PT J AU Zhu, G Brooks, PJ Mash, DC Goldman, D AF Zhu, G Brooks, PJ Mash, DC Goldman, D TI Differential allele expression of MPDZ - A candidate gene for alcohol withdrawal liability. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Miami, Dept Neurol, Miami, FL 33136 USA. Changhai Hosp, Shanghai 200433, Peoples R China. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2185 BP 541 EP 541 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702184 ER PT J AU Tang, J Stern-Nezer, S Liu, P Matyakhina, L Luban, N Kaler, SG AF Tang, J Stern-Nezer, S Liu, P Matyakhina, L Luban, N Kaler, SG TI Mutation in GPIb beta impairs assembly of the platelet von Willebrand factor receptor and causes Bernard-Souller syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, Unite Pediat Genet, LCG, NIH, Bethesda, MD USA. NICHD, Sect Genet & Endocrinol, DEB, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2286 BP 558 EP 558 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702285 ER PT J AU Hatchwell, E Tommerup, N Kristoffersson, U Stanyon, R Kantarci, S AF Hatchwell, E Tommerup, N Kristoffersson, U Stanyon, R Kantarci, S TI Joubert syndrome: a patient with a de novo t(2;22)(q13;q11.1). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Univ Copenhagen, Panum Inst, IMBG, Dpt Med Genet, DK-1168 Copenhagen, Denmark. Univ Lund Hosp, Dpt Clin Genet, S-22185 Lund, Sweden. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2334 BP 566 EP 566 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702333 ER PT J AU Aksentijevich, I Austin, F Chae, JJ Mansky, RG Kastner, DL AF Aksentijevich, I Austin, F Chae, JJ Mansky, RG Kastner, DL TI Neonatal Onset Multisystem Inflammatory Disease (NOMID): further evidence for genetic heterogeneity and search for novel additional NOMID causing genes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA. NIAMS, Off Clin Director, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2352 BP 569 EP 569 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702351 ER PT J AU Sambuughin, N Christodoulou, K Holley, H Tsingis, M Sivakumar, K Goldfarb, L Nicholson, G AF Sambuughin, N Christodoulou, K Holley, H Tsingis, M Sivakumar, K Goldfarb, L Nicholson, G TI Charcot-Marie-Tooth type 2D in a large Australian family of English origin is associated with a novel (H418A) mutation in the glycyl tRNA synthetase gene SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Barrow Neurol Inst, Phoenix, AZ 85013 USA. Cyprus Inst Neurol & Genet, Nicosia, Cyprus. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2360 BP 571 EP 571 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702361 ER PT J AU Wise, CA Smith, EJ Bennett, LB Zhang, D Wood, G Kastner, DL Pascual, VM AF Wise, CA Smith, EJ Bennett, LB Zhang, D Wood, G Kastner, DL Pascual, VM TI Characterization of the PSTPIP1-mediated inflammatory pathway involved in PAPA syndrome, an autoinflammatory disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Texas Scottish Rite Hosp Children, Seay Res Ctr, Dallas, TX 75219 USA. Univ Texas, SW Med Sch, Dallas, TX 75230 USA. Baylor Inst Immunol Res, Dallas, TX USA. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2361 BP 571 EP 571 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702364 ER PT J AU Dagvadorj, A Olive, M Urtizberea, JA Halle, M Shatunov, A Bonnemann, C Park, KY Goebel, H Ferrer, I Vicart, P Dalakas, M Goldfarb, L AF Dagvadorj, A Olive, M Urtizberea, JA Halle, M Shatunov, A Bonnemann, C Park, KY Goebel, H Ferrer, I Vicart, P Dalakas, M Goldfarb, L TI A West European cluster of severe cardiac and skeletal myopathy associated with a de novo R406W mutation in desmin. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NINDS, NIH, Bethesda, MD 20892 USA. Hosp Liobregat, Ciutat Sanitana Univ Bellvitge, Inst Neuropatol, Barcelona, Spain. Hop Haymond Poincare, Garches, France. Univ Gottingen, Med Klin, D-3400 Gottingen, Germany. Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. Univ Mainz, Med Ctr, Dept Neuropathol, Mainz, Germany. Fac Med Pitie Salpetriere, Lab Cytosquelette & Dev, Paris, France. RI Shatunov, Aleksey/E-6946-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2389 BP 575 EP 575 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702390 ER PT J AU Shatunov, A Pagan, F Fridman, E Leib, J Hallett, M Goldfarb, L AF Shatunov, A Pagan, F Fridman, E Leib, J Hallett, M Goldfarb, L TI Probable mechanism of trinucleotide repeat expansion-in a patient with SCA17. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NINDS, NIH, Bethesda, MD 20892 USA. RI Shatunov, Aleksey/E-6946-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2457 BP 587 EP 587 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702460 ER PT J AU Wang, T Zhang, L Obie, C Boytner, P Schwartz, C Wright, A Trent, J Valle, D AF Wang, T Zhang, L Obie, C Boytner, P Schwartz, C Wright, A Trent, J Valle, D TI Reduced expression of proteolipid protein 2 in XLMR patients with mild mental retardation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Clemson Univ, Clemson, SC 29631 USA. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. NHGRI, Bethesda, MD 20892 USA. NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2471 BP 589 EP 589 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702472 ER PT J AU Hanson, RL Knowler, WC AF Hanson, RL Knowler, WC TI Linkage analysis with adjustment for associated marker genotypes in fine-mapping studies. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIDDK, DAES, Phoenix, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2574 BP 607 EP 607 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702576 ER PT J AU Yao, Y Sorant, AJM Wilson, AF AF Yao, Y Sorant, AJM Wilson, AF TI Effects of ascertainment on the power of variations of the Haseman-Elston method for a quantitative trait. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. NHGRI, IDRB, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2580 BP 608 EP 608 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702582 ER PT J AU Presciuttini, S Toni, C Spinetti, I Domenici, R Bailey-Wilson, JE AF Presciuttini, S Toni, C Spinetti, I Domenici, R Bailey-Wilson, JE TI The number of STR markers required to resolve relationships between pairs individuals. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Univ Pisa, Dept Biomed, I-56127 Pisa, Italy. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Univ Pisa, Unit Legal Med, I-56100 Pisa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2586 BP 609 EP 609 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702588 ER PT J AU Morris, R Martin, E Kaplan, N AF Morris, R Martin, E Kaplan, N TI Family-based tests of association for X-linked markers SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2630 BP 616 EP 616 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702631 ER PT J AU Raben, N Danon, M Gilbert, A Nagaraju, K Plotz, P AF Raben, N Danon, M Gilbert, A Nagaraju, K Plotz, P TI Replacing a deficient enzyme in Pompe disease: two approaches, one result. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NIAMS, ARB, NIH, Bethesda, MD USA. Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2674 BP 624 EP 624 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702677 ER PT J AU Banikazemi, M Schiffmann, R Bultas, J Linthorst, GE Packman, S Sorensen, SA Wilcox, WR Desnick, RJ AF Banikazemi, M Schiffmann, R Bultas, J Linthorst, GE Packman, S Sorensen, SA Wilcox, WR Desnick, RJ TI Natural history of Fabry disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 Mt Sinai Sch Med, New York, NY USA. NIH, DMNB, Bethesda, MD 20892 USA. Univ Hosp, Prague, Czech Republic. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Copenhagen, DK-1168 Copenhagen, Denmark. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2698 BP 628 EP 628 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702701 ER PT J AU Letocha, AD Cintas, HL Paul, SM Gerber, NL Marini, JC AF Letocha, AD Cintas, HL Paul, SM Gerber, NL Marini, JC TI Controlled trial of Pamidronate in children with types III and IVOI: Lack of effect on motor function and pain. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CALIFORNIA SP Amer Soc Human Genet C1 NICHD, BEMB, NIH, Bethesda, MD USA. NIH, Dept Rehabil Med, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 MA 2700 BP 628 EP 628 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 726LC UT WOS:000185599702702 ER PT J AU Martin, ER Bass, MP Hauser, ER Kaplan, NL AF Martin, ER Bass, MP Hauser, ER Kaplan, NL TI Accounting for linkage in family-based tests of association with missing parental genotypes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PEDIGREE DISEQUILIBRIUM TEST; TRANSMISSION/DISEQUILIBRIUM TEST; PARKINSON-DISEASE; TAU-GENE; HAPLOTYPE; TRANSMISSION; POPULATION AB In studies of complex diseases, a common paradigm is to conduct association analysis at markers in regions identified by linkage analysis, to attempt to narrow the region of interest. Family-based tests for association based on parental transmissions to affected offspring are often used in fine-mapping studies. However, for diseases with late onset, parental genotypes are often missing. Without parental genotypes, family-based tests either compare allele frequencies in affected individuals with those in their unaffected siblings or use siblings to infer missing parental genotypes. An example of the latter approach is the score test implemented in the computer program TRANSMIT. The inference of missing parental genotypes in TRANSMIT assumes that transmissions from parents to affected siblings are independent, which is appropriate when there is no linkage. However, using computer simulations, we show that, when the marker and disease locus are linked and the data set consists of families with multiple affected siblings, this assumption leads to a bias in the score statistic under the null hypothesis of no association between the marker and disease alleles. This bias leads to an inflated type I error rate for the score test in regions of linkage. We present a novel test for association in the presence of linkage (APL) that correctly infers missing parental genotypes in regions of linkage by estimating identity-by-descent parameters, to adjust for correlation between parental transmissions to affected siblings. In simulated data, we demonstrate the validity of the APL test under the null hypothesis of no association and show that the test can be more powerful than the pedigree disequilibrium test and family-based association test. As an example, we compare the performance of the tests in a candidate-gene study in families with Parkinson disease. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Martin, ER (reprint author), Duke Univ, Med Ctr, Dept Med, 595 LaSalle St,Box 3468, Durham, NC 27710 USA. FU NIA NIH HHS [R01 AG020135, R01 AG20135]; NIMH NIH HHS [R01 MH59528, R01 MH059528]; NINDS NIH HHS [5 P50 NS39764-03, P50 NS039764] NR 25 TC 69 Z9 69 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 BP 1016 EP 1026 DI 10.1086/378779 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 742AR UT WOS:000186493400004 PM 14551902 ER PT J AU Zhang, JH Rowe, WL Clark, AG Buetow, KH AF Zhang, JH Rowe, WL Clark, AG Buetow, KH TI Genomewide distribution of high-frequency, completely mismatching SNP haplotype pairs observed to be common across human populations SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DROSOPHILA-MELANOGASTER; BLOCKS AB Knowledge of human haplotype structure has important implications for strategies of disease-gene mapping and for understanding human evolutionary history. Many attributes of SNPs and haplotypes appear to exhibit highly nonrandom behavior, suggesting past operation of selection or other nonneutral forces. We report the exceptional abundance of a particular haplotype pattern in which two high-frequency haplotypes have different alleles at every SNP site (hence the name "yin yang haplotypes"). Analysis of common haplotypes in 62 random genomic loci and 85 gene coding regions in humans shows that the proportion of the genome spanned by yin yang haplotypes is 75%-85%. Population data of 28 genomic loci in Drosophila melanogaster reveal a similar pattern. The high recurrence (greater than or equal to85%) of these haplotype patterns in four distinct human populations suggests that the yin yang haplotypes are likely to predate the African diaspora. The pattern initially appeared to suggest deep population splitting or maintenance of ancient lineages by selection; however, coalescent simulation reveals that the yin yang phenomenon can be explained by strictly neutral evolution in a well-mixed population. C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA. RP Zhang, JH (reprint author), NCI, Lab Populat Genet, NIH, 8424 Helgerman Court,Room 101,MSC 8302, Bethesda, MD 20892 USA. NR 12 TC 75 Z9 76 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 BP 1073 EP 1081 DI 10.1086/379154 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 742AR UT WOS:000186493400009 PM 14560401 ER PT J AU Zhu, M Yang, T Wei, S DeWan, AT Morell, RJ Elfenbein, JL Fisher, RA Leal, SM Smith, RJH Friderici, KH AF Zhu, M Yang, T Wei, S DeWan, AT Morell, RJ Elfenbein, JL Fisher, RA Leal, SM Smith, RJH Friderici, KH TI Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HEARING-LOSS; BINDING-SITE; HAIR-CELLS; COCHLEAR PATHOLOGY; CUTICULAR PLATE; 2 GENOTYPES; LATE-ONSET; INNER-EAR; FILAMENTS; PROTEIN AB Age-related hearing loss (presbycusis) is a significant problem in the population. The genetic contribution to age-related hearing loss is estimated to be 40%-50%. Gene mutations that cause nonsyndromic progressive hearing loss with early onset may provide insight into the etiology of presbycusis. We have identified four families segregating an autosomal dominant, progressive, sensorineural hearing loss phenotype that has been linked to chromosome 17q25.3. The critical interval containing the causative gene was narrowed to similar to2 million bp between markers D17S914 and D17S668. Cochlear-expressed genes were sequenced in affected family members. Sequence analysis of the gamma-actin gene (ACTG1) revealed missense mutations in highly conserved actin domains in all four families. These mutations change amino acids that are conserved in all actins, from protozoa to mammals, and were not found in 1100 chromosomes from normal hearing individuals. Much of the specialized ultrastructural organization of the cells in the cochlea is based on the actin cytoskeleton. Many of the mutations known to cause either syndromic or nonsyndromic deafness occur in genes that interact with actin (e.g., the myosins, espin, and harmonin). The mutations we have identified are in various binding domains of actin and are predicted to mildly interfere with bundling, gelation, polymerization, or myosin movement and may cause hearing loss by hindering the repair or stability of cochlear cell structures damaged by noise or aging. This is the first description of a mutation in cytoskeletal, or nonmuscle, actin. C1 Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. Michigan State Univ, Genet Program, E Lansing, MI 48824 USA. Michigan State Univ, Dept Audiol & Speech Sci, E Lansing, MI 48824 USA. Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. Univ Iowa, Interdept Genet Program, Iowa City, IA USA. Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Friderici, KH (reprint author), Michigan State Univ, Dept Microbiol & Mol Genet, 5163 Biomed Phys Sci Bldg, E Lansing, MI 48824 USA. OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [R29 DC003594, Z01 DC000039, R01 DC003544, R01-DC04568, DC03594, R01 DC004568, 1Z01DC00039-06, R01 DC003594, R01-DC03544] NR 41 TC 101 Z9 109 U1 1 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2003 VL 73 IS 5 BP 1082 EP 1091 DI 10.1086/379286 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 742AR UT WOS:000186493400010 PM 13680526 ER PT J AU Reynolds, JC Agodoa, LY Yuan, CM Abbott, KC AF Reynolds, JC Agodoa, LY Yuan, CM Abbott, KC TI Thrombotic microangiopathy after renal transplantation in the United States SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hemolytic uremic syndrome (HUS); thrombotic thrombocytopenic purpura; thrombotic microangiopathy (TMA); immunosuppression; recurrence; age; complications; tacrolimus; cyclosporine; calcineurin inhibitor; sirolimus; United States Renal Data System (USRDS) ID HEMOLYTIC-UREMIC SYNDROME; SIROLIMUS-BASED IMMUNOSUPPRESSION; THROMBOCYTOPENIC PURPURA; CYCLOSPORINE-A; MARROW TRANSPLANTATION; KIDNEY-TRANSPLANTATION; ALLOGRAFT RECIPIENT; PROGNOSTIC FACTORS; DISEASE; RECURRENCE AB Background: Analysis of the incidence, time to event, and risk factors for thrombotic microangiopathy (TMA) after renal transplantation (RT), has not been reported in a national population. Methods: This is a historical cohort study of 15,870 RT recipients in the United States Renal Data System (USRDS) with Medicare as their primary payer between January 1, 1998, and July 31, 2000, followed until December 31, 2000. Patients with Medicare claims with a diagnosis of TMA (International Classification of Diseases, 9th Revision, codes 283.11x or 446.6x) after RT were assessed by Cox regression. Results: Among patients with end-stage renal disease owing to hemolytic uremic syndrome (HUS), 29.2% later had TMA versus 0.8% of patients with ESRD owing to other causes. The incidence of TMA in RT recipients was 5.6 episodes per 1,000 person-years (PY; 189/1,000 PY; for recurrent TMA versus 4.9/1,000 PY for de novo TMA). The risk of TMA was highest for the first 3 months after transplant. Risk factors for de novo TMA included younger recipient age, older donor age, female recipient, and initial use of sirolimus. Patient survival rate after TMA was approximately 50% at 3 years. Conclusion: De novo TMA is uncommon and may occur later after RT than previously reported. Risk factors for de novo TMA were also identified. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDK, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 43 TC 95 Z9 100 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2003 VL 42 IS 5 BP 1058 EP 1068 DI 10.1053/S0272-6386(03)01019-9 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 742AH UT WOS:000186492200021 PM 14582050 ER PT J AU Cohen, MM Turner, JT Biesecker, LG AF Cohen, MM Turner, JT Biesecker, LG TI Proteus syndrome: Misdiagnosis with PTEN mutations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Editorial Material ID GERMLINE MUTATION; HEMIHYPERTROPHY; MOSAICISM C1 Dalhousie Univ, Dept Oral & Maxillofacial Surg, Halifax, NS B3H 3J5, Canada. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, MM (reprint author), Dalhousie Univ, Dept Oral & Maxillofacial Surg, Halifax, NS B3H 3J5, Canada. NR 14 TC 27 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 1 PY 2003 VL 122A IS 4 BP 323 EP 324 DI 10.1002/ajmg.a.20474 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 733PU UT WOS:000186010500008 PM 14518070 ER PT J AU Makariou, E Pikis, A Harley, EH AF Makariou, E Pikis, A Harley, EH TI Cystic hygroma of the neck: Association with a growing venous aneurysm SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID LYMPHANGIOMAS; CHILDREN AB Venous anomalies are rarely seen with cystic hygromas. We describe an unusual case of cystic hygroma of the neck associated with a saccular venous aneurysm that was increasing in size. A multi-modality examination of the neck-including CT, Doppler sonography, and MR imaging-revealed multiloculated cystic lesions bilaterally with predominance on the left side. A saccular venous aneurysm was noted within one of the sacs. Comparison with previous CT images showed that the aneurysm enlarged from 0.8 X 0.5 x 1.5 cm to 3.0 x 1.3 X 2.1 cm over 2 years. Identification of these malformations before surgery is critical. C1 Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Bethesda, MD USA. RP Makariou, E (reprint author), Georgetown Univ, Med Ctr, Dept Radiol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 10 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2003 VL 24 IS 10 BP 2102 EP 2104 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 746KD UT WOS:000186744800034 PM 14625242 ER PT J AU Kalache, K Romero, R Goncalves, LF Chaiworapongsa, T Espinoza, J Schoen, ML Treadwell, MC Lee, W AF Kalache, K Romero, R Goncalves, LF Chaiworapongsa, T Espinoza, J Schoen, ML Treadwell, MC Lee, W TI Three-dimensional color power imaging of the fetal hepatic circulation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE prenatal diagnosis; ultrasonography; three-dimensional power Doppler; ductus venosus; umbilical vein; congenital anomalies; fetal hepatic circulation ID RIGHT UMBILICAL VEIN; DUCTUS VENOSUS AGENESIS; GROWTH-RESTRICTED FETUS; PRENATAL-DIAGNOSIS; CONGENITAL ABSENCE; HYDROPS-FETALIS; RIGHT ATRIUM; IN-UTERO; ULTRASONOGRAPHIC DIAGNOSIS; DOPPLER ULTRASONOGRAPHY AB OBJECTIVE: The purpose of this study was to describe the use of three-dimensional power Doppler ultrasonography to identify vascular congenital anomalies of fetal portosystemic and umbilical venous systems. STUDY DESIGN: In a prospective study, the hepatic and umbilical venous systems were examined in 390 fetuses with two-dimensional ultrasonography, color, and spectral Doppler imaging. Fetuses suspected to have anomalies of the portal system and ductus venosus were additionally examined with three-dimensional power Doppler ultrasonography. RESULTS: Vascular anomalies were identified in 8 fetuses (absent ductus venosus, n = 4; direct connection between the umbilical vein and the right atrium, n = 2; and direct connection between the umbilical vein and the inferior vena cava, n = 2) out of the 310 in which the venous system could be adequately imaged (prevalence = 2.6%). Three-dimensional power Doppler imaging showed the course of the umbilical vein, its relationship to the portosystemic circulation, and whether a ductus venosus was present. CONCLUSION: Three-dimensional power Doppler ultrasonography can be used to image normal fetal hepatic and portal circulation, as well as identify anomalies of the fetal portosystemic and umbilical venous systems. C1 NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. RP Romero, R (reprint author), Wayne State Hosp, Hutzel Hosp, NICHD, DHHS,NIH,Perinatal Res Branch,Dept Obstet & Gynec, 4707 St Antoine Blvd, Detroit, MI 48201 USA. NR 42 TC 18 Z9 21 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2003 VL 189 IS 5 BP 1401 EP 1406 DI 10.1067/S0002-9378(03)00774-9 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 750EZ UT WOS:000186979500035 PM 14634577 ER PT J AU McAllister, RD Singh, Y du Bois, WD Potter, M Boehm, T Meeker, ND Fillmore, PD Anderson, LM Poynter, ME Teuscher, C AF McAllister, RD Singh, Y du Bois, WD Potter, M Boehm, T Meeker, ND Fillmore, PD Anderson, LM Poynter, ME Teuscher, C TI Susceptibility to anthrax lethal toxin is controlled by three linked quantitative trait loci SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BACILLUS-ANTHRACIS; AUTOIMMUNE-DISEASE; GENETIC-CONTROL; KINASE-KINASE; IN-VIVO; MACROPHAGES; RESISTANCE; MICE; ENCEPHALOMYELITIS; IDENTIFICATION AB Anthrax lethal toxin (LT) is the principal virulence factor associated with lethal pathologies following infection with Bacillus anthracis. Macrophages are the primary effector cells mediating lethality since macrophage-depleted mice are resistant to LT challenge. Recently, Ltxs1, the gene controlling differential susceptibility of murine macrophages to cytolysis following In vitro exposure to LT, was identified as Kif1c. To directly assess the in vivo role of Kif1c alleles in mortality, we studied a panel of interval-specific recombinant congenic lines carrying various segments of central chromosome 11 derived from LT-resistant DBA/2 mice on the LT-susceptible BALB/c background. The results of this study reveal that mortality is controlled by three linked quantitative trait loci (QTL): Ltxs1/Kif1c (42-43 cM), Ltxs2 (35-37 cM), and Ltxs3 (45-47 cM). The Ltxs3 interval encompasses Nos2, which is an attractive candidate gene for Ltxs3. in this regard, we demonstrate that selective, pharmacologically based inhibition of Nos2 activity in vivo partially overrides genetic resistance to LT and that Nos2 expression as determined by reverse transcription-polymerase chain reaction differs significantly between DBA/2 and BALB/c macrophages. Additionally, to recapitulate dominant resistance to mortality as seen in (BALB/c X DBA/2) F, hybrids, DBA/2 alleles are required at all three QTL. C1 Univ Vermont, Dept Med, Burlington, VT 05405 USA. Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA. Inst Genom & Integrat Biol, Delhi, India. NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD USA. Max Planck Inst Immunobiol, Dept Dev Immunol, Freiburg, Germany. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Illinois, Dept Vet Pathobiol, Urbana, IL 61801 USA. RP Teuscher, C (reprint author), Univ Vermont, Dept Med, C317 Givenm Med Bldg, Burlington, VT 05405 USA. RI Ganju, Shahji/F-3409-2012 FU NIAID NIH HHS [AI 45105] NR 29 TC 35 Z9 35 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 NOV PY 2003 VL 163 IS 5 BP 1735 EP 1741 DI 10.1016/S0002-9440(10)63532-8 PG 7 WC Pathology SC Pathology GA 736AP UT WOS:000186148200008 PM 14578173 ER PT J AU Fueger, PT Heikkinen, S Bracy, DP Malabanan, CM Pencek, RR Laakso, M Wasserman, DH AF Fueger, PT Heikkinen, S Bracy, DP Malabanan, CM Pencek, RR Laakso, M Wasserman, DH TI Hexokinase II partial knockout impairs exercise-stimulated glucose uptake in oxidative muscles of mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE muscle glucose uptake; phosphorylation; transport; distributed control; 2-deoxyglucose ID SKELETAL-MUSCLE; TRANSGENIC MICE; INSULIN; METABOLISM; NIDDM; RAT; LIMITATIONS; INHIBITION; GENE; PHOSPHORYLATION AB Muscle glucose uptake (MGU) is distributively controlled by three serial steps: delivery of glucose to the muscle membrane, transport across the muscle membrane, and intracellular phosphorylation to glucose 6-phosphate by hexokinase (HK). During states of high glucose fluxes such as moderate exercise, the HK activity is of increased importance, since augmented muscle perfusion increases glucose delivery, and increased GLUT4 at the cell membrane increases glucose transport. Because HK II overexpression augments exercise-stimulated MGU, it was hypothesized that a reduction in HK II activity would impair exercise-stimulated MGU and that the magnitude of this impairment would be greatest in tissues with the largest glucose requirement. To this end, mice with a HK II partial knockout (HK+/-) were compared with their wild-type control (WT) littermates during either sedentary or moderate exercise periods. R-g, an index of glucose metabolism, was measured using 2-deoxy-[H-3]glucose. No differences in glucose metabolism were detected between sedentary groups. The increase in Rg due to exercise was impaired in the highly oxidative heart and soleus muscles of HK+/- compared with WT mice (7 +/- 10 vs. 29 +/- 9 and 8 +/- 3 vs. 25 +/- 7 mumol.100 g(-1)-min(-1), respectively). However, the increase in Rg due to exercise was not altered in gastrocnemius and superficial vastus lateralis muscles in HK+/- and WT mice (8 +/- 2 vs. 12 +/- 3 and 5 +/- 2 vs. 8 +/- 2 mumol.100 g(-1).min(-1), respectively). In conclusion, MGU is impaired by reductions in HK activity during exercise, a physiological condition characterized by high glucose flux. This impairment is critically dependent on the tissue's glucose metabolic rate and correlates with tissue oxidative capacity. C1 Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. Univ Kuopio, AI Virtanen Inst, FIN-70211 Kuopio, Finland. Univ Kuopio, Dept Biochem & Biotechnol, FIN-70211 Kuopio, Finland. Univ Kuopio, Dept Med, FIN-70211 Kuopio, Finland. RP Fueger, PT (reprint author), Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. RI Heikkinen, Sami/L-1460-2013 OI Heikkinen, Sami/0000-0002-6083-2402 FU NIDDK NIH HHS [R01 DK-54902, U24 DK-59637] NR 33 TC 46 Z9 47 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E958 EP E963 DI 10.1152/ajpendo.00190.2003 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500004 PM 12865258 ER PT J AU Faris, OP Evans, FJ Dick, AJ Raman, VK Ennis, DB Kass, DA McVeigh, ER AF Faris, OP Evans, FJ Dick, AJ Raman, VK Ennis, DB Kass, DA McVeigh, ER TI Endocardial versus epicardial electrical synchrony during LV free-wall pacing SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE resynchronization; mapping; heart failure ID INTRAVENTRICULAR-CONDUCTION DELAY; CONGESTIVE-HEART-FAILURE; BUNDLE-BRANCH BLOCK; DILATED CARDIOMYOPATHY; VENTRICULAR CONTRACTION; RESYNCHRONIZATION; ACTIVATION; STRAIN AB Cardiac resynchronization therapy has been most typically achieved by biventricular stimulation. However, left ventricular (LV) free-wall pacing appears equally effective in acute and chronic clinical studies. Recent data suggest electrical synchrony measured epicardially is not required to yield effective mechanical synchronization, whereas endocardial mapping data suggest synchrony ( fusion with intrinsic conduction) is important. To better understand this disparity, we simultaneously mapped both endocardial and epicardial electrical activation during LV free-wall pacing at varying atrioventricular delays ( AV delay 0 - 150 ms) in six normal dogs with the use of a 64-electrode LV endocardial basket and a 128-electrode epicardial sock. The transition from dyssynchronous LV-paced activation to synchronous RA-paced activation was studied by constructing activation time maps for both endo-and epicardial surfaces as a function of increasing AV delay. The AV delay at the transition from dyssynchronous to synchronous activation was defined as the transition delay (AV(t)). AV(t) was variable among experiments, in the range of 44 - 93 ms on the epicardium and 47 - 105 ms on the endocardium. Differences in endo- and epicardial AV(t) were smaller ( - 17 to + 12 ms) and not significant on average ( - 5.0 +/- 5.2 ms). In no instance was the transition to synchrony complete on one surface without substantial concurrent transition on the other surface. We conclude that both epicardial and endocardial synchrony due to fusion of native with ventricular stimulation occur nearly concurrently. Assessment of electrical epicardial delay, as often used clinically during cardiac resynchronization therapy lead placement, should provide adequate assessment of stimulation delay for inner wall layers as well. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. RP McVeigh, ER (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,Rm B1D416, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL004609-08] NR 18 TC 23 Z9 24 U1 0 U2 0 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 NOV PY 2003 VL 285 IS 5 BP H1864 EP H1870 DI 10.1152/ajpheart.00282.2003 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 732NE UT WOS:000185951800008 PM 12855422 ER PT J AU Mammen, PPA Kanatous, SB Yuhanna, IS Shaul, PW Garry, MG Balaban, RS Garry, DJ AF Mammen, PPA Kanatous, SB Yuhanna, IS Shaul, PW Garry, MG Balaban, RS Garry, DJ TI Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE nitric oxide; knockout mice; cardiac systolic function ID NITRIC-OXIDE SYNTHASE; CYTOCHROME-C-OXIDASE; MYOCARDIAL OXYGEN-CONSUMPTION; ISOLATED CARDIAC MYOCYTES; CONGESTIVE-HEART-FAILURE; RESPIRATORY-CHAIN; ENDOTHELIAL-CELLS; GENE-EXPRESSION; CA2+ CURRENT; RAT-HEART AB Myoglobin-deficient mice are viable and have preserved cardiac function due to their ability to mount a complex compensatory response involving increased vascularization and the induction of the hypoxia gene program (hypoxia-inducible factor-1alpha, endothelial PAS, heat shock protein27, etc.). To further define and explore functional roles for myoglobin, we challenged age- and gender-matched wild-type and myoglobin-null mice to chronic hypoxia (10% oxygen for 1 day to 3 wk). We observed a 30% reduction in cardiac systolic function in the myoglobin mutant mice exposed to chronic hypoxia with no changes observed in the wild-type control hearts. The cardiac dysfunction observed in the hypoxic myoglobin-null mice was reversible with reexposure to normoxic conditions and could be prevented with treatment of an inhibitor of nitric oxide (NO) synthases. These results support the conclusion that hypoxia-induced cardiac dysfunction in myoglobin-null mice occurs via a NO-mediated mechanism. Utilizing enzymatic assays for NO synthases and immunohistochemical analyses, we observed a marked induction of inducible NO synthase in the hypoxic myoglobin mutant ventricle compared with the wild-type hypoxic control ventricle. These new data establish that myoglobin is an important cytoplasmic cardiac hemoprotein that functions in regulating NO homeostasis within cardiomyocytes. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA. NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Univ Texas, SW Med Ctr, Dept Internal Med, NB11-118A,5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM daniel.garry@utsouthwestern.edu RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 FU NHLBI NIH HHS [HL-63788] NR 65 TC 22 Z9 24 U1 0 U2 5 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 NOV PY 2003 VL 285 IS 5 BP H2132 EP H2141 DI 10.1152/ajpheart.00147.2003 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 732NE UT WOS:000185951800039 PM 12881221 ER PT J AU Shukla, A Jung, M Stern, M Fukagawa, NK Taatjes, DJ Sawyer, D Van Houten, B Mossman, BT AF Shukla, A Jung, M Stern, M Fukagawa, NK Taatjes, DJ Sawyer, D Van Houten, B Mossman, BT TI Asbestos induces mitochondrial DNA damage and dysfunction linked to the development of apoptosis SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE mitochondria; mesothelial cells; oxidants ID PULMONARY EPITHELIAL-CELLS; OXIDATIVE DAMAGE; CROCIDOLITE ASBESTOS; MESOTHELIAL CELLS; DEGENERATIVE DISEASES; HYDROGEN-PEROXIDE; GENE-EXPRESSION; REPAIR; MECHANISMS; OXIDANTS AB To test the hypothesis that asbestos-mediated cell injury is mediated through an oxidant-dependent mitochondrial pathway, isolated mesothelial cells were examined for mitochondrial DNA damage as determined by quantitative PCR. Mitochondrial DNA damage occurred at fourfold lower concentrations of crocidolite asbestos compared with concentrations required for nuclear DNA damage. DNA damage by asbestos was preceded by oxidant stress as shown by confocal scanning laser microscopy using MitoTracker Green FM and the oxidant probe Redox Sensor Red CC-1. These events were associated with dose-related decreases in steady-state mRNA levels of cytochrome c oxidase, subunit 3 ( COIII), and NADH dehydrogenase 5. Subsequently, dose-dependent decreases in formazan production, an indication of mitochondrial dysfunction, increased mRNA expression of pro- and antiapoptotic genes, and increased numbers of apoptotic cells were observed in asbestos-exposed mesothelial cells. The possible contribution of mitochondrial-derived pathways to asbestos-induced apoptosis was confirmed by its significant reduction after pretreatment of cells with a caspase-9 inhibitor. Apoptosis was decreased in the presence of catalase. Last, use of HeLa cells transfected with a mitochondrial transport sequence targeting the human DNA repair enzyme 8-oxoguanine DNA glycosylase to mitochondria demonstrated that asbestos-induced apoptosis was ameliorated with increased cell survival. Studies collectively indicate that mitochondria are initial targets of asbestos-induced DNA damage and apoptosis via an oxidant-related mechanism. C1 Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ Texas, Galveston, TX 77555 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Mossman, BT (reprint author), Univ Vermont, Coll Med, Dept Pathol, 89 Beaumont Ave, Burlington, VT 05405 USA. FU NHLBI NIH HHS [P01-HL-67004]; NIEHS NIH HHS [R01 ES/HL09213] NR 41 TC 47 Z9 49 U1 0 U2 5 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 NOV 1 PY 2003 VL 285 IS 5 BP L1018 EP L1025 DI 10.1152/ajplung.00038.2003 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 730HA UT WOS:000185822300006 PM 12909582 ER PT J AU Yaghi, A Bradbury, JA Zeldin, DC Mehta, S Bend, JR McCormack, DG AF Yaghi, A Bradbury, JA Zeldin, DC Mehta, S Bend, JR McCormack, DG TI Pulmonary cytochrome P-450 2J4 is reduced in a rat model of acute Pseudomonas pneumonia SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE cytochrome P-450; inflammation; Western blotting; cytochrome P-2J4 and cytochrome P-4A protein content; peptide antibodies ID ARACHIDONIC-ACID METABOLISM; NITRIC-OXIDE; VASCULAR REACTIVITY; MOLECULAR-CLONING; EPOXYEICOSATRIENOIC ACIDS; FUNCTIONAL-SIGNIFICANCE; LIVER CYTOCHROME-P450; EXTRAHEPATIC TISSUES; HYPERDYNAMIC SEPSIS; EXPRESSION AB We previously reported that the levels of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are depressed in microsomes prepared from lungs of rats with acute Pseudomonas pneumonia. We also showed a potential role for cytochrome P-450 (CYP) metabolites of arachidonic acid ( AA) in contractile responses of both normal pulmonary arteries and pulmonary arteries from rats with pneumonia. The CYP2J subfamily enzymes ( endogenous source of EETs and HETEs) are constitutively expressed in human and rat lungs where they are localized in vascular smooth muscle and endothelium. The purpose of this study was to determine if CYP2J proteins are modified in pneumonia. Pseudomonas organisms were injected via a tracheostomy in the lungs of rats. Later ( 44 h), lungs were frozen, and microsomes were prepared from pneumonia and control rat lung homogenates. Lung microsomal proteins were then immunoblotted with anti-CYP2B1/2B2, anti-CYP4A, anti-CYP2J9pep2 ( which reacts with rat CYP2J3), anti-CYP2J6pep1 ( which reacts with rat CYP2J4), anti-CYP2J2pep4, or anti-CYP2J2pep3 ( both of which react with all known CYP2J isozymes). Western blotting revealed a prominent 55-kDa band with anti-CYP2J2pep3, anti-CYP2J2pep4, and anti-CYP2J6pep1 ( but not anti-CYP2J9pep2) that was reduced in pneumonia compared with control lung microsomes. The CYP2B bands ( 51 52 kDa) were less prominent and not different between pneumonia and control lungs. CYP4A proteins (20-HETE sources) were not detected in rat lung microsomes. Therefore, rat lung contains a protein with immunological characteristics similar to CYP2J4, and this CYP is reduced after pneumonia. We speculate that CYP2J ( but not CYP2B) enzymes and their AA metabolic products ( EETs) are involved in the modulation of pulmonary vascular tone in pneumonia in rats. C1 London Hlth Sci Ctr, Lawson Hlth Res Inst, AC Burton Vasc Biol Lab, London, ON N6A 4G5, Canada. Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1, Canada. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP McCormack, DG (reprint author), London Hlth Sci Ctr, Lawson Hlth Res Inst, AC Burton Vasc Biol Lab, Victoria Campus,375 South St, London, ON N6A 4G5, Canada. NR 55 TC 11 Z9 13 U1 0 U2 0 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 NOV 1 PY 2003 VL 285 IS 5 BP L1099 EP L1105 DI 10.1152/ajplung.00039.2003 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 730HA UT WOS:000185822300014 PM 12882760 ER PT J AU Cadnapaphornchai, MA Summer, SN Falk, S Thurman, JM Knepper, MA Schrier, RW AF Cadnapaphornchai, MA Summer, SN Falk, S Thurman, JM Knepper, MA Schrier, RW TI Effect of primary polydipsia on aquaporin and sodium transporter abundance SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE urinary concentrating ability ID WATER CHANNEL EXPRESSION; URINARY CONCENTRATING ABILITY; INDUCED DOWN-REGULATION; RAT-KIDNEY MEDULLA; NEPHROTIC SYNDROME; COLLECTING DUCT; VASOPRESSIN; DEFECT AB Chronic primary polydipsia (POLY) in humans is associated with impaired urinary concentrating ability. However, the molecular mechanisms responsible for this finding have not been elucidated. The purpose of this study was to examine the effect of chronic primary POLY on water metabolism and renal aquaporin (AQP) water channels and sodium and urea transporter abundance in rats. Primary POLY was induced in male Sprague-Dawley rats by daily administration of 15 g powdered rat chow mixed in 100 ml water for 10 days. Control rats (CTL) received 15 g powdered rat chow per day and ad libitum drinking water. Rats were studied following this period before further intervention and with a 36-h period of water deprivation to examine maximal urinary concentrating ability. At baseline, POLY rats demonstrated significantly greater water intake (100+/-1 vs. 22+/-2 ml/ day, P<0.0001) and urinary output (80 +/- 1 vs. 11 +/- 1 ml/ day, P<0.0001) and decreased urinary osmolality (159+/-13 vs. 1,365+/-188 mosmol/kgH(2)O, P<0.001) compared with CTL rats. These findings were accompanied by decreased inner medulla AQP-2 protein abundance in POLY rats compared with CTL rats before water deprivation (76 +/- 2 vs. 100 +/- 7% CTL mean, P<0.007). With water deprivation, maximal urinary osmolality was impaired in POLY vs. CTL rats (2,404+/-148 vs. 3,286+/-175 mosmol/kgH(2)O, P<0.0005). This defect occurred despite higher plasma vasopressin concentrations and similar medullary osmolalities in POLY rats. In response to 36-h water deprivation, inner medulla AQP-2 protein abundance was decreased in POLY rats compared with CTL rats (65 +/- 5 vs. 100 +/- 5% CTL mean, P<0.0006). No significant differences were noted in renal protein abundance of either AQP-3 or AQP-4 or sodium and urea transporters. We conclude that the impaired urinary concentrating ability associated with primary POLY in rats is due to impaired osmotic equilibration in the collecting duct that is mediated primarily by decreased AQP-2 protein abundance. C1 Univ Colorado, Sch Med, Dept Med, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Pediat, Denver, CO 80262 USA. NHLBI, Renal Mech Sect, NIH, Bethesda, MD 20892 USA. RP Schrier, RW (reprint author), Univ Colorado, Sch Med, Dept Med, 4200 E 9th Ave,Box B173, Denver, CO 80262 USA. EM Robert.Schrier@UCHSC.EDU FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NIDDK NIH HHS [DK-19928] NR 22 TC 18 Z9 19 U1 0 U2 0 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 NOV 1 PY 2003 VL 285 IS 5 BP F965 EP F971 DI 10.1152/ajprenal.00085.2003 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 729WY UT WOS:000185799100016 PM 12876065 ER PT J AU Li, CL Wang, WD Kwon, TH Knepper, MA Nielsen, S Frokiaer, J AF Li, CL Wang, WD Kwon, TH Knepper, MA Nielsen, S Frokiaer, J TI Altered expression of major renal Na transporters in rats with bilateral ureteral obstruction and release of obstruction SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE proximal tubule; thick ascending limb of Henle's loop; distal convoluted tubule; collecting duct; Na-Cl cotransporters; sodium excretion ID THICK ASCENDING LIMB; K-CL COTRANSPORTER; CORTICAL COLLECTING DUCT; NEPHRON SEGMENTS; DOWN-REGULATION; POSTOBSTRUCTIVE DIURESIS; CONCENTRATING DEFECT; NA+/H+ EXCHANGER; PROXIMAL TUBULE; ALPHA-ENAC AB Urinary tract obstruction impairs urinary concentrating capacity and reabsorption of sodium. To clarify the molecular mechanisms of these defects, expression levels of renal sodium transporters were examined in rats with 24-h bilateral ureteral obstruction (BUO) or at day 3 or 14 after release of BUO (BUO-R). BUO resulted in downregulation of type 3 Na(+)/H(+) exchanger (NHE3) to 41+/-14%, type 2 Na-Pi cotransporter (NaPi-2) to 26+/-6%, Na-K-ATPase to 67+/-8%, type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) to 20+/-7%, and thiazide-sensitive cotransporter (TSC) to 37+/-9%. Immunocytochemistry confirmed downregulation of NHE3, NaPi-2, Na-K-ATPase, BSC-1, and TSC. Consistent with this downregulation, BUO-R was associated with polyuria, reduced urinary osmolality, and increased urinary sodium and phosphate excretion. BUO-R for 3 days caused a persistant downregulation of NHE3 to 53+/-10%, NaPi-2 to 57+/-9%, Na-K-ATPase to 62+/-8%, BSC-1 to 50+/-12%, and TSC to 56+/-16%, which was associated with a marked reduction in the net renal reabsorption of sodium (616+/-54 vs. 944+/-24 mumol.min(-1).kg(-1); P<0.05) and phosphate (6.3 +/- 0.9 vs. 13.1 +/- 0.4 mu mol.min(-1).kg(-1); P<0.05) demonstrating a defect in renal sodium and phosphate reabsorption capacity. Moreover, downregulation of Na-K-ATPase and TSC persisted in BUO-R for 14 days, whereas NHE3, NaPi-2, and BSC-1 were normalized to control levels. In conclusion, downregulation of renal Na transporters in rats with BUO and release of BUO are likely to contribute to the associated urinary concentrating defect, increased urinary sodium excretion, and postobstructive polyuria. C1 Univ Aarhus, Hosp Skejby, Inst Expt Clin Res, Water & Salt Res Ctr, DK-8200 Aarhus N, Denmark. Univ Aarhus, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Univ Aarhus, Hosp Skejby, Dept Clin Physiol, DK-8200 Aarhus N, Denmark. Dongguk Univ, Sch Med, Dept Physiol, Kyungju 780714, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Frokiaer, J (reprint author), Univ Aarhus, Hosp Skejby, Inst Expt Clin Res, Water & Salt Res Ctr, DK-8200 Aarhus N, Denmark. EM JF@IEKF.AU.DK FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 62 TC 32 Z9 32 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 NOV 1 PY 2003 VL 285 IS 5 BP F889 EP F901 DI 10.1151/ajprenal.00170.2003 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 729WY UT WOS:000185799100008 PM 12865255 ER PT J AU Turban, S Wang, XY Knepper, MA AF Turban, S Wang, XY Knepper, MA TI Regulation of NHE3, NKCC2, and NCC abundance in kidney during aldosterone escape phenomenon: role of NO SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE pressure natriuresis; Na/H exchanger 3; Na-K-2Cl cotransporter; Na-Cl cotransporter ID THICK ASCENDING LIMB; NA-CL COTRANSPORTER; PROXIMAL TUBULE; NITRIC-OXIDE; TRANSPORTER ABUNDANCE; ANGIOTENSIN-II; BRUSH-BORDER; HYPERTENSION; ABSORPTION; RAT AB Escape from aldosterone-induced renal NaCl retention is an important homeostatic mechanism in pathophysiological states in which plasma aldosterone levels are inappropriately elevated, e. g., in primary aldosteronism. Our previous studies demonstrated that the escape process occurs largely as a result of a marked suppression of the abundance of the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule but have also demonstrated a paradoxical increase in the protein abundance of the apical Na/H exchanger of the proximal tubule (NHE3). In the present study, we confirmed the increase in NHE3 and also showed that a similar increase in NHE3 protein abundance occurs in escape from ANG II-mediated NaCl retention. To investigate the potential role of nitric oxide (NO) in the observed upregulation of NHE3, we repeated the aldosterone escape experiment with a superimposed infusion of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). L-NAME infusion abolished the increase in NHE3 protein abundance. Furthermore, in a different experiment, NO synthase inhibition uncovered an associated decrease in the abundance of the Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb, not seen with simple aldosterone escape. However, NO synthase inhibition did not block the decrease in NCC abundance normally seen with aldosterone escape. Furthermore, L-NAME infusion in aldosterone-treated rats markedly decreased both NHE3 and NKCC2 protein abundance, without changes in the corresponding mRNA levels. We conclude that NHE3 and NKCC2 protein abundances in kidney are positively regulated by NO and that the increase in NHE3 abundance seen in the aldosterone escape phenomenon is NO dependent. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21]; NHLBI NIH HHS [Z01-HL-01282-KE] NR 36 TC 33 Z9 35 U1 0 U2 0 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 NOV 1 PY 2003 VL 285 IS 5 BP F843 EP F851 DI 10.1152/ajprenal.00110.2003 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 729WY UT WOS:000185799100003 PM 12837683 ER PT J AU Volkow, ND Swanson, JM AF Volkow, ND Swanson, JM TI Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID DEFICIT HYPERACTIVITY DISORDER; NUCLEUS-ACCUMBENS; HUMAN BRAIN; INTRAVENOUS METHYLPHENIDATE; DOPAMINE TRANSPORTER; ACUTE TOLERANCE; D-AMPHETAMINE; EXTRACELLULAR DOPAMINE; ORAL METHYLPHENIDATE; COCAINE AB Objective: Methylphenidate, the most common treatment for attention deficit hyperactivity disorder (ADHD), increases extracellular dopamine in the brain, which is associated with its reinforcing as well as its therapeutic effects. The authors evaluated variables that distinguish these two properties. Method: The brain imaging and clinical literatures were analyzed to identify variables that contribute to the abuse liability as well as to the clinical efficacy of methylphenidate. Results: Four variables were identified. 1) Dose-there is a threshold for methylphenidate-induced dopamine increases to be perceived as reinforcing and to produce therapeutic effects. 2) Pharmacokinetics-the reinforcing effects of methylphenidate are associated with rapid changes in serum concentrations and presumably fast dopamine increases (as achieved with intravenous injection or insufflation), whereas the therapeutic effects are associated with slowly ascending serum concentrations and presumably smoothly rising dopamine levels (as achieved with oral administration). 3) individual differences-sensitivity to methylphenidate varies across individuals and sets a threshold for blood and brain levels required for reinforcing effects (drug liking) and for therapeutic effects (symptom reduction). 4) Context-the effects of methylphenidate are modulated by different settings in abuse (rituals of self-administration and powerful conditioning) and in clinical use (external demands of low activity and focused attention). Conclusions: Reinforcing effects occur when methylphenidate elicits large and fast dopamine increases that mimic those of phasic dopamine cell firing, whereas therapeutic effects occur when methylphenidate elicits slow, steady-state dopamine increases that mimic those of tonic firing. Thus, the characteristics of clinical use (low doses administered orally and titrated for therapeutic effects) constrain methylphenidate's abuse. C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA. SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274-MSC 9581, Bethesda, MD 20892 USA. FU NIDA NIH HHS [DA 00280, DA 7092-01] NR 60 TC 237 Z9 244 U1 6 U2 20 PU AMER PSYCHIATRIC PRESS, 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 NOV PY 2003 VL 160 IS 11 BP 1909 EP 1918 DI 10.1176/appi.ajp.160.11.1909 PG 10 WC Psychiatry SC Psychiatry GA 740PB UT WOS:000186409800002 PM 14594733 ER PT J AU Bjork, JM Grant, SJ Hommer, DW AF Bjork, JM Grant, SJ Hommer, DW TI Cross-sectional volumetric analysis of brain atrophy in alcohol dependence: Effects of drinking history and comorbid substance use disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID COCAINE DEPENDENCE; GRAY-MATTER; HUMANS; COCAETHYLENE; COMPLICATIONS; ADOLESCENTS; TOXICITY; ETHANOL; ADDICTS; RATIO AB Objective: The authors assessed whether individual differences in drinking history as well as lifetime incidence of comorbid cocaine or marijuana use disorder underlie differential patterns of brain atrophy in subjects with alcohol dependence. Method: Segmented magnetic resonance images were used to compare whole brain cerebral gray matter and white matter in 134 male subjects age 30-50 with alcohol dependence, either alone or with comorbid cocaine or marijuana use disorder. Results: Across all subjects, drinking history variables correlated negatively with both gray matter and white matter after age was controlled. Alcohol-dependent subjects with no comorbid substance use disorder (N=51) showed a steeper negative correlation between age and the gray matter/white matter ratio than did alcohol-dependent subjects with a comorbid lifetime cocaine use disorder diagnosis (N=50). Alcohol-dependent subjects with comorbid cocaine use disorder tended to have a steeper negative correlation between age and white matter (adjusted for intracranial volume) than did alcohol-dependent subjects with no comorbid substance use disorder. After age and the greater estimated cumulative alcohol consumption of alcohol-dependent subjects with comorbid cocaine use disorder were controlled in a multiple regression analysis, however, comorbid cocaine use disorder did not account for any independent variance in any volumetric measure. Conclusions: Brain atrophy among subjects with alcohol dependence reflects individual differences in exposure to alcohol, and the data provide mixed evidence that comorbid cocaine use disorder may exacerbate white matter atrophy in alcoholism. C1 NIAAA, NIH, Clin Studies Lab, Bethesda, MD 20892 USA. NIDA, Bethesda, MD 20892 USA. RP Bjork, JM (reprint author), NIAAA, NIH, Clin Studies Lab, 10 Ctr Dr,Rm 3C-103, Bethesda, MD 20892 USA. NR 34 TC 38 Z9 38 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, 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 NOV PY 2003 VL 160 IS 11 BP 2038 EP 2045 DI 10.1176/appi.ajp.160.11.2038 PG 8 WC Psychiatry SC Psychiatry GA 740PB UT WOS:000186409800022 PM 14594753 ER PT J AU Solomon, DA Leon, AC Endicott, J Coryell, WH Mueller, TI Posternak, MA Keller, MB AF Solomon, DA Leon, AC Endicott, J Coryell, WH Mueller, TI Posternak, MA Keller, MB TI Unipolar mania over the course of a 20-year follow-up study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DIAGNOSTIC CRITERIA; RELIABILITY AB Objective: Using data from a longitudinal study of the mood disorders, the investigators address the phenomenon of unipolar mania. Method: Subjects diagnosed as having Research Diagnostic Criteria mania at intake into the study were prospectively followed for up to 20 years. Results: Twenty-seven subjects had the diagnosis of unipolar mania at the time they entered the study and had no history of major depression before enrolling in the study. Seven of these subjects did not suffer any episodes of major depression during the 15- to 20-year follow-up. Conclusions: These data support the diagnostic validity of unipolar mania. C1 Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Brown Univ, NIMH, Collaborat Program Psychobiol Depress Clin Studie, Providence, RI 02912 USA. Cornell Univ, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, Dept Res & Training, New York, NY 10032 USA. Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. RP Solomon, DA (reprint author), Rhode Isl Hosp, Dept Psychiat, Mood Disorders Program, 593 Eddy St, Providence, RI 02903 USA. FU NIMH NIH HHS [R01 MH025478] NR 8 TC 36 Z9 37 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, 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 NOV PY 2003 VL 160 IS 11 BP 2049 EP 2051 DI 10.1176/appi.ajp.160.11.2049 PG 3 WC Psychiatry SC Psychiatry GA 740PB UT WOS:000186409800024 PM 14594755 ER PT J AU Weidner, G Cain, VS AF Weidner, G Cain, VS TI Coronary heart disease mortality in Russia and Eastern Europe - Weidner and Cain respond SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID HEALTH C1 Res Inst Prevent Med, Sausalito, CA 94965 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Weidner, G (reprint author), Res Inst Prevent Med, 900 Bridgeway, Sausalito, CA 94965 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2003 VL 93 IS 11 BP 1793 EP 1794 DI 10.2105/AJPH.93.11.1793-a PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 738VE UT WOS:000186307900002 ER PT J AU Hoshino, T Nakamura, H Okamoto, M Kato, S Araya, S Nomiyama, K Oizumi, K Young, HA Aizawa, H Yodoi, J AF Hoshino, T Nakamura, H Okamoto, M Kato, S Araya, S Nomiyama, K Oizumi, K Young, HA Aizawa, H Yodoi, J TI Redox-active protein thioredoxin prevents proinflammatory cytokine- or bleomycin-induced lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE thioredoxin; redox; interstitial lung diseases; cytokine; bleomycin ID IDIOPATHIC PULMONARY-FIBROSIS; T-CELLS; INDUCED CYTOTOXICITY; POTENTIAL ROLE; FACTOR ADF; MICE; IL-18; EXPRESSION; GENE; CHEMOTAXIS AB Thioredoxin (TRX) is a multifunctional redox (reduction/oxidation)-active protein that scavenges reactive oxygen species by itself or together with TRX-dependent peroxiredoxin. TRX also has chemo-taxis-modulating functions and suppresses leukocyte infiltration into sites of inflammation. Leukocyte infiltration and oxidative stress may be involved in the pathogenesis of several diseases, including interstitial lung diseases (ILD). We examined the effects of TRX in two mouse models of human ILD. Recently, we established a new mouse model for human ILD in which daily administration of proinflammatory cytokine interleukin (IL)-18 with IL-2 induces lethal lung injury accompanied by acute interstitial inflammatory responses. Administration of recombinant TRX suppressed IL-18/IL-2-induced interstitial infiltration of cells and prevented death and lung tissue damage. TRX-transgenic mice also showed resistance to lethal lung injury caused by IL-18/IL-2. Administration of bleomycin induces the infiltration of polymorphonuclear and mononuclear leukocytes in the pulmonary interstitium, followed by progressive fibrosis. Wild-type mice given recombinant TRX treatment and TRX-transgenic mice demonstrated a decrease in bleomycin-induced cellular infiltrates and fibrotic changes in the lung tissue. These results suggest that TRX modulates pulmonary inflammatory responses and acts to prevent lung injury. TRX may have clinical benefits in human ILD, including lung fibrosis, for which no effective therapeutic strategy currently exists. C1 Kurume Univ, Sch Med, Dept Internal Med 1, Kurume, Fukuoka 8300011, Japan. Kurume Univ, Dept Pathol, Kurume, Fukuoka 8300011, Japan. Kyoto Univ, Inst Virus Res, Dept Biol Res, Kyoto 606, Japan. NCI, Expt Immunol Lab, DBS, Frederick, MD 21701 USA. RP Hoshino, T (reprint author), Kurume Univ, Sch Med, Dept Internal Med 1, 67 Asahimachi, Kurume, Fukuoka 8300011, Japan. NR 32 TC 108 Z9 114 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2003 VL 168 IS 9 BP 1075 EP 1083 DI 10.1164/rccm.200209-982OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 736QY UT WOS:000186185700013 PM 12816738 ER PT J AU Xu, H Elster, EA Blair, PJ Burkly, LC Tadaki, DK Harlan, DM Kirk, AD AF Xu, H Elster, EA Blair, PJ Burkly, LC Tadaki, DK Harlan, DM Kirk, AD TI Effects of combined treatment with CD25-and CD154-specific monoclonal antibodies in non-human primate allotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE costimulation; immunosuppression; kidney; rejection ID RENAL-ALLOGRAFT REJECTION; HUMAN IL-2 RECEPTOR; CROSS-LINKING; CD40; TRANSPLANTATION; EXPRESSION; INDUCTION; LIGAND; CD154; ACTIVATION AB The CD154-specific monoclonal antibody (Mab) hu5c8 greatly prolongs allograft survival in primates. The CD25-specific Mab daclizumab has not, to date, been paired with hu5c8. We evaluated the effects of hu5c8 in vitro, alone and in combination with daclizumab on rhesus-mixed lymphocyte reactions (MLRs). We then evaluated therapy with hu5c8 and daclizumab in four monkey renal allograft recipients compared with monkeys untreated or contemporaneously treated with hu5c8 alone. Lymphocyte proliferation in MLR was reduced by both daclizumab and hu5c8, and their combined effects were additive. Rejection-free allograft survival in monkeys treated with both hu5c8 and daclizumab (74-479 days) was not significantly better than animals treated with hu5c8 alone (257-587 days), and one combined therapy animal rejected while still on hu5c8 therapy, a condition not typically seen with hu5c8 monotherapy. Although daclizumab and hu5c8 are additively effective in MLR, they do not appear to be synergistic in vivo in rhesus monkeys. C1 NIDDKD, Transplantat & Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. USN, Med Res Ctr, Bethesda, MD USA. Biogen Inc, Cambridge, MA 02142 USA. RP Kirk, AD (reprint author), NIDDKD, Transplantat & Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 FU NIAID NIH HHS [U19 AI43900-01] NR 20 TC 10 Z9 12 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2003 VL 3 IS 11 BP 1350 EP 1354 DI 10.1046/j.1600-6135.2003.00235.x PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA 737LA UT WOS:000186230800004 PM 14525594 ER PT J AU Drachenberg, CB Papadimitriou, JC Wali, R Cubitt, CL Ramos, E AF Drachenberg, CB Papadimitriou, JC Wali, R Cubitt, CL Ramos, E TI BK polyoma virus allograft nephropathy: Ultrastructural features from viral cell entry to lysis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE caveolae; cell injury; cytopathic changes; kidney; SV40; transplantation ID SIMIAN VIRUS-40; MONOPINOCYTOTIC VESICLES; EPITHELIAL-CELLS; EARLY EVENTS; SIMIAN-VIRUS-40; REPLICATION; INFECTION; CAVEOLAE; MEMBRANE; VIRIONS AB BK virions must enter the host cell and target their genome to the nucleus in order to complete their life cycle. The mechanisms by which the virions accomplish these tasks are not known. In this morphological study we found that BK virions localized beneath the host cell cytoplasmic membrane in 60-70-nm, smooth (non-coated) monopinocytotic vesicles similar to, or consistent with, caveolae. In the cytoplasm, the monopinocytotic vesicles carrying virions appeared to fuse with a system of smooth, vesicles and tubules that communicated with the rough endoplasmic reticulum and was continuous with the Golgi system. Membrane-bound single virions and large tubuloreticular complexes loaded with virions accumulated in paranuclear locations. Occasional nuclei displayed virions within the perinuclear cisterna in association to the perinuclear viral accumulations. Tubular cells with mature productive infection had large nuclei, distended by daughter virions, whereas they lacked significant numbers of cytoplasmic virions. In addition to virally induced cell necrosis, there was extensive tubular cell damage (apoptosis and necrosis) in morphologically non-infected tubules. The observed ultrastructural interactions between the BK virions and host cells are remarkably similar to viral cell entry and nuclear targeting described for SV40 virus. C1 Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Papadimitriou, JC (reprint author), Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. NR 48 TC 61 Z9 63 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2003 VL 3 IS 11 BP 1383 EP 1392 DI 10.1046/j.1600-6135.2003.00237.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 737LA UT WOS:000186230800009 PM 14525599 ER PT J AU Sattabongkot, J Tsuboi, T Hisaeda, H Tachibana, M Suwanabun, N Rungruang, T Cao, YM Stowers, AW Sirichaisinthop, J Coleman, RE Torii, M AF Sattabongkot, J Tsuboi, T Hisaeda, H Tachibana, M Suwanabun, N Rungruang, T Cao, YM Stowers, AW Sirichaisinthop, J Coleman, RE Torii, M TI Blocking of transmission to mosquitoes by antibody to Plasmodium vivax malaria vaccine candidates Pvs25 and Pvs28 despite antigenic polymorphism in field isolates SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID OOKINETE SURFACE-ANTIGENS; CONSERVED REGIONS; MINIMAL VARIATION; FALCIPARUM; PROTEIN; PFS25; BERGHEI; HOMOLOGS; IMMUNITY; YOELII AB We have previously demonstrated that mouse antisera against yeast-produced recombinant forms of the ookinete surface proteins of Plasmodium vivax (Pvs25 and Pvs28) blocks transmission of the homologous P. vivax (Sal I strain). In this study, we developed mouse and rabbit antisera against Pvs25 and Pvs28 and evaluated the efficacy of these vaccine candidates against natural isolates of P. vivax in Thailand. Although both Pvs25 and Pvs28 genes are polymorphic. sera from mice immunized using alum adjuvant completely inhibited oocyst development for most human isolates. whereas sera from rabbits immunized with either alum or Freund's adjuvant were partially inhibitory. All inhibition occurred in an antibody dose dependent fashion. Data from this study clearly demonstrates that antibodies raised against Sal I-based vaccines overcome the genetic polymorphism of Pvs25 and Pvs28 present in natural isolates of P. vivax. suggesting the wide range applicability of Sal I based vaccines. C1 Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime 7908577, Japan. Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand. Kyushu Univ, Fac Med Sci, Dept Immunol & Parasitol, Fukuoka 8128582, Japan. Ehime Univ, Sch Med, Dept Mol Parasitol, Shigenobu, Ehime 7910295, Japan. China Med Univ, Coll Preclin Med, Dept Immunol, Shenyang 110001, Peoples R China. NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. Off Vector Borne Dis Control 1, Sara Buri 18120, Thailand. RP Tsuboi, T (reprint author), Ehime Univ, Cell Free Sci & Technol Res Ctr, 3 Bunkyo Cho, Matsuyama, Ehime 7908577, Japan. EM tsuboi@m.ehime-u.ac.jp NR 28 TC 35 Z9 43 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2003 VL 69 IS 5 BP 536 EP 541 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 750WY UT WOS:000187022500016 PM 14695092 ER PT J AU Djimde, AA Doumbo, OK Traore, O Guindo, AB Kayentao, K Diourte, Y Niare-Doumbo, S Coulibaly, D Kone, AK Cissoko, Y Tekete, M Fofana, B Dicko, A Diallo, DA Wellems, TE Kwiatkowski, D Plowe, CV AF Djimde, AA Doumbo, OK Traore, O Guindo, AB Kayentao, K Diourte, Y Niare-Doumbo, S Coulibaly, D Kone, AK Cissoko, Y Tekete, M Fofana, B Dicko, A Diallo, DA Wellems, TE Kwiatkowski, D Plowe, CV TI Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CHLOROQUINE TREATMENT; TREATMENT FAILURE; PYRIMETHAMINE-SULFADOXINE; MOLECULAR MARKERS; INTERFERON-GAMMA; AFRICAN INFANTS; MUTATIONS; CHILDREN; PFCRT; PREDICTORS AB Residents of malaria-endemic areas sometimes spontaneously clear Plasmodium falciparum infection without drug treatment, implying an important role for host factors such as immunity in this clearance. Host factors may also contribute to clearance of parasites resistant to a treatment drug. Chloroquine resistance is caused by point mutations in P. falciparum chloroquine resistance transporter (pfcrt) gene. We investigated the clearance of malaria parasites carrying the key chloroquine resistance-conferring PfCRT mutation K76T in patients treated with chloroquine. We found that the ability to clear these resistant parasites is strongly dependent on age (the best surrogate for protective immunity in endemic areas), suggesting that host immunity plays a critical role in the clearance of resistant P. falciparum infections. Age-adjusted comparison of subjects able to clear resistant parasites and those unable to do so provides a new phenotype for identifying host immune and genetic factors responsible for protective immunity against malaria. C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Malaria Sect, Columbia, MD 21044 USA. Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bandiagara Malaria Project, Bamako, Mali. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Univ Bamako, Fac Med Pharm & Dent, Dept Hematol, Bamako, Mali. RP Plowe, CV (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, Malaria Sect, 685 W Baltimore St,HSF 480, Columbia, MD 21044 USA. FU NIAID NIH HHS [5P50AI39469, N01-AI-85346] NR 39 TC 116 Z9 119 U1 0 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2003 VL 69 IS 5 BP 558 EP 563 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 750WY UT WOS:000187022500021 PM 14695097 ER PT J AU Parniak, MA Min, KL Budihas, SR Le Grice, SFJ Beutler, JA AF Parniak, MA Min, KL Budihas, SR Le Grice, SFJ Beutler, JA TI A fluorescence-based high-throughput screening assay for inhibitors of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H activity SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE reverse transcriptase; ribonuclease H; fluorescence resonance energy transfer; chemical library screening ID RENATURATION GEL ASSAY; HYDRAZONE AB A fluorescence resonance energy transfer assay readily applicable to 96-well and 384-well microplate formats with robotic operation was developed to enable high-throughput screening for inhibitors of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT)-associated RNase H activity, an underexplored target for antiretroviral development. The assay substrate is an 18-nucleotide 3'-fluorescein-labeled RNA annealed to a complementary 18-nucleotide 5'-Dabcyl- modified DNA. The intact duplex has an extremely low background fluorescent signal and provides up to 50-fold fluorescent signal enhancement following hydrolysis. The size and sequence of the duplex are such that HIV-1 RT-RNase H cuts the RNA strand close to the 3' end. The fluorescein-labeled ribonucleotide fragment readily dissociates from the complementary DNA at room temperature with immediate generation of a fluorescent signal. This assay is rapid, inexpensive, and robust, providing Z' factors of 0.8 and coefficients of variation of about 5%. The assay can be carried out both in real-time (continuous) and in "quench" modes; the latter requires only two addition steps with no washing and is thus suitable for robotic operation. Several chemical libraries totaling more than 106,000 compounds were screened with this assay in approximately 1 month. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. McGill Univ, Dept Chem, Montreal, PQ H3A 2T5, Canada. NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NCI, Mol Targets Dev Program, Frederick, MD 21701 USA. RP Parniak, MA (reprint author), Univ Pittsburgh, Dept Med, 930 Scaife Hall, Pittsburgh, PA 15261 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU NIGMS NIH HHS [GM066671] NR 21 TC 84 Z9 87 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 2003 VL 322 IS 1 BP 33 EP 39 DI 10.1016/j.ab.2003.06.001 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 733PA UT WOS:000186008800004 PM 14705777 ER PT J AU Janini, GM Zhou, M Yu, LR Blonder, J Gignac, M Conrads, TP Issaq, HJ Veenstra, TD AF Janini, GM Zhou, M Yu, LR Blonder, J Gignac, M Conrads, TP Issaq, HJ Veenstra, TD TI On-column sample enrichment for capillary electrophoresis sheathless electrospray ionization mass spectrometry: Evaluation for peptide analysis and protein identification SO ANALYTICAL CHEMISTRY LA English DT Article ID SOLID-PHASE EXTRACTION; CODED AFFINITY TAGS; ZONE-ELECTROPHORESIS; ATTOMOLE LEVEL; INTERFACE; MIXTURES; SEPARATIONS; PERFORMANCE; DESIGN; JOINT AB Although several designs have been advanced for coupling sample enrichment devices to a sheathless electrospray ionization-mass spectrometry (MS) interface on a capillary electrophoresis (CE) column, most of these approaches suffer from difficulties in fabrication, and the CE separation efficiency is degraded as a result of the presence of coupling sleeves. We have developed a design that offers significant improvements in terms of ease of fabrication, durability, and maintenance of the integrity of the CE-separated analyte zones. Capillaries with different inside and outside diameters were evaluated to optimize the performance of the CE-MS system, resulting in a mass limit of detection of 500 amol for tandem MS analysis of a standard peptide using a 20-mum-i.d. capillary. The improved design incorporates an efficient method to preconcentrate a sample directly within the CE capillary followed by its electrophoretic separation and detection using a true zero dead-volume sheathless CE-MS interface. Testing of this novel CE-MS system showed its ability to characterize proteomic samples such as protein digests, in-gel-digested proteins, and hydrophobic peptides as well as to quantitate ICAT-labeled peptides. C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Image Anal Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Janini, GM (reprint author), NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 50 TC 52 Z9 53 U1 1 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 2003 VL 75 IS 21 BP 5984 EP 5993 DI 10.1021/ac0301548 PG 10 WC Chemistry, Analytical SC Chemistry GA 739HL UT WOS:000186339000047 PM 14588041 ER PT J AU Vupputuri, S Sandler, DP AF Vupputuri, S Sandler, DP TI Lifestyle risk factors and chronic kidney disease SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE kidney diseases; alcohol consumption; smoking; body mass index ID BODY-MASS-INDEX; IMPAIRED GLUCOSE-TOLERANCE; INSULIN-TREATED DIABETICS; REPORTED SMOKING STATUS; BLOOD LEAD LEVELS; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; MANIFEST NEPHROPATHY; PROXY RESPONDENTS; RENAL-DISEASE AB PURPOSE: To examine the effects of lifestyle risk factors such as alcohol consumption, cigarette smoking and body mass index (BMI) on the development of chronic kidney disease. METHODS: We used a case-control study of 554 hospital cases and 516 age, race, and gender-matched community controls. The main outcome measure was newly-diagnosed chronic kidney disease, assessed by chart review. Self-reported history of alcohol consumption, smoking, and BMI as well as other co-variables were obtained during telephone interviews. Logistic regression models assessed the association between lifestyle risk factors and chronic kidney disease and were adjusted for important co-variables. RESULTS: We found no significant associations between alcohol consumption and chronic kidney disease, with the exception of moonshine, which resulted in an increased risk of chronic kidney disease (including all subtypes). The effects of smoking on chronic kidney disease were inconsistent, but pointed to no appreciable excess risk among smokers. Increasing quartiles of BMI were positively and significantly associated with nephrosclerosis (ORs [95% CI]: 2.5 [1.0-6.0], 2.8 [1.2-6.8] and 4.6 [1.8-11.6], for the second, third, and fourth quartiles of BMI, respectively). CONCLUSIONS: Our study revealed a significant positive association between BMI and nephrosclerosis. We did not find an increased risk of chronic kidney disease associated with alcohol or cigarette smoking. (C) 2003 Elsevier Inc. All rights reserved. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Vupputuri, S (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI Sandler, Dale/0000-0002-6776-0018 NR 52 TC 41 Z9 42 U1 0 U2 5 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 NOV PY 2003 VL 13 IS 10 BP 712 EP 720 DI 10.1016/S1047-2797(03)00066-8 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 741PX UT WOS:000186467400008 PM 14599736 ER PT J AU Yabroff, KR Gordis, L AF Yabroff, KR Gordis, L TI Assessment of a National Health Interview Survey-based method of measuring community socioeconomic status SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE socioeconomic factors; residence characteristics; breast neoplasms; all-cause mortality ID BREAST-CANCER MORTALITY; LONG-TERM ILLNESS; INCOME INEQUALITY; UNITED-STATES; MULTILEVEL ANALYSIS; BIRTH-WEIGHT; BLACK-WOMEN; RISK; CENSUS; AREA AB PURPOSE: Increasingly researchers are interested in assessing the rote of community socioeconomic status (SES) in poor health outcomes, above and beyond the influence of low individual SES. However, the feasibility of conducting these multi-level studies is often limited by restrictions on release of confidential identifiers for linkage to census data, resources for the linkage, and the availability of data sources with individual SES measures. This study assessed a new method of measuring community socioeconomic status (SES) that can be used with the publicly available National Health Interview Survey (NHIS) and preserves confidentiality and can be used with individual SES measures from the NHIS. METHODS: The associations between community SES and mortality from all causes and breast cancer in women were assessed in two samples: 1) deaths in 1987-1993 NHIS respondents linked to community SES measures developed with the new method; and 2) deaths in 1991 from the National Multiple Cause of Death Files linked to 1990 county-level census SES measures. The magnitude of crude mortality rates, direction of trend, and age-adjusted relative risk of mortality for low vs. high SES were compared in the two samples. RESULTS: Crude all-cause mortality and breast cancer mortality rates were similar in both samples in terms of magnitude and direction of trend. In both samples, as SES decreased, rates of all-cause mortality increased, whereas breast cancer mortality rates tended to decrease. Age-adjusted relative risks of mortality from all causes and breast cancer for low vs. high SES were similar in the two samples. CONCLUSIONS: Similarity of associations between community SES and mortality from all causes and breast cancer in the two samples provides support for the validity of a new NHIS-based method of measuring community SES. Since the NHIS is a large, nationally representative survey with high response rates and low loss to mortality follow-up, this method represents an important resource for multi-level studies. (C) 2003 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Yabroff, KR (reprint author), NCI, Div Canc Control & Populat Sci, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. OI Yabroff, K. Robin/0000-0003-0644-5572 FU NCI NIH HHS [T32 CA09314] NR 47 TC 6 Z9 6 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 NOV PY 2003 VL 13 IS 10 BP 721 EP 726 DI 10.1016/S1047-2797(03)00057-7 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 741PX UT WOS:000186467400009 PM 14599737 ER PT J AU Zheng, G Chen, Z Li, Z AF Zheng, G Chen, Z Li, Z TI Tests for candidate-gene association using case-parents design SO ANNALS OF HUMAN GENETICS LA English DT Article DE genetic model; MAX; restricted likelihood ratio test; robust; TDT; trio ID DISCORDANT SIB PAIRS; ASYMPTOTIC PROPERTIES; TDT AB In the case-parents design for testing candidate-gene association, the conditional likelihood method based on genotype relative risks has been developed recently. A specific relation of the genotype relative risks is referred to as a genetic model. The efficient score tests have been used when the genetic model is correctly specified under the alternative hypothesis. In practice, however, it is usually not able to specify the genetic model correctly. In the latter situation, tests such as the likelihood ratio test (LRT) and the MAX3 (the maximum of the three score statistics for dominant, additive, and recessive models) have been used. In this paper, we consider the restricted likelihood ratio test (RLRT). For a specific genetic model, simulation results demonstrate that RLRT is asymptotically equivalent to the score test, and both are more powerful than the LRT. When the genetic model cannot be correctly specified, the simulation results show that RLRT is most robust and powerful in the situations we studied. MAX3 is the next most robust and powerful test. The TDT is the easiest statistic to compute, compared to MAX3 and RLRT. When the recessive model can be eliminated, it is also as robust and powerful as RLRT for other genetic models. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. George Washington Univ, Dept Stat, Washington, DC 20052 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov FU NEI NIH HHS [EY14478] NR 8 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD NOV PY 2003 VL 67 BP 589 EP 597 DI 10.1046/j.1529-8817.2003.00065.x PN 6 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 755ZU UT WOS:000187442000011 PM 14641246 ER PT J AU Sumner, CJ Huynh, TN Markowitz, JA Perhac, JS Hill, B Coovert, DD Schussler, K Chen, XC Jarecki, J Burghes, AHM Taylor, JP Fischbeck, KH AF Sumner, CJ Huynh, TN Markowitz, JA Perhac, JS Hill, B Coovert, DD Schussler, K Chen, XC Jarecki, J Burghes, AHM Taylor, JP Fischbeck, KH TI Valproic acid increases SMN levels in spinal muscular atrophy patient cells SO ANNALS OF NEUROLOGY LA English DT Article ID MOTOR-NEURON SMN; HISTONE DEACETYLASE; SINGLE NUCLEOTIDE; EXON-7 INCLUSION; DETERMINING GENE; SURVIVAL; PROTEIN; MOUSE; PHARMACOKINETICS; ANTICONVULSANT AB Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by mutation of the telomeric copy of the survival motor neuron gene (SMN1). Although a centromeric copy of the survival motor neuron gene (SMN2) is retained in all patients with SMA, it differs from SMN1 at a critical nucleotide such that the majority of SMN2 transcripts lack exon 7 and encode an unstable, truncated protein. Here, we show that valproic acid increases levels of exon 7-containing SMN transcript and SMN protein in type I SMA patient-derived fibroblast cell lines. Valproic acid may increase SMN levels both by activating the SMN promoter and by preventing exon 7 skipping in SMN transcripts. Valproic acid and related compounds warrant further investigation as potential treatment for SMA. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. Ohio State Univ, Coll Biol Sci, Dept Mol Genet, Columbus, OH 43210 USA. Vertex Pharmaceut Inc, San Diego, CA USA. Ohio State Univ, Coll Med, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Dept Neurol, Columbus, OH 43210 USA. RP Sumner, CJ (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 10,Room 3B-14,10 Ctr Dr MSC 1250, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS 38650] NR 37 TC 191 Z9 194 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2003 VL 54 IS 5 BP 647 EP 654 DI 10.1002/ana.10743 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 738WZ UT WOS:000186312000011 PM 14595654 ER PT J AU Goel, S Bulgaru, A Hochster, H Wadler, S Zamboni, W Egorin, M Ivy, P Leibes, L Muggia, F Lockwood, G Harvey, E Renshaw, G Mani, S AF Goel, S Bulgaru, A Hochster, H Wadler, S Zamboni, W Egorin, M Ivy, P Leibes, L Muggia, F Lockwood, G Harvey, E Renshaw, G Mani, S TI Phase I clinical study of infusional 5-fluorouracil with oxaliplatin and gemcitabine (FOG regimen) in patients with solid tumors SO ANNALS OF ONCOLOGY LA English DT Article DE 5-fluorouracil; gemcitabine; oxaliplatin; phase I; solid tumors ID PANCREATIC-CANCER; CELL-LINES; COMBINATION; FLUOROURACIL; 2',2'-DIFLUORODEOXYCYTIDINE; ADENOCARCINOMA; CISPLATIN; COLON AB Background: The aim of this study was to determine the maximum tolerated dose, recommended phase II dose (RPTD) and toxicities of the FOG regimen (infusional 5-fluorouracil, oxaliplatin, gemcitabine). Patients and methods: Patients with advanced solid tumors were treated in an accelerated titration scheme. 5-Fluorouracil was administered intravenously at 200 mg/m(2)/day for 14 days and repeated every 21 days (one cycle). Gemcitabine was administered on days 1 and 8 over 30 min at 450-650 mg/m(2). Oxaliplatin was administered on day 1 over 2 h at 85-130 mg/m(2). For cycles 1, 3 and beyond, gemcitabine followed oxaliplatin; for cycle 2, gemcitabine preceded oxaliplatin. Results: Forty-five and 39 patients were assessable for toxicity and response, respectively. Cycle 1 dose-limiting toxicities (DLT) included neutropenia, thrombocytopenia and diarrhea. No DLT was observed in cycle 1 at the first four dose levels (DL). At DL-5, two of four (50%) patients experienced DLT in cycle 1. Expanding DL-4, nine of 26 (35%) patients experienced DLT in cycle 1. Because recurrent grade 3 toxicities were observed in three of six (50%) patients at DL-3, DL-2 was considered the RPTD. At the RPTD, three patients had a partial response (response rate 23%). Conclusions: The RPTD for the 5-fluorouracil-oxaliplatin-gemcitabine combination is 200/100/450 mg/m(2). This novel regimen has demonstrated activity in advanced solid tumors and merits further investigation. C1 Albert Einstein Comprehens Canc Ctr, Dept Oncol, New York, NY USA. Montefiore Med Ctr, New York, NY USA. Albert Einstein Coll Med, New York, NY USA. NYU, Ctr Comprehens Canc, New York, NY USA. Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. Sanofi Synthelabo Inc, Malvern, PA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Mani, S (reprint author), Yeshiva Univ Albert Einstein Coll Med, Jack D Weiler Hosp, Dept Oncol, 1825 Eastchester Rd, Bronx, NY 10461 USA. FU CCR NIH HHS [GCRC M01 RR00096]; NCI NIH HHS [CA 39821, CA 13330-30, U01 CA76642-01, R03 CA 86807] NR 26 TC 4 Z9 4 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 NOV PY 2003 VL 14 IS 11 BP 1682 EP 1687 DI 10.1093/annonc/mdg453 PG 6 WC Oncology SC Oncology GA 740PP UT WOS:000186411000015 PM 14581279 ER PT J AU Oppenheim, JJ Biragyn, A Kwak, LW Yang, D AF Oppenheim, JJ Biragyn, A Kwak, LW Yang, D TI Roles of antimicrobial peptides such as defensins in innate and adaptive immunity SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID DENDRITIC CELLS; ANTIBACTERIAL PEPTIDE; BETA-DEFENSINS; HOST-DEFENSE; MAST-CELLS; BETA-DEFENSIN-1; LL-37; NEUTROPHILS; IDENTIFICATION; CATHELICIDIN AB A number of antimicrobial peptides such as defensins have multiple functions in host defence. Defensins are produced not only by phagocytic cells and lymphocytes, but also by the epithelial cell lining of the gastrointestinal and genitourinary tracts, the tracheobronchial tree, and keratinocytes. Some are produced constitutively, whereas others are induced by proinflammatory cytokines and exogenous microbial products. Defensins produced by cells in the course of innate host defence serve as signals which initiate, mobilise, and amplify adaptive immune host defences. Administration of defensins with antigens to mice enhances both cellular (Th1-dependent) and humoral (Th2-dependent) cytokine production and immune responses. Linkage of defensins to weak tumour antigens potentiates their immunoadjuvant effects. Defensins use multiple cellular receptors, which endows them with the capacity to marshall adaptive host defences against microbial invaders. C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 560,Room 21-89A, Frederick, MD 21702 USA. NR 44 TC 192 Z9 206 U1 3 U2 12 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 NOV PY 2003 VL 62 SU 2 BP 17 EP 21 PG 5 WC Rheumatology SC Rheumatology GA 729GY UT WOS:000185766200005 ER PT J AU Kinsel, JF Sitkovsky, MV AF Kinsel, JF Sitkovsky, MV TI Possible targeting of G protein coupled receptors to manipulate inflammation in vivo using synthetic and natural ligands SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ADENOSINE A(3) RECEPTORS; NECROSIS-FACTOR-ALPHA; EXTRACELLULAR ADENOSINE; ENDOTOXEMIC MICE; A(2A) RECEPTORS; A(2B) ADENOSINE; PHOSPHOLIPASE-C; HUMAN MONOCYTES; TNF-ALPHA; KINASE-C AB Cyclic AMP elevating Gs protein coupled receptors were considered for a long time to be immunosuppressive. One of these receptors, adenosine A(2A) receptor, was implicated in a physiological mechanism that down regulates inflammation and protects tissues from excessive immune mediated damage. Targeting of these receptors by selective agonists may lead to better protocols of anti-inflammatory treatments. At the same time inhibiting the Gs protein coupled mediated signalling with antagonists could be explored in studies of approaches to enhance inflammation and tissue damage. Enhancement of targeted tissue damage is highly desirable when it is cancerous tissue, while enhancement of inflammatory events might be desirable in the development of new vaccine adjuvants. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, 10-11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 44 TC 5 Z9 6 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2003 VL 62 SU 2 BP 22 EP 24 PG 3 WC Rheumatology SC Rheumatology GA 729GY UT WOS:000185766200006 ER PT J AU Kok, MR Baum, BJ Tak, PP Pillemer, SR AF Kok, MR Baum, BJ Tak, PP Pillemer, SR TI Use of localised gene transfer to develop new treatment strategies for the salivary component of Sjogren's syndrome SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Review ID MESSENGER-RNA EXPRESSION; T-CELL CLONES; IN-VIVO; ADENOASSOCIATED VIRUS; RHEUMATOID-ARTHRITIS; CYTOKINE EXPRESSION; PAROTID-GLAND; VIRAL VECTORS; ALPHA-FODRIN; AUTOIMMUNE SIALADENITIS AB Effective treatment for Sjogren's syndrome (SS) might be developed locally by introducing genes encoding cytokines, which are potentially anti-inflammatory, or by introducing a cDNA encoding a soluble form of a key cytokine receptor, which can act as an antagonist and decrease the availability of certain cytokines, such as soluble tumour necrosis factor alpha receptors. Currently, the preferred choice of viral vector for immunomodulatory gene transfer is recombinant adeno-associated virus. The use of gene transfer to help determine the pathophysiology and to alter the course of the SS-like disease in the NOD mouse model can ultimately lead to the development of new treatments for managing the salivary component in patients with SS. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. RP Kok, MR (reprint author), Maibergdreef 9,Room F4-218, NL-1105 AZ Amsterdam, Netherlands. NR 96 TC 18 Z9 21 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2003 VL 62 IS 11 BP 1038 EP 1046 DI 10.1136/ard.62.11.1038 PG 9 WC Rheumatology SC Rheumatology GA 736PT UT WOS:000186179800003 PM 14583564 ER PT J AU Takada, K Danning, CL Kuroiwa, T Schlimgen, R Tassiulas, IO Davis, JC Yarboro, CH Fleisher, TA Boumpas, DT Illei, GG AF Takada, K Danning, CL Kuroiwa, T Schlimgen, R Tassiulas, IO Davis, JC Yarboro, CH Fleisher, TA Boumpas, DT Illei, GG TI Lymphocyte depletion with fludarabine in patients with psoriatic arthritis: clinical and immunological effects SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID E-SELECTIN; RHEUMATOID-ARTHRITIS; P-SELECTIN; EXPRESSION; CYTOKINE; ALPHA; CELLS AB Objective: To obtain preliminary information on the safety and efficacy of fludarabine in PsA and analyse its immunomodulatory effects in peripheral blood and synovial tissue. Methods: 15 patients with active PsA who did not respond to DMARDs were randomly allocated to receive fludarabine every four weeks or placebo. Primary outcomes were the proportion of patients who met the ACR20 and the psoriatic arthritis response criteria (PsARC) at 16 weeks. Secondary outcomes were changes in tender or swollen joint counts and scores of the psoriasis area and severity index (PASI). Phenotypic analysis of peripheral blood mononuclear cells (PBMC) synovial immunohistochemistry, and functional analysis of PBMC were used to determine the immunomodulatory effects of fludarabine. Results: At 16 weeks the ACR20 criteria were met by 3/7 (43%) fludarabine treated v 0/8 placebo treated patients (p = 0.08); the PsARC was achieved by 417 (57%) fludarabine treated v 2/8 (25%) placebo treated patients; and 3/7 (43%) fludarabine treated v 0/7 placebo treated patients had greater than or equal to20% improvement in the PASI. Marked peripheral lymphopenia involving naive (CD4(+)CD45RA(+)) and memory (CD4(+)CD45RO(+)) T cells, CD8(+) T cells, and B cells was seen in fludarabine treated patients. Conclusions: In PsA fludarabine induces significant peripheral, but modest, synovial lymphopenia, and a trend towards improved clinical response. C1 NIAMSD, Off Clin Director, NIH, DHHS, Bethesda, MD 20892 USA. Gunma Univ, Sch Med, Dept Internal Med 3, Gunma, Japan. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27706 USA. Univ Calif San Francisco, Div Rheumatol, San Francisco, CA 94143 USA. NIH, Serv Immunol, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr,DHHS, Bethesda, MD 20892 USA. Univ Crete, Sch Med, Iraklion, Greece. RP Takada, K (reprint author), NIAMSD, Off Clin Director, NIH, DHHS, 10 Ctr Dr,Bldg 10,Room 9S-205, Bethesda, MD 20892 USA. NR 13 TC 11 Z9 11 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2003 VL 62 IS 11 BP 1112 EP 1115 DI 10.1136/ard.62.11.1112 PG 4 WC Rheumatology SC Rheumatology GA 736PT UT WOS:000186179800016 PM 14583577 ER PT J AU Budge, PJ Lebowitz, J Graham, BS AF Budge, PJ Lebowitz, J Graham, BS TI Antiviral activity of RhoA-derived peptides against respiratory syncytial virus is dependent on formation of peptide dimers SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CRYSTAL-STRUCTURE; IN-VITRO; FUSION GLYCOPROTEIN; ATTACHMENT; PROTEIN; REPLICATION; INFECTIVITY; INHIBITORS; POLYMERS; ANALOG AB A synthetic peptide containing amino acids 77 to 95 of the intracellular GTPase RhoA has previously been shown to inhibit replication of respiratory syncytial virus (RSV) in cultured cells. We show that residues 80 to 90 of RhoA are sufficient for this activity and that the cysteine residue at position 83 is critical. Further studies with an optimal peptide sequence containing amino acids 80 to 94 of RhoA revealed that the antiviral potency of the peptide is dependent on the oxidation of cysteine 83. Size-exclusion chromatography and sedimentation equilibrium studies of the peptide comprising residues 80 to 94 revealed that it is capable of forming aggregates in both reduced and oxidized states. A peptide (83A) in which the cysteine residue is replaced by an alanine does not form dimers or higher-order aggregates and did not inhibit RSV replication at any concentration tested. These data indicate that formation of peptide multimers is necessary for the antiviral activities of RhoA-derived peptides and suggest that the observed antiviral activities of these peptides may be unrelated to the biological functions of their parent molecule. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, MSC 3017,Bldg 40,Room 2502,40 Convent Dr, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R01-AI-33933, R01 AI033933] NR 30 TC 8 Z9 9 U1 0 U2 0 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 NOV PY 2003 VL 47 IS 11 BP 3470 EP 3477 DI 10.1128/AAC.47.11.3470-3477.2003 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 738WT UT WOS:000186311400014 PM 14576104 ER PT J AU Kessler, RC Merikangas, KR Berglund, P Eaton, WW Koretz, DS Walters, EE AF Kessler, RC Merikangas, KR Berglund, P Eaton, WW Koretz, DS Walters, EE TI Mild disorders should not be eliminated from the DSM-V SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; MENTAL-DISORDERS; CLINICAL-SIGNIFICANCE; DIAGNOSTIC INTERVIEWS; UNITED-STATES; COMMUNITY; PREVALENCE; DEPRESSION; LIFETIME; LIMITATIONS AB Background: High prevalence estimates in epidemiological surveys have led to concerns that the DSM system is overly inclusive and that mild cases should be excluded from future DSM editions. Objective: To demonstrate that the DSM-III-R disorders in the baseline National Comorbidity Survey (NCS) can be placed on a severity gradient that has a dose-response relationship with outcomes assessed a decade later in the NCS follow-up survey (NCS-2) and that no inflection point exists at the mild severity level. Methods: The NCS was a nationally representative household survey of DSM-III-R disorders in the 3-year time span 1990-1992. The NCS-2 is a follow-up survey of 4375 NCS respondents (76.6% conditional response rate) reinterviewed in 2000 through 2002. The NCS-2 outcomes include hospitalization for mental health or substance disorders, work disability due to these disorders, suicide attempts, and serious mental illness. Results: Twelve-month NCS/DSM-III-R disorders were disaggregated into 3.2% severe, 3.2% serious, 8.7% moderate, and 16.0% mild case categories. All 4 case categories were associated with statistically significantly (P<.05, 2-sided tests) elevated risk of the NCS-2 outcomes compared with baseline noncases, with odds ratios of any outcome ranging monotonically from 2.4 (95% confidence interval, 1.6-3.4) to 15.1 (95% confidence interval, 10.0-22.9) for mild to severe cases. Odds ratios comparing mild to moderate cases were generally nonsignificant. Conclusions: There is a graded relationship between mental illness severity and later clinical outcomes. Retention of mild cases in the DSM is important to represent the fact that mental disorders (like physical disorders) vary in severity. Decisions about treating mild cases should be based on cost-effectiveness not current severity. Cost-effectiveness analysis should include recognition that treatment of mild cases might prevent a substantial proportion of future serious cases. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. Univ Michigan, Inst Social Res, Ann Arbor, MI USA. NIMH, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU NIDA NIH HHS [DA 12058]; NIMH NIH HHS [MH 00507, MH 46376, MH 49098, MH 52861] NR 36 TC 165 Z9 166 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2003 VL 60 IS 11 BP 1117 EP 1122 DI 10.1001/archpsyc.60.11.1117 PG 6 WC Psychiatry SC Psychiatry GA 744DH UT WOS:000186612300007 PM 14609887 ER PT J AU Winterer, G Egan, MF Raedler, T Sanchez, C Jones, DW Coppola, R Weinberger, DR AF Winterer, G Egan, MF Raedler, T Sanchez, C Jones, DW Coppola, R Weinberger, DR TI P300 and genetic risk for schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID EVENT-RELATED POTENTIALS; VISUAL-STIMULI; INTRACEREBRAL POTENTIALS; TEMPORAL-LOBE; RARE TARGET; SUBCOMPONENT ABNORMALITIES; UNAFFECTED SIBLINGS; NEGATIVE SYMPTOMS; BRAIN POTENTIALS; REDUCTION AB Background: We assessed the suitability of event-related potential frontal and temporoparietal P300 changes as intermediate phenotypes in genetic studies of schizophrenia. We applied a principal component analysis approach based on the notion that P300 abnormalities in siblings of schizophrenic patients may involve a widespread network of relatively weak cortical generators and because an earlier, smaller study that used a topographic analysis of covariance model did not show that localized P300 changes predict risk for schizophrenia. Methods: P300 changes in 66 schizophrenic patients, 115 healthy siblings of schizophrenic patients, and 89 unrelated controls were studied during a standard auditory oddball paradigm. Principal components were calculated across electrodes, revealing frontal and temporoparietal components for latency and amplitude, respectively. For the frontal and temporoparietal P300 amplitude and latency components, the intraclass correlations (ICCs) between sib-pairs (pairs of unaf-fected siblings and schizophrenic index patients) and the relative risk ratios (gimel) were determined. Results: Compared with controls, schizophrenic patients and their unaffected siblings showed significant reductions in the temporoparietal P300 amplitude component. Both groups were also characterized by a significantly higher frontal P300 amplitude component. Significant ICCs and increased relative risk ratios were found for the frontal (ICCU= 0.18; P=.04; gimel =3.4) and temporoparietal (ICCU=0.24; P=.01; gimel=1.7) P300 amplitude components. Conclusions: Temporoparietal P300 amplitude reduction and frontal P300 amplitude increase seem to be quantitative phenotypes associated with increased risk of schizophrenia. Both measures may be useful for increasing the statistical power of genetic studies of schizophrenia. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Winterer, G (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Room 4S229A,Mail Stop Code 1379, Bethesda, MD 20892 USA. NR 78 TC 66 Z9 67 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2003 VL 60 IS 11 BP 1158 EP 1167 DI 10.1001/archpsyc.60.11.1158 PG 10 WC Psychiatry SC Psychiatry GA 744DH UT WOS:000186612300011 PM 14609891 ER PT J AU Spencer, WH Chan, CC Shen, D Rao, NA AF Spencer, WH Chan, CC Shen, D Rao, NA TI Detection of Histoplasma capsulatum DNA in lesions of chronic ocular histoplasmosis syndrome SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID UVEITIS AB Objective: To evaluate choroidal lesions in histological sections from the enucleated eye of a patient with chronic ocular histoplasmosis syndrome for the presence of Histoplasma capsulatum DNA. Methods: Laser-capture microdissection was used to procure cells from macular and midperipheral choroidal lesions in a deparaffinized hematoxylin-eosin-stained section prepared from the enucleated left eye of a patient with an ipsilateral choroidal melanoma and bilateral chronic histoplasmosis syndrome. The captured cells were initially subjected to polymerase chain reaction (PCR) amplification using a pair of primers unique to each end of the nucleotide sequences that are complementary to the DNA known to flank the internal transcribed spacer regions of the ribosomal RNA genes of H capsulatum. This product was then reamplified using a second set of internally situated nested primers. The results were compared with a positive control sample of H capsulatum DNA and with a negative microdissected sample from noninflamed choroid in the same slide. Results: Products of H capsulatum DNA were identified in both samples of microdissected tissue and the positive control. They were absent in the negative control. Conclusion: The observations provide molecular biological evidence linking the chronic choroidal lesions to earlier infection by H capsulatum. C1 Calif Pacific Med Ctr, Dept Ophthalmol, San Francisco, CA 94115 USA. NEI, Immunol Lab, NIH, Bethesda, MD USA. Doheny Eye Inst, Los Angeles, CA 90033 USA. RP Spencer, WH (reprint author), Calif Pacific Med Ctr, Dept Ophthalmol, 2340 Clay St,Room 201, San Francisco, CA 94115 USA. NR 15 TC 11 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2003 VL 121 IS 11 BP 1551 EP 1555 DI 10.1001/archopht.121.11.1551 PG 5 WC Ophthalmology SC Ophthalmology GA 741QC UT WOS:000186467900003 PM 14609910 ER PT J AU Nansel, TR Overpeck, MD AF Nansel, TR Overpeck, MD TI Operationally defining "Bullying" - In reply SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Washington, DC USA. RP Nansel, TR (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Washington, DC USA. NR 6 TC 8 Z9 8 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD NOV PY 2003 VL 157 IS 11 BP 1135 EP 1135 DI 10.1001/archpedi.157.11.1135 PG 1 WC Pediatrics SC Pediatrics GA 743BD UT WOS:000186551800017 ER PT J AU Li, XL Wu, JM Carter, RH Edberg, JC Su, KH Cooper, GS Kimberly, RP AF Li, XL Wu, JM Carter, RH Edberg, JC Su, KH Cooper, GS Kimberly, RP TI A novel polymorphism in the Fc gamma receptor IIB (CD32B) transmembrane region alters receptor signaling SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CD19 CYTOPLASMIC TYROSINES; B-CELL; DEFICIENT MICE; AUTOIMMUNE-DISEASE; REVISED CRITERIA; DENDRITIC CELLS; LYMPHOCYTES-B; RIIB; SUSCEPTIBILITY AB Objective. The low-affinity receptor Fcgamma receptor IIb (FcgammaRIIIb), with an immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic domain, down-regulates humoral immune responses and modulates the risk of autoimmunity in animal models. The transmembrane domain of FcgammaRIIb may also contribute to receptor signaling. Therefore, we investigated the biologic significance of single-nucleotide polymorphisms (SNPs) throughout the coding region. Methods. Discovery of SNPs in FCGR2B was performed by direct cycle sequencing of complementary DNA samples derived by reverse transcriptase-polymerase chain reaction. To assess the biologic significance of the nonsynonymous transmembrane SNP, we studied 3 functions influenced by the FcgammaRIIb transmembrane domain: tyrosine dephosphorylation of CD19, inhibition of B cell receptor (BCR)-induced calcium response, and modulation of BCR- or anti-Fas-induced apoptosis. Results. The nonsynonymous C-to-T transition in the first cytoplasmic exon, originally reported in the Raji cell line, was not found in either the African-American or the Caucasian population, but a nonsynonymous T-to-C transition at nucleotide 775 in exon 4 of FCGR2B, which changes isoleucine to threonine at residue 187 in the transmembrane domain, was significantly more common in African Americans. Using the FcgammaRIIb-negative mouse B cell line IIA1.6, we expressed both allelic forms as both full-length and truncated cytoplasmic domain constructs. The FCGR2B-187T allele mediated a higher level of CD19 dephosphorylation (P = 0.029) and a greater degree of inhibition of the calcium response (P = 0.003) when co-engaged with BCR than did FCGR2B-187I, independent of the presence of the ITIM. In contrast, FcgammaRIIb modulation of BCR-induced and anti-Fas antibody-induced cell death rates were similar in IIA1.6 cells expressing either the 1871 or the 187T allelic form. Conclusion. The differential activity of FCGR2B alleles suggests a novel mechanism of FcgammaRIIb regulation that may influence the risk of autoimmune disease. C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Kimberly, RP (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, 429 THT,1900 Univ Blvd, Birmingham, AL 35294 USA. FU NCRR NIH HHS [M01-RR-00032]; NIAMS NIH HHS [P50-AR-45231, R01-AR-42476, P01-AR-49084] NR 53 TC 125 Z9 130 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2003 VL 48 IS 11 BP 3242 EP 3252 DI 10.1002/art.11313 PG 11 WC Rheumatology SC Rheumatology GA 741GV UT WOS:000186451100033 PM 14613290 ER PT J AU Troyk, P Bak, T Berg, J Bradley, D Cogan, S Erickson, R Kufta, C McCreery, D Schmidt, E Towle, T AF Troyk, P Bak, T Berg, J Bradley, D Cogan, S Erickson, R Kufta, C McCreery, D Schmidt, E Towle, T TI A model for intracortical visual prosthesis research SO ARTIFICIAL ORGANS LA English DT Article DE visual prosthesis; intracortical microelectrodes; animal model; cortical interface; sensory; perception; memory ID HUMAN OCCIPITAL CORTEX; ELECTRICAL-STIMULATION; STRIATE CORTEX; ARTIFICIAL VISION; BLIND; MICROSTIMULATION; MONKEY AB In the field of visual prosthesis research, it has generally been held that animal models are limited to testing the safety of implantable hardware due to the inability of the animal to provide a linguistic report of perceptions. In contrast. vision scientists make extensive use of trained animal models to investigate the links between visual stimuli, neural activities. and perception. We describe an animal model for cortical visual prosthesis research in which novel animal psychophysical testing has been employed to compensate for the lack of a linguistic report. One hundred and fifty-two intracortical microelectrodes were chronically implanted in area V1 of a male macaque. Receptive field mapping was combined with eye-tracking to develop a reward-based training procedure. The animal was trained to use electrically induced point-flash percepts, called phosphenes, in performing a memory saccade task. It is our long-term goal to use this animal model to investigate stimulation strategies in developing a multichannel sensory cortical interface. C1 IIT, Pritzker Inst Biomed Sci & Engn, Chicago, IL 60616 USA. NIH, Neural Control Lab, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. EIC Labs, Norwood, MA 02062 USA. Huntington Med Res Inst, Pasadena, CA USA. RP Troyk, P (reprint author), IIT, Pritzker Inst Biomed Sci & Engn, 10 W 32nd St, Chicago, IL 60616 USA. NR 26 TC 81 Z9 89 U1 0 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD NOV PY 2003 VL 27 IS 11 BP 1005 EP 1015 DI 10.1046/j.1525-1594.2003.07308.x PG 11 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 742AE UT WOS:000186491900006 PM 14616519 ER PT J AU Molloy, EA Blumenthal, J Clasen, LS Zijdenbos, A Rapoport, JL Giedd, JN AF Molloy, EA Blumenthal, J Clasen, LS Zijdenbos, A Rapoport, JL Giedd, JN TI Brain morphometry and IQ in pediatric monozygotic twins SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 NIMH, Sect Brain Imaging, Child Psychiat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2003 VL 33 IS 6 BP 712 EP 713 PG 2 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 732TN UT WOS:000185961800070 ER PT J AU Jutkiewicz, EM Rice, KC Woods, H Winsauer, PJ AF Jutkiewicz, EM Rice, KC Woods, H Winsauer, PJ TI Effects of the delta-opioid receptor agonist SNC80 on learning relative to its antidepressant-like effects in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE SNC80; delta-opioid receptors; scopolamine; repeated-acquisition; forced swim test; rat ID FORCED SWIMMING TEST; SPRAGUE-DAWLEY RATS; REPEATED ACQUISITION; SQUIRREL-MONKEYS; MEMORY; STIMULATION; PERFORMANCE; SCOPOLAMINE; ANTAGONIST; CONVULSANT AB Delta-opioid receptor agonists produce decreases in immobility in the forced swim test, suggesting that these compounds have antidepressant-like activity. There is also the possibility that these compounds decrease immobility in the forced swim test by disrupting learning processes that occur during the swim, or with successive swim exposures, thus falsely identifying them as having 'antidepressant' potential. This study investigated the effects of the delta-opioid receptor agonist, SNC80, on responding in a repeated-acquisition procedure and in the forced swim test in rats, and the effects were compared directly to those of scopolamine, a compound known to disrupt memory and learning. SNC80 disrupted acquisition of a response sequence (learning) and produced a significant antidepressant-like effect in the forced swim test Scopolamine, however, produced larger decrements in learning without producing behavioral changes consistent with an antidepressant-like profile of action. These results suggest that SNC80 produces antidepressant-like activity through a mechanism independent of its disruptive effects on learning. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48104 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol & Expt Therapeut, New Orleans, LA USA. RP Jutkiewicz, EM (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48104 USA. FU NIAAA NIH HHS [AA 09803]; NIDA NIH HHS [DA 00254, DA 07267, DA 12427]; NIGMS NIH HHS [GM 07767] NR 33 TC 29 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 2003 VL 14 IS 7 BP 509 EP 516 DI 10.1097/01.fbp.0000095080-80017.gd PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 907SO UT WOS:000227738500003 PM 14557718 ER PT J AU Bossert, JM Biskin, S Franklin, KBJ AF Bossert, JM Biskin, S Franklin, KBJ TI Systemic and intracerebroventricular administration of sodium barbital induced a place preference in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE barbiturate; ventricles; conditioning trial duration; reinforcement; rat ID CONDITIONING TRIAL DURATION; RHESUS-MONKEYS; PARA-CHLOROPHENYLALANINE; PHYSICAL-DEPENDENCE; NUCLEUS-ACCUMBENS; INJECTION SPEED; CROSS-TOLERANCE; COCAINE; MORPHINE; ETHANOL AB We have shown previously that 15 mg/kg pentobarbital induces a conditioned place preference (CPP), but it is unsuitable for intracranial administration. Since the long-acting barbiturate, sodium barbital, is soluble at a. neutral pH, we tested whether it would induce a CPP when administered centrally. Furthermore, because barbital has a long duration of action, and because we obtained a significant CPP to systemically administered barbital using 30-minute conditioning trials, we tested whether longer conditioning trials would produce a more robust CPP. Using a three-compartment apparatus and an unbiased procedure, we found that systemic administration of barbital induced a significant CPP at 8 and 24 mg/kg, but not 2.7 or 72 mg/kg (i.p.). When rats were conditioned to 24 mg/kg barbital for conditioning trials of 1/2, 1, 3, or 6 hours, only the 30-min conditioning trial produced a CPP. Finally, 240 and 480 mu g intracerebroventricular (ICV) barbital induced a significant CPP, but 60 or 120 mu g did not These findings suggest that: (1) like pentobarbital, barbital has reinforcing properties measured in the CPP test; (2) the CPP is impaired, rather than enhanced, by increasing the duration of drug-context pairing; and (3) the reinforcing effects of barbiturates are centrally mediated. C1 McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD USA. RP Franklin, KBJ (reprint author), McGill Univ, Dept Psychol, 1205 Dr Penfield Ave, Montreal, PQ H3A 1B1, Canada. EM keith.franklin@mcgill.ca RI Biskin, Robert/J-4989-2012 NR 49 TC 1 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 2003 VL 14 IS 7 BP 517 EP 523 DI 10.1097/01.fbp.0000095081.80017.d4 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 907SO UT WOS:000227738500004 PM 14557719 ER PT J AU Jaenicke, E Walsh, PJ Decker, H AF Jaenicke, E Walsh, PJ Decker, H TI Isolation and characterization of haemoporin, an abundant haemolymph protein from Aplysia calitornica SO BIOCHEMICAL JOURNAL LA English DT Article DE Aplysia; channel protein; helix; haemolymph; polyalanine; pore protein ID AMINO-ACIDS; THERMODYNAMIC SCALE; HELIX PROPENSITIES; HEMOCYANIN; ACETYLCHOLINESTERASE; CALIFORNICA; REGENERATION; NEURONS AB In the present study, we show the isolation and characterization of the protein haemoporin, which constitutes the second most abundant protein fraction in the haemolymph of the marine gastropod Aplysia californica. Although Aplysia is commonly used to investigate the molecular basis of learning, not much is known about the proteins in its haemolymph, which is in contact with the neurons owing to the open circulatory system of molluscs. In the native state, haemoporin is a macromolecular complex forming a cylinder with a central solvent-filled pore. The native complex most probably is a homopentamer made up from 70 kDa subunits with a molecular mass of 360 kDa and a sedimentation coefficient of 11.7 S. Prediction of the secondary structure by CD spectroscopy revealed that haemoporin contains 36 % alpha-helices and 19 % beta-strands. An absorption band in the 300-400 nm region indicates that haemoporin probably contains a bound substance. Haemoporin also contains a below average amount of tryptophan as evident from absorption and fluorescence spectra. The specific absorption coefficient at 280 nm (a(280 nm, 1 mg/ml)) varies between 0.42 and 0.59 1 . g(-1) . cm(-1) depending on the method. The function of the protein is not yet known, but there are structural parallels between haemoporin and a pore protein reported previously in the haemolymph of another marine gastropod Megathura crenulata. The alanine-rich N-terminal sequence (AAVPEAAAEATAEAAPVSEF) is unique among protein sequences and indicates an alpha-helical structure. Whereas one side of the helix is hydrophobic and faces the interior of the protein, the other side contains a glutamic cluster, which may form the channel of the pore in the quaternary structure. Thus both proteins might belong to a new class of haemolymph proteins present in the haemolymph of marine gastropods. C1 Univ Mainz, Inst Mol Biophys, D-55099 Mainz, Germany. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. RP Jaenicke, E (reprint author), Univ Mainz, Inst Mol Biophys, D-55099 Mainz, Germany. RI Jaenicke, Elmar/A-5317-2010 OI Jaenicke, Elmar/0000-0002-5157-7219 FU NCRR NIH HHS [RR10294] NR 39 TC 3 Z9 4 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2003 VL 375 BP 681 EP 688 DI 10.1042/BJ20030726 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 744QQ UT WOS:000186643900018 PM 12889987 ER PT J AU Haley, JD Smith, DE Schwedes, J Brennan, R Pearce, C Moore, C Wang, F Petti, F Grosveld, F Jane, SM Noguchi, CT Schechter, AN AF Haley, JD Smith, DE Schwedes, J Brennan, R Pearce, C Moore, C Wang, F Petti, F Grosveld, F Jane, SM Noguchi, CT Schechter, AN TI Identification and characterization of mechanistically distinct inducers of gamma-globin transcription SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE sickle disease; gamma-globin transcription; histone deacetylase; globin-switching ID SICKLE-CELL-ANEMIA; FETAL-HEMOGLOBIN INDUCTION; KRUPPEL-LIKE FACTOR; BETA-GLOBIN; TRANSGENIC MICE; ERYTHROID-CELLS; GENE PROMOTER; HISTONE DEACETYLASE; NUCLEAR-PROTEIN; IN-VIVO AB Inhibition of HbS polymerization is a major target for therapeutic approaches in sickle cell anemia. Toward this goal, initial efforts at pharmacological elevation of fetal hemoglobin (HbF) has shown therapeutic efficacy. In order to identify well-tolerated, novel agents that induce HbF in patients, we developed a high-throughput screening approach based on induction of gamma-globin gene expression in erythroid cells. We measured gamma-globin transcription in K562 cells transfected with either 7 promoter elements fused with the locus control region hypersensitivity site 2 and luciferase reporter gene (HS2gamma) or a beta-yeast artificial chromosome in which the luciferase reporter gene was recombined into the gamma-globin coding sequences (gammaYAC). Corresponding pharmacological increases in HbF protein were confirmed in both K562 cells and in human primary erythroid progenitor cells. Approximately 186,000 defined chemicals and fungal extracts were evaluated for their ability to increase gamma gene transcription in either HS2gamma or gammaYAC models. Eleven distinct classes of compounds were identified, the majority of which were active within 24-48 hr. The short chain hydroxamate-containing class generally exhibited delayed maximal activity. which continued to increase transcription up to 120 hr. The cyclic tetrapeptide OSI-2040 and the hydroxamates were shown to have histone deacetylase inhibitory activity. In primary hematopoietic progenitor cell cultures, OSI-2040 increased HbF by 4.5-fold at a concentration of only 40 nM, comparable to the effects of hydroxyurea at 100 muM. This screening methodology successfully identifies active compounds for further mechanistic and preclinical evaluation as potential therapeutic agents for sickle cell anemia. (C) 2003 Elsevier Inc. All rights reserved. C1 OSI Pharmaceut Inc, Farmingdale, NY 11735 USA. Erasmus Univ, Rotterdam, Netherlands. Royal Melbourne Hosp, Res Fdn, Rotary Bone Marrow Res Labs, Parkville, Vic 3050, Australia. NIDDK, NIH, Bethesda, MD USA. RP Haley, JD (reprint author), OSI Pharmaceut Inc, Farmingdale, NY 11735 USA. RI Jane, Stephen/D-6659-2011; OI Schechter, Alan N/0000-0002-5235-9408 FU NHLBI NIH HHS [R43 HL062849-01, R01 HL057595-03, R01 HL57595, R44 HL50935]; NICHD NIH HHS [R01 HD057595] NR 43 TC 9 Z9 9 U1 0 U2 1 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 NOV 1 PY 2003 VL 66 IS 9 BP 1755 EP 1768 DI 10.1016/S0006-2952(03)00542-2 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 737FM UT WOS:000186219800009 PM 14563486 ER PT J AU Harrigan, JA Bohr, VA AF Harrigan, JA Bohr, VA TI Human diseases deficient in RecQ helicases SO BIOCHIMIE LA English DT Article DE Bloom syndrome; helicase; RecQ; Rothmund-Thompson syndrome; Werner syndrome ID ROTHMUND-THOMSON-SYNDROME; WERNER-SYNDROME PROTEIN; BLOOMS SYNDROME FIBROBLASTS; SYNDROME GENE-PRODUCT; TOPOISOMERASE-III-ALPHA; DNA-REPAIR CAPACITY; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; REPLICATION ARREST; GENOMIC STRUCTURE AB RecQ helicases are conserved from bacteria to man. Mutations in three of the human RecQ family members give rise to genetic disorders characterized by genomic instability and a predisposition to cancer. RecQ helicases are therefore caretakers of the genome, and although they do not directly regulate tumorigenesis, they influence stability and the rate of accumulation of genetic alterations, which in turn, result in tumorigenesis. Maintenance of genome stability by RecQ helicases likely involves their participation in DNA replication, recombination, and repair pathways. (C) 2003 Elsevier SAS. All rights reserved. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 87 TC 33 Z9 33 U1 1 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD NOV PY 2003 VL 85 IS 11 BP 1185 EP 1193 DI 10.1016/j.biochi.2003.10.006 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 769FP UT WOS:000188616000013 PM 14726023 ER PT J AU Contoreggi, C Herning, RI Na, P Gold, PW Chrousos, G Negro, PJ Better, W Cadet, JL AF Contoreggi, C Herning, RI Na, P Gold, PW Chrousos, G Negro, PJ Better, W Cadet, JL TI Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease SO BIOLOGICAL PSYCHIATRY LA English DT Article DE corticotropin-releasing hormone; adrenocorticotrophin; cortisol; substance abuse ID CORTISOL RESPONSE; FACTOR RECEPTORS; BETA-ENDORPHIN; CUSHINGS-SYNDROME; MAJOR DEPRESSION; INDUCED RELAPSE; ANTAGONIST; ALCOHOLICS; COCAINE; RATS AB Background: Preclinical data indicate a crucial role of stress in the acute effects of drugs of abuse, maintenance of self-administration, and susceptibility to relapse. Stress system activation may serve as a marker for a neurochemical dysfunction with prognostic significance in patients with addiction. Methods: We tested pituitary adrenocorticotrophin (ACTH) and adrenal cortisol response to ovine corticotropin-releasing hormone (oCRH) to assess the reactivity of the hypthalamic-pituitary-adrenal (HPA) axis in seven nonsubstance-abusing subjects, 31 polysubstance-abusing subjects without depressive symptoms, and seven subjects with substance abuse and depressive symptoms. No subject met diagnostic criteria for depression or other severe psychiatric disease. Results: Compared with normal control subjects, substance abusers showed significantly lower ACTH and cortisol responses over the course of oCRH stimulation (p < .0001). Substance abusers with depressive symptoms showed similarly blunted responses. Conclusions: Polysubstance abusers with no past or current diagnosis of other Axis I disorders show blunted ACTH and cortisol responses to oCRH administration. The finding of an activated HPA axis in this population suggests an overlapping role of central CRH and HPA axis activation in affective disorders and substance abuse, which is likely to constitute an endocrine milieu necessary for the maintenance of addictive behavior. These data support the role of future therapeutic trials with nonpeptide CRH receptor 1 antagonists in these patients. (C) 2003 Society of Biological Psychiatry C1 NIDA, Brain Imaging Sect, Intramural Res Program, Baltimore, MD USA. NIDA, Mol Neuropsychiat Sect, Intramural Res Program, Baltimore, MD USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. NICHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. RP Contoreggi, C (reprint author), Brain Imaging Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 30 TC 28 Z9 30 U1 0 U2 0 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 NOV 1 PY 2003 VL 54 IS 9 BP 873 EP 878 DI 10.1016/S0006-3223(03)00167-7 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 734NH UT WOS:000186062000002 PM 14573313 ER PT J AU Wernicke, C Samochowiec, J Schmidt, LG Winterer, G Smolka, M Kucharska-Mazur, J Horodnicki, J Gallinat, E Rommelspacher, H AF Wernicke, C Samochowiec, J Schmidt, LG Winterer, G Smolka, M Kucharska-Mazur, J Horodnicki, J Gallinat, E Rommelspacher, H TI Polymorphisms in the N-methyl-D-aspartate receptor 1 and 2B subunits are associated with alcoholism-related traits SO BIOLOGICAL PSYCHIATRY LA English DT Article DE GRIN1; GRIN2B; alcoholism; withdrawal; TDT; FRET probes ID ETHANOL WITHDRAWAL SEIZURES; GENE; INHIBITION; DOMAIN; SCHIZOPHRENIA; EXPRESSION; ANTAGONIST; INTERVIEW; GRIN2B AB Background: This study examined the hypothesis that allelic variants of the ionotropic glutamatergic N-methyl-D-aspartate receptor (NMDAR) are associated with vulnerability to alcoholism and some related traits. Methods: We investigated the silent G2108A and C2664T polymorphisms of the NMDAR1 and the NMDAR2B genes, respectively. The case control study included 367 alcoholic and 335 control subjects of German origin. The family-based study comprised 81 Polish alcoholic patients and their parents using the transmission disequilibrium test. Results: The genotype frequencies of the NMDAR1 polymorphism differed significantly between control and alcoholic subjects. This difference was also observed in more homogenous subgroups of alcoholic subjects with vegetative withdrawal syndrome and Cloninger type 1. Patients with a history of delirium tremens or seizures during withdrawal showed a significantly increased prevalence of the A allele. Genotyping of the NMDAR2B polymorphism revealed a significantly reduced T allele in Cloninger type 2 alcoholics and in patients reporting an early onset compared with control subjects. Our family-based study for NMDAR2B, revealed a trend to a preferred transmission of the C allele by the fathers, and families with early-onset patients contributed most to this trend. Conclusions: These results suggest that variants in NMDAR genes are associated with alcoholism and related traits. (C) 2003 Society of Biological Psychiatry. C1 Free Univ Berlin, Hosp Benjamin Franklin, Dept Clin Neurobiol, D-14050 Berlin, Germany. Free Univ Berlin, Hosp Benjamin Franklin, Dept Psychiat, D-14050 Berlin, Germany. Pomeranian Acad Med, Dept Psychiat, Szczecin, Poland. Univ Mainz, Psychiat Clin, D-6500 Mainz, Germany. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Wernicke, C (reprint author), Free Univ Berlin, Hosp Benjamin Franklin, Dept Clin Neurobiol, Ulmenallee 32, D-14050 Berlin, Germany. RI Smolka, Michael/B-4865-2011; Samochowiec, Jerzy/G-8175-2014; Kucharska-Mazur, Jolanta/O-7796-2014 OI Smolka, Michael/0000-0001-5398-5569; Samochowiec, Jerzy/0000-0003-1438-583X; Kucharska-Mazur, Jolanta/0000-0002-8063-3662 NR 26 TC 42 Z9 43 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2003 VL 54 IS 9 BP 922 EP 928 DI 10.1016/S0006-3223(03)00072-6 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 734NH UT WOS:000186062000009 PM 14573320 ER PT J AU Haverkos, HW Battula, N Drotman, DP Rennert, OM AF Haverkos, HW Battula, N Drotman, DP Rennert, OM TI Enteroviruses and type 1 diabetes mellitus SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE enterovirus; type 1 diabetes mellitus; cofactors ID COXSACKIE-B-VIRUS; MOLECULAR MIMICRY; JUVENILE-ONSET; ENCEPHALOMYOCARDITIS VIRUS; CELL AUTOIMMUNITY; IDENTICAL-TWINS; IGM RESPONSES; RISK-FACTOR; HLA-DQ; CHILDREN C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Haverkos, HW (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD-530,5600 Fishers Lane, Rockville, MD 20857 USA. NR 90 TC 24 Z9 24 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD NOV PY 2003 VL 57 IS 9 BP 379 EP 385 DI 10.1016/j.biopha.2003.03.001 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 746CC UT WOS:000186728100001 PM 14652163 ER PT J AU Mohan, S Sinha, N Smith-Gill, J AF Mohan, S Sinha, N Smith-Gill, J TI Modeling the binding sites of anti-hen egg white lysozyme antibodies HyHEL-8 and HyHEL-26: An insight into the molecular basis of antibody cross-reactivity and specificity SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN-PROTEIN INTERFACES; CRYSTAL-STRUCTURE; COMBINING SITE; MONOCLONAL-ANTIBODIES; SALT BRIDGES; DIRECTED MUTAGENESIS; STRUCTURAL MODEL; HYPERVARIABLE REGIONS; ANTILYSOZYME ANTIBODY; CANONICAL STRUCTURES AB Three antibodies, HyHEL-8 (HH8), HyHEL-10 (HH10), and HyHEL-26 (HH26) are specific for the same epitope on hen egg white lysozyme (HEL), and share >90% sequence homology. Their affinities vary by several orders of magnitude, and among the three antibodies, HH8 is the most cross-reactive with kinetics of binding that are relatively invariable compared to HH26, which is highly specific and has quite variable kinetics. To investigate structural correlates of these functional variations, the Fv regions of HH8 and HH26 were homology-modeled using the x-ray structure of the well-characterized HH10-HEL complex as template. The binding site of HH26 is most charged, least hydrophobic, and has the greatest number of intramolecular salt bridges, whereas that of HH8 is the least charged, most hydrophobic and has the fewest intramolecular salt bridges. The modeled HH26-HEL structure predicts the recently determined x-ray structure of HH26, (Li et al., 2003, Nat. Struct. Biol. 10:482-488) with a root-mean-square deviation of 1.03 Angstrom. It is likely that the binding site of HH26 is rendered rigid by a network of intramolecular salt bridges whereas that of HH8 is flexible due to their absence. HH26 also has the most intermolecular contacts with the antigen whereas HH8 has the least. HH10 has these properties intermediate to HH8 and HH26. The structurally rigid binding site with numerous specific contacts bestows specificity on HH26 whereas the flexible binding site with correspondingly fewer contacts enables HH8 to be cross-reactive. Results suggest that affinity maturation may select for high affinity antibodies with either "lock-and-key'' preconfigured binding sites, or "preconfigured flexibility'' by modulating combining site flexibility. C1 NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Smith-Gill, J (reprint author), NCI, Struct Biophys Lab, Ctr Canc Res, POB B,Bldg 469,Rm 206, Frederick, MD 21702 USA. EM smithgil@helix.nih.gov NR 99 TC 22 Z9 22 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV 1 PY 2003 VL 85 IS 5 BP 3221 EP 3236 PG 16 WC Biophysics SC Biophysics GA 736UA UT WOS:000186190500041 PM 14581222 ER PT J AU Esposito, D Gillette, WK Hartley, JL AF Esposito, D Gillette, WK Hartley, JL TI Blocking oligonucleotides improve sequencing through inverted repeats SO BIOTECHNIQUES LA English DT Article ID STRATEGY; GENOME C1 NCI, Prot Express Lab, SAIC, Frederick, MD 21702 USA. RP Esposito, D (reprint author), NCI, Prot Express Lab, SAIC, Bldg 327,POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 8 TC 4 Z9 7 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 2003 VL 35 IS 5 BP 914 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 744QL UT WOS:000186643500003 PM 14628662 ER PT J AU Choy, G O'Connor, S Diehn, FE Costouros, N Alexander, HR Choyke, P Libutti, SK AF Choy, G O'Connor, S Diehn, FE Costouros, N Alexander, HR Choyke, P Libutti, SK TI Comparison of noninvasive fluorescent and bioluminescent small animal optical imaging SO BIOTECHNIQUES LA English DT Article ID IN-VIVO; GENE-EXPRESSION; ORTHOTOPIC MODEL; PROTEIN; CANCER; METASTASIS; REPORTER; TUMORS; GROWTH; CELLS AB Optical imaging is a modality that is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. For this study, we used a green fluorescent protein (GFP)- and luciferase-expressing mouse tumor model to compare and contrast the quantitative and qualitative capabilities of a fluorescent reporter gene (GFP) and a bioluminescent reporter gene (luciferase). We describe the relationship between tumor volume, tumor mass, and bioluminescent/fluorescent intensity for both GFP and luciferase. Bioluminescent luciferase imaging was shown to be more sensitive than fluorescent GFP imaging. Luciferase-expressing tumors were detected as early as 1 day after tumor cell inoculation, whereas GFP-expressing tumors were not detected until 7 days later. Both bioluminescent and fluorescent intensity correlated significantly and linearly with tumor volume and tumor weight, as measured by caliper Compared to bioluminescent imaging,fluorescent imaging does not require the injection of a substrate and may be appropriate for applications where sensitivity is not as critical. Knowing the relative strengths of each imaging modality will be important in guiding the decision to use fluorescence or bioluminescence. C1 NCI, Surg Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Canc Res Ctr, 10 Ctr Dr,Room 2B07, Bethesda, MD 20892 USA. NR 28 TC 81 Z9 85 U1 5 U2 22 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 2003 VL 35 IS 5 BP 1022 EP + PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 744QL UT WOS:000186643500017 PM 14628676 ER PT J AU Klarmann, K Ortiz, M Davies, M Keller, JR AF Klarmann, K Ortiz, M Davies, M Keller, JR TI Identification of in vitro growth conditions for c-Kit-negative hematopoietic stem cells SO BLOOD LA English DT Article ID BONE-MARROW; PROGENITOR CELLS; FUNCTIONAL-CHARACTERIZATION; COLONY FORMATION; FACTOR-BETA; MURINE; MOUSE; EXPRESSION; VIVO; PLURIPOTENT AB Our laboratory recently identified a quiescent class of pluripotent hematopoietic stem cells (PHSCs) that are lineage negative (Lin(neg)), lack c-Kit, and are able to give rise to c-Kit-positive (c-Kit(pos)) PHSCs in vivo. This population fails to proliferate in vitro but has delayed reconstituting activity in vivo. In this study, we purified these cells to enrich for the PHSCs and we identified in vitro conditions capable of supporting their maturation. The c-Kit-negative (c-Kit(neg)) cells exhibited differential expression of Sca-1, CD34, CD43, CD45, and Thy 1.2. We purified the cells based on Sca-1, as it is expressed on active PHSCs. We detected pre-colony-forming unit spleen (pre-CFU-s) activity in both the Sca-1(neg) and Sca-1(pos) populations, indicating the presence of primitive PHSCs in both populations. However, our in vitro studies suggest that the Sca-1(pos) population is enriched for PHSCs. The in vitro systems that support the growth of these dormant cells include a modified long-term marrow culture and various stromal cell lines. In modified long-term bone marrow cultures, c-Kit(neg) cells gave rise to c-Kit(pos) PHSCs, with long-term reconstitution activity in vivo. Thus we have established an in vitro system to examine PHSC maturation that will allow us to study the mediators of the c-Kit(neg) to c-Kit(pos) transition. (C) 2003 by The American Society of Hematology. C1 NCI, Mol Immunoregulat Lab, Basic Res Program, Sci Applicat Int Corp,Ctr Canc Res, Frederick, MD 21702 USA. RP Klarmann, K (reprint author), NCI, Mol Immunoregulat Lab, Basic Res Program, Sci Applicat Int Corp,Ctr Canc Res, Bldg 560,Rm 12-03, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 47 TC 16 Z9 16 U1 0 U2 1 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 NOV 1 PY 2003 VL 102 IS 9 BP 3120 EP 3128 DI 10.1182/blood-2003-04-1249 PG 9 WC Hematology SC Hematology GA 736BA UT WOS:000186149400016 PM 12855562 ER PT J AU Golding, H Aliberti, J King, LR Manischewitz, J Andersen, J Valenzuela, J Landau, NR Sher, A AF Golding, H Aliberti, J King, LR Manischewitz, J Andersen, J Valenzuela, J Landau, NR Sher, A TI Inhibition of HIV-1 infection by a CCR5-binding cyclophilin from Toxoplasma gondii SO BLOOD LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CCR5; SMALL-MOLECULE INHIBITOR; CELL-LINE; STRUCTURAL DETERMINANTS; MONOCLONAL-ANTIBODIES; PRIMARY MACROPHAGES; CORECEPTOR ACTIVITY; CXCR4 CORECEPTOR; DENDRITIC CELLS AB The activation of murine dendritic cells by Toxoplasma gondii has recently been shown to depend on a parasite protein that signals through the chemokine receptor CCR5. Here we demonstrate that this molecule, cyclophilin-18 (C-18), is an inhibitor of HIV-1 cell fusion and infection with cell-free virus. T gondii C-18 efficiently blocked syncytium formation between human T cells and effector cells expressing R5 but not X4 envelopes. Neither human nor Plasmodium falciparum cyclophilins possess such inhibitory activity. Importantly, C-18 protected peripheral blood leukocytes from infection with multiple HIV-1 R5 primary isolates from several clades. C-18 bound directly to human CCR5, and this interaction was partially competed by the beta-chemokine macrophage inflammatory protein 1beta (MIP-1beta) and by HIV-1 R5 gp120. In contrast to several other antagonists of HIV coreceptor function, C-18 mediated inhibition did not induce beta-chemokines or cause CCR5 down-modulation, suggesting direct blocking of envelope binding to the receptor. These data support the further development of C-18 derivatives as HIV-1 inhibitors for preventing HIV-1 transmission and for postexposure prophylaxis. (C) 2003 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Infect Dis Lab, La Jolla, CA 92037 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Rm 1A21,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 44 TC 26 Z9 28 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2003 VL 102 IS 9 BP 3280 EP 3286 DI 10.1182/blood-2003-04-1096 PG 7 WC Hematology SC Hematology GA 736BA UT WOS:000186149400037 PM 12855560 ER PT J AU Yang, D Rosenberg, HF Chen, Q Dyer, KD Kurosaka, K Oppenheim, JJ AF Yang, D Rosenberg, HF Chen, Q Dyer, KD Kurosaka, K Oppenheim, JJ TI Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells SO BLOOD LA English DT Article ID DIFFERENTIAL REGULATION; ANTIBACTERIAL PEPTIDE; HUMAN-NEUTROPHILS; P42/44 MAPK; GENE FAMILY; RIBONUCLEASE; CHEMOATTRACTANT; DEFENSINS; RECEPTOR; EXPRESSION AB Recent publications have highlighted the chemotactic activities of antimicrobial proteins derived from the granules of neutrophils and basophils. Eosinophil granules also contain antimicrobial proteins. One of them is eosinophil-derived neurotoxin (EDN), a protein belonging to the ribonuclease A (RNase A) superfamily, which has recently been found to have antiviral activity in vitro. We found that EDN was selectively chemotactic for dendritic cells (DCs). The DC chemotactic activity of EDN was inhibited by either pretreatment of DCs with pertussis toxin or by simultaneous addition of placental RNase inhibitor to inhibit the activity of EDN. EDN was not chemotactic for leukocytes other than DCs. Mouse eosinophil-associated RNase 2 (mEAR2), one of a cluster of divergent orthologs of human EDN, was also chemotactic for human as well as mouse DCs. Sequence and mutational analysis demonstrated the importance of the N-terminal region of mEAR2 in mediating its chemotactic effect on DCs. EDN also induced the activation of p42/44 mitogen-activated protein kinase (MAPK) in DCs. Furthermore, injection of mEAR2 into the air pouches of mice resulted in the recruitment of DCs into the air pouches. Thus, EDN and its mouse ortholog, mEAR2, are eosinophil granule-derived antimicrobial RNases that function as chemoattractants for DCs in vitro and in vivo. (C) 2003 by The American Society of Hematology. C1 NCI, CCR, SAIC Frederick, BRP, Frederick, MD 21702 USA. Natl Canc Inst, Ctr Canc Res, Mol Immunoregulat Lab, NIH, Frederick, MD USA. NIAID, Eosinophil Pathophysiol Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Yang, D (reprint author), NCI, CCR, SAIC Frederick, BRP, Bldg 560,Rm 31-19, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 44 TC 72 Z9 79 U1 0 U2 1 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 NOV 1 PY 2003 VL 102 IS 9 BP 3396 EP 3403 DI 10.1182/blood-2003-01-0151 PG 8 WC Hematology SC Hematology GA 736BA UT WOS:000186149400053 PM 12855582 ER PT J AU Jung, U Foley, JE Erdmann, AA Eckhaus, MA Fowler, DH AF Jung, U Foley, JE Erdmann, AA Eckhaus, MA Fowler, DH TI CW/CD28-costimulated T1 and T2 subsets: differential in vivo allosensitization generates distinct GVT and GVHD effects SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CD28 COSTIMULATION; FAS-LIGAND; CELL SUBPOPULATIONS; ADOPTIVE TRANSFER; TH2 CYTOKINES; IFN-GAMMA; GRAFT; TUMOR AB Adoptive T-cell therapy using CD3/CD28 co-stimulation likely requires in vivo generation of antigen specificity. Because CD28 promotes T(H)1/T(C)1 (T1) or T(H)2/T(C)2 (T2) differentiation, costimulation may generate donor T1 or T2 cells capable of differentially mediating allogeneic graft-versus-tumor (GVT) effects and graft-versus-host disease (GVHD). Costimulation under T1 or T2 conditions indeed generated murine T(H)1/T(C)1 cells secreting interleukin-2/interferon-gamma (IL-2/ IFN-gamma) or T(H)2/T(C)2 cells secreting IL-4/IL-5/IL-10. In vivo, allogeneic T1 cells expanded, maintained T1 secretion, and acquired allospecificity involving IFN-gamma and IL-5. In contrast, allogeneic T2 cells expanded less and maintained T2 secretion but did not develop significant allospecificity. Allogeneic, but not syngeneic, T1 cells mediated a GVT effect against host-type breast cancer cells, as median survival time (MST) increased from 25.6 +/- 2.6 (tumor controls) to 69.2 +/- 5.9 days (P < 1.2 x 10(-9)). This T1 -associated GVT effect operated independently of fasL because T1 cells from gld mice mediated tumor-free survival. In contrast, allogeneic T2 cells mediated a modest, noncurative GVT effect (MST, 29 +/- 1.3 days; P <.0019). T1 recipients had moderate GVHD (histologic score, 4 of 12) that contributed to lethality after bone marrow transplantation; in contrast, T2 recipients had minimal GVHD (histologic score, 1 of 12). CD3/CD28 costimulation, therefore, generates T1 or T2 populations with differential in vivo capacity for expansion to alloantigen, resulting in differential GVT effects and GVHD. (C) 2003 by The American Society of Hematology. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Off Res Serv, Vet Resources Program, Bethesda, MD 20892 USA. RP Jung, U (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 55 TC 36 Z9 40 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2003 VL 102 IS 9 BP 3439 EP 3446 DI 10.1182/blood-2002-12-3936 PG 8 WC Hematology SC Hematology GA 736BA UT WOS:000186149400058 PM 12855580 ER PT J AU Gordeuk, VR Caleffi, A Corradini, E Ferrara, F Jones, RA Castro, O Onyekwere, O Kittles, R Pignatti, E Montosi, G Garuti, C Gangaidzo, IT Gomo, ZAR Moyo, VM Rouault, TA MacPhail, P Pietrangelo, A AF Gordeuk, VR Caleffi, A Corradini, E Ferrara, F Jones, RA Castro, O Onyekwere, O Kittles, R Pignatti, E Montosi, G Garuti, C Gangaidzo, IT Gomo, ZAR Moyo, VM Rouault, TA MacPhail, P Pietrangelo, A TI Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article ID AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; HEREDITARY HEMOCHROMATOSIS; SLC11A3; DELETION AB The product of the SLC40A1 gene, ferroportin 1, is a main iron export protein. Pathogenic mutations in ferroportin I lead to an autosomal dominant hereditary iron overload syndrome characterized by high serum ferritin concentration, normal transferrin saturation, iron accumulation predominantly in macrophages, and marginal anemia. Iron overload occurs in both the African and the African-American populations, but a possible genetic basis has not been established. We analyzed the ferroportin I gene in 19 unrelated patients from southern Africa (N = 15) and the United States (N = 4) presenting with primary iron overload. We found a new c. 744 C-->T (Q248H) mutation in the SLC40A1 gene in 4 of these patients (3 Africans and I African-American). Among 22 first degree family members, 10 of whom were Q248H heterozygotes, the mutation was associated with a trend to higher serum ferritin to amino aspartate transferase ratios (means of 14.8 versus 4.3 mug/U; P = 0.1) and lower hemoglobin concentrations (means of 11.8 versus 13.2 g/dL; P = 0.1). The ratio corrects serum ferritin concentration for alcohol-induced hepatocellular damage. We also found heterozygosity for the Q248H mutation in 7 of 51 (14%) southern African community control participants selected because they had a serum ferritin concentration below 400 mug/L and in 5 of 100 (5%) anonymous African-Americans, but we did not find the change in 300 Caucasians with normal iron status and 25 Caucasians with non-HFE iron overload. The hemoglobin concentration was significantly lower in the African community controls with the Q248H mutation than in those without it. We conclude that the Q248H mutation is a common polymorphism in the ferroportin I gene in African populations that may be associated with mild anemia and a tendency to iron loading. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Modena, Dept Internal Med, Policlin, I-41100 Modena, Italy. Howard Univ, Coll Med, Washington, DC 20059 USA. Chattanooga Oncol & Hematol Associates, Chattanooga, TN 37404 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Univ Connecticut, Dept Med, Storrs, CT 06269 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Univ Witwatersrand, Dept Med, ZA-2001 Johannesburg, South Africa. RP Pietrangelo, A (reprint author), Univ Modena, Dept Internal Med, Policlin, Via Pozzo 71, I-41100 Modena, Italy. RI Corradini, Elena/O-4167-2016; Pietrangelo, Antonello/K-1517-2016 OI Corradini, Elena/0000-0001-9477-2164; Pietrangelo, Antonello/0000-0002-7411-935X FU NCRR NIH HHS [M01 RR 10284]; NHLBI NIH HHS [UH1 HL 03679-05] NR 18 TC 119 Z9 121 U1 1 U2 3 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 NOV-DEC PY 2003 VL 31 IS 3 BP 299 EP 304 DI 10.1016/S1079-9796(03)00164-5 PG 6 WC Hematology SC Hematology GA 748DD UT WOS:000186846200001 PM 14636642 ER PT J AU Sloand, E Childs, RW Solomon, S Greene, A Young, NS Barrett, AJ AF Sloand, E Childs, RW Solomon, S Greene, A Young, NS Barrett, AJ TI The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia SO BONE MARROW TRANSPLANTATION LA English DT Article DE chronic myelogenous leukemia; graft-versus-leukemia; nonmyeloablative stem cell transplantation ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; TOTAL-BODY IRRADIATION; IMMUNOTHERAPY; CYCLOPHOSPHAMIDE; BUSULFAN; THERAPY; RELAPSE AB We treated 12 patients with chronic myelogenous leukemia (CML) with a low-intensity preparative regimen followed by allogeneic stem cell transplantation in an attempt to confer a curative graft-versus-leukemia (GVL) effect with minimum morbidity. Seven patients in first chronic phase (CP1) and five in second chronic phase (CP2) (age 15-68 years) received a nonmyeloablative conditioning regimen of fludarabine and cyclophosphamide, followed by a G-CSF-mobilized peripheral blood stem cell (PBSC) transplant from an HLA-identical sibling. Cyclosporine (CsA) was used for graft-versus-host disease (GVHD) prophylaxis. Median follow-up was 384 days. Neutrophil recovery occurred at a median of 12 days. There was no transplant-related mortality. Of the seven CP1 patients transplanted, seven achieved a stable molecular remission; two with no post-transplant intervention, three after donor lymphocytes, imatinib and interferon, and two after a myeloablative stem cell transplant. Four of five CP2 patients died in blast crisis and one survived in molecular remission. Of the 12 patients with durable engraftment, six had Grades II-IV acute GVHD; six had limited chronic GVHD. These results suggest that cytoreduction is required to optimize the curative effect of allogeneic stem cell transplantation for CML. C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10 Rm 7C103, Bethesda, MD 20892 USA. NR 17 TC 28 Z9 29 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2003 VL 32 IS 9 BP 897 EP 901 DI 10.1038/sj.bmt.1704231 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 733NW UT WOS:000186008400007 PM 14561990 ER PT J AU Pompeia, C Cury-Boaventura, MF Curi, R AF Pompeia, C Cury-Boaventura, MF Curi, R TI Arachidonic acid triggers an oxidative burst in leukocytes SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE arachidonic acid; NADPH oxidase; nitroblue tetrazolium; leukocytes; reactive oxygen species ID PROTEIN-KINASE-C; UNSATURATED FATTY-ACIDS; NADPH OXIDASE ACTIVITY; PHOSPHOLIPASE A(2); POLYMORPHONUCLEAR LEUKOCYTES; SUPEROXIDE GENERATION; SIGNALING PATHWAYS; PHORBOL ESTER; FREE-RADICALS; IN-VITRO AB The change in cellular reducing potential, most likely reflecting an oxidative burst, was investigated in arachidonic acid- (AA) stimulated leukocytes. The cells studied included the human leukemia cell lines HL-60 (undifferentiated and differentiated into macrophage-like and polymorphonuclear-like cells), Jurkat and Raji, and thymocytes and macrophages from rat primary cultures. The oxidative burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative burst until an optimum AA concentration was reached and the burst decreased thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to 400 muM (up to 16-fold), whereas in rat cells it varied from 10 to 20 muM. Initial rates of superoxide generation were high, decreasing steadily and ceasing about 2 h post-treatment. The continuous presence of AA was not needed to stimulate superoxide generation. It seems that the NADPH oxidase system participates in AA-stimulated superoxide production in these cells since the oxidative burst was stimulated by NADPH and inhibited by N-ethylmaleimide, diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the oxidative burst may be due to its detergent action. There apparently was no contribution of other superoxide-generating systems Such as xanthine-xanthine oxidase, cytochromes P-450 and mitochondrial electron transport chain, as assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem to interfere with the AA-stimulated oxidative burst since there was no systematic effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but lipid peroxides may play a role, as indicated by the inhibition of nitroblue tetrazolium reduction promoted by tocopherol. C1 NCI, NIH, Frederick, MD 21702 USA. Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, Lab Fisiol Celular, BR-05508 Sao Paulo, Brazil. RP Pompeia, C (reprint author), NCI, NIH, Bldg 560,Rm 31-76,POB B, Frederick, MD 21702 USA. RI Cury-Boaventura, Maria Fernanda/B-3945-2012 NR 32 TC 32 Z9 32 U1 1 U2 2 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD NOV PY 2003 VL 36 IS 11 BP 1549 EP 1560 DI 10.1590/S0100-879X2003001100013 PG 12 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 740CN UT WOS:000186383700012 PM 14576910 ER PT J AU Battiwalla, M Melenhorst, J Saunthararajah, Y Nakamura, R Molldrem, J Young, NS Barrett, AJ AF Battiwalla, M Melenhorst, J Saunthararajah, Y Nakamura, R Molldrem, J Young, NS Barrett, AJ TI HLA-DR4 predicts haematological response to cyclosporine in T-large granular lymphocyte lymphoproliferative disorders SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE large granular lymphocytic leukaemia; T-cell large granular lymphocyte (T-LGL); human leucocyte antigen (HLA); cyclosporine ID MYELODYSPLASTIC SYNDROME; PROLIFERATIVE DISORDERS; RHEUMATOID-ARTHRITIS; APLASTIC-ANEMIA; FELTYS-SYNDROME; P-GLYCOPROTEIN; LGL LEUKEMIA; EXPRESSION; NEUTROPENIA; DISEASES AB T-cell large granular lymphocytic lymphoproliferative disease (T-LGL) is often associated with life-threatening cytopenias. Twenty-five subjects with anaemia and/or neutropenia caused by T-LGL were treated with cyclosporin A (CSA) 5-10 mg/kg/d for at least 3 months. Eighteen patients survived between 35 and 77 months after starting treatment. Fourteen patients [56%; 95% confidence interval (CI) 35-76%] responded to CSA with sustained improvement in the neutrophil count or transfusion independence. Seven had complete normalization of blood counts, and four achieved a durable response only after the addition of erythropoietin. Sustained response required continued low-dose CSA. In a multivariate analysis, HLA-DR4 was highly predictive of CSA responsiveness (odds ratio 18; 95% CI 1.8-184). T-LGL subtype, LGL counts after therapy, lymphocytic marrow infiltration and bone marrow cellularity did not significantly affect the probability of response. We conclude that CSA is effective in inducing haematological responses in HLA-DR4-positive patients and that T-LGL is likely to have an immune pathogenesis. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Illinois, Hematol Oncol Sect, Chicago, IL USA. City Hope Natl Med Ctr, Div Hematol & Bone Marrow Transplantat, Duarte, CA 91010 USA. Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 31 Z9 34 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2003 VL 123 IS 3 BP 449 EP 453 DI 10.1046/j.1365-2141.2003.04613.x PG 5 WC Hematology SC Hematology GA 734HE UT WOS:000186048600010 PM 14617004 ER PT J AU Pawlosky, R Hibbeln, J Lin, YH Salem, N AF Pawlosky, R Hibbeln, J Lin, YH Salem, N TI n-3 Fatty acid metabolism in women SO BRITISH JOURNAL OF NUTRITION LA English DT Editorial Material ID ALPHA-LINOLENIC ACID C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Pawlosky, R (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Room 116,12420 Parklawn Dr, Rockville, MD 20852 USA. NR 4 TC 68 Z9 68 U1 0 U2 0 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD NOV PY 2003 VL 90 IS 5 BP 993 EP 994 DI 10.1079/BJN2003985 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 739WW UT WOS:000186370600016 PM 14667193 ER PT J AU Gerdeman, GL Lovinger, DM AF Gerdeman, GL Lovinger, DM TI Emerging roles for endocannabinoids in long-term synaptic plasticity SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE striatum; nucleus accumbens; hippocampus; long-term potentiation; long-term depression; cannabinoids; CB1 receptor; retrograde messenger ID DEPOLARIZATION-INDUCED SUPPRESSION; ENDOGENOUS CANNABINOID ANANDAMIDE; METABOTROPIC GLUTAMATE RECEPTORS; PRECIPITATED WITHDRAWAL SIGNS; CEREBELLAR PURKINJE-CELLS; RAT PREFRONTAL CORTEX; ACID AMIDE HYDROLASE; CB1 RECEPTOR; HIPPOCAMPAL SYNAPSES; PYRAMIDAL NEURONS C1 NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. Univ Arizona, Hlth Sci Ctr, Dept Pharmacol, Tucson, AZ 85724 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Room 158H,Pk 5 Bldg,12420 Parklawn Dr, Rockville, MD 20852 USA. NR 78 TC 77 Z9 81 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD NOV PY 2003 VL 140 IS 5 BP 781 EP 789 DI 10.1038/sj.bjp.0705466 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 737PK UT WOS:000186240800001 PM 14504143 ER PT J AU Chen, E Yuan, ZA Wright, JT Hong, SP Li, Y Collier, PM Hall, B D'Angelo, M Decker, S Piddington, R Abrams, WR Kulkarni, AB Gibson, CW AF Chen, E Yuan, ZA Wright, JT Hong, SP Li, Y Collier, PM Hall, B D'Angelo, M Decker, S Piddington, R Abrams, WR Kulkarni, AB Gibson, CW TI The small bovine amelogenin LRAP fails to rescue the amelogenin null phenotype SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE enamel; amelogenin; null and transgenic mice; leucine-rich amelogenin peptide (LRAP); hypoplasia ID DEVELOPING DENTAL ENAMEL; MOUSE TOOTH DEVELOPMENT; MATRIX PROTEINS; GENE-EXPRESSION; IMPERFECTA AIH1; TRANSLATION PRODUCT; MESSENGER-RNAS; IN-VIVO; MUTATION; IDENTIFICATION AB Amelogenins are the most abundant secreted proteins in developing dental enamel. These evolutionarily-conserved proteins have important roles in enamel mineral formation, as mutations within the amelogenin gene coding region lead to defects in enamel thickness or mineral structure. Because of extensive alternative splicing of the primary RNA transcript and proteolytic processing of the secreted proteins, it has been difficult to assign functions to individual amelogenins. To address the function of one of the amelogenins, we have created a transgenic mouse that expresses bovine leucine-rich amelogenin peptide (LRAP) in the enamel-secreting ameloblast cells of the dental organ. Our strategy was to breed this transgenic mouse with the recently generated amelogenin knockout mouse, which makes none of the amelogenin proteins and has a severe hypoplastic and disorganized enamel phenotype. It was found that LRAP does not rescue the enamel defect in amelogenin null mice. and enamel remains hypoplastic and disorganized in the presence of this small amelogenin. In addition, LRAP overexpression in the transgenic mouse (wildtype background) leads to pitting in the enamel surface, which may result from excess protein production or altered protein processing due to minor differences between the amino acid compositions of murine and bovine LRAP. Since introduction of bovine LRAP into the amelogenin null mouse does not restore normal enamel structure, it is concluded that other amelogenin proteins are essential for normal appearance and function. C1 Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC USA. NIDCR, Funct Genom Unit & Gene Targeting Facil, NIH, Bethesda, MD USA. RP Gibson, CW (reprint author), Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, 240 S 40th St, Philadelphia, PA 19104 USA. EM gibson@biochem.dental.upenn.edu RI Abrams, William/A-5782-2008 FU NIDCR NIH HHS [DE11089, DE12879] NR 64 TC 28 Z9 28 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD NOV PY 2003 VL 73 IS 5 BP 487 EP 495 DI 10.1007/s00223-002-0036-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 748BQ UT WOS:000186842300009 PM 12958690 ER PT J AU Wang, W Macaulay, RJB AF Wang, W Macaulay, RJB TI Cell-cycle gene expression in lovastatin-induced medulloblastoma apoptosis SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID PRIMITIVE NEUROECTODERMAL TUMORS; DEPENDENT KINASE INHIBITORS; CENTRAL-NERVOUS-SYSTEM; C-MYC EXPRESSION; WILD-TYPE P53; P53-DEPENDENT APOPTOSIS; ISOPRENOID BIOSYNTHESIS; SUPPRESSOR GENES; BREAST CELLS; DNA DAMAGE AB Background: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a key rate-limiting enzyme in the mevalonate pathway, which generates precursors both for cholesterol biosynthesis and for the production of nonsteroidal mevalonate derivatives that are involved in a number of growth-regulatory processes. We have reported that lovastatin, a competitive inhibitor of HMG-CoA reductase, not only inhibits medulloblastoma proliferation in vitro, but also induces near-complete cell death via apoptosis. The mechanism of this phenomenon is unclear. Possible involvement of changes in expression of certain cell-cycle related genes led us to study some of them in more detail. Methods: Medulloblastoma cell lines were exposed in vitro to lovastatin, and the effects of gene expression changes were studied using RT-PCR, antisense oligonucleotide, DNA electrophoresis and Western blotting analysis. Results: 1) Levels of total Ras gene mRNA and individual Ras gene mRNA are stable in lovastatin treatment in all examined medulloblastoma cell lines. 2) Blocking c-myc gene over-expression does not enhance medulloblastoma cell sensitivity to lovastatin. 3) Following lovastatin treatment, p16 expression exhibits no change, but pronounced increases of p27(KIP1) protein are observed in all examined cell lines. Lovastatin induces pronounced increases of p21(WAF1) protein only in Daoy and UW228, but not in D283 Med and D341 Med. 4) Following lovastatin treatment. increased p53 protein is detected only in D341 Med, and bax protein is unchanged in all cell lines. Conclusions: Lovastatin-induced growth inhibition and apoptosis in medulloblastoma are not dependent on the regulation of Ras and c-myc gene expression, but may be mediated by p27(KIP1) gene expression. Lovastatin-induced apoptosis in medulloblastoma is probably p53 independent, but p53 and p21(WAF1) gene expression may also mediate anti-proliferative effects of lovastatin on specific medulloblastoma cell lines. C1 QEII, Hlth Sci Ctr, Dept Pathol, Dept Pathol & Lab Med, Halifax, NS B3H 1V8, Canada. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Dalhousie Univ, Halifax, NS B3H 1V8, Canada. RP Macaulay, RJB (reprint author), QEII, Hlth Sci Ctr, Dept Pathol, Dept Pathol & Lab Med, QEII HSC,Room 738,5788 Univ Ave, Halifax, NS B3H 1V8, Canada. NR 76 TC 10 Z9 10 U1 0 U2 2 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY, AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD NOV PY 2003 VL 30 IS 4 BP 349 EP 357 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 744WN UT WOS:000186656000010 PM 14672267 ER PT J AU Forman, MR Ballard-Barbash, R Kipnis, V AF Forman, MR Ballard-Barbash, R Kipnis, V TI Nutritional strategies for breast cancer prevention: What have we learned and where do we go from here? SO CANCER LA English DT Editorial Material ID HIGH-FIBER DIET; SERUM ESTROGEN CONCENTRATIONS; LOW-FAT DIET; PREMENOPAUSAL WOMEN; PLASMA CAROTENOIDS; HORMONE LEVELS; HIGH-FRUIT; RISK; INTERVENTION; CONSUMPTION C1 NCI, Basic Res Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Forman, MR (reprint author), NCI, Basic Res Lab, Ctr Canc Res, 6116 Execut Blvd,Suite 702-Rm 7220, Bethesda, MD 20892 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2003 VL 98 IS 9 BP 1782 EP 1785 DI 10.1002/cncr.11732 PG 4 WC Oncology SC Oncology GA 736BG UT WOS:000186150000002 PM 14584058 ER PT J AU Trimble, EL Cornelison, TL Follen, M Montz, FJ AF Trimble, EL Cornelison, TL Follen, M Montz, FJ TI Foreword: Convening an international conference on cervical cancer SO CANCER LA English DT Editorial Material C1 Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Johns Hopkins Med Inst, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Follen, M (reprint author), Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, 1515 Holcombe Blvd,Unit 193, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2003 VL 98 IS 9 SU S BP 2001 EP 2002 DI 10.1002/cncr.11675 PG 2 WC Oncology SC Oncology GA 737ML UT WOS:000186236300001 ER PT J AU Follen, M Meyskens, FL Alvarez, RD Walker, JL Bell, MC Storthz, KA Sastry, J Roy, K Richards-Kortum, R Cornelison, TL AF Follen, M Meyskens, FL Alvarez, RD Walker, JL Bell, MC Storthz, KA Sastry, J Roy, K Richards-Kortum, R Cornelison, TL TI Cervical cancer chemoprevention, vaccines, and surrogate endpoint biomarkers SO CANCER LA English DT Article; Proceedings Paper CT 2nd International Conference on Cervical Cancer CY APR 11-14, 2002 CL HOUSTON, TEXAS DE cervical cancer; cervical intraepithelial neoplasia (CIN); chemoprevention; micronutrients; human papillomavirus (HPV); vaccines; antiviral agents; peptides ID TRANS-RETINOIC ACID; RANDOMIZED CLINICAL-TRIAL; PHASE-I TRIAL; INTRAEPITHELIAL NEOPLASIA; BETA-CAROTENE; COLLAGEN SPONGE; FOLIC-ACID; DYSPLASIA; CIDOFOVIR; REGRESSION AB At the Second International Conference on Cervical Cancer, held April 11-14, 2002, experts in cervical cancer prevention, detection, and treatment reviewed the need for more research in chemoprevention, including prophylactic and therapeutic vaccines, immuno modulators, peptides, and surrogate endpoint biomarkers. Investigators and clinicians noted the need for more rigorous Phase I randomized clinical trials, more attention to the risk factors that can affect study results in this patient population, and validation of optical technologies that will provide valuable quantitative information in real time regarding disease regression and progression. They discussed the role of the human papillomavirus (HPV) in cervical cancer development and the importance of developing strategies to suppress HPV persistence and progression. Results in Phase I randomized clinical trials have been disappointing because few have demonstrated statistically significant regression attributable to the agent tested. Researchers recommended using a transgenic mouse model to test and validate new compounds, initiating vaccine and immunomodulator trials, and developing immunologic surrogate endpoint biomarkers. (C) 2003 American Cancer Society. C1 Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, Dept Gynecol Oncol, Houston, TX 77030 USA. Chao Family Comprehens Canc Ctr, Orange, CA USA. Univ Alabama, Ctr Med, Birmingham, AL USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. Univ S Dakota, Ctr Med, Sioux Valley Hosp, Obstet & Gynecol Ltd, Sioux Falls, SD USA. Univ Texas, Hlth Sci Ctr, Houston Dent Branch, Dept Basic Sci, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Dept Vet Sci, Bastrop, TX USA. Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. NCI, Breast Gynecol Canc Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Follen, M (reprint author), Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, Dept Gynecol Oncol, 1515 Holcombe Blvd,Unit 193, Houston, TX 77030 USA. RI Richards-Kortum, Rebecca/P-4074-2014 OI Richards-Kortum, Rebecca/0000-0003-2347-9467 NR 37 TC 6 Z9 7 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2003 VL 98 IS 9 SU S BP 2044 EP 2051 DI 10.1002/cncr.11674 PG 8 WC Oncology SC Oncology GA 737ML UT WOS:000186236300007 PM 14603541 ER PT J AU Trimble, EL Bell, M Wolf, J Alvarez, R AF Trimble, EL Bell, M Wolf, J Alvarez, R TI Grantsmanship and career development for gynecologic cancer investigators SO CANCER LA English DT Article; Proceedings Paper CT 2nd International Conference on Cervical Cancer CY APR 11-14, 2002 CL HOUSTON, TEXAS DE grantsmanship; economics; health care economics and organizations; organized financing AB The gynecologic cancer investigator faces many challenges. Successful career development requires choosing commitments wisely after completing clinical training, earning board certification, and completing a fellowship. Finding protected time for research requires cooperation from the department chair, and lining up funding for research begins with the researcher's own institution and stretches as far away as European funding groups. State and federal agencies, particularly the National Cancer Institute, offer a wide range of opportunities to obtain funding and to seek information about how to shape research and applications. Professional societies and charities also fund initiatives. Advantages of working with a clinical trials cooperative group include large fund reserves, centralized data management, statistical support, the potential of rapid accrual from multiple sites, and an established infrastructure. Seeking multiple sources of funding probably is wise, and meeting grant deadlines requires organization and planning. Working with industry requires legal review; avoiding conflict of interest; working with appropriate federal agencies, such as the U.S. Food and Drug Administration; and careful review of contractual agreements. Today's successful investigator who wants to reduce the burden of cervical cancer seeks funding from multiple sources, including industry; makes use of the consulting advice available from state and federal governments and nonprofit organizations; establishes clear channels of communication; and consults appropriate legal and scientific advisors in planning a trial. Developing a successful academic career with a focus on research in gynecologic cancer requires planning and a supportive environment. 2003 American Cancer Society. C1 Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, Dept Gynecol Oncol, Houston, TX 77030 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Sioux Valley Univ Hosp, Dept Obstet & Gynecol, Sioux Falls, SD USA. Univ Alabama, Dept Gynecol Oncol, Birmingham, AL USA. RP Trimble, EL (reprint author), Univ Texas, MD Anderson Canc Ctr, Ctr Biomed Engn, Dept Gynecol Oncol, 1515 Holcombe Blvd,Unit 193, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2003 VL 98 IS 9 SU S BP 2075 EP 2081 DI 10.1002/cncr.11683 PG 7 WC Oncology SC Oncology GA 737ML UT WOS:000186236300011 PM 14603545 ER PT J AU Dancey, JE AF Dancey, JE TI Recent advances of molecular targeted agents - Opportunities for imaging SO CANCER BIOLOGY & THERAPY LA English DT Review DE molecular targets; cancer; review ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; HUMAN CANCER-CELLS; PHASE-I; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; LUNG-CANCER; RAPAMYCIN; MTOR; EXPRESSION AB A number of agents targeting components of pathways and processes critical to neoplastic transformation and progression are ongoing clinical development. Notable successes include imatinib mesylate (ST1571, Gleevec) in Chronic Myelogenous Leukemia (CML), and Gastrointestinal Stromal Tumors (GIST) and trastuzumab (Herceptin) in HER2 amplified breast carcinoma. More recently, gefitinib (ZD1839, Iressa) and bortezomib (PS-341, Velcade) have been approved for refractory nonsmall cell lung carcinoma (NSCLC) and multiple myeloma (MM), respectively. In addition, promising results from randomized studies of bevacizumab (Avastin) and cetuximab (IMC-225, Erbitux) have been reported and shortly may lead to their approval for the treatment of colorectal carcinoma (CRC). To what degree the success or failure of these agents has been due to target, the agent, the dose or the selection of patients is uncertain. Certainly, further evaluation of these factors is required to optimize the therapeutic impact of targeted agents and imaging modalities may play a vital role in this process. The purpose of this review is to summarize recent results from trials of selected targeted agents and to suggest roles imaging may play in the further development of these and other targeted agents. C1 NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Dancey, JE (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, 6130 Execut Blvd,Room 7131, Bethesda, MD 20892 USA. EM danceyi@ctep.nci.nih.gov NR 100 TC 11 Z9 12 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV-DEC PY 2003 VL 2 IS 6 BP 601 EP 609 PG 9 WC Oncology SC Oncology GA 772MQ UT WOS:000188846200001 PM 14688462 ER PT J AU Makrigiannis, AP Anderson, SK AF Makrigiannis, AP Anderson, SK TI Regulation of natural killer cell function SO CANCER BIOLOGY & THERAPY LA English DT Review DE NK cells; MHC; tumor; Ly49 ID TUMOR-NECROSIS-FACTOR; APOPTOSIS-INDUCING LIGAND; NK-MEDIATED LYSIS; IN-VIVO; NKG2D RECEPTOR; GENE-COMPLEX; MULTIGENE FAMILY; SURFACE-MOLECULE; C57BL/6 MICE; TARGET-CELLS AB Individuals lacking natural killer (NK) cells have persistent viral infections and as a consequence die prematurely. In addition, mice with decreased NK cell function are more susceptible to carcinogen-induced cancers. Current evidence strongly suggests that downregulation of MHC by certain tumors and virally-infected cells results in NK cell attack due to the inability to trigger inhibitory Ly49, KIR, and NKG2A/CD94 class la and Ib MHC receptors. Extreme haplotype diversity is present in both mouse and human chromosomal segments coding for NK cell class la MHC receptors resulting in different numbers and types of receptors being expressed in individuals and different inbred mouse strains. Whether the absence or presence of a particular NK cell receptor gene is advantageous or deleterious for an individual with respect to immunity to pathogens and cancer is a question of paramount importance. Recent advances in our understanding of NK cell function are due to the identification of activating NK cell receptors, such as Ly49H and NKG2D, for specific viral and tumor ligands (m 157 and Rae1, respectively). In a clinical setting, such MHC class I receptor diversity is advantageous with respect to preventing leukemic relapse in individuals treated for leukemia and receiving bone marrow transplants. Further delineation of NK cell receptors and tumor ligands will help researchers to exploit the innate immune system to better treat such diseases. C1 Clin Res Inst Montreal, Lab Mol Immunol, Montreal, PQ H2W 1R7, Canada. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21701 USA. RP Makrigiannis, AP (reprint author), Clin Res Inst Montreal, Lab Mol Immunol, Rm 1340,110 Pine Ave W, Montreal, PQ H2W 1R7, Canada. EM makriga@ircm.qc.ca RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-12400] NR 86 TC 23 Z9 25 U1 1 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV-DEC PY 2003 VL 2 IS 6 BP 610 EP 616 PG 7 WC Oncology SC Oncology GA 772MQ UT WOS:000188846200002 PM 14688463 ER PT J AU Freedman, DM Sigurdson, A Doody, MM Rao, RS Linet, MS AF Freedman, DM Sigurdson, A Doody, MM Rao, RS Linet, MS TI Risk of melanoma in relation to smoking, alcohol intake, and other factors in a large occupational cohort SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; body mass index; height; melanoma; menarche; oral contraceptive use; parity; radiologic technologists; smoking; weight ID CUTANEOUS MALIGNANT-MELANOMA; ORAL-CONTRACEPTIVE USE; SQUAMOUS-CELL CARCINOMA; DANISH CASE-CONTROL; REPRODUCTIVE FACTORS; UNITED-STATES; SKIN-CANCER; RADIOLOGIC TECHNOLOGISTS; CIGARETTE-SMOKING; WOMEN AB Objective: To investigate whether smoking, alcohol intake, female hormonal or anthropometric factors affect melanoma risk. Methods: Using Cox proportional hazards regression analyses, we analyzed 68,588 white subjects (79% female) from the US Radiologic Technologists (USRT) Study who were cancer-free (other than non-melanoma skin cancer) as of the first of two self-administered questionnaires. Follow-up covered 698, 028 person-years, with 207 cases of melanoma. Results: We found that melanoma risk was not associated with height, weight or BMI, nor with age at menarche, menopausal status, use of hormone replacement therapy, parity, age at first birth or oral contraceptive use. Melanoma risk was elevated with increasing alcohol use (RR: 2.1; 95% CI: 0.9-4.8, for > 14 drinks/week compared to never drinking; (p(trend) = 0.08)). Smoking for long durations compared to never smoking was inversely related to melanoma risk (RR: 0.6; 0.3-1.3; greater than or equal to30 years; p(trend) = 0.03), though risk was not associated with number of packs smoked per day. Conclusions: None of the anthropometric or female reproductive/hormonal factors evaluated were related to melanoma risk. It is unclear whether the positive association with alcohol intake and inverse association with smoking for long duration are causal. The alcohol and smoking findings warrant detailed assessment in studies with substantial statistical power where potential biases can be more fully evaluated. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Freedman, DM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Room 7036,6120 Execut Plaza Blvd, Bethesda, MD 20892 USA. NR 57 TC 63 Z9 64 U1 3 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2003 VL 14 IS 9 BP 847 EP 857 DI 10.1023/B:CACO.0000003839.56954.73 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 744CA UT WOS:000186609300005 PM 14682442 ER PT J AU Chen, JD Lui, WO Vos, MD Clark, GJ Takahashi, M Schoumans, J Khoo, SK Petillo, D Lavery, T Sugimura, J Astuti, D Zhang, C Kagawa, S Maher, ER Larsson, C Alberts, AS Kanayama, HO Teh, BT AF Chen, JD Lui, WO Vos, MD Clark, GJ Takahashi, M Schoumans, J Khoo, SK Petillo, D Lavery, T Sugimura, J Astuti, D Zhang, C Kagawa, S Maher, ER Larsson, C Alberts, AS Kanayama, HO Teh, BT TI The t(1;3) breakpoint-spanning involved in clear cell renal cell genes LSAMP and NORE1 are carcinomas SO CANCER CELL LA English DT Article ID TUMOR-SUPPRESSOR GENE; CHROMOSOME-TRANSLOCATION; EPIGENETIC INACTIVATION; MOLECULAR ANALYSIS; FHIT GENE; CANCER; RASSF1A; IDENTIFICATION; PROTEIN; 3P21.3 AB By positional cloning, we identified two breakpoint-spanning genes in a familial clear cell renal cell carcinoma (CCRCC)-associated t(1;3)(q32.1;q13.3): LSAMP and NORE1 (RASSF1 homolog). Both genes are downregulated in 9 of 9 RCC cell lines. While the NORE1A promoter predominantly presents partial methylation in 6 of the cell lines and 17/53 (32%) primary tumors, the LSAMP promoter is completely methylated in 5 of 9 cell lines and in 14/53 (26%) sporadic and 4 familial CCRCCs. Expression of LSAMP and NORE1 A proteins in CCRCC cell lines inhibited cell proliferation. These characteristics indicate that LSAMP and NORE1A may represent new candidate tumor suppressors for CCRCC. C1 Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA. Van Andel Res Inst, Lab Cell Struct & Signal Integrat, Grand Rapids, MI 49503 USA. Karolinska Hosp, Dept Mol Med, SE-17176 Stockholm, Sweden. NCI, Dept Cell & Canc Biol, NIH, Rockville, MD 20850 USA. Univ Tokushima, Sch Med, Dept Urol, Tokushima 770, Japan. Univ Birmingham, Sch Med, Canc Res UK Renal Mol Oncol Res Grp, Sect Med & Mol Genet, Birmingham, W Midlands, England. RP Teh, BT (reprint author), Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA. RI MAHER, EAMONN/A-9507-2008; Lui, Weng-Onn/G-6703-2013 OI MAHER, EAMONN/0000-0002-6226-6918; Lui, Weng-Onn/0000-0003-4717-4473 NR 40 TC 73 Z9 79 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2003 VL 4 IS 5 BP 405 EP 413 DI 10.1016/S1535-6108(03)00269-1 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 748KX UT WOS:000186862000011 PM 14667507 ER PT J AU Thompson, P Balis, F Serabe, BM Berg, S Adamson, P Klenke, R Aiken, A Packer, R Murry, DJ Jakacki, R Blaney, SM AF Thompson, P Balis, F Serabe, BM Berg, S Adamson, P Klenke, R Aiken, A Packer, R Murry, DJ Jakacki, R Blaney, SM TI Pharmacokinetics of phenylacetate administered as a 30-min infusion in children with refractory cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE pharmacokinetic; phenylacetate; pediatric; phenylacetylglutamine ID PHASE-I; DIFFERENTIATION; CELLS; ACID AB Purpose. Phenylacetate (PAA), a deaminated metabolite of phenylalanine, suppresses tumor growth and induces differentiation in preclinical tumor models. We performed a pharmacokinetic study, as part of a phase I trial, of PAA in children with refractory cancer. Methods. PAA was administered as a 30-min i.v. infusion at a dose of 1.8 or 2.5 g/m(2). Serial plasma samples were collected for up to 24 h after the end of the infusion in 27 children. The concentrations of PAA and its inactive metabolite, phenylacetylglutamine (PAG), were measured using a reverse-phase high-performance liquid chromatography assay with ultraviolet detection. Results. PAA and PAG concentrations were best described by a two-compartment model (one compartment for each compound) with capacity-limited conversion of PAA to PAG. The half-life of PAA was 55+/-18 min at the 1.8 g/m(2) dose and 77+/-22 min at the 2.5 g/m(2) dose. The half-life of PAG was 112+/-53 min at the 1.8 g/m(2) dose and 135+/-75 min at the 2.5 g/m(2) dose. The clearance of PAA was 66+/-33 ml/min per m(2) at the 1.8 g/m(2) dose and 60+/-24 ml/min per m(2) at the 2.5 g/m(2) dose. The Michaelis-Menten constants describing the conversion of PAA to PAG in the model (V-m and K-m) were (means+/-SD) 18.4+/-13.8 mg/m(2) per min and 152+/-155 mug/ml, respectively. The volumes of distribution for PAA and PAG (Vd-PAA and Vd-PAG) were 7.9+/-3.4 l/m(2) and 34.4+/-16.1 l/m(2), respectively. The first-order elimination rate constant for PAG (k(e-PAG)) was 0.0091+/-0.0039 min(-1). Conclusions. The capacity-limited conversion of PAA to PAG has important implications for the dosing of PAA, and the pharmacokinetic model described here may be useful for individualizing the infusion rate of the drug in future clinical trials. C1 Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. James Whitcomb Riley Hosp Children, Div Hematol Oncol, Indianapolis, IN 46202 USA. RP Blaney, SM (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, 6621 Fannin,MC 3-3320, Houston, TX 77030 USA. FU NCRR NIH HHS [M01-RR00188] NR 16 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2003 VL 52 IS 5 BP 417 EP 423 DI 10.1007/s00280-003-0674-0 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 732TB UT WOS:000185960700007 PM 12879279 ER PT J AU Daling, JR Malone, KE Doody, DR Voigt, LF Bernstein, L Marchbanks, PA Coates, RJ Norman, SA Weiss, LK Ursin, G Burkman, RT Deapen, D Folger, SG McDonald, JA Simon, MS Strom, BL Spirtas, R AF Daling, JR Malone, KE Doody, DR Voigt, LF Bernstein, L Marchbanks, PA Coates, RJ Norman, SA Weiss, LK Ursin, G Burkman, RT Deapen, D Folger, SG McDonald, JA Simon, MS Strom, BL Spirtas, R TI Association of regimens of hormone replacement therapy to prognostic factors among women diagnosed with breast cancer aged 50-64 years SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HISTOLOGIC TYPE; UNITED-STATES; RISK; ESTROGEN; PROGESTIN; CARCINOMA AB This study was conducted to assess the histopathological features of breast cancers in women diagnosed with breast cancer at 50-64 years of age who have and have not used hormone replacement therapy (HRT). A case-case analysis of the tumors from women aged 50-64 years who participated in a multicenter population-based case-control study of invasive breast cancer was conducted. In-person interviews collected a detailed history of all episodes of hormone use. Information was collected on selected tumor characteristics from 2346 women with breast cancer. Polytomous logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), contrasting the histopathological characteristics of the tumors of women who used various regimens of HRT with those of women who have never used HRT. The tumors of cases who used each regimen of HRT were smaller and of earlier stage than those of non-HRT users. Adjustment for screening diminished the magnitude of the effect, and only cases who used estrogen alone (estrogen replacement therapy) had reduced odds of being diagnosed with later-stage disease (regional or distant) than cases who never used HRT (OR, 0.7; 95% CI, 0.6-0.9). Higher proportions of estrogen receptor (ER)- and progesterone receptor (PR)positive tumors were seen in cases who used any regimen of HRT versus those who did not use HRT. However, after adjustment for age and race, only the tumors of cases who used continuous combined HRT remained more likely to be ER+ and PR+ [OR ER- = 0.6 (95% CI, 0.4-0.9) and OR PR- = 0.5 (95% CI, 0.4-0.7)]. The tumors of women with breast cancer who used HRT have some better prognostic factors than those of women who have not used HRT. However, with the exception of the results noted above, this advantage may be due to the racial and age differences in those who use the various regimens of HRT and the effect of more frequent screening among HRT users, leading to earlier diagnosis. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Ctr Dis Control & Prevent, Canc Div, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Wayne State Univ, Karmanos Canc Inst, Div Epidemiol, Detroit, MI USA. Bay State Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA. NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, Bethesda, MD 20892 USA. RP Daling, JR (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N MP 381,POB 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [N01 PC 67006, N01 CN 0532, N01 PC 67010, N01 CN 65064]; NICHD NIH HHS [N01 HD 3-3174, N01 HD 3-3175, N01 HD3-3168, N01 HD 2-3166, N01 HD 3-3176] NR 22 TC 32 Z9 33 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 NOV PY 2003 VL 12 IS 11 BP 1175 EP 1181 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700008 PM 14652277 ER PT J AU Kilkkinen, A Virtamo, J Virtanen, MJ Adlercreutz, H Albanes, D Pietinen, P AF Kilkkinen, A Virtamo, J Virtanen, MJ Adlercreutz, H Albanes, D Pietinen, P TI Serum enterolactone concentration is not associated with prostate cancer risk in a nested case-control study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TIME-RESOLVED FLUOROIMMUNOASSAY; ISOFLAVONOID PHYTOESTROGENS; PLASMA ENTEROLACTONE; TOBACCO USE; LIGNANS; ADENOCARCINOMA; CARCINOMAS; INHIBITION; ANTIGEN; GROWTH AB The lignan enterolactone, produced by the intestinal microflora from dietary precursors, has been hypothesized to protect against hormone-dependent cancers and cardiovascular diseases. We conducted a nested case-control study to examine the relationship between serum enterolactone concentration and prostate cancer. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum collected at baseline in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study from 214 men with prostate cancer diagnosed during a 6-year follow-up and from 214 controls matched by age, date of baseline blood collection, intervention group, and local study area. Mean serum enterolactone concentration (in nmol/liter) did not differ significantly between case and control subjects [15.9 (SD, 15.2) versus 16.9 (SD, 14.9), respectively (P = 0.42)]. Odds ratios for prostate cancer risk estimated by conditional logistic regression for increasing quartiles of enterolactone concentration were 1.00 (referent), 0.72 [95% confidence interval (CI), 0.43-1.23], 0.98 (95% CI, 0.58-1.68), and 0.71 (95% Cl, 0.42-1.21). Our findings do not support the hypothesis that enterolactone is involved in the development of prostate cancer. C1 Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, SF-00300 Helsinki, Finland. Folkhalsan Res Ctr, Inst Prevent Med Nutr & Canc, Helsinki, Finland. Univ Helsinki, Div Clin Chem, Helsinki, Finland. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Kilkkinen, A (reprint author), Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Mannerheimintie 166, SF-00300 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN-45165] NR 32 TC 32 Z9 33 U1 0 U2 3 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 NOV PY 2003 VL 12 IS 11 BP 1209 EP 1212 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700014 PM 14652283 ER PT J AU Takimoto, CH Glover, K Huang, XK Hayes, SA Gallot, L Quinn, M Jovanovic, BD Shapiro, A Hernandez, L Goetz, A Llorens, V Lieberman, R Crowell, JA Poisson, BA Bergan, RC AF Takimoto, CH Glover, K Huang, XK Hayes, SA Gallot, L Quinn, M Jovanovic, BD Shapiro, A Hernandez, L Goetz, A Llorens, V Lieberman, R Crowell, JA Poisson, BA Bergan, RC TI Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOCAL ADHESION KINASE; BODY-SURFACE AREA; PROSTATE-CANCER; JAPANESE WOMEN; CHOLESTEROL CONCENTRATION; SOYBEAN ISOFLAVONES; GUT MICROFLORA; DIETARY-INTAKE; GENISTEIN; MEN AB Preclinical studies suggest that the isoflavone genistein may have prostate cancer chemopreventive activity. Genistein has been shown to alter cellular levels of protein-tyrosine phosphorylation and is present at high levels in soy. This study was designed to measure the pharmacokinetic parameters of two different preparations of unconjugated soy isoflavones, PTI G-2535 and PTI G-4660 (which contain 43% and 90% genistein, respectively), in human subjects with cancer, to evaluate toxicity and obtain pilot data on in vivo effects on protein-tyrosine phosphorylation. Cohorts of four patients were given single doses of each preparation; each dose was separated by 1 week. Sequential cohorts received genistein at 2, 4, or 8 mg/kg orally. Pharmacokinetic sampling was performed after each dose, and tyrosine phosphorylation was measured in proteins extracted from peripheral blood mononuclear cells. One of 13 patients treated developed a treatment-related rash. No other toxicities were observed. Maximal plasma concentrations (C-max) ranged between 4.3 and 16.3 mum for total genistein and 0.066 and 0.17 mum for free genistein. For PTI G-2535 and PTI G-4660, half-life was 15.03 and 22.41 h, respectively, and volume of distribution was 189.9 and 653.8 liters, respectively, and there was a trend toward higher area under the concentration curve for PTI G-2535 (P = 0.07 at the 8 mg/kg dose). Treatment-related increases in tyrosine phosphorylation were observed in peripheral blood mononuclear cells. Oral administration of soy isoflavones gives plasma concentrations of genistein that have been associated with antimetastatic activity in vitro. C1 NCI, Chemoprevent Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78284 USA. Northwestern Univ, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. RP Bergan, RC (reprint author), Olson 8524,710 N Fairbanks, Chicago, IL 60611 USA. OI Glover-Cutter, Kira/0000-0002-7321-8604 FU NCI NIH HHS [CA90386]; NCRR NIH HHS [M01 RR00048]; NIA NIH HHS [T32 AG00260] NR 51 TC 77 Z9 86 U1 3 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 NOV PY 2003 VL 12 IS 11 BP 1213 EP 1221 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700015 PM 14652284 ER PT J AU Stolzenberg-Solomon, RZ Qiao, YL Abnet, CC Ratnasinghe, DL Dawsey, SM Dong, ZW Taylor, PR Mark, SD AF Stolzenberg-Solomon, RZ Qiao, YL Abnet, CC Ratnasinghe, DL Dawsey, SM Dong, ZW Taylor, PR Mark, SD TI Esophageal and gastric cardia cancer risk and folate- and vitamin B-12-related polymorphisms in Linxian, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; CASE-COHORT; METHYLENETETRAHYDROFOLATE REDUCTASE; MINERAL SUPPLEMENTATION; PERNICIOUS-ANEMIA; POPULATION; VITAMIN; ADENOCARCINOMA; DYSPLASIA AB Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in the world. Its inhabitants have documented chronic nutritional inadequacies, including folate and vitamin B-12 deficiencies. Using a cohort we have been studying in Linxian since 1985, we examined the relationship between incident ESCC and GCA cancers and three polymorphisms in two genes that code for enzymes that require folate and B-12 as cofactors: methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. We conducted a case-cohort study among 4005 individuals in our cohort who were alive and cancer free in 1991 and had blood samples adequate for DNA extraction. Polymorphisms were measured on all 219 incident cancers (129 ESCCs and 90 GCAs) that developed through May 1996 and on 398 controls. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Individuals with the MTHFR 677TT genotype had significantly higher combined ESCC/GCA risks (RR, 1.45; 95% CI, 1.02-2.05) than those with CC or CT genotypes. The only subjects to have MTHFR 1298CC were three ESCC cases (P = 0.03). Compared with subjects with the MTRR 66AA genotype, subjects with the AG or GG genotypes had significantly higher risk of ESCC (RR, 1.59; 95% CI, 1.04-2.42). No association was observed for GCA. Our results suggest that the MTHFR C677T and MTRR A66G polymorphisms influence the risk of ESCC and GCA in this population. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. US FDA, Ctr Populat Genomics, Natl Ctr Toxicol Res, Jefferson, AR USA. NCI, Canc Prevent Studies Branch, Ctr Canc Res, Rockville, MD USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. NCI, Div Canc Prevent, Rockville, MD USA. RP Stolzenberg-Solomon, RZ (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320 MSC 7232, Rockville, MD 20852 USA. RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 24 TC 88 Z9 95 U1 1 U2 18 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 NOV PY 2003 VL 12 IS 11 BP 1222 EP 1226 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700016 PM 14652285 ER PT J AU Peters, U DeMarini, DM Sinha, R Brooks, LR Warren, SH Chatterjee, N Rothman, N AF Peters, U DeMarini, DM Sinha, R Brooks, LR Warren, SH Chatterjee, N Rothman, N TI Urinary mutagenicity and colorectal adenoma risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HETEROCYCLIC AMINES; DNA-ADDUCTS AB We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenicity was determined in Salmonella YG1024 +S9 (Ames test). Adenoma risk was 2.4-fold higher in subjects in the highest versus the lowest quintile of urinary mutagenicity (95% confidence interval = 1.1-5.1). Combining urinary mutagenicity with intake of meat-derived mutagenicity (from our earlier analysis) resulted in a 5.6-fold increase in adenoma risk (95% confidence interval = 2.2-13.9, comparing the highest with the lowest quintile). In our study population, diet may have contributed to mutagenic exposure, which was positively associated with colorectal adenoma risk. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. US EPA, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. RP Peters, U (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 3024, Bethesda, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 13 TC 11 Z9 11 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 NOV PY 2003 VL 12 IS 11 BP 1253 EP 1256 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700021 PM 14652290 ER PT J AU Troisi, R Potischman, N Johnson, CN Roberts, JM Lykins, D Harger, G Markovic, N Siiteri, P Hoover, RN AF Troisi, R Potischman, N Johnson, CN Roberts, JM Lykins, D Harger, G Markovic, N Siiteri, P Hoover, RN TI Estrogen and androgen concentrations are not lower in the umbilical cord serum of pre-eclamptic pregnancies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material AB Reductions in breast cancer risk observed in daughters of pre-eclamptic pregnancies are hypothesized to be mediated by lower in utero estrogen concentrations. Whereas maternal urinary estriol excretion is generally lower in pre-eclamptic women, results for maternal blood concentrations are equivocal, and little is known about estrogen concentrations in the cord of pre-eclamptic pregnancies. Unconjugated estrogen and androgen concentrations were measured in mixed umbilical cord sera from 86 pre-eclamptic and 86 uncomplicated, singleton pregnancies, matched on length of gestation, maternal age, parity, and type of delivery. Pre-eclamptic and uncomplicated pregnancies were similar in maternal age, prepregnancy weight, maternal height, type of delivery, use and type of anesthesia, and sex of offspring. Estriol, estradiol, estrone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, and testosterone concentrations measured in cord sera were not significantly different in pre-eclamptics compared with uncomplicated pregnancies. Estriol was 9% lower (P = 0.43), and all of the other hormones were actually higher in pre-eclamptics with testosterone and estradiol approaching statistical significance (P = 0.06 and P 0.12, respectively). These data do not support the hypothesis that the lower breast cancer risk in daughters of pre-eclamptic pregnancies is explained by lower in utero estrogen exposure. C1 Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, 1 Med Ctr Dr,7927 Rubin Bldg, Lebanon, NH 03756 USA. FU NCRR NIH HHS [5 M01-RR00056]; NICHD NIH HHS [2 P01-HD30367] NR 7 TC 21 Z9 22 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 NOV PY 2003 VL 12 IS 11 BP 1268 EP 1270 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700024 PM 14652293 ER PT J AU Weinstein, SJ Hartman, TJ Stolzenberg-Solomon, R Pietinen, P Barrett, MJ Taylor, PR Virtamo, J Albanes, D AF Weinstein, SJ Hartman, TJ Stolzenberg-Solomon, R Pietinen, P Barrett, MJ Taylor, PR Virtamo, J Albanes, D TI Null association between prostate cancer and serum folate, vitamin B-6, vitamin B-12, and homocysteine SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID METHYLATION C1 NCI, Nutrit Epidemiol Branch, DCEG, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. RP Weinstein, SJ (reprint author), NCI, Nutrit Epidemiol Branch, DCEG, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Suite 320, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC45035]; NCI NIH HHS [N01-CN45165] NR 7 TC 67 Z9 69 U1 0 U2 3 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 NOV PY 2003 VL 12 IS 11 BP 1271 EP 1272 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 750NB UT WOS:000187001700025 PM 14652294 ER PT J AU Coughlin, S Tanner, B Wilson, K Briss, P Smith, J Breslow, R White, C Lee, N Saraiya, M Rimer, B Kerner, J AF Coughlin, S Tanner, B Wilson, K Briss, P Smith, J Breslow, R White, C Lee, N Saraiya, M Rimer, B Kerner, J TI A systematic review of small media, one-on-ona education, and group education interventions to increase breast, cervical, and colorectal cancer screening. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 CDC, Atlanta, GA 30333 USA. NCI, Washington, DC USA. NR 0 TC 0 Z9 0 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 NOV PY 2003 VL 12 IS 11 SU S BP 1278S EP 1278S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300011 ER PT J AU Linden, KG Carpenter, PM McLaren, CE Barr, RJ Arain, S Hite, P Sun, JD Li, KT Viner, JL Meyskens, FL AF Linden, KG Carpenter, PM McLaren, CE Barr, RJ Arain, S Hite, P Sun, JD Li, KT Viner, JL Meyskens, FL TI Epigallocatechin gallate in the chemoprevention of non-melanoma skin cancer, with biomarker studies of actinic keratoses, sun-damaged, and non sun-damaged skin: Results of a clinical trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Calif Irvine, Orange, CA 92668 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 NOV PY 2003 VL 12 IS 11 SU S BP 1280S EP 1280S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300016 ER PT J AU Martinez, ME Lanza, E Alberts, DS Schatzkin, A Jacobs, E Einspahr, J Green, S Reid, ME Ratnasinghe, L Gunter, EW AF Martinez, ME Lanza, E Alberts, DS Schatzkin, A Jacobs, E Einspahr, J Green, S Reid, ME Ratnasinghe, L Gunter, EW TI Blood selenium and colorectal adenoma recurrence; Pooled analyses from the wheat bran fiber trial and the polyp prevention trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Arizona, Tucson, AZ USA. NCI, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1280S EP 1280S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300017 ER PT J AU Llosa, A Gail, MH You, WC Li, JY Parsonnet, J AF Llosa, A Gail, MH You, WC Li, JY Parsonnet, J TI Evaluation of a gastric pathology index to predict cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. NCI, Div Epidemiol & Biostat, Bethesda, MD 20892 USA. Peking Univ, Beijing Inst Canc Res, Beijing 100871, Peoples R China. Peking Univ, Sch Oncol, Beijing 100871, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1283S EP 1283S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300028 ER PT J AU Irwin, M Aiello, E Gilliland, F McTiernan, A Baumgartner, R Bernstein, L Ballard-Barbash, R AF Irwin, M Aiello, E Gilliland, F McTiernan, A Baumgartner, R Bernstein, L Ballard-Barbash, R TI The association between physical activity levels and mammographic breast density in pre- and post-menopausal women: The health, eating, activity, and lifestyle (HEAL) study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Yale Univ, New Haven, CT USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Los Angeles, CA USA. Univ New Mexico, Albuquerque, NM 87131 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1284S EP 1285S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300034 ER PT J AU Schernhammer, E Kang, JH Chan, AT Michaud, DS Skinner, HG Giovannucci, E Colditz, GA Fuchs, CS AF Schernhammer, E Kang, JH Chan, AT Michaud, DS Skinner, HG Giovannucci, E Colditz, GA Fuchs, CS TI A prospective study of aspirin use and risk of pancreatic cancer in women. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Channing Labs, Boston, MA USA. NCI, Nutr Epidemiol Branch, Rockville, MD USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Skinner, Halcyon/A-1049-2009; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1292S EP 1292S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300065 ER PT J AU Bostick, RM Coker, WJ Xie, DW Cunningham, JE Taylor, JA AF Bostick, RM Coker, WJ Xie, DW Cunningham, JE Taylor, JA TI Prooxidant cigarette smoking and high fat intake and risk for incident sporadic colorectal adenomas according to haplotypes of the XRCC1 DNA repair gene. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ S Carolina, Columbia, SC 29208 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1293S EP 1293S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300069 ER PT J AU Mahabir, S Leitzmann, ME Virtamo, J Pietinen, P Albanes, D Taylor, PR AF Mahabir, S Leitzmann, ME Virtamo, J Pietinen, P Albanes, D Taylor, PR TI Prospective study of alcohol drinking and renal cell cancer risk in a cohort of Finnish men. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1294S EP 1294S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300074 ER PT J AU Decensi, A Robertson, C Guerrieri-Gonzaga, A Cazzaniga, M Johansson, H Serrano, D Mora, S Gulisano, M Intra, M Greco, M Cassano, E Franchi, D Johnson, K Bonanni, B AF Decensi, A Robertson, C Guerrieri-Gonzaga, A Cazzaniga, M Johansson, H Serrano, D Mora, S Gulisano, M Intra, M Greco, M Cassano, E Franchi, D Johnson, K Bonanni, B TI A randomized 2x2 biomarker trial of low-dose tamoxifen and fenretinide in premenopausal women at-high risk for breast cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 European Inst Oncol, Milan, Italy. Univ Strathclyde, Glasgow, Lanark, Scotland. Osped S Bortolo, Vicenza, Italy. Ist Nazl Tumori, I-20133 Milan, Italy. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 NOV PY 2003 VL 12 IS 11 SU S BP 1300S EP 1300S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300095 ER PT J AU Eng-Wong, J Stratton, P Forman, M Venzon, D Remaley, A Zujewski, JA AF Eng-Wong, J Stratton, P Forman, M Venzon, D Remaley, A Zujewski, JA TI Effect of raloxifene on menstrual cycle length and quality of life in premenopausal women at high risk for invasive breast cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NICHHD, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 0 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 NOV PY 2003 VL 12 IS 11 SU S BP 1300S EP 1300S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300096 ER PT J AU Colbert, LH Westerlind, KC Perkins, SN Wimbrow, H Hursting, SD AF Colbert, LH Westerlind, KC Perkins, SN Wimbrow, H Hursting, SD TI Treadmill and running wheel exercise are not beneficial to survival in a p53-deficient Wnt-I transgenic mouse model of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Wisconsin, Madison, WI USA. AMC Canc Res Ctr, Denver, CO USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1302S EP 1302S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300101 ER PT J AU Taylor, K Turner, RO Davis, JL Schwartz, MD Kerner, J Johnson, L Leak, C AF Taylor, K Turner, RO Davis, JL Schwartz, MD Kerner, J Johnson, L Leak, C TI The prostate cancer screening dilemma: One-year follow-up results from a randomized decision making intervention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Georgetown Univ, Washington, DC USA. Trifax Inc, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1303S EP 1303S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300105 ER PT J AU Elmore, E Jain, A Siddiqui, S Tohidian, N Meyskens, FL Steele, VE Redpath, JL AF Elmore, E Jain, A Siddiqui, S Tohidian, N Meyskens, FL Steele, VE Redpath, JL TI Development of an in vitro human cell screening assay for identifying melanoma prevention agents SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Calif Irvine, Irvine, CA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1306S EP 1306S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300114 ER PT J AU Port, JL Yamaguchi, K Do, BH De Lorenzo, M Chang, M Heerdt, P Kopelovich, L Altorki, NK Subbaramaiah, K Dannenberg, AJ AF Port, JL Yamaguchi, K Do, BH De Lorenzo, M Chang, M Heerdt, P Kopelovich, L Altorki, NK Subbaramaiah, K Dannenberg, AJ TI Cytochrome P4501B1 is induced by tobacco smoke in the aerodigestive tract SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 New York Presbyterian Hosp, Strang Canc Prevent Ctr, New York, NY USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1308S EP 1308S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300123 ER PT J AU Nakshatri, H Crean, C Goulet, R Mehta, SA Shay, JW Kopelovich, L AF Nakshatri, H Crean, C Goulet, R Mehta, SA Shay, JW Kopelovich, L TI Tamoxifen-induced growth arrest but not apoptosis of immortalized mammary epithelial cells is enhanced by estrogen receptor alpha SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Indiana Canc Res Inst, Indianapolis, IN USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NCI, CADRG, DCP, Bethesda, MD 20892 USA. RI Shay, Jerry/F-7878-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1310S EP 1310S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300130 ER PT J AU Wanke, K Augustson, EM AF Wanke, K Augustson, EM TI The relation of depression to the stages of smoking: Results from NHANES III SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, SAIC, Bethesda, MD 20892 USA. NR 0 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 NOV PY 2003 VL 12 IS 11 SU S BP 1312S EP 1312S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300140 ER PT J AU Sturgeon, SR Schairer, C El Ghormli, L Grauman, D Devesa, S AF Sturgeon, SR Schairer, C El Ghormli, L Grauman, D Devesa, S TI Trends in US breast cancer mortality rates by region, 1950-69 to 1990-99 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Massachusetts, Amherst, MA 01003 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1313S EP 1314S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300144 ER PT J AU Freedman, AN Graubard, BI Rao, RS McCaskill-Stevens, W Ballard-Barbash, R Gail, MH AF Freedman, AN Graubard, BI Rao, RS McCaskill-Stevens, W Ballard-Barbash, R Gail, MH TI Tamoxifen eligibility, net benefit and use for breast cancer chemoprevention among white women in the US SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1314S EP 1314S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300145 ER PT J AU Hakim, I Harris, R Dean, M Chow, HHS Ali, L AF Hakim, I Harris, R Dean, M Chow, HHS Ali, L TI Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: Role of hogg1 genotype SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1315S EP 1315S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300149 ER PT J AU Lim, U Stolzenberg-Solomon, R Virtamo, J Pietinen, P Taylor, PR Albanes, D AF Lim, U Stolzenberg-Solomon, R Virtamo, J Pietinen, P Taylor, PR Albanes, D TI Dietary B vitamins and the risk of lymphoid cancers in male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Rockville, MD USA. Natl Publ Hlth Inst, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1315S EP 1315S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300151 ER PT J AU Millen, A Tucker, MA Hartge, P Potischman, N AF Millen, A Tucker, MA Hartge, P Potischman, N TI Diet and risk of malignant melanoma in a case-control study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Rockville, MD USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1315S EP 1315S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300150 ER PT J AU Flood, A Peters, U Jenkins, D Chatterjee, N Subar, A Schatzkin, A Hayes, R AF Flood, A Peters, U Jenkins, D Chatterjee, N Subar, A Schatzkin, A Hayes, R TI Carbohydrate, glycemic index, and glycemic load and colorectal adenomas in the prostate, lung, colorectal, and ovarian (PLCO) cancer-screening study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Minnesota, Minneapolis, MN USA. NCI, Bethesda, MD 20892 USA. Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1316S EP 1316S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300154 ER PT J AU Leitzmann, M Chang, SC Andriole, G Chatterjee, N Huang, WY Hsing, A Kirsh, V Peters, U Schatzkin, A Hayes, R AF Leitzmann, M Chang, SC Andriole, G Chatterjee, N Huang, WY Hsing, A Kirsh, V Peters, U Schatzkin, A Hayes, R TI Interrelation of energy intake, body size, and physical activity with prostate cancer in the PLCO screening trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, NIH, Rockville, MD USA. Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1316S EP 1317S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300156 ER PT J AU Nesterova, M Cho-Chung, YS AF Nesterova, M Cho-Chung, YS TI Antisense PKA RI alpha blocks the initial phase of DMBA-mammary carcinogenesis and reduces mammary tumor production in rats SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1319S EP 1319S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300165 ER PT J AU Ruffin, MT Normolle, DP Heath, DD Bailey, JM Murray, SI Boggs, ME Crowell, JA Rock, CL Brenner, DE AF Ruffin, MT Normolle, DP Heath, DD Bailey, JM Murray, SI Boggs, ME Crowell, JA Rock, CL Brenner, DE TI Dose escalation of curcumin in healthy adults SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 6 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 NOV PY 2003 VL 12 IS 11 SU S BP 1324S EP 1324S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300186 ER PT J AU McCormick, DL Johnson, WD Lubet, RA Steele, VE Bosland, MC AF McCormick, DL Johnson, WD Lubet, RA Steele, VE Bosland, MC TI Lack of chemopreventive activity of selenium compounds in the Wistar-Unilever rat prostate cancer model SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 IIT, Res Inst, Chicago, IL 60616 USA. NCI, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1327S EP 1327S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300198 ER PT J AU Dhar, A Brindley, JM Colburn, NH AF Dhar, A Brindley, JM Colburn, NH TI Low-dose nitric oxide prevents transformation and reverts transformation-sensitivc phenotype. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1334S EP 1334S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300226 ER PT J AU Baumgartner, K Hunt, WC Baumgartner, RN Bernstein, L Gilliland, FD McTiernen, A Ballard-Barbash, R AF Baumgartner, K Hunt, WC Baumgartner, RN Bernstein, L Gilliland, FD McTiernen, A Ballard-Barbash, R TI Relationship of obesity with p53 and other tumor markers among Hispanic and non-Hispanic white women. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Univ New Mexico, Albuquerque, NM 87131 USA. Univ So Calif, Los Angeles, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1337S EP 1338S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300239 ER PT J AU Chang, SC Leitzmann, M Stolzenberg-Solomon, R Lacey, J Huang, WY Ziegler, R Hoover, R Hartge, P Buys, S Schatzkin, A AF Chang, SC Leitzmann, M Stolzenberg-Solomon, R Lacey, J Huang, WY Ziegler, R Hoover, R Hartge, P Buys, S Schatzkin, A TI Interrelation of energy intake, body size, and physical activity with breast cancer in the PLCO screening trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1338S EP 1338S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300241 ER PT J AU Dorgan, JE Boayke, NA Fears, TR Schleicher, RL Helsel, W Anderson, C Robinson, J Guin, JD Lessin, S Ratnasinghe, LD Tangrea, JA AF Dorgan, JE Boayke, NA Fears, TR Schleicher, RL Helsel, W Anderson, C Robinson, J Guin, JD Lessin, S Ratnasinghe, LD Tangrea, JA TI Serum carotenoids and alpha-tocopherol and risk of non-melanoma skin cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. NCI, Bethesda, MD 20892 USA. Ctr Dis Control, Atlanta, GA 30333 USA. Informat Management Serv Inc, Silver Spring, MD USA. Loyola Univ, Chicago, IL 60611 USA. Univ Arkansas, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1339S EP 1339S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300245 ER PT J AU Lavigne, JA Judd, JT Wimbrow, HH Albert, PS Reichman, ME Campbell, WS Barrett, JC Clevidence, BA Hursting, SD Taylor, PR AF Lavigne, JA Judd, JT Wimbrow, HH Albert, PS Reichman, ME Campbell, WS Barrett, JC Clevidence, BA Hursting, SD Taylor, PR TI Effects of alcohol and menstrual cycle on insulin-like growth factor-I and insulin-like growth factor binding protein-3. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, CCR, Bethesda, MD 20892 USA. ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1339S EP 1339S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300244 ER PT J AU Stolzenberg-Solomon, R Limburg, P Pollak, M Taylor, P Virtamo, J Albanes, D AF Stolzenberg-Solomon, R Limburg, P Pollak, M Taylor, P Virtamo, J Albanes, D TI Insulin-like growth factor (IGF)-1, IGF-binding protein (BP)-3 and pancreatic cancer in male smokers. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Rockville, MD USA. Mayo Clin, Rochester, MN USA. McGill Univ, Montreal, PQ, Canada. NPHI, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1339S EP 1339S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300247 ER PT J AU Patel, AC Zeytin, HE Mai, V Perkins, SN Schlom, J Hursting, SD Greiner, JW AF Patel, AC Zeytin, HE Mai, V Perkins, SN Schlom, J Hursting, SD Greiner, JW TI Effect of dietary modifications on the immune response in Apc(Min) mice, a model for intestinal carcinogenesis. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 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 NOV PY 2003 VL 12 IS 11 SU S BP 1342S EP 1342S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300259 ER PT J AU Seo, HS Kim, HT Kong, G Dupre, E Lamph, WW Johnson, KA Brown, PH AF Seo, HS Kim, HT Kong, G Dupre, E Lamph, WW Johnson, KA Brown, PH TI Rexinoid-regulated biomarkers: Up-regulation of IGFBP-6 correlates with rexinoid-induced growth suppression of normal and malignant breast cells. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Baylor Coll Med, Breast Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Ligand Pharmaceut Inc, Dept Retinoid Res, San Diego, CA 92121 USA. NIH, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1345S EP 1345S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300270 ER PT J AU Shen, Q Lu, CH Hill, J Zhang, Y Kim, HT Young, M Colburn, N Brown, PH AF Shen, Q Lu, CH Hill, J Zhang, Y Kim, HT Young, M Colburn, N Brown, PH TI Targeting transcription factor AP-1 for the prevention of breast cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Baylor Coll Med, Houston, TX 77030 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1345S EP 1345S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300269 ER PT J AU Ouyang, N Williams, JL Gao, JJ Iatropoulos, MJ Tsioulias, DJ Kopelovich, L Kashfi, K Rigas, B AF Ouyang, N Williams, JL Gao, JJ Iatropoulos, MJ Tsioulias, DJ Kopelovich, L Kashfi, K Rigas, B TI Marked prevention of pancreatic cancer by NO-donating aspirin in a hamster model. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 Inst Canc Prevent, Valhalla, NY USA. NCI, Chemoprevent Branch, NIH, Bethesda, MD 20892 USA. CUNY, Sch Med, New York, NY 10031 USA. New York Med Coll, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1350S EP 1350S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300285 ER PT J AU Hawk, E Umar, A Viner, JL AF Hawk, E Umar, A Viner, JL TI Defining primary, secondary, and tertiary prevention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, DCP, Bethesda, MD USA. NR 0 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 NOV PY 2003 VL 12 IS 11 SU S BP 1356S EP 1356S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300307 ER PT J AU Merlino, G AF Merlino, G TI Chemoprevention of melanoma: Genetically engineered mouse models SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1357S EP 1357S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300309 ER PT J AU Parnes, H AF Parnes, H TI Prostate cancer prevention agent development SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1362S EP 1362S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300326 ER PT J AU Devesa, S Bray, FI Vizcaino, AP Parkin, DM AF Devesa, S Bray, FI Vizcaino, AP Parkin, DM TI International lung cancer trends overall and by histologic type SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Div Canc Etiol, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1363S EP 1363S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300328 ER PT J AU Colburn, N Young, MR Matthews, C Bowden, T Jansen, AP AF Colburn, N Young, MR Matthews, C Bowden, T Jansen, AP TI Molecular target validation and discovery in transgenic mouse models of cancer prevention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1368S EP 1369S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300343 ER PT J AU Lam, S leRiche, JC MacAulay, C McWilliams, A Szabo, E Gazdar, AF AF Lam, S leRiche, JC MacAulay, C McWilliams, A Szabo, E Gazdar, AF TI Progress in the treatment of lung intraepithelial neoplastic lesions SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NCI, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1369S EP 1369S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300346 ER PT J AU Rowland, J AF Rowland, J TI Cancer prevention and control among survivors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, DCCPS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1369S EP 1369S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300344 ER PT J AU Ballard-Barbash, R AF Ballard-Barbash, R TI Obesity and cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1371S EP 1371S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300351 ER PT J AU Schatzkin, A AF Schatzkin, A TI Diet and cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2003 VL 12 IS 11 SU S BP 1371S EP 1371S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300350 ER PT J AU Schlom, J Hodge, JW Tsang, KY Zeytin, HE Patel, AC Hursting, SD Greiner, JW AF Schlom, J Hodge, JW Tsang, KY Zeytin, HE Patel, AC Hursting, SD Greiner, JW TI Vector-based vaccines for the immunotherapy and immunoprevention of cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 2nd Annual AACR International Conference on Frontiers in Cancer Prevention Research CY OCT 26-30, 2003 CL PHOENIX, ARIZONA SP Amer Assoc Canc Res, Pfizer, AstraZeneca, Canc Res & Prevent Fdn, SuperGen, AFLAC Inc, Avon Fdn, Bristol Myers Squibb, Eli Lilly & Co, NCI, Takeda Pharmaceut N Amer Inc, Calif Breast Canc Res Program C1 NCI, NIH, Potomac, MD USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 0 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 NOV PY 2003 VL 12 IS 11 SU S BP 1375S EP 1376S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 752GT UT WOS:000187153300362 ER PT J AU Habermann, JK Upender, MB Roblick, UJ Kruger, S Freitag, S Blegen, H Bruch, HP Schimmelpenning, H Auer, G Ried, T AF Habermann, JK Upender, MB Roblick, UJ Kruger, S Freitag, S Blegen, H Bruch, HP Schimmelpenning, H Auer, G Ried, T TI Pronounced chromosomal instability and multiple gene amplifications characterize ulcerative colitis-associated colorectal carcinomas SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; LAMININ-5 GAMMA-2 CHAIN; CANCER CELL-LINES; CYCLIN-A; COLON CARCINOMAS; RAS MUTATIONS; EXPRESSION; BREAST; P53; SURVEILLANCE AB Patients with ulcerative colitis have a significantly increased lifetime risk for the development of colorectal carcinomas. While genetic and genomic changes during carcinogenesis have been thoroughly studied in sporadic colorectal cancers, less is known about ulcerative colitis-associated colorectal carcinomas. The aim of this study was to extend the identification of specific genomic imbalances to ulcerative colitis-associated colorectal carcinomas and to establish a comprehensive map of DNA gains and losses by investigating 23 tumor specimens from 23 patients. The molecular cytogenetic characterization was performed using comparative genomic hybridization; immunohistochemistry was used to measure proliferative activity and laminin-5 expression as a marker for invasiveness. The results indicate that these tumors are invariably aneuploid, with a high proliferative activity and increased invasive potential. The average number of copy alterations correlates with increased cyclin A levels (P = 0.044), which is an independent predictor of risk of carcinoma development in ulcerative colitis. Despite severe genetic instability, the general pattern of specific chromosomal aberrations that defines sporadic colorectal carcinomas is maintained in ulcerative colitis-associated malignancies. High-level copy number increases (amplifications) are dispersed throughout the genome. Strikingly, these amplifications are much more frequent than in sporadic carcinomas and map to chromosomal regions that have not been described before. (C) 2003 Elsevier Inc. All fights reserved. C1 NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Canc Ctr Karolinska, Stockholm, Sweden. Univ Hosp Schleswig, Dept Surg, Lubeck, Germany. Univ Hosp Schleswig, Inst Pathol, Lubeck, Germany. Univ Hosp Schleswig, Inst Med Informat & Stat, Kiel, Germany. RP Ried, T (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH, Bldg 50,Room 1408,50 South Dr, Bethesda, MD 20892 USA. RI Bruch, Hans-Peter/E-7731-2010; Habermann, Jens/E-2968-2010 NR 24 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD NOV PY 2003 VL 147 IS 1 BP 9 EP 17 DI 10.1016/S0165-4608(03)00219-X PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 739TT UT WOS:000186363100002 PM 14580765 ER PT J AU Vortmeyer, AO Frank, S Jeong, SY Yuan, K Ikejiri, B Lee, YS Bhowmick, D Lonser, RR Smith, R Rodgers, G Oldfield, EH Zhuang, ZP AF Vortmeyer, AO Frank, S Jeong, SY Yuan, K Ikejiri, B Lee, YS Bhowmick, D Lonser, RR Smith, R Rodgers, G Oldfield, EH Zhuang, ZP TI Developmental arrest of angioblastic lineage initiates tumorigenesis in von Hippel-Lindau disease SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; EMBRYONIC LETHALITY; GENE; VASCULOGENESIS; EXPRESSION; HEMANGIOBLASTOMAS; ANGIOGENESIS; CELLS; MICE AB The nature of the cell responsible for von Hippel-Lindau (VHL) disease-associated tumor formation has been controversial for decades. We demonstrate that VHL disease-associated central nervous system tumors are composed of developmentally arrested angioblasts that coexpress erythropoietin (Epo) and Epo receptor. The angioblasts are capable of differentiating into RBCs via formation of blood islands with extramedullary hematopoiesis. Because of VHL deficiency, Epo receptor-expressing, developmentally arrested angioblasts simultaneously coexpress Epo, which may represent a crucial pathogenetic step in tumor formation. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Vortmeyer, AO (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 25 TC 62 Z9 64 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 NOV 1 PY 2003 VL 63 IS 21 BP 7051 EP 7055 PG 5 WC Oncology SC Oncology GA 742UA UT WOS:000186535400006 PM 14612494 ER PT J AU Laine, JP Opresko, PL Indig, FE Harrigan, JA von Kobbe, C Bohr, VA AF Laine, JP Opresko, PL Indig, FE Harrigan, JA von Kobbe, C Bohr, VA TI Werner protein stimulates topoisomerase I DNA relaxation activity SO CANCER RESEARCH LA English DT Article ID NUCLEAR-LOCALIZATION; RECQ HELICASES; SYNDROME GENE; CELL-LINES; III-ALPHA; LIFE-SPAN; S-PHASE; RECOMBINATION; DAMAGE; CAMPTOTHECIN AB Werner syndrome (WS) is a human premature aging disorder characterized by the early onset of age-related clinical features and an elevated incidence of cancer. The Werner protein (WRN) belongs to the RecQ family of DNA helicases and is required for the maintenance of genomic stability in human cells. Potential cooperation between RecQ helicases and topoisomerases in many aspects of DNA metabolism, such as the progression of replication forks, transcription, recombination, and repair, has been reported. Here, we show a physical and functional interaction between WRN and topoisomerase I (topo I). WRN colocalizes and interacts directly with topo I. WRN stimulates the ability of topo I to relax negatively supercoiled DNA and specifically stimulates the religation step of the relaxation reaction. Moreover, cell extracts from WS fibroblasts exhibit a decrease in the relaxation activity of negatively supercoiled DNA. We have identified two regions of WRN that mediate functional interaction with topo I, and they are located at the NH2 and COOH termini of the WRN protein. In a reciprocal functional interaction, topo I inhibits the ATPase activity of WRN. Our data provide new insight into the interrelationship between RecQ helicases and topoisomerases in the maintenance of genomic integrity and prevention of tumorigenesis. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. RP Laine, JP (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Opresko, Patricia/0000-0002-6470-2189 NR 46 TC 49 Z9 51 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 NOV 1 PY 2003 VL 63 IS 21 BP 7136 EP 7146 PG 11 WC Oncology SC Oncology GA 742UA UT WOS:000186535400019 PM 14612507 ER PT J AU Milyavsky, M Shats, I Erez, N Tang, XH Senderovich, S Meerson, A Tabach, Y Goldfinger, N Ginsberg, D Harris, CC Rotter, V AF Milyavsky, M Shats, I Erez, N Tang, XH Senderovich, S Meerson, A Tabach, Y Goldfinger, N Ginsberg, D Harris, CC Rotter, V TI Prolonged culture of telomerase-immortalized human fibroblasts leads to a premalignant phenotype SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; HUMAN-DIPLOID FIBROBLASTS; REPLICATIVE LIFE-SPAN; PREMATURE SENESCENCE; TUMOR-SUPPRESSOR; CONTACT-INHIBITION; GENE-EXPRESSION; ONCOGENIC RAS; HUMAN CANCERS; INK4A LOCUS AB Telomere shortening in primary human fibroblasts results in replicative senescence, which can be overcome by telomerase (hTERT) overexpression. However, because immortalization is one of the hallmarks of malignant transformation, careful analysis of hTERT-immortalized cells is of crucial importance for understanding both processes. To this end, we infected WI-38 fibroblasts with a retrovirus carrying the hTERT cDNA and analyzed their proliferative behavior during 600 days [similar to500 population doublings (PDLs)] of continuous culture. Growth of three independent mass cultures was uniform for similar to150 PDLs after telomerase infection, followed by a progressive acceleration of growth in two of three cultures. Expression of p16(INK4A) was significantly elevated in the immortalized cells but gradually disappeared during the accelerated growth phase. This alteration correlated with loss of the contact inhibition response and conferred the cells with sensitivity to H-Ras-induced transformation. In contrast, the p53- and pRb-mediated checkpoints such as the DNA damage response, chromosomal stability and entry into quiescence remained intact, irrespective of INK4A locus expression. Importantly, detailed examination of one of the WI-38/hTERT cultures during the accelerated growth phase revealed overexpression of the c-myc and Bmi-1 oncogenes, as well as loss of p14(ARF) expression. Collectively, our results indicate that although hTERT-immortalized cells behave similarly to primary cells during the first 150 PDLs, long-term growth in culture may favor the appearance of clones carrying potentially malignant alterations. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Milyavsky, M (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RI Milyavsky, Michael/E-8306-2011 NR 79 TC 114 Z9 116 U1 0 U2 8 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 NOV 1 PY 2003 VL 63 IS 21 BP 7147 EP 7157 PG 11 WC Oncology SC Oncology GA 742UA UT WOS:000186535400020 PM 14612508 ER PT J AU Cunliffe, HE Ringner, M Bilke, S Walker, RL Cheung, JM Chen, YD Meltzer, PS AF Cunliffe, HE Ringner, M Bilke, S Walker, RL Cheung, JM Chen, YD Meltzer, PS TI The gene expression response of breast cancer to growth regulators: Patterns and correlation with tumor expression profiles SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; ESTROGEN-RECEPTOR-ALPHA; MCF-7 CELLS; PHORBOL ESTERS; INDUCED ACTIVATION; COUPLED RECEPTOR; CDNA MICROARRAY; TAMOXIFEN; PATHWAY; IDENTIFICATION AB The effects of hormone and growth factor signaling on gene expression contribute significantly to breast tumorigenesis and disease progression; however, the targets of signaling networks associated with deregulated growth are not well understood. We defined the dynamic transcriptional effects elicited in MCF7, T-47D, and MDA-MB-436 breast cancer cell lines by nine regulators of growth and differentiation (17beta-estradiol, antiestrogens fulvestrant and tamoxifen, progestin R5020, antiprogestin RU486, all-trans-retinoic acid, epidermal growth factor, mitogen-activated protein/extracellular signal-regulated kinase 1/2 inhibitor U0126 and phorbol ester 12-O-tetradecanoylphorbol-13-acetate) and compared the patterns of gene regulation to published tumor expression profiles. The complex pattern of response to these agents revealed unexpected relationships between their effects, including a profound overlap in genes regulated by both steroids and epidermal growth factor, and striking overlaps between fulvestrant and all-trans-retinoic acid. Estrogen-responsive genes could be divided into two major clusters, only one of which is associated with cell proliferation. Gene ontology analysis was used to highlight functionally distinct biological responses to different mitogens. Significant correlations were identified between several clusters of drug-responsive genes and genes that discriminate estrogen receptor status or disease outcome in patient samples. The majority of estrogen receptor status discriminators were not responsive in our dataset and are therefore likely to reflect underlying differences in histogenesis and disease progression rather than growth factor signaling. This article highlights the overall impact at the gene expression level of diverse regulators of breast cancer growth and links the behavior of breast cancer cells in culture to important clinical properties of human breast tumors. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Lund Univ, Complex Syst Div, Dept Theoret Phys, SE-22362 Lund, Sweden. NCI, Ctr Adv Technol, Gaithersburg, MD 20877 USA. RP Cunliffe, HE (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA. RI Ringner, Markus/G-3641-2011 OI Ringner, Markus/0000-0001-5469-8940 NR 57 TC 65 Z9 72 U1 0 U2 0 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 NOV 1 PY 2003 VL 63 IS 21 BP 7158 EP 7166 PG 9 WC Oncology SC Oncology GA 742UA UT WOS:000186535400021 PM 14612509 ER PT J AU Burk, RD Terai, M Gravitt, PE Brinton, LA Kurman, RJ Barnes, WA Greenberg, MD Hadjimichael, OC Fu, LP McGowan, L Mortel, R Schwartz, PE Hildesheim, A AF Burk, RD Terai, M Gravitt, PE Brinton, LA Kurman, RJ Barnes, WA Greenberg, MD Hadjimichael, OC Fu, LP McGowan, L Mortel, R Schwartz, PE Hildesheim, A TI Distribution of human papillomavirus types 16 and 18 variants in squamous cell carcinomas and adenocarcinomas of the cervix SO CANCER RESEARCH LA English DT Article ID LONG CONTROL REGION; ORAL-CONTRACEPTIVE USE; UTERINE CERVIX; UNITED-STATES; SEQUENCE-ANALYSIS; IN-SITU; RISK; NEOPLASIA; CANCER; E6 AB The distributions of human papillomavirus (HPV) types detected in cervical adenocarcinomas and squamous cell tumors differ. However, whether the distributions of intratypic HPV variants seen in these two histological forms of cervical disease differ is unknown. Our objective was to compare the distribution of HPV intratypic variants observed in squamous cell carcinomas (SCC) and cervical tumors of glandular origin (e.g., adenocarcinomas; AC) for two HPV types commonly observed in cervical tumors, HPV16 and HPV18. Participants in a multicenter case-control study of AC and SCC conducted in the eastern United States were studied. A total of 85 HPV16 and/or HPV18 positive individuals (31 diagnosed with AC, 43 diagnosed with SCC, and 11 population controls) were included. For HPV16-positive individuals, both the noncoding long control region and the E6 open reading frame were sequenced, and classified into phylogenetic-based lineage groups (European, Asian-American, African1, and African2). For HPV18-positive individuals, the long control region region only was sequenced and classified into known intratypic lineages (European, Asian-Amerindian, and African). The distribution of these different intratypic lineages among AC cases, SCC cases, and population controls was compared using standard methods. Non-European HPV16 and/or HPV18 intratypic variants were observed in 42% of ACs compared with 16% of SCCs and 18% of population controls (P = 0.04). Intratypic variants from the Asian-American lineage of HPV16 accounted for the differences seen between histological groups. The differences observed between AC and SCC cases were strongest for HPV16, and persisted in analysis restricted to Caucasian women, suggesting that the effect cannot be explained by differences in the ethnic make-up of AC versus SCC cases. Cervical AC and SCC differ not only with respect to the distribution of HPV types detected but also with respect to intratypic variants observed. Non-European HPV16 and/or HPV18 variants are commonly seen in AC. A possible hormonal mechanism is suggested to explain the observed findings. C1 Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10461 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA. Grad Hosp Philadelphia, Philadelphia, PA 19146 USA. Yale Univ, Sch Med, New Haven, CT 06510 USA. George Washington Univ, Div Genet Oncol, Washington, DC 20037 USA. Milton S Hershey Med Ctr, Hershey, PA 17033 USA. RP Burk, RD (reprint author), Albert Einstein Coll Med, Dept Pediat, 1300 Morris Pk Ave,Ullman 515, Bronx, NY 10461 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 32 TC 93 Z9 94 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 NOV 1 PY 2003 VL 63 IS 21 BP 7215 EP 7220 PG 6 WC Oncology SC Oncology GA 742UA UT WOS:000186535400028 PM 14612516 ER PT J AU Kim, MS Blake, M Baek, JH Kohlhagen, G Pommier, Y Carrier, F AF Kim, MS Blake, M Baek, JH Kohlhagen, G Pommier, Y Carrier, F TI Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA SO CANCER RESEARCH LA English DT Article ID TOPOISOMERASE-II INHIBITORS; ETOPOSIDE-INDUCED APOPTOSIS; TUMOR-SUPPRESSOR GENES; CHROMATIN-STRUCTURE; CELL-CYCLE; IN-VIVO; CLEAVAGE SITES; TRICHOSTATIN-A; CANCER CELLS; P53 GENE AB Several anticancer drugs target DNA or enzymes acting on the DNA. Because chromatin DNA is tightly compacted, accessibility to the drug target may reduce the efficiency of these anticancer drugs. We thus treated four human cancer cell lines and two normal epithelial cell lines with either trichostatin A (TSA) or SAHA, two histone deacetylase inhibitors, before exposing the cells to VP-16, ellipticine, camptothecin, doxorubicin, cisplatin, 5-fluorouracil, or cyclophosmamide. Pretreatment with TSA or SAHA increased the killing efficiency of VP-16, ellipticine, doxorubicin, and cisplatin. The magnitude of sensitization is cell type specific and is >10-fold for VP-16 in D54, a brain tumor cell line intrinsically resistant to topoisomerase II inhibitors. Topoisomerase II levels and activity were not affected by this treatment, but p53, p21, and Gadd45 protein levels were markedly induced. Moreover, pretreatment with TSA also increased VP-16-induced apoptosis in a p53-dependent and -independent manner. Treating the cells in the reverse order (anticancer drug First, followed by TSA or SAHA) had no more cytotoxic effect than the drug alone. These data suggest that loosening-up the chromatin structure by histone acetylation can increase the efficiency of several anticancer drugs targeting DNA. This may be advantageous for treating tumors intrinsically resistant to these drugs. C1 Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Univ, Baltimore, MD 21231 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Carrier, F (reprint author), Univ Maryland, Dept Biochem & Mol Biol, Sch Med, 108 N Greene St,Room 330, Baltimore, MD 21201 USA. RI Carrier, France/C-3063-2008 FU NIGMS NIH HHS [R01 GM 57827-01] NR 56 TC 337 Z9 351 U1 2 U2 19 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 NOV 1 PY 2003 VL 63 IS 21 BP 7291 EP 7300 PG 10 WC Oncology SC Oncology GA 742UA UT WOS:000186535400038 PM 14612526 ER PT J AU Russell, JS Brady, K Burgan, WE Cerra, MA Oswald, KA Camphausen, K Tofilon, PJ AF Russell, JS Brady, K Burgan, WE Cerra, MA Oswald, KA Camphausen, K Tofilon, PJ TI Gleevec-mediated inhibition of Rad51 expression and enhancement of tumor cell radiosensitivity SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGE; IONIZING-RADIATION; C-ABL; SACCHAROMYCES-CEREVISIAE; RECOMBINATION PROTEIN; ANTISENSE INHIBITION; IN-VITRO; RESISTANCE; REPAIR; RECA AB Rad51 is an essential component of the homologous DNA repair pathway and has been implicated as a determinant of cellular radiosensitivity. Gleevec is a relatively specific inhibitor of c-Abl, a tyrosine kinase that can play a role in the regulation Rad51. The aim of this study was to determine the effects of Gleevec on Rad51 levels and the radiosensitivity of two human glioma cell lines and a nonimmortalized normal human fibroblast cell line. Exposure of both glioma cell lines to radiation resulted in an increase in Rad51 expression; Gleevec treatment alone reduced Rad51 expression. When glioma cells were pretreated with Gleevec, radiation-induced Rad51 expression and nuclear foci formation were reduced. Accordingly, pretreatment of the glioma cells with Gleevec resulted in an enhancement in their radiosensitivity. These data indicate that Gleevec enhances radiation-induced tumor cell killing and suggest that the mechanism involves the reduction in Rad51 levels. In contrast to the glioma cell lines, radiation or Gleevec treatments had no effect on Rad51 expression or foci formation in the normal fibroblast cells. Consistent with these observations, Gleevec did not modify the radiosensitivity of the normal cell line. These results suggest that Rad51 expression is subject to different regulatory processes in the glioma and normal cell lines and further suggest that Rad51 may be an appropriate target for selectively enhancing the radiosensitivity of brain tumor cells. C1 NCI, Mol Radiat Therapeut Branch, Radiat Oncol Sci Program, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, Bethesda, MD 20892 USA. RP Tofilon, PJ (reprint author), NCI, Mol Radiat Therapeut Branch, Radiat Oncol Sci Program, EPN-6015A,6130 Execut Blvd,MSC 7440, Bethesda, MD 20892 USA. NR 26 TC 123 Z9 127 U1 0 U2 4 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 NOV 1 PY 2003 VL 63 IS 21 BP 7377 EP 7383 PG 7 WC Oncology SC Oncology GA 742UA UT WOS:000186535400048 PM 14612536 ER PT J AU Seong, YS Min, C Li, LW Yang, JY Kim, SY Cao, XD Kim, K Yuspa, SH Chung, HH Lee, KS AF Seong, YS Min, C Li, LW Yang, JY Kim, SY Cao, XD Kim, K Yuspa, SH Chung, HH Lee, KS TI Characterization of a novel cyclin-dependent kinase 1 inhibitor, BMI-1026 SO CANCER RESEARCH LA English DT Article ID ANAPHASE-PROMOTING COMPLEX; TUMOR AMPLIFIED KINASE; CELL-CYCLE; PROTEIN-KINASE; POLY(ADP-RIBOSE) POLYMERASE; MITOTIC SPINDLE; CARCINOMA-CELLS; HUMAN CDK2; MITOSIS; ARREST AB Cyclin-dependent kinases (Cdks) have been attractive targets for the development of anticancer therapeutic agents. In an effort to generate a new class of anti-Cdk inhibitors, we synthesized aryl aminopyrimidines and examined the effect of these compounds in both in vitro kinase assays and cultured cells. Two of these compounds, BMI-1026 and BMI-1042, induced a strong cell cycle alteration with potent inhibitory activities against cyclin-dependent kinases, collectively known as Cdks. Characterization of BMI-1026 revealed that it imposes a potent G(2)-M arrest and mild G(1)-S and S arrests. In vitro biochemical analyses and in vivo time-lapse microscopy studies revealed that it induces a mitotic catastrophe and precocious mitotic exit even in the presence of nocodazole. These defects appeared to lead to apoptotic cell death in tumorigenic cell lines. Consistent with the induction of mitotic defects and apopitosis, BMI-1026 imposed a selective sensitivity to proliferating versus differentiating or growth-arrested mouse keratinocytes. These data suggest that BMI-1026 could be developed as a potential anti-Cdk1 chemotherapeutic agent. C1 NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Lab Cellular Carcinogenesis & Tumor Promot, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Dankook Med Coll, Dept Biochem, Seoul 330714, South Korea. LG Biomed Inst, La Jolla, CA 92037 USA. RP Lee, KS (reprint author), NCI, Lab Metab, Canc Res Ctr, NIH, 9000 Rockville Pike,Bldg 37,Room 2D11, Bethesda, MD 20892 USA. NR 29 TC 31 Z9 33 U1 0 U2 0 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 NOV 1 PY 2003 VL 63 IS 21 BP 7384 EP 7391 PG 8 WC Oncology SC Oncology GA 742UA UT WOS:000186535400049 PM 14612537 ER PT J AU Antony, S Jayaraman, M Laco, G Kohlhagen, G Kohn, KW Cushman, M Pommier, Y AF Antony, S Jayaraman, M Laco, G Kohlhagen, G Kohn, KW Cushman, M Pommier, Y TI Differential induction of topoisomerase I-DNA cleavage complexes by the indenoisoquinoline MJ-III-65 (NSC 706744) and camptothecin: Base sequence analysis and activity against camptothecin-resistant topoisomerases I SO CANCER RESEARCH LA English DT Article ID CELL-LINES; SITE; INHIBITORS; DERIVATIVES; MECHANISM; ABSENCE; LACTONE; BREAKS; MODEL; HOMOCAMPTOTHECIN AB Camptothecin (CPT) and its derivatives target mammalian DNA topoisomerase I (top1) and are among the most effective novel anticancer drugs. However, the activity of CPTs is limited by several factors, including drug inactivation by lactone ring opening, tumor drug resistance, and toxicity in patients. Novel top1 inhibitors are being searched to overcome such limitations and expand the anticancer spectrum of camptothecins. MJ-III-65 (NSC 706744) is among the most promising indenoisoquinolines to date. In this study, we show that MJ-III-65 enhances top1 cleavage complexes by both inhibiting their reversal (religation) more efficiently than CPT and by enhancing their formation. The top1 DNA cleavage complexes induced by MJ-III-65 exhibit a different distribution pattern compared with CPT and exhibit different base sequence preferences immediately around the top1 cleavage sites. Although CPTs have a preference for thymine at the (-1) position and guanine at the (+1) position of the top1-mediated DNA cleavage sites, MJ-III-65 can accommodate different base pairs at the (-1), (+1), or (+2) position, with a preference for a cytosine at the (-1) position on the scissile strand. Another difference with CPTs is the activity of MJ-III-65 against CPT-resistant top1 enzymes, implying that the amino acid residue interactions with top1 are different for MJ-III-65 and CPTs. As with CPT, MJ-III-65 is inactive against vaccinia top1. This study shows the specific molecular interactions of MJ-III-65 with top1 and demonstrates that MJ-III-65 is a potentially useful top1 inhibitor that enhances and traps top1 cleavage sites not sensitive to CPTs. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Purdue Univ, Dept Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. NR 51 TC 83 Z9 84 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 NOV 1 PY 2003 VL 63 IS 21 BP 7428 EP 7435 PG 8 WC Oncology SC Oncology GA 742UA UT WOS:000186535400054 PM 14612542 ER PT J AU Lavergne, E Combadiere, B Bonduelle, O Iga, M Gao, JL Maho, M Boissonnas, A Murphy, PM Debre, P Combadiere, C AF Lavergne, E Combadiere, B Bonduelle, O Iga, M Gao, JL Maho, M Boissonnas, A Murphy, PM Debre, P Combadiere, C TI Fractalkine mediates natural killer-dependent antitumor responses in vivo SO CANCER RESEARCH LA English DT Article ID IFN-GAMMA; MELANOMA-CELLS; RECEPTOR CX(3)CR1; INTERFERON-GAMMA; T-CELLS; CHEMOKINES; CANCER; GROWTH; EXPRESSION; ADHESION AB CX3CR1 has been described previously as a marker of human cytotoxic effector cells. We evaluated the possibility of using its ligand, CX3CL1 to redirect immune response against tumors. When murine lymphoma cell lines (EL4 and its derivative EG7) stably transfected with human-CX3CL1 were injected s.c. into C57BL/6 mice, the tumor growth was severely impaired when compared with the growth of control cell lines. This antitumor effect of CX3CL1 was also found in T- and B-cell-deficient Rag1-/- mice but vanished in natural killer (NK) cell-deficient beige mice and in CX3CR1-/- mice, suggesting the involvement of CX3CR1-expressing NK cells. In addition, increased NK cell infiltration was observed in CX3CL1-producing tumors compared with controls. The effect of CX3CR1 on tumor growth required host cytotoxic effector cell functions because both IFNgamma-/- and perforin-/- mice were resistant to CX3CL1 antitumor effect. Finally, intratumoral injection of DNA plasmid coding for a chimeric immunoglobulin presenting the CX3CL1 chemokine domain provided strong antitumor activity. Together, these data demonstrate that the CX3CL1 can reduce incidence and size of lymphoma in vivo through increased recruitment of activated NK cytotoxic cells. These findings offer the first evidence of the potential of chimeric immunoglobulin-chemokines in anticancer therapy. C1 Hop La Pitie Salpetriere, INSERM, U543, Lab Immunol Cellularie & Tissulaire, F-75634 Paris 13, France. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Combadiere, C (reprint author), Hop La Pitie Salpetriere, INSERM, U543, Assistance Publ Hop Paris, 91 Blvd Hop, F-75634 Paris 13, France. RI Combadiere, Christophe/I-5639-2013; Combadiere, Behazine/G-3881-2013; Boissonnas, Alexandre/A-2801-2016 OI Combadiere, Christophe/0000-0002-1755-4531; Boissonnas, Alexandre/0000-0002-7770-7210 NR 42 TC 73 Z9 75 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 NOV 1 PY 2003 VL 63 IS 21 BP 7468 EP 7474 PG 7 WC Oncology SC Oncology GA 742UA UT WOS:000186535400059 PM 14612547 ER PT J AU Schroeder, JC Conway, K Li, Y Mistry, K Bell, DA Taylor, JA AF Schroeder, JC Conway, K Li, Y Mistry, K Bell, DA Taylor, JA TI p53 mutations in bladder cancer: Evidence for exogenous versus endogenous risk factors SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION-COUPLED REPAIR; HYDROCARBON-DNA ADDUCTS; HUMAN URINARY-BLADDER; TUMOR-SUPPRESSOR; GENE-MUTATIONS; 4-AMINOBIPHENYL-DNA ADDUCTS; MOLECULAR EPIDEMIOLOGY; CARCINOGEN-METABOLISM; CYTOSINE METHYLATION; UROTHELIAL CELLS AB Bladder cancer is associated with smoking, occupational exposures, and glutathione S-transferase (GST) M1 and N-acetyltransferase (NAT) 2 polymorphisms that may influence carcinogen metabolism, but somatic p53 mutations are often CpG dinucleotide G:C-A:T transitions that can occur spontaneously. We conducted a case-control study to determine whether p53 mutation characteristics might distinguish cases with environmental versus endogenous causes. p53 exons 4-9 were amplified from 146 bladder tumors by PCR, screened by single-strand conformational polymorphism analysis, and sequenced. Thirty-one cases were p53-positive, and 112 were p53-negative (germ line or silent). G:C-A:T transitions were also subclassified as CpG or non-CpG. Cases and 215 clinic controls were interviewed. GSTM1, NAT1, and NAT2 polymorphisms were assayed from peripheral blood. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic and polytomous regression. Case-control ORs for smoking, occupations, and NAT1*10 genotype were similar for p53-positive and p53-negative cases. Associations with GSTM1-null and NAT2-slow genotypes were somewhat stronger for p53-positive [OR, 3.3; CI, 1.4-7.8 (GSTM1 null); OR, 1.8; CI, 0.8-4.0 (NAT2 slow)] than p53-negative cases [OR, 1.5; CI:0.9-2.3 (GSTM1 null); OR, 0.9; CI, 0.6-1.4 (NAT2 slow)]. Smoking was strongly associated with CpG G:CA:T (OR, 15.3; CI:3.6-65) versus other G:C-A:T (OR, 1.8; CI, 0.3-9.8). NAT2 slow genotypes were also associated with CpG G:C-A:T (OR, 6.2; CI:0.7-52), whereas GSTM1 null was associated with non-CpG G:C-A:T (OR, 7.8; CI, 0.9-65). Associations were not substantially different for case subtypes defined by p53 mutation status alone. Estimates for p53 subtypes were imprecise but support in vitro evidence that some CpG G:C-A:T transitions may be caused by smoking and other environmental mutagens. C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol & Genet Epidemiol Grp, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. RP Taylor, JA (reprint author), NIEHS, Epidemiol Branch, NIH, POB 12233,MD A3-05,Room A362,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. OI taylor, jack/0000-0001-5303-6398 NR 72 TC 24 Z9 25 U1 1 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 NOV 1 PY 2003 VL 63 IS 21 BP 7530 EP 7538 PG 9 WC Oncology SC Oncology GA 742UA UT WOS:000186535400068 PM 14612556 ER PT J AU Brady, M Koban, MU Dellow, KA Yacoub, M Boheler, KR Fuller, SJ AF Brady, M Koban, MU Dellow, KA Yacoub, M Boheler, KR Fuller, SJ TI Sp1 and Sp3 transcription factors are required for trans-activation of the human SERCA2 promoter in cardiomyocytes SO CARDIOVASCULAR RESEARCH LA English DT Article DE sarcoplasmic reticulum Ca2+-ATPase; gene expression; cardiac myocytes; transcription factors; promoter ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; PRESSURE-OVERLOAD HYPERTROPHY; GENE-EXPRESSION; HEART-FAILURE; VENTRICULAR CARDIOMYOCYTES; CARDIAC-HYPERTROPHY; SKELETAL-MUSCLE; RAT; PROTEINS; MYOCARDIUM AB Objectives: The sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) is essential to the removal of cytosolic calcium following cardiac contraction, and its abundance and activity are significantly altered during perinatal development and in failing myocardium. The objective of the current study was to identify cis regulatory elements and nuclear transcription factors responsible for transactivating SERCA2 gene expression in cardiomyocytes. Methods: Primary cultures of neonatal rat ventricular myocytes were transiently transfected with luciferase (LUX) reporter gene constructs containing deletions of the SERCA2 promoter or which harbored mutations in consensus Sp1 transcription factor binding sites. Cotransfection assays, electrophoretic mobility shift, and supershift assays were also performed to delineate the regulatory role of specific transcription factors. Results: We identified a putative AP-1-like element and a consensus Egr-1 binding site, but neither Egr-1 nor 12-O-tetradecanoylphorbol 13-acetate (TPA) significantly modified human SERCA2 promoter activity in vitro. Maximal activity of the SERCA2 promoter required the proximal 177 bp, and strong activation was observed with a 125-bp construct, within which an Sp1 site and a CAAT box were important. Mutation analysis also revealed the importance of two Sp1 sites between -125 and -200. Sp1 and Sp3 transcription factors were subsequently identified to bind to oligonucleotide probes corresponding to only the two most proximal Sp1 sites. Conclusions: These studies provide direct evidence that regulation of human SERCA2 gene expression in cardiomyocytes depends on transactivation events elicited by Sp1 and Sp3 transcription factors. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst Div, London SW3 6LY, England. NIA, NIH, Baltimore, MD 21224 USA. RP Fuller, SJ (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst Div, Guy Scadding Bldg,Dovehouse St, London SW3 6LY, England. NR 38 TC 22 Z9 22 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV 1 PY 2003 VL 60 IS 2 BP 347 EP 354 DI 10.1016/S0008-6363(03)00529-7 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 739RD UT WOS:000186359500019 PM 14613864 ER PT J AU McNairy, SA AF McNairy, SA TI Message from the Director SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Editorial Material C1 NIH, Div Res Infrastruct, Natl Ctr Res Resources, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP McNairy, SA (reprint author), NIH, Div Res Infrastruct, Natl Ctr Res Resources, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD NOV PY 2003 VL 49 IS 7 BP 1003 EP 1004 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757VT UT WOS:000187582700002 ER PT J AU Crawford, KW Bittman, R Chun, J Byun, HS Bowen, WD AF Crawford, KW Bittman, R Chun, J Byun, HS Bowen, WD TI Novel ceramide analogues display selective cytotoxicity in drug-resistant breast tumor cell lines compared to normal breast epithelial cells SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Research-Centers-in-Minority-Institutions CY DEC, 2002 CL UNIV HAWAII MANOA, HONOLULU, HAWAII SP Res Ctr Minor Inst HO UNIV HAWAII MANOA DE ceramides; cytotoxicity; breast tumor cells ID CANCER-CELLS; GLUCOSYLCERAMIDE SYNTHASE; MULTIDRUG-RESISTANCE; ANTICANCER DRUG; ACID CERAMIDASE; IN-VITRO; APOPTOSIS; DEATH; GROWTH; PROTEIN AB The sphingolipid ceramide is involved in diverse cell signaling pathways related to proliferation and differentiation. Elevated ceramide also triggers apoptosis. Synthetic ceramide derivatives have been shown to be cytotoxic to tumors, yet few studies have evaluated whether cytotoxicity of synthetic ceramides is selective for tumor cells. We have evaluated the cytotoxic potency of several novel ceramide analogues in the drug-resistant breast tumor cell lines, SKBr3 and MCF-7/Adr, and compared their cytotoxicity in normal breast epithelial cells. Cytotoxicity was assessed using release of lactate dehydrogenase into the culture medium. (2S, 3S)3-(6'-Dodecylpyridin-2'-yl)-2-butanoylamidopropane-1,3-diol (pyridine-C4-ceramide) produced non-selective cytotoxicity across the three cell types (EC50= 12.8-16.7 muM, at 24 hr). However, 2S,5R-2-(octanoylamido-(3E))-octadecene-1,5-diol (5R-OH-3E-C8-ceramide), (2S,3R)-2-(N-adamantoyl)-(4E)-octadecen-1,3-diol (adamantyl-ceramide), and (2S,3R)-3-(3'-dodecylphenyl)-2butanoylamidopropane-1,3-diol (benzene-C4-ceramide) exhibited increased cytotoxicity in the tumor cell lines compared to the normal breast epithelial cells. The EC50 values (muM) at 24 hr for these compounds in SKBr3 cells, MCF-7/Adr cells, and normal breast epithelial cells, respectively, were as follows: 5R-OH-3E-C8-ceramide, 18.3, 21.2 and 58.7; adamantyl-ceramide, 10.9, 24.9 and >100; benzene-C4-ceramide, 18.9, 45.5 and >100. At a concentration of 30 M, the fold increase in cytotoxicity in breast tumor cell lines compared with normal breast epithelial cells was as follows: 5R-OH-3E-C8-ceramide, 23.7 and 19; adamantyl-ceramide, 11.2 and 10.3 and benzene-C4-ceramide, 79.3 and 77.2, for SKBr3 and MCF-7/Adr cells, respectively. Possible mechanisms accounting for selectivity are discussed. Ceramide analogues with relatively selective toxicity against tumor cells may have potential as therapeutic agents. Elucidating the mechanisms of selective cytotoxicity could identify novel targets that may lead to development of antineoplastic agents with a higher therapeutic index. C1 Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. CUNY Queens Coll, Dept Chem & Biochem, Flushing, NY 11367 USA. NIDDKD, Unit Receptor Biochem & Pharmacol, Med Chem Lab, Bethesda, MD 20982 USA. RP Crawford, KW (reprint author), Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. NR 36 TC 29 Z9 31 U1 1 U2 4 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD NOV PY 2003 VL 49 IS 7 BP 1017 EP 1023 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757VT UT WOS:000187582700005 PM 14682383 ER PT J AU Tchounwou, PB Yedjou, CG Dorsey, WC AF Tchounwou, PB Yedjou, CG Dorsey, WC TI Arsenic trioxide-induced transcriptional activation of stress genes and expression of related proteins in human liver carcinoma cells (HepG2) SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Research-Centers-in-Minority-Institutions CY DEC, 2002 CL UNIV HAWAII MANOA, HONOLULU, HAWAII SP Res Ctr Minor Inst HO UNIV HAWAII MANOA DE arsenic; genotoxicity; c-fos; HMTIIA; HSP70; p53; HepG(2) cells ID SODIUM ARSENITE; DRINKING-WATER; ENDEMIC AREA; DNA-DAMAGE; TRANSFORMATION; CARCINOGENESIS; INDUCTION; MECHANISMS; APOPTOSIS; EXPOSURE AB Arsenic is a naturally occurring element, but anthropogenic activities can lead to a substantial contamination of the environment. Exposure to arsenic has been associated with a significant number of adverse health effects in humans including: cardiovascular disease, diabetes, hearing loss, developmental abnormalities, anemia, neurologic and neurobehavioral disorder, leukopenia, eosinophilia, fibrosis of the liver and the kidney and various neoplasms. However, the cellular and molecular events associated with arsenic toxicity are poorly understood. Also, the precise mechanisms by which arsenic acts as a carcinogen in humans remain to be elucidated. In the present study, we used human liver carcinoma (HepG(2)) cells as a model to study the molecular mechanisms of arsenic-induced toxicity and carcinogenesis. We hypothesized that arsenic-induced expression of stress genes and related proteins may play a role in the cellular and molecular events leading to toxicity and tumorigenesis in liver cells. To test this hypothesis, we performed the MTT-assay for cell viability, the CAT-Tox (L) assay for gene induction, and the Western Blot analysis to assess the expression of cellular proteins including c-fos, HMTHA, HSP70 and p53. Data obtained from the MTT assay indicated a strong dose-response relationship with respect to arsenic trioxide toxicity. Upon 48 hr of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50) was computed to be 8.55 +/- 0.58 mug/ml. The CAT-Tox (L) assay showed statistically significant inductions (p<0.05) of c-fos, HMTIIA, and HSP70. Western blot analysis also demonstrated a dose-response relationship with regard to expression of specific cellular proteins. The p53 protein was expressed in arsenic trioxide-treated cells, however, the densitometric analysis did not show any significant differences (p<0.05) between treated and control cells. The lack of a significant induction of p53 may be due to the potential mitogenic effect of arsenic at low levels of arsenic exposure. C1 Jackson State Univ, Sch Sci & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Sch Sci & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. FU NCRR NIH HHS [1G12RR13459] NR 69 TC 29 Z9 30 U1 0 U2 3 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD NOV PY 2003 VL 49 IS 7 BP 1071 EP 1079 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757VT UT WOS:000187582700011 PM 14682389 ER PT J AU Biessmann, H Mason, JM AF Biessmann, H Mason, JM TI Telomerase-independent mechanisms of telomere elongation SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE telomere; recombination; gene conversion; transposable elements; capping; Drosophila ID DROSOPHILA HETEROCHROMATIN PROTEIN-1; POSITION-EFFECT VARIEGATION; MOSQUITO ANOPHELES-GAMBIAE; TARGETED-GENE REPLACEMENT; BROKEN CHROMOSOME ENDS; HET-A; CHIRONOMUS-PALLIDIVITTATUS; TRANSPOSABLE ELEMENTS; DNA-SEQUENCES; MOLECULAR CHARACTERIZATION AB The ends of linear chromosomes must be elongated in a DNA-replication-independent fashion. For chromosome end elongation the majority of eukaryotes use a specialized reverse transcriptase, telomerase, which adds a short, tandemly repeated DNA sequence motif to chromosome ends. Chromosome elongation can also be achieved, however, by mechanisms other than telomerase. Such elongation events have been detected under conditions where telomerase has been inactivated experimentally and in the few organisms that naturally lack telomerase. We will summarize current knowledge on these telomerase-independent elongation mechanisms in yeast and mammalian cells and will discuss in more detail the telomere elongation mechanism by retrotransposons in Drosophila melanogaster. C1 Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Biessmann, H (reprint author), Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. FU NIGMS NIH HHS [GM-56729] NR 105 TC 35 Z9 36 U1 0 U2 4 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2003 VL 60 IS 11 BP 2325 EP 2333 DI 10.1007/s00018-003-3247-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 744LQ UT WOS:000186632400006 PM 14625679 ER PT J AU Finkelstein, SE Schrump, DS Nguyen, DM Hewitt, SM Kunst, MF Summers, RM AF Finkelstein, SE Schrump, DS Nguyen, DM Hewitt, SM Kunst, MF Summers, RM TI Comparative evaluation of super high-resolution CT scan and virtual bronchoscopy for the detection of tracheobronchial malignancies SO CHEST LA English DT Article; Proceedings Paper CT Chest 2002 Meeting CY NOV 05, 2002 CL SAN DIEGO, CALIFORNIA DE bronchoseopy; cancer; CT; endoscopy; imaging; thoracic; virtual ID FIBEROPTIC BRONCHOSCOPY; LUNG-CANCER; LIMITATIONS; CARCINOMA; ENDOSCOPY AB Objectives: Novel imaging modalities are currently available for the noninvasive evaluation of the tracheobronchial tree. This study was undertaken to compare the diagnostic potentials of conventional CT scanning, super high-resolution CT (SHR-CT) scanning, and virtual bronchoscopy (VB) directly with fiberoptic bronchoscopy (FB) for the detection of tracheobronchial neoplasms. Design: Prospective observer study, in which 44 consecutive patients with thoracic malignancies were evaluated using several diagnostic imaging modalities. Images of the thorax were interpreted by individuals blind to the results of FB for the detection of endoluminal, obstructive, or mucosal lesions. Measurements and results: Image acquisition and simulation of the tracheobronchial anatomy were created successfully in all patients. Thirty-two patients who underwent both SHR-CT scanning and VB had correlative FBs within 1 month. In all nine patients who had a normal anatomy, SHR-CT scanning and VB accurately correlated with the FB findings. However, CT scanning demonstrated two false-positive obstructive lesions in one patient. Twenty-three patients had a total of 35 abnormal FB findings. The sensitivities of SHR-CT scanning and VB for the detection of endoluminal, obstructive, and mucosal lesions were 90%, 100%, and 16%, respectively. The overall sensitivities and specificities of SHR-CT scanning and VB were 83% and 100%, respectively. In contrast, CT scanning had sensitivities of 50%, 72%, and 0% for the detection of endoluminal, obstructive, and mucosal lesions with an overall sensitivity and specificity of 59%, and 85%, respectively. There was no case in which conventional CT scanning was better at detecting lesions than either SHR-CT scanning or VB. Conclusions: SHR-CT scanning and VB are accurate, noninvasive methods for identifying obstructions and endoluminal lesions within the respiratory tract. Thus, these novel imaging techniques are valuable as complementary modalities to FB, providing information that is useful for the detection and management of airway malignancies. C1 NCI, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NCI, Thorac Oncol Sect, NIH, Bldg 10,Room 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 16 TC 36 Z9 38 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2003 VL 124 IS 5 BP 1834 EP 1840 DI 10.1378/chest.124.5.1834 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 743UH UT WOS:000186591600036 PM 14605057 ER PT J AU Allhusen, V Belsky, J Booth, CL Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Houts, R Kelly, JF Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Robeson, W Spieker, S Vandell, DL Weinraub, M AF Allhusen, V Belsky, J Booth, CL Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Houts, R Kelly, JF Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Robeson, W Spieker, S Vandell, DL Weinraub, M CA Natl Ist Child Hlth Human Dev Earl TI Social functioning in first grade: Associations with earlier home and child care predictors and with current classroom experiences SO CHILD DEVELOPMENT LA English DT Article ID 1ST 3 YEARS; LANGUAGE-DEVELOPMENT; MATERNAL EMPLOYMENT; BEHAVIOR PROBLEMS; SCHOOL ENTRY; OUTCOMES; QUALITY; TEACHER; KINDERGARTEN; NICHD AB Family and child care factors from birth to 54 months, achievement and social outcomes at entry to school, and qualities of first-grade classrooms were used to predict first-grade social functioning for 864 children from the NICHD Study of Early Child Care. Child gender, mothers' partner status, maternal education and depressive symptoms, sensitivity of mothering, and amount of time spent in nonmaternal child care were significant predictors. Home and child care variables predicted social functioning through associations with prior social functioning rather than directly. More teacher-led structured activities in first-grade classrooms predicted mother's reports of more internalizing behavior. Classrooms rated as more emotionally supportive predicted lower levels of mother-reported internalizing behavior and concurrently observed indicators of competence. C1 NICHD, Early Child Care Res Network, OEP, Rockville, MD 20852 USA. RP Allhusen, V (reprint author), NICHD, Early Child Care Res Network, OEP, 6100 Execut Blvd,4A01, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012 NR 85 TC 106 Z9 106 U1 12 U2 23 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD NOV-DEC PY 2003 VL 74 IS 6 BP 1639 EP 1662 PG 24 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 746PV UT WOS:000186755500005 ER PT J AU Fusaro, VA Stone, JH AF Fusaro, VA Stone, JH TI Mass spectrometry-based proteomics and analyses of serum: A primer for the clinical investigator SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Review DE proteomics; vasculitis; mass spectrometry ID PEPTIDES; CANCER; ELECTROPHORESIS; IDENTIFICATION; PATTERNS; PLASMA AB The vocabulary of proteomics and the swiftly-developing, technological nature of the field constitute substantial barriers to clinical investigators. In recent years, mass spectrometry has emerged as the most promising technique in this field. The purpose of this review is to introduce the field of mass spectrometry-based proteomics to clinical investigators, to explain Many of the relevant terms, to introduce the equipment employed in this field, and to outline approaches to asking clinical questions using a proteomic approach. Examples of clinical applications of proteomic techniques are provided from the fields of cancer and vasculitis research, with an emphasis on a pattern recognition approach. C1 US FDA, Natl Canc Inst, Clin Proteom Program, Rockville, MD 20857 USA. Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD 21218 USA. RP Stone, JH (reprint author), Johns Hopkins Vasculitis Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. NR 21 TC 9 Z9 10 U1 0 U2 3 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 NOV-DEC PY 2003 VL 21 IS 6 SU 32 BP S3 EP S14 PG 12 WC Rheumatology SC Rheumatology GA 758HC UT WOS:000187627400002 PM 14740422 ER PT J AU Plasschaert, SLA van der Kolk, DM de Bout, ESJM Kamps, WA Morisaki, K Bates, SE Scheffer, GL Scheper, RJ Vellenga, E de Vries, EGE AF Plasschaert, SLA van der Kolk, DM de Bout, ESJM Kamps, WA Morisaki, K Bates, SE Scheffer, GL Scheper, RJ Vellenga, E de Vries, EGE TI The role of breast cancer resistance protein in acute lymphoblastic leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID P-GLYCOPROTEIN EXPRESSION; ACUTE MYELOID-LEUKEMIA; MULTIDRUG-RESISTANCE; CELL-LINES; CHILDHOOD LEUKEMIA; EFFLUX PUMP; STEM-CELLS; MXR ABCG2; DE-NOVO; ADULT AB Purpose: Overexpression of the transporter ABCG2, also known as breast cancer resistance protein and mitoxantrone resistance protein, can confer resistance to a variety of cytostatic drugs, such as mitoxantrone, topotecan, doxorubicin, and daunorubicin. This study analyzes the ABCG2 expression and activity in 46 human de novo acute lymphoblastic leukemia B- and T-lineage (ALL) samples. Experimental Design: ABCG2 expression was measured flow cytometrically with the BXP-34 monoclonal antibody. ABCG2 functional activity was determined flow cytometrically by measuring mitoxantrone accumulation in combination with the ABCG2 inhibitor fumitremorgin C (FTC). To determine a possible effect of the transporters P-glycoprotein and multidrug resistance-associated protein (MRP1 and MRP2) on mitoxantrone accumulation, the accumulation was investigated in the presence of the P-glycoprotein inhibitor PSC 833 and MRP inhibitor MK-571. The ABCG2 gene was sequenced to investigate the amino acid at position 482. Results: In B-lineage ALL (n = 23), the median BXP-34:IgG1 ratio was higher, namely 2.4 (range, 1.7-3.7), than in T-lineage ALL (n = 23; 1.9; range, 1.2-6.6; P = 0.003). The addition of FTC to mitoxantrone treatment caused a median increase in mitoxantrone accumulation of 21% (range, 0-140%) in B-lineage ALL. In T-lineage ALL, this FTC effect was less pronounced (5%; range, 0-256%; P = 0.013). The influence of FTC on mitoxantrone accumulation correlated with ABCG2 protein expression (r = 0.52; P < 0.001; n = 43). The increase in mitoxantrone accumulation, when FTC was added to cells treated with both PSC 833 and MK-571, correlated with the ABCG2 expression in B-lineage ALL but not in T-lineage ALL. Sequencing the ABCG2 gene revealed no ABCG2 mutation at position 482 in patients who accumulated more rhodamine after FTC. Conclusions: This study shows that ABCG2 is expressed higher and functionally more active in B-lineage than in T-lineage ALL. C1 Univ Groningen Hosp, Div Pediat Oncol & Hematol, NL-9713 GZ Groningen, Netherlands. Univ Groningen Hosp, Div Hematol, NL-9713 GZ Groningen, Netherlands. Univ Groningen Hosp, Div Med Oncol, NL-9713 GZ Groningen, Netherlands. Free Univ Amsterdam, Med Ctr, Div Pathol, Amsterdam, Netherlands. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP de Vries, EGE (reprint author), Univ Groningen Hosp, Div Med Oncol, Dept Internal Med, Hanzeplein 1, NL-9713 GZ Groningen, Netherlands. NR 40 TC 38 Z9 43 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2003 VL 9 IS 14 BP 5171 EP 5177 PG 7 WC Oncology SC Oncology GA 743EA UT WOS:000186558400015 PM 14613996 ER PT J AU Goldsmith, ME Kitazono, M Fok, P Aikou, T Bates, S Fojo, T AF Goldsmith, ME Kitazono, M Fok, P Aikou, T Bates, S Fojo, T TI The histone deacetylase inhibitor FK228 preferentially enhances adenovirus transgene expression in malignant cells SO CLINICAL CANCER RESEARCH LA English DT Article ID MEDIATED MULTIDRUG-RESISTANCE; GENE-TRANSFER; IN-VITRO; HEMATOPOIETIC-CELLS; DEPSIPEPTIDE FR901228; SODIUM-BUTYRATE; BLADDER-CANCER; GLIOMA-CELLS; RECEPTOR; VECTOR AB Purpose: Efficient adenovirus infection requires coxsackie-adenovirus receptor (CAR) and alpha(v) integrin. Whereas many malignant cells express these proteins poorly, normal tissues, especially liver, express high levels and are susceptible to adenovirus infection. Our previous studies showed that treatment of cancer cell lines with low concentrations of the histone deacetylase inhibitor FK228 (FR901228, depsipeptide), a drug in Phase II clinical trials, before infection was associated with an increase in adenovirus transgene expression. The purpose of these studies was to analyze the effects of FK228 on cultured normal human cells before initiating animal studies. Experimental Design: Cancer and normal cells from the corresponding tissue were treated with FK228 and analyzed for the proteins needed for infection and the infection efficiency. Results: Treatment of cancer cell lines with 1 ng/ml FK228 increased CAR RNA, a, integrin RNA, and histone H3 acetylation levels, and was associated with a 4-10-fold increase in the number of infected cells expressing the transgene. Similar treatment of normal human mammary epithelial cells, renal proximal tubule epithelial cells, and hepatocytes had little effect. The insensitivity of cultured normal cells may be explained, in part, by expression of the drug efflux pump P-glycoprotein, because addition of the P-glycoprotein inhibitor XR9576 (tariquidar) with FK228 resulted in increased histone acetylation and CAR expression. Conclusion: These studies suggest that low concentrations of FK228 preferentially increase the efficiency of adenoviral transgene expression in cancer cells compared with cultured normal cells from the corresponding tissue and may increase the efficiency of adenovirus therapies in vivo. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Kagoshima Univ, Fac Med, Dept Surg 1, Kagoshima 890, Japan. RP Fojo, T (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bldg 10,Room 12C103,MSC 1903,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 59 TC 48 Z9 49 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2003 VL 9 IS 14 BP 5394 EP 5401 PG 8 WC Oncology SC Oncology GA 743EA UT WOS:000186558400044 PM 14614025 ER PT J AU Marcovina, SM Koschinsky, ML Albers, JJ Skarlatos, S AF Marcovina, SM Koschinsky, ML Albers, JJ Skarlatos, S TI Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and cardiovascular disease: Recent advances and future directions SO CLINICAL CHEMISTRY LA English DT Editorial Material ID EXPRESSING HUMAN APOLIPOPROTEIN(A); LOW-DENSITY-LIPOPROTEIN; INDEPENDENT RISK-FACTOR; LP(A) GLYCOPROTEIN PHENOTYPES; CORONARY-ARTERY DISEASE; PLASMA LIPOPROTEIN(A); TRANSGENIC MICE; ATHEROSCLEROTIC LESIONS; VENOUS THROMBOEMBOLISM; POSTMENOPAUSAL WOMEN AB It has been estimated that approximately 37% of the US population judged to be at high risk for developing coronary artery disease (CAD), based on the National Cholesterol Education Program guidelines, have increased plasma lipoprotein(a) [Lp(a)], whereas Lp(a) is increased in only 14% of those judged to be at low risk. Therefore, the importance of establishing a better understanding of the relative contribution of Lp(a) to the risk support burden for CAD and other forms of vascular disease, as well as the underlying mechanisms, is clearly evident. However, the structural complexity and size heterogeneity of Lp(a) have hindered the development of immunoassays to accurately measure Lp(a) concentrations in plasma. The large intermethod variation in Lp(a) values has made it difficult to compare data from different clinical studies and to achieve a uniform interpretation of clinical data. A workshop was recently convened by the National Heart, Lung and Blood Institute (NHLBI) to evaluate our current understanding of Lp(a) as a risk factor for atherosclerotic disorders; to determine how future studies could be designed to more clearly define the extent to which, and mechanisms by which, Lp(a) participates in theses processes; and to present the results of the NHLBI-supported program for the evaluation and standardization of Lp(a) immunoassays. This report includes the most recent data presented by the workshop participants and the resulting practical and research recommendations. C1 Univ Washington, Dept Med, NW Lipid Res Lab, Seattle, WA 98103 USA. Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada. Vascular Biol Prog, NIH NHLBI DHVD, Bethesda, MD 20892 USA. RP Marcovina, SM (reprint author), Univ Washington, Dept Med, NW Lipid Res Lab, 2121 N 35th St, Seattle, WA 98103 USA. FU NHLBI NIH HHS [N01 HV88175] NR 86 TC 136 Z9 151 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2003 VL 49 IS 11 BP 1785 EP 1796 DI 10.1373/clinchem.2003.023689 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 736EC UT WOS:000186157300053 PM 14578310 ER PT J AU de Serres, FJ Blanco, I Fernandez-Bustillo, E AF de Serres, FJ Blanco, I Fernandez-Bustillo, E TI Genetic epidemiology of alpha-1 antitrypsin deficiency in North America and Australia/New Zealand: Australia, Canada, New Zealand and the United States of America SO CLINICAL GENETICS LA English DT Review DE alpha-1 antitrypsin deficiency; alpha-1 protease inhibitor; alpha-1 protease; Australia; Canada; genetic epidemiology; New Zealand; Pi phenotypes; Pi subtypes; population genetics; United States of America ID OBSTRUCTIVE PULMONARY-DISEASE; PROTEASE INHIBITOR PHENOTYPES; ALPHA(1)-ANTITRYPSIN DEFICIENCY; ALPHA1-ANTITRYPSIN DEFICIENCY; PI PHENOTYPES; CLINICAL-FEATURES; LIVER-DISEASE; LUNG-DISEASE; GENERAL-POPULATION; PUBLISHED SURVEYS AB Alpha-1-antitrypsin deficiency (AAT deficiency) is one of the most common serious hereditary disorders in the world, as its affects all major racial subgroups worldwide, and there are an estimated 120.5 million carriers and deficient subjects worldwide. This genetic disease is related to susceptibility for development of jaundice in infants, liver disease in children and adults and pulmonary emphysema in adults. Moreover, AAT deficiency carrier phenotypes (PiMS and PiMZ) and deficiency allele phenotypes (PiSS, PiSZ and PiZZ) are suspected to predispose subjects to a variety of other adverse health effects. Because there is a limited database on the number of individuals affected by this disease worldwide, we have collected data on control cohorts in genetic epidemiological studies published on case-control studies in the peer-reviewed literature worldwide. Based on these data, we estimated the numbers of carriers and deficiency allele combinations for the two most common defective alleles, namely PiS and PiZ in 58 countries worldwide. The present paper focuses on the distribution of the PiS and PiZ deficiency alleles in Australia, Canada, New Zealand and the United States of America. A total of 31,042,232 individuals at risk for adverse health effects have been calculated in these four countries: 2,144,158 in Australia, 3,258,564 in Canada, 430,922 in New Zealand and 24,909,548 in the United States of America. The prevalences for all five phenotypic classes of AAT deficiency in each of these countries is as follows: Australia 1 out of 8.9, Canada 1 out of 9.8, New Zealand 1 out of 8.5 and the United States of America 1 out of 11.3. The geographical distribution of individual control cohorts and estimates of the numbers of carriers and deficiency allele phenotypes in each of these four countries are given in individual tables. C1 NIEHS, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Hosp Valle Nalon, Resp Dis Branch, Sama De Langreo, Spain. Univ Oviedo, Hosp Cent Asturias, Biostat Unit, E-33080 Oviedo, Principado Astu, Spain. RP de Serres, FJ (reprint author), NIEHS, Mol Toxicol Lab, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 101 TC 46 Z9 48 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD NOV PY 2003 VL 64 IS 5 BP 382 EP 397 DI 10.1034/j.1399-0004.2003.00143.x PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 734TZ UT WOS:000186075200004 PM 14616761 ER PT J AU Neeman, Z Libutti, SK Patti, JW Wood, BJ AF Neeman, Z Libutti, SK Patti, JW Wood, BJ TI Percutaneous radiofrequency ablation of hepatocellular carcinoma in the presence of portal vein thrombosis SO CLINICAL IMAGING LA English DT Article DE hepatocellular carcinoma (HCC); portal vein thrombosis (PVT); radiofrequency ablation (RFA) ID INTERSTITIAL THERMAL ABLATION AB Portal vein thrombosis (PVT) may not be an absolute contraindication for hepatic radiofrequency ablation (RFA). Although the data are sparse, PVT is commonly considered a contraindication to RFA. PVT has actually been described as a complication following RFA. RFA was used to treat a 3.9 x 2.9 cut primary hepatocellular carcinoma (HCC) in a patient with concomitant PVT without complication. RFA can be safely performed in this setting but further studies could clarify this issue. Published by Elsevier Inc. All rights reserved. C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Imaging Sci Program, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Ctr Clin, Imaging Sci Program, Bldg 10,Room 1C660,Room 1C387, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 14 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD NOV-DEC PY 2003 VL 27 IS 6 BP 417 EP 420 DI 10.1016/S0899-7071(03)00015-9 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 744KE UT WOS:000186627500012 PM 14585572 ER PT J AU Breen, EC Boscardin, WJ Detels, R Jacobson, LP Smith, MW O'Brien, SJ Chmiel, JS Rinaldo, CR Lai, SH Martinez-Maza, O AF Breen, EC Boscardin, WJ Detels, R Jacobson, LP Smith, MW O'Brien, SJ Chmiel, JS Rinaldo, CR Lai, SH Martinez-Maza, O TI Non-Hodgkin's B cell lymphoma in persons with acquired immunodeficiency syndrome is associated with increased serum levels of IL10, or the TL10 promoter-592 C/C genotype SO CLINICAL IMMUNOLOGY LA English DT Article DE interleukin-10; B cell; lymphoma; AIDS; serum; predictor; single-nucleotide polymorphism; genotype; haplotype; cytokine ID HIV-INFECTION; INTERLEUKIN-10 IL-10; MESSENGER-RNA; AIDS; VIRUS; POLYMORPHISMS; EXPRESSION; ACTIVATION; RISK; PATHOGENESIS AB Interleukin-10 (IL10) may contribute to the development of non-Hodgkin's B cell lymphoma, especially in the context of acquired immunodeficiency syndrome (AIDS), where lymphoma incidence is greatly increased. Utilizing specimens from the Multicenter AIDS Cohort Study (MACS) obtained prior to diagnosis of AIDS-associated lymphoma, detectable serum human IL10 was seen much more frequently in lymphoma cases (n = 61, 26%) compared to CD4-matched AIDS controls (5%, P = 0.004), or to HIV-infected (2%, P = 0.002) or HIV uninfected subjects (0%, P = 0.0003). In longitudinal studies, detectable IL10 occurred at times closest to but preceding lymphoma diagnosis (P = 0.01). In an independent genetic analysis of single-nucleotide polymorphisms within the promoter region of the IL10 gene in 1157 MACS subjects, a high IL10-expressing genotype (-592 C/C) was overrepresented among lymphoma subjects (P = 0.009), even when controlling for race (P = 0.006). These results suggest that elevated serum IL10 or the IL10 promoter -592 C/C genotype are associated with development of AIDS lymphoma. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Sci Applicat Int Corp, Intramural Res Support Program, Ft Detrick, MD 21702 USA. Natl Canc Inst Frederick, Lab Genom Divers, Ft Detrick, MD 21702 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Breen, EC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, CHS 27-139, Los Angeles, CA 90095 USA. RI Martinez-Maza, Otoniel/B-2667-2009; Smith, Michael/B-5341-2012 OI Martinez-Maza, Otoniel/0000-0003-1364-0675; FU NCI NIH HHS [CA57152, CA96888]; NCRR NIH HHS [5-M01-RR00722]; NIAID NIH HHS [AI35040, U01-AI35039, U01-AI35040, U01-AI35042, U01-AI35043, U01-AI37984]; ODCDC CDC HHS [CD73475] NR 43 TC 64 Z9 66 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 2003 VL 109 IS 2 BP 119 EP 129 DI 10.1016/S1521-6616(03)00214-6 PG 11 WC Immunology SC Immunology GA 741UH UT WOS:000186478400002 PM 14597210 ER PT J AU Stewart, DM McAvoy, MJ Hilbert, DM Nelson, DL AF Stewart, DM McAvoy, MJ Hilbert, DM Nelson, DL TI B lymphocytes from individuals with common variable immunodeficiency respond to B lymphocyte stimulator (BLyS protein) in vitro SO CLINICAL IMMUNOLOGY LA English DT Article DE human; immunodeficiency diseases; B lymphocytes; cytokines; cytokine receptors ID NECROSIS-FACTOR FAMILY; IMMUNOGLOBULIN PRODUCTION; CELL DIFFERENTIATION; TNF RECEPTOR; IL-10; INTERLEUKIN-2; BAFF; HYPOGAMMAGLOBULINEMIA; LIGAND; MEMBER AB B lymphocyte stimulator (BLyS protein) is a member of the human TNF family of ligands. BLyS induces B-lymphocyte proliferation and Ig secretion in vitro and in vivo. These qualities suggest that it may be useful as a therapeutic in the treatment of immunodeficiencies characterized by low or absent serum immumoglobulin, such as common variable immunodeficiency (CVID). CVID is characterized by the inability to generate adequate serum Ig despite normal or slightly depressed peripheral B, T, and myeloid cell populations. We tested the ability of BLyS to stimulate B lymphocytes obtained from CVID patients. Among five patients studied, 60% (three of five) produced normal quantities of IgM when cultured in the presence of BLyS. B-cell proliferation among patients was comparable, with 60% (three of five) responding to BLyS stimulation. These results suggest that BLyS induces proliferative and Ig-secretory responses in B lymphocytes isolated from some CVID patients and lend support to its potential use in therapy of this disorder. (C) 2003 Elsevier Inc. All rights reserved. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Human Genome Sci Inc, Rockville, MD 20850 USA. RP Stewart, DM (reprint author), NCI, Metab Branch, NIH, 10 Ctr Dr MSC 1374, Bethesda, MD 20892 USA. NR 32 TC 23 Z9 25 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 2003 VL 109 IS 2 BP 137 EP 143 DI 10.1016/S1521-6616(03)00215-8 PG 7 WC Immunology SC Immunology GA 741UH UT WOS:000186478400004 PM 14597212 ER PT J AU Dorshkind, K Welniak, L Gault, RA Hixon, J Montecino-Rodriguez, E Horseman, ND Gertner, JM Murphy, WJ AF Dorshkind, K Welniak, L Gault, RA Hixon, J Montecino-Rodriguez, E Horseman, ND Gertner, JM Murphy, WJ TI Effects of housing on the thymic deficiency in dwarf mice and its reversal by growth hormone administration SO CLINICAL IMMUNOLOGY LA English DT Article DE thymopoiesis; growth hormone; stress; T cell progenitor ID BONE-MARROW-TRANSPLANTATION; T-CELL DEVELOPMENT; FACTOR-I; NEUROENDOCRINE HORMONES; IMMUNOLOGICAL CAPACITY; LYMPHOID TISSUES; PROLACTIN; RECONSTITUTION; MOUSE; LYMPHOCYTES AB Initial studies on T cell development in the Snell Dwarf (dw/dw) strain of mice, which are deficient in the production of anterior pituitary hormones, have been interpreted to indicate a clear dependence of T cell development on endocrine system-derived factors. However, normal thymopoiesis in this strain has also been reported. The aim of the present study was to reconcile these contradictory data in order to define the role of anterior pituitary hormones in the thymus. The results indicated that if female dw/dw mice are housed together with their normal-sized littermates, thymic cellularity and the frequency of CD4(+)CD8(+) thymocytes are markedly reduced. However, administration of growth hormone could reverse these decreases seen in the double-positive T progenitor cells. Taken together, the data indicate that stress is the unifying parameter that can explain the disparate dw/dw mouse literature and suggest that endocrine effects on the T cell development can best be understood by interpreting the literature in this context. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. NCI, Frederick, MD 21702 USA. Univ Cincinnati, Dept Mol & Cellular Physiol, Cincinnati, OH USA. Serono Inc, Rockland, MA 02370 USA. RP Murphy, WJ (reprint author), Univ Nevada, Sch Med, Dept Microbiol, MS320, Reno, NV 89557 USA. EM wmurphy@unr.edu FU NIA NIH HHS [AG022661, R01 AG022661, R01 AG022661-02]; NIAID NIH HHS [AI21256] NR 31 TC 11 Z9 12 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 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 2003 VL 109 IS 2 BP 197 EP 202 DI 10.1016/S1521-6616(03)00181-5 PG 6 WC Immunology SC Immunology GA 741UH UT WOS:000186478400010 PM 14597218 ER PT J AU Benson, CA Williams, PL Currier, JS Holland, F Mahon, LF MacGregor, RR Inderlied, CB Flexner, C Neidig, J Chaisson, R Notario, GF Hafner, R AF Benson, CA Williams, PL Currier, JS Holland, F Mahon, LF MacGregor, RR Inderlied, CB Flexner, C Neidig, J Chaisson, R Notario, GF Hafner, R CA AIDS Clinical Trials Grp 223 Proto TI A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; INFECTED PATIENTS; AIDS PATIENTS; VIRUS; BACTEREMIA; RIFAMPIN; THERAPY; CIPROFLOXACIN; EPIDEMIOLOGY AB This multicenter, randomized, open-label phase 3 clinical trial compared the safety and efficacy of 3 clarithromycin-containing combination regimens for the treatment of disseminated Mycobacterium avium complex( MAC) disease in persons with acquired immunodeficiency syndrome. A total of 160 eligible patients with bacteremic MAC disease were randomized to receive clarithromycin with either ethambutol (C+E), rifabutin (C+R), or both (C+E+R) for 48 weeks. After 12 weeks of treatment, the proportion of subjects with a complete microbiologic response was not statistically significantly different among treatment arms: the proportion was 40% in the C+E group, 42% in the C+R group, and 51% in the C+E+R group (P = .454). The proportion of patients with complete or partial responses who experienced a relapse while receiving C+R (24%) was significantly higher than that of patients receiving C+E+R (6%; P = .027) and marginally higher than that of patients receiving C+E (7%; Pp. 027). Subjects in the C+E+R group had improved survival, compared with the C+E group ( hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.83) and the C+R group ( HR, 0.49; 95% CI, 0.26-0.92). C1 Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO USA. Univ So Calif, Childrens Hosp, Los Angeles, CA 90027 USA. Univ Calif Los Angeles, CARE Ctr, Los Angeles, CA USA. AIDS Clin Trials Grp Operat Ctr, Silver Spring, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Williams, PL (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 655 Huntington Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [U01 AI38858, U01 AI38855] NR 30 TC 62 Z9 64 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2003 VL 37 IS 9 BP 1234 EP 1243 DI 10.1086/378807 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 731ZK UT WOS:000185916200014 PM 14557969 ER PT J AU Shuangshoti, S Hjardermaal, GM Ahmad, Y Arden, JL Herman, MM AF Shuangshoti, S Hjardermaal, GM Ahmad, Y Arden, JL Herman, MM TI Concurrence of multiple sclerosis and intracranial glioma - Report of a case and review of the literature SO CLINICAL NEUROPATHOLOGY LA English DT Review DE multiple sclerosis; brain tumor; glioma; glioblastoma ID GLIOBLASTOMA; OLIGODENDROGLIOMA; TUMOR AB We report a 39-year-old female patient known to have multiple sclerosis (MS), who later developed cerebral glioblastoma. The tumor was documented on the brain-magnetic resonance imaging (MRI) during the work-up for an apparent relapsing MS, and was subsequently confirmed pathologically by stereotactic biopsy and the postmortem brain examination. Our case, as well as others, re-emphasizes the need to evaluate the symptoms and brain MRI carefully, even in well-documented MS subjects. The concurrence of MS and intracranial glioma is uncommon. The possible relationship between the 2 diseases was discussed, and related literature reviewed. C1 Chulalongkorn Univ, Fac Med, Dept Pathol, Bangkok 10330, Thailand. NIMH, Clin Brain Disorders Branch, Sect Neuropathol, Intramural Res Program,NIH, Bethesda, MD 20892 USA. Off Chief Med Examiner, Washington, DC USA. RP Shuangshoti, S (reprint author), Chulalongkorn Univ, Fac Med, Dept Pathol, Bangkok 10330, Thailand. NR 21 TC 21 Z9 21 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0722-5091 J9 CLIN NEUROPATHOL JI Clin. Neuropathol. PD NOV-DEC PY 2003 VL 22 IS 6 BP 304 EP 308 PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 752VX UT WOS:000187197800007 PM 14672509 ER PT J AU Kearns, GL Jungbluth, GL Abdel-Rahman, SM Hopkins, NK Welshman, IR Grzebyk, RP Bruss, JB van den Anker, JN AF Kearns, GL Jungbluth, GL Abdel-Rahman, SM Hopkins, NK Welshman, IR Grzebyk, RP Bruss, JB van den Anker, JN CA Pediat Pharmacology Res Unit Netwo TI Impact of ontogeny on linezolid disposition in neonates and infants SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID RESISTANT ENTEROCOCCUS-FAECIUM; PHARMACOKINETICS; CHILDREN; OXAZOLIDINONES AB The impact of age on linezolid disposition during the first few months of life has not been previously investigated. We characterized linezolid pharmacokinetics after a single, 10.0-mg/kg intravenous dose in 42 infants stratified as follows: group 1 (n = 9), gestational age < 34 weeks and postnatal age < 8 days; group 2 (n = 7), gestational age < 34 weeks and postnatal age 8 days to 12 weeks; group 3 (n = 11), gestational age greater than or equal to34 weeks and postnatal age <8 days; and group 4 (n = 15), gestational age greater than or equal to34 weeks and postnatal age 8 days to 12 weeks. Linezolid was quantitated by a validated HPLC-triple-quadrupole mass spectrometer method from repeated blood samples (n = 7, 0.3 mL each) obtained over a 12-hour period. Pharmacokinetic parameters were determined by standard model-dependent techniques. The values (mean +/- SD) for total body clearance (CL) (0.25 +/- 0.12 L . h(-1) . kg(-1)), apparent volume of distribution (VDss) (0.75 +/- 0.19 L/kg), and elimination half-life (t(1/2)) (2.8 +/- 2.1 hours) from the entire study cohort were similar to values reported previously for children and adolescents. Examination of the linezolid pharmacokinetics as a function of age revealed that CL increased rapidly during the first week of life and as a function of postnatal age. Age stratification revealed lower values for CL in those infants aged less than 8 days (group 1, 0.12 +/- 0.06 L . h(-1) . kg(-1); group 3, 0.23 +/- 0.12 L . h(-1) . kg(-1)) as compared with those aged 8 days to 12 weeks (group 2, 0.31 +/- 0.07 L . h(-1) . kg(-1); group 4, 0.31 +/- 0.10 L . h(-1) . kg(-1)). In contrast to the results for CL, gestational age served to be the most useful predictor of VDss. Evaluation of the pharmacokinetic data would appear to support the use of linezolid dosing regimens currently approved for infants and young children in neonates with postnatal age greater than 7 days. C1 Childrens Mercy Hosp & Clin, Div Pediat Pharmacol & Med Toxicol, Kansas City, MO 64108 USA. Clin Pharmacol & Infect Dis Clin Res Pharmacia, Kalamazoo, MI USA. Columbus Childrens Hosp, Div Pediat Clin Pharmacol & Med Toxicol, Columbus, OH 43205 USA. Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. Ohio State Univ, Dept Pharmacol, Columbus, OH 43210 USA. NICHHD, Bethesda, MD 20892 USA. RP Kearns, GL (reprint author), Childrens Mercy Hosp & Clin, Div Pediat Pharmacol & Med Toxicol, 2401 Gillham Rd, Kansas City, MO 64108 USA. FU NICHD NIH HHS [U10 HD31313-09] NR 19 TC 32 Z9 32 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2003 VL 74 IS 5 BP 413 EP 422 DI 10.1016/S0009-9236(03)00226-1 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 740BY UT WOS:000186382000003 PM 14586382 ER PT J AU ten Tije, AJ Loos, WJ Verweij, J Baker, SD Dinh, K Figg, WD Sparreboom, A AF ten Tije, AJ Loos, WJ Verweij, J Baker, SD Dinh, K Figg, WD Sparreboom, A TI Disposition of polyoxyethylated excipients in humans: Implications for drug safety and formulation approaches SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Letter ID CREMOPHOR EL; IN-VIVO; POLYSORBATE-80; DOCETAXEL; SAMPLES; VEHICLE C1 Erasmus MC Daniel Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. Sidney Kimmel Comprehens Canc Ctr, Div Expt Therapeut, Baltimore, MD USA. Natl Canc Inst, Bethesda, MD USA. RP ten Tije, AJ (reprint author), Erasmus MC Daniel Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 10 TC 13 Z9 13 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2003 VL 74 IS 5 BP 509 EP 510 DI 10.1016/j.clpt.2003.08.004 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 740BY UT WOS:000186382000013 PM 14586392 ER PT J AU Rasgon, NL Pumphrey, L Prolo, P Elman, S Negrao, AB Licinio, J Garfinkel, A AF Rasgon, NL Pumphrey, L Prolo, P Elman, S Negrao, AB Licinio, J Garfinkel, A TI Emergent oscillations in mathematical model of the human menstrual cycle SO CNS SPECTRUMS LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; POLYCYSTIC-OVARY-SYNDROME; LUTEINIZING-HORMONE; BIPOLAR DISORDER; DEPRESSIVE ILLNESS; WOMEN; SECRETION; LITHIUM; CHAOS; TESTOSTERONE AB Background:The aim of this study was to develop a mathematical model of the hypothalamo-pituitary-gonadal axis that would reflect available data in humans. Methods: A model of hormonal relationships at the early follicular and midluteal phases of the human menstrual cycle is proposed. Findings: Two distinct temporal Patterns of oscillatory behavior have been demonstrated for both pituitary and gonadal steroids in the early follicular phase: first, rapid oscillations in gonadotropin releasing hormone, follicle stimulating hormone, and luteinizing hormone (Q-1 hour) that were an immediate consequence of the programmed equations. Second, there were slower, undulating, emergent rhythms in luteinizing hormone and follicle stimulating hormone, and also in estrogen, having oscillatory periods of 2-12 hours. There was also a Longer-period (Q2-3 days) emergent rhythm in progesterone. In the mid-luteal phase, estrogen and progesterone rhythms were correlated, and all hormones showed an similar to6-hour periodicity. Conclusion: To our knowledge, the oscillatory behavior of peripheral sex steroids in the follicular phase has not been previously noted. C1 Stanford Univ, Sch Med, Dept Psychiat & Biobehav Sci, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Womens Wellness Program, Stanford, CA 94305 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Inst Neuropsychiat, Los Angeles, CA 90024 USA. NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Dent, Lab Human Oral & Mol Immunol, Sect Diagnost Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90024 USA. RP Rasgon, NL (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Biobehav Sci, 401 Quarry Rd,Room 2360, Stanford, CA 94305 USA. RI Negrao, Andre Brooking/C-9526-2014; Licinio, Julio/L-4244-2013 OI Negrao, Andre Brooking/0000-0002-8133-6723; Licinio, Julio/0000-0001-6905-5884 FU NCRR NIH HHS [RR017611, RR000865, RR016996]; NHGRI NIH HHS [HG002500]; NHLBI NIH HHS [HL004526]; NIDDK NIH HHS [DK058851, DK063240]; NIGMS NIH HHS [GM061394] NR 48 TC 15 Z9 15 U1 0 U2 5 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 NOV PY 2003 VL 8 IS 11 BP 805 EP 814 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 754CC UT WOS:000187284300003 PM 14702003 ER PT J AU Bergman, AN Laurent, P Otiang'a-Owiti, G Bergman, HL Walsh, PJ Wilson, P Wood, CM AF Bergman, AN Laurent, P Otiang'a-Owiti, G Bergman, HL Walsh, PJ Wilson, P Wood, CM TI Physiological adaptations of the gut in the Lake Magadi tilapia, Alcolapia grahami, an alkaline- and saline-adapted teleost fish SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Article DE acid-base regulation; alkaline environment; base transport; digestive function; drinking; gut anatomy; ionoregulation ID OREOCHROMIS-ALCALICUS-GRAHAMI; NITROGEN-METABOLISM; EXTREME ALKALINITY; UREA PRODUCTION; CICHLID FISH; ENVIRONMENT; STRATEGIES; DIGESTION; TRANSPORT; AMMONIA AB We describe the gut physiology of the Lake Magadi tilapia (Alcolapia grahami), specifically those aspects associated with feeding and drinking while living in water of unusually high carbonate alkalinity (titratable base = 245 mequiv l(-1)) and pH (9.85). Drinking of this highly alkaline lake water occurs at rates comparable to or higher than those seen in marine teleosts. Eating and drinking take place throughout the day, although drinking predominates during hours of darkness. The intestine directly intersects the esophagus at the anterior end of the stomach forming a 'T', and the pyloric sphincter, which comprises both smooth and striated muscle, is open when the stomach is empty and closed when the stomach is full. This unique configuration (a functional trifurcation) allows imbibed alkaline water to bypass the empty stomach, thereby avoiding a reactive mixing with acidic gastric fluids, and minimizes interference with a full stomach. No titratable base was present in the stomach, where the mean pH was 3.55, but the intestine was progressively more alkaline (foregut 6.96, midgut 7.74, hindgut 8.12, rectum 8.42); base levels in the intestinal fluid were comparable to those in lake water. The gut was highly efficient at absorbing water (76.6%), which accompanied the absorption of Na+ (78.5%). titratable base (80.8%), and Cl- (71.8%). The majority of Na+, base and water absorption occurred in the foregut by an apparent Na+ plus base co-transport system. Overall, more than 70% of the intestinal flux occurred via Na+ plus base co-transport, and less than 30% by Na+ plus Cl- co-transport, a very different situation from the processes in the intestine of a typical marine teleost. (C) 2003 Elsevier Inc. All rights reserved. C1 McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82071 USA. CNRS, Ctr Ecol & Physiol Energet, F-67087 Strasbourg, France. Univ Nairobi, Dept Vet Anat, Nairobi, Kenya. Univ Miami, NIEHS Marine & Freshwater Biomed Sci Ctr, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, Miami, FL 33149 USA. Trent Univ, Dept Chem, Wildlife Forens DNA Lab, Peterborough, ON K9J 7B8, Canada. RP Wood, CM (reprint author), McMaster Univ, Dept Biol, 1280 Main St W, Hamilton, ON L8S 4K1, Canada. NR 43 TC 21 Z9 24 U1 1 U2 24 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 NOV PY 2003 VL 136 IS 3 BP 701 EP 715 DI 10.1016/S1095-6433(03)00223-X PG 15 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 748MT UT WOS:000186866200021 PM 14613798 ER PT J CA ARDS Clinical Trials Network Natl Heart Lung Blood Inst Natl Inst Hlth TI Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 97th International Conference of the American-Thoracic-Society CY MAY 18-23, 2001 CL SAN FRANCISCO, CA SP Amer Thorac Soc DE respiratory distress syndrome; adult; ventilators; mechanical; atelectasis; acute lung injury ID TIDAL VOLUME; GAS-EXCHANGE; MECHANICAL VENTILATION; PROTECTIVE-VENTILATION; ALVEOLAR RECRUITMENT; INFLATION; PULMONARY; SURFACTANT; STRATEGY; FAILURE C1 Denver Hlth Med Ctr, Denver, CO USA. Denver VA Med Ctr, Denver, CO USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Johns Hopkins Univ, Bayview Med Ctr, Baltimore, MD 21218 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. LDS Hosp, Salt Lake City, UT USA. McKay Dee Hosp, Ogden, UT USA. Metrohlth Med Ctr, Cleveland, OH 44109 USA. San Francisco Gen Hosp, Med Ctr, San Francisco, CA 94110 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Utah Hosp, Salt Lake City, UT 84112 USA. Washington Univ, Harborview Med Ctr, St Louis, MO 63130 USA. Utah Valley Reg Med Ctr, Provo, UT USA. Vanderbilt Univ, Nashville, TN USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Coordinating Ctr, Cambridge, MA 02138 USA. NHLBI, ARDS Clin Trials Network, NIH, Bethesda, MD USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 33 TC 1 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2003 VL 31 IS 11 BP 2592 EP 2597 DI 10.1097/01.CCM.0000090001.91640.45 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 744JT UT WOS:000186626000005 ER PT J AU Panigada, M Berra, L Kolobow, T AF Panigada, M Berra, L Kolobow, T TI Bacterial colonization of the respiratory tract under artificial ventilation: Trachea and tracheal tube orientation SO CRITICAL CARE MEDICINE LA English DT Letter C1 Osped Maggiore Policlin, IRCCS, Milan, Italy. NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. RP Panigada, M (reprint author), Osped Maggiore Policlin, IRCCS, Milan, Italy. RI Panigada, Mauro/K-4650-2014 OI Panigada, Mauro/0000-0003-4841-9794 NR 2 TC 3 Z9 3 U1 1 U2 1 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 NOV PY 2003 VL 31 IS 11 BP 2715 EP 2715 DI 10.1097/01.CCM.0000092450.09939.F6 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 744JT UT WOS:000186626000033 PM 14605557 ER PT J AU Sharma, J Barr, SM Geng, YX Yun, Y Higgins, RD AF Sharma, J Barr, SM Geng, YX Yun, Y Higgins, RD TI Ibuprofen improves oxygen-induced retinopathy in a mouse model SO CURRENT EYE RESEARCH LA English DT Article DE angiogenesis; ibuprofen; mouse; oxygen; retinopathy ID PATENT DUCTUS-ARTERIOSUS; BLOOD-FLOW AUTOREGULATION; PRETERM INFANTS; NEWBORN PIGLETS; REGIONAL CIRCULATION; INDOMETHACIN; PIG; PROSTANOIDS; THROMBOXANE; PREVENTION AB Purpose. Retinopathy of prematurity is a developmental vascular anomaly occurring in the incompletely vascularized retina of the premature infant. Ibuprofen is a nonsteroidal anti-inflammatory agent similar to indomethacin, but with less pronounced side-effects. The goal of the study was to test the hypothesis that ibuprofen would improve oxygen-induced retinopathy in a mouse model. Methods. C57BL6 mice pups were exposed to 75% oxygen from postnatal day 7 through postnatal day 12. Ibuprofen was administered along with oxygen exposure as a single subcutaneous dose of 40 mg/kg/day for 5 days. Animals were sacrificed on postnatal day 17 through postnatal day 20. The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein-conjugated dextran-perfused retinal flat mounts and by quantitation of extra-retinal nuclei by use of periodic acid-Schiff-stained retinal sections. Results. Animals that received ibuprofen during hyperoxia exposure had a significantly lower median (25(th), 75(th) quartile) retinopathy score of 6 (5, 7.5) compared with animals that received oxygen only, with a score of 12 (10.5, 12.5), with p < 0.005. Animals given ibuprofen during hyperoxia exposure had a significantly lower extra-retinal nuclei count per section (14.2 +/- 3.6) compared with animals that were only exposed to oxygen (26.8 +/- 5.8), with p < 0.005. Ibuprofen did not affect the growth of the animals. Conclusion. Ibuprofen improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development of the animals. C1 Georgetown Univ, Childrens Med Ctr, Dept Pediat, Div Neonatol, Washington, DC 20007 USA. RP Higgins, RD (reprint author), NICHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA. NR 31 TC 13 Z9 14 U1 0 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD NOV PY 2003 VL 27 IS 5 BP 309 EP 314 PG 6 WC Ophthalmology SC Ophthalmology GA 745QK UT WOS:000186699400006 PM 14562167 ER PT J AU Shiao, YH AF Shiao, YH TI The von Hippel-Lindau gene and protein in tumorigenesis and angiogenesis: A potential target for therapeutic designs SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE von Hippel-Lindau; alterations in sporadic tumors; tumorigenesis; angiogenesis; humans; animals; functions; and therapeutic designs ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; HYPOXIA-INDUCIBLE FACTORS; CENTRAL-NERVOUS-SYSTEM; TRANSMEMBRANE CARBONIC-ANHYDRASES; BIOLOGICALLY-ACTIVE PRODUCT; POLYMERASE-CHAIN-REACTION; REQUIRES DIRECT BINDING; VHL GENE AB The von Hippel-Lindau (VHL) protein is able to suppress tumor growth and to down-regulate many angiogenic factors, and is ubiquitously detected in adult and fetal tissues. This makes VHL an excellent target for therapeutic intervention. Observation of VHL alterations in sporadic tumors has been increasing as a result of examination of abnormalities other than intragenic mutations. These abnormalities include loss of chromosome 3p25, changes in the promoter, down-regulation of transcript, and changes in protein level. This article also presents the finding of differential expression of two common VHL proteins among rat tissues, suggesting tissue- and development-dependent functional difference between these two isoforms. Molecular pathways linking VHL to angiogenesis have been extensively characterized and mechanisms have been proposed to explain how altered VHL leads to tumorigenesis. VHL functions in the presence of oxygen and/or oxygen species. Two strategies are proposed here for anti-tumor and anti-angiogenic treatments of VHL-deficient tumors and those without detectable VHL intragenic mutations. One is to restore wild-type VHL function in VHL-deficient, tumors and the other is to enhance wild-type VHL expression and activity in tumors under hypoxic conditions. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. RP Shiao, YH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, NIH, Bldg 538,Room 205, Frederick, MD 21702 USA. NR 181 TC 7 Z9 8 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD NOV PY 2003 VL 10 IS 22 BP 2461 EP 2470 DI 10.2174/0929867033456639 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 732LL UT WOS:000185947100010 PM 14529485 ER PT J AU Harris-Love, MO AF Harris-Love, MO TI Physical activity and disablement in the idiopathic inflammatory myopathies SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE disablement; myositis; rehabilitation; exercise; physical activity ID QUALITY-OF-LIFE; INCLUSION-BODY MYOSITIS; HOME EXERCISE PROGRAM; JUVENILE DERMATOMYOSITIS; POLYMYOSITIS DERMATOMYOSITIS; MUSCLE STRENGTH; FOLLOW-UP; POLYMYOSITIS/DERMATOMYOSITIS PATIENTS; NEUROMUSCULAR DISEASES; THERAPEUTIC ASPECTS AB Purpose of review The sequelae associated with idiopathic inflammatory myopathy (IIM) often result in disability and decreased quality of life. Our understanding of how exercise mitigates disability may be facilitated through the use of a conceptual model. This review describes the enablement-disablement model applied to myositis and explores the role of physical activity in the enablement process. Recent findings National and international organizations have revised their disablement models by acknowledging disability as a relational concept, refining the relationship of disability to quality of life, and incorporating the role of intervention through the enablement process. Disability associated with IN may be complicated by aging-related comorbidities and decreased physical activity. However, data indicate that both short-term and long-term aerobic training results in improved aerobic capacity and decreased disability in adults with IIM. Strengthening regimens have also resulted in decreased functional limitations and disability for adults with polymyositis and dermatomyositis. While comprehensive exercise programs have not been shown to exacerbate disease activity or damage in people with IIM, their effectiveness for individuals with inclusion body myositis (IBM) remains uncertain. Summary Physical activity constitutes a valuable enablement strategy that can reduce disability in adults with IIM. Use of the disablement-enablement model and ICF taxonomy in conjunction with outcomes across disablement domains may augment further investigation of the effectiveness of exercise interventions. Additional research is needed to better understand the relationship between disease severity and optimal exercise dosage, the effects of long-term exercise in children with IIM, and the physiologic response to exercise in people with IBM. C1 NIH, Phys Therapy Sect, Dept Rehabil Med, Warren G Magnuson Clin Ctr,US Dept HHS, Bethesda, MD 20892 USA. RP Harris-Love, MO (reprint author), NIH, Phys Therapy Sect, Dept Rehabil Med, Warren G Magnuson Clin Ctr,US Dept HHS, 10 Ctr Dr,MSC 1604,Bldg 10,Room 6S-235, Bethesda, MD 20892 USA. RI Harris-Love, Michael/J-1359-2014 OI Harris-Love, Michael/0000-0002-1842-3269 NR 111 TC 9 Z9 13 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD NOV PY 2003 VL 15 IS 6 BP 679 EP 690 DI 10.1097/00002281-200311000-00002 PG 12 WC Rheumatology SC Rheumatology GA 737DU UT WOS:000186214900002 PM 14569196 ER PT J AU Lebowitz, PF Zujewski, J AF Lebowitz, PF Zujewski, J TI Hormonal therapy of breast cancer SO CURRENT PROBLEMS IN CANCER LA English DT Review ID SURGICAL-ADJUVANT-BREAST; ONCOLOGY TECHNOLOGY-ASSESSMENT; FIRST-LINE THERAPY; SELECTIVE AROMATASE INHIBITOR; NEOADJUVANT ENDOCRINE THERAPY; BRCA2 MUTATION CARRIERS; ESTROGEN-RECEPTOR BETA; BONE-MINERAL DENSITY; LIGAND-BINDING ASSAY; POSTMENOPAUSAL WOMEN C1 NCI, Med Oncol Clin Res Unit, Bethesda, MD USA. NCI, Ctr Canc Res, Med Oncol Clin Res Unit, Breast Canc Clin Res Sect, Bethesda, MD USA. RP Lebowitz, PF (reprint author), NCI, Med Oncol Clin Res Unit, Bethesda, MD USA. NR 153 TC 2 Z9 2 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD NOV-DEC PY 2003 VL 27 IS 6 BP 279 EP 331 DI 10.1067/S01748-0272(03)00049-7 PG 53 WC Oncology SC Oncology GA 747HG UT WOS:000186798700002 PM 14624232 ER PT J AU Andreazzoli, M Gestri, G Cremisi, F Casarosa, S Dawid, IB Barsacchi, G AF Andreazzoli, M Gestri, G Cremisi, F Casarosa, S Dawid, IB Barsacchi, G TI Xrx1 controls proliferation and neurogenesis in Xenopus anterior neural plate SO DEVELOPMENT LA English DT Article DE Xrx1; Xhairy2; Zic2; p27Xic1; XBF-1; Xenopus laevis; proliferation; neurogenesis; retinoic acid ID CYCLE INHIBITOR P27(XIC1); NEURONAL DIFFERENTIATION; HOMEOBOX GENE; RETINOIC ACID; GLAND DEVELOPMENT; IROQUOIS COMPLEX; PROGENITOR CELLS; LAEVIS EMBRYO; SPINAL-CORD; EYE AB In Xenopus neuroectoderm, posterior cells start differentiating at the end of gastrulation, while anterior cells display an extended proliferative period and undergo neurogenesis only at tailbud stage. Recent studies have identified several important components of the molecular pathways controlling posterior neurogenesis, but little is known about those controlling the timing and positioning of anterior neurogenesis. We investigate the role of Xrx1, a homeobox gene required for eye and anterior brain development, in the control of proliferation and neurogenesis of the anterior neural plate. Xrx1 is expressed in the entire proliferative region of the anterior neural plate delimited by cells expressing the neuronal determination gene X-ngnr-1, the neurogenic gene X-Delta-1, and the cell cycle inhibitor p27Xic1. Positive and negative signals position Xrx1 expression to this region. Xrx1 is activated by chordin and Hedgehog gene signaling, which induce anterior and proliferative fate, and is repressed by the differentiation-promoting activity of neurogenin and retinoic acid. Xrx1 is required for anterior neural plate proliferation and, when overexpressed, induces proliferation, inhibits X-ngnr-1, X-Delta-1 and N-tubulin and counteracts X-ngnr-1- and retinoic acid-mediated differentiation. We find that Xrx1 does not act by increasing lateral inhibition but by inducing the antineurogenic transcriptional repressors Xhairy2 and Zic2, and by repressing p27Xic1. The effects of Xrx1 on proliferation, neurogenesis and gene expression are restricted to the most rostral region of the embryo, implicating this gene as an anterior regulator of neurogenesis. C1 Univ Pisa, Dipartimento Fisiol & Biochim, Sezione Biol Cellulare & Sviluppo, I-56010 Pisa, Italy. Univ Pisa, Ctr Eccellenza AmbiSEN, Pisa, Italy. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Scuola Normale Super Pisa, I-56100 Pisa, Italy. RP Andreazzoli, M (reprint author), Univ Pisa, Dipartimento Fisiol & Biochim, Sezione Biol Cellulare & Sviluppo, Via Carducci 13, I-56010 Pisa, Italy. OI Andreazzoli, Massimiliano/0000-0001-9633-204X; Casarosa, Simona/0000-0002-7744-8183 NR 55 TC 54 Z9 56 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2003 VL 130 IS 21 BP 5143 EP 5154 DI 10.1242/dev.00665 PG 12 WC Developmental Biology SC Developmental Biology GA 755JK UT WOS:000187399600009 PM 12975341 ER PT J AU Long, WW Wagner, KU Lloyd, KCK Binart, N Shillingford, JM Hennighausen, L Jones, FE AF Long, WW Wagner, KU Lloyd, KCK Binart, N Shillingford, JM Hennighausen, L Jones, FE TI Impaired differentiation and lactational failure of Erbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5 SO DEVELOPMENT LA English DT Article DE differentiation; ERBB; lactation; mammary gland development; STAT5; tissue specific gene deletion; mouse ID EPIDERMAL-GROWTH-FACTOR; LOBULOALVEOLAR DEVELOPMENT; SIGNALING NETWORK; FACTOR RECEPTOR; BREAST-CANCER; EXPRESSION; MOUSE; MICE; ACTIVATION; PROLACTIN AB The ERBB family of type 1 receptor tyrosine kinases and their ligands have crucial functions during mammopoiesis, but the signaling networks that ultimately regulate ERBB activity in the breast have remained elusive. Here, we show that mice with Cre-lox mediated deletions of both Erbb4 alleles within the developing mammary gland (Erbb4(Flox/Flox)Wap-Cre) fail to accumulate lobuloalveoli or successfully engage lactation at parturition owing, in part, to impaired epithelial proliferation. Analysis of the mammary differentiation factor STAT5 by immunohistochemistry and western blot revealed a complete ablation of STAT5 activation in Erbb4(Flox/Flox)Wap-Cre mammary epithelium at parturition. Consistent with disrupted STAT5 function, Erbb4(Flox/Flox)Wap-Cre mammary glands at parturition failed to express the mammary epithelial differentiation marker NPT2B. Defects in epithelial functional differentiation at parturition were accompanied by a profound reduction in expression of the STAT5-regulated milk genes casein beta and whey acidic protein. We propose that ERBB4 functions as an essential mediator of STAT5 signaling, and that loss of STAT5 activity contributes to the impaired functional differentiation of mammary glands observed in mice containing conditional Erbb4 deletions. C1 Tulane Univ, Hlth Sci Ctr, Tulane Canc Ctr, Dept Struct & Cellular Biol, New Orleans, LA 70112 USA. NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Fac Med Necker Enfants Malad, F-75730 Paris, France. Univ Calif Davis, Sch Vet Med, Ctr Comparat Med, Davis, CA 95616 USA. Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. RP Jones, FE (reprint author), Tulane Univ, Hlth Sci Ctr, Tulane Canc Ctr, Dept Struct & Cellular Biol, 1430 Tulane Ave, New Orleans, LA 70112 USA. EM fjones@tulane.edu RI Wagner, Kay-Uwe/B-6044-2009 FU NCI NIH HHS [1R01CA95783-01] NR 38 TC 101 Z9 104 U1 0 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 NOV PY 2003 VL 130 IS 21 BP 5257 EP 5268 DI 10.1242/dev.00715 PG 12 WC Developmental Biology SC Developmental Biology GA 755JK UT WOS:000187399600018 PM 12954715 ER PT J AU Isogai, S Lawson, ND Torrealday, S Horiguchi, M Weinstein, BM AF Isogai, S Lawson, ND Torrealday, S Horiguchi, M Weinstein, BM TI Angiogenic network formation in the developing vertebrate trunk SO DEVELOPMENT LA English DT Article DE zebrafish; transgenics; intersegmental vessels; vascular development ID ENDOTHELIAL-GROWTH-FACTOR; VASCULAR DEVELOPMENT; ZEBRAFISH EMBRYO; DANIO-RERIO; FACTOR VEGF; DIFFERENTIATION; DISRUPTION; NOTCH AB We have used time-lapse multiphoton microscopy of living Tg(fli1:EGFP)(y1) zebrafish embryos to examine how a patterned, functional network of angiogenic blood vessels is generated in the early vertebrate trunk. Angiogenic vascular sprouts emerge from the longitudinal trunk axial vessels (the dorsal aorta and posterior cardinal vein) in two spatially and temporally distinct steps. Dorsal aorta-derived sprouts form an initial primary network of vascular segments, followed by emergence of vein-derived secondary vascular sprouts that interact and interconnect dynamically with the primary network to initiate vascular flow. Using transgenic silent heart mutant embryos, we show that the gross anatomical patterning of this network of vessels does not require blood circulation. However, our results suggest that circulatory flow dynamics play an important role in helping to determine the pattern of interconnections between the primary network and secondary sprouts, and thus the final arterial or venous identity of the vessels in the functional network. We discuss a model to explain our results combining genetic programming of overall vascular architecture with hemodynamic determination of circulatory flow patterns. C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Iwate Med Univ, Sch Med, Dept Anat, Morioka, Iwate 020, Japan. RP Weinstein, BM (reprint author), NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [Z01-HD-01000] NR 26 TC 286 Z9 295 U1 4 U2 30 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 NOV PY 2003 VL 130 IS 21 BP 5281 EP 5290 DI 10.1242/dev.00733 PG 10 WC Developmental Biology SC Developmental Biology GA 755JK UT WOS:000187399600020 PM 12954720 ER PT J AU Kozmik, Z Daube, M Frei, E Norman, B Kos, L Dishaw, LJ Noll, M Piatigorsky, J AF Kozmik, Z Daube, M Frei, E Norman, B Kos, L Dishaw, LJ Noll, M Piatigorsky, J TI Role of Pax genes in eye evolution: A cnidarian PaxB gene uniting Pax2 and Pax6 functions SO DEVELOPMENTAL CELL LA English DT Article ID TRANSCRIPTION FACTOR BSAP; DNA-BINDING; PAIRED DOMAIN; LENS CRYSTALLINS; CEREBELLUM DEVELOPMENT; CUBOMEDUSAN JELLYFISH; SEQUENCE RECOGNITION; DROSOPHILA EYE; EYELESS GENE; SEA-URCHIN AB PaxB from Tripedalia cystophora, a cubomedusan jellyfish possessing complex eyes (ocelli), was characterized. PaxB, the only Pax gene found in this cnidarian, is expressed in the larva, retina, lens, and statocyst. PaxB contains a Pax2/5/8-type paired domain and octapeptide, but a Pax6 prd-type homeodomain. Pax2/ 5/8-like properties of PaxB include a DNA binding specificity of the paired domain, activation and inhibitory domains, and the ability to rescue spa(pol), a Drosophila Pax2 eye mutant. Like Pax6, Pax13 activates jellyfish crystallin and Drosophila rhodopsin rh6 promoters and induces small ectopic eyes in Drosophila. Pax6 has been considered a "master" control gene for eye development. Our data suggest that the ancestor of jellyfish PaxB, a PaxB-Iike protein, was the primordial Pax protein in eye evolution and that Pax6-like genes evolved in triploblasts after separation from Cnidaria, raising the possibility that cnidarian and sophisticated triploblastic eyes arose independently. C1 NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland. Florida Int Univ, Dept Sci Biol, Miami, FL 33199 USA. RP Piatigorsky, J (reprint author), NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. RI Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014; Dishaw, Larry/A-9930-2010 OI Dishaw, Larry/0000-0002-2705-4573 NR 71 TC 101 Z9 103 U1 3 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD NOV PY 2003 VL 5 IS 5 BP 773 EP 785 DI 10.1016/S1534-5807(03)00325-3 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 742XX UT WOS:000186544400014 PM 14602077 ER PT J AU Bingham, S Chaudhari, S Vanderlaan, G Itoh, M Chitnis, A Chandrasekhar, A AF Bingham, S Chaudhari, S Vanderlaan, G Itoh, M Chitnis, A Chandrasekhar, A TI Neurogenic phenotype of mind bomb mutants leads to severe patterning defects in the zebrafish hindbrain SO DEVELOPMENTAL DYNAMICS LA English DT Article DE zebrafish; hindbrain; motor neuron; induction; rhombomere; green fluorescent protein; neurogenesis; neuroepithelial cell; Notch-Delta signaling; ventral midline ID BRANCHIOMOTOR NEURONS; EMBRYONIC ZEBRAFISH; LATERAL INHIBITION; DANIO-RERIO; DM-GRASP; EXPRESSION; GENE; DELTA; MUTATIONS; HOMOLOG AB Failure of Notch signaling in zebrafish mind bomb (mib) mutants results in a neurogenic phenotype where an overproduction of early differentiating neurons is accompanied by the loss of later-differentiating cell types. We have characterized in detail the hindbrain phenotype of mib mutants. Hindbrain branchiomotor neurons (BMNs) are reduced in number but not missing in mib mutants. In addition, BMN clusters are frequently fused across the midline in mutants. Mosaic analysis indicates that the BMN patterning and fusion defects in the mib hindbrain arise non-cell autonomously. Ventral midline signaling is defective in the mutant hindbrain, in part due to the differentiation of some midline cells into neural cells. Interestingly, while early hindbrain patterning appears normal in mib mutants, subsequent rhombomere-specific gene expression is completely lost. The defects in ventral midline signaling and rhombomere patterning are accompanied by an apparent loss of neuroepithelial cells in the mutant hindbrain. These observations suggest that, by regulating the differentiation of neuroepithelial cells into neurons, Notch signaling preserves a population of non-neuronal cells that are essential for maintaining patterning mechanisms in the developing neural tube. (C) 2003 Wiley-Liss, Inc. C1 Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. RP Chandrasekhar, A (reprint author), Univ Missouri, Div Biol Sci, Room 205 Lefevre Hall, Columbia, MO 65211 USA. EM anandc@missouri.edu FU NINDS NIH HHS [NS40449, R01 NS040449, R01 NS040449-03, R56 NS040449] NR 51 TC 28 Z9 29 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2003 VL 228 IS 3 BP 451 EP 463 DI 10.1002/dvdy.10429 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 738PB UT WOS:000186296100015 PM 14579383 ER PT J AU Rasooly, RS Henken, D Freeman, N Tompkins, L Badman, D Briggs, J Hewitt, AT AF Rasooly, RS Henken, D Freeman, N Tompkins, L Badman, D Briggs, J Hewitt, AT CA Natl Inst Hlth Trans NIH Zebrafish TI Genetic and genomic tools for zebrafish research: The NIH zebrafish initiative SO DEVELOPMENTAL DYNAMICS LA English DT Article DE zebrafish; Danio rerio; research resources; ESTs; cDNA; genomics; ZFIN; NIH AB The National Institutes of Health (NIH) has been a leading advocate of the zebrafish as a model organism for the study of vertebrate development, physiology, and disease. Genomic tools, developed with the support of NIH funding, have made zebrafish even more attractive as a genetic system and have stimulated research using this model. The NIH continues to provide support for new and existing community resources, such as the Zebrafish International Resource Center and the Zebrafish Information Network, research tool development and mutant screens, and a wide array of investigator-initiated studies that are using zebrafish to elucidate many aspects of vertebrate biology. Published 2003 Wiley-Liss, Inc.dagger C1 NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NIDOCD, NIH, Bethesda, MD USA. NIGMS, NIH, Bethesda, MD USA. RP Rasooly, RS (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, NIH, 2 Democracy Plaza,6707 Democracy Blvd,MSC 5458, Bethesda, MD 20892 USA. RI Briggs, Josephine/B-9394-2009; OI Briggs, Josephine/0000-0003-0798-1190; Rasooly, Rebekah/0000-0002-6357-5528 NR 0 TC 27 Z9 27 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2003 VL 228 IS 3 BP 490 EP 496 DI 10.1002/dvdy.10366 PG 7 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 738PB UT WOS:000186296100019 PM 14579387 ER PT J AU Bornstein, MH Arterberry, ME AF Bornstein, MH Arterberry, ME TI Recognition, discrimination and categorization of smiling by 5-month-old infants SO DEVELOPMENTAL SCIENCE LA English DT Article ID TO-FACE INTERACTION; FACIAL EXPRESSIONS; EMOTIONAL EXPRESSIONS; 3-MONTH-OLD INFANTS; 6-MONTH-OLD INFANTS; 7-MONTH-OLD INFANTS; CATEGORICAL PERCEPTION; REPRESENTATION; DIFFERENTIATION; ATTACHMENT AB Perceiving emotions correctly is foundational to the development of interpersonal skills. Five-month-old infants' abilities to recognize, discriminate and categorize facial expressions of smiling were tested in three coordinated experiments. Infants were habituated to four degrees of smiling modeled by the same or different people; following habituation, infants were presented with a new degree of smile worn by the same and by a new person (Experiment 1), a new degree of smile and a fearful expression worn by the same person (Experiment 2) or a new degree of smile and a fearful expression worn by new people (Experiment 3). Infants showed significant novelty preferences for the new person smiling and for the fearful expressions over the new degree of smiling. These findings indicate that infants at 5 months can categorize the facial expression of smiling in static faces, and yet recognize the same person despite changes in facial expression; this is the youngest age at which these abilities have been demonstrated. The findings are discussed in light of the significance of emotion expression face processing in social interaction and infants' categorization of faces. C1 NICHHD, Child & Family Res, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, Child & Family Res, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 92 TC 65 Z9 65 U1 3 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1363-755X J9 DEVELOPMENTAL SCI JI Dev. Sci. PD NOV PY 2003 VL 6 IS 5 BP 585 EP 599 DI 10.1111/1467-7687.00314 PG 15 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 747CQ UT WOS:000186788000015 ER PT J AU Terry, PD Weiderpass, E Ostenson, CG Cnattingius, S AF Terry, PD Weiderpass, E Ostenson, CG Cnattingius, S TI Cigarette smoking and the risk of gestational and pregestational diabetes in two consecutive pregnancies SO DIABETES CARE LA English DT Article ID MELLITUS; MEN; ETHNICITY; WEIGHT; COHORT; WOMEN AB OBJECTIVE - Cigarette smoking during pregnancy may increase the risk of gestational diabetes mellitus (GDM) or pregestational diabetes mellitus (PDM). Smoking has been associated positively with hyperinsulinemia and insulin rest stance in experimental studies, although the association with diabetes remains unclear. To further explore this issue, we examined the association with smoking in the largest prospective cohort study of GDM and PDM to date. RESEARCH DESIGN AND METHODS - The study population comprised 212,190 women in the population-based Swedish Birth Registry who had their first and second deliveries between January 1987 and December 1995. Maternal characteristics were recorded in a standardized manner at the first prenatal visit, followed by a clinical examination and a standardized in-person interview to assess lifestyle habits. Women were categorized as nonsmokers, light smokers (one to nine cigarettes per day), or moderate-to-heavy smokers (at least 10 cigarettes per day). RESULTS - Women with GDM in their first pregnancy experienced an eight- to ninefold in risk of GDM or PDM in their second pregnancy. Cigarette smoking was not associated with increased risk of these conditions. Neither women who smoked during their first and second pregnancies nor those who commenced smoking between pregnancies had a higher risk of GDM or PDM than nonsmokers. CONCLUSIONS - Our findings do not support an association between cigarette smoking and risk of GDM or PDM in young women of childbearing age. C1 Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. IARC, Lyon, France. Karolinska Hosp, Dept Endocrinol, S-10401 Stockholm, Sweden. RP Terry, PD (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD a3-05, Res Triangle Pk, NC 27709 USA. RI Weiderpass, Elisabete/M-4029-2016 OI Weiderpass, Elisabete/0000-0003-2237-0128 NR 30 TC 16 Z9 18 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 NOV PY 2003 VL 26 IS 11 BP 2994 EP 2998 DI 10.2337/diacare.26.11.2994 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738CL UT WOS:000186269100004 PM 14578229 ER PT J AU Digon, BJ Rother, KI Hirshberg, B Harlan, DM AF Digon, BJ Rother, KI Hirshberg, B Harlan, DM TI Sirolimus-induced interstitial pneumonitis in an islet transplant recipient SO DIABETES CARE LA English DT Letter C1 NIDDK, US PHS, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Harlan, DM (reprint author), NIDDK, US PHS, Transplantat & Autoimmun Branch, NIH, DHHS Bldg 10,Room 8N307, Bethesda, MD 20892 USA. NR 4 TC 18 Z9 18 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 NOV PY 2003 VL 26 IS 11 BP 3191 EP 3191 DI 10.2337/diacare.26.11.3191 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738CL UT WOS:000186269100041 PM 14578266 ER PT J AU de Courten, BV de Courten, M Hanson, RL Zahorakova, A Egyenes, HP Tataranni, PA Bennett, PH Vozar, J AF de Courten, BV de Courten, M Hanson, RL Zahorakova, A Egyenes, HP Tataranni, PA Bennett, PH Vozar, J TI Higher prevalence of type 2 diabetes, metabolic syndrome and cardiovascular diseases in gypsies than in non-gypsies in Slovakia SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE ethnicity; Roma; obesity; cardiovascular disease; type 2 diabetes ID RISK-FACTORS; PLASMA; HEALTH; HOMEOSTASIS; CHOLESTEROL; POPULATION; MELLITUS; GLUCOSE; OBESITY; PEOPLE AB Objective: Gypsies (or Roma) recently experienced a transition from a traditional to a Westernized lifestyle. Although mortality in this population is 4-fold higher compared with non-Gypsies, very limited information is available on their morbidity especially with regard to non-communicable diseases. Our aim was to determine the prevalence of type 2 diabetes mellitus (T2DM), metabolic syndrome and cardiovascular diseases in Gypsies and non-Gypsies living in the same region of southern Slovakia. Materials and methods: We examined 156 Gypsies and 501 non-Gypsies who participated in a population survey. Age- and sex-standardized prevalence rates were computed for each of the following: T2DM, obesity, hyperlipidemia, hypertension, hyperinsulinemia, elevated albumin/creatinine ratio (ACR), metabolic syndrome and cardiovascular disease. Results: Age-sex standardized prevalence of T2DM was 30% (95% CI = 22-39) in Gypsies and 10% (8-13, P = 0.0001 for comparison of ethnic groups) in non-Gypsies. Corresponding prevalence of the other variables are: 65% (56-74) and 30% (26-34, P = 0.0001) for obesity, 69% (61-76) and 59% (5463, P = 0.04) for hypercholesterolemia, 66% (59-74) and 39% (35-43, P = 0.009) for hypertriglyceridemia, 49% (4256) and 43% (39-47, P = 0.1) for hypertension, 33% (26-50) and 8% (2-14, P = 0.002) for hyperinsulinemia, 16% (922) and 5% (3-7, P = 0.0001) for elevated ACR, 20% (12-27) and 4% (3-6, P = 0.0001) for metabolic syndrome and 35% (28-43) and 26% (22-29, P = 0.004) for cardiovascular disease. Conclusions: Compared with non-Gypsies, Gypsies had a much higher prevalence of T2DM, metabolic syndrome and cardiovascular disease, which may contribute to their higher mortality. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Comenius Univ, Fac Med, Dept Internal Med 3, Bratislava, Slovakia. WHO, Off Representat S Pacific, Suva, Fiji. Specialized Outpatient Ctr Internal Med Diabetol, Samorin, Slovakia. RP de Courten, BV (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St,Rm 5-41, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; de Courten, Maximilian/0000-0001-9997-9359; de Courten, Barbora/0000-0001-8760-2511 NR 20 TC 42 Z9 44 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD NOV PY 2003 VL 62 IS 2 BP 95 EP 103 DI 10.1016/S0168-8227(03)00162-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 742QQ UT WOS:000186529900004 ER PT J AU Lee, YH Tokraks, S Pratley, RE Bogardus, C Permana, PA AF Lee, YH Tokraks, S Pratley, RE Bogardus, C Permana, PA TI Identification of differentially expressed genes in skeletal muscle of non-diabetic insulin-resistant and insulin-sensitive Pima Indians by differential display PCR SO DIABETOLOGIA LA English DT Article DE Pima Indians; insulin resistance; Type 2 diabetes; skeletal muscle; gene expression; differential display; real-time PCR ID DIABETES-SUSCEPTIBILITY GENES; AUTOSOMAL GENOMIC SCAN; SECRETORY DYSFUNCTION; MITOCHONDRIAL-DNA; NA+/K+-ATPASE; MESSENGER-RNA; MELLITUS; PROTEIN; OBESITY; LOCI AB Aims/hypothesis. Whole body insulin resistance results largely from impaired insulin-stimulated glucose disposal into skeletal muscle. We carried out muscle gene expression profiling to identify differentially expressed genes associated with insulin resistance. Methods. Skeletal muscle total RNA samples from six pairs of non-diabetic insulin-resistant and insulin-sensitive Pima Indians matched for percent body fat were analyzed by DDPCR with 90 primer combinations. The mRNA expression concentrations of selected 13 known genes and four expressed sequences tags were measured by quantitative real-time RT-PCR in 50 non-diabetic Pima subjects. Results. From over 6500 displayed DDPCR cDNA bands, 36 of the most differentially expressed cDNAs were identified, revealing 29 unique sequences: 16 known genes, 10 expressed sequences tags and three unknown transcripts. Multiple regression analyses indicated that whole body insulin-mediated glucose disposal rates of the subjects, independent of age, sex, and percent body fat, were negatively correlated with mRNA concentrations of an EST (DD23; r=-0.38, p=0.007), ATP1A2 (r=-0.27, p=0.05), MAP2K4 (r=-0.34, p=0.02), and PRPSAP1 (r=-0.37, p=0.008). Transcript concentrations of DD23 (r=0.27, p=0.05) and MTND4 (r=-0.29, p=0.05) were correlated with plasma insulin concentration, independent of age, sex, and percent body fat. Conclusion/interpretation. Altered expression concentrations of these genes might be causes or consequences of insulin resistance, and these genes serve as candidate susceptibility genes for insulin resistance. C1 Carl T Hayden Vet Affairs Med Ctr, Phoenix, AZ 85012 USA. NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Novartis Pharmaceut Corp, Dept Cardiovasc Metab & Endocrine Clin Res, E Hanover, NJ USA. RP Permana, PA (reprint author), Carl T Hayden Vet Affairs Med Ctr, ERS-151,650 E Indian Sch Rd, Phoenix, AZ 85012 USA. NR 39 TC 8 Z9 9 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2003 VL 46 IS 11 BP 1567 EP 1575 DI 10.1007/s00125-003-1226-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 745KC UT WOS:000186687000013 PM 14576983 ER PT J AU Swanson, EA Gloss, B Belke, DD Kaneshige, M Cheng, SY Dillmann, WH AF Swanson, EA Gloss, B Belke, DD Kaneshige, M Cheng, SY Dillmann, WH TI Cardiac expression and function of thyroid hormone receptor beta and its PV mutant SO ENDOCRINOLOGY LA English DT Article ID HEART-RATE; MICE; ALPHA; RESISTANCE; ISOFORMS; KINDREDS; DISEASE; GENE AB Thyroid hormone (T-3) influences cardiac function, and mice with deletion of thyroid hormone receptor (TR)alpha have diminished cardiac function. TRalpha1 represents 70% and TRbeta1 represents the remaining 30% of TR in ventricular myocytes, and its role in cardiac function is not well established. To determine the role of TRbeta1 in detail, we compared contractility in isolated perfused hearts from wild-type (WT) and TRbeta knockout mice under normal and increased work load. TRbeta knockout hearts showed contractile function similar to WT hearts at baseline and under conditions of enhanced demand. To gain insight into the role of TRbeta, we used mice with a homozygous mutation in exon 10 of TRbeta encoding the dominant negative PV mutant (TRbetaPV) expressed from the endogenous TRbeta promoter. TRbetaPV mice treated with 6-propyl-2-thiouracil and supplemented with T3 to make them euthyroid have decreased contractility with negative and positive rates of relaxation and contraction as well as peak systolic pressure diminished by 35 +/- 5, 34 +/- 6, and 35 +/- 6% in comparison with WT mice. Heart rate is diminished by 36 +/- 7%, which is accompanied by decreased expression of the pacemaker-related gene hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4). The expression of TRbeta1 in the pacemaker myocytes of the sinoatrial node was confirmed by quantitation of TRalpha1 and TRbeta1 mRNA in sinoatrial node, which showed that TRbeta1 mRNA represents 27.5 +/- 1.6% of the ligand-binding isoforms of the TR. In summary, although TRbeta is expressed at much lower levels in all regions of the heart than TRalpha1, expression of the strong dominant negative TRbetaPV mutant results in decreased contractile function and heart rate. C1 Univ Calif San Diego, Div Endocrinol & Metab, La Jolla, CA 92093 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dillmann, WH (reprint author), Univ Calif San Diego, Div Endocrinol & Metab, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NHLBI NIH HHS [HL 25022-19] NR 23 TC 23 Z9 23 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2003 VL 144 IS 11 BP 4820 EP 4825 DI 10.1210/en.2003-0522 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 736PB UT WOS:000186178300023 PM 12959993 ER PT J AU Liu, DX Zhang, ZP Gladwell, W Teng, CT AF Liu, DX Zhang, ZP Gladwell, W Teng, CT TI Estrogen stimulates estrogen-related receptor alpha gene expression through conserved hormone response elements SO ENDOCRINOLOGY LA English DT Article ID INDEPENDENT TRANSCRIPTIONAL ACTIVATION; HUMAN LACTOFERRIN GENE; ERR-1 ORPHAN RECEPTOR; CHAIN ACYL-COENZYME; NUCLEAR RECEPTORS; MOLECULAR-MECHANISMS; DEHYDROGENASE GENE; ER-BETA; PROMOTER; COACTIVATOR AB The estrogen-related receptor alpha gene encodes a nuclear receptor protein, ERRalpha, whose structure is closely related to the estrogen receptors. ERRalpha modulates estrogen receptor ( ER)mediated signaling pathways both positively and negatively. It is selectively expressed in a variety of cell types during development and in adult tissues. We have previously shown that estrogen stimulates the expression of the ERRalpha gene in mouse uterus. In this study, we found that the ERRalpha gene is stimulated by estrogen in mouse uterus and heart but not in liver. Estrogen also stimulates the expression of ERRalpha in the human breast and endometrial cell lines. The human ERRalpha gene promoter contains multiple Sp1 binding sites, and the Sp1 protein is required for the promoter activity. The major estrogen response is mediated by a 34-bp DNA element that contains multiple steroid hormone response element half-sites (MHREs) that are conserved between the human and mouse ERRalpha gene promoters. Mutations made at a single or multiple sites of the MHREs abolished the ER-mediated transcription of the element in transient transfection experiments. By chromatin immunoprecipitation assay, we demonstrated the interaction between ERalpha and MHREs of the endogenous ERRalpha gene promoter in MCF-7 cells. Estrogen treatment further enhanced the association of ERalpha and MHREs in vivo. The present study demonstrated that the ERRalpha gene is a downstream target of ERalpha. C1 NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), 111 Alexander Dr,POB 12233,MD E201, Res Triangle Pk, NC 27709 USA. NR 66 TC 50 Z9 60 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2003 VL 144 IS 11 BP 4894 EP 4904 DI 10.1210/en.2003-0432 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 736PB UT WOS:000186178300032 PM 12960079 ER PT J AU Sharp, RR de Serres, F Newman, L Sandhaus, RA Walsh, JW Hood, E Harry, GJ AF Sharp, RR de Serres, F Newman, L Sandhaus, RA Walsh, JW Hood, E Harry, GJ TI Environmental, occupational, and genetic risk factors for alpha-1 antitrypsin deficiency SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE alpha-1 antitrypsin deficiency; chronic obstructive pulmonary disease; emphysema; environmental risk factors; gene-environment interactions; genetic testing; liver disease; neutrophil elastase; occupational health ID SEVERE ALPHA(1)-ANTITRYPSIN DEFICIENCY; AUGMENTATION THERAPY; LUNG-FUNCTION; EMPHYSEMA; REGISTRY; LIVER; POLYMERIZATION; EXPRESSION; PROSPECTS; PATIENT AB alpha-1 Antitrypsin (AAT) deficiency is an inherited genetic disorder currently diagnosed in approximately 5,000 people in the United States. Although some individuals with ANT deficiency are asymptomatic, the condition often leads to deterioration of lung function in adults and is associated with emphysema, asthma, chronic obstructive pulmonary disease, and other respiratory diseases. In children, AAT deficiency can result in severe liver disease, including fatal cirrhosis in newborn infants. Although much is known about the clinical pathology of AAT deficiency, researchers are just beginning to characterize environmental, occupational, and genetic modifiers affecting the onset and progression of diseases related to AAT deficiency. On 19 August 2002, a group of basic scientists, clinicians, environmental health researchers, and public interest groups gathered at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, to discuss ongoing research on these topics. The goals of this workshop were to a) assess the present state of knowledge regarding environmental and occupational risk factors contributing to ANT deficiency morbidity and mortality, b) define future research needs in this area, and c) explore collaborative opportunities to advance understanding of risk factors affecting the progression of AAT deficiency-related disease. Participants agreed that new research initiatives in these areas represent an opportunity to benefit both basic science, through enhanced understanding of gene-environment interaction, and the AAT deficiency patient community, through innovative new approaches to disease management and treatment. C1 NIEHS, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Baylor Coll Med, Houston, TX 77030 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Alpha 1 Fdn, Miami, FL USA. AlphaNet, Miami, FL USA. InSight Prod Inc, Durham, NC USA. RP Harry, GJ (reprint author), NIEHS, Mol Toxicol Lab, Environm Toxicol Program, MD C1-04,POB 12233, Res Triangle Pk, NC 27709 USA. NR 46 TC 6 Z9 6 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2003 VL 111 IS 14 BP 1749 EP 1752 DI 10.1289/ehp.6325 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 741GD UT WOS:000186449600028 PM 14594626 ER PT J AU Kamel, F Rowland, AS Park, LA Anger, WK Baird, DD Gladen, BC Moreno, T Stallone, L Sandler, DA AF Kamel, F Rowland, AS Park, LA Anger, WK Baird, DD Gladen, BC Moreno, T Stallone, L Sandler, DA TI Neurobehavioral performance and work experience in Florida farmworkers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE citrus fruit; cognitive function; farm work; neurobehavioral performance; nurseries; ornamental ferns; psychomotor function ID RESEARCH SYSTEM BARS; CHRONIC NEUROLOGICAL SEQUELAE; FARM-WORKERS; ORGANOPHOSPHATE PESTICIDES; BEHAVIORAL-ASSESSMENT; HEALTH-STATUS; EXPOSURE; APPLICATORS; TESTS; SYMPTOMS AB Farmworkers experience many work-related hazards, including exposure to neurotoxicants. We compared neurobehavioral performance of 288 farmworkers in central Florida who had done farm work for at least 1 month with 51 controls who had not. Most of the farmworkers had worked in one or more of three types of agriculture: ornamental ferns, nurseries, or citrus fruit. We collected information on farm work history in a structured interview and evaluated neurobehavioral performance using a battery of eight tests. Analyses were adjusted for established confounders including age, sex, education, and acculturation. Ever having done farm work was associated with poor performance on four tests-digit span [odds ratio (OR) = 1.90; 95% confidence interval (CI), 1.02-3.53], tapping (coefficient = 4.13; 95% CI, 0.00-8.27), Santa Ana test (coefficient = 1.34; 95% CI, 0.29-2.39), and postural sway (coefficient = 4.74; 95% CI, -2-20 to 11.7)-but had little effect on four others: symbol digit latency, vibrotactile threshold, visual contrast sensitivity, and grip strength. Associations with farm work were similar in magnitude to associations with personal characteristics such as age and sex. Longer duration of farm work was associated with worse performance. Associations with fern work were more consistent than associations with nursery or citrus work. Deficits related to the duration of work experience were seen in former as well as current farmworkers, and decreased performance was related to chronic exposure even in the absence of a history of pesticide poisoning. We conclude that long-term experience of farm work is associated with measurable deficits in cognitive and psychomotor function. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Westat Corp, Durham, NC USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Farmworkers Assoc Florida, Apopka, FL USA. CODA, Durham, NC USA. RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, Box 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI Kamel, Freya/0000-0001-5052-6615; Baird, Donna/0000-0002-5544-2653; Sandler, Dale/0000-0002-6776-0018 NR 43 TC 54 Z9 57 U1 0 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2003 VL 111 IS 14 BP 1765 EP 1772 DI 10.1289/ehp.6341 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 741GD UT WOS:000186449600031 PM 14594629 ER PT J AU Weed, DL McKeown, RE AF Weed, DL McKeown, RE TI Science and social responsibility in public health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE environmental justice; epidemiology; ethics; professional ethics; public health; social responsibility ID ENVIRONMENTAL JUSTICE; PARTICIPATORY RESEARCH; ETHICS; EPIDEMIOLOGY; POLICY; AMERICAN; HAZARDS AB Epidemiologists and environmental health researchers have a joint responsibility to acquire scientific knowledge that matters to public health and to apply the knowledge gained in public health practice. We examine the nature and source of these social responsibilities, discuss a debate in the epidemiological literature on roles and responsibilities, and cite approaches to environmental justice as reflective of them. At one level, responsibility refers to accountability, as in being responsible for actions taken. A deeper meaning of responsibility corresponds to commitment to the pursuit and achievement of a valued end. Epidemiologists are committed to the scientific study of health and disease in human populations and to the application of scientific knowledge to improve the public's health. Responsibility is also closely linked to reliability. Responsible professionals reliably perform the tasks they set for themselves as well as the tasks society expects them to undertake. The defining axiom for our approach is that the health of the public is a social good we commit ourselves to pursue, thus assuming an obligation to contribute to its achievement. Epidemiologists cannot claim to be committed to public health as a social good and not accept the responsibility of ensuring that the knowledge gained in their roles as scientists is used to achieve that good. The social responsibilities of environmental health researchers are conspicuous in the environmental justice movement, for example, in community-based participatory research. Responsibility is an ethical concept particularly well suited to frame many key aspects of the ethics of our profession. C1 NCI, Off Prevent Oncol, Div Canc Prevent, Rockville, MD 20852 USA. Univ S Carolina, Norman J Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. RP Weed, DL (reprint author), NCI, Off Prevent Oncol, Div Canc Prevent, Execut Plaza N,Ste 3109,6130 Execut Blvd, Rockville, MD 20852 USA. OI McKeown, Robert/0000-0002-8829-5784 NR 43 TC 21 Z9 22 U1 2 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2003 VL 111 IS 14 BP 1804 EP 1808 DI 10.1289/ehp.6198 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 741GD UT WOS:000186449600038 PM 14602514 ER PT J AU De Roos, AJ Ward, MH Lynch, CF Cantor, KP AF De Roos, AJ Ward, MH Lynch, CF Cantor, KP TI Nitrate in public water supplies and the risk of colon and rectum cancers SO EPIDEMIOLOGY LA English DT Article DE colon; rectum; nitrate; drinking water; N-nitroso compounds ID N-NITROSO COMPOUNDS; CHLORINATION BY-PRODUCTS; MUNICIPAL DRINKING-WATER; CURED MEAT-PRODUCTS; ENDOGENOUS FORMATION; BLADDER-CANCER; CIGARETTE-SMOKING; NITROSAMINES; NITRITE; EXPOSURE AB Background:Nitrate is a widespread contaminant of drinking water, but its potential health effects are unclear. In the body, nitrate is reduced to nitrite, which can react with amines and amides by nitrosation to form N-nitroso compounds, known animal carcinogens. N-nitroso compound formation is inhibited by certain nutrients, such as vitamin C, and increased by meat intake. Methods: We investigated the association of nitrate in public water supplies with incident colon and rectum cancers in a case-control study conducted in Iowa from 1986 to 1989. Nitrate levels in Iowa towns were linked to the participants' water source histories. We focused our analyses on the period from 1960 onward, during which nitrate measurements were more frequent, and we restricted analyses to those persons with public water supplies that had nitrate data (actual or imputed) for greater than 70% of this time period (376 colon cancer cases, 338 rectum cancer cases, and 1244 controls). Results: There were negligible overall associations of colon or rectum cancers with measures of nitrate in public water supplies, including average nitrate and the number of years with elevated average nitrate levels. For more than 10 years with average nitrate greater than 5 mg/L, the odds, ratio (OR) for colon cancer was 1.2 (95% confidence interval [CI] = 0.9-1.6) and for rectum the OR was 1.1 (CI = 0.7-1.5). However, nitrate exposure (>10 years with average nitrate >5 mg/L) was associated with increased colon cancer risk among subgroups with low vitamin C intake (OR = 2.0; CI = 1.2-3.3) and high meat intake (OR = 2.2; CI = 1.4-3.6). These patterns were not observed for rectum cancer. Conclusions: Our analyses suggest that any increased risk of colon cancer associated with nitrate in public water supplies might occur only among susceptible subpopulations. C1 NCI, Occupat & Environm Epidemiol Branch, Div Can Epidemiol & Genet, Rockville, MD USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. RP De Roos, AJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MP-474,POB 19024, Seattle, WA 98109 USA. NR 49 TC 78 Z9 78 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2003 VL 14 IS 6 BP 640 EP 649 DI 10.1097/01.ede.0000091605.01334.d3 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 736FG UT WOS:000186160300003 PM 14569178 ER PT J AU Rutter, JL Chatterjee, N Wacholder, S Struewing, J AF Rutter, JL Chatterjee, N Wacholder, S Struewing, J TI The HER2 I655V polymorphism and breast cancer risk in ashkenazim SO EPIDEMIOLOGY LA English DT Article DE kin-cohort; polymorphism; risk; breast cancer; epidermal growth factor receptor ID POINT MUTATION; NEU ONCOGENE; KIN-COHORT; ESTIMATING PENETRANCE; TRANSMEMBRANE DOMAIN; GENETIC-POLYMORPHISM; CUMULATIVE RISK; BRCA2 MUTATIONS; ERBB-2; CARRIERS AB Background: Over-expression of the human epidermal growth factor receptor 2 (Her2) protooncogene is associated with poor prognosis among female patients with breast cancer. A polymorphism in the HER2 gene (1655V) has been associated with an elevated risk of breast cancer in some ethnic groups. Methods: Subjects from a community-based study of 5318 Ash-kenazim from the Washington, DC area were selected for analysis of the 1655V HER2 germline polymorphism. We estimated age-specific breast cancer risk from HER2 1655V based on the family history data, using the female first-degree relatives of the study participants and a novel extension of the kin cohort method. Results: The estimated cumulative risk of breast cancer to age 70 was approximately 30% higher among HER2 1655V carriers than noricarriers (RR = 1.33; 95% confidence interval [CI] = 1.03-1.83). The effect of the allele seems stronger at younger ages (among women younger than 50 years, RR = 2.11; CI = 1.39-3.28) and especially among younger women with a family history of breast cancer (RR = 8.9; CI = 1.9-19.7). Increased risk of breast cancer associated with the 1655V allele was also observed among BRCA1/2 mutation carriers, although these results are based on small numbers. Conclusion: These analyses suggest that the HER2 valine allele might be associated with increased risk of breast cancer, especially in young women and in women with a family history of the disease. C1 NCI, Dept Hlth & Human Serv, Lab Populat Genet, Ctr Canc Res,NIH, Bethesda, MD USA. NCI, Dept Hlth & Human Serv, Biostat Branch, Div Can Epidemiol & Genet,NIH, Bethesda, MD USA. RP Rutter, JL (reprint author), 6001 Execut Blvd,Room 4282,MSC 9555, Bethesda, MD 20892 USA. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013; OI Struewing, Jeffery/0000-0002-4848-3334; Rutter, Joni/0000-0002-6502-2361 NR 38 TC 23 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2003 VL 14 IS 6 BP 694 EP 700 DI 10.1097/01.ede00000832227.74669.7b PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 736FG UT WOS:000186160300010 PM 14569185 ER PT J AU Clement, PMJ Henderson, CA Jenkins, ZA Smit-McBride, Z Wolff, EC Hershey, JWB Park, MH Johansson, HE AF Clement, PMJ Henderson, CA Jenkins, ZA Smit-McBride, Z Wolff, EC Hershey, JWB Park, MH Johansson, HE TI Identification and characterization of eukaryotic initiation factor 5A-2 SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE deoxyhypusine; eIF5A; eIF5A-2; hypusine; polyamines; post-translational modification ID YEAST SACCHAROMYCES-CEREVISIAE; HYPUSINE-CONTAINING PROTEINS; ENDOTHELIAL-CELL GROWTH; DEOXYHYPUSINE SYNTHASE; TRANSLATION INITIATION; OVARIAN-CANCER; ANGSTROM RESOLUTION; MOUSE NEUROBLASTOMA; NUCLEAR EXPORT; MESSENGER-RNA AB The phylogenetically conserved eukaryotic translation initiation factor 5A(eIF5A) is the only known cellular protein to contain the post-translationally derived amino acid hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine]. Both eIF5A and its hypusine modi. cation are essential for sustained cell proliferation. Normally only one eIF5A protein is expressed in human cells. Recently, we identified a second human EIF5A gene that would encode an isoform (eIF5A-2) of 84% sequence identity. Overexpression of eIF5A-2 mRNA in certain human cancer cells, in contrast to weak normal expression limited to human testis and brain, suggests EIF5A2 as a potential oncogene. However, eIF5A-2 protein has not been described in human or mammalian cells heretofore. Here, we describe the identification of eIF5A-2 protein in human colorectal and ovarian cancer lines, SW-480 and UACC-1598, that overexpress eIF5A-2 mRNAs. Functional characterization of the human isoforms revealed that either human EIF5A gene can complement growth of a yeast strain in which the yeast EIF5A genes were disrupted. This indicates functional similarity of the human isoforms in yeast and suggests that eIF5A-2 has an important role in eukaryotic cell survival similar to that of the ubiquitous eIF5A-1. Detectable structural differences were also noted, including lack of immunological cross-reactivity, formation of different complexes with deoxyhypusine synthase, and K-m values (1.5 +/- 0.2 vs. 8.3 +/- 1.4 muM for eIF5A-1 and -2, respectively) as substrates for deoxyhypusine synthase in vitro. These physical characteristics and distinct amino acid sequences in the C- terminal domain together with differences in gene expression patterns imply differentiated, tissue-specific functions of the eIF5A-2 isoform in the mammalian organism and in cancer. C1 Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. Univ Calif Davis, Sch Med, Dept Biol Chem, Davis, CA 95616 USA. Univ Uppsala, Dept Cell & Mol Biol, S-75105 Uppsala, Sweden. RP Johansson, HE (reprint author), Childrens Hosp Oakland, Res Inst, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA. RI Smit-McBride, Zeljka/F-5524-2010; OI Smit-McBride, Zeljka/0000-0003-0275-8088; Johansson, Hans/0000-0001-9495-6107 FU NIGMS NIH HHS [R01-GM22135] NR 60 TC 54 Z9 63 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV PY 2003 VL 270 IS 21 BP 4254 EP 4263 DI 10.1046/j.1432-1033.2003.03806.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738QW UT WOS:000186300200003 PM 14622290 ER PT J AU Trabulsi, J Troiano, RP Subar, AF Sharbaugh, C Kipnis, V Schatzkin, A Schoeller, DA AF Trabulsi, J Troiano, RP Subar, AF Sharbaugh, C Kipnis, V Schatzkin, A Schoeller, DA TI Precision of the doubly labeled water method in a large-scale application: Evaluation of a streamlined-dosing protocol in the Observing Protein and Energy Nutrition (OPEN) study SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE doubly labeled water; total energy expenditure; stable isotopes; reproducibility ID EXPENDITURE; HUMANS; O-18; REQUIREMENTS; COMPONENTS; ACCURACY AB Objective: To evaluate whether the doubly labeled water (DLW) method is precise under conditions required for a large-scale evaluation of dietary intake instruments. Design: Energy expenditure was measured in 484 subjects ( main study). Subjects received one of five different weight DLW dose bottles prepared in advance of the study. A repeat energy expenditure measure was obtained in a subset of 24 subjects (substudy). DLW measures of energy expenditure were performed over a 2-week interval with urine collection at the beginning and end. Setting: Free-living environment with three clinic visits in the Maryland suburban area of Washington, DC. Subjects: A total of 484 subjects ( 261 men and 223 women) aged 40 - 69 y, 24 of whom ( 13 men and 11 women) participated in a substudy in which DLW was administered a second time. Results: The coefficient of variation of the DLW energy expenditure measurement was 5.1%. This included a 2.9% analytical and a 4.2% physiologic variation. Based on observed initial isotopic enrichment, the preweighed dosages were optimal in 70% of the main study subjects, and 9% received a dose that was less than optimal. Only six subjects (1%) were excluded because the final isotopic enrichment was too low to conduct precise measurement. Conclusions: Use of preweighed DLW dosages did not compromise the precision of the DLW method. The DLW method is a reliable measure of energy expenditure for large-scale evaluations of dietary intake instruments. Sponsorship: The National Cancer Institute. C1 Univ Wisconsin, Dept Nutr Sci, Madison, WI 53715 USA. NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. RP Schoeller, DA (reprint author), Univ Wisconsin, Dept Nutr Sci, 1415 Linden Dr, Madison, WI 53715 USA. OI Troiano, Richard/0000-0002-6807-989X NR 22 TC 34 Z9 34 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD NOV PY 2003 VL 57 IS 11 BP 1370 EP 1377 DI 10.1038/sj.ejcn.1601698 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 735VQ UT WOS:000186135600002 PM 14576749 ER PT J AU Zeiger, JS Hetmanski, JB Beaty, TH VanderKolk, CA Wyszynski, DF Bailey-Wilson, JE de Luna, RO Perandones, C Tolarova, MM Mosby, T Bennun, R Segovia, M Calda, P Pugh, EW Doheny, K Mcintosh, I AF Zeiger, JS Hetmanski, JB Beaty, TH VanderKolk, CA Wyszynski, DF Bailey-Wilson, JE de Luna, RO Perandones, C Tolarova, MM Mosby, T Bennun, R Segovia, M Calda, P Pugh, EW Doheny, K Mcintosh, I TI Evidence for linkage of nonsyndromic cleft lip with or without cleft palate to a region on chromosome 2 SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE cleft lip and palate; linkage analysis; transmission disequilibrium test; chromosome 2 ID FAMILIAL OROFACIAL CLEFT; FACTOR-ALPHA LOCUS; CANDIDATE REGIONS; MULTIPLEX FAMILIES; GENOME SCAN; NO EVIDENCE; GENE; ASSOCIATION; MARKERS; MALFORMATION AB Results from a genome-wide screen of 10 multiplex families ascertained through probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in Mexico, Argentina, and the United States yielded suggestive evidence of linkage to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except chromosome 2. Subsequent analysis was performed on the original 10 families plus an additional 16 families using 31 markers on chromosome 2. This analysis showed intriguing evidence of linkage to 2q (Zlr = 2.26, empirical P- value = 0.028 in a chromosome-wide analysis). Transmission disequilibrium tests also revealed evidence of linkage and disequilibrium for two markers in this region ( D2S168 and D2S1400 with P- values = 0.022 and 0.006, respectively). A subset of these 26 families provided additional evidence for a susceptibility gene for CL/P on 2q, suggesting that further studies of genes in this region are warranted. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHGRI, NIH, Baltimore, MD USA. Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. Ctr Nacl Genet Med, Buenos Aires, DF, Argentina. Asociac Piel, Buenos Aires, DF, Argentina. Univ Pacific, Sch Dent, San Francisco, CA 94115 USA. Charles Univ, Sch Med 1, Prague, Czech Republic. RP Zeiger, JS (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Room 6513,615 N Wolfe St, Baltimore, MD 21205 USA. RI Calda, Pavel /C-9171-2017; OI Calda, Pavel /0000-0002-2903-5026; Bailey-Wilson, Joan/0000-0002-9153-2920 FU NHGRI NIH HHS [N01-HG-65403]; NIDCR NIH HHS [P60-DE-13078] NR 32 TC 20 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2003 VL 11 IS 11 BP 835 EP 839 DI 10.1038/sj.ejhg.5201052 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 734TN UT WOS:000186074200003 PM 14571267 ER PT J AU Kucukguzel, SG Mazi, A Sahin, F Ozturk, S Stables, J AF Kucukguzel, SG Mazi, A Sahin, F Ozturk, S Stables, J TI Synthesis and biological activities of diflunisal hydrazide-hydrazones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE hydrazide-hydrazones; diflunisal; antibacterial activity; anticonvulsant activity; HETCOR ID ANTITUBERCULOTIC ACTIVITY; ANTICONVULSANT ACTIVITY; DERIVATIVES; ACID; 4-THIAZOLIDINONES; SEMICARBAZONES; PRODUCTS; AGENTS AB Several diflunisal hydrazide-hydrazone derivatives namely 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid [(5-nitro-2-furyl/substitutedphenyl)methylene] hydrazide (3a-o) have been synthesised. Methyl 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylate (1) and 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid hydrazide (2) were also synthesised and used as intermediate compounds. All synthesised compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37 Rv, antimicrobial activities against various bacteria, fungi and yeast species. Compound 3a have shown activity against Staphylococcus epidermis HE-5 and Staphylococcus aureus HE-9 at 18.75 and 37.5 mug mL(-1), respectively. Compound 3o have exhibited activity against Acinetobacter calcoaceticus IO-16 at a concentration of 37.5 mug mL(-1), whereas Cefepime, the drug used as standard, have been found less active against the microorganisms mentioned above. The synthesised compounds were found to provide 12-34% inhibition of mycobacterial growth of M. tuberculosis H37 Rv in the primary screen at 6.25 mug mL-1. Anticonvulsant activity of the compounds were also determined by maximal electroshock (MES) and subcutaneous metrazole (scMET) tests in mice and rats following the procedures of antiepileptic drug development (ADD) program of the National Institutes of Health (NIH). Compound 3k showed 25% protection against MES induced seizures in p.o. rat screening at a dose level of 30 mg kg(-1) whereas 3n and 3o showed neurotoxicity after 4 and 0.5 h at a dose level of 100 and 300 mg kg(-1) respectively. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Marmara Univ, Fac Pharm, Dept Pharmaceut Chem, TR-81010 Istanbul, Turkey. Ataturk Univ, Biotechnol Applicat & Res Ctr, TR-25240 Erzurum, Turkey. NINDS, NIH, Bethesda, MD 20892 USA. RP Kucukguzel, SG (reprint author), Marmara Univ, Fac Pharm, Dept Pharmaceut Chem, TR-81010 Istanbul, Turkey. EM gkucukguzel@marmara.edu.tr NR 24 TC 132 Z9 132 U1 2 U2 13 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD NOV-DEC PY 2003 VL 38 IS 11-12 BP 1005 EP 1013 DI 10.1016/j.ejmech.2003.08.004 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 762UK UT WOS:000188000400011 PM 14642333 ER PT J AU McCrone, P Chisholm, D Knapp, M Hughes, R Comi, G Dalakas, MC Illa, I Kilindireas, C Nobile-Orazio, E Swan, A Van den Bergh, P Willison, HJ AF McCrone, P Chisholm, D Knapp, M Hughes, R Comi, G Dalakas, MC Illa, I Kilindireas, C Nobile-Orazio, E Swan, A Van den Bergh, P Willison, HJ CA INCAT Study Grp TI Cost-utility analysis of intravenous immunoglobulin and prednisolone for chronic inflammatory demyelinating polyradiculoneuropathy SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE CIDP; cost-effectiveness analysis; economic evaluation; IVIg; peripheral nerve disorders; prednisolone; QALYs ID GUILLAIN-BARRE-SYNDROME; PLASMA-EXCHANGE; DOUBLE-BLIND; POLYNEUROPATHY; COMPLICATIONS; PREVALENCE; DISEASES; GLOBULIN; TRIALS AB The aim of this study was to provide an incremental cost-effectiveness analysis comparing intravenous immunoglobulin (IVIg) and prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy. Patients were recruited to a double-blind randomized crossover trial from nine European centres and received either prednisolone or IVIg during the first 6-week treatment period on which the economic evaluation was based. A societal perspective was adopted in measuring service use and costs, although the costs of lost employment were not included. The main outcome measure in the economic evaluation was the number of quality adjusted life years (QALYs) gained, with change in a 11-point disability scale used to measure clinical outcomes. Service use and quality of life data were available for 25 patients. Baseline costs were controlled for using a bootstrapped multiple regression model. The cost difference between the two treatments was estimated to be e3754 over the 6-week period. Health-related quality of life, as measured by the EuroQol EQ-5D instrument, increased more in the IVIg group but the difference was not statistically significant. Using a net-benefit approach it was shown that the probability of IVIg being cost-effective in comparison with prednisolone was 0.5 or above (i.e. was more likely to be cost-effective than cost-ineffective) only if one QALY was valued at over e250 000. The cost-effectiveness of IVIg is greatly affected by the price of IVIg and the amount administered. The impact of later side-effects of prednisolone on long-term costs and quality of life are likely to reduce the cost per QALY of IVIg treatment. C1 Univ London Kings Coll, Inst Psychiat, Hlth Serv Res Dept, Ctr Econ Mental Hlth, London SE5 8AF, England. London Sch Econ, Personal Social Serv Res Unit, London, England. Guys Kings & St Thomas Sch Med, Dept Clin Neurosci, London, England. Univ Vita Salute, IRCCS S Raffaele, Dept Neurol, Milan, Italy. Univ Athens, Sch Med, Eginit Univ Hosp, GR-11527 Athens, Greece. NIH, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. Hosp Univ Sta Creu & St Pau, Serv Neurol, Barcelona, Spain. Univ Milan, IRCCS, Osped Maggiore Policlin, Dept Neurol Sci, Milan, Italy. Univ Catholique Louvain, Clin Univ St Luc, Serv Neurol, B-1200 Brussels, Belgium. Univ Glasgow, So Gen Hosp, Dept Neurol, Glasgow, Lanark, Scotland. RP McCrone, P (reprint author), Univ London Kings Coll, Inst Psychiat, Hlth Serv Res Dept, Ctr Econ Mental Hlth, PO24,De Crespigny Pk, London SE5 8AF, England. RI Nobile-Orazio, Eduardo/B-7915-2013 NR 27 TC 49 Z9 49 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD NOV PY 2003 VL 10 IS 6 BP 687 EP 694 DI 10.1046/j.1351-5101.2003.00701.x PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 735MM UT WOS:000186119200012 PM 14641514 ER PT J AU Pike, VW Halldin, C Nobuhara, K Hiltunen, J Mulligan, RS Swahn, CG Karlsson, P Olsson, H Hume, SP Hirani, E Whalley, J Pilowsky, LS Larsson, S Schnell, PO Ell, PJ Farde, L AF Pike, VW Halldin, C Nobuhara, K Hiltunen, J Mulligan, RS Swahn, CG Karlsson, P Olsson, H Hume, SP Hirani, E Whalley, J Pilowsky, LS Larsson, S Schnell, PO Ell, PJ Farde, L TI Radioiodinated SB 207710 as a radioligand in vivo: imaging of brain 5-HT(4) receptors with SPET SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE [(123)I]SB 207710; 5-HT(4) receptors; brain; imaging; single-photon emission tomography; radioligand ID POSTMORTEM HUMAN BRAIN; RAT-BRAIN; BINDING-SITES; H-3 GR113808; GUINEA-PIG; REGIONAL-DISTRIBUTION; SEROTONIN 5-HT4; HIGHLY POTENT; ANTAGONIST; PET AB Single-photon emission tomography (SPET) and positron emission tomography (PET), when coupled to suitable radioligands, are uniquely powerful for investigating the status of neurotransmitter receptors in vivo. The serotonin subtype-4 (5-HT(4)) receptor has discrete and very similar distributions in rodent and primate brain. This receptor population may play a role in normal cognition and memory and is perhaps perturbed in some neuropsychiatric disorders. SB 207710 [(1-butyl-4-piperidinylmethyl)-8-amino-7-iodo-1,4-benzodioxan-5-carboxylate] is a selective high-affinity antagonist at 5-HT(4) receptors. We explored radioiodinated SB 207710 as a possible radioligand for imaging 5-HT(4) receptors in vivo. Rats were injected intravenously with iodine-125 labelled SB 207710, euthanised at known times and dissected to establish radioactivity content in brain tissues. Radioactivity entered brain but cleared rapidly and to a high extent from blood and plasma. Between 45 and 75 min after injection, the ratios of radioactivity concentration in each of 12 selected brain tissues to that in receptor-poor cerebellum correlated with previous measures of 5-HT(4) receptor density distribution in vitro. The highest ratio was about 3.4 in striatum. SB 207710 was labelled with iodine-123 by an iododestannylation procedure. A cynomolgus monkey was injected intravenously with [(123)I]SB 207710 and examined by SPET. Maximal whole brain uptake of radioactivity was 2.3% of the injected dose at 18 min after radioligand injection. Brain images acquired between 9 and 90 min showed high radioactivity uptake in 5-HT(4) receptor-rich regions, such as striatum, and low uptake in receptor-poor cerebellum. At 169 min the ratio of radioactivity concentration in striatum to that in cerebellum was 4.0. In a second SPET experiment, the cynomolgus monkey was pretreated with a selective 5-HT(4) receptor antagonist, SB 204070, at 20 min before [(123)I]SB 207710 injection. Radioactivity in all brain regions was reduced almost to the level in cerebellum by 176 min after radioligand injection. These findings show that [(123)I]SB 207710 is an effective radioligand for imaging brain 5-HT(4) receptors in vivo. C1 NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Hammersmith Hosp, Imperial Coll Sch Med, MRC, Cyclotron Unit, London, England. Karolinska Inst, Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, S-10401 Stockholm, Sweden. MAP Med Technol Oy, Tikkakoski, Finland. Inst Psychiat, London, England. UCL Royal Free & Univ Coll, Sch Med, Inst Nucl Med, London, England. Austin & Repatriat Med Ctr, Ctr PET, Heidelberg, Vic, Australia. Hammersmith Hosp, Imaging Res Solut Ltd, London, England. RP Pike, VW (reprint author), NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM victor.pike@nih.gov FU NIMH NIH HHS [MH41205, MH44814] NR 42 TC 16 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD NOV PY 2003 VL 30 IS 11 BP 1520 EP 1528 DI 10.1007/s00259-003-1307-x PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 735XK UT WOS:000186139700013 PM 14579092 ER PT J AU Ries, M Ramaswami, U Parini, R Lindblad, B Whybra, C Willers, I Gal, A Beck, M AF Ries, M Ramaswami, U Parini, R Lindblad, B Whybra, C Willers, I Gal, A Beck, M TI The early clinical phenotype of Fabry disease: a study on 35 European children and adolescents SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE adolescence; child; Fabry disease; females; genetics ID ANGIOKERATOMA CORPORIS DIFFUSUM; REPLACEMENT THERAPY; NEUROPATHIC PAIN; STORAGE DISEASE; MANIFESTATIONS; DEFICIENCY; SYMPTOMS; IMPACT; COHORT; FEMALE AB Fabry disease (FD) is a debilitating progressive multisystem X-linked lysosomal storage disorder. It was generally believed that the disease affects only adult males. Through systematic pedigree analysis, we identified 35 paediatric FD patients (age 1 to 21 years, mean 12.6 years) in 25 families. Predominant signs in this cohort were: acroparesthesia, hypohidrosis, and cornea verticillata. Neurological and psychological changes, such as tinnitus, recurrent vertigo, headache, diminished level of activity, fatigue, and depression were often observed. Angiokeratoma and gastrointestinal symptoms were frequent. Some patients also showed cardiac abnormalities. Six children and adolescents (three males and three females) over 14 years of age had renal involvement (all with proteinuria, one male had a decreased creatinine clearance of 62 ml/min). No males, but three females (1.5, 4 and 9 years of age), were free of signs and symptoms. Males (n=15, age 1 to 21 years, mean 12.4 years) and females (n=20, age 1.5 to 20 years, mean 12.7 years) showed comparable disease severity. However, the clinical courses demonstrated a wide intra- and interfamilial variability and tended to be more heterogeneous in the girls. Female patients are frequently affected at an early age, not much differently than males. They should be carefully examined because most carriers are symptomatic. Conclusion: Fabry disease usually becomes clinically manifest in childhood. Renal involvement can begin in adolescence. The diagnosis is made following a high level of suspicion or systematic pedigree analysis. It is crucial for paediatric Fabry disease patients to have early access to optimal supportive symptomatic management. Enzyme replacement therapy has shown promising effectiveness in adults. Considering its widespread therapeutic and potential preventive benefits, enzyme replacement therapy should be initiated at an early stage, prior to the onset of irreversible complications. C1 Univ Mainz, Childrens Hosp, Ctr Lysosomal Storage Disorders, D-55101 Mainz, Germany. Addenbrookes Hosp, Dept Paediat Endocrinol Diabet & Metab, Cambridge CB2 2QQ, England. Ist Clin Perfezionamento, Paediat Ctr Clin Genet, Dept Paediat, I-20122 Milan, Italy. Gothenburg Univ, Goteborg Paediat Growth Res Ctr, Queen Silvia Childrens Hosp, Inst Hlth Women & Children, S-41685 Gothenburg, Sweden. Univ Hosp Eppendorf, Inst Human Genet, D-22529 Hamburg, Germany. RP Ries, M (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Room 3D03,10 Ctr Dr, Bethesda, MD 20892 USA. OI Ries, Markus/0000-0002-5054-5741 NR 29 TC 127 Z9 131 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD NOV PY 2003 VL 162 IS 11 BP 767 EP 772 DI 10.1007/s00431-003-1299-3 PG 6 WC Pediatrics SC Pediatrics GA 738HB UT WOS:000186279800006 PM 14505049 ER PT J AU Yogeeswari, P Sriram, D Saraswat, V Ragavendran, JV Kumar, MM Murugesan, S Thirumurugan, R Stables, JP AF Yogeeswari, P Sriram, D Saraswat, V Ragavendran, JV Kumar, MM Murugesan, S Thirumurugan, R Stables, JP TI Synthesis and anticonvulsant and neurotoxicity evaluation of N-4-phthalimido phenyl (thio) semicarbazides SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE phthalimides; semicarbazides; thiosemicarbazides; anticonvulsants; CNS depressants ID ANTIEPILEPTIC DRUG DEVELOPMENT; MAXIMAL ELECTROSHOCK SCREEN; DERIVATIVES; RATS; ARYL; ANALOGS; AGENTS; THIOSEMICARBAZONES; ARYLIDENE; KETONES AB The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were synthesized and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (i.p.), maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in mice. Compound 2c afforded protection in all the three screens. Compounds except 1d, 2a and 2d showed no neurotoxicity up to 300 mg/kg. Compounds 1a, 1b, 2c, 2d, 2g and 2i were found to show oral MES activity. The compounds exhibited CNS depression and behavioral despair side effects, lesser than the conventional antiepileptic drugs. (C) 2003 Published by Elsevier B.V. C1 Birla Inst Technol & Sci, Pharm Grp, Med Chem Res Lab, Pilani 333031, Rajasthan, India. NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Yogeeswari, P (reprint author), Birla Inst Technol & Sci, Pharm Grp, Med Chem Res Lab, Pilani 333031, Rajasthan, India. EM pyogie_2000@rediffmail.com OI Rathinasabapathy, Thirumurugan/0000-0002-7330-0552 NR 32 TC 36 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD NOV PY 2003 VL 20 IS 3 BP 341 EP 346 DI 10.1016/j.ejps.2003.08.002 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 748JG UT WOS:000186858300010 PM 14592700 ER PT J AU Vourlekis, JS Szabo, E AF Vourlekis, JS Szabo, E TI Major conceptual change required to improve lung cancer: see a respiratory physician SO EUROPEAN RESPIRATORY JOURNAL LA English DT Letter ID BETA-CAROTENE; SMOKERS C1 Natl Canc Inst, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, NIH,Inst Hlth, Bethesda, MD 20892 USA. Natl Canc Inst, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, NIH,Inst Hlth & Human Serv, Bethesda, MD USA. RP Vourlekis, JS (reprint author), Natl Canc Inst, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, NIH,Inst Hlth, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD NOV PY 2003 VL 22 IS 5 BP 866 EP 866 DI 10.1183/09031936.03.00068403 PG 1 WC Respiratory System SC Respiratory System GA 739UE UT WOS:000186364200029 PM 14621099 ER PT J AU Nyska, A Moomaw, CR Ezov, N Shabat, S Levin-Harrus, T Nyska, M Redlich, M Mittelman, M Yedgar, S Foley, JF AF Nyska, A Moomaw, CR Ezov, N Shabat, S Levin-Harrus, T Nyska, M Redlich, M Mittelman, M Yedgar, S Foley, JF TI Ocular expression of vascular cell adhesion molecule (VCAM-1) in 2-butoxyethanol-induced hemolysis and thrombosis in female rats SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE hemolysis; thrombosis; eye; female rat; 2-butoxyethanol; VCAM-1 ID BETA-THALASSEMIA; P-SELECTIN; F344 RATS; INHALATION EXPOSURE; INFARCTION; DISEASE; ACTIVATION; HYPOXIA; INJURY AB We demonstrated previously that exposure of rats to 2-butoxyethanol (BE) was associated with morphological changes in red blood cells, hemolytic anemia, and disseminated thrombosis and infarction in different organs including the eyes. In order to elucidate the mechanism of thrombosis formation, we examined in this study the histology and immunohistochemical expression of vascular cell adhesion molecule-1 (VCAM-1), endothelial intercellular adhesion molecule-1 (ICAM-1), and P-selectin in the eyes of the female F344 rat exposed to 2, 3, or 4 daily doses of BE/250 mg/kg body weight. In this BE hemolysis and thrombosis model, positive VCAM-1 expression occurred only in eyes of rats exposed to 3 and 4 doses and was localized in the iris (epithelium lining the posterior surface, anterior mesenchymal epithelium), ciliary processes (lining epithelium, stromal cells), and retina (hypertrophic retinal pigment epithelium). Only weak immunolabeling was seen in eyes exposed to 2 doses. The appearance of VCAM-1 immunostaining correlated with the development of thrombosis located in the same structures. No change in ICAM-1 or P-selectin expression was seen. This immunolabeling distribution suggests that VCAM-1 functions in the pathogenesis of BE-related thrombosis by promoting adhesion of erythrocytes to the endothelium. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Harlan Biotech Israel Ltd, Kiryat Weizmann, Rehovot, Israel. Sapir Med Ctr, Dept Orthopaed Surg, Kefar Sava, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Fac Med Dent, Dept Orthodont, IL-91010 Jerusalem, Israel. Hasharon Hosp, Rabin Med Ctr, Dept Internal Med B, IL-49372 Petah Tiqwa, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91010 Jerusalem, Israel. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, MD B3-06,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 32 TC 10 Z9 12 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD NOV PY 2003 VL 55 IS 4 BP 231 EP 236 DI 10.1078/0940-2993-00321 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 755QN UT WOS:000187421500002 PM 14703767 ER PT J AU Pi, JB Qu, W Reece, JM Kumagai, Y Waalkes, MP AF Pi, JB Qu, W Reece, JM Kumagai, Y Waalkes, MP TI Transcription factor Nrf2 activation by inorganic arsenic in cultured keratinocytes: involvement of hydrogen peroxide SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE arsenic; Nrf2; antioxidant response element; hydrogen peroxide; keratinocyte; Keap1; oxidative stress ID ANTIOXIDANT-RESPONSE-ELEMENT; HEME OXYGENASE-1 GENE; REACTIVE OXYGEN; MEDIATED EXPRESSION; OXIDATIVE STRESS; DRINKING-WATER; NF-E2-RELATED FACTOR-2; SULFHYDRYL-GROUPS; ANIMAL-MODEL; INDUCTION AB Inorganic arsenic is a well-documented human carcinogen that targets the skin. The induction of oxidative stress, as shown with arsenic, may have a bearing on the carcinogenic mechanism of this metalloid. The transcription factor Nrf2 is a key player in the regulation of genes encoding for many antioxidative response. enzymes. Thus, the effect of inorganic arsenic (as sodium arsenite) on Nrf2 expression and localization was studied in HaCaT cells, an immortalized human keratinocyte cell line. We found, for the first time, that arsenic enhanced cellular expression of Nrf2 at the transcriptional and protein levels and activated expression of Nrf2-related genes in these cells. In addition, arsenic exposure caused nuclear accumulation of Nrf2 in association with downstream activation of Nrf2-mediated oxidative response genes. Arsenic simultaneously increased the expression of Keap1, a regulator of Nrf2 activity. The coordinated induction of Keap1 expression and nuclear Nrf2 accumulation induced by arsenic suggests that Keap1 is important to arsenic-induced Nrf2 activation. Furthermore, when cells were pretreated with scavengers of hydrogen peroxide (H2O2) such as catalase-polyethylene glycol (PEG-CAT) or Tiron, arsenic-induced nuclear Nrf2 accumulation was suppressed, whereas CuDIPSH, a cell-permeable superoxide dismutase (SOD) mimic compound that produces H2O2 from superoxide (.O-2(-)), enhanced Nrf2 nuclear accumulation. These results indicate that H2O2, rather than .O-2(-), is the mediator of nuclear Nrf2 accumulation. Additional study showed that arsenic causes increased cellular H2O2 production and that H2O2 itself has the ability to increase Nrf2 expression at both the transcription and protein levels in HaCaT cells. Taken together, these data clearly show that arsenic increases Nrf2 expression and activity at multiple levels and that H2O2 is one of the mediators of this process. (C) 2003 Elsevier Inc. All rights reserved. C1 NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab,NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ Tsukuba, Inst Community Med, Dept Environm Med, Tsukuba, Ibaraki 3058575, Japan. RP Waalkes, MP (reprint author), NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab,NIH, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 51 TC 139 Z9 149 U1 3 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 1 PY 2003 VL 290 IS 2 BP 234 EP 245 DI 10.1016/S0014-4827(03)00341-0 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 735UG UT WOS:000186132500006 PM 14567983 ER PT J AU Hidaka, K Kanematsu, T Caffrey, JJ Takeuchi, H Shears, SB Hirata, M AF Hidaka, K Kanematsu, T Caffrey, JJ Takeuchi, H Shears, SB Hirata, M TI The importance to chondrocyte differentiation of changes in expression of the multiple inositol polyphosphate phosphatase SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE chondrocyte; ATDC5; inositol phosphates; MIPP/Minpp; endochondral bone formation ID SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; KINASE; 3,4,5,6-TETRAKISPHOSPHATE; HEXAKISPHOSPHATE; 3-PHOSPHATASE; HYPERTROPHY; CARTILAGE; CALCIUM; MINPP1 AB It is important to both physiological and pathological osteogenesis to understand the significance of changes in gene expression in growth-plate chondrocytes that transit between the proliferative and hypertrophic states. MINPP is one such gene of interest. The Minpp protein dephosphorylates highly phosphorylated inositol signaling molecules InsP(5) and InsP(6). We show here that the ATDC5 chondrocyte progenitor cell line can recapitulate developmentally specific changes in MINPP expression previously only seen in longitudinal bone growth plates-both an initial 2-3-fold increase and a subsequent decrease back to initial levels during transition to hypertrophy. The increase in MINPP expression was accompanied by a 40% decrease in InsP(6) levels in ATDC5 cells. However, InSP5 levels were not modified. Furthermore, throughout the hypertrophic phase, during which MINPP expression decreased, there were no alterations in InSP5 and InsP(6) levels. We also created an ATDC5 line that stably overexpressed Minpp at 2-fold higher levels than in wild-type cells. This had no significant effect upon cellular levels of InSP5 and InSP6. Thus, substantial changes in MINPP expression can occur without a net effect upon InsP(5) and InsP(6) turnover in vivo. On the other hand, Minpp-overexpressing cells showed impaired chondrogenesis. We noted that the expression of alkaline phosphatase activity was inversely correlated with the expression of MINPP. The ATDC5 cells that overexpress Minpp failed to show an insulin-dependent increase in alkaline phosphatase levels, which presumably affects phosphate balance [J. Biol. Chem. 276 (2001) 33995], and may be the reason cellular differentiation was impaired. In any case, we conclude that Minpp is important to chondrocyte differentiation, but in a manner that is, surprisingly, independent of inositol polyphosphate turnover. (C) 2003 Elsevier Inc. All rights reserved. C1 Natl Inst Environm Hlth Sci, Phosphoinositide Sect, Inositide Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA. Kyushu Univ, Fac Dent Sci, Lab Mol & Cellular Biochem, Fukuoka 8128582, Japan. Kyushu Univ, Stn Collaborat Res, Fukuoka 8128582, Japan. RP Hidaka, K (reprint author), Natl Inst Environm Hlth Sci, Phosphoinositide Sect, Inositide Signaling Grp, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 35 TC 6 Z9 7 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 1 PY 2003 VL 290 IS 2 BP 254 EP 264 DI 10.1016/S0014-4827(03)00337-9 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 735UG UT WOS:000186132500008 PM 14567985 ER PT J AU Rhee, DJ Fariss, RN Brekken, R Sage, EH Russell, P AF Rhee, DJ Fariss, RN Brekken, R Sage, EH Russell, P TI The matricellular protein SPARC is expressed in human trabecular meshwork SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE trabecular meshwork; extracellular matrix; cell culture; proteoglycans; glaucoma ID MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; CYSTEINE SPARC; AQUEOUS-HUMOR; ORGAN-CULTURE; NULL MICE; IN-VIVO; OSTEONECTIN; BINDING AB Purpose. This investigation was undertaken to determine whether the matricellular protein SPARC is expressed in the human trabecular meshwork (TM) and cultured human trabecular meshwork cells. Methods. Human donor trabecular meshwork and cultured cells obtained from trabecular meshwork were used in this study. Total RNA was obtained from TM and cultured TM endothelial cells, and RT-PCR was done with primers specific for SPARC. Western blotting was performed on donor TMs using an anti-SPARC monoclonal antibody prepared against rHuSPARC. Confocal microscopy was used to determine the distribution of SPARC in human anterior segments, and immunofluorescence on cultured TM cells was performed with the anti-SPARC antibody. Results. SPARC mRNA was expressed both in TM and in cultured TM cells. Immunoblotting for SPARC showed a doublet with a molecular mass similar to43 kDa. The ratio of the doublet bands varied with each of the samples; some of the cultured cells and the tissue samples exhibited more of the upper band, and other cultured cells contained almost equal amounts of the two bands. The upper band was shown to be a glycosylated form of SPARC. Immunofluorescence showed that SPARC was expressed in the cultured TM, and confocal microscopy with the anti-SPARC antibody demonstrated the presence of this protein in the TM and in other tissues in the anterior segment. Conclusions. Our data conclusively show that SPARC mRNA and protein are present in non-glaucomatous TM tissue and in cultured TM cells. Because of its effect on matrix metalloproteinases, SPARC may play a role in the regulation of intraocular pressure. (C) 2003 Elsevier Ltd. All rights reserved. C1 NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. Univ Texas, Hamon Ctr Therapeut Oncol Res, SW Med Ctr, Dallas, TX USA. Hope Heart Inst, Dept Vasc Biol, Seattle, WA USA. RP Rhee, DJ (reprint author), Wills Eye Hosp & Res Inst, Glaucoma Serv, 840 Walnut St,Suite 1110, Philadelphia, PA 19107 USA. FU NEI NIH HHS [EY 13180]; NHLBI NIH HHS [HL 10352-03]; NIGMS NIH HHS [GM 40711] NR 46 TC 36 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2003 VL 77 IS 5 BP 601 EP 607 DI 10.1016/S0014-4835(03)00190-8 PG 7 WC Ophthalmology SC Ophthalmology GA 733HA UT WOS:000185992900009 PM 14550402 ER PT J AU Ginis, I Rao, MS AF Ginis, I Rao, MS TI Toward cell replacement therapy: promises and caveats SO EXPERIMENTAL NEUROLOGY LA English DT Review DE transplantation; neurons; glia; neural precursors; mouse models; immune response; allelic variability; clinical trials; neurological disease ID EMBRYONIC STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; NEURAL PROGENITOR CELLS; LEUKEMIA INHIBITORY FACTOR; CHEMOKINE RECEPTOR CXCR4; GLIAL PRECURSOR CELL; HUMAN NEURONAL CELLS; CULTURED ES CELLS; HUMAN SPINAL-CORD AB Studies in animal models have suggested a role for stem cells in repair and regeneration of the nervous system. Human equivalents of stem and precursor cells have been isolated and their efficacy is being evaluated in rodent and primate models. Difficulties exist in translating results of these preclinical models to therapy in humans. Evolutionary differences among rodents, primates, and humans; fundamental differences in the anatomy and physiology; differences in immune responses in xenotransplant models; the paucity of good transplant models of chronic disease; and allelic variability in the cells themselves make any study evaluating the efficacy of cells in transplant models difficult to interpret. As no better alternatives to testing in animals exist, we suggest that at this early stage a considered step-by-step approach to testing and comparison of different transplant strategies in isolation will prepare us better for clinical trials than simple evaluation of functional outcomes in various models of disease. We emphasize that we do not recommend delaying or abandoning clinical trials; rather, we suggest that one anticipate failures and design experiments and data collection such that we learn from these failures to ensure future success in as rapid a time frame as possible. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Neurosci Lab,NIH, Baltimore, MD 21224 USA. RP Rao, MS (reprint author), NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Neurosci Lab,NIH, 5600 Nathan Shock Dr,Room 4E02, Baltimore, MD 21224 USA. NR 142 TC 32 Z9 34 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2003 VL 184 IS 1 BP 61 EP 77 DI 10.1016/S0014-4886(03)00256-5 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 747KZ UT WOS:000186804800013 PM 14637081 ER PT J AU Bibbiani, F Oh, JD Petzer, JP Castagnoli, N Chen, JF Schwarzschild, MA Chase, TN AF Bibbiani, F Oh, JD Petzer, JP Castagnoli, N Chen, JF Schwarzschild, MA Chase, TN TI A(2A) antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Parkinson's disease; A(2A) receptor; KW-6002; MPTP; dyskinesia; PKA; primates; rodents ID PROTEIN-KINASE-A; CENTRAL-NERVOUS-SYSTEM; RECEPTOR ANTAGONIST; ADENOSINE RECEPTORS; IN-VIVO; PHOSPHORYLATION SITES; AMPA RECEPTORS; RAT; MONKEYS; DYSKINESIA AB Adenosine A(2A) receptors, abundantly expressed on striatal medium spiny neurons, appear to activate signaling cascades implicated in the regulation of coexpressed ionotropic glutamatergic receptors. To evaluate the contribution of adenosinergic mechanisms to the pathogenesis of the response alterations induced by dopaminergic treatment, we studied the ability of the selective adenosine A(2A) receptor antagonist KW-6002 to prevent as well as palliate these syndromes in rodent and primate models of Parkinson's disease. In rats, KW-6002 reversed the shortened motor response produced by chronic levodopa treatment while reducing levodopa-induced hyperphosphorylation at S845 residues on AMPA receptor GluR1 subunits. In primates, KW-6002 evidenced modest antiparkinsonian activity when given alone. Once-daily coadministration of KW-6002 with apomorphine prevented the development of dyskinesias, which appeared in control animals 7-10 days after initiating apomorphine treatment. Animals initially given apornorphine plus KW-6002 for 3 weeks did not begin to manifest apomorphine-induced dyskinesias until 10-12 days after discontinuing the A(2A) antagonist. These results suggest that KW-6002 can attenuate the induction as well as the expression of motor response alterations to chronic dopaminergic stimulation in parkinsonian animals, possibly by blocking A(2A) receptor-stimulated signaling pathways. Our findings strengthen the rationale for developing A(2A) antagonists as an early treatment strategy for Parkinson's disease. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Mol Neurobiol Lab, Boston, MA 02114 USA. Virginia Tech, Dept Chem, Blacksburg, VA USA. Cent Michigan Univ, Dept Psychol, Mt Pleasant, MI 48859 USA. RP Chase, TN (reprint author), Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, NIH, Bldg 10,Room 5C103, Bethesda, MD 20892 USA. RI Petzer, Jacobus/E-8747-2011; OI Petzer, Jacobus/0000-0002-7114-8120 NR 52 TC 135 Z9 138 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2003 VL 184 IS 1 BP 285 EP 294 DI 10.1016/S0014-4886(03)00250-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 747KZ UT WOS:000186804800031 PM 14637099 ER PT J AU Malone, W Perloff, M Crowell, J Sigman, C Higley, H AF Malone, W Perloff, M Crowell, J Sigman, C Higley, H TI Fenretinide: a prototype cancer prevention drug SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE 4-HPR; cancer; chemoprevention; fenretinide; retinoid ID SYNTHETIC RETINOID FENRETINIDE; ABERRANT CRYPT FOCI; SQUAMOUS INTRAEPITHELIAL LESIONS; URINARY-BLADDER CARCINOGENESIS; OVARIAN-CARCINOMA XENOGRAFT; RANDOMIZED CLINICAL-TRIAL; INDUCED MAMMARY-TUMORS; METHYL-N-NITROSOUREA; EARLY BREAST-CANCER; GROWTH-FACTOR-BETA AB Fenretinide (N-4-hydroxyphenylretinamide [4-HPR]) is a synthetic retinoid that has been examined in in vitro assays, preclinical animal models and clinical trials as a cancer chemopreventive agent. Its pharmacology, toxicity and mechanisms of action initially suggested an increased therapeutic index relative to native retinoids for the control of tumours of the breast, prostate, bladder, colon, cervix and head and neck. Although fenretinide at the doses and schedules used in several pivotal Phase II and III clinical trials has not been proven to be efficacious in reducing the incidence of cancer or in retarding the development of preneoplastic lesions, encouraging observations regarding unanticipated preventative activity, such as for ovarian cancer control, have arisen from these studies. Research in cancer therapy and the elucidation of molecular pathways activated by fenretinide have also yielded clues about how this agent might be better used in a prevention setting. Current trials are underway to re-examine both dose and schedule of fenretinide administration as well as the target tissues of interest. Investigations of potential synergism between fenretinide and other candidate chemopreventative molecules with complementary mechanisms of action may support future assessments of this prototype cancer prevention drug or its newer analogues. C1 NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Crowell, J (reprint author), NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. NR 149 TC 34 Z9 37 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD NOV PY 2003 VL 12 IS 11 BP 1829 EP 1842 DI 10.1517/13543784.12.11.1829 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742KA UT WOS:000186514900008 PM 14585058 ER PT J AU Swamynathan, SK Crawford, MA Robison, WG Kanungo, J Piatigorsky, J AF Swamynathan, SK Crawford, MA Robison, WG Kanungo, J Piatigorsky, J TI Adaptive differences in the structure and macromolecular compositions of the air and water corneas of the "four-eyed" fish (Anableps anableps) SO FASEB JOURNAL LA English DT Article ID DROSOPHILA-MELANOGASTER; PRIMARY SPECTACLE; REFRACTIVE STATE; SEA LAMPREY; GELSOLIN; VISION; GLYCOGEN; EYE; EPITHELIUM; MECHANISMS AB The water meniscus bisects the eyes of the "four-eyed" fish Anableps anableps, resulting in simultaneous vision in air and water. We compare the structure and macromolecular compositions of the Anableps dorsal (air) and ventral (water) corneas with the fully aquatic zebrafish cornea. The Anableps dorsal corneal epithelium is thicker (>20 cell layers), flatter (similar to 1. 94 nun radius of curvature), and contains similar to 15-fold more glycogen (0. 16 mug/mug water-soluble protein) than the ventral corneal epithelium (5-7 cell layers; similar to1.63 nun radius of curvature; 0.01 mug glycogen/mug watersoluble protein), which resembles the zebrafish corneal epithelium. Gelsolin is the major water-soluble protein in the zebrafish (similar to50%) and Anableps dorsal (similar to38%) and ventral (similar to21%) corneal epithelia, suggesting that gelsolin was recruited for high corneal expression before these two species diverged at least 100 million years ago and that abundant corneal gelsolin is not limited to aquatic vision. Anableps gelsolin, deduced from its cDNA, is 57% identical to zebrafish gelsolin. Paucity of Anableps corneal F-actin (consistent with high gelsolin) was confirmed by the absence of rhodamine-phalloidin staining. We suggest amphibious refraction and protection from UV irradiation and desiccation in air as selective constraints for the specializations of the Anableps dorsal cornea. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, 7 Mem Dr,Bldg 7,Room 100A, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov OI Swamynathan, Shivalingappa/0000-0002-9158-1511 NR 37 TC 23 Z9 25 U1 2 U2 10 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 NOV PY 2003 VL 17 IS 14 BP 1996 EP 2005 DI 10.1096/fj.03-0122com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 750AA UT WOS:000186961200036 PM 14597669 ER PT J AU Mills, JL England, L Granath, F Chattingius, S AF Mills, JL England, L Granath, F Chattingius, S TI Smoking and sex selection? Not proven yet - Reply of the authors SO FERTILITY AND STERILITY LA English DT Letter C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. RP Mills, JL (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. NR 1 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2003 VL 80 IS 5 BP 1290 EP 1290 DI 10.1016/S0015-0282(03)02180-0 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 741EB UT WOS:000186444800051 ER PT J AU Simpson, JL de la Cruz, F Swerdloff, RS Samango-Sprouse, C Skakkeback, NE Graham, JM Hassold, T Aylstock, M Meyer-Bahlburg, HFL Willard, HF Hall, JG Salameh, W Boone, K Staessen, C Geschwind, D Giedd, J Dobs, AS Rogol, A Brinton, B Paulsen, CA AF Simpson, JL de la Cruz, F Swerdloff, RS Samango-Sprouse, C Skakkeback, NE Graham, JM Hassold, T Aylstock, M Meyer-Bahlburg, HFL Willard, HF Hall, JG Salameh, W Boone, K Staessen, C Geschwind, D Giedd, J Dobs, AS Rogol, A Brinton, B Paulsen, CA TI Klinefelter syndrome: Expanding the phenotype and identifying new research directions SO GENETICS IN MEDICINE LA English DT Article DE Klinefelter syndrome; seminiferous tubules; neurocognitive; language ID IN-SITU HYBRIDIZATION; SEX-CHROMOSOME ABNORMALITIES; SERTOLI CELLS; 47,XXY; TRISOMY-21; SPERM; BOYS; NONDISJUNCTION; SPERMATOZOA; ANEUPLOIDY AB Purpose: The purpose of this study is to summarize new data on etiology and clinical features of Klinefelter syndrome in order to derive research priorities. Methods: This study was conducted using critical reviews of selective topics, emphasizing less well-recognized clinical findings. Results And Conclusions: The phenotype of the prototypic 47,XXY case is well recognized: seminiferous tubule dysgenesis and androgen deficiency. Less well appreciated is the varied expressivity of 47,XXY Klinefelter syndrome, in particular neurological/cognitive perturbations like language and behavioral problems. Effective therapies are available. Reproductive technologies allow 47,XXY men to sire offspring through intracytoplasmic sperm injection (ICSI); however, genetic counseling is complex and success is low. Behavioral and expressive language difficulties are amenable to treatment by androgen therapy and psychological help. Early treatment may be imperative for optimal outcome. C1 Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. NICHD, Bethesda, MD USA. Harbor UCLA, Res & Educ Inst, Torrance, CA USA. George Washington Univ, Washington, DC USA. Rigshosp, Univ Dept Growth & Reprod, DK-2100 Copenhagen, Denmark. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Klinefelter Syndrome & Assoc, Roseville, CA USA. Columbia Univ, New York, NY USA. Duke Univ, Durham, NC USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Dutch Speaking Free Univ, Brussels, Belgium. Univ Calif Los Angeles, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Virginia, Charlottesville, VA USA. Brigham Young Univ, Provo, UT 84602 USA. Univ Washington, Seattle, WA 98195 USA. RP Simpson, JL (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 6550 Fannin,Suite 901A, Houston, TX 77030 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 59 TC 93 Z9 93 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 2003 VL 5 IS 6 BP 460 EP 468 DI 10.1097/01.GIM.0000095626.54201.D0 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 741WF UT WOS:000186482800008 PM 14614399 ER PT J AU Cleaver, JE Collins, C Ellis, J Volik, S AF Cleaver, JE Collins, C Ellis, J Volik, S TI Genome sequence and splice site analysis of low-fidelity DNA polymerases H and I involved in replication of damaged DNA SO GENOMICS LA English DT Article DE Pol H; Pol I; xeroderma pigmentosum variant; alternative splice; donor; acceptor; DNA damage ID XERODERMA-PIGMENTOSUM; MATHEMATICAL-THEORY; BINDING-PROTEINS; ERROR-PRONE; Y-FAMILY; ETA; MUTATIONS; BYPASS; GENE; IOTA AB POLH and POL1 are paralogs encoding low-fidelity, class Y, DNA polymerases involved in replication of damaged DNA in the human disease xeroderma pigmentosum variant. Analysis of genomic regions for human and mouse homologs, employing the analytic tool Genome Cryptographer, detected low-repetitive or unique regions at exons and other potential control regions, especially within intron I of human POLH. The human and mouse homologs are structurally similar, but the paralogs have undergone evolutionary divergence. The information content of splice sites for human POLH, the probability that a base would contribute to splicing, was low only for the acceptor site of exon II, which is preceded by a region of high information content that could contain sequences controlling splicing. This analysis explains previous observations of tissue-specific skipping during mRNA processing, resulting in the loss of the transcription start site in exon II, in human tissues. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director, Bethesda, MD 20892 USA. RP Cleaver, JE (reprint author), Univ Calif San Francisco, Ctr Canc, Box 0808,Room N431, San Francisco, CA 94143 USA. FU NIEHS NIH HHS [1 R01 ES 8061] NR 29 TC 1 Z9 1 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 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 2003 VL 82 IS 5 BP 561 EP 570 DI 10.1016/S0888-7543(03)00180-0 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 733BK UT WOS:000185979900007 PM 14559213 ER PT J AU Proia, RL AF Proia, RL TI Physiologic functions of gangliosides SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 NIH, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 22 BP 834 EP 834 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200030 ER PT J AU Negishi, M AF Negishi, M TI Structure and function of glycosyltransferases SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 NIH, NIEHS, LRDT, Pharmacogent Sect, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 28 BP 835 EP 835 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200035 ER PT J AU Sparks, SE Lalor, M Orvisky, E Huizing, M Krasnewich, D Sun, MS Dalakas, M Gahl, WA AF Sparks, SE Lalor, M Orvisky, E Huizing, M Krasnewich, D Sun, MS Dalakas, M Gahl, WA TI Hereditary inclusion body myopathy; Epimerase activity, GNE mutations and treatment strategies SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NIH, NIMH, Neurogenet Sect, Bethesda, MD USA. NIH, Natl Inst Neurol & Stroke, Neuromuscular Dis Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 57 BP 841 EP 841 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200060 ER PT J AU Hanover, JA Hennessey, PT Love, DC Krause, MW AF Hanover, JA Hennessey, PT Love, DC Krause, MW TI Altered nuclear pore glycosylation in Caenorhabditis elegans lacking O-linked-N-acetylglucosaminyltransferase SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 109 BP 855 EP 855 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200112 ER PT J AU Boeggeman, E Ramakrishnan, B Qasba, PK AF Boeggeman, E Ramakrishnan, B Qasba, PK TI Mutation Met344His in bovine beta 1,4-Galactosyltransferase-1 broadens its primary metal ion specificity SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 NCI Frederick, CCR, LECB, Struct Glycobiol Sect, Frederick, MD USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 162 BP 869 EP 869 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200164 ER PT J AU Ramakrishnan, B Boeggeman, E Qasba, P AF Ramakrishnan, B Boeggeman, E Qasba, P TI Rational design of beta 1,4-Galactosyltransferase-I with high glucosyltransferase activity SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 NCI Frederick, CCR, LECB, Structural Glycobiol Section, Frederick, MD USA. SAIC Frederick Inc, IRSP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 170 BP 871 EP 871 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200172 ER PT J AU Saksena, R Ma, XQ Hoehn, G Kovac, P AF Saksena, R Ma, XQ Hoehn, G Kovac, P TI Controlled conjugation of synthetic Vibrio cholerae O : 1 antigens yields series of immunogens with predetermined carbohydrate-protein ratios SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 Ciphergen Biosyst Inc, Fremont, CA USA. NIH, LMC, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 203 BP 879 EP 879 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200203 ER PT J AU Huizing, M Rakocevic, G Sparks, S Gahl, W Dalakas, M Krasnewich, D AF Huizing, M Rakocevic, G Sparks, S Gahl, W Dalakas, M Krasnewich, D TI Incomplete glycosylation of alpha-dystroglycan in hereditary inclusion body myopathy SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NIH, Nat Inst Neurol & Stroke, Neuromuscular Dis Section, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 293 BP 903 EP 903 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200293 ER PT J AU Hawk, ET Viner, JL AF Hawk, ET Viner, JL TI Aspirin: still learning about the wonder drug SO GUT LA English DT Editorial Material ID ABERRANT CRYPT FOCI; PREVENT COLORECTAL ADENOMAS; RANDOMIZED-TRIAL; CANCER; COLON; RATS AB Aspirin, taken daily over at least one year, may exert chemopreventive effects against the early stages of colorectal carcinogenesis. C1 NCI, Gastrointestinal & Other Canc Res Grp, Div Canc Prevent, EPN, Bethesda, MD 20892 USA. RP Hawk, ET (reprint author), NCI, Gastrointestinal & Other Canc Res Grp, Div Canc Prevent, EPN, Suite 2141,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 16 TC 1 Z9 1 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD NOV PY 2003 VL 52 IS 11 BP 1535 EP 1536 DI 10.1136/gut.52.11.1535 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 734RJ UT WOS:000186070800002 PM 14570718 ER PT J AU Faden, RR Dawson, L Bateman-House, AS Agnew, DM Bok, H Brock, DW Chakravarti, A Gao, XJ Greene, M Hansen, JA King, PA O'Brien, SJ Sachs, DH Schill, KE Siegel, A Solter, D Suter, SM Verfaillie, CM Walters, LB Gearhart, JD AF Faden, RR Dawson, L Bateman-House, AS Agnew, DM Bok, H Brock, DW Chakravarti, A Gao, XJ Greene, M Hansen, JA King, PA O'Brien, SJ Sachs, DH Schill, KE Siegel, A Solter, D Suter, SM Verfaillie, CM Walters, LB Gearhart, JD TI Public stem cell banks: Considerations of justice in stem cell research and therapy SO HASTINGS CENTER REPORT LA English DT Article ID TRANSPLANTATION TOLERANCE; UNRELATED MARROW; MIXED CHIMERISM; HLA-A; DIVERSITY; PROBABILITY; DONORS; PLURIPOTENCY; POLYMORPHISM; RECIPIENTS C1 Johns Hopkins Univ, Phoebe R Berman Bioeth Inst, Dept Philosophy, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dev Genet Lab, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, MckUsick Nathans Inst Genet Med, Baltimore, MD 21218 USA. NCI, Frederick, MD 21701 USA. Johns Hopkins Univ, Greenwall Fellowship Program Bioeth & Hlth Policy, Baltimore, MD 21218 USA. Georgetown Univ, Ctr Law, Washington, DC 20057 USA. Amer Genet Assoc, Buckeystown, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res ctr, Boston, MA 02129 USA. Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. Max Planck Inst Immunbiol, Dept Dev Biol, D-7800 Freiburg, Germany. George Washington Univ, Sch Law, Washington, DC 20052 USA. Univ Minnesota, Stem cell Inst, Minneapolis, MN 55455 USA. Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21218 USA. RP Faden, RR (reprint author), Johns Hopkins Univ, Phoebe R Berman Bioeth Inst, Dept Philosophy, Baltimore, MD 21218 USA. OI Verfaillie, Catherine/0000-0001-7564-4079; Bateman-House, Alison/0000-0001-6921-9666 NR 35 TC 43 Z9 44 U1 1 U2 3 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD NOV-DEC PY 2003 VL 33 IS 6 BP 13 EP 27 DI 10.2307/3527822 PG 15 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 766TC UT WOS:000188390800016 PM 14983554 ER PT J AU Milich, D Liang, TJ AF Milich, D Liang, TJ TI Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection SO HEPATOLOGY LA English DT Review ID CORE NUCLEOTIDE-SEQUENCE; CELLULAR IMMUNE-RESPONSE; PRECORE-REGION DEFECTS; FULMINANT-HEPATITIS; TRANSGENIC MICE; VIRAL REPLICATION; WILD-TYPE; INTERFERON-ALPHA; LYMPHOBLASTOID INTERFERON; ENCODED ANTIGENS AB The function of the hepatitis B e antigen (HBeAg) is largely unknown because it is not required for viral assembly, replication, or infection. In this report we chronicle clinical and experimental studies in an attempt to understand the role of HBeAg in natural infection. These studies largely have focused on clinical-pathologic features of HBeAg-negative variants in acute and chronic HBV infection, mutational analysis in animal models of hepadnavirus infection, and the use of transgenic murine models. The clinical and experimental data suggest that serum HBeAg may serve an immunoregulatory role in natural infection. To the contrary, cytosolic HBeAg serves as a target for the inflammatory immune response. These dual roles of the HBeAg and its ability to activate or tolerize T cells show the complexity of the interactions between the HBeAg and the host during HBV infection. C1 Vaccine Res Inst San Diego, San Diego, CA 92109 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. RP Milich, D (reprint author), Vaccine Res Inst San Diego, 3030 Bunker Hill St,Suite 300, San Diego, CA 92109 USA. NR 105 TC 183 Z9 205 U1 2 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2003 VL 38 IS 5 BP 1075 EP 1086 DI 10.1053/jhep.2003.50453 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EW UT WOS:000186390800001 PM 14578844 ER PT J AU Ghany, MG Kleiner, DE AF Ghany, MG Kleiner, DE TI E1 therapeutic vaccination for chronic hepatitis C: All that glitters is not gold SO HEPATOLOGY LA English DT Editorial Material ID INTERFERON-ALPHA THERAPY; HEPATOCELLULAR-CARCINOMA; HISTOLOGIC IMPROVEMENT; SUSTAINED RESPONSE; VIRUS-INFECTION; LIVER FIBROSIS; PLUS RIBAVIRIN; FOLLOW-UP; PROGRESSION; INTEROBSERVER C1 NIDDK, LDS, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDK, LDS, NIH, Bldg 10,Room 9B-06,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 NR 28 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2003 VL 38 IS 5 BP 1092 EP 1094 DI 10.1053/jhep.2003.50499 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EW UT WOS:000186390800004 PM 14578847 ER PT J AU LeRoith, D AF LeRoith, D TI Emerging concepts in the role of IGFs and cancer SO HORMONE AND METABOLIC RESEARCH LA English DT Editorial Material C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10,Room 8 S235A, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV-DEC PY 2003 VL 35 IS 11-12 BP 649 EP 650 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761UB UT WOS:000187932900001 ER PT J AU Jackson-Booth, PG Terry, C Lackey, B Lopaczynska, M Nissley, P AF Jackson-Booth, PG Terry, C Lackey, B Lopaczynska, M Nissley, P TI Inhibition of the biologic response to insulin-like growth factor I in MCF-7 breast cancer cells by a new monoclonal antibody to the insulin-like growth factor-I receptor. The importance of receptor down-regulation SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE colon cancer cells; Akt; MAPK ID DOMINANT-NEGATIVE MUTANT; EWINGS-SARCOMA CELLS; IGF-I; ATHYMIC MICE; TRANSFORMED PHENOTYPE; CARCINOMA-CELLS; MELANOMA-CELLS; ANTISENSE RNA; LUNG-CANCER; TUMOR-CELLS AB We developed a mouse monoclonal antibody (4G11) against insulin-like growth factor I receptor by immunizing mice with mouse embryo fibroblasts overexpressing the human insulin-like growth factor-I receptor. Not only did the 4G11 antibody inhibit the binding of [I-125]insulin-like growth factor-I to the fibroblast receptor, but 4G11 antibody also potently down-regulated the insulin-like growth factor-I receptor. 4G11 Fab fragment inhibited ligand binding, but did not down-regulate the receptor, suggesting that receptor aggregation is required for down-regulation. 4611 antibody also down-regulated the receptor in MCF-7 breast cancer cells, a panel of colon cancer cells and MG-63 osteosarcoma cells. Receptor recovery in MCF-7 cells after down-regulation by 4G11 antibody was slow, requiring 32-48 h for full recovery. Receptor down-regulation in MCF-7 cells by 4G11 antibody was confirmed by FRCS analysis of intact and permeabilized cells. In contrast to 4G11 antibody, insulin-like growth factor-1 did not down-regulate the receptor in MCF-7 cells. Down-regulation of the receptor by 4G11 antibody in MCF-7 cells resulted in inhibition of Akt and MAPK activation by insulin-like growth factor-I. We conclude that the ability of a monoclonal antibody to down-regulate the receptor may be an important antibody property in targeting the insulin-like growth factor-I receptor for the treatment of certain cancers. C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nissley, P (reprint author), NCI, Metab Branch, Canc Res Ctr, NIH, Bldg 10,Rm 4N115, Bethesda, MD 20892 USA. EM spniss@mail.nih.gov NR 41 TC 19 Z9 19 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV-DEC PY 2003 VL 35 IS 11-12 BP 850 EP 856 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761UB UT WOS:000187932900028 PM 14710368 ER PT J AU Kok, MR Yamano, S Lodde, BM Wang, JH Couwenhoven, RI Yakar, S Voutetakis, A Leroith, D Schmidt, M Afione, S Pillemer, SR Tsutsui, MT Tak, PP Chiorini, JA Baum, BJ AF Kok, MR Yamano, S Lodde, BM Wang, JH Couwenhoven, RI Yakar, S Voutetakis, A Leroith, D Schmidt, M Afione, S Pillemer, SR Tsutsui, MT Tak, PP Chiorini, JA Baum, BJ TI Local adeno-associated virus-mediated interleukin 10 gene transfer has disease-modifying effects in a murine model of Sjogren's syndrome SO HUMAN GENE THERAPY LA English DT Article ID NONOBESE DIABETIC MICE; RAT SUBMANDIBULAR GLANDS; SALIVARY-GLANDS; NOD MICE; IN-VIVO; SYSTEMIC DELIVERY; GROWTH-HORMONE; PLASMID DNA; AUTOIMMUNE-DISEASES; ENDOCRINE SECRETION AB Female nonobese diabetic (NOD) mice develop spontaneous autoimmune sialadenitis and loss of salivary flow, and are a widely used model of Sjogren's syndrome. We examined the feasibility of local salivary gland immunomodulatory gene delivery to alter these sequelae in NOD mice. We constructed recombinant adeno-associated virus (rAAV) vectors encoding either human interleukin 10 (rAAVhIL-10) or beta-galactosidase (rAAVLacZ, control vector). Mice received rAAVhIL-10 or rAAVLacZ by retrograde submandibular ductal instillation either at age 8 weeks (early, before onset of sialadenitis), or at 16 weeks (late, after onset of sialadenitis). As a systemic treatment control, separate mice received intramuscular delivery of rAAVhIL-10 at each time point. Both submandibular and intramuscular delivery of vector led to low circulating levels of hIL-10. After submandibular administration of rAAVhIL-10, salivary flow rates at 20 weeks for both the early and late treatment groups were significantly higher than for both rAAVLacZ-administered and untreated mice. Systemic delivery of rAAVhIL-10 led to improved salivary flow in the late treatment group. Inflammatory infiltrates in submandibular glands, however, were significantly reduced only in mice receiving rAAVhIL-10 locally in the salivary gland compared with mice receiving this vector intramuscularly, or rAAVLacZ or no treatment. In addition, after submandibular rAAVhIL-10 delivery, NOD mice exhibited significantly lower blood glucose, and higher serum insulin, levels than all other groups, indicating some systemic benefit of this treatment. These studies show that expression of hIL-10 by rAAV vectors can have disease-modifying effects in the salivary glands of NOD mice, and suggest that local immunomodulatory gene transfer may be useful for managing the salivary gland pathology in Sjogren's syndrome. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1100 DD Amsterdam, Netherlands. Univ Maryland, Sch Dent, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, 10 Ctr Dr,MSC 1190,Bldg 10,Room 1N113, Bethesda, MD 20892 USA. OI Yamano, Seiichi/0000-0003-2056-4359 NR 63 TC 68 Z9 76 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2003 VL 14 IS 17 BP 1605 EP 1618 DI 10.1089/104303403322542257 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 742MX UT WOS:000186522600003 PM 14633403 ER PT J AU Lotery, AJ Yang, GS Mullins, RF Russell, SR Schmidt, M Stone, EM Lindbloom, JD Chiorini, JA Kotin, RM Davidson, BL AF Lotery, AJ Yang, GS Mullins, RF Russell, SR Schmidt, M Stone, EM Lindbloom, JD Chiorini, JA Kotin, RM Davidson, BL TI Adeno-associated virus type 5: Transduction efficiency and cell-type specificity in the primate retina SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; TRANSGENE EXPRESSION; NONHUMAN PRIMATE; MONKEY RETINA; VIRUS TYPE-5; DEGENERATION; DELIVERY; THERAPY; VECTORS; GENOME AB Gene transfer using adeno-associated viruses (AAVs) has been effective for treating inherited retinal diseases in animal models. Further evaluation in primates must be performed prior to clinical application, however, because of the difference between the retina of the primate and those of other animals. Prior work has shown that AAV2 can transduce rod-photoreceptor and RPE cells in the non-human primate retina and that AAV5 is more efficient at transducing photoreceptor cells than AAV2 in the rodent retina. In this study, we evaluated the efficiency of AAV5 in the non-human primate retina after subretinal injections of the vector to distinct anatomic retinal regions (superior, inferior, nasal, macula, temporal). rAAV5 led to a rapid onset of transgene expression (within 2 weeks), with expression persisting up to 10 months. Postoperative electrophysiology studies showed that global retinal function was preserved following gene transfer. Quantitative analysis of gene transfer demonstrated a maximum transduction efficiency of 22% in the injected areas. Evaluation of cell types using confocal microscopy and cone-specific antibodies revealed that AAV5, expressing reporter genes from the cytomegalovirus (CMV) promoter/enhancer, preferentially transduced rods. No significant differences were found in the regional tropism of AAV5 among the five areas injected despite variation in retinal topography. Immunohistochemical studies revealed that the AAV5 receptor, PDGFR-A, is localized to the outer segments of rods but not cones providing a basis for the observed tropism. Our results support the utility of AAV5 for rod photoreceptor degeneration therapies. C1 Roy J & Lucille A Carver Coll Med, Dept Ophthalmol, Iowa City, IA 52242 USA. Roy J & Lucille A Carver Coll Med, Dept Otolaryngol, Iowa City, IA 52242 USA. Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. Roy J & Lucille A Carver Coll Med, Dept Neurol, Iowa City, IA 52242 USA. Roy J & Lucille A Carver Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA. Roy J & Lucille A Carver Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA. NIDCR, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. RP Davidson, BL (reprint author), Univ Iowa, 200 EMRB, Iowa City, IA 52242 USA. RI kotin, robert/B-8954-2008 FU NICHD NIH HHS [HD33531]; NIDDK NIH HHS [DK54759] NR 27 TC 61 Z9 64 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2003 VL 14 IS 17 BP 1663 EP 1671 DI 10.1089/104303403322542301 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 742MX UT WOS:000186522600008 PM 14633408 ER PT J AU Wang, J Slunt, H Gonzales, V Fromholt, D Coonfield, M Copeland, NG Jenkins, NA Borchelt, DR AF Wang, J Slunt, H Gonzales, V Fromholt, D Coonfield, M Copeland, NG Jenkins, NA Borchelt, DR TI Copper-binding-site-null SOD1 causes ALS in transgenic mice: aggregates of non-native SOD1 delineate a common feature SO HUMAN MOLECULAR GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN-SUPEROXIDE-DISMUTASE; MOLECULAR-WEIGHT COMPLEXES; MOTOR-NEURON DEGENERATION; HEAT-SHOCK PROTEINS; WILD-TYPE; IN-VITRO; CU,ZN-SUPEROXIDE DISMUTASE; NEUROFIBRILLARY TANGLES; ALZHEIMERS-DISEASE AB Cu/Zn superoxide dismutase (SOD1), a crucial cellular antioxidant, can in certain settings mediate toxic chemistry through its Cu cofactor. Whether this latter property explains why mutations in SOD1 cause FALS has been debated. Here, we demonstrate motor neuron disease in transgenic mice expressing a SOD1 variant that mutates the four histidine residues that coordinately bind Cu. In-depth analyses of this new mouse model, previously characterized models and FALS human tissues revealed that the accumulation of detergent-insoluble forms of SOD1 is a common feature of the disease. These insoluble species include full-length SOD1 proteins, peptide fragments, stable oligomers and ubiquitinated entities. Moreover, chaperones Hsp25 and alphaB-crystallin specifically co-fractionated with insoluble SOD1. In cultured cells, all 11 of the FALS variants tested produced insoluble forms of mutant SOD1. Importantly, expression of recombinant peptide fragments of wild-type SOD1 in cultured cells also produced insoluble species, suggesting that SOD1 possesses elements with an intrinsic propensity to aggregate. Thus, modifications to the protein, such as FALS mutations, fragmentation and possibly covalent modification, may simply act to augment a natural, but potentially toxic, propensity to aggregate. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Borchelt, DR (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 720 Rutland Ave,Room 558, Baltimore, MD 21205 USA. FU NINDS NIH HHS [R01 NS037225] NR 62 TC 193 Z9 194 U1 1 U2 10 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 NOV 1 PY 2003 VL 12 IS 21 BP 2753 EP 2764 DI 10.1093/hmg/ddg312 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 738WH UT WOS:000186310500003 PM 12966034 ER PT J AU Lin, T Sandusky, SB Xue, HP Fishbein, KW Spencer, RG Rao, MS Francomano, CA AF Lin, T Sandusky, SB Xue, HP Fishbein, KW Spencer, RG Rao, MS Francomano, CA TI A central nervous system specific mouse model for thanatophoric dysplasia type II SO HUMAN MOLECULAR GENETICS LA English DT Article ID GROWTH-FACTOR RECEPTOR-3; EXPRESSION; DIFFERENTIATION; OLIGODENDROCYTE; FGFR3; MUTATIONS; GENE AB To investigate the specific effect of the Fgfr3 K644E mutation on central nervous system (CNS) development, we have generated tissue-specific TDII mice by crossing Fgfr3(+/K644E-neo) transgenic mice with CNS-specific Nestin-cre or cartilage-specific Col2a1-cre mice. TDII/Nestin-cre (TDII-N) neonates did not demonstrate a profound skeletal phenotype. TDII-N pups were comparable to their wild-type littermates in terms of tail length, fore and hindlimbs, and body weight; however, many pups exhibited notably round heads. MRI and histochemical analysis illustrated asymmetric changes in cortical thickness and cerebellar abnormalities in TDII-N mice, which correlate with brain abnormalities observed in human TDII patients. Such abnormalities were not seen in TDII/Col2a1-cre (TDII-C) mice. Upon examination of adult TDII-N spinal cord, premature differentiation of oligodendrocyte progenitors was observed. Overall, these data indicate that the tissue-specific mouse model is an excellent system for studying the role of Fgfr3 in the developing CNS. C1 NIA, Genet Lab, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. NIA, Clin Invest Lab, Nucl Magnet Resonance Unit, Baltimore, MD 21224 USA. RP Francomano, CA (reprint author), NIA, Genet Lab, 333 Cassell Dr, Baltimore, MD 21224 USA. OI Fishbein, Kenneth/0000-0002-6353-4603 NR 25 TC 10 Z9 12 U1 1 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 NOV 1 PY 2003 VL 12 IS 21 BP 2863 EP 2871 DI 10.1093/hmg/ddg309 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 738WH UT WOS:000186310500014 PM 12966031 ER PT J AU Jaakson, K Zernant, J Kulm, M Hutchinson, A Tonisson, N Glavac, D Ravnik-Glavac, M Hawlina, M Meltzer, MR Caruso, RC Testa, F Maugeri, A Hoyng, CB Gouras, P Simonelli, F Lewis, RA Lupski, JR Cremers, FPM Allikmets, R AF Jaakson, K Zernant, J Kulm, M Hutchinson, A Tonisson, N Glavac, D Ravnik-Glavac, M Hawlina, M Meltzer, MR Caruso, RC Testa, F Maugeri, A Hoyng, CB Gouras, P Simonelli, F Lewis, RA Lupski, JR Cremers, FPM Allikmets, R TI Genotyping microarray (gene chip) for the ABCR (ABCA4) gene SO HUMAN MUTATION LA English DT Article DE genotyping; microarray; ABCR; ABCA4; Stargardt disease; STGD1; mutation detection; mutation screening ID RECESSIVE RETINITIS-PIGMENTOSA; ARRAYED PRIMER EXTENSION; CONE-ROD DYSTROPHY; STARGARDT-DISEASE; MACULAR DEGENERATION; TRANSPORTER GENE; SEQUENCE VARIATION; MUTATION DETECTION; ALLELIC VARIATION; CYSTIC-FIBROSIS AB Genetic variation in the AB CR (ABCA4) gene has been associated with five distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone,rod dystrophy (CRD), and age,related macular degeneration (AMD). Comparative genetic analyses of ABCR variation and diagnostics have been complicated by substantial allelic heterogeneity and by differences in screening methods. To overcome these limitations, we designed A genotyping microarray (gene chip) for ABCR that includes all similar to400 disease-associated and other variants currently described, enabling simultaneous detection of all known ABCR variants. The ABCR genotyping microarray (the ABCR400 chip) was constructed by the arrayed primer extension (APEX) technology. Each sequence change in ABCR was included on the chip by synthesis and application of sequence-specific oligonucleotides. We validated the chip by screening 136 confirmed STGD patients and 96 healthy controls, each of whom we had analyzed previously by single strand conformation polymorphism (SSCP) technology and/or wheteroduplex analysis. The microarray was >98% effective in determining the existing genetic variation and was comparable to direct sequencing in that it yielded many sequence changes undetected by SSCP In STGD patient cohorts, the efficiency of the array to detect disease associated alleles was between 54% and 78%, depending on the ethnic composition and degree of clinical and molecular characterization of a cohort. In addition, chip analysis suggested a high carrier frequency (up to 1:10) of ABCR variants in the general population. The ABCR genotyping microarray is a robust, cost-effective, and comprehensive screening tool for variation in one gene in which mutations are responsible for a substantial fraction of retinal disease. The ABCR chip is a prototype for the next generation of screening and diagnostic tools in ophthalmic genetics, bridging clinical and scientific research. (C) 2003 Wiley-Liss, Inc. C1 Columbia Univ, Dept Ophthalmol, Eye Res Inst, New York, NY 10032 USA. Asper Biotech, Tartu, Estonia. Columbia Univ, Dept Pathol, New York, NY USA. Fac Med Ljubljana, Mol Genet Lab, Inst Pathol, Ljubljana, Slovenia. Fac Med Ljubljana, Inst Biochem, Ljubljana, Slovenia. Univ Ljubljana, Eye Clin, Med Ctr, Ljubljana, Slovenia. NEI, Ophthalm Genet & Visual Funct Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Naples 2, Eye Clin, Naples, Italy. Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands. Univ Nijmegen, Dept Ophthalmol, Med Ctr, Nijmegen, Netherlands. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Allikmets, R (reprint author), Columbia Univ, Dept Ophthalmol, Eye Res Inst, Rm 715,630 W 168th St, New York, NY 10032 USA. RI Testa, Francesco/J-3185-2012; Tonisson, Neeme/H-2783-2015; Hoyng, C.B./H-8050-2014; Cremers, Frans/A-5625-2014; OI Testa, Francesco/0000-0002-1482-1577 FU NEI NIH HHS [EY13255, EY13435] NR 31 TC 155 Z9 160 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD NOV PY 2003 VL 22 IS 5 BP 395 EP 403 DI 10.1002/humu.10263 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 738QJ UT WOS:000186299100007 PM 14517951 ER PT J AU Basso, O Baird, DD AF Basso, O Baird, DD TI Infertility and preterm delivery, birthweight, and Caesarean section: a study within the Danish National Birth Cohort SO HUMAN REPRODUCTION LA English DT Article DE birthweight; Caesarean section; infertility; preterm delivery; time to pregnancy ID SINGLETON PREGNANCIES; CHLAMYDIA-TRACHOMATIS; TIME; ASSOCIATION; INFECTION; RISK; SUBFERTILITY; PREDICTION; SOLVENTS; IVF AB Background: More than 10% of babies are born to couples taking >1 year to conceive (a common definition of infertility). Some evidence indicates that such pregnancies are at increased risk of preterm delivery and other adverse birth outcomes, but the problem has rarely been addressed in large, longitudinal studies enrolling couples irrespective of infertility treatment. Methods: We used data from the Danish National Birth Cohort: 55 906 singleton live births from women who reported their waiting time to pregnancy (TTP) and other covariates in an interview during the 2nd trimester of pregnancy. Results: A TTP >1 year was associated with an increased risk of all outcomes studied, including preterm birth [odds ratios and 95% confidence intervals were 1.5 (1.2, 1.8) among primiparas and 1.9 (1.5, 2.4) among multiparas]. Odds ratios for preterm remained elevated after adjustment for covariates. Among couples with a TTP >1 year, infertility treatment was associated with added risk only among multiparas. Conclusion: Infertile women are at higher risk of adverse birth outcomes even if they conceive without treatment. With >10% of babies born to infertile couples, it is important to consider this group as potentially high risk when providing prenatal care. C1 Aarhus Univ, Dept Epidemiol & Social Med, Danish Epidemiol Sci Ctr, DK-8000 Aarhus C, Denmark. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Basso, O (reprint author), Aarhus Univ, Dept Epidemiol & Social Med, Danish Epidemiol Sci Ctr, Bldg 260,Vennelyst Blvd 6, DK-8000 Aarhus C, Denmark. RI Basso, Olga/E-5384-2010; OI Basso, Olga/0000-0001-9298-4921; Baird, Donna/0000-0002-5544-2653 NR 31 TC 142 Z9 142 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 2003 VL 18 IS 11 BP 2478 EP 2484 DI 10.1093/humrep/deg444 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 741FF UT WOS:000186447500040 PM 14585905 ER PT J AU Zhao, CX Wang, PH Xiao, X Chao, J Chao, L Wang, DW Zeldin, DC AF Zhao, CX Wang, PH Xiao, X Chao, J Chao, L Wang, DW Zeldin, DC TI Gene therapy with human tissue kallikrein reduces hypertension and hyperinsulinemia in fructose-induced hypertensive rats SO HYPERTENSION LA English DT Article DE kinins; diabetes mellitus; hypertension, renal; endothelin; receptors, endothelin; angiotensin II ID DELIVERY ATTENUATES HYPERTENSION; HIGH BLOOD-PRESSURE; INSULIN-RESISTANCE; CARDIAC-HYPERTROPHY; RENAL KALLIKREIN; OVEREXPRESSION; EXCRETION; REDUCTION; RECEPTOR; SYSTEM AB This study investigates gene therapy with human tissue kallikrein as a treatment for fructose-induced hypertension in rats. Hypertension was induced by addition of 10% fructose to drinking water. Fructose-fed rats also had increased serum insulin and triglycerides, decreased urine osmolarity, increased urine volume and endothelin-1, and increased aortic endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 mRNA levels. Fructose-induced hypertensive and control rats were injected intravenously with a construct containing the human tissue kallikrein cDNA. Two weeks after injection of hypertensive rats, systolic blood pressure and serum insulin levels normalized, urine osmolarity increased, urine endothelin-1 levels decreased, and aortic endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 mRNA levels decreased. In contrast, injection of the human tissue kallikrein cDNA had minimal effect on blood pressure or insulin levels in control rats. These results suggest that gene therapy with human tissue kallikrein may have potential as a treatment for hypertension and associated insulin resistance. Moreover, our data suggest that the beneficial effects of human tissue kallikrein on these parameters are associated with changes in endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 expression. C1 Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Div Cardiovasc, Wuhan 430030, Peoples R China. Huazhong Univ Sci & Technol, Tongji Med Coll, Gene Therapy Ctr, Tongji Hosp, Wuhan 430030, Peoples R China. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Div Cardiovasc, Wuhan 430030, Peoples R China. NR 32 TC 36 Z9 47 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2003 VL 42 IS 5 BP 1026 EP 1033 DI 10.1161/01.HYP.0000097603.55404.35 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 740JJ UT WOS:000186399000028 PM 14568997 ER PT J AU Rohde, GK Aldroubi, A Dawant, BM AF Rohde, GK Aldroubi, A Dawant, BM TI The adaptive bases algorithm for intensity-based nonrigid image registration SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article; Proceedings Paper CT Medical Imaging 2002 Conference CY FEB 24-28, 2002 CL SAN DIEGO, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE adaptive bases algorithm; mutual information; nonrigid image registration ID MR-IMAGES; ALIGNMENT AB Nonrigid registration of medical images is important for a number of applications such as the creation of population averages, atlas-based segmentation, or geometric correction of functional magnetic resonance imaging (fMRI) images to name a few. In recent years, a number of methods have been proposed to solve this problem, one class of which involves maximizing a mutual information (MI)-based objective function over a regular grid of splines. This approach has produced good results but its computational complexity is proportional to the compliance of the transformation required to register the smallest structures in the image. Here, we propose a method that permits the spatial adaptation of the transformation's compliance. This spatial adaptation allows us to reduce the number of degrees of freedom in the overall transformation, thus speeding up the process and improving its convergence properties. To develop this method, we introduce several novelties: 1) we rely on radially symmetric basis functions rather than B-splines traditionally used to model the deformation field; 2) we propose a metric to identify regions that are poorly registered and over which the transformation needs to be improved; 3) we partition the global registration problem into several smaller ones; and 4) we introduce a new constraint scheme that allows us to produce transformations that are topologically correct. We compare the approach we propose to more traditional ones and show that our new algorithm compares favorably to those in current use. C1 Vanderbilt Univ, Dept Elect Engn & Comp Sci, Nashville, TN 37235 USA. NICHD, STBB, LIMB, NIH, Bethesda, MD 20872 USA. Univ Maryland, Sci Computat Program, College Pk, MD 02792 USA. Vanderbilt Univ, Dept Math, Nashville, TN 37235 USA. RP Vanderbilt Univ, Dept Elect Engn & Comp Sci, 221 Kirkland Hall, Nashville, TN 37235 USA. EM rohdeg@helix.nih.gov; benoit.dawant@vanderbilt.edu RI Aldroubi, Akram/J-7186-2012 NR 26 TC 256 Z9 258 U1 1 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD NOV PY 2003 VL 22 IS 11 BP 1470 EP 1479 DI 10.1109/TMI.2003.819299 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 738KQ UT WOS:000186286200013 PM 14606680 ER PT J AU Schwartzberg, PL AF Schwartzberg, PL TI Amplifying Btk's signal SO IMMUNITY LA English DT Editorial Material ID BRUTONS TYROSINE KINASE; CELL ANTIGEN RECEPTOR; TEC FAMILY KINASES; ACTIVATION C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 13 TC 14 Z9 14 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2003 VL 19 IS 5 BP 634 EP 636 DI 10.1016/S1074-7613(03)00304-2 PG 3 WC Immunology SC Immunology GA 745CY UT WOS:000186672200002 PM 14614849 ER PT J AU Zhu, JF Cote-Sierra, J Guo, LY Paul, WE AF Zhu, JF Cote-Sierra, J Guo, LY Paul, WE TI Stat5 activation plays a critical role in Th2 differentiation SO IMMUNITY LA English DT Article ID CYTOKINE GENE-EXPRESSION; PERIPHERAL T-CELLS; IN-VIVO; TRANSCRIPTION FACTOR; IL-4 PRODUCTION; COORDINATE REGULATOR; LINEAGE COMMITMENT; MAST-CELLS; GATA-3; RECEPTOR AB Upon TCR engagement, naive CD4 T cells differentiate toward the Th1 or Th2 phenotype. IL-4, acting through Stat6, plays a major role in Th2 differentiation; IL-2 has also been reported to be essential. Here, we report that retroviral (RV)-mediated expression of a constitutively active Stat5A mutant (STAT5A1*6) can fully restore IL-4 production when naive CD4 T cells are primed in the absence of IL-2. Furthermore, STAT5A1*6 expression causes Th2 differentiation in the absence of IL-4 or in Stat6- or IL-4Ralpha-deficient cells. Infection with STAT5A1*6-NGFR-RV does not enhance GATA-3 expression. STAT5A1*6-NGFR-RV and GATA-3-GFP-RV each render the II4 gene accessible, but the sites of restriction enzyme accessibility are different. Stat5A binds to HSII and HSIII sites of the II4 gene. Coinfection with STAT5A1*6-NGFR-RV and GATA-3-GFP-RV results in optimal Th2 priming. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Zhu, Jinfang/B-7574-2012 NR 42 TC 167 Z9 171 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2003 VL 19 IS 5 BP 739 EP 748 DI 10.1016/S1074-7613(03)00292-9 PG 10 WC Immunology SC Immunology GA 745CY UT WOS:000186672200013 PM 14614860 ER PT J AU McPherson, SW Yang, J Chan, CC Dou, CZ Gregerson, DS AF McPherson, SW Yang, J Chan, CC Dou, CZ Gregerson, DS TI Resting CD8 T cells recognize beta-galactosidase expressed in the immune-privileged retina and mediate autoimmune disease when activated SO IMMUNOLOGY LA English DT Article ID II-POSITIVE CELLS; DENDRITIC CELLS; POSTERIOR SEGMENT; SUBRETINAL SPACE; GENE-EXPRESSION; IN-VIVO; ANTIGEN; UVEORETINITIS; MEMORY; APOPTOSIS AB Although the expression of class II major histocompatibility complex (MHC) in retina is extremely low, it is an established fact that activated CD4 T cells, specific for retinal antigens (Ags), mediate experimental autoimmune uveoretinitis (EAU). Conversely, CD8 T cells have not been shown to recognize Ag in the retina. This study investigated whether retinal-specific Ags are detected by class I MHC-restricted CD8 T cells. Using a CD8 T-cell clone (beta3) specific for an immunodominant epitope of beta-galactosidase (beta-gal), local Ag recognition was shown by transfer of activated beta3 cells into beta-gal transgenic (Tg) mice expressing beta-gal in the retina (hi-arr-beta-gal mice), or in the brain and eye (GFAP-beta-gal mice). beta-gal-positive photoreceptor cells were damaged in the retina of hi-arr-beta-gal mice, and anterior segment disease was found in the eyes of GFAP-beta-gal mice. Ag recognition by resting CD8 T cells was also evaluated. Recovery of 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CFSE)-labelled beta3 cells from hi-arr-beta-gal mice was slightly decreased compared to recovery from B10.A mice, while recovery from GFAP-beta-gal mice was transiently increased. Conversely, recovery of CFSE- cells increased in hi-arr-beta-gal mice, consistent with an Ag-dependent response. The CFSE content of the CFSE+ population was unchanged relative to beta3 cells recovered from controls. Intracellular cytokine responses of beta3 cells recovered from hi-arr-beta-gal and GFAP-beta-gal mice correlated with the number of cells recovered, regardless of CFSE content. Even though their production of interferon-gamma and tumour necrosis factor-alpha was affected little by transfer into hi-arr-beta-gal recipients, the ability of beta3 cells to mediate delayed-type hypersesitivity was inhibited in hi-arr-beta-gal mice. These results show that resting CD8 T cells are affected by the presence of Ag that originates in retina and, when activated prior to transfer, mediate pathogenic autoimmunity against retinal and other ocular targets. C1 Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Gregerson, DS (reprint author), Univ Minnesota, Dept Ophthalmol, 2001 6th St SE, Minneapolis, MN 55455 USA. FU NEI NIH HHS [R01 EY011542, EY11542] NR 45 TC 22 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 2003 VL 110 IS 3 BP 386 EP 396 DI 10.1046/j.1365-2567.2003.01750.x PG 11 WC Immunology SC Immunology GA 736KP UT WOS:000186170200014 PM 14632667 ER PT J AU Bhamarapravati, S Pendland, SL Mahady, GB AF Bhamarapravati, S Pendland, SL Mahady, GB TI Extracts of spice and food plants from Thai traditional medicine inhibit the growth of the human carcinogen Helicobacter pylori SO IN VIVO LA English DT Article DE Helicobacter pylori; peptic ulcer; Thailand; traditional medicine; plant extracts ID MYRISTICA-FRAGRANS; CANCER STATISTICS; INFECTION; HOUTT; MACE AB Background: Helicobacter pylori (HP) is a gram-negative bacterium and well recognized as being the primary etiological agent responsible for the development of gastritis, dyspepsia, peptic ulcer disease and gastric cancer. In developing countries, a high prevalence of HP infection is associated with an increased incidence of gastric cancer. Thailand, however, while having a high prevalence of HP infections, has a lower than expected gastric cancer rate than other developing countries. It has been suggested that the diet and life style in Thailand may explain this discrepancy. Materials and Methods: The in vitro susceptibility of 18 strains of HP to 20 extracts of spice and food plants used in Thai traditional medicine for the treatment of GI disorders was assessed. Results: Methanol extracts of Myristica fragrans (aril) inhibited the growth of all HP strains with minimum inhibitory concentration (MIC) of 12.5 mug/ml; extracts from Barringtonia acutangula (leaf) and Kaempferia galanga (rhizome) had an MIC of 25.0 mug/ml; Cassia grandis (leaf), Cleome viscosa (leaf), Myristica fragrans (leaf) and Syzygium aromaticum (leaf) had MICs of 50.0 mug/ml. Extracts with an MIC of 100.0 mug/ml included Pouzolzia pentandra (leaf), Cycas siamensis (leaf), Litsea elliptica (leaf) and Melaleuca quinquenervia (leaf). Conclusion: Plants used in Thai traditional medicine to treat gastrointestinal ailments inhibit the growth of HP. These data indicate that these plants may have chemopreventative activities and thus may partly explain the reduced incidence of gastric cancer in Thailand. C1 Univ Illinois, Dept Pharm Practice, Chicago, IL 60612 USA. Univ Illinois, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. Mahidol Univ, Fac Sci, Dept Plant Sci, Bangkok 10400, Thailand. RP Mahady, GB (reprint author), Univ Illinois, Coll Pharm, NIH,Collaborating Ctr Tradit Med, Ctr Bot Dietary Supplements Res,PAHO,WHO, 833 S Wood St,MC 877, Chicago, IL 60612 USA. FU NCCIH NIH HHS [AT00412, R21 AT000412-01] NR 23 TC 24 Z9 28 U1 2 U2 5 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 2003 VL 17 IS 6 BP 541 EP 544 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 766CJ UT WOS:000188327600004 PM 14758718 ER PT J AU Russo, TA Davidson, BA Topolnycky, DM Olson, R Morrill, SA Knight, PR Murphy, PM AF Russo, TA Davidson, BA Topolnycky, DM Olson, R Morrill, SA Knight, PR Murphy, PM TI Human neutrophil chemotaxis is modulated by capsule and O antigen from an extraintestinal pathogenic Escherichia coli strain SO INFECTION AND IMMUNITY LA English DT Article ID HOSPITAL-ACQUIRED PNEUMONIA; NOSOCOMIAL INFECTIONS; IN-VIVO; ISOLATE; POLYSACCHARIDE; LIPOPOLYSACCHARIDE; IDENTIFICATION; MICROBIOLOGY; PREVENTION; COMPONENT AB Gram-negative enteric bacilli, such as Escherichia coli, are common causes of nosocomial pneumonia. The interaction between pulmonary neutrophils and the infecting pathogen is a critical step in determining the outcome. Previous studies from our laboratory, for which a rat model of pneumonia was used, established that pulmonary neutrophil recruitment was modulated by the E. coli virulence factors capsule and O-specific antigen. To begin to understand the mechanism by which this recruitment occurs, we conducted in vitro and ex vivo chemotaxis assays, for which we used a clinically relevant E. coli isolate (CP9) and isogenic derivatives that were deficient in only the O antigen (CP921) or capsule (CP9.137) as chemoattractants with or without the high-affinity N-formylmethionyl-leucyl-phenylalanine receptor antagonist N-tert-butoxycarbonyl-methionine-leucine-phenylalanine (N-t-BOC). Given that only live E. coli was used for the initial in vitro chemotaxis assays, it was predicted that only N-t-BOC-sensitive chemotaxis would occur. However, both N-t-BOC-sensitive and -insensitive chemotaxis was observed. N-t-BOC-insensitive chemotaxis was mediated in part by interleukin 8, which was produced by neutrophils that had migrated toward E. coli. N-t-BOC-insensitive chemotaxis was only observed when live E. coli bacteria, not cell-free E. coli culture supernatants, were used as chemoattractants, suggesting that a direct E. coli-neutrophil interaction was necessary. The presence of both capsule and O antigen diminished total, N-t-BOC-sensitive, and N-t-BOC-insensitive neutrophil chemotaxis in vitro. The presence of capsule significantly decreased total, N-t-BOC-sensitive, and N-t-BOC-insensitive neutrophil chemotaxis ex vivo when cell-free bronchoalveolar lavage fluid from infected rats was used as the source of chemotactic factors. These effects of E. coli capsule and O antigen on neutrophil chemotaxis are novel, and they expand our understanding of the mechanisms by which these virulence traits contribute to the pathogenesis of gram-negative pneumonia and other extraintestinal infections. C1 Vet Adm Western New York Healthcare Syst, Dept Med, Buffalo, NY 14214 USA. Vet Adm Western New York Healthcare Syst, Dept Microbiol, Buffalo, NY 14214 USA. Vet Adm Western New York Healthcare Syst, Witebsky Ctr Microbial Pathogenesis, Buffalo, NY 14214 USA. SUNY Buffalo, Dept Anesthesiol, Buffalo, NY 14214 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Russo, TA (reprint author), Div Infect Dis, Dept Med, 3435 Main St,Biomed Res Bldg,Room 141, Buffalo, NY 14214 USA. FU NHLBI NIH HHS [HL48889, HL69763, R01 HL048889, R01 HL069763]; NIAID NIH HHS [AI46534, R01 AI046534] NR 30 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2003 VL 71 IS 11 BP 6435 EP 6445 DI 10.1128/IAI.71.11.6435-6445.2003 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 736VR UT WOS:000186194300041 PM 14573665 ER PT J AU Gil-Lamaignere, C Roilides, E Lyman, CA Simitsopoulou, M Stergiopoulou, T Maloukou, A Walsh, TJ AF Gil-Lamaignere, C Roilides, E Lyman, CA Simitsopoulou, M Stergiopoulou, T Maloukou, A Walsh, TJ TI Human phagocytic cell responses to Scedosporium apiospermum (Pseudallescheria boydii): Variable susceptibility to oxidative injury SO INFECTION AND IMMUNITY LA English DT Article ID ASPERGILLUS-FUMIGATUS HYPHAE; COLONY-STIMULATING FACTOR; IN-VITRO ACTIVITIES; CANDIDA-ALBICANS; AMPHOTERICIN-B; PNEUMOCYSTIS-CARINII; ANTIFUNGAL ACTIVITY; FILAMENTOUS FUNGI; HUMAN-NEUTROPHILS; MANNOSE RECEPTOR AB Scedosporium apiospermurn (Pseudallescheria boydii) is an emerging opportunistic filamentous fungus that causes serious infections in both immunocompetent and immunocompromised patients. To gain insight into the immunopathogenesis of infections due to S. apiospermum, the antifungal activities of human polymorphonuclear leukocytes (PMNs), mononuclear leukocytes (MNCs), and monocyte-derived macrophages (MDMs) against two clinical isolates of S. apiospermum were evaluated. Isolate SA54A was amphotericin B resistant and was the cause of a fatal disseminated infection. Isolate SA1216 (cultured from a successfully treated localized subcutaneous infection) was susceptible to amphotericin B. MDMs exhibited similar phagocytic activities against conidia of both isolates. However, PMNs and MNCs responded differently to the hyphae of these two isolates. Serum opsonization of hyphae resulted in a higher-level of superoxide anion (O-2(-)) release by PMNs in response to SA54A (amphotericin B resistant) than that seen in response to SA1216 (amphotericin B susceptible; P < 0.001). Despite this increased O-2(-) production, PMNs and MNCs induced less hyphal damage to SA54A than to SA1216 (P < 0.001). To investigate the potential mechanisms responsible for these differences, hyphal damage was evaluated in the presence of antifungal oxidative metabolites as well as in the presence of a series of inhibitors and scavengers of antifungal PMN function. Mannose, catalase, superoxide dismutase, dimethyl sulfoxide, and heparin had no effect on PMN-induced hyphal damage to either of the two isolates. However, azide, which inhibits PMN myeloperoxidase activity, significantly reduced hyphal damage to SA1216 (P < 0.01) but not to SA54A. Hyphae of SA1216 were slightly more susceptible to oxidative pathway products, particularly HOCl, than those of SA54A. Thus, S. apiospermum is susceptible to antifungal phagocytic function to various degrees. The selective inhibitory pattern of azide with respect to hyphal damage and the parallel susceptibility to HOCl suggests an important difference in susceptibilities to myeloperoxidase products that may be related to the various levels of pathogenicity and amphotericin B resistance of S. apiospermum. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Pediat Dept 3, Thessaloniki 54642, Greece. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. RI Gil-Lamaignere, Cristina/A-3866-2013 NR 45 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2003 VL 71 IS 11 BP 6472 EP 6478 DI 10.1128/IAI.71.11.6472-6478.2003 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 736VR UT WOS:000186194300045 PM 14573669 ER PT J AU Pomerantsev, AP Kalnin, KV Osorio, M Leppla, SH AF Pomerantsev, AP Kalnin, KV Osorio, M Leppla, SH TI Phosphatidylcholine-specific phospholipase C and sphingomyelinase activities in bacteria of the Bacillus cereus group SO INFECTION AND IMMUNITY LA English DT Article ID NUCLEOTIDE-SEQUENCE; PLCR REGULON; GENE-EXPRESSION; ANTHRACIS; THURINGIENSIS; VIRULENCE; TOXIN; TRANSCRIPTION; PLASMID; IDENTIFICATION AB Bacillus anthracis is nonhemolytic, even though it is closely related to the highly hemolytic Bacillus cereus. Hemolysis by B. cereus results largely from the action of phosphatidyleholine-specific phospholipase C (PC-PLC) and sphingomyelinase (SPH), encoded by the plc and sph genes, respectively. In B. cereus, these genes are organized in an operon regulated by the global regulator PlcR. B. anthracis contains a highly similar cereolysin operon, but it is transcriptionally silent because the B. anthracis PlcR is truncated at the C terminus. Here we report the cloning, expression, purification, and enzymatic characterization of PC-PLC and SPH from B. cereus and B. anthracis. We also investigated the effects of expressing PlcR on the expression of plc and sph. In B. cereus, PlcR was found to be a positive regulator of plc but a negative regulator of sph. Replacement of the B. cereus plcR gene by its truncated orthologue from B. anthracis eliminated the activities of both PC-PLC and SPH, whereas introduction into B. anthracis of the B. cereus plcR gene with its own promoter did not activate cereolysin expression. Hemolytic activity was detected in B. anthracis strains containing the B. cereus plcR gene on a multicopy plasmid under control of the strong B. anthracis protective antigen gene promoter or in a strain carrying a multicopy plasmid containing the entire B. cereus plc-sph operon. Slight hemolysis and PC-PLC activation were found when PlcR-producing B. anthracis strains were grown under anaerobic-plus-CO2 or especially under aerobic-plus-CO2 conditions. Unmodified parental B. anthracis strains did not demonstrate obvious hemolysis under the same conditions. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. NR 45 TC 42 Z9 42 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2003 VL 71 IS 11 BP 6591 EP 6606 DI 10.1128/IAI.71.11.6591-6606.2003 PG 16 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 736VR UT WOS:000186194300057 PM 14573681 ER PT J AU Punareewattana, K Sharova, LV Li, W Ward, DL Holladay, SD AF Punareewattana, K Sharova, LV Li, W Ward, DL Holladay, SD TI Reduced birth defects caused by maternal immune stimulation may involve increased expression of growth promoting genes and cytokine GM-CSF in the spleen of diabetic ICR mice SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE diabetes; diabetic embryopathy; immune stimulation; teratogenesis; birth defects; CFA; GM-CSF; IFN-gamma ID MURINE MACROPHAGES; ARACHIDONIC-ACID; MOUSE EMBRYOS; TGF-BETA; APOPTOSIS; UTERUS; PREVENTION; CELLS; PROSTAGLANDINS; MALFORMATIONS AB Maternal immune stimulation in mice decreases fetal abnormalities caused by diverse etiologies. Growth factors produced by activated immune cells were proposed to be key mediators that may exert their effects on placenta or embryo. Diabetes disrupts the secretion of cytokines, which may associate with diabetic embryopathy. Three different methods of maternal immune stimulation that result in approximately equal reduction of diabetic embryopathy were used in the present studies: footpad injection with complete Freund's adjuvant (CFA), intraperitoneal (i.p.) injection with granulocyte-macrophage colony-stimulating factor (GM-CSF), or i.p. injection with interferon-gamma (IFN-gamma). A gene microarray was then used to examine expression of a selected gene panel in splenic leukocytes. We hypothesized that maternal immune stimulation may act by overcoming altered gene expression patterns of immune cells in the diabetic mice, which partially mitigates the teratogenic effect of diabetes. It further seemed likely that a shared profile of splenic gene expression changes induced by the different immune stimulation procedures may be identified and related to reduced teratogenesis. The three procedures produced a common altered gene expression profile. Significantly affected genes included apoptotic and anti-apoptotic genes, and genes controlling cellular proliferation, and likely reflect a state of immune activation. The GM-CSF gene was up-regulated by all three immune stimulation procedures. The protein product of this gene regulates placental development, and was recently associated with reduced cleft palate in immune-stimulated pregnant mice after exposure to urethane. These data suggest that further studies of GM-CSF as mediator of reduced birth defects in teratogen-challenged, immune-stimulated mice are warranted. (C) 2003 Elsevier B.V. All rights reserved. C1 Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathol, Blacksburg, VA 24061 USA. NIA, Genet Lab, Baltimore, MD 21224 USA. Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Off Res & Grad Studies, Blacksburg, VA 24061 USA. RP Holladay, SD (reprint author), Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathol, Phase 2,Southgate Dr, Blacksburg, VA 24061 USA. NR 48 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD NOV PY 2003 VL 3 IS 12 BP 1639 EP 1655 DI 10.1016/S1567-5769(03)00200-5 PG 17 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 738LA UT WOS:000186287800009 PM 14555289 ER PT J AU Player, A Gillespie, J Fujii, T Fukuoka, J Dracheva, T Meerzaman, D Hong, KM Curran, J Attoh, G Travis, W Jen, J AF Player, A Gillespie, J Fujii, T Fukuoka, J Dracheva, T Meerzaman, D Hong, KM Curran, J Attoh, G Travis, W Jen, J TI Identification of TDE2 gene and its expression in non-small cell lung cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE non-small cell lung cancer; TDE1; TDE2; Tms1; Tms2; serial analysis of gene expression (SAGE); in situ hybridization ID HIGH-FREQUENCY; TUMOR; ADENOCARCINOMA; CARCINOMAS; LOCUS; 1P AB TDE2, a gene with sequence similarity to the mouse testicular tumor-differentially-expressed (Tde1/MUSTETU) gene, was identified by serial analysis of gene expression (SAGE) in nonsmall cell lung cancers (NSCLC). Here we characterized the TDE2 gene and determined its transcript levels in a panel of lung tumors, adjacent nonmalignant lung tissues and a variety of normal human tissues. In addition, we show that TDE2 is a potential transmembrane protein with 11 putative trans- membrane helices. Using real-time quantitative PCR, we showed that TDE2 transcript levels were higher in NSCLC compared to nonmalignant samples. In nonpulmonary normal tissues, the level of TDE2 was the highest in bladder, kidney and muscle; moderate to low in stomach, liver, skin, placenta and ovary tissues; and undetectable in brain, spleen and heart. By in situ hybridization, we showed that 10 of 18 lung tumors and only 1 of 14 adjacent nonmalignant regions had high levels of TDE2 transcripts. Alternatively, only 2 of 18 tumors and 8 of 14 adjacent nonmalignant bronchiole epithelium regions demonstrated negative to low levels of TDE2 signals. (C) 2003 Wiley-Liss, Inc. C1 NCI, Canc Res Ctr, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pathol Lab, Pathogenet Unit, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Bethesda, MD USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. RP Jen, J (reprint author), NCI, Canc Res Ctr, Lab Populat Genet, NIH, 41 Lib Dr,Bldg 41 Room D702, Bethesda, MD 20892 USA. RI Fujii, Takeshi/D-5877-2014 OI Fujii, Takeshi/0000-0001-7237-1183 NR 21 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2003 VL 107 IS 2 BP 238 EP 243 DI 10.1002/ijc.11391 PG 6 WC Oncology SC Oncology GA 723CY UT WOS:000185415900011 PM 12949800 ER PT J AU Dahlgren, L Mellin, H Wangsa, D Heselmeyer-Haddad, K Bjornestal, L Lindholm, J Munck-Wkland, E Auer, G Ried, T Dalianis, T AF Dahlgren, L Mellin, H Wangsa, D Heselmeyer-Haddad, K Bjornestal, L Lindholm, J Munck-Wkland, E Auer, G Ried, T Dalianis, T TI Comparative genomic hybridization analysis of tonsillar cancer reveals a different pattern of genomic imbalances in human papillomavirus-positive and -negative tumors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human papillomavirus; tonsillar cancer; comparative genomic hybridization; chromosome 3q ID SQUAMOUS-CELL CARCINOMA; NECK-CANCER; CHROMOSOMAL-ABERRATIONS; E6 ONCOPROTEIN; GENE-PRODUCT; SOLID TUMORS; HPV DNA; HEAD; TYPE-16; ASSOCIATION AB Our aim was to map and compare genomic imbalances in human papillomavirus (HPV)-positive and -negative squamous cell carcinomas of the tonsil. Twenty-five primary carcinomas were analyzed by comparative genomic hybridization. Fifteen (60%) were found to be HPV-positive by PCR, and the majority were HPV-16. There were statistically Significant differences in the distribution of DNA gains and losses between the HPV-positive and -negative samples. Eleven of 15 HPV-positive samples (73%) showed gain on chromosome 3q24-qter, while only 4/10 (40%) HPV-negative samples had the same gain (p = 0.049). Furthermore, 4/10 (40%) HPV-negative samples but no HPV-positive samples had gain on chromosome 7q11.2-q22 (p = 0.017). As ex- pected, and similar to previous studies, patients with an HPV-positive tumor had a statistically significantly better disease-specific survival than patients with an HPV-negative tumor (p = 0.002). The most common changes, e.g., gain on 3q or 8q, loss on 11q or 13 and loss on chromosome 7q in HPV-negative tumors, did not have any influence on prognosis. However the number of cases in each subgroup was limited. (C) 2003 Wiley-Liss, Inc. C1 Karolinska Hosp, Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, SE-17176 Stockholm, Sweden. NCI, Ctr Canc Res, Genet Branch, NIH, Bethesda, MD 20892 USA. Karolinska Hosp, Karolinska Inst, Dept Otorhinolaryngol Head & Neck Surg, SE-17176 Stockholm, Sweden. RP Dahlgren, L (reprint author), Karolinska Hosp, Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, R8-01, SE-17176 Stockholm, Sweden. NR 37 TC 68 Z9 69 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2003 VL 107 IS 2 BP 244 EP 249 DI 10.1002/ijc.11371 PG 6 WC Oncology SC Oncology GA 723CY UT WOS:000185415900012 PM 12949801 ER PT J AU Madigan, MP Gao, YT Deng, J Pfeiffer, RM Chang, BL Zheng, SQ Meyers, DA Stanczyk, FZ Xu, JF Hsing, AW AF Madigan, MP Gao, YT Deng, J Pfeiffer, RM Chang, BL Zheng, SQ Meyers, DA Stanczyk, FZ Xu, JF Hsing, AW TI Cyp17 polymorphisms in relation to risks of prostate cancer and benign prostatic hyperplasia: A population-based study in China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE prostate cancer; benign prostatic hyperplasia; CYP17; genetic polymorphism; androgen; China ID GENE POLYMORPHISM; RECEPTOR GENE; SRD5A2 GENES; INSULIN; ASSOCIATION; METABOLISM AB Because androgens likely play a key role in prostate growth and prostate cancer development, variants of genes involved in androgen biosynthesis may be related to prostate cancer risk. The enzyme P450c17alpha encoded by the CYP17 gene, catalyzes the conversion of progesterone and pregnenolone into precursors of potent androgens. In the S' promoter region of the CYP17 gene, a T (A1 allele) to C substitution (A2 allele) has been hypothesized to increase CYP17 gene expression, resulting in higher levels of androgens. To investigate a possible role of CYP17 in prostate diseases, we evaluated the risk of prostate cancer and benign prostatic hyperplasia (BPH) in relation to variation in CYP17 genotype in a population-based case-control study conducted in Shanghai, China. The study included 174 prostate cancer cases, 182 BPH cases and 274 population controls. We observed no statistically significant overall associations of CYP17 genotypes with prostate cancer risk, although associations of the A1/A1 (odds ratio (OR) = 1.42, 95% confidence interval (CI) 0.83-2.48) and A1/A2 (OR 1.41, 95% Cl 0.91-2.17) genotypes with prostate cancer were suggested. A similar association of the A1/A1 genotype with BPH was suggested. We found no associations of CYP17 genotypes with serum sex hormone levels or other biomarkers after correction for multiple comparisons. Large population-based studies are needed to clarify whether CYP17 plays a role in prostate cancer risk and whether genotype effects vary in different racial/ethnic and other subgroups. (C) 2003 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Shanghai Canc Inst, Shanghai, Peoples R China. Wake Forest Univ, Ctr Human Genome, Winston Salem, NC 27109 USA. Univ So Calif, Sch Med, Dept Obstet & Gynecol & Prevent Med, Los Angeles, CA 90089 USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS MSC 7234,6120 Execut Blvd, Rockville, MD 20852 USA. RI Pfeiffer, Ruth /F-4748-2011 NR 30 TC 39 Z9 42 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2003 VL 107 IS 2 BP 271 EP 275 DI 10.1002/ijc.11378 PG 5 WC Oncology SC Oncology GA 723CY UT WOS:000185415900017 PM 12949806 ER PT J AU Pedeux, R Boniol, M Dore, JF Beauchesne, P AF Pedeux, R Boniol, M Dore, JF Beauchesne, P TI Ultrafractionation radiation therapy of human gliomas: A preclinical model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter ID CELL-LINES C1 Ctr Leon Berard, INSERM, Unite U453, F-69373 Lyon, France. Univ St Etienne, Ctr Hosp, Serv Neurochirurg, St Etienne, France. RP Pedeux, R (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37,37 Convent Dr,Room 3054, Bethesda, MD 20892 USA. RI Boniol, Mathieu/F-9623-2011 OI Boniol, Mathieu/0000-0003-1052-5604 NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2003 VL 107 IS 2 BP 334 EP 334 DI 10.1002/ijc.11368 PG 1 WC Oncology SC Oncology GA 723CY UT WOS:000185415900030 ER PT J AU Stevens, EV Liotta, LA Kohn, EC AF Stevens, EV Liotta, LA Kohn, EC TI Proteomic analysis for early detection of ovarian cancer: A realistic approach? SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE biomarker; mass spectroscopy; ovarian cancer; proteomic ID GENE-EXPRESSION PATTERNS; CLINICAL PROTEOMICS; TOPOISOMERASE-I; CELL-LINES; MICROARRAY; CA-125; SERUM; KEYNOTE; DISEASE; RISK AB Ovarian cancer is a multifaceted disease wherein most women are diagnosed with advanced stage disease. One of the most imperative issues in ovarian cancer is early detection. Biomarkers that allow cancer detection at stage 1, a time when the disease is amenable to surgical and chemotherapeutic cure in over 90% of patients, can dramatically alter the horizon for women with this disease. Recent developments in mass spectroscopy and protein chip technology coupled with bioinformatics have been applied to biomarker discovery. The complexity of the proteome is a rich resource from which the patterns can be gleaned; the pattern rather than its component parts is the diagnostic. Serum is a key source of putative protein biomarkers, and, by its nature, can reflect organ-confined events. Pioneering use of mass spectroscopy coupled with bioinformatics has been demonstrated as being capable of distinguishing serum protein pattern signatures of ovarian cancer in patients with early- and late-stage disease. This is a sensitive, precise, and promising tool for which further validation is needed to confirm that ovarian cancer serum protein signature patterns can be a robust biomarker approach for ovarian cancer diagnosis, yielding improved patient outcome and reducing the death and suffering from ovarian cancer. C1 NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), 10 Ctr Dr MSC 1500,Bldg 10,Room B1B51, Bethesda, MD 20892 USA. NR 35 TC 30 Z9 33 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV-DEC PY 2003 VL 13 SU 2 BP 133 EP 139 DI 10.1111/j.1525-1438.2003.13358.x PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 758ZG UT WOS:000187712100001 PM 14656269 ER PT J AU Franchini, G Fukumoto, R Fullen, JR AF Franchini, G Fukumoto, R Fullen, JR TI T-Cell control by human T-Cell leukemia/lymphoma virus type 1 SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Review DE human T-cell leukemia/lymphoma virus type 1; T-cells; adult T-cell leukemia/lymphoma ID NF-KAPPA-B; HTLV-I TAX; TROPICAL SPASTIC PARAPARESIS; BLOOD MONONUCLEAR-CELLS; LEUKEMIA-LYMPHOMA VIRUS; RECEPTOR GENE-EXPRESSION; CYCLIN-DEPENDENT KINASES; OPEN READING FRAMES; GROWTH-FACTOR-BETA; GENOMIC HYBRIDIZATION ANALYSIS AB Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) causes neoplastic transformation of human T-cells in a small number of infected individuals several years from infection. Collective evidence from in vitro studies indicates that several viral proteins act in concert to increase the responsiveness of T-cells to extracellular stimulation, modulate proapoptotic and antiapoptotic gene signals, enhance T-cell survival, and avoid immune recognition of the infected T-cells. The virus promotes T-cell proliferation by usurping several signaling pathways central to immune T-cell function, such as antigen stimulation and receptor-ligand interaction, suggesting that extracellular signals are important for HTLV-1 oncogenesis. Environmental factors such as chronic antigen stimulation may therefore be of importance, as also suggested by epidemiological data. Thus genetic and environmental factors together with the virus contribute to disease development. This review focuses on current knowledge of the mechanisms regulating HTLV-1 replication and the T-cell pathways that are usurped by viral proteins to induce and maintain clonal proliferation of infected T-cells. The relevance of these laboratory findings is related to clonal T-cell proliferation and adult T-cell leukemia/lymphoma development in vivo. (C) 2003 The Japanese Society of Hematology. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov NR 308 TC 45 Z9 46 U1 2 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD NOV PY 2003 VL 78 IS 4 BP 280 EP 296 DI 10.1007/BF02983552 PG 17 WC Hematology SC Hematology GA 805GE UT WOS:000220354000002 PM 14686485 ER PT J AU Yao, JH AF Yao, JH TI Non-rigid registration and correspondence finding in medical image analysis using multiple-layer flexible mesh template matching SO INTERNATIONAL JOURNAL OF PATTERN RECOGNITION AND ARTIFICIAL INTELLIGENCE LA English DT Article DE non-rigid registration; statistical model; multiple-layer flexible mesh template; correspondence ID MODELS AB In this paper we present a novel technique for non-rigid medical image registration and correspondence finding based on a multiple-layer flexible mesh template matching technique. A statistical anatomical model is built in the form of a tetrahedral mesh, which incorporates both shape and density properties of the anatomical structure. After the affine transformation and global deformation of the model are computed by optimizing an energy function, a multiple-layer flexible mesh template matching is applied to find the vertex correspondence and achieve local deformation. The multiple-layer structure of the template can be used to describe different scale of anatomical features; furthermore, the template matching is flexible which makes the correspondence finding robust. A leave-one-out validation has been conducted to demonstrate the effectiveness and accuracy of our method. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21210 USA. RP Yao, JH (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 37 TC 12 Z9 12 U1 0 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA JOURNAL DEPT PO BOX 128 FARRER ROAD, SINGAPORE 912805, SINGAPORE SN 0218-0014 J9 INT J PATTERN RECOGN JI Int. J. Pattern Recognit. Artif. Intell. PD NOV PY 2003 VL 17 IS 7 BP 1145 EP 1165 DI 10.1142/S0218001403002873 PG 21 WC Computer Science, Artificial Intelligence SC Computer Science GA 753GU UT WOS:000187224300006 ER PT J AU Brosschot, JF Thayer, JF AF Brosschot, JF Thayer, JF TI Heart rate response is longer after negative emotions than after positive emotions SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE heart rate reactivity; prolonged activation; heart rate recovery; emotional valence; emotional arousal; ambulatory ID SALIVARY CORTISOL; BLOOD-PRESSURE; STRESS; MOOD; REACTIVITY; RECOVERY; CONTEXT; STATES AB Recent ambulatory findings showing comparable cardiovascular effects of positive and negative emotions are not consistent with the assumed etiological role of negative affect in stress-related diseases. We tested the hypothesis that regardless of initial reactivity, responses associated with negative emotions would be prolonged compared to responses associated with positive emotions. During 8 h, 33 healthy subjects from a general population reported their emotional arousal, emotional valence and physical activity and recorded their heart rates (HR) after a beep at each 60th min ('initial HR'; TO), followed by two 'prolonged activation' recordings, respectively 5 min later (T1) and 10 min later (T2). While emotional arousal and activity predicted initial HR, prolonged activation at T1 was solely predicted by emotional valence (negative affect) at TO, independent of emotional recovery. The results lend support to the hypothesis that cardiovascular activation after negative emotions last longer than after positive emotions. This finding is consistent with the view that prolonged activation, and not so much reactivity, might be a mechanism underlying the etiological role of negative emotions ('stress') in somatic disease. Perseverative cognition (worry, rumination) might be responsible for this prolonged activation. (C) 2003 Elsevier B.V. All rights reserved. C1 Leiden Univ, Sect Clin & Hlth Psychol, NL-2300 RB Leiden, Netherlands. NIA, Baltimore, MD 21224 USA. RP Brosschot, JF (reprint author), Leiden Univ, Sect Clin & Hlth Psychol, POB 9555, NL-2300 RB Leiden, Netherlands. NR 25 TC 75 Z9 80 U1 1 U2 42 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD NOV PY 2003 VL 50 IS 3 BP 181 EP 187 DI 10.1016/S0167-8760(03)00146-6 PG 7 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 743VX UT WOS:000186595200001 PM 14585487 ER PT J AU Bisht, KS Bradbury, CM Zoberi, I Curry, HA Kaushal, A Roti, R Gius, D AF Bisht, KS Bradbury, CM Zoberi, I Curry, HA Kaushal, A Roti, R Gius, D TI Inhibition of cyclooxygenase-2 with NS-398 and the prevention of radiation-induced transformation, micronuclei formation and clonogenic cell death in C3H 10T1/2 cells SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID NF-KAPPA-B; 835.62 MHZ FDMA; INDUCED RADIOSENSITIZATION; RECOMMENDED PROTOCOLS; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; GAMMA-RADIATION; TUMOR RESPONSE; HELA-CELLS; EXPRESSION AB Purpose : Abnormally high levels of the cyclooxygenase (COX)-2 isozyme as well as the prostaglandin metabolites produced by the COX pathway have been observed in a variety of malignancies, including cancers of the skin, pancreas, colon, breast, cervix, prostate, and head and neck. Furthermore, exogenous genotoxic agents, including ionizing radiation (IR), have been shown to induce cellular transformation and to elevate COX-2 activity, whereas exposure to agents that specifically inhibit COX-2 activity have been shown to inhibit transformation. These data suggest a possible role of COX-2 both in IR-mediated cellular transformation processes and cell death. Materials and methods : C3H 10T1/2 and/or HeLa cells were treated with N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) and/or exposed to IR. Following treatment, cells were assayed for neoplastic transformation, clonogenicity, growth rates, cell cycle distribution, micronuclei formation and DNA damage by established methodologies. Statistical tests were performed on data as described. Results : In the present study, experiments in normal murine fibroblast C3H 10T1/2 cells demonstrated that the chemical inhibition of COX-2 activity with moderate doses of NS-398 abrogated IR-induced transformation events by fourfold and protected irradiated C3H 10T1/2 cells from clonogenic cell death. Considering that these doses of NS-398 had no significant effect on cellular proliferation or cell cycle distribution in C3H 10T1/2 cells, the results suggest that inhibition of COX-2 either increases DNA repair or prevents the accumulation of DNA damage. In supplemental experiments, treatment with NS-398 caused a 1.5-fold reduction in IR-induced micronuclei formation and a significant decrease in DNA damage. Conclusions : These results suggest a role for COX-2 inhibitors in the normal tissue response to IR when administered at therapeutically achievable doses and therefore may have clinical implications for radiation oncology patients in the prevention of IR-induced malignancy. C1 NCI, Mol Radiat Oncol Sect, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Radiat Oncol, Radiat & Canc Biol Div, St Louis, MO USA. RP Gius, D (reprint author), NCI, Mol Radiat Oncol Sect, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [1 K08 CA72602-01, R01 CA43198, P01 CA7556] NR 53 TC 5 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD NOV PY 2003 VL 79 IS 11 BP 879 EP 888 DI 10.1080/09553000310001621400 PG 10 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 758HR UT WOS:000187628800003 PM 14698956 ER PT J AU Langer, M Lee, EK Deasy, JO Rardin, RL Deye, JA AF Langer, M Lee, EK Deasy, JO Rardin, RL Deye, JA TI Operations research applied to radiotherapy, an NCI-NSF-sponsored workshop - February 7-9, 2002 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article C1 Indiana Univ, Med Ctr, Dept Radiat Oncol, Indianapolis, IN USA. Georgia Inst Technol, Sch Ind & Syst Engn, Atlanta, GA 30332 USA. Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA USA. Washington Univ, Dept Radiat Oncol, Sch Med, St Louis, MO USA. Washington Univ, Dept Biomed Engn, Sch Med, St Louis, MO USA. Washington Univ, Mallinckrodt Inst Radiol, Sch Med, St Louis, MO USA. Purdue Univ, Natl Sci Fdn, Purdue, IL USA. Purdue Univ, Sch Ind Engn, Purdue, IL USA. Natl Canc Inst, Radiat Res Programs, DCTD, Rockville, MD USA. RP Deye, JA (reprint author), NCI, Radiat Oncol Sci Program, Radiat Res Program, 6130 Execut Blvd,EPN-6000, Bethesda, MD 20892 USA. OI Deasy, Joseph/0000-0002-9437-266X NR 0 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2003 VL 57 IS 3 BP 762 EP 768 DI 10.1016/S0360-3016(03)00720-X PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 730GQ UT WOS:000185821200020 PM 14529782 ER PT J AU Hussain, M Vaishampayan, U Heilbrun, LK Jain, V LoRusso, PM Ivy, P Flaherty, L AF Hussain, M Vaishampayan, U Heilbrun, LK Jain, V LoRusso, PM Ivy, P Flaherty, L TI A phase II study of rebeccamycin analog (NSC-655649) in metastatic renal cell cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE rebeccamycin; renal cell carcinoma; chemotherapy ID CARCINOMA; SURVIVAL AB Objective: Rebeccamycin analog (NSC-655649) is an antibiotic with antitumor properties demonstrated in preclinical and phase I studies. We conducted a phase II trial to evaluate the efficacy and toxicity of this agent in patients with advanced renal cell cancer (RCC). Methods: Eligible patients had histologically or cytologically confirmed diagnosis of RCC that was either locally advanced unresectable, locally recurrent, or metastatic. Patients had to have measurable disease, no prior chemotherapy, life expectancy of greater than 12 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate-organ function, and be greater than or equal to18 years old. Patients were treated with NSC-655649 at a dose of 165 mg/m(2) daily i.v. over 30-60 min for 5 days. Treatment was repeated every 21 days. Response was assessed every two courses. Results: Twenty-four patients were enrolled. There were sixteen males and eight females with a median age of 60.5 years (range 42-76). Nineteen were Caucasians, seventeen had prior nephrectomy, and thirteen had prior immunotherapy. The major toxicity was myelosuppression with grade 3 and 4 neutropenia in 38% of patients and anemia in 33% of patients. There were two partial responses (2/24, 8%) and 11 patients (46%) achieved stable disease (SD). The 6-month progression-free rate for patients with SD was 30%. Of the seventeen patients with progressive disease at registration, one had a PR and eight had SD. The overall median survival time for all 24 patients was 10.0 months (90% Cl = 5.2, 17.4 months). The 12-month survival rate was 39%, with 90% Cl = (0.21, 0.58). Nine patients are still alive with survival times ranging from 3.8 to 24.2 months, at a median follow-up time of 11.9 months. Conclusion: Rebeccamycin analog (NSC-655649) is well tolerated and has modest antitumor activity in patients with advanced RCC. C1 Barbara Ann Karmanos Canc Inst, Div Hematol Oncol, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. NCI, Canc Treatment & Diag DCTD, Bethesda, MD 20892 USA. RP Hussain, M (reprint author), Univ Michigan, Ctr Canc, Div Hematol Oncol, 7314 CCGC,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 12 TC 17 Z9 17 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 2003 VL 21 IS 4 BP 465 EP 471 DI 10.1023/A:1026259503954 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 735QY UT WOS:000186127100010 PM 14586215 ER PT J AU Xu, H Silver, PB Tarrant, TK Chan, CC Caspi, RR AF Xu, H Silver, PB Tarrant, TK Chan, CC Caspi, RR TI TGF-beta inhibits activation and uveitogenicity of primary but not of fully polarized retinal antigen-specific memory-effector T cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE UVEITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; IL-12 RECEPTOR BETA-1; TRANSFORMING GROWTH-FACTOR-BETA-1; FUNCTIONAL-PROPERTIES; BINDING PROTEIN; LYMPHOCYTES-B; HELPER-CELLS; EXPRESSION AB PURPOSE. TGF-beta exerts suppressive effects on immunity, but its potential applications in therapy of ocular autoimmunity have not been widely explored. In the present study, the effects of TGF-beta on uveitogenic T cells were examined. METHODS. The effects of TGF-beta on newly primed cells from mice given a uveitogenic regimen of interphotoreceptor retinoid-binding protein (IRBP) were compared with the effects on fully polarized Th1 cells from a long-term uveitogenic T-cell line. The parameters measured were T-cell proliferation, IFN-gamma production, induction of IL-12R expression, triggering of pathogenicity, and expression of costimulatory molecules on antigen-presenting cells (APCs) during in vitro exposure to antigen. RESULTS. TGF-beta suppressed B7.1 expression on APCs in cultures of lymph node cells from immunized mice. It also suppressed T-cell proliferation, IFN-gamma production, IL-12 receptor accumulation, and the IL-12-promoted acquisition of uveitogenic function. In contrast, the polarized Th1 cells were either resistant to suppression or were enhanced by TGF-beta. CONCLUSIONS. The results suggest that TGF-beta suppresses acquisition of effector functions by autopathogenic T cells, in part by interfering with their response to IL-12 through down-regulation of IL-12R expression and in part through inhibition of APC function. The data suggest that although TGF-beta may effectively inhibit activation and recruitment of new T cells into the effector pool, it may be less effective in suppressing the reactivation of already polarized memory T cells that are less dependent on IL-12 and costimulation. C1 NEI, Lab Immunol, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Lab Immunol, NIH, Bldg 10,Rm 10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov NR 49 TC 13 Z9 13 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2003 VL 44 IS 11 BP 4805 EP 4812 DI 10.1167/iovs.02-0843 PG 8 WC Ophthalmology SC Ophthalmology GA 737LL UT WOS:000186231800029 PM 14578402 ER PT J AU Ball, LE Little, M Nowak, MW Garland, DL Crouch, RK Schey, KL AF Ball, LE Little, M Nowak, MW Garland, DL Crouch, RK Schey, KL TI Water permeability of C-terminally truncated aquaporin 0 (AQP0 1-243) observed in the aging human lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MAJOR INTRINSIC PROTEIN; XENOPUS-LAEVIS OOCYTES; NEPHROGENIC DIABETES-INSIPIDUS; HUMAN SENILE CATARACTOGENESIS; TRANSMEMBRANE PROTEIN; CONGENITAL CATARACT; POLYPEPTIDE MIP26K; RAT HEPATOCYTES; FIBER MEMBRANES; COVALENT CHANGE AB PURPOSE. To first assess the distribution of posttranslationally truncated products of aquaporin 0 (AQP0) in dissected sections of a normal human lens and to determine the effect of backbone cleavage on the water permeability of AQP0. METHODS. A 27-year-old lens was concentrically dissected into six sections. Membrane protein was isolated from each section and cleaved with cyanogen bromide, and the peptides were separated and analyzed by reverse-phase (RP)-HPLC-mass spectrometry (MS). The sites of posttranslational AQP0 C-terminal truncation were determined by mass spectrometry. Truncated forms of AQP0 were expressed in a Xenopus laevis oocyte system, and the effect of truncation on AQP0 water permeability was assessed in an oocyte osmotic swelling assay. RESULTS. The extent of truncation at many sites within the C terminus increased with fiber cell age, and the effects of truncations after residues 234, 238, and 243 on AQP0 water permeability were examined. Truncation after residue 243 resulted in an approximate 15% decrease in permeability compared with the full-length protein, AQP0 1-263. However, rather than a direct effect on water transport, analysis of surface protein expression indicated that the decrease in permeability was a result of less efficient protein trafficking to the oocyte surface and that the permeabilities of full-length and 1-243 AQP0 were indistinguishable. Further, C-terminal truncation of AQP0 to 1-234 and 1-238, completely impaired trafficking into the plasma membrane, precluding the measurement of permeability. CONCLUSIONS. These data provide evidence that loss of 20 amino acids from the C terminus may not directly affect the ability of AQP0 to transport water. C1 Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. NEI, NIH, Bethesda, MD USA. RP Schey, KL (reprint author), Med Univ S Carolina, Dept Pharmacol, Basic Sci Bldg, 171 Ashley ave, Charleston, SC 29425 USA. EM scheykl@musc.edu OI Nowak, Mark/0000-0001-5097-2682; Ball, Lauren/0000-0001-6780-1679 FU NEI NIH HHS [EY13462] NR 70 TC 45 Z9 46 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2003 VL 44 IS 11 BP 4820 EP 4828 DI 10.1167/iovs.02-1317 PG 9 WC Ophthalmology SC Ophthalmology GA 737LL UT WOS:000186231800031 PM 14578404 ER PT J AU Wang-Su, ST McCormack, AL Yang, SJ Hossler, MR Mixon, A Riviere, MA Wilmarth, PA Andley, UP Garland, D Li, H David, LL Wagner, BJ AF Wang-Su, ST McCormack, AL Yang, SJ Hossler, MR Mixon, A Riviere, MA Wilmarth, PA Andley, UP Garland, D Li, H David, LL Wagner, BJ TI Proteome analysis of lens epithelia, fibers, and the HLE B-3 cell line SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; MAJOR SOLUBLE-PROTEINS; ALDEHYDE DEHYDROGENASE; ALPHA-CRYSTALLIN; STRUCTURAL PROTEIN; MOUSE LENS; RAT LENS; C-MYC; EXPRESSION; ENOLASE AB PURPOSE. The purpose of this study is to compare the protein composition of the B-3 line of transformed human lens epithelial (HLE) cells to that of freshly dissected HLE cells. This provides baseline data on lens cell proteins from fresh lens cells and from the B-3 cell line, which is often used as a model system for the lens. METHODS. Human lens epithelial cells adherent to the lens capsule were dissected into central (undifferentiated) and peripheral (partially differentiated) populations. Fully differentiated human lens fiber cells were isolated from the outer cortical layers of the lens. HLE B-3 cells were analyzed at several passage levels. Extracts were prepared from each cell type and the proteins resolved by two-dimensional polyacrylamide gel electrophoresis (2-DE). Representative gel patterns were visually compared, spots excised, and trypsin digests prepared. The peptide compositions of the digests were analyzed using either liquid chromatography electrospray ionization tandem mass spectrometry or atmospheric pressure-matrix-assisted laser desorption ionization mass spectrometry, using a liquid chromatography classic ion trap (LCQ) mass spectrometer. RESULTS. Two-DE patterns were obtained for fresh and cultured cell types. Similar patterns were observed between central and peripheral HLE cells, both of which contained high levels of alphaA-, alphaB-, and betaB2-crystallins; alpha-enolase; and aldehyde dehydrogenase. HLE B-3 cultured cells were characterized by a marked loss of crystallins and a relatively higher level of noncrystallin proteins-most notably, high molecular weight, acidic proteins. Whereas subunit d of adenosine triphosphate (ATP) synthase, alphaB-crystallin, galectin, glyceraldehyde-3-phosphate dehydrogenase, a-enolase, actin, peptidylprolyl isomerase A, phosphatidylethanolamine-binding protein, and vimentin were present in both fresh and cultured lens epithelium, only the high abundance of alpha-enolase, galectin-1, and vimentin suggested that B-3 cells were lens derived. CONCLUSIONS. Freshly dissected noncultured HLE cells from both central and peripheral regions contain a high concentration of crystallins that mask the detection of less abundant proteins by 2-DE. Transformation and culture of HLE cells causes a loss of these crystallins and an increase in the relative concentration of other proteins. However, most of these noncrystallin proteins were different from those observed in noncultured HLE cells. These results suggest that transformation markedly alters the protein expression pattern in immortalized HLE cells and that caution should be exercised when using them to study properties of HLE cells in vivo. C1 UMDNJ NJ Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07101 USA. UMDNJ NJ Med Sch, Dept Ophthalmol, Newark, NJ 07101 USA. UMDNJ NJ Med Sch, Grad Sch Biol Sci, Newark, NJ 07101 USA. Oregon Hlth & Sci Univ, Det Integrat Biosci, Portland, OR USA. Washington Univ, Sch Med, Dept Ophthalmol, St Louis, MO 63110 USA. NEI, NIH, Bethesda, MD USA. RP Wagner, BJ (reprint author), UMDNJ NJ Med Sch, Dept Biochem & Mol Biol, 158 S Orange Ave,POB 1709, Newark, NJ 07101 USA. EM wagner@umdnj.edu FU NEI NIH HHS [EY02299, EY07755, EY10572, EY12016] NR 49 TC 38 Z9 42 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2003 VL 44 IS 11 BP 4829 EP 4836 DI 10.1167/iovs.03-0556 PG 8 WC Ophthalmology SC Ophthalmology GA 737LL UT WOS:000186231800032 PM 14578405 ER PT J AU Espinosa-Heidmann, DG Caicedo, A Hernandez, EP Csaky, KG Cousins, SW AF Espinosa-Heidmann, DG Caicedo, A Hernandez, EP Csaky, KG Cousins, SW TI Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID POSTNATAL NEOVASCULARIZATION; RETINAL NEOVASCULARIZATION; MACULAR DEGENERATION; STEM-CELL; ANGIOGENESIS; AGE; SEVERITY AB PURPOSE. The pathogenesis of choroidal neovascularization (CNV) is postulated to be driven by angiogenesis, a process in which the cellular components of the new vessel complex are derived from cells resident within an adjacent preexisting capillary. Recently, an alternative paradigm, termed postnatal vasculogenesis, has been shown to contribute to some forms of neovascularization. In vasculogenesis,the cellular components of the new vessel complex are derived from circulating vascular progenitors from bone marrow. In the current study, transplantation of green fluorescent protein (GFP)-labeled bone marrow and laser-induced CNV were combined to examine the contribution of vasculogenesis to the formation of CNV. METHODS. Ten adult C57BL/6 female mice were used as recipients for bone marrow transplantation. Bone marrow was obtained from three C57BL/6 female mice transgenic for the beta-actin promoter GFP. One month after bone marrow transplantation, CNV was induced in recipient mice by making four separate bums in the choroid of each eye with a red diode laser. Four weeks after CNV was induced, eyes of recipient mice were processed for immunohistochemistry to detect GFP and markers for vascular smooth muscle cells (alpha-smooth muscle actin, desmin, and NG2 chondroitin sulfate proteoglycan), endothelial cells (CD31, BS-1 lectin), or macrophages (F4/80). RESULTS. GFP-labeled cells represented 17% of the total cell population in the lesion. Many of the GFP-labeled cells were immunoreactive for alpha-smooth muscle actin (39%), desmin, NG2, CD31 (41%), BS-1 lectin, or F4/80. GFP-labeled cells were morphologically indistinguishable from cells, normally present in CNV lesions. CONCLUSIONS. This study is the first to demonstrate that bone marrow-derived progenitor cells are a source of endothelial and smooth musclelike cells in CNV. C1 Univ Miami, Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL USA. NEI, NIH, Bethesda, MD USA. RP Cousins, SW (reprint author), Bascom Palmer Eye Inst, William L McKnight Vis Res Ctr, 1638 NW 10th Ave, Miami, FL 33136 USA. EM scousins@miami.med.edu RI Caicedo, Alejandro/F-1202-2010 FU NEI NIH HHS [EY/AI 13318]; NIDCD NIH HHS [DC04525-01] NR 18 TC 95 Z9 109 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2003 VL 44 IS 11 BP 4914 EP 4919 DI 10.1167/iovs.03-0371 PG 6 WC Ophthalmology SC Ophthalmology GA 737LL UT WOS:000186231800044 PM 14578417 ER PT J AU Lu, AC Jones, EC Chow, C Miller, KD Herpin, B Rock-Kress, D Metcalf, JA Lane, HC Kovacs, JA AF Lu, AC Jones, EC Chow, C Miller, KD Herpin, B Rock-Kress, D Metcalf, JA Lane, HC Kovacs, JA TI Increases in CD4+ T lymphocytes occur without increases in thymic size in HIV-Infected subjects receiving interleukin-2 therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4+ T lymphocytes; computed tomography; x-ray; longitudinal studies; interleukin-2; immunotherapy; thymus gland ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERMITTENT INTERLEUKIN-2; POSITIVE PATIENTS; RANDOMIZED TRIAL; CELLS; IMMUNOTHERAPY; EXPANSION AB Objective: To examine the potential contribution of the thymus to CD4(+) T-lymphocyte increases in HIV-infected patients receiving intermittent interleukin-2 (IL-2) therapy. Design: Fifteen HIV-infected patients treated with antiretroviral regimens who were enrolled in a study of intermittent IL-2 therapy and were willing to undergo serial thymic computed tomography (CT) were prospectively studied. Methods: Thymic CT was performed before and -6 and 12-17 months after intermittent IL-2 therapy was started. Scans were graded in a blinded manner. Changes in lymphocyte subpopulations were determined by flow cytometry. Results: Statistically significant increases in CD4(+) T lymphocytes occurred with IL-2 administration, with a preferential increase in naive relative to memory CD4(+) T cells. Despite this increase in naive CD4(+) T cells, overall there was a modest decrease in thymic volume observed during the study period. No correlation was found between changes in thymic volume indices and total, naive, or memory CD4(+) T-lymphocyte counts. Conclusions: These findings demonstrate that the profound CD4(+) T-lymphocyte increases seen with intermittent IL-2 administration are not associated with increases in thymic volume and more likely are due to peripheral expansion rather than increased thymic output. C1 NIAID, NIH, Crit Care Med Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIAID, NIH, Diagnost Radiol Dept, Bethesda, MD 20892 USA. NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIAID, NIH, Crit Care Med Dept, Warren G Magnuson Clin Ctr, Bldg 10,Room 7D43,MSC 1662, Bethesda, MD 20892 USA. NR 14 TC 7 Z9 7 U1 0 U2 1 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 NOV 1 PY 2003 VL 34 IS 3 BP 299 EP 303 DI 10.1097/00126334-200311010-00007 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 740YW UT WOS:000186431700007 PM 14600575 ER PT J AU Fowler, MG Mofenson, L McConnell, M AF Fowler, MG Mofenson, L McConnell, M TI The interface of perinatal HIV prevention, antiretroviral drug resistance, and antiretroviral treatment - What so we really know? SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; MATERNAL-INFANT TRANSMISSION; VERTICAL TRANSMISSION; PREGNANT-WOMEN; REVERSE-TRANSCRIPTASE; ZIDOVUDINE RESISTANCE; NEVIRAPINE; TYPE-1; THERAPY; MUTATIONS C1 Ctr Dis Control & Prevent, Epidemiol Branch, Div HIV AIDS Prevent, Atlanta, GA USA. Ctr Dis Control & Prevent, Global Programme AIDS, Prevent Branch, Atlanta, GA USA. NICHHD, Ctr Res Mothers & Children, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD USA. RP Fowler, MG (reprint author), Ctr Dis Control & Prevent, Epidemiol Branch, Div HIV AIDS Prevent, Atlanta, GA USA. NR 37 TC 12 Z9 12 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 NOV 1 PY 2003 VL 34 IS 3 BP 308 EP 311 DI 10.1097/00126334-200311010-00009 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 740YW UT WOS:000186431700009 PM 14600577 ER PT J AU Segal, ZV Pearson, JL Thase, ME AF Segal, ZV Pearson, JL Thase, ME TI Challenges in preventing relapse in major depression - Report of a National Institute of Mental Health Workshop on state of the science of relapse prevention in major depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE major depressive disorder; relapse; epidemiology; pharmacological and psychological treatment; markers of relapse vulnerability; Ppevention of recurrence ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE THERAPY; PRIMARY-CARE; RECURRENT DEPRESSION; INTERPERSONAL PSYCHOTHERAPY; MAINTENANCE THERAPIES; PROSPECTIVE COMMUNITY; YOUNG-ADULTS; RISK-FACTORS; FOLLOW-UP AB On 21 and 22 May 2001, the National Institute of Mental Health convened a workshop to explore imminent scientific opportunities and encourage new research on preventing relapse in major depression, as a part of a larger effort to find treatments capable of producing durable long-term recovery from major depression. Participants considered definitional and developmental perspectives on depression relapse, the prophylactic potential of current treatments and their cost effectiveness and the neurobiological and psychological risk factors for episode return. It was recommended that the definition of the relapse construct be expanded to capture salient features of incomplete recovery or partial response to treatment that are associated with significant functional impairment. This information is often overlooked by the categorical criteria currently in use. With respect to interventions, there was support for sequencing pharmacological remission with psychological prophylaxis. Provision of focal, short-term treatments that embed relapse prevention skills augment the routes to effective prevention available to patients, beyond that afforded by continuation pharmacotherapy. The challenge will be to identify those subgroups of patients for whom each treatment algorithm is indicated. Finally, the link between basic science findings of biological and psychological markers of relapse vulnerability and treatment design needs to be strengthened. This could be accomplished by assessing patients in clinical prevention trials for the presence of, and changes in, relapse vulnerability markers, thereby providing direct, outcome-based data to gauge the protective value of different treatments that modify these markers. (C) 2002 Elsevier B.V. All rights reserved. C1 Univ Toronto, Cognit Behav Therapy Unit, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. NIMH, Rockville, MD USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. RP Segal, ZV (reprint author), Univ Toronto, Cognit Behav Therapy Unit, Ctr Addict & Mental Hlth, 250 Coll St, Toronto, ON M5T 1R8, Canada. RI Segal, Zindel/F-8008-2014 NR 61 TC 41 Z9 42 U1 2 U2 8 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 NOV PY 2003 VL 77 IS 2 BP 97 EP 108 DI 10.1016/S0165-0327(02)00112-X PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 745AM UT WOS:000186665100001 PM 14607387 ER PT J AU Shearer, WT Rosenblatt, HM Gelman, RS Oymopito, R Plaeger, S Stiehm, ER Wara, DW Douglas, SD Luzuriaga, K McFarland, EJ Yogev, R Rathore, MH Levy, W Graham, BL Spector, SA AF Shearer, WT Rosenblatt, HM Gelman, RS Oymopito, R Plaeger, S Stiehm, ER Wara, DW Douglas, SD Luzuriaga, K McFarland, EJ Yogev, R Rathore, MH Levy, W Graham, BL Spector, SA TI Lymphocyte subsets in healthy children from birth through 18 years of age: The pediatric AIDS clinical trials group P1009 study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE lymphocyte subsets; 3-colorflow cytometry; infants; children; adolescents; healthy control subjects ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED CHILDREN; PERIPHERAL-BLOOD; FLOW-CYTOMETRY; T-LYMPHOCYTES; UNINFECTED CHILDREN; REFERENCE VALUES; CELL MARKERS; WHOLE-BLOOD; SUBPOPULATIONS AB Background: Peripheral blood lymphocyte subsets need to be determined in a large, urban, minority-predominant cohort of healthy children to serve as suitable control subjects for the interpretation of the appearance of these cells in several disease conditions, notably pediatric HIV-1 infection. Objective: We sought to determine the distribution of lymphocyte subsets in healthy urban-dwelling infants, children, and adolescents in the United States. Methods: Lymphocyte subsets were determined by means of 3-color flow cytometry in a cross-sectional study of 807 HIV-unexposed children from birth through 18 years of age. Results: Cell-surface marker analysis demonstrated that age was an extremely important variable in 24 lymphocyte subset distributions measured as percentages or absolute counts-eg, the CD4 (helper) T cell, CD8 (cytotoxic) T cell, CD19 B cell, CD4CD45RACD62L (naive helper) T cell, CD3CD4CD45RO (memory helper) T cell, CD8HLA-DRCD38 (activated cytotoxic) T cell, and CD8CD28 (activation primed cytotoxic) T cell. The testing laboratory proved to be an important variable, indicating the need for using the same laboratory or group of laboratories to assay an individual's blood over time and to assay control and ill or treated populations. Sex and race-ethnicity were much less important. Conclusion: The results of this study provide a control population for assessment of the effects of HIV infection on the normal development and distribution of lymphocyte subsets in children of both sexes, all races, and all ethnic backgrounds from birth through 18 years of age in an urban population. This study's findings will also prove invaluable in interpreting the immune changes in children with many other chronic diseases, such as primary immunodeficiency, malignancy, rheumatoid arthritis, and asthma. C1 Baylor Coll Med, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NIAID, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Massachusetts, Worcester, MA 01003 USA. Univ Colorado, Ctr Hlth Sci, Denver, CO 80202 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Florida, Ctr Hlth Sci, Jacksonville, FL USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, 6621 Fannin St,MC FC330-01, Houston, TX 77030 USA. FU NCRR NIH HHS [M01 RR-00188, M01 RR-00865, M01 RR-01271, M01 RR-02240]; NIAID NIH HHS [U01 AI27541, P30 AI36211, R01 AI94029, U01 AI27551, U01 AI27559, U01 AI27750, U01 AI32907, U01 AI32921, U01 AI41089, U01 AI41110]; NICHD NIH HHS [N01 HD33162] NR 55 TC 349 Z9 362 U1 2 U2 16 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2003 VL 112 IS 5 BP 973 EP 980 DI 10.1067/mai.2003.1778 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 743BV UT WOS:000186553300022 PM 14610491 ER PT J AU Pang, ALY Taylor, HC Johnson, W Alexander, S Chen, YL Su, YA Li, XQ Ravindranath, N Dym, M Rennert, OM Chan, WY AF Pang, ALY Taylor, HC Johnson, W Alexander, S Chen, YL Su, YA Li, XQ Ravindranath, N Dym, M Rennert, OM Chan, WY TI Identification of differentially expressed genes in mouse spermatogenesis SO JOURNAL OF ANDROLOGY LA English DT Article DE type A spermatogonia; pachytene spermatocytes; round spermatids; spermatogenesis; complementary DNA microarray; quantitative polymerase chain reaction ID PROLYL OLIGOPEPTIDASE; ENDOPLASMIC-RETICULUM; X-CHROMOSOME; CELLS; PROTEIN; SPERMATOGONIA; PROFILES; TESTIS; CLONING; BAP31 AB Complementary DNA microarray and quantitative polymerase chain reaction were used as tools for discovering genes that are differentially expressed in the mouse under normal physiological conditions at distinctive stages of male germ cell development, that is, type A spermatogonia, pachytene spermatocytes, and round spermatids. By using this strategy, we identified a set of genes exhibiting differential expression patterns in spermatogenesis, suggesting that specific functions of the encoded products occurred during the developmental process. Among them were several genes previously not known to be active in testis, which signified undiscovered functional roles of these genes during spermatogenesis. Many of the genes identified were not previously characterized. This study highlights new targets for manipulation to unravel the molecular mechanism of spermatogenesis. C1 NICHHD, Sect Dev Genom, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Cell Biol, Washington, DC 20057 USA. Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. Loyola Univ, Dept Pathol, Med Ctr, Maywood, IL 60153 USA. RP Chan, WY (reprint author), NICHHD, Sect Dev Genom, Lab Clin Genom, NIH, 49 Convent Dr,Room 2A08,MSC 4429, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD36483, HD33728] NR 35 TC 34 Z9 36 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD NOV-DEC PY 2003 VL 24 IS 6 BP 899 EP 911 PG 13 WC Andrology SC Endocrinology & Metabolism GA 740LJ UT WOS:000186403600020 PM 14581517 ER PT J AU Lauretani, F Russo, CR Bandinelli, S Bartali, B Cavazzini, C Di Iorio, A Corsi, AM Rantanen, T Guralnik, JM Ferrucci, L AF Lauretani, F Russo, CR Bandinelli, S Bartali, B Cavazzini, C Di Iorio, A Corsi, AM Rantanen, T Guralnik, JM Ferrucci, L TI Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE elderly; muscle power; strength ID LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; PROTEIN-SYNTHESIS; GRIP STRENGTH; OLDER MEN; WOMEN; MASS; EPIDEMIOLOGY; RELIABILITY; PERFORMANCE AB Sarcopenia, the reduction of muscle mass and strength that occurs with aging, is widely considered one of the major causes of disability in older persons. Surprisingly, criteria that may help a clinician to identify persons with impaired muscle function are still lacking. Using data from a large representative sample of the general population, we examined how muscle function and calf muscle area change with aging and affect mobility in men and women free of neurological conditions. We tested several putative indicators of sarcopenia, including knee extension isometric torque, handgrip, lower extremity muscle power, and calf muscle area. For each indicator, sarcopenia was considered to be present when the measure was >2 SDs below the mean. For all four measures, the prevalence of sarcopenia increased with age, both in men and women. The age-associated gradient in prevalence was maximum for muscle power and minimum for calf-muscle area. However, lower extremity muscle power was no better than knee-extension torque or handgrip in the early identification of poor mobility, defined either as walking speed <0.8 m/s or inability to walk at least 1 km without difficulty and without developing symptoms. Optimal cutoff values that can be used in the clinical practice to identify older persons with poor mobility were developed. The findings of the study lay the basis for a cost-effective, clinical marker of sarcopenia based on a measure of isometric handgrip strength. Our findings should be verified in a longitudinal study. C1 Italian Natl Inst Res & Care Aging, Dept Geriatr, Lab Clin Epidemiol, I-50125 Florence, Italy. Univ Chieti, Geriatr Clin, Dept Med & Aging, I-66013 Chieti, Italy. Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla 40351, Finland. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Ferrucci, L (reprint author), NIH, Longitudinal Studies Sect, Clin Res Branch, ASTRA Unit,Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. RI Rantanen, Taina/O-6579-2016; Lauretani, Fulvio/K-5115-2016 OI Rantanen, Taina/0000-0002-1604-1945; Lauretani, Fulvio/0000-0002-5287-9972 FU NIMHD NIH HHS [263-MD-9164-13, 263-MD-821336] NR 37 TC 554 Z9 573 U1 15 U2 65 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV 01 PY 2003 VL 95 IS 5 BP 1851 EP 1860 DI 10.1152/japplphysiol.00246.2003 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 730VF UT WOS:000185850300013 PM 14555665 ER PT J AU Avichezer, D Liou, GI Chan, CC Lewis, GM Wiggert, B Donoso, LA Nickerson, JM Crawford, MA Caspi, RR AF Avichezer, D Liou, GI Chan, CC Lewis, GM Wiggert, B Donoso, LA Nickerson, JM Crawford, MA Caspi, RR TI Interphotoreceptor retinoid-binding protein (IRBP)-deficient C57BL/6 mice have enhanced immunological and immunopathogenic responses to IRBP and an altered recognition of IRBP epitopes SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT Meeting of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY MAY 15-19, 2003 CL PARIS, FRANCE SP Fed Clin Immunol Soc DE autoimmune disease; experimental autoimmune uveitis; pinealitis; central tolerance; immune privilege ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; TARGETED DISRUPTION; PIGMENT-EPITHELIUM; ADOPTIVE TRANSFER; VITAMIN-A; UVEITIS; GENE; REGENERATION; EXPRESSION; MECHANISMS AB Experimental autoimmune uveitis (EAU) and pinealitis (EAP) can be induced in susceptible mice by immunization with immunologically privileged retinal antigens. In the present study, we analyzed the immunologic and immunopathologic responses of mice deficient in the retinal autoantigen interphotoreceptor retinoid-binding protein (IRBP). The consequences of IRBP deficiency on the T-cell repertoire were also investigated. IRBP+/+, IRBP+/- and IRBP-/- mice on the C57BL/6 background were immunized with IRBP or with a pathogenic epitope, IRBP(1-20) peptide in adjuvant, and were evaluated for disease severity and immunological responses. C57BL/6 IRBP-/- mice were completely resistant to EAU and EAP, and had enhanced immunological responses to IRBP and to its pathogenic peptide 1-20, as compared to their IRBP+/+ counterparts. IRBP-/- mice exhibited an altered IRBP epitope recognition. T cell epitope mapping revealed a response to IRBP peptide 271-290 in IRBP-/- mice, that was absent in the wild type. Primed T cells of IRBP-/- mice transferred an exacerbated form of EAU to naive wild type recipients. A gene-dose effect was evident in that C57BL/6 IRBP+/- mice, exhibited intermediate immunological responses and lower disease scores compared to wild type. We conclude that expression of IRBP in target tissues is a necessary prerequisite for disease induction, excluding other retinoid-binding or vision-related proteins as surrogate targets. Furthermore, endogenous expression of IRBP is directly responsible for lowering the threshold of susceptibility to uveitic disease. (C) 2003 Published by Elsevier Ltd. C1 NIH, Immunol Lab, Sect Immunoregulat, Bethesda, MD 20892 USA. Emory Univ, Emory Eye Ctr, Dept Ophthalmol, Atlanta, GA 30322 USA. Wills Eye Hosp & Res Inst, Retinal Sect, Philadelphia, PA 19107 USA. NEI, Histol Core Facil, NIH, Bethesda, MD 20892 USA. NIH, Lab Cell & Mol Biol, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. RP Caspi, RR (reprint author), NIH, Immunol Lab, Sect Immunoregulat, 10 Ctr Dr,10-10N222, Bethesda, MD 20892 USA. OI Caspi, Rachel/0000-0002-7140-7671 NR 42 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD NOV PY 2003 VL 21 IS 3 BP 185 EP 194 DI 10.1016/j.jaut.2003.08.004 PG 10 WC Immunology SC Immunology GA 742VQ UT WOS:000186539100002 PM 14599843 ER PT J AU Nussenblatt, RB Thompson, DJS Li, ZQ Peterson, JS Robinson, RR Shames, RS Nagarajan, S Tang, MT Mailman, M Velez, G Roy, C Levy-Clarke, GA Suhler, EB Djalilian, A Sen, HN Al-Khatib, S Ursea, R Srivastava, S Bamji, A Mellow, S Sran, P Waldmann, TA Buggage, RR AF Nussenblatt, RB Thompson, DJS Li, ZQ Peterson, JS Robinson, RR Shames, RS Nagarajan, S Tang, MT Mailman, M Velez, G Roy, C Levy-Clarke, GA Suhler, EB Djalilian, A Sen, HN Al-Khatib, S Ursea, R Srivastava, S Bamji, A Mellow, S Sran, P Waldmann, TA Buggage, RR TI Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT Meeting of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY MAY 15-19, 2003 CL PARIS, FRANCE SP Fed Clin Immunol Soc DE autoimmunity; IL-2 receptor; immunosuppression; inflammation; uveitis; daclizumab ID ANTI-TAC; POSTERIOR UVEITIS; T-CELLS; INTERLEUKIN-2-RECEPTOR; INTERMEDIATE; BLOCKADE AB Therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make lone-term therapy difficult. A long-term (>4 year) Phase I/II single armed interventional study using intravenous anti-IL-2 receptor alpha treatments (daclizumab) and a short-term Phase 11 study evaluating the use of a subcutaneous daclizumab formulation were conducted. Patients were tapered off their systemic immunosuppressive therapy and received daclizumab infusions or subcutaneous injections at intervals varying from 2 to 6 weeks. In the long-term study, seven of ten enrolled patients were tapered from their original immunosuppressive medications and maintained exclusively on repeated daclizumab infusions for control of their uveitis for over 4 years. No patient was permanently removed from therapy for an adverse event ascribed to the medication. The use of 6-week infusion intervals led to recurrence of uveitis, while 2- to 4-week intervals did not. Only one patient developed measurable anti-daclizumab antibodies but this disappeared when subcutaneous therapy was begun. In the short-term study, four of the five patients receiving the subcutaneous formulation met the study endpoints for success within the first 12 weeks. All five were successful by 26 weeks. These studies provide preliminary evidence that regularly administered long-term daclizumab therapy can be given in lieu of standard immunosuppression for years to treat severe uveitis and that subcutaneously administered daclizumab appeared to be a clinically viable treatment strategy. These studies suggest that anti-IL-2 receptor blockade could be useful in the treatment of Th1-mediated autoimmune conditions. (C) 2003 Elsevier Ltd. All rights reserved. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD USA. Prot Design Labs Inc, Fremont, CA USA. EMMES Corp, Rockville, MD USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-1-2113] NR 13 TC 66 Z9 71 U1 1 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD NOV PY 2003 VL 21 IS 3 BP 283 EP 293 DI 10.1016/S0896-8411(03)00113-6 PG 11 WC Immunology SC Immunology GA 742VQ UT WOS:000186539100013 PM 14599854 ER PT J AU Repoila, F Gottesman, S AF Repoila, F Gottesman, S TI Temperature sensing by the dsrA promoter SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COLI RNA-POLYMERASE; ESCHERICHIA-COLI; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; -35 REGIONS; DNA; RPOS; SEQUENCES; COMPILATION; RECOGNITION AB Synthesis of the small regulatory RNA DsrA is under temperature control. The minimal dsrA promoter of 36 bp contains sufficient information to ensure such regulation. In vivo, we have analyzed the critical elements responsible for the temperature control of dsrA by using a collection of chimeric promoters combining various elements of the dsrA promoter and the lacUV5 promoter, which does not respond to temperature. Our results favor an RNA polymerase-DNA interaction model instead of a trans-acting factor for temperature regulation. While all of the elements of the dsrA promoter contribute to temperature-sensitive expression, the sequence of the -10 box and the spacer region are the essential elements for the thermal response of the dsrA promoter. The proper context for these promoter elements, including at least one of the flanking elements, the -35 region or the start site region, is also required. Point mutations demonstrate that the sequence of the -10 box imposes constraints on the length and the sequence of the spacer and/or its AT richness, even at low temperature. These results show a complex interdependence of different regions in the promoter for temperature regulation. C1 INRA, ENVT, Mol Microbiol Lab, UMR 1225, Toulouse, France. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NIH, Bldg 37,Rm 5132, Bethesda, MD 20892 USA. OI Repoila, Francis/0000-0001-5149-9698 NR 28 TC 37 Z9 38 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2003 VL 185 IS 22 BP 6609 EP 6614 DI 10.1128/JB.185.22.6609-6614.2003 PG 6 WC Microbiology SC Microbiology GA 741AU UT WOS:000186436600014 PM 14594834 ER PT J AU Somerville, GA Cockayne, A Durr, M Peschel, A Otto, M Musser, JM AF Somerville, GA Cockayne, A Durr, M Peschel, A Otto, M Musser, JM TI Synthesis and deformylation of Staphylococcus aureus delta-toxin are linked to tricarboxylic acid cycle activity SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GENE REGULATOR AGR; PEPTIDE DEFORMYLASE; MESSENGER-RNA; IDENTIFICATION; ACONITASE; TRANSLATION; EXPRESSION; HEMOLYSIN; SEQUENCE; FERRITIN AB In bacteria, translation initiates with formyl-methionine; however, the N-terminal formyl group is usually removed by peptide deformylase, an enzymatic activity requiring iron. Staphylococcus aureus delta-toxin is a 26-amino-acid polypeptide secreted predominantly with a formylated N-terminal methionine, which led us to investigate regulation of delta-toxin deformylation. We observed that during exponential and early postexponential growth, delta-toxin accumulated in the culture medium in formylated and deformylated forms. In contrast, only formylated delta-toxin accumulated after the early postexponential phase. The transition from producing both species of delta-toxin to producing only formyl-methionine-containing delta-toxin coincided with increased tricarboxylic acid (TCA) cycle activity. The TCA cycle contains several iron-requiring enzymes, which led us to hypothesize that TCA cycle induction depletes the iron in the culture medium, thereby inhibiting peptide deformylase activity. As expected, S. aureus depletes the iron in the culture medium between the postexponential and stationary phases of growth. Inhibition of delta-toxin deformylation was relieved by TCA cycle inactivation or by addition of supplemental iron to the culture medium. Of interest, peptides containing formyl-methionine are potent chemoattractants for neutrophils, suggesting that delta-toxin deformylation may have functional consequences. We found neutrophil chemotactic activity only with formylated delta-toxin. The S. aureus TCA cycle is derepressed upon depletion of rapidly catabolizable carbon sources; this coincides with the transition to producing only formylated delta-toxin and results in an increased inflammatory response. The proinflammatory response should increase host cell damage and result in the release of nutrients. Taken together, these results establish that there is an important linkage between bacterial metabolism and pathogenesis. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ Nottingham, Inst Infect & Immun, Nottingham NG7 2UH, England. Univ Tubingen, D-72076 Tubingen, Germany. RP NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM gsomerville@niaid.nih.gov RI Somerville, Greg/B-1326-2013 OI Somerville, Greg/0000-0002-0991-8737 NR 30 TC 59 Z9 61 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2003 VL 185 IS 22 BP 6686 EP 6694 DI 10.1128/JB.185.22.6686-6694.2003 PG 9 WC Microbiology SC Microbiology GA 741AU UT WOS:000186436600023 PM 14594843 ER PT J AU Baba, S Takahashi, K Koyanagi, Y Yamamoto, N Takaku, H Gorelick, RJ Kawai, G AF Baba, S Takahashi, K Koyanagi, Y Yamamoto, N Takaku, H Gorelick, RJ Kawai, G TI Role of the zinc fingers of HIV-1 nucleocapsid protein in maturation of genomic RNA SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE DIS; HIV-1; maturation; nucleocapsid protein; zinc finger ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACID-CHAPERONE ACTIVITY; DIMERIZATION INITIATION SITE; RECOGNITION; NCP7 AB The nucleocapsid protein of HIV-1 consists of two basic amino acid regions and two zinc fingers. We investigated the requirement of these domains for the structural conversion of a 39mer RNA covering the dimerization initiation site by using three peptides; wild-type NCp7, a mutant in which the two zinc fingers are mutated, and another mutant in which the two zinc fingers are deleted. The two mutants exhibited similar conversion activities to each other, which were lower than that of the wildtype, indicating that the two basic regions exhibit some activity for RNA chaperone, as we suggested before, and the zinc fingers enhance the efficiency of this activity. C1 Chiba Inst Technol, Fac Engn, Dept Ind Chem, Narashino, Chiba 2750016, Japan. Tohoku Univ, Sch Med, Dept Virol, Aoba Ku, Sendai, Miyagi 9808575, Japan. Tokyo Med & Dent Univ, Fac Med, Dept Mol Virol, Tokyo 1138519, Japan. NCI, SAIC Frederick Inc, dAIDS Vaccine Program, Frederick, MD 21702 USA. RP Kawai, G (reprint author), Chiba Inst Technol, Fac Engn, Dept Ind Chem, 2-17-1 Tsudanuma, Narashino, Chiba 2750016, Japan. FU NCI NIH HHS [N01-CO-12400] NR 18 TC 17 Z9 17 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-924X J9 J BIOCHEM JI J. Biochem. PD NOV PY 2003 VL 134 IS 5 BP 637 EP 639 DI 10.1093/jh/mvg200 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756QR UT WOS:000187492900003 PM 14688228 ER PT J AU Saito, S Tatsumoto, T Lorenzi, MV Chedid, M Kapoor, V Sakata, H Rubin, J Miki, T AF Saito, S Tatsumoto, T Lorenzi, MV Chedid, M Kapoor, V Sakata, H Rubin, J Miki, T TI Rho exchange factor ECT2 is induced by growth factors and regulates cytokinesis through the N-terminal cell cycle regulator-related domains SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE cell division; mitogen; serum induction; small GTPase; oncogene ID REPLICATION CHECKPOINT CONTROL; DNA-REPLICATION; FISSION YEAST; BINDING; DAMAGE; REPAIR; CUT5; HYBRIDIZATION; INITIATION; EXPRESSION AB The ECT2 protooncogene plays a critical role in cytokinesis, and its C-terminal half encodes a DbI homology-pleckstrin homology module, which catalyzes guanine nucleotide exchange on the Rho family of small GTPases. The N-terminal half of ECT2 (ECT2-N) contains domains related to the cell cycle regulator/checkpoint control proteins including human XRCC1, budding yeast CLB6, and fission yeast Cut5. The Cut5-related domain consists of two BRCT repeats, which are widespread to repair/checkpoint control proteins. ECT2 is ubiquitously expressed in various tissues and cell lines, but elevated levels of ECT2 expression were found in various tumor cell lines and rapidly developing tissues in mouse embryos. Consistent with these findings, induction of ECT2 expression was observed upon stimulation by serum or various growth factors. In contrast to other oncogenes whose expression is induced early in G1, ECT2 expression was induced later, coinciding with the initiation of DNA synthesis. To test the role of the cell cycle regulator/checkpoint control protein-related domains of ECT2 in cytokinesis, we expressed various ECT2 derivatives in U2OS cells, and analyzed their DNA content by flow cytometry. Expression of the N-terminal half of ECT2, which lacks the catalytic domain, generated cells with more than 4N DNA content, suggesting that cytokinesis was inhibited in these cells. Interestingly, ECT2-N lacking the nuclear localization signals inhibited cytokinesis more strongly than the derivatives containing these signals. Mutational analyses revealed that the XRCC1, CLB6, and BRCT domains in ECT2-N are all essential for the cytokinesis inhibition by ECT2-N. These results suggest that the XRCC1, CLB6, and BRCT domains of ECT2 play a critical role in regulating cytokinesis. Published 2003 Wiley-Liss, Inc. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Mol Tumor Biol Sect, Basic Res Lab, Bethesda, MD 20892 USA. RP Miki, T (reprint author), NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NR 25 TC 44 Z9 45 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD NOV 1 PY 2003 VL 90 IS 4 BP 819 EP 836 DI 10.1002/jcb.10688 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 740XN UT WOS:000186428100014 PM 14587037 ER PT J AU Tsokos, GC Tsokos, M AF Tsokos, GC Tsokos, M TI The TRAIL to arthritis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; APOPTOSIS-INDUCING LIGAND; DENDRITIC CELLS; T-CELL; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; GENE-THERAPY; MICE; DEFICIENT AB Antigen-specific lymphocytes are involved in synovial proliferation within inflamed joints. Activated lymphocytes and synoviocytes from patients with rheumatoid arthritis express receptors that can bind TNF-related apoptosis-inducing ligand (TRAIL). A new study demonstrates that DCs pulsed with collagen and transduced with an adenovirus-based vector able to express TRAIL limit the incidence of arthritis in a model of collagen-induced arthritis and joint inflammation (see the related article beginning on page 1332). These results suggest that gene-modified cell therapy represents a therapeutic option for systemic rheumatic diseases. C1 Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD 20910 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Tsokos, GC (reprint author), Walter Reed Army Inst Res, Dept Cellular Injury, Bldg 503,Room 1A32,Robert Grand Rd, Silver Spring, MD 20910 USA. NR 21 TC 15 Z9 17 U1 0 U2 0 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 NOV PY 2003 VL 112 IS 9 BP 1315 EP 1317 DI 10.1172/JCI200320297 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 739YT UT WOS:000186374800010 PM 14597758 ER PT J AU Takagi, S Tojo, H Tomita, S Sano, S Itami, S Hara, M Inoue, S Horie, K Kondoh, G Hosokawa, K Gonzalez, FJ Takeda, J AF Takagi, S Tojo, H Tomita, S Sano, S Itami, S Hara, M Inoue, S Horie, K Kondoh, G Hosokawa, K Gonzalez, FJ Takeda, J TI Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID EPIDERMAL PERMEABILITY BARRIER; ARYL-HYDROCARBON RECEPTOR; NUCLEAR TRANSLOCATOR PROTEIN; TANDEM MASS-SPECTROMETRY; INDUCIBLE FACTOR 1-ALPHA; X-RAY-DIFFRACTION; STRATUM-CORNEUM; AH RECEPTOR; OMEGA-HYDROXYCERAMIDES; TRANSGLUTAMINASE 1 AB Aryl hydrocarbon receptor nuclear translocator (ARNT), a transcription factor of the Per/AHR/ARNT/Sim family, regulates gene expression in response to environmental stimuli including xenobiotics and hypoxia. To examine its role in the epidermis, the Cre-loxP system was used to disrupt the Arnt gene in a keratinocyte-specific manner. Gene-targeted, newborn mice with almost normal appearance died neonatally of severe dehydration caused by water loss. Histology showed small changes in the architecture of cornified layers, with apparently preserved intercorneocyte lamellar structures responsible for the skin barrier function. In contrast, HPLC/ion-trap mass spectrometry revealed significant alterations in the compositions of ceramides, the major components of the lamellae. The murine epidermal ceramides normally contain 4-sphingenine and 4-hydroxysphinganine. In Arnt-null epidermis, 4-sphingenine was largely replaced by sphinganine and the amounts of ceramides with 4-hydroxysphinganine were greatly decreased, suggesting deficiency of dihydroceramide desaturases that catalyze the formation of both 4-sphingenyl and 4-hydroxysphinganyl moieties. A desaturase isoenzyme, DES-1, prefers desaturation, but DES-2 catalyzes both reactions to a similar extent. Transcript levels of Des-2, but not Des-1, were considerably decreased in cultured keratinocytes from Arnt-null epidermis. These results indicate that proper ceramide compositions through 4-desaturation regulated by ARNT are crucial for maintaining the epidermal barrier function. C1 Osaka Univ, Grad Sch Med, Dept Social & Environm Med, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Dept Plast Surg, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Dept Biochem & Mol Biol, Osaka 5650871, Japan. RIKEN, Res Ctr Allergy & Immunol, Dept Immune Syst Dev, Tokushima, Japan. Osaka Univ, Grad Sch Med, Dept Dermatol, Osaka, Japan. Kanebo Ltd, Basic Res Lab, Kanagawa, Japan. Collaborat Res Ctr Adv Sci & Technol, Osaka, Japan. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Takeda, J (reprint author), Osaka Univ, Grad Sch Med, Dept Social & Environm Med, Osaka 5650871, Japan. OI Inoue, Shintaro/0000-0002-4996-5693 NR 47 TC 41 Z9 42 U1 0 U2 7 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 NOV PY 2003 VL 112 IS 9 BP 1372 EP 1382 DI 10.1172/JCI200318513 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 739YT UT WOS:000186374800016 PM 14597763 ER PT J AU Sato, M Muragaki, Y Saika, S Roberts, AB Ooshima, A AF Sato, M Muragaki, Y Saika, S Roberts, AB Ooshima, A TI Targeted disruption of TGF-beta 1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-BETA; TUBULAR EPITHELIAL-CELLS; SMOOTH-MUSCLE CELLS; MICE LACKING SMAD3; TGF-BETA; MESENCHYMAL TRANSDIFFERENTIATION; INTERSTITIAL FIBROSIS; ENDOTHELIAL-CELLS; GENE-EXPRESSION; ANGIOTENSIN-II AB Tubulointerstitial fibrosis is the final common result of a variety of progressive injuries leading to chronic renal failure. Transforming growth factor-beta (TGF-beta) is reportedly upregulated in response to injurious stimuli such as unilateral ureteral obstruction (UUO), causing renal fibrosis associated with epithelial-mesenchymal transition (EMT) of the renal tubules and synthesis of extracellular matrix. We now show that mice lacking Smad3 (Smad3(ex8/ex8)) a key signaling intermediate downstream of the TGF-beta receptors, are protected against tubulointerstitial fibrosis following UUO as evidenced by blocking of EMT and abrogation of monocyte influx and collagen accumulation. Culture of primary renal tubular epithelial cells from wild-type or Smad3-null mice confirms that the Smad3 pathway is essential for TGF-beta1-induced EMT and autoinduction of TGF-beta1. Moreover, mechanical stretch of the cultured epithelial cells, mimicking renal tubular distention due to accumulation of urine after UUO induces EMT following Smad3-mediated upregulation of TGF-beta1. Exogenous bone marrow monocytes accelerate EMT of the cultured epithelial cells and renal tubules in the obstructed kidney after UUO dependent on Smad3 signaling. Together the data demonstrate that the Smad3 pathway is central to the pathogenesis of interstitial fibrosis and suggest that inhibitors of this pathway may have clinical application in the treatment of obstructive nephropathy. C1 Wakayama Med Univ, Dept Pathol, Wakayama 6410012, Japan. Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Ooshima, A (reprint author), Wakayama Med Univ, Dept Pathol, 811-1 Kimiidera, Wakayama 6410012, Japan. NR 46 TC 441 Z9 475 U1 5 U2 23 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 NOV PY 2003 VL 112 IS 10 BP 1486 EP 1494 DI 10.1172/JCI200319270 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 743NU UT WOS:000186580400007 PM 14617750 ER PT J AU Grammer, AC Slota, R Fischer, R Gur, H Girschick, H Yarboro, C Illei, GG Lipsky, PE AF Grammer, AC Slota, R Fischer, R Gur, H Girschick, H Yarboro, C Illei, GG Lipsky, PE TI Abnormal germinal center reactions in systemic lupus erythematosus demonstrated by blockade of CD154-CD40 interactions SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; HUMAN B-CELLS; CD40-CD40 LIGAND INTERACTION; SMOOTH-MUSCLE-CELLS; IMMUNOGLOBULIN-SECRETING CELLS; HUMAN ATHEROSCLEROTIC LESIONS; ADHESION MOLECULE EXPRESSION; HYPER-IGM SYNDROME; CD40 LIGAND; PLASMA-CELLS AB To determine the role of CD154-CD40 interactions in the B cell overactivity exhibited by patients with active systemic lupus erythematosus (SLE), CD19(+) peripheral B cells were examined before and after treatment with humanized anti-CD154 mAb (BG9588, 5c8). Before treatment, SLE patients manifested activated B cells that expressed CD154, CD69, CD38, CD5, and CD27. Cells expressing CD38, CD5, or CD27 disappeared from the periphery during treatment with anti-CD154 mAb, and cells expressing CD69 and CD154 disappeared from the periphery during the post-treatment period. Before treatment, active-SLE patients had circulating CD38(bright) Ig-secreting cells that were not found in normal individuals. Disappearance of this plasma cell subset during treatment was associated with decreases in anti-double-stranded DNA (anti-dsDNA) Ab levels, proteinuria, and SLE disease activity index. Consistent with this finding, peripheral B cells cultured in vitro spontaneously proliferated and secreted Ig in a manner that was inhibited by anti-CD154 mAb. Finally, the CD38(+)/(++)IgD(+), CD38(+++), and CD38(+)IgD(-) B cell subsets present in the peripheral blood also disappeared following treatment with humanized anti-CD154. Together, these results indicate that patients with active lupus nephritis exhibit abnormalities in the peripheral B cell compartment that are consistent with intensive germinal center activity, are driven via CD154-CD40 interactions, and may reflect or contribute to the propensity of these patients to produce autoantibodies. C1 NIAMSD, Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIAMSD, Off Clin Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIAMSD, Intramural Res Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Grammer, AC (reprint author), NIAMSD, Autoimmun Branch, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike,Bldg 10,Room 6D47A, Bethesda, MD 20892 USA. NR 90 TC 154 Z9 166 U1 1 U2 3 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 NOV PY 2003 VL 112 IS 10 BP 1506 EP 1520 DI 10.1172/JCI200319301 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 743NU UT WOS:000186580400009 PM 14617752 ER PT J AU Yepes, M Sandkvist, M Moore, EG Bugge, TH Strickland, DK Lawrence, DA AF Yepes, M Sandkvist, M Moore, EG Bugge, TH Strickland, DK Lawrence, DA TI Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; LONG-TERM POTENTIATION; TPA-DEFICIENT MICE; LIPOPROTEIN RECEPTOR; THERAPEUTIC WINDOW; NERVOUS-SYSTEM; GELATINASE-B; WILD-TYPE; GENE; MATRIX-METALLOPROTEINASE-9 AB The regulation of cerebrovascular permeability is critical for normal brain homeostasis, and the "breakdown" of the blood-brain barrier (BBB) is associated with the development of vasogenic edema and intracranial hypertension in a number of neurological disorders. In this study we demonstrate that an increase in endogenous tissue-type plasminogen activator (tPA) activity in the perivascular tissue following cerebral ischemia induces opening of the BBB via a mechanism that is independent of both plasminogen (Plg) and MMP-9. We also show that injection of tPA into the cerebrospinal. fluid in the absence of ischemia results in a rapid dose-dependent increase in vascular permeability. This activity is not seen with urokinase-type Plg activator (uPA) but is induced in Plg(-/-) mice, confirming that the effect is Plg-independent. However, the activity is blocked by antibodies to the LDL receptor-related protein (LRP) and by the LRP antagonist, receptor-associated protein (RAP), suggesting a receptor-mediated process. Together these studies demonstrate that tPA is both necessary and sufficient to directly increase vascular permeability in the early stages of BBB opening, and suggest that this occurs through a receptor-mediated cell signaling event and not through generalized degradation of the vascular basement membrane. C1 Amer Red Cross, Holland Lab, Vasc Biol Dept, Rockville, MD 20855 USA. Georgetown Univ Hosp, Dept Neurol, Washington, DC 20007 USA. Amer Red Cross, Holland Lab, Dept Biochem, Rockville, MD 20855 USA. Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Lawrence, DA (reprint author), Amer Red Cross, Holland Lab, Vasc Biol Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. RI Yepes, Manuel/C-3576-2011 FU NHLBI NIH HHS [HL-55374, HL-55747, P01 HL054710, HL-54710, R01 HL055374, R01 HL055747]; NINDS NIH HHS [K08 NS002223, NS-02223] NR 47 TC 321 Z9 334 U1 0 U2 13 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 NOV PY 2003 VL 112 IS 10 BP 1533 EP 1540 DI 10.1172/JCI200319212 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 743NU UT WOS:000186580400011 PM 14617754 ER PT J AU Philipp, MT Marques, AR Fawcett, PT Dally, LG Martin, DS AF Philipp, MT Marques, AR Fawcett, PT Dally, LG Martin, DS TI C-6 test as an indicator of therapy outcome for patients with localized or disseminated Lyme borreliosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; ANTIBIOTIC-TREATMENT; INVARIABLE REGION; ANTIBODY-RESPONSE; VLSE LIPOPROTEIN; ERYTHEMA MIGRANS; BURGDORFERI VLSE; DISEASE; SERODIAGNOSIS; PEPTIDE AB Management of Lyme disease would benefit from a test to assess therapy outcome. Such a test could be employed to ascertain if treatment of early Lyme disease was successful and would be helpful to clinicians assessing patients with lingering posttreatment symptoms. We reported recently that levels of the antibody to C-6, a Borrelia burgdorferi-derived peptide that is used as an antigen in the C-6-Lyme diagnostic test, declined after successful antibiotic treatment of Lyme borreliosis patients. We assessed retrospectively the change in anti-C-6 antibody titers in 131 patients with either early localized disease (erythema migrans) or disseminated disease. All of these patients were treated with antibiotics and were free of the clinical signs shown at presentation within 12 weeks after the initiation of treatment. Decreases in reciprocal geometric mean titers (rGMT) of the anti-C-6 antibody were quantified for the subpopulation of 45 patients whose baseline rGMT were greater than or equal to80 and whose second serum specimens were obtained at least 6 months after the baseline specimen. Eighty percent of this patient group (36 of 45) experienced a greater than or equal to4-fold decrease in their rGMT (P < 0.0003). These results suggest that a change in the anti-C-6 antibody titer may serve as an indicator of therapy outcome for patients with localized or disseminated Lyme borreliosis. C1 Tulane Univ, Ctr Hlth Sci, Tulane Natl Primate Res Ctr, Dept Bacteriol & Parasitol, Covington, LA 70433 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Alfred 1 DuPont Hosp Children, Wilmington, DE USA. RP Philipp, MT (reprint author), Tulane Univ, Ctr Hlth Sci, Tulane Natl Primate Res Ctr, Dept Bacteriol & Parasitol, 18703 3 Rivers Rd, Covington, LA 70433 USA. FU NCRR NIH HHS [P51 RR000164, RR00164]; NIAID NIH HHS [R01 AI049976, R01-AI49976] NR 23 TC 25 Z9 25 U1 0 U2 0 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 NOV PY 2003 VL 41 IS 11 BP 4955 EP 4960 DI 10.1128/JCM.41.11.4955-4960.2003 PG 6 WC Microbiology SC Microbiology GA 745AR UT WOS:000186665500006 PM 14605123 ER PT J AU Roper, P Callaway, J Shevchenko, T Teruyama, R Armstrong, W AF Roper, P Callaway, J Shevchenko, T Teruyama, R Armstrong, W TI AHP's, HAP's and DAP's: How potassium currents regulate the excitability of rat supraoptic neurones SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article ID MAGNOCELLULAR NEUROSECRETORY-CELLS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MAMMALIAN NEUROENDOCRINE CELLS; HIPPOCAMPAL PYRAMIDAL NEURONS; DEPOLARIZING AFTER-POTENTIALS; TRANSIENT K+ CURRENT; VASOPRESSIN NEURONS; IN-VITRO; ADULT-RAT; LABELING IMMUNOFLUORESCENCE AB We have constructed mathematical models of the electrical activity of two hypothalamic supraoptic neuro-secretory cell-types, and we support our models with new calcium imaging and in vitro electrophysiological data. These cells are neurones that project to the pituitary gland and secrete either of two hormones, oxytocin or vasopressin, into the blood from their axonal terminals. Oxytocin-secreting and vasopressin-secreting cells are closely related and physically they differ only subtly, however when physiologically stressed their discharge patterns are dramatically distinct. We first show how each potassium current contributes to the action-potentials and after-potentials observed in these cells, and we show how these after-potentials are correlated to intra-cellular calcium elevations. We then show how these currents regulate the excitability of these cells and consequently shape their discharge pattern. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Coll Med, Dept Anat & Neurobiol, Memphis, TN 38163 USA. RP Roper, P (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS 23941, NS 42276] NR 92 TC 43 Z9 44 U1 2 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD NOV-DEC PY 2003 VL 15 IS 3 BP 367 EP 389 DI 10.1023/A:1027424128972 PG 23 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 740VA UT WOS:000186421200006 PM 14618071 ER PT J AU Cassarino, DS Fullen, DR Sondak, VK Duray, PH AF Cassarino, DS Fullen, DR Sondak, VK Duray, PH TI Metastatic nevoid melanoma in a 4 1/2-year-old child SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; CYCLIN D1; NEVI; EXPRESSION; RISK; P53 AB Background: Childhood melanoma is a rare and controversial diagnosis. Methods: We present the case of a 41/2-year-old child found to have an expanding, elevated pigmented lesion on her back. Results: The biopsy showed a symmetrical, well circumscribed lesion. However, higher magnification revealed sheets of nevoid cells infiltrating deep into the dermis, lacking maturation, and exhibiting a high mitotic rate (average 5/10 high-power field) with deep mitoses. The possibility of nevoid melanoma was raised, and re-excision and sentinel lymph node (SLN) biopsy were recommended. Two SLNs were positive for melanoma, verified by immunohistochemical staining. In order to further characterize this melanoma, we performed immunohistochemistry for the tumor-suppressor p53, proliferation marker MIB-1, and oncogenes Bcl-2, cyclin D-1, and MDM-2. Staining for p53 was diffusely positive in the primary and the metastasis; MIB-1 showed moderate proliferative rate in the primary (approximately 10%); Bcl-2 was weakly positive in the primary and showed focal staining in the metastasis; cyclin D-1 was strongly positive in the primary and metastasis; and MDM-2 staining showed scattered positive cells in both lesions. Conclusions: These findings are consistent with a metastatic nevoid melanoma arising in the absence of predisposing disease in a young child, a distinctly unusual occurrence. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ctr Canc, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Dept Surg & Comprehens, Ann Arbor, MI 48109 USA. RP Cassarino, DS (reprint author), Univ Calif Irvine, Dermatopathol Lab, 101 City Dr S,Rt 98,Bldg 52, Orange, CA 92868 USA. NR 21 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD NOV PY 2003 VL 30 IS 10 BP 647 EP 651 DI 10.1034/j.1600-0560.2003.00123.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 735VU UT WOS:000186135900009 PM 14744091 ER PT J AU Burch, CL Turner, PE Hanley, KA AF Burch, CL Turner, PE Hanley, KA TI Patterns of epistasis in RNA viruses: a review of the evidence from vaccine design SO JOURNAL OF EVOLUTIONARY BIOLOGY LA English DT Review DE attenuation; epistasis; evolution; mutation; RNA virus; vaccine ID RESPIRATORY SYNCYTIAL VIRUS; BORNE ENCEPHALITIS-VIRUS; TO-ALANINE MUTAGENESIS; ATTENUATION PHENOTYPES; DELETERIOUS MUTATIONS; TEMPERATURE SENSITIVITY; DROSOPHILA-MELANOGASTER; CANDIDATE CPTS248/404; SYNERGISTIC EPISTASIS; NATURAL-POPULATIONS AB Epistasis results when the fitness effects of a mutation change depending on the presence or absence of other mutations in the genome. The predictions of many influential evolutionary hypotheses are determined by the existence and form of epistasis. One rich source of data on the interactions among deleterious mutations that has gone untapped by evolutionary biologists is the literature on the design of live, attenuated vaccine viruses. Rational vaccine design depends upon the measurement of individual and combined effects of deleterious mutations. In the current study, we have reviewed data from 29 vaccine-oriented studies using 14 different RNA viruses. Our analyses indicate that (1) no consistent tendency towards a particular form of epistasis exists across RNA viruses and (2) significant interactions among groups of mutations within individual viruses occur but are not common. RNA viruses are significant pathogens of human disease, and are tractable model systems for evolutionary studies - we discuss the relevance of our findings in both contexts. C1 Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Burch, CL (reprint author), Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA. NR 65 TC 28 Z9 28 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1010-061X J9 J EVOLUTION BIOL JI J. Evol. Biol. PD NOV PY 2003 VL 16 IS 6 BP 1223 EP 1235 DI 10.1046/j.1420-9101.2003.00632.x PG 13 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 733EY UT WOS:000185988000017 PM 14640414 ER PT J AU Mahanty, S Saul, A Miller, LH AF Mahanty, S Saul, A Miller, LH TI Progress in the development of recombinant and synthetic blood-stage malaria vaccines SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Review DE malaria; vaccine; blood stage; recombinant antigen; Plasmodium falciparum; clinical trials; antigenic polymorphism ID FALCIPARUM-INFECTED ERYTHROCYTES; MEROZOITE SURFACE PROTEIN-1; NATURALLY ACQUIRED-IMMUNITY; APICAL MEMBRANE ANTIGEN-1; GLUTAMATE-RICH PROTEIN; PAPUA-NEW-GUINEA; PLASMODIUM-FALCIPARUM; AOTUS MONKEYS; T-CELLS; PROTECTIVE IMMUNITY AB The use of asexual blood-stage proteins as malaria vaccines is strongly supported by experimental data directly implicating antibodies induced by these antigens in parasite clearance and protection from re-challenge. The selection of blood-stage antigens is based on their ability to interfere with the pathogenesis of clinical malaria by reducing parasitemias. These vaccines could complement other vaccines aimed at preventing infection, such as those targeted at pre-erythrocytic or mosquito stages of the parasite. Asexual blood-stage vaccines may reduce disease by blockade of red blood cell invasion, inhibition of parasite. growth in red cells or interference in cytoadherence of infected red cells. Clearance of blood-stage parasites is dependent primarily on antibody-mediated mechanisms, but CD4 T cells may also play an important role in help for B cells and probably have a direct effector function in the clearance of blood-stage parasites. Since asexual blood-stage parasites reside within erythrocytes, they are accessible to immune clearance mechanisms only for a short time, which imposes special requirements on vaccines. For example, immunity that induces high titers of antibody will be required. Antigenic variation and extensive polymorphism of malarial proteins also needs to be addressed. Several recombinant antigens derived from blood-stage proteins have moved beyond basic research and are now poised for phase I trials in endemic countries. In this review we discuss the state of asexual blood-stage vaccines, focusing on recombinant antigens from Plasmodium falciparum. The significance of polymorphism and antigenic variation, the relevance of parasite immune evasion mechanisms, the need for reliable measures of successful intervention and new adjuvants are reviewed. Results from trials of asexual blood stage vaccine that support the continued effort to develop these antigens as key ingredients of multicomponent, multistage malaria vaccines are documented. C1 NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. RP Mahanty, S (reprint author), NIAID, Malaria Vaccine Dev Unit, NIH, Twin Brook 1,5640 Fishers Lane, Rockville, MD 20852 USA. RI Saul, Allan/I-6968-2013; OI Saul, Allan/0000-0003-0665-4091; Mahanty, Siddhartha/0000-0003-1068-0524 NR 84 TC 53 Z9 55 U1 0 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD NOV PY 2003 VL 206 IS 21 BP 3781 EP 3788 DI 10.1242/jeb.00646 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 755FW UT WOS:000187393700013 PM 14506213 ER PT J AU Chepelinsky, AB AF Chepelinsky, AB TI The ocular lens fiber membrane specific protein MIP/aquaporin 0 SO JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-COMPARATIVE EXPERIMENTAL BIOLOGY LA English DT Article; Proceedings Paper CT 14th International Congress of Pure and Applied Biophysics CY MAY, 2002 CL MIAMI, FLORIDA ID MAJOR INTRINSIC PROTEIN; AQUAPORIN WATER CHANNELS; RAT LENS; CLINICAL MEDICINE; ATOMIC-STRUCTURE; POLYPEPTIDE MIP; GENE; CATARACTS; SEQUENCE; FAMILY C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chepelinsky, AB (reprint author), NEI, Mol & Dev Biol Lab, NIH, 7 Mem Dr,MSC 0704, Bethesda, MD 20892 USA. NR 46 TC 19 Z9 19 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-104X J9 J EXP ZOOL PART A JI J. Exp. Zool. Part A PD NOV 1 PY 2003 VL 300A IS 1 BP 41 EP 46 DI 10.1002/jez.a.10307 PG 6 WC Zoology SC Zoology GA 738MQ UT WOS:000186292800007 PM 14598384 ER PT J AU Miller, DS AF Miller, DS TI Confocal imaging of xenobiotic transport across the blood-brain barrier SO JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-COMPARATIVE EXPERIMENTAL BIOLOGY LA English DT Article; Proceedings Paper CT 14th International Congress of Pure and Applied Biophysics CY MAY, 2002 CL MIAMI, FLORIDA ID P-GLYCOPROTEIN; ORAL BIOAVAILABILITY; ENDOTHELIAL-CELLS; PACLITAXEL TAXOL; MICE; MICROVESSELS; EXPRESSION; DRUGS; GENE; PERMEABILITY AB The brain capillary endothelium is a formidable barrier to entry of foreign chemicals into the central nervous system (CNS). For the most part it poorly distinguishes between therapeutics and neurotoxins and thus the blood-brain barrier both protects the brain from toxic chemicals and limits our ability to treat a variety of CNS disorders. Two elements underlie the barrier function of the brain capillary endothelium: 1) a physical barrier comprised of tight junctions, which form an effective seal to intercellular diffusion, and the cells themselves, which exhibit a low rate of endocytosis, and 2) a metabolic/active barrier, comprised of specific membrane transporters expressed by the endothelial cells. We have recently developed an experimental system based on confocal microscopy to study mechanisms of transport in freshly isolated brain capillaries. Here I review studies demonstrating a major role for the ATP-driven, xenobiotic export pump, p-glycoprotein, in barrier function and recent experiments showing that transient inhibition of pump function can have substantial benefit for chemotherapy in an animal model of brain cancer. (C) 2003 Wiley-Liss, Inc. C1 NIEHS, NIH, LPC, Res Triangle Pk, NC 27709 USA. RP Miller, DS (reprint author), NIEHS, NIH, LPC, POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 6 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-104X J9 J EXP ZOOL PART A JI J. Exp. Zool. Part A PD NOV 1 PY 2003 VL 300A IS 1 BP 84 EP 90 DI 10.1002/jez.a.10313 PG 7 WC Zoology SC Zoology GA 738MQ UT WOS:000186292800013 PM 14598390 ER PT J AU Sukhareva, M Hackos, DH Swartz, K AF Sukhareva, M Hackos, DH Swartz, K TI Constitutive activation of the Shaker Kv channel SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE voltage-dependent gating; hanatoxin; agitoxin; mutagenesis; potassium channel ID VOLTAGE-SENSING DOMAINS; DEPENDENT K+ CHANNEL; GATED ION CHANNELS; GATING MODIFIER TOXIN; POTASSIUM CHANNEL; INACTIVATION GATE; CRYSTAL-STRUCTURE; CLOSED STATE; MOVING PARTS; PORE AB Indifferent types of K+ channels the primary activation gate is thought to reside near the intracellular entrance to the ion conduction pore. In the Shaker Kv channel the gate is closed at negative membrane voltages, but can be opened with membrane depolarization. In a previous study of the S6 activation gate in Shaker (Hackos, D.H., T.H. Chang, and KJ. Swartz. 2002. J Gen. Physiol. 119:521-532.), we found that mutation of Pro 475 to Asp results in a channel that displays a large macroscopic conductance at negative membrane voltages, with only small increases in conductance with membrane depolarization. In the present study we explore the mechanism underlying this constitutively conducting phenotype using both macroscopic and single-channel recordings, and probes that interact with the voltage sensors or the intracellular entrance to the ion conduction pore. Our results suggest that constitutive conduction results from a dramatic perturbation of the closed-open equilibrium, enabling opening of the activation gate without voltage-sensor activation. This mechanism is discussed in the context of allosteric models for activation of Kv channels and what is known about the structure of this critical region in K+ channels. C1 NINDS, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Swartz, K (reprint author), NINDS, Mol Physiol & Biophys Sect, NIH, Bldg 36,Room 2C19,36 Convent Dr,MSC 4066, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA NS002945-13] NR 64 TC 59 Z9 61 U1 2 U2 3 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 NOV PY 2003 VL 122 IS 5 BP 541 EP 556 DI 10.1085/jgp.200308905 PG 16 WC Physiology SC Physiology GA 741YL UT WOS:000186487900007 PM 14557403 ER PT J AU Feng, CG Scanga, CA Collazo-Custodio, CM Cheever, AW Hieny, S Caspar, P Sher, A AF Feng, CG Scanga, CA Collazo-Custodio, CM Cheever, AW Hieny, S Caspar, P Sher, A TI Mice lacking myeloid differentiation factor 88 display profound defects in host resistance and immune responses to Mycobacterium avium infection not exhibited by Toll-like receptor 2 (TLR2)- and TLR4-deficient animals SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CUTTING EDGE; TUBERCULOSIS INFECTION; MYD88-DEFICIENT MICE; IL-18-DEFICIENT MICE; DENDRITIC CELLS; T-CELLS; INNATE; GENE; RECOGNITION; NEUTROPHILS AB To assess the role of Toll-like receptor (TLR) signaling in host resistance to Mycobacterium avium infection, mice deficient in the TLR adaptor molecule myeloid differentiation factor 88 (MyD88), as well as TLR2(-/-) and TLR4(-/-) animals, were infected with a virulent strain of M. avium, and bacterial burdens and immune responses were compared with those in wild-type (WT) animals. MyD88(-/-) mice failed to control acute and chronic M. avium growth and succumbed 9-14 wk postinfection. Infected TLR2(-/-) mice also showed increased susceptibility, but displayed longer survival and lower bacterial burdens than MyD88(-/-) animals, while TLR4(-/-) mice were indistinguishable from their WT counterparts. Histopathological examination of MyD88-/- mice revealed massive destruction of lung tissue not present in WT, TLR2(-/-), or TLR4(-/-) mice. In addition, MyD88(-/-) and TLR2(-/-), but not TLR4(-/-), mice displayed marked reductions in hepatic neutrophil infiltration during the first 2 h of infection. Although both MyD88(-/-) and TLR2(-/-) macrophages showed profound defects in IL-6, TNF, and IL-12p40 responses to M. avium stimulation in vitro, in vivo TNF and IL-12p40 mRNA induction was impaired only in infected MyD88(-/-) mice. Similarly, MyD88(-/-) mice displayed a profound defect in IFN-gamma response that was not evident in TLR2(-/-) or TLR4(-/-) mice or in animals deficient in IL-18. These findings indicate that resistance to mycobacterial infection is regulated by multiple MyD88-dependent signals in addition to those previously attributed to TLR2 or TLR4, and that these undefined elements play a major role in determining bacterial induced proinflammatory as well as IFN-gamma responses. C1 NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Feng, CG (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Room 6148,Bldg 50,50 S Dr, Bethesda, MD 20892 USA. NR 51 TC 136 Z9 140 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2003 VL 171 IS 9 BP 4758 EP 4764 PG 7 WC Immunology SC Immunology GA 735WD UT WOS:000186136800034 PM 14568952 ER PT J AU Chen, X Beutler, JA Oppenheim, JJ Howard, OMZ AF Chen, X Beutler, JA Oppenheim, JJ Howard, OMZ TI Tannic acid is a novel SDF-1a/CXCR4 inhibitor with potential anti-angiogenic activity SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Mol Targets Discovery Program, Frederick, MD 21701 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. RI Beutler, John/B-1141-2009; Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Beutler, John/0000-0002-4646-1924; Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 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 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S29 EP S29 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100092 ER PT J AU Finkelstein, S Antony, P Klebanoff, C Hwang, L Spiess, P Surman, D Palmer, D Heimann, D Yu, ZY Rosenberg, S Restifo, N AF Finkelstein, S Antony, P Klebanoff, C Hwang, L Spiess, P Surman, D Palmer, D Heimann, D Yu, ZY Rosenberg, S Restifo, N TI Adoptive transfer of CD8+T lymphocytes into lympho-depleted recipients results in breaking of tolerance, autoimmunity, and cancer regression SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S19 EP S20 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100064 ER PT J AU Giuseppe, S Fujiwara, H Rezvani, K Keyvanfar, K El Ouriaghli, F Adams, M Hensel, N Barrett, J AF Giuseppe, S Fujiwara, H Rezvani, K Keyvanfar, K El Ouriaghli, F Adams, M Hensel, N Barrett, J TI CD34+cells cultured in stem cell factor and IL-2 generate CD56+cells with antiproliferative effects on tumor cell lines SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S4 EP S4 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100014 ER PT J AU Gruys, ME Back, T Murphy, W Welniak, L Subleski, J Wiltrout, R AF Gruys, ME Back, T Murphy, W Welniak, L Subleski, J Wiltrout, R TI Subclones of a streptozotocin induced renal cell carcinoma as a new model for investigation of treatments for kidney cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Program, Frederick, MD USA. Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S39 EP S39 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100125 ER PT J AU Khan, T Hixon, J Stauffer, J Lincoln, E Back, T Wigginton, J AF Khan, T Hixon, J Stauffer, J Lincoln, E Back, T Wigginton, J TI IL-12 induced regression of orthotopic neuroblastoma tumors: Potential role for reversal of intrinsic mechanisms of resistance to tumor cell apoptosis SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, Pediat Oncol Branch, CCR, Frederick, MD 21701 USA. SAIC Frederick, IRSP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S24 EP S24 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100076 ER PT J AU Lathey, J Zhang, YP Gregory, S Manak, M D'Souza, P Lopaczynski, W AF Lathey, J Zhang, YP Gregory, S Manak, M D'Souza, P Lopaczynski, W TI Precision of the Elispot assay SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 BBI Biotech, Virol Immunol, Gaithersburg, MD USA. NIAID, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S47 EP S47 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100149 ER PT J AU Letsch, A Keilholz, U Mailaender, V Nagorsen, D Asemissen, AM Thiel, E Scheibenbogen, C AF Letsch, A Keilholz, U Mailaender, V Nagorsen, D Asemissen, AM Thiel, E Scheibenbogen, C TI Peptide vaccination induces specific effector and memory effector T cells but fails to enhance preexisting T cell immunity SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 Charite Univ Med, Hosp Benjamin Franklin, Med Clin 3, Berlin, Germany. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RI Mailander, Volker /H-3589-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S9 EP S9 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100032 ER PT J AU Malyguine, A Strobl, S Shafer-Weaver, K Derby, E Burkett, M Ulderich, T Baseler, M AF Malyguine, A Strobl, S Shafer-Weaver, K Derby, E Burkett, M Ulderich, T Baseler, M TI Elispot assay modifications in immunological monitoring SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, SAIC Frederick Inc, Clin Serv Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S48 EP S48 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100152 ER PT J AU Monsurro, V Wang, E Yamano, Y Migueles, S Panelli, M Smith, K Nagorsen, D Connors, M Jacobson, S Marincola, F AF Monsurro, V Wang, E Yamano, Y Migueles, S Panelli, M Smith, K Nagorsen, D Connors, M Jacobson, S Marincola, F TI Quiescent phenotype of tumor-specific CD8+T cells following immunization SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NIH, Immunogenet Sect, Dept Transfus Med, CC, Bethesda, MD 20892 USA. NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S31 EP S31 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100099 ER PT J AU Morrison, B Sakai, Y Janik, J Morris, J AF Morrison, B Sakai, Y Janik, J Morris, J TI Adenoviral transduction efficiency and phenotype of human monocyte-derived dendritic cells cultured with either fetal calf serum, human plasma, or under serum free conditions SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S10 EP S11 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100037 ER PT J AU Nagorsen, D Wang, E Monsurro, V Marincola, F Panelli, M AF Nagorsen, D Wang, E Monsurro, V Marincola, F Panelli, M TI Polarized macrophage response to cytokine stimulation SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NIH, Immunogenet Sect, DTM, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S11 EP S11 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100039 ER PT J AU Provenzano, M Mocellin, S Nagorsen, D Marincola, F Stroncek, D AF Provenzano, M Mocellin, S Nagorsen, D Marincola, F Stroncek, D TI Short-term ex vivo sensitization of memory T cells among PBMCs from seropositive subjects using cancer-related viral peptides is sufficient to evaluate immune reactivity at a molecular level SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Padua, Surg Branch, Dept Oncol & Surg Sci, I-35100 Padua, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S22 EP S22 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100070 ER PT J AU Qian, JH Dong, YJ Pang, YYS Ibrahim, R Engelhand, VH Berzofsky, JA Schiller, JT Khleif, SN AF Qian, JH Dong, YJ Pang, YYS Ibrahim, R Engelhand, VH Berzofsky, JA Schiller, JT Khleif, SN TI Augmentation of immune response to HPV 16 E7 using VLP-E7 chimeric fusion protein with GM-CSF and anti-CD40 in HLA-A2 transgenic mice SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat Branch, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Charlottesville, VA 22903 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S12 EP S12 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100041 ER PT J AU Sakai, Y Morrison, B Burke, J Janik, J Terabe, M Park, JM Forni, G Berzofsky, J Morris, J AF Sakai, Y Morrison, B Burke, J Janik, J Terabe, M Park, JM Forni, G Berzofsky, J Morris, J TI Vaccination by genetically modified dendritic cells expressing the HER-2/neu oncogene prevents development of spontaneous breast cancer in transgenic mice SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, NIH, Metab Branch, Bethesda, MD 20892 USA. Univ Turin, Orbassano, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S13 EP S14 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100046 ER PT J AU Sayers, T Brooks, A Onksen, J Elliott, P Murphy, W AF Sayers, T Brooks, A Onksen, J Elliott, P Murphy, W TI The proteasome inhibitor VELCADE (TM) sensitizes tumor cells to TRAIL-mediated apoptosis SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. Univ Nevada, Dept Microbiol, Reno, NV 89557 USA. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S35 EP S35 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100112 ER PT J AU Shorts, L Back, T Blazer, B Murphy, W Wiltrout, R AF Shorts, L Back, T Blazer, B Murphy, W Wiltrout, R TI CD40 signaling in renal cell carcinoma leads to increased cytokine expression and decreased tumor size SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, CCR, Expt Immunol Lab, Frederick, MD 21701 USA. SAIC, Expt Immunol Lab, Frederick, MD USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 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 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S41 EP S42 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100131 ER PT J AU Stauffer, JK Hixon, JA Back, TC Lincoln, E Khan, T Wigginton, JM AF Stauffer, JK Hixon, JA Back, TC Lincoln, E Khan, T Wigginton, JM TI Fluorescence-based in vivo models for monitoring and quantitating cytokine- or chemotherapy-induced alterations in the growth, metastasis, angiogenesis and apoptosis of neuroblastoma tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, CCR, Pediat Oncol Branch, Frederick, MD 21701 USA. SAIC Frederick, IRSP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S25 EP S25 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100079 ER PT J AU Thomasson, D Choyke, P Dwyer, A Yao, J AF Thomasson, D Choyke, P Dwyer, A Yao, J TI A comparison of pharmacokinetic modeling of dynamic contrast enhanced MRI for evaluating response in angiogenic inhibitor therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S26 EP S26 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100081 ER PT J AU Watanabe, M Yazawa, H Back, T Vasquez, D Bromberg, N Murakami, T Shorts, L Subleski, J Wiltrout, R AF Watanabe, M Yazawa, H Back, T Vasquez, D Bromberg, N Murakami, T Shorts, L Subleski, J Wiltrout, R TI Hydrodynamic gene delivery of Kringle-5 domain of plasminogen suppresses lung metastasis in mouse renal cell carcinoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, LEI, CCR, Frederick, MD 21701 USA. NCI, LMI, CCR, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S30 EP S30 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100096 ER PT J AU Wigginton, J Donovan, C Choyke, P Wiltrout, R Janik, J AF Wigginton, J Donovan, C Choyke, P Wiltrout, R Janik, J TI A phase I investigation of dose-intensive intravenous IL-12/pulse IL-2 in adults with advanced solid tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, CCR, Pediat Oncol Branch, Frederick, MD 21701 USA. Dept Radiol, Funct Tumor Imaging Grp, Bethesda, MD USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. NCI, CCR, Metab Branch, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S42 EP S43 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100135 ER PT J AU Yao, ZS Dai, WL Perry, J Brechbiel, M Sung, C AF Yao, ZS Dai, WL Perry, J Brechbiel, M Sung, C TI Effect of albumin fusion on the biodistribution of interleukin-2 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 Human Genome Sci Inc, Clin & Preclin Pharmacol, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S37 EP S37 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100117 ER PT J AU Yazawa, H Murakami, T Back, T Suzuki, Y Parsoneault, E Gruys, M Wiltrout, R AF Yazawa, H Murakami, T Back, T Suzuki, Y Parsoneault, E Gruys, M Wiltrout, R TI Anti-VEGF therapy by hydrodynamic delivery suppresses growth of renal cell carcinoma that expresses multiple pro-angiogenic factors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 NCI, LEI, CCR, Frederick, MD 21701 USA. NCI, LMI, CCR, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S30 EP S30 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100097 ER PT J AU Terunuma, A Jackson, KL Kapoor, V Telford, WG Vogel, JC AF Terunuma, A Jackson, KL Kapoor, V Telford, WG Vogel, JC TI Side population keratinocytes resembling bone marrow side population stem cells are distinct from label-retaining keratinocyte stem cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE ABC transporters; Hoechst 33342; integrins ID TRANSIT AMPLIFYING CELLS; IN-VIVO; HEMATOPOIETIC PROGENITORS; MULTIDRUG-RESISTANCE; SURFACE PHENOTYPE; EFFLUX PUMP; EXPRESSION; CD34; TERM; SKIN AB Very primitive hematopoietic stem cells have been identified as side population cells based on their ability to efflux a fluorescent vital dye, Hoechst 33342. In this study we show that keratinocytes with the same side population phenotype are also present in the human epidermis. Although side population keratinocytes have the same dye-effluxing phenotype as bone marrow side population cells and can be blocked by verapamil, they do not express increased levels of the ABCG2 transporter that is believed to be responsible for the bone marrow side population phenotype. Because bone marrow side population cells have stem cell characteristics, we sought to determine if side population keratinocytes represent a keratinocyte stem cell population by comparing side population keratinocytes with a traditional keratinocyte stem cell candidate, label-retaining keratinocytes. Flow cytometric analyses demonstrated that side population keratinocytes have a different cell surface phenotype (low beta1 integrin and low alpha6 integrin expression) than label-retaining keratinocytes and represent a unique population of keratinocytes distinctly different from the traditional keratinocyte stem cell candidate. Future in vivo studies will be required to analyze the function of side population keratinocytes in epidermal homeostasis and to determine if side population keratinocytes have characteristics of keratinocyte stem cells. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Vogel, JC (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12 N260,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. NR 44 TC 78 Z9 80 U1 2 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1095 EP 1103 DI 10.1046/j.1523-1747.2003.12531.x PG 9 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200030 PM 14708612 ER PT J AU Noonan, FP Muller, HK Fears, TR Kusewitt, DF Johnson, TM De Fabo, EC AF Noonan, FP Muller, HK Fears, TR Kusewitt, DF Johnson, TM De Fabo, EC TI Mice with genetically determined high susceptibility to ultraviolet (UV)-induced immunosuppression show enhanced UV carcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE skin cancer; risk factor; ultraviolet radiation; immunosuppression ID SQUAMOUS-CELL CARCINOMAS; SKIN-CANCER; IMMUNOLOGICAL-UNRESPONSIVENESS; TUMOR PROGRESSION; IRRADIATED MICE; RADIATION; MOUSE; INVASION; MODELS AB To assess the premise that genetically determined differences in susceptibility to UV-induced immunosuppression are reflected in UV carcinogenesis, we investigated UV skin cancer induction in two strains of reciprocal F-1 hybrid mice CB6F(1) males with high susceptibility to UV immunosuppression and a BALB/c X-chromosome and B6CF(1) males with low susceptibility to UV immunosuppression and a C57BL/6 X-chromosome. Four experimental groups comprising both strains treated three times weekly with two UV regimens (daily doses incremented from 2.25 to 6 or 4.5 to 12 kJ per m(2)) were monitored for skin tumor development. Survival without a skin tumor differed over the four groups (p< 0.0001) and differed according to UV regimen within each strain (p<0.0005). Differences between strains were significant for the higher dose (p=0.03) but not for the lower dose (p=0.19) of UV, suggesting a dose-strain interaction. Comparing the higher UV dose regimen to the lower UV dose regimen within a strain at three reference points, tumor-free survival was reduced significantly more (p<0.05) in the CB6F(1) mice than in the B6CF(1) mice. Histologic assessment of all tumors revealed fibrosarcomas, squamous carcinomas, and mixed tumors. Immunohistochemistry of the mixed tumors for vimentin, keratin, and E-cadherin confirmed the presence of squamous and fibrosarcomatous elements. The enhanced susceptibility to UV carcinogenesis of CB6F(1) males treated with the higher UV pro-tocol was attributable to a significantly enhanced proportion (p<0.005) of mixed tumors. Analysis of the data by comparing the proportion of animals tumor free at three reference time points confirmed a dose-strain interaction only in the development of mixed tumors, putatively the malignantly advanced carcinomas (p<0.03). A dose-strain interaction was also observed for systemic UV immunosuppression of contact hypersensitivity (p<0.025). These findings support the concept that genetic differences in susceptibility to UV-induced immunosuppression may be a risk factor for skin cancer. C1 George Washington Univ, Med Ctr,Lab Photobiol & Photoimmunol, Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Washington, DC 20037 USA. Univ Tasmania, Sch Med, Discipline Pathol, Hobart, Tas, Australia. NCI, Biostat Branch, Bethesda, MD 20892 USA. Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. RP Noonan, FP (reprint author), George Washington Univ, Med Ctr,Lab Photobiol & Photoimmunol, Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Ross Hall,Room 113,2300 Eye St NW, Washington, DC 20037 USA. FU NCI NIH HHS [CA53765] NR 34 TC 15 Z9 15 U1 3 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1175 EP 1181 DI 10.1046/j.1523-1747.2003.12560.x PG 7 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200041 PM 14708623 ER PT J AU Trempus, CS Morris, RJ Cotsarelis, G Tennant, RW AF Trempus, CS Morris, RJ Cotsarelis, G Tennant, RW TI CD34 in human hair follicle - Response SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter C1 NIEHS, Natl Ctr Toxicogen, Res Triangle Pk, NC 27709 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA. RP Trempus, CS (reprint author), NIEHS, Natl Ctr Toxicogen, POB 12233, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1220 EP 1221 DI 10.1046/j.1523-1747.2003.12550_3.x PG 2 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200049 ER PT J AU Udey, M Ehrchen, J Belkaid, Y Lopez-Kostka, S Molle, K Knop, J Sunderkotter, C von Stebut, E AF Udey, M Ehrchen, J Belkaid, Y Lopez-Kostka, S Molle, K Knop, J Sunderkotter, C von Stebut, E TI IL-1 alpha promotes Th(1-)differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Langerhans Cells CY SEP 05-07, 2003 CL TOKYO, JAPAN C1 NCI, Ctr Canc Res, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. Univ Cincinnati, Childrens Hosp Res Fdn, Dept Mol Immunol, Cincinnati, OH 45221 USA. Univ Munster, Inst Expt Dermatol, D-4400 Munster, Germany. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1234 EP 1234 PG 1 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200065 ER PT J AU Tada, YY Riedl, E Udey, MC AF Tada, YY Riedl, E Udey, MC TI Generation and characterization of recombinant soluble mouse Langerin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Langerhans Cells CY SEP 05-07, 2003 CL TOKYO, JAPAN C1 NCI, Ctr Canc Res, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1236 EP 1236 PG 1 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200076 ER PT J AU Kopp, T Lenz, P Bello-Fernandez, C Kastelein, RA Kupper, TS Stingl, G AF Kopp, T Lenz, P Bello-Fernandez, C Kastelein, RA Kupper, TS Stingl, G TI IL-23 production by cosecretion of endogenous p19 and transgenic p40 in K14/p40 Transgenic mice: Evidence for enhanced cutaneous immunity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Langerhans Cells CY SEP 05-07, 2003 CL TOKYO, JAPAN C1 Univ Vienna, Dept Dermatol, DIAID, Sch Med, Vienna, Austria. Univ Vienna, Inst Immunol, Sch Med, Vienna, Austria. NCI, Bethesda, MD 20892 USA. DNAX Res Inst Molec & Cellular Biol Inc, Palo Alto, CA USA. Harvard Skin Dis Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1238 EP 1238 PG 1 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200085 ER PT J AU Cardones, A Murakami, T Hwang, S AF Cardones, A Murakami, T Hwang, S TI Ligation of CD86 increases dendritic cell (DC) capture of naive T cells and upregulates CD40 and MHC II expression SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Langerhans Cells CY SEP 05-07, 2003 CL TOKYO, JAPAN C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1239 EP 1239 PG 1 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200091 ER PT J AU Kawamura, T Sugaya, M Shimada, S Blauvelt, A AF Kawamura, T Sugaya, M Shimada, S Blauvelt, A TI R5 HIV interacts with LC through a CCR5-dependent, DC-SIGN-independent infection pathway SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Langerhans Cells CY SEP 05-07, 2003 CL TOKYO, JAPAN C1 Yamanashi Univ, Dept Dermatol, Yamanashi, Japan. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1240 EP 1240 PG 1 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200100 ER PT J AU Riedl, E Tada, Y Udey, MC AF Riedl, E Tada, Y Udey, MC TI Expression analysis of mouse Langerin and an alternatively spliced isoform in fetal skin-derived dendritic cells and mouse tissues SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 8th International Workshop on Langerhans Cells CY SEP 05-07, 2003 CL TOKYO, JAPAN C1 Univ Vienna, Dept Dermatol, Vienna, Austria. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 1244 EP 1244 PG 1 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200118 ER PT J AU Lu, SY Hong, JS Pike, VW AF Lu, SY Hong, JS Pike, VW TI Synthesis of NCA [carbonyl-C-11]amides by direct reaction of in situ generated [C-11]carboxymagnesium halides with amines under microwave-enhanced conditions SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE carbon-11; amide; grignard reagent; microwave; [C-11]carbon dioxide ID 5-HT1A RECEPTORS; GRIGNARD-REAGENT; CARBOXYLIC-ACIDS; RAPID SYNTHESIS; RADIOLIGAND; AMIDES; DERIVATIVES; CHLORIDES; AGENTS; SYSTEM AB No-carrier-added (NCA) aromatic and aliphatic [carbonyl-C-11]amides were rapidly (<5 min) synthesized in one pot in useful radiochemical yields (20-65%, decay-corrected) by directly coupling amines with NCA [C-11]carboxy-magnesium halides generated in situ from Grignard reagents and cyclotron-produced [C-11]carbon dioxide. In this system cyclohexylcarboxymagnesium chloride (1b) is more reactive than 4-fluorophenylcarboxymagnesium bromide (2b) and primary amines (e.g. aniline, aminopyridines) far more reactive than secondary amines (e.g. 2-(methylamino)pyridine). The scope of the reaction was widened considerably by the application of microwaves, which allowed reactions to be carried out at much higher temperature than the boiling point of the solvent (i.e. tetrahydrofuran, b.p. 67degreesC). Copyright (C) 2003 John Wiley Sons, Ltd. C1 NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Lu, SY (reprint author), NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, NIH, Bldg 10,Room B3C346,10 Ctr Dr, Bethesda, MD 20892 USA. EM lus@intra.nimh.nih.gov OI Lu, Shuiyu/0000-0003-0310-4318 NR 27 TC 15 Z9 15 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 2003 VL 46 IS 13 BP 1249 EP 1259 DI 10.1002/jlcr.786 PG 11 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 751HP UT WOS:000187060000008 ER PT J AU Wahl, SM Greenwell-Wild, T Peng, G Ma, G Orenstein, JM Vazquez, N AF Wahl, SM Greenwell-Wild, T Peng, G Ma, G Orenstein, JM Vazquez, N TI Viral and host cofactors facilitate HIV-1 replication in macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE opportunistic infections; cDNA expression array; p21; SLPI; Vpr ID IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE PROTEASE INHIBITOR; NF-KAPPA-B; MONOCYTE-DERIVED MACROPHAGES; CELLS EFFICIENTLY TRANSMIT; IMMATURE DENDRITIC CELLS; CD4(+) T-CELLS; GENE-EXPRESSION; DC-SIGN; MONONUCLEAR PHAGOCYTES AB Human immunodeficiency virus type 1 (HIV-1) infection of CD4(+) T lymphocytes leads to their progressive loss, whereas HIV-1-infected macrophages appear to resist HIV-1-mediated apoptotic death. The differential response of these two host-cell populations may be critical in the development of immunodeficiency and long-term persistence of the virus. Multiple contributing factors may favor the macrophage as a resilient host, not only supporting infection by HIV-1 but also promoting replication and persistence of this member of the lentivirus subfamily of primate retroviruses. An encounter between macrophages and R5 virus engages a signal cascade eventuating in transcriptional regulation of multiple genes including those associated with host defense, cell cycle, nuclear factor-kappaB regulation, and apoptosis. It is important that enhanced gene expression is transient, declining to near control levels, and during this quiescent state, the virus continues its life cycle unimpeded. However, when viral replication becomes prominent, an increase in host genes again occurs under the orchestration of viral gene products. This biphasic host response must fulfill. the needs of the parasitic virus as viral replication activity occurs and leads to intracellular and cell surface-associated viral budding. Inroads into understanding how HIV-1 co-opts host factors to generate a permissive environment for viral replication and transmission to new viral hosts may provide opportunities for targeted interruption of this lethal process. J. Leukoc. Biol. 74: 726-735; 2003. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Dept Pathol, Washington, DC 20052 USA. RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 320,30 Convent Dr,MSC4352, Bethesda, MD 20892 USA. NR 108 TC 46 Z9 46 U1 0 U2 1 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 NOV PY 2003 VL 74 IS 5 BP 726 EP 735 DI 10.1189/jlb.0503220 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755FG UT WOS:000187392400013 PM 12960226 ER PT J AU Igarashi, T Imamichi, H Brown, CR Hirsch, VM Martin, MA AF Igarashi, T Imamichi, H Brown, CR Hirsch, VM Martin, MA TI The emergence and characterization of macro phage-tropic SIV/HIV chimeric viruses (SHIVs) present in CD4(+) T cell-depleted rhesus monkeys SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE immunodeficiency; in situ hybridization; viral load; lymphocyte depletion; HIV env; V2 loop ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR-BINDING; TYPE-1 ISOLATE; CONFORMATIONAL-CHANGES; ALVEOLAR MACROPHAGES; GP120 GLYCOPROTEIN; HIV INFECTION; DUAL TROPISM; V2 REGION; IN-VITRO AB Highly pathogenic simian immunodeficiency virus/human immunodeficiency virus type 1 chimeric viruses (SHIVs) induce an extremely rapid, systemic, and irreversible depletion of CD4(+) T lymphocytes following their inoculation into rhesus macaques. Confocal fluorescence microscopy was used to demonstrate that high levels of viremia in infected animals were sustained by virus-producing tissue macrophage (mphi) following the irreversible elimination of CD4(+) T lymphocytes by highly pathogenic SHIVDH12R. The envelope glycoproteins carried by plasma virus in CD4-depleted animals were found to contain specific alterations affecting the V2 region of gp120; similar V2 changes were observed during independent monkey infections. The altered V2 loops contained double amino acid deletions and the loss of a highly conserved N-linked glycosylation site. In contrast to the starting highly pathogenic SHIV, which is exclusively T cell-tropic, some mphi-phase SHIVs, bearing altered V2 regions, were able to establish spreading infections of cultured alveolar mphi. J. Leukoc. Biol. 74: 772-780; 2003. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp Frederick Inc, Frederick, MD USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 35 Z9 37 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 NOV PY 2003 VL 74 IS 5 BP 772 EP 780 DI 10.1189/jlb.0503196 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755FG UT WOS:000187392400018 PM 14595005 ER PT J AU Villalba, S Salvucci, O Aoki, Y Sierra, MD Gupta, G Davis, D Wyvill, K Little, R Yarchoan, R Tosato, G AF Villalba, S Salvucci, O Aoki, Y Sierra, MD Gupta, G Davis, D Wyvill, K Little, R Yarchoan, R Tosato, G TI Serum inactivation contributes to the failure of stromal-derived factor-1 to block HIV-1 infection in vivo SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemokine; cytokine; chemokine processing; AIDS; anti-HIV therapy ID CHEMOKINE RECEPTOR CXCR4; HEMATOPOIETIC PROGENITOR CELLS; HUMAN ENDOTHELIAL-CELLS; BONE-MARROW; LYMPHOCYTE CHEMOATTRACTANT; MOLECULAR-CLONING; B-LYMPHOPOIESIS; FLOW CONDITIONS; GENE VARIANT; SDF-1 AB The chemokine stromal-derived factor-1 (SDF-1) can block human immunodeficiency virus type I (HIV-1) infection in vitro by binding to the CXC chemokine receptor, CXCR-4, which serves as a coreceptor for T cell tropic HIV-1. In spite of being constitutively expressed in vivo, SDF-1 does not appear to block HIV-1 infection and spread in vivo. We report that SDF-1 is consistently measured in normal serum (15.4 +/- 3.0 ng/ml; mean +/- SD) and in serum from AIDS patients (16.6 +/- 3.7 ng/ml). However, we find that circulating SDF-1 is modified to an inactive form. When exposed to serum, recombinant SDF-1 is specifically and rapidly altered to yield an apparently smaller chemokine that does not bind to SDF-1 receptor-expressing cells, does not have chemoattractive or pre-B cell stimulatory activity, and does not block HIV-1 infection. Thus, serum modification and inactivation contribute to the failure of SDF-1 to block HIV-1 infection and spread in man. The inactivation of circulating SDF-1 may be critical in permitting local gradients to develop and direct cell trafficking. C1 NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat, Rockville, MD USA. RP Villalba, S (reprint author), NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 12N226,MSC 1907, Bethesda, MD 20892 USA. NR 55 TC 24 Z9 25 U1 0 U2 0 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 NOV PY 2003 VL 74 IS 5 BP 880 EP 888 DI 10.1189/jlb.0403149 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755FG UT WOS:000187392400028 PM 12960279 ER PT J AU Kellman, P Derbyshire, JA McVeigh, ER AF Kellman, P Derbyshire, JA McVeigh, ER TI Automatic in-plane rotation for doubly-oblique cardiac imaging SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the International-Society-of-Magnetic-Resonance-in-Medicine CY JUL 10-16, 2003 CL TORONTO, CANADA SP Int Soc Magnet Resonance Med DE MRI; oblique; in-plane rotation; cardiac imaging; SENSE AB Purpose: To develop and test a method for automatically calculating the in-plane rotation for doubly-oblique slice geometry in order to minimize wrap artifacts for a given FOV. Materials and Methods: The equations for in-plane rotation were formulated for doubly-oblique imaging of a cylindrical body with elliptical cross-section. Based on this formulation, automatic in-plane rotation was implemented and tested on a commercial scanner using nominal values for ellipticity of the body. Results: Short axis, doubly oblique, cardiac imaging were acquired with and without in-plane rotation. The desired in-plane rotation proved to be relatively insensitive to the ellipticity of the body, permitting an automatic solution based on a nominal value. Conclusion: In-plane rotation is desirable for doubly oblique imaging (e.g., cardiac applications), particularly for reduced-FOV accelerated imaging such as SENSE. The proposed method, which provides an approximate solution for automatic, in-plane rotation for doubly-oblique imaging, was demonstrated. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC-1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL004608-08] NR 3 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2003 VL 18 IS 5 BP 612 EP 615 DI 10.1002/jmri.10398 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 738NT UT WOS:000186295300012 PM 14579405 ER PT J AU Sinz, A Jin, AJ Zschornig, O AF Sinz, A Jin, AJ Zschornig, O TI Evaluation of the metal binding properties of a histidine-rich fusogenic peptide by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE bindin; binding constant; copper(II) binding; electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry; peptide-metal interaction ID FERTILIZATION PROTEIN BINDIN; PRION PROTEIN; CAPILLARY-ELECTROPHORESIS; MEMBRANE-FUSION; COPPER-BINDING; COMPLEXES; STABILITY; SEQUENCE; LIGANDS; SPERM AB Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS) was used to investigate metal ion interactions of the 18 amino acid peptide fragment B18 (LGLLLRHLRHH SNLLANI), derived from the membrane-associated protein bindin. The peptide sequence B18 represents the minimal membrane-binding motif of bindin and resembles a putative fusion peptide. The histidine-rich peptide has been shown to self-associate into distinct supramolecular structures, depending on the presence of Zn2+ and Cu2+. We examined the binding of B18 to the metal ions Cu2+, Zn2+, Mg2+, Ca2+, Mn2+ and La3+. For Cu2+, we compared the metal binding affinities of the wild-type B18 peptide with those of its mutants in which one, two or three histidine residues have been replaced by serines. Upon titration of B18 with Cu2+ ions, we found sequential binding of two Cu2+ ions with dissociation constants of similar to34 and similar to725 mum. Mutants of 1318, in which one histidine residue is replaced by serine, still exhibit sequential binding of two copper ions with affinities for the first Cu2+ ion comparable to that of wild-type B18 peptide, but with a greatly reduced affinity for the second Cu2+ ion in mutants H112S and H113S. For mutants in which two histidines are replaced by serines, the affinity for the first Cu2+ ion is reduced similar to3-10 times in comparison with B18. The mutant in which all three histidine residues are replaced by serines exhibits an similar to14-fold lower binding for the first Cu2+ ion compared with B18. For the other metal ions under investigation (Zn2+, Mg2+, Ca2+, Mn2+ and La3+), a modest affinity to B18 was detected binding to the peptide in a 1:1 stoichiometry. Our results show a high affinity of the wild-type fusogenic peptide B18 for Cu2+ ions whereas the Zn2+ affinity was found to be comparable to that of other di- and trivalent metal ions. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Leipzig, Fac Chem & Mineral, Biotechnol & Biomed Ctr, D-04103 Leipzig, Germany. NIH, Div Bioengn & Phys Sci, ORS, Off Director, Bethesda, MD 20892 USA. Univ Leipzig, Dept Med Phys & Biophys, Leipzig, Germany. RP Sinz, A (reprint author), Univ Leipzig, Fac Chem & Mineral, Biotechnol & Biomed Ctr, Linnestr 3, D-04103 Leipzig, Germany. EM sinz@chemie.uni-leipzig.de OI Jin, Albert/0000-0003-3826-1081 NR 26 TC 13 Z9 13 U1 2 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD NOV PY 2003 VL 38 IS 11 BP 1150 EP 1159 DI 10.1002/jms.532 PG 10 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 749VC UT WOS:000186948700003 PM 14648822 ER PT J AU Ma, L Kutty, G Jia, QY Kovacs, JA AF Ma, L Kutty, G Jia, QY Kovacs, JA TI Characterization of variants of the gene encoding the p55 antigen in Pneumocystis from rats and mice SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID MAJOR SURFACE GLYCOPROTEIN; DIHYDROFOLATE-REDUCTASE GENE; CARINII; EXPRESSION; ANTIBODIES; FAMILY AB Variants of the p55 gene in rat-derived Pneumocystis carinii have been identified and its counterpart in mouse-derived P. carinii f. sp. muris has been cloned. By PCR amplification of P. carinii genomic DNA, five variants were identified that differed from each other in size and sequence, primarily in the number and size of encoded amino acid repeats. For P. carinii f. sp. muris, a single PCR fragment (471 bp) was obtained, which contained an incomplete ORF encoding a 157 aa protein that was most similar to a p55 variant in P. carinii, with nucleotide and amino acid sequence identity of 79 and 68%, respectively. Southern blot analysis revealed the presence of more than one copy of the p55 gene in both Pneumocystis species. Thus, like other Pneumocystis antigens, p55 exhibits polymorphism that could potentially benefit the organism in host interactions. C1 Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. EM jkovacs@nih.gov NR 18 TC 11 Z9 19 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD NOV PY 2003 VL 52 IS 11 BP 955 EP 960 DI 10.1099/jmm.0.05131-0 PG 6 WC Microbiology SC Microbiology GA 803NW UT WOS:000220238800004 PM 14532339 ER PT J AU Chen, SHM Stins, MF Huang, SH Chen, YH Kwon-Chung, KJ Chang, Y Kim, KS Suzuki, K Jong, AY AF Chen, SHM Stins, MF Huang, SH Chen, YH Kwon-Chung, KJ Chang, Y Kim, KS Suzuki, K Jong, AY TI Cryptococcus neoformans induces alterations in the cytoskeleton of human brain microvascular endothelial cells SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID TIGHT JUNCTION PERMEABILITY; ESCHERICHIA-COLI INVASION; CAPSULE-ASSOCIATED GENE; ACTIN CYTOSKELETON; LIM-KINASE; IN-VITRO; PROTEIN-KINASE; VIRULENCE; OCCLUDIN; BARRIER AB The fungal pathogen Cryptococcus neoformans has a predilection for the central nervous system (CNS), resulting in devastating meningoencephalitis. At present, it is unclear how C. neoformans traverses the blood-brain barrier (BBB) and causes CNS infection. The present study has examined and characterized the interaction of C. neoformans with human brain microvascular endothelial cells (HBMEC), which constitute the BBB. Adhesion of and transcytosis of HBMEC by C. neoformans was inoculum- and time-dependent and occurred with both encapsulated and acapsulated strains. C. neoformans induced marked morphological changes in HBMEC, for example membrane ruffling, irregular nuclear morphology and swelling of the mitochondria and the ER. These findings suggest that C. neoformans induced actin cytoskeletal reorganization of the host cells. In addition, it was observed that the dephosphorylated form of cofilin was increased during cryptococcal adherence to HBMEC concomitant with the actin rearrangement. Cryptococcal binding to HBMEC was increased in the presence of Y27632, a Rho kinase (ROCK)-specific inhibitor. Since ROCK activates LIM kinase (LIMK), which phosphorylates cofilin (inactive form), this suggests the involvement of the ROCK--> LIMK-->cofilin pathway. In contrast, the phosphatase inhibitor sodium orthovanadate decreased adherence of Cryptococcus to HBMEC, concomitant with the increase of phosphorylation of cofilin. Furthermore, the tight junction marker protein occludin became Triton-extractable, indicating alteration of tight junctions in brain endothelial cells. This is the first demonstration that C. neoformans is able to adhere to and transcytose across the HBMEC monolayer and alter the cytoskeleton morphology in HBMEC. Further characterization of the interactions between C. neoformans and HBMEC should help the development of novel strategies to prevent cryptococcal meningitis and its associated morbidity. C1 Childrens Hosp Los Angeles, Div Hematol & Oncol, Los Angeles, CA 90027 USA. Childrens Hosp Los Angeles, Div Infect Dis, Los Angeles, CA 90027 USA. Johns Hopkins Univ, Baltimore, MD 21287 USA. NIAID, Lab Clin Invest, Bethesda, MD 20892 USA. Natl Inst Hlth Sci, Tokyo 158, Japan. RP Jong, AY (reprint author), Childrens Hosp Los Angeles, Div Hematol & Oncol, Los Angeles, CA 90027 USA. EM ajong@chia.usc.edu FU NHLBI NIH HHS [HL 61951]; NIAID NIH HHS [R29 AI 40635, AI 47225]; NINDS NIH HHS [R01 NS 26310] NR 54 TC 97 Z9 114 U1 0 U2 7 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD NOV PY 2003 VL 52 IS 11 BP 961 EP 970 DI 10.1002/jmm.0.05230-0 PG 10 WC Microbiology SC Microbiology GA 803NW UT WOS:000220238800005 PM 14532340 ER PT J AU Bhagwat, AA Phadke, RP Wheeler, D Kalantre, S Gudipati, M Bhagwat, M AF Bhagwat, AA Phadke, RP Wheeler, D Kalantre, S Gudipati, M Bhagwat, M TI Computational methods and evaluation of RNA stabilization reagents for genome-wide expression studies SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE gene arrays; E. coli; gene expression ID ESCHERICHIA-COLI; GENE-EXPRESSION; DNA MICROARRAYS; GLOBAL ANALYSIS; ACID CHALLENGE; ENCYCLOPEDIA; DATABASE AB Gene expression studies require high quality messenger RNA (mRNA) in addition to other factors such as efficient primers and labeling reagents. To prevent RNA degradation and to improve the quality of gene array expression data, several commercial reagents have become available. We examined a conventional hot-phenol lysis method and RNA stabilization reagents, and generated comparative gene expression profiles from Escherichia coli cells grown on minimal medium. Our data indicate that certain RNA stabilization reagents induce stress responses and proper caution must be exercised during their use. We observed that the laboratory reagent (phenol/EtOH, 5:95, v/v) worked efficiently in isolating high quality mRNA and reproducibility was such that reliable gene expression profiles were generated. To assist in the analysis of gene expression data, we wrote a number of macros that use the most recent gene annotation and process data in accordance with gene function. Scripts were also written to examine the occurrence of artifacts, based on GC content, length of the individual open reading frame (ORF), its distribution on plus and minus DNA strands, and the distance from the replication origin. Published by Elsevier B.V. C1 USDA ARS, Beltsville Agr Res Ctr, Produce Qual & Safety Lab, Beltsville, MD 20705 USA. Ramnarain Ruia Coll, Dept Microbiol, Bombay 400019, Maharashtra, India. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Bhagwat, AA (reprint author), USDA ARS, Beltsville Agr Res Ctr, Produce Qual & Safety Lab, 10300 Baltimore Ave, Beltsville, MD 20705 USA. NR 18 TC 27 Z9 28 U1 0 U2 0 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 NOV PY 2003 VL 55 IS 2 BP 399 EP 409 DI 10.1016/S0167-7012(03)00175-1 PG 11 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 733NA UT WOS:000186006000007 PM 14529961 ER PT J AU Naykova, TM Kondrakhin, YV Rogozin, IB Voevoda, MI Yudin, NS Romaschenko, AG AF Naykova, TM Kondrakhin, YV Rogozin, IB Voevoda, MI Yudin, NS Romaschenko, AG TI Concerted changes in the nucleotide sequences of the intragenic promoter regions of eukaryotic genes for tRNAs of all specificities SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE eukaryotic tRNA genes; intragenic promoters; particular types of tRNA genes ID POLYMERASE-III; TRANSCRIPTION; COMPLEXES AB RNA polymerase III promoter is located within the coding region in all eukaryotic tRNA genes, whereas in prokaryotic tRNA genes, the promoter is located upstream of the transcription initiation site. We analyzed the nucleotide sequence context of the A and B boxes of RNA polymerase III promoters from different unicellular eukaryotes, plants, and animals and the homologous sequences in the tRNA genes of prokaryotic species (Archaea, Eubacteria). The long and short sequence variants of the A box are nonrandomly distributed across different types of the eukaryotic tRNA genes. In contrast, the sequences from the prokaryotic counterparts of the long and short variants are randomly scattered among prokaryotic tRNA genes. The sequence diversity of the 3' portion of the A box in the eukaryotic tRNA genes was sharply reduced compared to that of the homologous segments of the prokaryotic tRNA genes. Analysis of the frequencies of oligonucleotide variants from different parts of the A box suggested that the prominent changes in the structure of the A box occurred at about the same time in all tRNA genes during the prokaryote-eukaryote evolutionary transition. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Lab Anim Mol Genet, Novosibirsk 630090, Russia. RP Romaschenko, AG (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD NOV PY 2003 VL 57 IS 5 BP 520 EP 532 DI 10.1007/s00239-003-2504-8 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 737XL UT WOS:000186257600004 PM 14738310 ER PT J AU Chang, FR Hayashi, K Chen, IH Liaw, CC Bastow, KF Nakanishi, Y Nozaki, H Cragg, GA Wu, YC Lee, KH AF Chang, FR Hayashi, K Chen, IH Liaw, CC Bastow, KF Nakanishi, Y Nozaki, H Cragg, GA Wu, YC Lee, KH TI Antitumor agents. 228. Five new agarofurans, reissantins A-E, and cytotoxic principles from Reissantia buchananiii SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID SESQUITERPENE PYRIDINE ALKALOIDS; TRITERPENES; CONSTITUENTS; DATURADIOL; TERPENOIDS; DITERPENES; WILFORDII; STEROIDS AB Twenty-one compounds, including five new agarofuran sesquiterpenes, reissantins A-E (1-5), were isolated from Reissantia buchananii by means of bioassay-directed fractionation and their structures identified from spectral data. Reissantins A-C are the first reported simple agarofuran sesquiterpenes to contain a 5-carboxy-N-methyl-2-pyridone (CNMP) substituent, which has previously been found only in macroring agarofuran pyridine alkaloids. The major terpenoid components, celastrol (6) and its methyl ester derivative, pristimerin (7), were significantly active against nine cancer cell lines, including A549, MCF-7, HCT-8, KB, KB-VIN, U-87-MG, PC-3, 1A9, and PTX10 cell lines, with ED50 values ranging from 0.076 to 0.34 mug/mL. C1 Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA. NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. Okayama Univ Sci, Fac Sci, Dept Biochem, Okayama 7000005, Japan. Kaohsiung Med Univ, Grad Inst Nat Prod, Kaohsiung 807, Taiwan. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA. EM khlee@unc.edu RI Chang, Fang-Rong/C-5692-2009; Wu, Yang-Chang/D-1471-2011; Wu, Yang-Chang/C-5682-2009 FU NCI NIH HHS [CA-17625] NR 23 TC 54 Z9 71 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD NOV PY 2003 VL 66 IS 11 BP 1416 EP 1420 DI 10.1021/np030241v PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 749GW UT WOS:000186912400003 PM 14640511 ER PT J AU Barnes, CC Smalley, MK Manfredi, KP Kindscher, K Loring, H Sheeley, DM AF Barnes, CC Smalley, MK Manfredi, KP Kindscher, K Loring, H Sheeley, DM TI Characterization of an anti-tuberculosis resin glycoside from the prairie medicinal plant Ipomoea leptophylla SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID RHIZOMA-JALAPAE-BRAZILIENSIS; OPERCULIN-II; ROOTS; STANS; IV AB The organic soluble extract from the leaves of the native North American prairie plant Ipomoea leptophylla (big root morning glory) showed in vitro activity against M. tuberculosis. Bioassay-guided fractionation of this extract resulted in the identification of two new resin glycosides (6, 7). Base-catalyzed hydrolysis of these glycosides gave operculinic acid (1) as the glycosidic acid component as well as trans-cinnamic acid, propanoic acid, and lauric acid. The complete structure elucidation was accomplished through derivatization, 1D and 2D NMR spectroscopy (TOCSY, ROESY, HSQC, HMBC), and MS/MS experiments on 6 and 7 as well as the permethylated derivative 8. C1 Univ No Iowa, Dept Chem, Cedar Falls, IA 50614 USA. NIH, NCRR, Bethesda, MD 20892 USA. Univ Kansas, Kansas Biol Survey, Lawrence, KS 66047 USA. RP Manfredi, KP (reprint author), Univ No Iowa, Dept Chem, Cedar Falls, IA 50614 USA. EM manfredi@uni.edu NR 22 TC 38 Z9 42 U1 3 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD NOV PY 2003 VL 66 IS 11 BP 1457 EP 1462 DI 10.1021/np030197j PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 749GW UT WOS:000186912400010 PM 14640518 ER PT J AU Chang, LC Whittaker, NF Bewley, CA AF Chang, LC Whittaker, NF Bewley, CA TI Crambescidin 826 and dehydrocrambine A: New polycyclic guanidine alkaloids from the marine sponge Monanchora sp that inhibit HIV-1 fusion SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ENVELOPE GLYCOPROTEIN GP120; CRAMBE-CRAMBE; PTILOMYCALIN-A; CELL-FUSION; BINDING; CD4; SITE; MINIPROTEIN; ANTIBODIES; EPITOPES AB Two new polycyclic guanidine alkaloids, crambescidin 826 (1) and dehydrocrambine A (2), and the known compounds crambescidin 800 (3) and fromiamycalin (4) were isolated from the marine sponge Monanchora sp. The structures of 1 and 2 were elucidated by 2D NMR and mass spectrometry, and relative stereochemistry was established by analysis of coupling constants and ROESY spectra. The pentacyclic guanidine alkaloids 1, 3, and 4 inhibit HIV-1 envelope-mediated fusion in vitro with IC50's of 1-3 muM, while compound 2, a tricyclic guanidine alkaloid, showed weaker inhibition, with an IC50 of similar to35 muM. C1 NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM caroleb@intra.niddk.nih.gov NR 23 TC 61 Z9 66 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD NOV PY 2003 VL 66 IS 11 BP 1490 EP 1494 DI 10.1021/np030256t PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 749GW UT WOS:000186912400017 PM 14640525 ER PT J AU Abbott, KC Trespalacios, FC Agodoa, LY AF Abbott, KC Trespalacios, FC Agodoa, LY TI Arteriovenous fistula use and heart disease in long-term elderly hemodialysis patients: Analysis of United States renal data system dialysis morbidity and mortality wave II SO JOURNAL OF NEPHROLOGY LA English DT Article DE arteriovenous fistula; vascular access; heart failure; acute coronary syndromes; myocardial infarction; survival; blood pressure; United States Renal Data System ID OUTPUT CARDIAC-FAILURE; VASCULAR ACCESS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; AV FISTULAS; SEPTICEMIA; OUTCOMES; IMPACT AB Background. There are some concerns that arteriovenous fistula (AVF) use or other dialysis specific factors may exacerbate cardiovascular disease in long-term hemodialysis (HD) patients. Methods: We performed a historical cohort study of the United States Renal Data System Dialysis Morbidity and Mortality Wave II study, limited to 993 patients who started HD in 1996 with valid information on vascular access and who were primarily eligible for Medicare at the start of the study. We assessed the association between hemodialysis vascular access and heart disease, defined as Medicare Claims for heart failure (HF, International Classification of Diseases (ICD9) code 428.x) and acute coronary syndromes (ACS, ICD9 code 410.x and 411.x). Cox proportional hazards regression (using propensity analysis) was used to model adjusted hazard ratios (AHR) for the association between patients factors and heart disease after dialysis. Results: The rate of HF per 100 person years at risk (PYAR) was 19.6 among AVF users, 25.7 among patients using polytetrafluoroethylene grafts (grafts), and 31.1 among patients temporary catheters. Corresponding rates of ACS were 8.2 among AVF users, 11.0 among users of grafts, and 12.4 among users of temporary catheters. In Cox Regression analysis, there was no significant association between AVF use and either BY or ACS. This lack of association was consistent across gender, diabetes, race, and age. Conclusions: We found that AVF use had no significant association with the incidence of HF or ACS. We conclude that use of AVF by 60 days after the start of dialysis is not associated with an increased risk of later non-fatal cardiovascular outcomes in long-term hemodialysis patients. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Madigan Army Med Ctr, Serv Nephrol, Ft Lewis, WA USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 28 TC 11 Z9 11 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1121-8428 J9 J NEPHROL JI J. Nephrol. PD NOV-DEC PY 2003 VL 16 IS 6 BP 822 EP 830 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 753ZM UT WOS:000187278300006 PM 14736009 ER PT J AU Burchett, SA AF Burchett, SA TI In through the out door: nuclear localization of the regulators of G protein signaling SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE nuclear translocation; phosphorylation; 14-3-3 proteins; regulator of G protein signaling ID GTP-BINDING PROTEIN; RETROGRADE AXONAL-TRANSPORT; SUBCELLULAR-LOCALIZATION; RGS PROTEINS; ACTIVATING PROTEIN; PLASMA-MEMBRANE; GGL DOMAIN; TRANSLOCATION; SUBUNIT; ALPHA AB The regulators of G protein signaling (RGS) are an extraordinary class of diverse multifunctional signaling proteins best known for their potent capacity to down-regulate the activity of Galpha subunits at the plasma membrane. In certain circumstances, some RGS proteins undergo translocation to the nucleus or plasma membrane from the cytoplasm. Translocation demonstrates a potentially dynamic alternative mechanism for Galpha subunit or effector regulation. The nuclear localization of the regulators of G protein signaling proteins further suggests these proteins possess even greater functional heterogeneity than that envisioned previously, as regulators of transcription and cell cycle control. C1 NICHHD, NIH, Lab Neural Connect, Bethesda, MD 20892 USA. RP Burchett, SA (reprint author), NICHHD, NIH, Lab Neural Connect, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. NR 54 TC 42 Z9 42 U1 2 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2003 VL 87 IS 3 BP 551 EP 559 DI 10.1046/j.1471-4159.2003.02047.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 732LJ UT WOS:000185946700002 PM 14535939 ER PT J AU Ghribi, O Herman, MM Pramoonjago, P Savory, J AF Ghribi, O Herman, MM Pramoonjago, P Savory, J TI MPP+ induces the endoplasmic reticulum stress response in rabbit brain involving activation of the ATF-6 and NF-kappa B signaling pathways SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ATF-6; caspase-3; endoplasmic reticulum; gadd 153; JNK; MPP+; NF-kappa B ID UNFOLDED PROTEIN RESPONSE; GLUCOSE-REGULATED PROTEINS; DOPAMINERGIC-NEURONS; PARKINSONIAN NEUROTOXIN; NUCLEAR TRANSLOCATION; CELLULAR-MODELS; CYTOCHROME-C; DISEASE; HIPPOCAMPUS; JNK AB Inhibition of mitochondrial function and the subsequent generation of oxidative stress are strongly suggested to underlie MPTP/MPP+-induced neurotoxicity, which has been used extensively as a model for Parkinson disease. In the present study we have examined the hypothesis that MPPI targets the endoplasmic reticulum. Because rabbits possess more genetic similarities to primates than to rodents we have selected this animal model system for our MPPI neurotoxicity studies. MPP+ was administered directly into the brain of New Zealand white rabbits via the intracisternal route, and the effects on tissue from the substantia nigra were examined. Here we demonstrate that MPPI in a dose-dependent manner induces the loss of tyrosine hydroxylase activity, oxidative DNA damage, and activation of the endoplasmic reticulum stress response. The endoplasmic reticulum response, mediated by activation of ATF-6 and NF-kappaB, leads to activation of gadd 153. These effects correlate with the activation of caspase-3 and of c-Jun N-terminal kinase (INK) kinase. We propose that pharmacological agents that inhibit the perturbation of endoplasmic reticulum function or the activation of INK may represent a potential therapeutic approach for the prevention of neurotoxin-induced Parkinson disease. C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. NIMH, IRP, NIH, Bethesda, MD 20892 USA. RP Ghribi, O (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, Box 800214, Charlottesville, VA 22908 USA. NR 29 TC 26 Z9 29 U1 1 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2003 VL 62 IS 11 BP 1144 EP 1153 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 744CV UT WOS:000186611100006 PM 14656072 ER PT J AU Kinney, HC Randall, LL Sleeper, LA Willinger, M Belliveau, RA Zec, N Rava, LA Dominici, L Iyasu, S Randall, B Habbe, D Wilson, H Mandell, F McClain, M Welty, TK AF Kinney, HC Randall, LL Sleeper, LA Willinger, M Belliveau, RA Zec, N Rava, LA Dominici, L Iyasu, S Randall, B Habbe, D Wilson, H Mandell, F McClain, M Welty, TK TI Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE alcohol; American Indian/Alaska Native; arcuate nucleus; cigarette smoking; Raphe; sudden infant death ID UTERO ETHANOL EXPOSURE; ARCUATE NUCLEUS; RECEPTOR-BINDING; DEVELOPMENTAL-CHANGES; NEURONS; HYPOPLASIA; TRANSMISSION; MEDULLA; SMOKING; SYSTEM AB The rate of the sudden infant death syndrome (SIDS) among American Indian infants in the Northern Plains is almost 6 times higher than in U.S. white infants. In a study of infant mortality among Northern Plains Indians, we tested the hypothesis that receptor binding abnormalities to the neurotransmitter serotonin (5-HT) in SIDS cases, compared with autopsied controls, occur in regions of the medulla oblongata that contain 5-HT neurons and that are critical for the regulation of cardiorespiration and central chemosensitivity during sleep, i.e. the medullary 5-HT system. Tritiated-lysergic acid diethylamide binding to 5-HT1D-D and 5-HT2 receptors was measured in 19 brainstem nuclei in 23 SIDS and 6 control infants using tissue receptor autoradiography. Binding in the arcuate nucleus, a part of the medullary 5-HT system along the ventral surface, in the SIDS infants (mean age-adjusted binding 7.1 +/- 0.8 fmol/mg tissue, n = 23) was significantly lower than in controls (mean age-adjusted binding 13.1 +/- 1.6 fmol/mg tissue, n 5) (p = 0.003). Binding also demonstrated significant diagnosis X age interactions (p < 0.04) in 4 other nuclei that are components of the 5-HT system. These data suggest that medullary 5-HT dysfunction can lead to sleep-related, sudden death in affected SIDS infants, and confirm the same binding abnormalities reported by us in a larger dataset of non-American Indian SIDS and control infants. This study also links 5-HT abnormalities in the arcuate nucleus with exposure to adverse prenatal exposures, i.e. cigarette smoking (p = 0.011) and alcohol (p = 0.075), during the periconceptional period or throughout pregnancy. Prenatal exposure to cigarette smoke and/or alcohol may contribute to abnormal fetal medullary 5-HT development in SIDS infants. C1 Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. US Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA USA. New England Res Inst, Watertown, MA 02172 USA. NICHHD, NIH, Bethesda, MD USA. Univ S Dakota, Sch Med, Dept Pathol, Sioux Falls, SD USA. Rapid City Reg Hosp, Dept Pathol, Rapid City, SD USA. Providence Mem Hosp, Dept Pathol, El Paso, TX USA. Boston Med Ctr, Dept Pediat, Boston, MA USA. Aberdeen Area Indian Hlth Serv, Rapid City, SD USA. RP Kinney, HC (reprint author), Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. FU PHS HHS [CRMC-92-05] NR 31 TC 111 Z9 116 U1 0 U2 7 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2003 VL 62 IS 11 BP 1178 EP 1191 PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 744CV UT WOS:000186611100009 PM 14656075 ER PT J AU Read, JCA Cumming, BG AF Read, JCA Cumming, BG TI Testing quantitative models of binocular disparity selectivity in primary visual cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CAT STRIATE CORTEX; SIMPLE CELLS; HORIZONTAL DISPARITY; COMPLEX CELLS; V1 NEURONS; DEPTH DISCRIMINATION; SPATIAL-FREQUENCY; NEURAL MECHANISMS; CORTICAL-NEURONS; ENERGY MODELS AB Disparity-selective neurons in striate cortex (V1) probably implement the initial processing that supports binocular vision. Recently, much progress has been made in understanding the computations that these neurons perform on retinal inputs. The binocular energy model has been highly successful in providing a simple theory of these computations. A key feature of the energy model is that it is linear until after inputs from the two eyes are combined. Recently, however, a modified version of the energy model, incorporating threshold nonlinearities before binocular combination, has been proposed to account for the weaker disparity tuning observed with anticorrelated stimuli. In this study, we present new data needed for a critical assessment of these two models. We compare two key predictions of the models with responses of disparity-selective neurons recorded from V1 of awake fixating monkeys. We find that the original energy model, and a family of generalizations retaining linear binocular combination, are quantitatively inconsistent with the response of V1 neurons. In contrast, the modified version incorporating threshold nonlinearities can explain both sets of observations. We conclude that the energy model can be reconciled with experimental observations by adding a threshold before binocular combination. This gives us the clearest picture yet of the computation being carried out by disparity-selective V1 neurons. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Read, JCA (reprint author), Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. RI Read, Jenny/A-7493-2013 OI Read, Jenny/0000-0002-9029-5185 FU NEI NIH HHS [Z01 EY000404-04] NR 35 TC 48 Z9 48 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV 1 PY 2003 VL 90 IS 5 BP 2795 EP 2817 DI 10.1152/jn.01110.2002 PG 23 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 742ZH UT WOS:000186547600001 PM 12867533 ER PT J AU Degen, JW Walbridge, S Vortmeyer, AO Oldfield, EH Lonser, RR AF Degen, JW Walbridge, S Vortmeyer, AO Oldfield, EH Lonser, RR TI Safety and efficacy of convection-enhanced delivery of gemcitabine or carboplatin in a malignant glioma model in rats SO JOURNAL OF NEUROSURGERY LA English DT Article DE glioma; carboplatin; chemotherapy; gemcitabine; convection-enhanced delivery; rat ID BRAIN-TUMOR; PRIMATE BRAIN; COMPUTERIZED-TOMOGRAPHY; INTRACEREBRAL CLYSIS; PHASE-II; INFUSION; MACROMOLECULES; MICROINFUSION; TRIAL; CELLS AB Object. Convection-enhanced delivery (CED) can be used safely to perfuse regions of the central nervous system (CNS) with therapeutic agents in a manner that bypasses the blood-brain barrier (131313). These features make CED a potentially ideal method for the distribution of potent chemotherapeutic agents with certain pharmacokinetic properties to tumors of the CNS. To determine the safety and efficacy of the CED of two chemotherapeutic agents (with properties ideal for this method of delivery) into the CNS, the authors perfused naive rats and those harboring 9L gliomas with carboplatin or gemcitabine. Methods. Dose-escalation toxicity studies were performed by perfusing the striatum (10 mul, 24 rats) and brainstem (10 mul, 16 rats) of naive rats with carboplatin (0.1, 1, and 10 mg/ml) or gemcitabine (0.4, 4, and 40 mg/ml) via CED. Efficacy trials involved the intracranial implantation of 9L tumor cells in 20 Fischer 344 rats. The tumor and surrounding regions were perfused with 40 mul of saline (control group, four rats), I mg/ml of carboplatin (four rats), or 4 mg/ml of gemcitabine (four rats) 7 days after implantation. Eight rats harboring the 9L glioma were treated with the systemic administration of 60 mg/kg of carboplatin (four rats) or 150 mg/kg of gemcitabine (four rats) 7 days postimplantation. Clinical, gross, and histological analyses were used to determine toxicity and efficacy. Toxicity occurred in rats that had received only the highest dose of the CED of carboplatin or gemcitabine. Among rats with 9L gliomas, all control and systemically treated animals died within 26 days of tumor implantation. Longterm survival (120 days) and eradication of the tumor occurred in both CED-treated groups (75% of rats in the carboplatin group and 50% of rats in the gemcitabine group). Furthermore, animals harboring the 9L glioma and treated with intratumoral CED of carboplatin or gemcitabine survived significantly longer than controls treated with intratumoral saline (p < 0.01) or systemtic chemotherapy (p < 0.01). Conclusions. The perfusion of sensitive regions of the rat brain can be accomplished without toxicity by using therapeutic concentrations of carboplatin or gemcitabine. In addition, CED of carboplatin or gemcitabine to tumors in this glioma model is safe and has potent antitumor effects. These findings indicate that similar treatment paradigms may be useful in the treatment of glial neoplasms in humans. C1 NINDS, Surg Neruol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Ctr Med, Dept Neurosurg, Washington, DC USA. RP Lonser, RR (reprint author), NINDS, Surg Neruol Branch, NIH, Bldg 10,Rm 5D37, Bethesda, MD 20892 USA. NR 31 TC 82 Z9 86 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2003 VL 99 IS 5 BP 893 EP 898 DI 10.3171/jns.2003.99.5.0893 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 737MY UT WOS:000186237400017 PM 14609170 ER PT J AU Russo, GT Friso, S Jacques, PF Rogers, G Cucinotta, D Wilson, PWF Ordovas, JM Rosenberg, IH Selhub, J AF Russo, GT Friso, S Jacques, PF Rogers, G Cucinotta, D Wilson, PWF Ordovas, JM Rosenberg, IH Selhub, J TI Age and gender affect the relation between methylenetetrahydrofolate reductase C677T genotype and fasting plasma homocysteine concentrations in the Framingham Offspring Study cohort SO JOURNAL OF NUTRITION LA English DT Article DE homocysteine; methylenetetrahydrofolate reductase; age; sex; folate; genetics ID HORMONE REPLACEMENT THERAPY; CORONARY-ARTERY DISEASE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; VASCULAR-DISEASE; HEART-DISEASE; POSTMENOPAUSAL WOMEN; COMMON MUTATION; FOLATE STATUS; MYOCARDIAL-INFARCTION AB The C677T variant of methylenetetrahydrofolate reductase (MTHFR), a key enzyme in the remethylation of homocysteine to methionine, is a frequent genetic cause of mild hyperhomocysteinemia among individuals with low folate status. However, little is known about the influence of subject characteristics, such as age and sex, on the relation between the C677T MTHFR polymorphism and fasting plasma total homocysteine (tHcy) concentrations, The aim of the present study was to explore the influence of age and gender, together with folate status, on the association between the C677T polymorphism and tHcy concentrations. The C677T genotype was determined for 1820 participants from the fifth examination of the Framingham Offspring Study. Mean age of the participants was 56 y (range 28-82 y). The allelic distribution was not different from the Hardy-Weinberg equilibrium, with a TT frequency comparable in men and women (14%). Geometric mean tHcy was 15% higher in men than in women (P < 0.001), and women had significantly higher plasma folate levels (P < 0.001). Geometric mean tHcy was significantly higher in TT participants (P = 0.001) than in participants with the CC and CT genotypes among those with plasma folate <12.5 nmol/L, but not among those with higher folate status. Because of a significant age and sex interaction (P = 0.02), we further stratified the low folate group by age and sex, and observed that the association between genotype and tHcy was confined to men <55 y old (P < 0.001). Our results suggest that age and sex modify the contribution of the MTHFR C677T mutation to fasting tHcy concentrations. C1 Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. Univ Messina, Dept Internal Med, Messina, Italy. Univ Verona, Policlin GB Rossi, Dept Clin & Exptl Med, I-37100 Verona, Italy. Boston Univ, Sch Med, Framingham, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Jacques, PF (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. RI cucinotta, domenico/F-4832-2014; OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [N01-HC-38038]; NIDDK NIH HHS [1R01 DK 56105-01] NR 65 TC 52 Z9 55 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2003 VL 133 IS 11 BP 3416 EP 3421 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 744UE UT WOS:000186650600015 PM 14608052 ER PT J AU Lomnitski, L Padilla-Banks, E Jefferson, WN Nyska, A Grossman, S Newbold, RR AF Lomnitski, L Padilla-Banks, E Jefferson, WN Nyska, A Grossman, S Newbold, RR TI A natural antioxidant mixture from spinach does not have estrogenic or antiestrogenic activity in immature CD-1 mice SO JOURNAL OF NUTRITION LA English DT Article DE phytochemicals; uterotrophic bioassay; antioxidants; flavonoids; environmental estrogens ID WATER-SOLUBLE ANTIOXIDANT; UTERINE ADENOCARCINOMA; BREAST-CANCER; END-POINTS; VITAMIN-A; PHYTOESTROGENS; CAROTENOIDS; CHEMICALS; APOCYNIN; MODEL AB The use of natural antioxidants and flavonoids in nutritional and pharmaceutical applications is increasing. Because some phytochemicals such as genistein, found in soy products, have estrogenic activity, we investigated the estrogenic potential of a natural antioxidant mixture (NAO) isolated from spinach leaves, using an in vivo uterotrophic bioassay and an in vitro transcriptional activation assay for the estrogen receptor (ER). Outbred female CD-1 mice (17 d old) were given subcutaneous injections of 17beta-estradiol or genistein [500 and 500,000 mug /(kg (.) d), respectively] as positive controls or NAO [1000 to 1,000,000 mug/(kg (.) d)] for 3 d. Uterine wet weight/body weight ratios were determined. Both 17beta-estradiol and genistein significantly increased uterine wet weight ratios compared with untreated controls, but NAO did not. Histological examination of the uterus showed that 17beta-estradiol and genistein increased epithelial cell height, number and gland development, but NAO did not. Estrogenic activity of NAO was investigated in vitro using the ER transcriptional activation assay. BG1Luc4E2 cells expressing ER were stably transfected with a luciferase reporter gene responsive to estrogens. 17beta-estradiol dose dependently increased luciferase activity; NAO had no effect. When NAO was tested for antiestrogenic activity, it did not lessen the effects of 17beta-estradiol. These data suggest that NAO does not have estrogenic or antiestrogenic activity. Thus, an antioxidant mixture has been identified that does not have potentially adverse estrogenic activity. C1 NIEHS, Mol Toxicol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Mol Toxicol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 31 TC 7 Z9 7 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2003 VL 133 IS 11 BP 3584 EP 3587 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 744UE UT WOS:000186650600040 PM 14608077 ER PT J AU Norman, HA Butrum, RR Feldman, E Heber, D Nixon, D Picciano, MF Rivlin, R Simopoulos, A Wargovich, MJ Weisburger, EK Zeisel, SH AF Norman, HA Butrum, RR Feldman, E Heber, D Nixon, D Picciano, MF Rivlin, R Simopoulos, A Wargovich, MJ Weisburger, EK Zeisel, SH TI The role of dietary supplements during cancer therapy SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition and Cancer CY JUL 17-18, 2003 CL WASHINGTON, D.C. SP Amer Inst Canc Res, World Canc Res Fund Int, Balchem Corp, BASF Aktiengesell, Calif Dried Plum Board, Campbell Soup Co, Danisco USA Inc, Hills Pet Nutrit Inc, IP 6 Int Inc, Mead Johnson Nutrit, Roche Vitamins Inc, Ross Prod Div, Abbot Labs, Solae Co DE dietary antioxidant; dietary supplement; micronutrients; chemotherapy ID POLYUNSATURATED FATTY-ACIDS; VITAMIN-D ANALOGS; BREAST-CANCER; ANTIOXIDANT VITAMINS; ALPHA-TOCOPHEROL; C INTAKE; IN-VIVO; CHEMOTHERAPY; CELLS; ENHANCEMENT AB This guide was compiled after recommendations by the American Institute for Cancer Research (AICR) Cancer Resource Advisory Council. It encompasses the AICR position on current issues in nutrition for cancer survivors during treatment and is intended to provide advice about dietary supplements for cancer survivors who are still being treated. Current scientific findings about the safety and effectiveness of some commonly used dietary antioxidants and nonantioxidant supplements during chemotherapy are presented and assessed. Use of dietary supplements during cancer treatment remains controversial. Patients are cautioned that vitamin and mineral supplements as therapies are not substitutes for established medicine. The current recommendation for cancer patients is to only take moderate doses of supplements because evidence from human clinical studies that confirm their safety and benefits is limited. A daily multivitamin containing supplements at the levels of the Dietary Reference Intakes can be used safely as part of a program of healthy nutrition. In addition, the AICR Cancer Resource Advisory Council concluded that further scientific research is needed to provide a set of firm guidelines for the use of vitamin and mineral supplements by cancer patients during treatment. C1 Amer Inst Canc Res, Washington, DC 20009 USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA USA. Amer Hlth Fdn, New York, NY 10017 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Ctr Genet Nutr & Hlth, Washington, DC USA. S Carolina Canc Ctr, Columbia, SC USA. Univ N Carolina, Chapel Hill, NC USA. RP Norman, HA (reprint author), Amer Inst Canc Res, Washington, DC 20009 USA. NR 56 TC 31 Z9 35 U1 1 U2 7 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2003 VL 133 IS 11 SU 1 BP 3794S EP 3799S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 745UP UT WOS:000186708400011 PM 14608116 ER PT J AU Milner, JA AF Milner, JA TI Incorporating basic nutrition science into health interventions for cancer prevention SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition and Cancer CY JUL 17-18, 2003 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Balchem Corp, BASF Aktiengesell, Calif Dried Plum Board, Campbell Soup Co, Danisco USA Inc, Hills Pet Nutr Inc, IP 6 Int Inc, Mead Johnson Nutr, Roche Vitamins Inc, Ross Prod Div, Abbott Labs, Solae Co DE nutrigenetics; nutrigenomics; proteomics; metabolomics; bioinformatics ID BREAST-CANCER; GENETIC POLYMORPHISMS; PROSTATE-CANCER; DIET; MECHANISMS; SELENIUM; RISK; GENOMICS; DISEASE; CHEMOPREVENTION AB Increasing evidence points to numerous dietary components that modify cancer incidence as well as the biological behavior of tumors. These inhibitory or stimulatory effects depend not only on the dietary component examined, but on a number of factors including the cellular DNA profile (nutrigenetic and nutrigenomic effects), protein formation and regulation (proteomic effect), and the effective delivery of the active intermediate at specific target sites (metabolomic effect). Unfortunately, the diet and cancer research domain is strewn with studies that were inadequately designed to monitor biological endpoints, used invalid biomarkers, or monitored irrelevant intakes or exposures. The scientific frontiers in health risk prediction and disease prevention strategies will greatly expand with the building of reliable nutrition and cancer biomarker databases that use modeling techniques to integrate information about intakes, effect biomarkers, and susceptibility biomarkers. Fundamental to this database will be the elucidation of the specific molecular sites of action (targets) for the specific dietary component. Clustering techniques that build on either genes or ratios of genetic expressions or their products will be needed to assess the merit of a particular dietary intervention. Models are already surfacing about how dietary-induced fluctuations in genes and their expression products can modify pathways associated with carcinogen activation and detoxification, alter rates of cellular proliferation, influence apoptosis, and modify angiogenesis. Embracing new genomic technologies offers exciting opportunities for advancing nutrition, especially those related to cancer prevention. We must effectively communicate, within a responsible bioethical framework, the potential value of knowledge about genes and gene products. RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. EM milnerj@mail.nih.gov NR 61 TC 20 Z9 22 U1 1 U2 5 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2003 VL 133 IS 11 SU 1 BP 3820S EP 3826S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 745UP UT WOS:000186708400015 PM 14608120 ER PT J AU Robertson, K AF Robertson, K TI DNA methyltransferase function and regulation. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 17-18, 2003 CL WASHINGTON, D.C. SP Amer Inst Canc Res, World Canc Res Fund Int, Balchem Corp, BASF Aktiengesell, Calif Dried Plum Board, Campbell Soup Co, Danisco USA Inc, Hills Pet Nutrit Inc, IP 6 Int Inc, Mead Johnson Nutrit, Roche Vitamins Inc, Ross Prod Div, Abbot Labs, Solae Co C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2003 VL 133 IS 11 SU 1 BP 3845S EP 3845S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 745UP UT WOS:000186708400021 ER PT J AU Travis, LB AF Travis, LB TI Second primary cancers: An overview. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 17-18, 2003 CL WASHINGTON, D.C. SP Amer Inst Canc Res, World Canc Res Fund Int, Balchem Corp, BASF Aktiengesell, Calif Dried Plum Board, Campbell Soup Co, Danisco USA Inc, Hills Pet Nutrit Inc, IP 6 Int Inc, Mead Johnson Nutrit, Roche Vitamins Inc, Ross Prod Div, Abbot Labs, Solae Co C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2003 VL 133 IS 11 SU 1 BP 3849S EP 3849S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 745UP UT WOS:000186708400030 ER PT J AU Schumann, M Nakagawa, T Mantey, SA Tokita, K Venzon, DJ Hocart, SJ Benya, RV Jensen, RT AF Schumann, M Nakagawa, T Mantey, SA Tokita, K Venzon, DJ Hocart, SJ Benya, RV Jensen, RT TI Importance of amino acids of the central portion of the second intracellular loop of the gastrin-releasing peptide receptor for phospholipase C activation, internalization, and chronic down-regulation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SITE-DIRECTED MUTAGENESIS; PROTEIN-KINASE-C; MUSCARINIC ACETYLCHOLINE-RECEPTOR; BETA-ADRENERGIC RECEPTORS; BETA-2-ADRENERGIC RECEPTOR; TYROSINE PHOSPHORYLATION; STRUCTURAL REQUIREMENTS; SIGNAL-TRANSDUCTION; ACTIN CYTOSKELETON; BOMBESIN RECEPTORS AB Little is known about the function of the central portion of the second intracellular loop (i2 loop) of peptide receptors in activation of downstream pathways and receptor modulatory processes such as receptor internalization or chronic down-regulation (DR). Recent data suggest a role for i2 loop hydrophobic amino acids in these processes. We used site-directed mutagenesis to address these issues with the gastrin-releasing peptide receptor (GRP-R). Each i2 loop residue from 142 to 148 was mutated and the receptors were expressed in Balb 3T3 cells. Two mutants showed a minimal (<2-fold) decrease in affinity. Five mutants showed decreased efficacy for activating phospholipase C (PLC). Two double mutants (IM(143.147)AA and VM(144.147)AA) showed a minimal decrease in affinity but had a decreased ability to fully activate PLC. Only the IM double mutation had decreased maximal internalization, whereas the R(145)A single mutant showed an increase, suggesting a tonic inhibitory role for Arg-145 in internalization. Three single and both double mutants showed decreases in receptor DR. There was a weak correlation between the extent of GRP-R internalization and the maximal PLC activation, whereas changes in the maximal PLC activation were significantly (p = 0.008) coupled to receptor DR. This study shows that amino acids of the i2 loop of the GRP-R are important in activation of PLC, internalization and down-regulation, but not for affinity. Our results support the proposal that internalization and chronic down-regulation have differing dependence on PLC and are largely independent processes, because some mutants showed no changes in internalization, but significant alterations in down-regulation. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA 70118 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; Schumann, Michael/K-6426-2013 OI Schumann, Michael/0000-0001-6391-9979 NR 57 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2003 VL 307 IS 2 BP 597 EP 607 DI 10.1124/jpet.103.055087 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734UP UT WOS:000186076600021 PM 12970386 ER EF