FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lerman, C Caporaso, N Bush, A Zheng, L Audrain, J Shields, P AF Lerman, C Caporaso, N Bush, A Zheng, L Audrain, J Shields, P TI Association of tryptophan hydroxylase (TPH) gene with smoking behavior. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Canc Control Res, LCC, Washington, DC USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2023 BP 362 EP 362 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702026 ER PT J AU Cabral, WA Chernoff, EJ Marini, JC AF Cabral, WA Chernoff, EJ Marini, JC TI Type I collagen alpha 1 Gly 76-Glu substitution in a child with type IIIOI causes increased susceptibility of the N-terminal end of the helix to enzymatic cleavage. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Sect Connect Tissue Disorders, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2063 BP 369 EP 369 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702065 ER PT J AU Green, LK Cabral, WA Fertala, A Korkko, J Forlino, A Marini, JC AF Green, LK Cabral, WA Fertala, A Korkko, J Forlino, A Marini, JC TI COL1A1 IVS A(+4) C mutation causes splicing out of exon 41 and confirms importance of this region for fibril self-assembly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. Med Coll Penn & Hahnemann Univ, Ctr Gene Therapy, Philadelphia, PA USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2064 BP 369 EP 369 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702063 ER PT J AU Bennett, CL Blair, IP Abel, A Fischbeck, KH Griffin, JW Cornblath, RA Chance, PF AF Bennett, CL Blair, IP Abel, A Fischbeck, KH Griffin, JW Cornblath, RA Chance, PF TI A positional cloning strategy to identify the gene for an autosomal dominant juvenile ALS on chromosome 9q34. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Washington, Dept Pediat, Seattle, WA 98195 USA. NIH, Neurogenet Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2087 BP 373 EP 373 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702089 ER PT J AU Jackson, CE Bi, LL Fischer, RE Davis, J Niemela, J Dale, JK Fleisher, TA Lenardo, MJ Straus, SE Puck, JM AF Jackson, CE Bi, LL Fischer, RE Davis, J Niemela, J Dale, JK Fleisher, TA Lenardo, MJ Straus, SE Puck, JM TI Clinical and genetic diversity in autoimmune lymphoproliferative syndrome (ALPS), an inherited disorder of lymphocyte apoptosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, GMBB, Bethesda, MD 20892 USA. NIH, NHGRI, Bethesda, MD 20892 USA. NIH, Clin Invest Lab, Bethesda, MD 20892 USA. NIH, Immunol Lab, Bethesda, MD 20892 USA. NIH, NIAID, Bethesda, MD 20892 USA. NIH, Clin Ctr Clin Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2125 BP 379 EP 379 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702126 ER PT J AU Acierno, JS Falardeau, J Kennedy, JC Leyne, M Bromley, MC Colman, M Sun, M Bove, C Bach, G Ashworth, L Schiripo, T Ma, S Helbling, LA Goldin, E Schiffmann, R Slaugenhaupt, SA AF Acierno, JS Falardeau, J Kennedy, JC Leyne, M Bromley, MC Colman, M Sun, M Bove, C Bach, G Ashworth, L Schiripo, T Ma, S Helbling, LA Goldin, E Schiffmann, R Slaugenhaupt, SA TI Precise genetic mapping and haplotype analysis of the Mucolipidosis IV candidate region on human chromosome 19p13.2-13.3. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel. Univ Calif Lawrence Livermore Natl Lab, Ctr Human Genome, Livermore, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2150 BP 384 EP 384 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702151 ER PT J AU dela Cruz, JM Bamford, RN Roessler, E Muenke, M AF dela Cruz, JM Bamford, RN Roessler, E Muenke, M TI Potential role of NODAL and CRIPTO in holoprosencephaly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2156 BP 385 EP 385 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702157 ER PT J AU Everman, DB Robin, NH Marcelino, J Thomas, JT Hecht, JT Warman, ML AF Everman, DB Robin, NH Marcelino, J Thomas, JT Hecht, JT Warman, ML TI Heterozygous mutations in CDMP1 cause a spectrum of skeletal phenotypes through different effects on protein production and function. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. NIH, Bethesda, MD 20892 USA. Univ Texas, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2217 BP 395 EP 395 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702220 ER PT J AU Brown, N Tieu, M DiGiovanna, JJ Bale, SJ Uitto, J Richard, G AF Brown, N Tieu, M DiGiovanna, JJ Bale, SJ Uitto, J Richard, G TI The spectrum of novel mutations in ATP2C1 in Hailey-Hailey Disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Brown Univ, Providence, RI 02912 USA. Rhode Isl Hosp, Providence, RI USA. NIH, NIAMS, Genet Study Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2238 BP 398 EP 398 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702237 ER PT J AU Lin, T Suchy, SF Nussbaum, RL AF Lin, T Suchy, SF Nussbaum, RL TI Lowe syndrome carrier testing by denaturing HPLC. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2261 BP 402 EP 402 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702263 ER PT J AU Torosyan, Y Aksentijevich, I Sarkisian, T Ajrapetyan, H Amaryan, G Astvatsatryan, V Kastner, DL AF Torosyan, Y Aksentijevich, I Sarkisian, T Ajrapetyan, H Amaryan, G Astvatsatryan, V Kastner, DL TI Role of complex alleles and gender in susceptibility to Familial Mediterranean Fever in the Armenian population. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Ctr Med Genet, Yerevan, Armenia. Yerevan State Univ, Yerevan 375049, Armenia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2275 BP 404 EP 404 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702276 ER PT J AU Ren, Z Lin, PY Klintworth, GK Munier, FL Shorderet, DF El Matri, L Kaiser-Kupfer, MJ Hejtmancik, JF AF Ren, Z Lin, PY Klintworth, GK Munier, FL Shorderet, DF El Matri, L Kaiser-Kupfer, MJ Hejtmancik, JF TI Alellic and locus heterogeneity in autosomal recessive gelatinous drop-like corneal dystrophy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Duke Univ, Dept Pathol, Durham, NC 27706 USA. Duke Univ, Dept Ophthalmol, Durham, NC USA. Univ Lausanne, Oculogenet Unit, Lausanne, Switzerland. Inst Hedi Rais Ophtalmol, Tunis, Tunisia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2279 BP 405 EP 405 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702281 ER PT J AU Richard, G Sprecher, E Chavanas, S Miller, C Bale, SJ DiGiovanna, JJ Hovnanian, A Uitto, J AF Richard, G Sprecher, E Chavanas, S Miller, C Bale, SJ DiGiovanna, JJ Hovnanian, A Uitto, J TI Linkage studies and mutation analysis of SPINK5 in an international cohort of 24 families with Netherton syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wellcome Trust Ctr Human Genet, Oxford, England. NIAMS, NIH, Bethesda, MD USA. Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2278 BP 405 EP 405 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702278 ER PT J AU Hodges, AK Maynard, J Parry, L DeClue, JE Cheadle, J Sampson, J AF Hodges, AK Maynard, J Parry, L DeClue, JE Cheadle, J Sampson, J TI Pathological mutations of tuberin affect interaction with hamartin. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Wales Coll Med, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RI Parry, Lee/A-9623-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2287 BP 406 EP 406 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702288 ER PT J AU Neocleous, V Humphray, SJ Howard, PJ Hammond, S Tsingis, M Georgiou, A Al-Qudah, AK Mubaidin, A Horani, K Askanas, V Engel, K Dalakas, M Rowland, LP Mirabella, M Zamba, E Kyriakides, T Middleton, LT Christodoulou, K AF Neocleous, V Humphray, SJ Howard, PJ Hammond, S Tsingis, M Georgiou, A Al-Qudah, AK Mubaidin, A Horani, K Askanas, V Engel, K Dalakas, M Rowland, LP Mirabella, M Zamba, E Kyriakides, T Middleton, LT Christodoulou, K TI BAC based physical map of the distal hereditary motor neuronopathy (HMN-J) and autosomal recessive inclusion body myopathy (AR-IBM) region on chromosome 9p21.1-p12. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Cyprus Inst Neurol & Genet, Nicosia, Cyprus. Sanger Ctr, Cambridge, England. Univ Hosp, Amman, Jordan. King Hussein Med Ctr, Amman, Jordan. Univ So Calif, Sch Med, Los Angeles, CA USA. NIH, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Catholic Univ, UILDM, Rome, Italy. Glaxo Wellcome, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2291 BP 407 EP 407 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702293 ER PT J AU Wan, M Zhao, K Lee, SS Song, HR Schanen, NC Francke, U AF Wan, M Zhao, K Lee, SS Song, HR Schanen, NC Francke, U TI MECP2 truncating mutations cause histone H4 hyperacetylation in Rett syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Stanford Univ, Med Ctr, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. NIH, NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2325 BP 413 EP 413 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702328 ER PT J AU Wapner, RJ Jackson, LG Pergament, E AF Wapner, RJ Jackson, LG Pergament, E TI First trimester Down syndrome screening utilizing nuchal translucency measurements: Can we do it? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, FIRST Study Grp, Bethesda, MD 20205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2406 BP 426 EP 426 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702405 ER PT J AU Haskins, ME Melniczek, JR Licht, T Whitwam, T Bodine, DM Puck, JM Henthorn, PS AF Haskins, ME Melniczek, JR Licht, T Whitwam, T Bodine, DM Puck, JM Henthorn, PS TI Retroviral marking of canine bone marrow: high level expression of human IL-2 receptor common gamma chain and multiple drug resistance 1 in canine peripheral blood and bone marrow after Taxol therapy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Sch Vet Med, Med Genet Sect, Philadelphia, PA 19104 USA. NIH, NHGRI, Genet & Mol Biol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2423 BP 429 EP 429 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702422 ER PT J AU Raben, N Lu, N Nagaraju, K Byrne, B Plotz, P AF Raben, N Lu, N Nagaraju, K Byrne, B Plotz, P TI Conditional expression of the human acid alpha-glucosidase (GAA) gene in GAA knockout mice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, ARB, NIH, Bethesda, MD USA. Univ Florida, Gilis Inst, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2431 BP 431 EP 431 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702432 ER PT J AU Pfeifer, K AF Pfeifer, K TI Mechanisms of genomic imprinting SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Review ID BECKWITH-WIEDEMANN-SYNDROME; PRADER-WILLI-SYNDROME; MOUSE H19 GENE; SYNDROME CRITICAL REGION; METHYLATED CPG ISLAND; ANGELMAN-SYNDROME; DNA METHYLATION; SNRPN GENE; EPIGENETIC MODIFICATION; EXPRESSED TRANSCRIPT AB Imprinted genes represent a curious defiance of normal Mendelian genetics. Mammals inherit two complete sets of chromosomes, one from the mother and one from the father, and most autosomal genes will be expressed from both the maternal and the paternal alleles. Imprinted genes, however, are expressed from only one chromosome, in a parent-of-origin-dependent manner. Because silent and active promoters are present in a single nucleus, the differences in activity cannot be explained by transcription-factor abundance. Thus, transcription of imprinted genes represents a clear situation in which epigenetic mechanisms restrict gene expression and, therefore, offers a model for understanding the role of DNA modifications and chromatin structure in maintaining appropriate patterns of expression. Furthermore, because of their parent-of-origin-restricted expression, phenotypes determined by imprinted genes are susceptible not only to genetic alterations in the genes but also to disruptions in the epigenetic programs controlling regulation. Imprinted genes are often associated with human diseases, including disorders affecting cell growth, development, and behavior. C1 NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Pfeifer, K (reprint author), NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. OI Pfeifer, Karl/0000-0002-0254-682X NR 98 TC 72 Z9 78 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 BP 777 EP 787 DI 10.1086/303101 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 360DL UT WOS:000089651100001 PM 10986038 ER PT J AU Johnston, JJ Kelley, RI Crawford, TO Morton, DH Agarwala, R Koch, T Schaffer, AA Francomano, CA Biesecker, LG AF Johnston, JJ Kelley, RI Crawford, TO Morton, DH Agarwala, R Koch, T Schaffer, AA Francomano, CA Biesecker, LG TI A novel nemaline myopathy in the Amish caused by a mutation in troponin T1 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LINKAGE ANALYSIS; CAENORHABDITIS-ELEGANS; GENE TPM3; MUSCLE; TROPOMYOSIN; SKELETAL; STRATEGIES; SYSTEM; CELLS AB The nemaline myopathies are characterized by weakness and eosinophilic, rodlike (nemaline) inclusions in muscle fibers. Amish nemaline myopathy is a form of nemaline myopathy common among the Old Order Amish. In the first months of life, affected infants have tremors with hypotonia and mild contractures of the shoulders and hips. Progressive worsening of the proximal contractures, weakness, and a pectus carinatum deformity develop before the children die of respiratory insufficiency, usually in the second year. The disorder has an incidence of similar to 1 in 500 among the Amish, and it is inherited in an autosomal recessive pattern. Using a genealogy database, automated pedigree software, and linkage analysis of DNA samples from four sibships, we identified an similar to 2-cM interval on chromosome 19q13.4 that was homozygous in all affected individuals. The gene for the sarcomeric thin-filament protein, slow skeletal muscle troponin T (TNNT1), maps to this interval and was sequenced. We identified a stop codon in exon 11, predicted to truncate the protein at amino acid 179, which segregates with the disease. We conclude that Amish nemaline myopathy is a distinct, heritable, myopathic disorder caused by a mutation in TNNT1. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Informat Engn Branch, Bethesda, MD 20892 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD USA. Johns Hopkins Univ, Dept Neurol & Pediat, Baltimore, MD USA. Clin Special Children, Strasburg, PA USA. Konrad Zuse Zentrum Informat Tech, Berlin, Germany. RP Johnston, JJ (reprint author), NHGRI, Med Genet Branch, NIH, Rm 3D-45,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. RI Crawford, Thomas/E-6307-2012; Schaffer, Alejandro/F-2902-2012 NR 29 TC 169 Z9 176 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 BP 814 EP 821 DI 10.1086/303089 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 360DL UT WOS:000089651100005 PM 10952871 ER PT J AU Gastwirth, JL AF Gastwirth, JL TI The efficiency of pooling in the detection of rare mutations SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID PREVALENCE; DISEASE; HIV C1 NCI, Biostat Branch, Div Canc Genet & Epidemiol, Bethesda, MD 20892 USA. RP Gastwirth, JL (reprint author), NCI, Biostat Branch, Div Canc Genet & Epidemiol, 6120 Execut Blvd,MS 7244, Bethesda, MD 20892 USA. NR 12 TC 20 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 BP 1036 EP 1039 DI 10.1086/303097 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 360DL UT WOS:000089651100033 PM 10986050 ER PT J AU Kazerouni, N Thomas, TL Petralia, SA Hayes, RB AF Kazerouni, N Thomas, TL Petralia, SA Hayes, RB TI Mortality among workers exposed to cutting oil mist: Update of previous reports SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE cohort study; cutting oil mist; automotive workers; lung cancer; liver and biliary tract cancer; Hodgkin's disease; testicular cancer; asthma; emphysema ID MACHINING-FLUID EXPOSURE; AUTOMOBILE-INDUSTRY; N-NITROSODIETHANOLAMINE; RESPIRATORY SYMPTOMS; MANUFACTURING PLANT; OCCUPATIONAL ASTHMA; LUNG-CANCER; ENGINE; RATIO; MEN AB Background Earlier reports of the mortality experience of this cohort of automotive workers followed from 1938 to 1967 who were exposed to cutting oil mist noted mt excess of gastrointestinal cancel: The present report describes the mortality experience of these workers followed for mortality through 1980. Methods Cause-specific standardized mortality ratios were calculated by comparing the observed number of deaths to the expected numbers based on rates for the U.S. male population. Results The SMRs for liver and biliary tract and testicular cancers were significantly elevated. Among the subset of workers with heavy oil mist exposure, SMRs were significantly elevated for cancers of the lung and testis, and for Hodgkin's disease. The risk of death due to lung cancer was greatest among workers with heavy exposure to oil mist employed for 15 or more gears. Mortality due to stomach cancer was in excess among workers with heavy exposure to oil mist who were employed for 5 or more gears. There were significant excesses of deaths due to asthma and emphysema, Conclusions Further studies with information on the presence of contaminants and additives in oil mists will help elucidate the relationship between oil mist exposure and cancer. Published 2000 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. RP Kazerouni, N (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Plaza S 7013, Rockville, MD 20892 USA. NR 37 TC 23 Z9 23 U1 0 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 2000 VL 38 IS 4 BP 410 EP 416 DI 10.1002/1097-0274(200010)38:4<410::AID-AJIM6>3.0.CO;2-5 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 351DT UT WOS:000089143100006 PM 10982981 ER PT J AU Knepper, MA AF Knepper, MA TI Understanding how aldosterone increases sodium transport - Reply SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr MSC-1603, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 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 OCT PY 2000 VL 36 IS 4 BP 868 EP + PG 33 WC Urology & Nephrology SC Urology & Nephrology GA 358HJ UT WOS:000089552300030 ER PT J AU Bulte, JWM Frank, JA AF Bulte, JWM Frank, JA TI Imaging macrophage activity in the brain by using ultrasmall particles of iron oxide SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Letter ID MODEL; ENCEPHALOMYELITIS; BARRIER; MRI C1 NIH, Lab Diagost Radiol Res, Bethesda, MD 20892 USA. RP Bulte, JWM (reprint author), NIH, Lab Diagost Radiol Res, Bldg 10, Bethesda, MD 20892 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 5 TC 9 Z9 9 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 OCT PY 2000 VL 21 IS 9 BP 1767 EP 1768 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 368HD UT WOS:000090110900035 PM 11039364 ER PT J AU Levine, RJ Ewell, MG Hauth, JC Curet, LB Catalano, PM Morris, CD Choudhary, G Sibai, BM AF Levine, RJ Ewell, MG Hauth, JC Curet, LB Catalano, PM Morris, CD Choudhary, G Sibai, BM TI Should the definition of preeclampsia include a rise in diastolic blood pressure of >= 15 mm Hg to a level < 90 mm Hg in association with proteinuria? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 31-FEB 05, 2000 CL MIAMI BEACH, FL SP Soc Maternal Fetal Med DE definition; diastolic blood pressure; normotensive; preeclampsia ID HEALTHY NULLIPAROUS WOMEN; PREGNANCY; CALCIUM; TRIAL AB OBJECTIVE: This study was undertaken to compare baseline characteristics and pregnancy outcomes between normotensive women who did and those who did not have a rise in diastolic blood pressure of greater than or equal to 15 mm Hg in association with proteinuria. STUDY DESIGN: We studied 4302 healthy nulliparous women from the Calcium for Preeclampsia Prevention trial who were delivered at greater than or equal to 20 weeks' gestation. We selected as the study group normotensive women who developed proteinuria within 7 days of a rise in diastolic blood pressure of greater than or equal to 15 mm Hg with respect to baseline on 2 occasions 4 to 168 hours apart. Baseline blood pressure was the mean of measurements at 2 clinic visits before 22 weeks' gestation. Other normotensive women used for comparison were those who did not develop gestational hypertension or a rise in diastolic blood pressure of greater than or equal to 15 mm Hg in association with proteinuria. RESULTS: Except for greater weight (P<.001), body mass index (P<.001), and systolic blood pressure (P=.05) the baseline characteristics of the 82 women with a rise in diastolic blood pressure of greater than or equal to 15 mm Hg in association with proteinuria did not differ significantly from those of the other normotensive women. Although they had a greater rate of weight gain (P<.005), larger babies (P=.06), and a 2-fold increase in abdominal delivery (P<.001), there was little other evidence of adverse pregnancy outcomes among these women. CONCLUSION: During normotensive pregnancy a rise in diastolic blood pressure of greater than or equal to 15 mm Hg in association with proteinuria appears to be benign and is not a useful clinical construct. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Obstet & Gynecol, Tuscaloosa, AL 35487 USA. Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA. Oregon Hlth & Sci Univ, Div Med Informat & Outcomes Res, Portland, OR 97201 USA. Univ Tennessee, Coll Med, Dept Obstet & Gynecol, Knoxville, TN 37996 USA. RP NICHHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Bldg,Rm 7B03 MSC 7510, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01HD13121, N01HD13126, N01HD23154] NR 16 TC 36 Z9 37 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2000 VL 183 IS 4 BP 787 EP 792 DI 10.1067/mob.2000.108865 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 366AT UT WOS:000089983200001 PM 11035314 ER PT J AU Maymon, E Romero, R Pacora, P Gervasi, MT Gomez, R Edwin, SS Yoon, BH AF Maymon, E Romero, R Pacora, P Gervasi, MT Gomez, R Edwin, SS Yoon, BH TI Evidence of in vivo differential bioavailability of the active forms of matrix metalloproteinases 9 and 2 in parturition, spontaneous rupture of membranes, and intra-amniotic infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 31-FEB 05, 2000 CL MIAMI BEACH, FLORIDA SP Soc Maternal Fetal Med DE active forms; gelatinases; matrix metalloproteinases; MMP-2; MMP-9; microbial invasion of the amniotic cavity; parturition; rupture of membranes ID TUMOR-NECROSIS-FACTOR; PRETERM PREMATURE RUPTURE; FETAL MEMBRANES; ALPHA; LABOR; TERM; POLYMORPHISM; PROMOTER; ASSAY; RISK AB OBJECTIVE: Matrix metalloproteinases (MMP-9 and MMP-2) have been implicated in the digestion of fetal membranes. The purpose of this study was to determine the amniotic fluid concentrations of active forms of MMP-2 and MMP-9 and to explore the participation of these enzymes in labor (term and preterm), rupture of membranes (term and preterm), and microbial invasion of the amniotic cavity. STUDY DESIGN: A cross-sectional study was conducted with 291 women in the following categories: (1) term not in labor, (2) term in labor, (3) preterm labor and intact membranes who delivered at term, (4) preterm labor who delivered preterm, (5) preterm labor with microbial invasion of the amniotic cavity, (6) preterm premature rupture of membranes without microbial invasion of the amniotic cavity, (7) preterm premature rupture of membranes with microbial invasion of the amniotic cavity, (8) term premature rupture of membranes not in labor, and (9) mid trimester. Active forms of MMP-2 and MMP-9 were measured by a novel assay that uses a substrate developed by protein engineering. RESULTS: (1) MMP-2 and MMP-9 were detected in 88% and 96% of amniotic fluid samples, respectively (255/291 and 279/291). (2) The concentrations of active forms of MMP-2 and MMP-9 changed with advancing gestational age. (3) Spontaneous term parturition was associated with a significant increase in the median concentration of the active forms of MMP-9 (P < .005) and a significant decrease in the median concentration of the active forms of MMP-2 (P < .003). (4) Preterm labor with intact membranes leading to preterm delivery in the absence of infection was associated with a significant increase in the median concentration of the active forms of MMP-9 (P < .005) but not of the active forms of MMP-2 (P = .2). (5) Rupture of membranes (either term or preterm) was associated with a significant increase in the concentration of the active forms of MMP-9 and with a significant decrease in the concentration of the active forms of MMP-2 (P < .005 for term and P < .03 and P < .003 for preterm, respectively). (6) Microbial invasion of the amniotic cavity in women with preterm premature rupture of membranes was also associated with a significant increase in the concentration of the active forms of MMP-9 (P < .03) and a decrease in the concentration of the active forms of MMP-2 (P < .05). (7) Microbial invasion of the amniotic cavity in patients with preterm labor was associated with a significant increase in the median concentration of the active forms of MMP-9 (P < .005) but not of the active forms of MMP-2 (P = .6). CONCLUSION: Spontaneous rupture of membranes (either term or preterm), parturition (either term or preterm), and microbial invasion of the amniotic cavity were associated with significant increases in the amniotic fluid concentration of the active forms of MMP-9. In contrast, the concentration of the active forms of MMP-2 either decreased or remained the same in these conditions. Our observations provide evidence for a novel regulation of gelatinolytic activity in vivo. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHHD,Perinatol Res Branch, Detroit, MI 48201 USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul 151, South Korea. RP Maymon, E (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHHD,Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011 NR 24 TC 92 Z9 101 U1 0 U2 3 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 OCT PY 2000 VL 183 IS 4 BP 887 EP 894 DI 10.1067/mob.2000.108878 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 366AT UT WOS:000089983200019 PM 11035332 ER PT J AU Pacora, P Maymon, E Gervasi, MT Gomez, R Edwin, SS Yoon, BH Romero, R AF Pacora, P Maymon, E Gervasi, MT Gomez, R Edwin, SS Yoon, BH Romero, R TI Lactoferrin in intrauterine infection, human parturition, and rupture of fetal membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 31-FEB 05, 2000 CL MIAMI BEACH, FL SP Soc Maternal Fetal Med DE amniotic fluid; intra-amniotic infection; lactoferrin; maternal plasma; parturition; rupture of membranes; umbilical cord plasma; preterm ID AMNIOTIC-FLUID; MULTIFUNCTIONAL GLYCOPROTEIN; BINDING AB OBJECTIVE: Lactoferrin is an iron-binding protein with antimicrobial properties. This study was undertaken to determine whether amniotic fluid concentrations of this protein change with gestational age, infection, labor, and rupture of membranes. STUDY DESIGN: This cross-sectional study included women who underwent transabdominal amniocentesis (n = 268) in the following groups: (1) mid trimester of pregnancy; (2) preterm labor who delivered at term, preterm labor who delivered preterm with intra-amniotic infection, and preterm labor who delivered preterm without intra-amniotic infection; (3) preterm premature rupture of membranes in the presence or absence of intra-amniotic infection, (4) term with intact membranes not in labor, in labor, and in labor with intra-amniotic infection, and (5) premature rupture of membranes at term not in labor. In addition, lactoferrin concentrations were determined in maternal plasma and cord brood of patients at term not in labor. Lactoferrin concentration was measured with an immunoassay. RESULTS: (1) Lactoferrin was detectable in 85.4% (229/268) of amniotic fluid samples, not detectable in all fluid obtained in the mid trimester, and detectable in all maternal and cord plasma samples. (2) The concentration of lactoferrin increased with advancing gestational age (r = 0.68; P < .0001). (3) Intra-amniotic infection was associated with significant increases in amniotic fluid lactoferrin concentrations in patients with preterm labor (no intra-amniotic infection median, 1641.2 ng/mL; range, <1.24-35,090.0 ng/mL; vs intra-amniotic infection median, 3833.6 ng/mL; range, 746.0-47,020.0 ng/mL; P < .001), term labor (no intra-amniotic infection median, 2085.8 ng/mL; range, 425.0-23,230.0 ng/mL; vs intra-amniotic infection median, 5627.0 ng/mL; range, <1.24-19,220.0 ng/mL; P < .001), and preterm premature rupture of membranes (no intra-amniotic infection median. 2190 ng/mL; range, <1.24-7456.1 ng/mL; vs intra-amniotic infection median. 3449.3 ng/mL; range, <1.24-83,600.0; P < .01). (4) Spontaneous labor at term but not preterm was associated with a significant decrease in amniotic fluid lactoferrin concentration (P < .05). (5) Spontaneous term parturition was associated with a significant increase in umbilical cord plasma lactoferrin concentration (P < .005). CONCLUSION: (1) Intra-amniotic infection was consistently associated with dramatically increased concentrations of lactoferrin in amniotic fluid. (2) Term parturition was associated with a significant increase in lactoferrin concentration in the fetal compartment (umbilical cord blood) and a decrease in the amniotic compartment. We propose that lactoferrin is part of the repertoire of host defense mechanisms against intra-amniotic infection. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHHD,Perinatol Res Branch, Detroit, MI 48201 USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul 151, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHHD,Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011 NR 18 TC 31 Z9 33 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2000 VL 183 IS 4 BP 904 EP 910 DI 10.1067/mob.2000.108882 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 366AT UT WOS:000089983200022 PM 11035335 ER PT J AU Maymon, E Romero, R Pacora, P Gervasi, MT Bianco, K Ghezzi, F Yoon, BH AF Maymon, E Romero, R Pacora, P Gervasi, MT Bianco, K Ghezzi, F Yoon, BH TI Evidence for the participation of interstitial collagenase (matrix metalloproteinase 1) in preterm premature rupture of membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 31-FEB 05, 2000 CL MIAMI BEACH, FLORIDA SP Soc Maternal Fetal Med DE collagenase 1; interstitial collagenase; matrix metalloproteinase; MMP-1; microbial invasion of the amniotic cavity: parturition; preterm rupture of membranes; rupture of membranes ID HUMAN FETAL MEMBRANES; AMNIOTIC MEMBRANES; ACTIVATION; PLACENTA; CELLS; MECHANISMS; DECIDUA AB OBJECTIVE: Rupture of membranes is thought to result from the effects of physical forces in localized areas of the membranes weakened by the degradation of structural collagens. Matrix metalloproteinases are enzymes that degrade extracellular matrix components and have been implicated in membrane rupture. The objective of this study was to determine whether spontaneous rupture of membranes is associated with a change in the amniotic fluid concentration of interstitial collagenase (matrix metalloproteinase 1 [MMP-1]), a major collagenase. STUDY DESIGN: A cross-sectional study was conducted to determine MMP-1 concentrations in amniotic fluid from 353 women in the following categories: (1) term with intact membranes not in labor and in labor, (2) preterm labor who delivered at term, (3) preterm labor who delivered preterm without microbial invasion of the amniotic cavity, (4) preterm labor who delivered preterm with microbial invasion of the amniotic cavity, (5) preterm premature rupture of membranes with and without microbial invasion of the amniotic cavity, (6) term premature rupture of membranes not in labor and in labor, and (7) mid trimester of pregnancy. Microbial invasion of the amniotic cavity was determined by an amniotic fluid culture positive for microorganisms. MMP-1 concentrations in amniotic fluid were determined by means of sensitive and specific immunoassays. RESULTS: (1) MMP-1 was detectable in 81.3% of amniotic fluid samples (287/353), and its concentrations increased with advancing gestational age (r = 0.4; P < .001). (2) Preterm premature rupture of membranes was associated with a significant increase in the median amniotic fluid concentration of MMP-1 (P = .02). (3) Women with term premature rupture of membranes had a significantly lower amniotic fluid MMP-1 concentration than those with intact membranes at term not in labor (P < .001). (4) Microbial invasion of the amniotic cavity in patients in preterm labor with intact membranes and in patients with preterm premature rupture of membranes was also associated with significant increases in the median amniotic fluid MMP-1 concentrations (P < .05 and P < .01, respectively). (5) Patients with preterm premature rupture of membranes and microbial invasion of the amniotic cavity had a significantly higher median amniotic fluid MMP-1 concentration than those with intact membranes and microbial invasion of the amniotic cavity (P = .01). (6) Neither term nor preterm parturition was associated with changes in amniotic fluid MMP-1 concentrations (P = .6 and P = .3, respectively). CONCLUSION: (1) Collagenase 1 (MMP-1) is a physiologic constituent of amniotic fluid. (2) Preterm premature rupture of membranes (in both the presence and absence of infection) was associated with an increase in the amniotic fluid MMP-1 concentrations. (3) Neither term nor preterm parturition was associated with a significant increase in the amniotic fluid concentration of MMP-1. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHHD,Perinatol Res Branch, Detroit, MI 48201 USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul 151, South Korea. RP Maymon, E (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHHD,Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011; OI Ghezzi, Fabio/0000-0003-3949-5410 NR 28 TC 85 Z9 89 U1 0 U2 4 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 OCT PY 2000 VL 183 IS 4 BP 914 EP 920 DI 10.1067/mob.2000.108879 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 366AT UT WOS:000089983200024 PM 11035337 ER PT J AU Ghia, N Spong, CY Starbuck, VN Scialli, AR Ghidini, A AF Ghia, N Spong, CY Starbuck, VN Scialli, AR Ghidini, A TI Magnesium sulfate therapy affects attention and working memory in patients undergoing preterm labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 31-FEB 05, 2000 CL MIAMI BEACH, FLORIDA SP Soc Maternal Fetal Med DE magnesium sulfate; preterm labor; informed consent; comprehension; tocolysis; attention ID INFORMED CONSENT; INFLAMMATORY RESPONSE; RECALL; PARTURITION; SURGERY AB OBJECTIVE: Patients commonly consent to undergoing invasive procedures while receiving magnesium sulfate therapy. This study evaluated the effects of magnesium sulfate on attention, comprehension, and memory in patients undergoing preterm labor. STUDY DESIGN: Consenting patients were studied while receiving(study) and not receiving (control) intravenous magnesium sulfate tocolysis for preterm labor. Excluded were patients with possible preeclampsia, imminent delivery. sedative administration, or prior mental illness. Patient comprehension was assessed with the Boston Diagnostic Aphasia Examination. Level of attention and working memory were evaluated with the Paced Auditory Serial Addition Test. Verbal learning, short-term memory, and recognition were determined with the Hopkins Verbal Learning Test. Gross mental-neurologic deficits were evaluated with the Mini-Mental Status Examination. The tests were administered by the same examiner. Control testing was performed >24 hours after intravenous magnesium sulfate was discontinued. Magnesium levels were obtained at the time of testing. The primary outcome measure was the Paced Auditory Serial Addition Test score because of its ability to elicit subtle differences in attention capacity. Statistical analysis included the paired t test and the McNemar test. RESULTS: Fifteen patients completed the study. Paced Auditory Serial Addition Test scores were significantly higher (ie, more errors were made) during magnesium sulfate therapy than periods without therapy (14 +/- 8 vs 7 +/- 7; P < .05). Comprehension (Boston Diagnostic Aphasia Examination score) was not different between the groups (P = .7). There was no difference in short-term memory (Hopkins Verbal Learning Test) or gross mental-neurologic deficits between the 2 groups (all P > .1). CONCLUSIONS: Magnesium sulfate therapy appears to have an effect on attention and working memory but not on long-term memory or comprehension. The significant differences in Paced Auditory Serial Addition Test scores reveal deficits in information-processing ability in patients on a regimen of magnesium sulfate therapy. C1 Georgetown Univ, Med Ctr 3PHC, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. NICHHD, Dev Neurobiol Lab, Sect Dev & Mol Pharmacol, Bethesda, MD USA. RP Ghidini, A (reprint author), Georgetown Univ, Med Ctr 3PHC, Dept Obstet & Gynecol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 22 TC 18 Z9 19 U1 0 U2 0 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 OCT PY 2000 VL 183 IS 4 BP 940 EP 944 DI 10.1067/mob.2000.109045 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 366AT UT WOS:000089983200030 PM 11035343 ER PT J AU Dublin, S Lydon-Rochelle, M Kaplan, RC Watts, DH Critchlow, CW AF Dublin, S Lydon-Rochelle, M Kaplan, RC Watts, DH Critchlow, CW TI Maternal and neonatal outcomes after induction of labor without an identified indication SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cesarean delivery; induction of labor; instrumental delivery; shoulder dystocia ID ELECTIVE INDUCTION; PROSTAGLANDIN E(2); CESAREAN DELIVERY; TERM AB OBJECTIVE: This study was undertaken to examine associations between induction of labor and maternal and neonatal outcomes among women without an identified indication for induction. STUDY DESIGN: This was a population-based cohort study of 2886 women with induced labor and 9648 women with spontaneous labor who were delivered at 37 to 41 weeks' gestation, all without identified medical and obstetric indications for induction. RESULTS: Among nulliparous women 19% of women with induced labor versus 10% of those with spontaneous labor underwent cesarean delivery (adjusted relative risk, 1.77; 95% confidence interval, 1.50-2.08). No association was seen in multiparous women (relative risk, 1.07; 95% confidence interval, 0.81-1.39). Among all women induction was associated with modest increases in instrumental delivery (19% vs 15%; relative risk, 1.20; 95% confidence interval, 1.09-1.32) and shoulder dystocia (3.0% vs 1.7%; relative risk, 1.32; 95% confidence interval, 1.02-1.69). CONCLUSION: Among women who lacked an identified indication for induction of labor, induction was associated with increased likelihood of cesarean delivery for nulliparous but not multiparous women and with modest increases in the risk of instrumental delivery and shoulder dystocia for all women. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Med Scientist Training Program, Seattle, WA 98195 USA. Univ Washington, Womens Hlth Nursing Res Training Program, Seattle, WA 98195 USA. NICHHD, Maternal AIDS Branch, Ctr Res Mothers & Children, Bethesda, MD USA. RP Critchlow, CW (reprint author), Univ Washington, Dept Epidemiol, B509 Hlth Sci Bldg,Box 357475, Seattle, WA 98195 USA. RI Kaplan, Robert/A-2526-2011 FU NIGMS NIH HHS [5T32GM007266]; NINR NIH HHS [1P30NR04001] NR 25 TC 64 Z9 67 U1 0 U2 0 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 OCT PY 2000 VL 183 IS 4 BP 986 EP 994 DI 10.1067/mob.2000.106748 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 366AT UT WOS:000089983200038 PM 11035351 ER PT J AU Alexander, JM Mercer, BM Miodovnik, M Thurnau, GR Goldenberg, RL Das, AF Meis, PJ Moawad, AH Iams, JD VanDorsten, JP Paul, RH Dombrowski, MP Roberts, JM McNellis, D AF Alexander, JM Mercer, BM Miodovnik, M Thurnau, GR Goldenberg, RL Das, AF Meis, PJ Moawad, AH Iams, JD VanDorsten, JP Paul, RH Dombrowski, MP Roberts, JM McNellis, D TI The impact of digital cervical examination on expectantly managed preterm rupture of membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE digital cervical examination; preterm rupture of membranes ID PREMATURE RUPTURE; PERIOD; INFANT AB OBJECTIVE: The purpose of this study was to examine the effects of digital cervical examination on maternal and neonatal outcomes among women with preterm rupture of membranes. STUDY DESIGN: This analysis includes data from a previously reported trial of antibiotic treatment during expectant management of rupture of membranes at 24 to 32 weeks' gestation in singleton and twin gestations. Patients from both the randomized trial (n = 299 in the antibiotic group and n = 312 in the placebo group) and the observational component (n = 183) are included in this analysis. The groups were divided into those with one (n = 161) or two digital cervical examinations (n = 27) and those with no digital cervical examinations (n = 606). RESULTS: The gestational ages at enrollment were similar in the two groups (29 +/- 2 weeks' gestation for one or two examinations vs 29 +/- 2 weeks' gestation for no examinations; P = .85). There were no differences in chorioamnionitis (27% vs 29%; P = .69), endometritis (13% vs 11%; P = .5), or wound infection (0.5% vs 1%; P > .999) between the group with one or two examinations and the no-examination group. Infant outcomes were also similar in the two groups, including early sepsis (6% vs 5%; P = .68), respiratory distress syndrome (51% vs 45%; P = .18), intraventricular hemorrhage (7% vs 7%; P = .67), necrotizing enterocolitis (5% vs 3%; P = .19), and perinatal death (7% vs 5%; P = .45). A composite outcome made up of these neonatal outcomes was not different (56% vs 48%; P = .10) between the group with one or two examinations and the no-examination group. The time from rupture to delivery was shorter in the digital examination group (median value, 3 vs 5 days; P < .009). Multivariable analysis to adjust for antibiotic study group, group B streptococcal culture status, race, and maternal transfer did not modify these results. CONCLUSION: Performance of one or two digital cervical examinations during the course of expectant management of rupture of membranes between 24 and 32 weeks' gestation was associated with shorter latency but did not appear to worsen either maternal or neonatal outcome. C1 NICHHD, Maternal Fetal Med Units Network, Bethesda, MD USA. RP Alexander, JM (reprint author), Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NICHD NIH HHS [U10HD27915, U10HD27917, U10HD21434] NR 4 TC 27 Z9 27 U1 0 U2 3 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 OCT PY 2000 VL 183 IS 4 BP 1003 EP 1007 DI 10.1067/mob.2000.106765 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 366AT UT WOS:000089983200041 PM 11035354 ER PT J AU Bressler, NM Bressler, SB Hawkins, BS Marsh, MJ Sternberg, P Thomas, MA de Juan, E Campochiaro, PA Haller, JA Schachat, P Belt, J Cain, T Hartnett, M Hawse, P Herring, M Imach, J McDonald, J Porter, T Holekamp, NM Meredith, TA Barts, B Breeding, L Dahl, J Gualdoni, JL Hoffmeyer, G Nobel, V Ort, E Capone, A Lim, JI Brown, JM Gibbs, DK Gilman, J Johnson, J Swords, R Waldron, RG Williams, GA Garretson, BR Cumming, KL Medina, T Mitchell, B Regan, V Streasick, P Szydlowski, LD Zajechowski, M Toth, CA Jaffe, GJ Anderson, MM Hawks, TJ Heinis, R Schirmer, R Singerman, LJ Rice, TA Pendergast, SD DuBois, J Ilc, MA Knight, D Lichterman, SE Tilocco, KA Bergren, RL Campbell, A Sedory, K Steinberg, D Vagstad, G Wellman, L Wilcox, L Lewis, H Conway, J Holody, LJ Vargo, PJ McDonald, HR Johnson, RN DiAngelo, M Rozenfeld, I Uy, J Wild, S Wood, P Lambert, HM Miller, P Shigley, J Brucker, AJ Dupont, J Lurcott, J Weeney, L Wood, WJ McDowell, LC Oldroyd, M Slade, E Wolfe, JL Lopez, PF Nichols, T Walonker, FA Freeman, WR Clark, T Ochabski, R Ramirez, B Wilson, M Hammer, ME Malenfant, WJ Rollins, J Traynom, J Bressler, NM Childs, DA Felicetti, IL Orr, PR Staflin, P Bass, EB Hawkins, BS Casper, RG Dong, LM Grubb, SC Kiah, TR Lassiter, LA Marsh, MJ McCaffrey, LD Miskala, PH Newhouse, MM Prusakowski, NA Smith, DK Mangione, CM Rubin, GS Bressler, SB Alexander, J Manos, KS Mills, I Philips, DA Strozykowski, RW Tian, Y Orr, PR Gualdoni, JB Hartnett, M Hawse, P Cotch, MF Hillis, AI Abrams, GW Connett, JE Grady, C Harrison, E Jampol, LM Bressler, NM Alexander, J Hawkins, BS Maguire, MG Bressler, SB Fine, SL Green, WR Brucker, AJ de Juan, E Lambert, HM Lopez, PF Sternberg, P Thomas, MA Bressler, NM Bass, EB Bressler, SB Cotch, MF Grossniklaus, HE Haller, JA Hawkins, BS Holton, JL Mangione, CM Orr, PR Schwartz, SD Sipperley, JO Sternberg, P Thomas, MA Williams, GA AF Bressler, NM Bressler, SB Hawkins, BS Marsh, MJ Sternberg, P Thomas, MA de Juan, E Campochiaro, PA Haller, JA Schachat, P Belt, J Cain, T Hartnett, M Hawse, P Herring, M Imach, J McDonald, J Porter, T Holekamp, NM Meredith, TA Barts, B Breeding, L Dahl, J Gualdoni, JL Hoffmeyer, G Nobel, V Ort, E Capone, A Lim, JI Brown, JM Gibbs, DK Gilman, J Johnson, J Swords, R Waldron, RG Williams, GA Garretson, BR Cumming, KL Medina, T Mitchell, B Regan, V Streasick, P Szydlowski, LD Zajechowski, M Toth, CA Jaffe, GJ Anderson, MM Hawks, TJ Heinis, R Schirmer, R Singerman, LJ Rice, TA Pendergast, SD DuBois, J Ilc, MA Knight, D Lichterman, SE Tilocco, KA Bergren, RL Campbell, A Sedory, K Steinberg, D Vagstad, G Wellman, L Wilcox, L Lewis, H Conway, J Holody, LJ Vargo, PJ McDonald, HR Johnson, RN DiAngelo, M Rozenfeld, I Uy, J Wild, S Wood, P Lambert, HM Miller, P Shigley, J Brucker, AJ Dupont, J Lurcott, J Weeney, L Wood, WJ McDowell, LC Oldroyd, M Slade, E Wolfe, JL Lopez, PF Nichols, T Walonker, FA Freeman, WR Clark, T Ochabski, R Ramirez, B Wilson, M Hammer, ME Malenfant, WJ Rollins, J Traynom, J Bressler, NM Childs, DA Felicetti, IL Orr, PR Staflin, P Bass, EB Hawkins, BS Casper, RG Dong, LM Grubb, SC Kiah, TR Lassiter, LA Marsh, MJ McCaffrey, LD Miskala, PH Newhouse, MM Prusakowski, NA Smith, DK Mangione, CM Rubin, GS Bressler, SB Alexander, J Manos, KS Mills, I Philips, DA Strozykowski, RW Tian, Y Orr, PR Gualdoni, JB Hartnett, M Hawse, P Cotch, MF Hillis, AI Abrams, GW Connett, JE Grady, C Harrison, E Jampol, LM Bressler, NM Alexander, J Hawkins, BS Maguire, MG Bressler, SB Fine, SL Green, WR Brucker, AJ de Juan, E Lambert, HM Lopez, PF Sternberg, P Thomas, MA Bressler, NM Bass, EB Bressler, SB Cotch, MF Grossniklaus, HE Haller, JA Hawkins, BS Holton, JL Mangione, CM Orr, PR Schwartz, SD Sipperley, JO Sternberg, P Thomas, MA Williams, GA TI Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: I. Ophthalmic outcomes - Submacular surgery trials pilot study report number 1 SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Macula-Society CY FEB 26, 1999 CL SAN DIEGO, CA SP Macula Soc ID SURGICAL REMOVAL; SUBFOVEAL NEOVASCULARIZATION; MEMBRANES; MANAGEMENT AB PURPOSE: To report complications and changes in vision during 2 years of follow-up of patients with age-related macular degeneration assigned randomly to surgical removal or to laser photocoagulation of subfoveal recurrent neovascular lesions in a pilot trial designed to test methods, to refine estimates of outcome rates, and to project patient accrual rates for a larger multicenter randomized trial to evaluate submacular surgery. PATIENTS AND METHODS: Eligible patients with previous laser photocoagulation of extrafoveal or juxtafoveal choroidal neovascularization secondary to age-related macular degeneration were enrolled at 15 collaborating clinical centers. Assignments to treatment arm were made by personnel at a central coordinating center. Adherence to eligibility criteria and treatment assignment was assessed centrally at a photograph reading center. Patients were examined at 3, 6, 12, and 24 months after treatment for data collection purposes, Outcome measures reported include treatment complications, adverse events, requirements for additional treatment, and 2-year changes in visual acuity from baseline. RESULTS: Of 70 patients enrolled, 36 were assigned to laser photocoagulation and 34 to submacular surgery; all were treated as assigned. One patient in each group died before the 2-year examination. Visual acuity was measured at the 2-year examination for 31 of the surviving patients (89%) in the laser arm and for 28 of the surviving patients (85%) in the surgery arm. The 2-year measurements for 36 of the 59 patients (61%) were made by an examiner masked to treatment assignment and to the identity of the study eye. Improvements and losses of visual acuity were observed in both treatment arms; 20 of 31 study eyes (65%) in the laser arm and 14 of 28 study eyes (50%) in the surgery arm had visual acuity 2 years after enrollment that was better than or no more than 1 line worse than the baseline level. Changes in visual acuity and the size of the central macular lesions from baseline to the 2-year examination were similar in the treatment arms. Few serious complications were observed in either arm at the time of initial treatment; serious adverse events were rare. During follow-up, 11 laser-treated eyes and 18 surgically treated eyes had additional intraocular procedures. CONCLUSIONS: The data from this pilot trial suggest no reason to prefer submacular surgery over laser photocoagulation for treatment of patients with age-related macular degeneration who have lesions similar to those studied in this pilot trial. Any clinical trial designed to compare submacular surgery with laser photocoagulation in eyes with age-related macular degeneration and subfoveal recurrent neovascular lesions must enroll several hundred patients in order to reach a statistically valid conclusion regarding differences between these two methods of treatment with respect to either changes in visual acuity or complication rates. (C) 2000 by Elsevier Science Inc. All rights reserved. C1 Barnes Retina Inst, St Louis, MO USA. Emory Univ, Ctr Eye, Atlanta, GA 30322 USA. Assoc Retinal Consultants, Royal Oak, MI USA. Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. Retina Associates Cleveland, Cleveland, OH USA. Retina Vitreous Consultants, Pittsburgh, PA USA. Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. Retina & Vitreous Texas, Houston, TX USA. Scheie Eye Inst, Philadelphia, PA USA. Retina & Vitreous Associates Kentucky, Lexington, KY USA. Doheny Eye Inst, Los Angeles, CA 90033 USA. Shiley Eye Ctr, San Diego, CA USA. Retina Associates Florida, Tampa, FL USA. Wilmer Ophthalmol Inst, Chairmans Off, Retinal Vasc Ctr, Baltimore, MD USA. Wilmer Ophthalmol Inst, Coordinating Ctr, Baltimore, MD USA. Wilmer Ophthalmol Inst, Wilmer Photograph Reading Ctr, Baltimore, MD USA. NEI, NIH, Bethesda, MD 20892 USA. RP Hawkins, BS (reprint author), Submacular Surg Trials Coordinating Ctr, 550 N Broadway,9th Floor, Baltimore, MD 21205 USA. EM bhawkins@jhmi.edu RI toth, cynthia/F-5614-2011 FU NEI NIH HHS [U10EY11547, R21EY10823] NR 25 TC 73 Z9 76 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2000 VL 130 IS 4 BP 387 EP 407 PG 21 WC Ophthalmology SC Ophthalmology GA 362BV UT WOS:000089759500001 PM 11024412 ER PT J AU Van Veldhuisen, PC Ederer, F Gaasterland, DE Sullivan, EK Beck, A Prum, BE Cyrlin, MN Weiss, H AF Van Veldhuisen, PC Ederer, F Gaasterland, DE Sullivan, EK Beck, A Prum, BE Cyrlin, MN Weiss, H CA AGIS Inv TI The advanced glaucoma intervention study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; RISK-FACTORS; DAMAGE; DESIGN; EYE AB PURPOSE: To investigate the association between control of intraocular pressure after surgical intervention for glaucoma and visual field deterioration. METHODS: In the Advanced Glaucoma Intervention Study, eyes were randomly assigned to one of two sequences of glaucoma surgery, one beginning with argon laser trabeculoplasty and the other trabeculectomy. In the present article we examine the relationship between intraocular pressure and progression of visual field damage over 6 or more years of follow-up. In the first analysis, designated Predictive Analysis, we categorize 738 eyes into three groups based on intraocular pressure determinations over the first three 6-month follow-up visits. In the second analysis, designated Associative Analysis, we categorize 586 eyes into four groups based on the percent of B-month visits over the first 6 follow-up years in which eyes presented with intraocular pressure less than 18 mm Hg, The outcome measure in both analyses is change from baseline in follow-up visual field defect score (range, 0 to 20 units). RESULTS: In the Predictive Analysis, eyes with early average intraocular pressure greater than 17.5 mm Hg had an estimated worsening during subsequent follow-up that was 1 unit of visual field defect score greater than eyes with average intraocular pressure less than 14 mm Hg (P = .002). This amount of worsening was greater at 7 years (1.89 units; P < .001) than at 2 years (0.64 units; P = .071), In the Associative Analysis, eyes with 100% of visits with intraocular pressure less than 18 mm Hg over 6 years had mean changes from baseline in visual field defect score close to zero during follow-up, whereas eyes with less than 50% of visits with intraocular pressure less than 18 mm Hg had an estimated worsening over follow-up of 0.63 units of visual field defect score (P = .083). This amount of worsening was greater at 7 years (1.93 units; P < .001) than at 2 years (0.25 units; P = .572). CONCLUSIONS: In both analyses low intraocular pressure is associated with reduced progression of visual field defect, supporting evidence from earlier studies of a protective role for low intraocular pressure in visual field deterioration. (C) 2000 by Elsevier Science Inc. All rights reserved. C1 Emory Univ, Atlanta, GA 30322 USA. Georgetown Univ, Washington, DC USA. Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. Ohio State Univ, Columbus, OH 43210 USA. Piedmont Hosp, Atlanta, GA USA. Sinai Hosp Detroit, Southfield, MI USA. Univ Illinois, Chicago, IL USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Virginia, Charlottesville, VA USA. Washington Hosp Ctr, Chevy Chase, MD USA. Wills Eye Hosp & Res Inst, Philadelphia, PA USA. Yale Univ, New Haven, CT USA. EMMES Corp, Potomac, MD USA. NEI, Bethesda, MD USA. RP Van Veldhuisen, PC (reprint author), AGIS Coordinating Ctr, Adv Glaucoma Intervent Study, 11325 7 Locks Rd,Suite 214, Potomac, MD 20854 USA. NR 22 TC 1167 Z9 1191 U1 3 U2 40 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2000 VL 130 IS 4 BP 429 EP 440 PG 12 WC Ophthalmology SC Ophthalmology GA 362BV UT WOS:000089759500004 ER PT J AU Jabs, DA Rosenbaum, JT Foster, CS Holland, GN Jaffe, GJ Louie, JS Nussenblatt, RB Stiehm, ER Tessler, H Van Gelder, RN Whitcup, SM Yocum, D AF Jabs, DA Rosenbaum, JT Foster, CS Holland, GN Jaffe, GJ Louie, JS Nussenblatt, RB Stiehm, ER Tessler, H Van Gelder, RN Whitcup, SM Yocum, D TI Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: Recommendations of an expert panel SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Review ID RHEUMATOID-ARTHRITIS PATIENTS; BEHCETS-DISEASE; REFRACTORY UVEITIS; WEGENERS GRANULOMATOSIS; MULTIFOCAL CHOROIDITIS; POSTERIOR UVEITIS; RANDOMIZED TRIAL; CYCLOSPORINE-A; MASKED TRIAL; CLINICAL PHARMACOKINETICS AB PURPOSE: To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders. PARTICIPANTS: A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care. EVIDENCE: Published clinical study results. Recommendations were rated according to the quality and strength of available evidence. PROCESS: The panel was convened in September of 1999 and met regularly through May 2000. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although corticosteroids represent one of the mainstays in the management: of patients with ocular inflammation, in many patients, the severity of the disease, the presence of corticosteroid side effects, or the requirement for doses of systemic corticosteroids highly likely to result in corticosteroid complications supports the rationale for immunosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in the management of these patients. Because of the potential for side effects, treatment must be individualized and regular monitoring performed. With careful use of immunosuppressive drugs for treatment of ocular inflammatory disorders, many patients will benefit from them either with better control of the ocular inflammation or with a decrease in corticosteroid side effects. (C) 2000 by Elsevier Science Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Oregon Hlth Sci Univ, Casey Eye Inst, Dept Ophthalmol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Casey Eye Inst, Dept Med, Portland, OR 97201 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90024 USA. Duke Univ, Ctr Eye, Durham, NC USA. Harbor Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Univ Illinois, Eye & Ear Infirm, Chicago, IL 60612 USA. Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO USA. Univ Arizona, Hlth Sci Ctr, Dept Med, Tucson, AZ USA. RP Jabs, DA (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. NR 122 TC 347 Z9 370 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2000 VL 130 IS 4 BP 492 EP 513 DI 10.1016/S0002-9394(00)00659-0 PG 22 WC Ophthalmology SC Ophthalmology GA 362BV UT WOS:000089759500012 PM 11024423 ER PT J AU Stark, KL Gibson, JB Hertle, RW Brodsky, MC AF Stark, KL Gibson, JB Hertle, RW Brodsky, MC TI Ocular motor signs in an infant with carbohydrate-deficient glycoprotein syndrome type Ia SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To document the evolution of ocular motor abnormalities in an infant with carbohydrate-deficient glycoprotein syndrome. METHODS: Case report. An infant with carbohydrate-deficient glycoprotein syndrome type la underwent magnetic resonance imaging and infrared eye movement recording. RESULTS: A 10-month-old male with carbohydrate-deficient glycoprotein syndrome type Ia had rapid horizontal oscillations of the eyes when startled or awakened from sleep. Clinical examination confirmed this finding and disclosed congenital ocular motor apraxia with a reduced vestibule-ocular reflex. Infrared eye movement recording showed ocular flutter and square wave jerks superimposed on a horizontal pendular nystagmus, Magnetic resonance imaging showed diffuse cerebellar hypoplasia. CONCLUSION: Carbohydrate-deficient glycoprotein syndrome type Ia can be associated with multiple cerebellar eye signs including ocular flutter, square-wave jerks, and congenital ocular motor apraxia. (C) 2000 by Elsevier Science Inc. C1 Univ Arkansas Med Sci, Dept Ophthalmol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. NEI, Sensorimotor Res Lab, NIH, Washington, DC USA. RP Brodsky, MC (reprint author), Arkansas Childrens Hosp, 800 Marshall St, Little Rock, AR 72202 USA. NR 9 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2000 VL 130 IS 4 BP 533 EP 535 DI 10.1016/S0002-9394(00)00569-9 PG 3 WC Ophthalmology SC Ophthalmology GA 362BV UT WOS:000089759500024 PM 11024435 ER PT J AU Siefert, K Bowman, PJ Heflin, CM Danziger, S Williams, DR AF Siefert, K Bowman, PJ Heflin, CM Danziger, S Williams, DR TI Social and environmental predictors of maternal depression in current and recent welfare recipients SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; INTERNATIONAL DIAGNOSTIC INTERVIEW; PRIMARY-CARE PRACTICE; MAJOR DEPRESSION; LIFE EVENTS; PSYCHIATRIC-DISORDER; ANXIETY DISORDERS; MENTAL-HEALTH; SOCIOECONOMIC-STATUS AB Depression is highly prevalent in welfare recipients, and is associated with failure to move from welfare to work. This paper examines the relationship between social and environmental factors in a large, community-based sample of mothers who currently or recently received welfare benefits. Specific and modifiable risk factors related to poverty, gender, and race were found to predict major depression beyond traditional risk factors. Research and practice implications are discussed. C1 Univ Michigan, Sch Social Work, NIMH Res Ctr Poverty Risk & Mental Hlth, Ann Arbor, MI 48104 USA. Calif State Univ Los Angeles, Med Ctr, Los Angeles, CA 90032 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI USA. RP Siefert, K (reprint author), Univ Michigan, Sch Social Work, NIMH Res Ctr Poverty Risk & Mental Hlth, 540 E Liberty,Suite 202, Ann Arbor, MI 48104 USA. FU NIMH NIH HHS [R-24-MH51363] NR 116 TC 78 Z9 78 U1 4 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0002-9432 EI 1939-0025 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD OCT PY 2000 VL 70 IS 4 BP 510 EP 522 DI 10.1037/h0087688 PG 13 WC Psychiatry; Social Work SC Psychiatry; Social Work GA 372YR UT WOS:000165262100009 PM 11086529 ER PT J AU Janczewski, AM Lakatta, EG Stern, MD AF Janczewski, AM Lakatta, EG Stern, MD TI Voltage-independent changes in L-type Ca2+ current uncoupled from SR Ca2+ release in cardiac myocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE excitation-contraction coupling; local Ca2+ control; ryanodine receptor; corbular sarcoplasmic reticulum; FPL-64176 ID SARCOPLASMIC-RETICULUM; RYANODINE RECEPTORS; VENTRICULAR MYOCYTES; LOCAL-CONTROL; RAT; CONTRACTION; CELLS; CALCIUM; CHANNEL; MUSCLE AB To determine the effect of voltage-independent alterations of L-type Ca2+ current (I-Ca)on the sarcoplasmic reticular (SR) Ca2+ release in cardiac myocytes, we measured I-Ca and cytosolic Ca2+ transients (Ca-i(2+); intracellular Ca2+ concentration) in voltage-clamped rat ventricular myocytes during 1) an abrupt increase of extracellular [Ca2+] (Ca-o(2+)) or 2) application of 1 mu M FPL-64176, a Ca2+ channel agonist, to selectively alter I-Ca in the absence of changes in SR Ca2+ loading. On the first depolarization in higher Ca-o(2+), peak I-Ca was increased by 46 +/- 6% (P < 0.001), but the increases in the maximal rate of rise of Ca-i(2+) (dCa(i)(2+)/dt(max), where t is time; an index of SR Ca2+ release flux) and the Ca-i(2+) transient amplitude were not significant. Rapid exposure to FPL-64176 greatly slowed inactivation of I-Ca, increasing its time integral by 117 +/- 8% (P < 0.001) without significantly increasing peak I-Ca, dCac(i)(2+)/ dt(max), or amplitude of the corresponding Ca-i(2+) transient. Prolongation of exposure to higher Ca-o(2+) or FPL-64176 did not further increase peak I-Ca but greatly increased dCa(i)(2+)/ dt(max),Cac(i)(2+) transient amplitude, and the gain of Ca2+ release (dCa(i)(2+) (dt(max) /I-Ca), evidently due to augmentation of the SR Ca2+ loading. Also, the time to peak dCa(i)(2+)/dtmax was significantly increased in the continuous presence of higher Ca-o(2+) (by 37 +/- 5%, P < 0.001) or FPL-64176 (by 63 +/- 5%, P < 0.002). Our experiments provide the first evidence of a marked disparity between an increased peak I-Ca and the corresponding SR Ca2+ release. We attribute this to saturation of the SR Ca2+ release flux as predicted by local control theory. Prolongation of the SR Ca2+ release flux, caused by combined actions of a larger I-Ca and maximally augmented SR Ca2+ loading, might reflect additional Ca2+ release from corbular SR. C1 NIA, Intramural Res Program, Gerontol Res Ctr, Lab Cardiovasc Sci,NIH, Baltimore, MD 21224 USA. RP Stern, MD (reprint author), NIA, Intramural Res Program, Gerontol Res Ctr, Lab Cardiovasc Sci,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 26 TC 9 Z9 9 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2000 VL 279 IS 4 BP H2024 EP H2031 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 358FK UT WOS:000089547600068 PM 11009494 ER PT J AU Younes, A Pepe, S Barron, BA Spurgeon, HA Lakatta, EG Caffrey, JL AF Younes, A Pepe, S Barron, BA Spurgeon, HA Lakatta, EG Caffrey, JL TI Cardiac synthesis, processing, and coronary release of enkephalin-related peptides SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE enkephalin-containing peptides; opioids; rat heart ID PRIMARY HEREDITARY CARDIOMYOPATHY; PREPROENKEPHALIN MESSENGER-RNA; RAT-HEART; OPIOID RECEPTORS; GENE-EXPRESSION; MYOCARDIAL-INFARCTION; HYPERTENSIVE RATS; MET-ENKEPHALIN; SYRIAN-HAMSTER; MYOCYTES AB Although preproenkephalin mRNA is abundant in the heart, the myocardial synthesis and processing of proenkephalin is largely undefined. Isolated working rat hearts were perfused to determine the rate of myocardial proenkephalin synthesis, its processing into enkephalin-containing peptides, their subsequent release into the coronary arteries, and the influence of prior sympathectomy. Enkephalin-containing peptides were separated by gel filtration and quantified with antisera for specific COOH-terminal sequences. Proenkephalin, peptide B, and [Met(5)]enkephalin-Arg(6)-Phe(7) (MEAP) comprised 95% of the extracted myocardial enkephalins (35 pmol/g). Newly synthesized enkephalins, estimated during a 1-h perfusion with [C-14] phenylalanine (4 pmol . h(-1) . g wet wt(-1)), were rapidly cleared from the heart during a second isotope-free hour. Despite a steady release of enkephalins into the coronary effluent (4 pmol . h(-1) . g wet wt(-1)), enkephalin replacement apparently exceeded its release, and tissue enkephalins actually accumulated during hour 2. In contrast to the tissue, methionine-enkephalin accounted for more than half of the released enkephalin. Chemical sympathectomy produced an increase in total enkephalin content similar to that observed after 2-h control perfusion. This observation suggested that the normal turnover of myocardial enkephalin may depend in part on continued sympathetic influences. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Auvergne, Inst Univ Technol, F-63172 Aubiere, France. Baker Med Res Inst, Melbourne, Vic 8008, Australia. Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Ft Worth, TX 76107 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 41 TC 29 Z9 29 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2000 VL 279 IS 4 BP H1989 EP H1998 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 358FK UT WOS:000089547600063 PM 11009489 ER PT J AU Glasgow, E Murase, T Zhang, BJ Verbalis, JG Gainer, H AF Glasgow, E Murase, T Zhang, BJ Verbalis, JG Gainer, H TI Gene expression in the rat supraoptic nucleus induced by chronic hyperosmolality versus hyposmolality SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE vasopressin; oxytocin; neurophysin; PEP-19; gene for oligodendrocyte lineage-myelin basic protein; magnocellular neuron ID BASIC-PROTEIN GENE; MESSENGER-RNA; DEVELOPMENTAL EXPRESSION; CHRONIC HYPOOSMOLALITY; CYTOCHROME-OXIDASE; BRATTLEBORO RAT; RGS PROTEINS; VASOPRESSIN; NEURONS; BRAIN AB Magnocellular neurons of the hypothalamo-neurohypophysial system play a fundamental role in the maintenance of body homeostasis by secreting vasopressin and oxytocin in response to systemic osmotic perturbations. During chronic hyperosmolality, vasopressin and oxytocin mRNA levels increase twofold, whereas, during chronic hyposmolality, these mRNA levels decrease to 10-20% of that of normoosmolar control animals. To determine what other genes respond to these osmotic perturbations, we have analyzed gene expression during chronic hyper- versus hyponatremia. Thirty-seven cDNA clones were isolated by differentially screening cDNA libraries that were generated from supraoptic nucleus tissue punches from hyper- or hyponatremic rats. Further analysis of 12 of these cDNAs by in situ hybridization histochemistry confirmed that they are osmotically regulated. These cDNAs represent a variety of functional classes and include cytochrome oxidase, tubulin, Na+-K+-ATPase, spectrin, PEP-19, calmodulin, GTPase, DnaJ-like, clathrin-associated, synaptic glycoprotein, regulator of GTPase stimulation, and gene for oligodendrocyte lineage-myelin basic proteins. This analysis therefore suggests that adaptation to chronic osmotic stress results in global changes in gene expression in the magnocellular neurons of the supraoptic nucleus. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D20,MSC 4130, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK-38094] NR 51 TC 12 Z9 13 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD OCT PY 2000 VL 279 IS 4 BP R1239 EP R1250 PG 12 WC Physiology SC Physiology GA 357DN UT WOS:000089483400012 PM 11003989 ER PT J AU Howell, MR McKee, KT Gaydos, JC Quinn, TC Gaydos, CA AF Howell, MR McKee, KT Gaydos, JC Quinn, TC Gaydos, CA TI Point-of-entry screening for C-trachomatis in female army recruits - Who derives the cost savings? SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE Chlamydia trachomatis; costs and cost-analysis; cost-benefit analysis; military personnel; prevention, primary; mass screening; sexually transmitted diseases ID PELVIC INFLAMMATORY DISEASE; FAMILY-PLANNING CLINICS; LIGASE CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS; INFECTIONS; WOMEN; URINE; TRENDS AB Background: Screening women fbr genital Chlamydia trachomatis at entry to military service provides an opportunity to reduce costs associated with sequelae of this infection. However, financial responsibility for screening may be debated. More than 50% of recruits return to civilian life within 2 years. The military and the civilian health care systems would both benefit from a screening program; Objective: To assess the cost-effectiveness and relative cost savings to the military and civilian health sectors of three screening strategies for U.S. Army female recruits for C. trachomatis using urine ligase chain reaction: screening all recruits, screening recruits aged less than or equal to 25 years, and no screening. Methods: We applied a decision analytic model. Cost factors included screening, lost military training, morbid pelvic inflammatory disease, and other sequelae. Using a 5-year analytic horizon, we conducted analyses from military and civilian perspectives. Results: Screening 10,000 female army recruits would cost $193,500 and prevent 282 cases of sequelae, with a projected savings of $53,325 to the military and $505,053 to the civilian sector. From a military perspective, screening women aged less than or equal to 25 years provided the highest cost savings. Screening all female recruits incurred an incremental cost of $1199 per sequela prevented. From a civilian perspective, screening all recruits offered the greatest cost savings. Conclusions: Screening female Army recruits for C. trachomatis offers substantial savings in health care costs for both the military and civilian health care systems. Relative financial benefit. derived from recruit screening is disproportionate; greatest cost savings are enjoyed by the civilian sector. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. Womack Army Med Ctr, Ft Bragg, NC USA. Walter Reed Army Inst Res, Dept Def Global Emerging Infect Surveillance & Re, Silver Spring, MD USA. Henry M Jackson Fdn, Rockville, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Div Infect Dis, Ross Res Bldg,Room 1159,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 20 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2000 VL 19 IS 3 BP 160 EP 166 DI 10.1016/S0749-3797(00)00202-6 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 361ME UT WOS:000089726200004 PM 11020592 ER PT J AU Callicott, JH Bertolino, A Egan, MF Mattay, VS Langheim, FJP Weinberger, DR AF Callicott, JH Bertolino, A Egan, MF Mattay, VS Langheim, FJP Weinberger, DR TI Selective relationship between prefrontal N-acetylaspartate measures and negative symptoms in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBRAL BLOOD-FLOW; WORKING-MEMORY DEFICITS; MAGNETIC-RESONANCE SPECTROSCOPY; CARD SORTING TEST; STRUCTURAL ABNORMALITIES; BRAIN; DYSFUNCTION; PATHOLOGY; PATTERNS; CORTEX AB Objective: Certain cognitive, behavioral, and emotional deficits (so-called negative symptoms) in patients with schizophrenia have often been attributed to prefrontal cortical pathology, but direct evidence for a relationship between prefrontal neuronal pathology and negative symptoms has been lacking. The authors hypothesized that an in vivo measure of prefrontal neuronal pathology (N-acetylaspartate [NAA] levels) in patients with schizophrenia would predict negative symptoms. Method: Proton magnetic resonance spectroscopic imaging (H-1-MRSI) and rating scales for negative and positive symptoms were used to study 36 patients with schizophrenia. Magnetic resonance spectra were analyzed as metabolite ratios, and parametric correlations were performed. Results: A regionally selective negative correlation was found between prefrontal NAA-creatine ratio and negative symptom ratings in this group of patients with schizophrenia. Conclusions: Lower prefrontal NAA-and by inference greater neuronal pathology-predicted more severe negative symptoms in patients with schizophrenia. These data demonstrate a relationship between an intraneuronal measure of dorsolateral prefrontal cortex integrity and negative symptoms in vivo and represent further evidence for the involvement of the dorsolateral prefrontal cortex in negative symptoms associated with schizophrenia. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Callicott, JH (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, 10 Ctr Dr,Rm 4D-20,MSC 1389, Bethesda, MD 20892 USA. RI Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380 NR 70 TC 82 Z9 88 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2000 VL 157 IS 10 BP 1646 EP 1651 DI 10.1176/appi.ajp.157.10.1646 PG 6 WC Psychiatry SC Psychiatry GA 359VZ UT WOS:000089633900016 PM 11007719 ER PT J AU Helfand, WH Lazarus, J Theerman, P AF Helfand, WH Lazarus, J Theerman, P TI Cholera in Paris SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Theerman, P (reprint author), Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 2 Z9 2 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 OCT PY 2000 VL 90 IS 10 BP 1530 EP 1530 DI 10.2105/AJPH.90.10.1530 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 358LJ UT WOS:000089559300005 PM 11029983 ER PT J AU Millar, EV O'Brien, KL Levine, OS Kvamme, S Reid, R Santosham, M AF Millar, EV O'Brien, KL Levine, OS Kvamme, S Reid, R Santosham, M TI Toward elimination of Haemophilus influenzae type B carriage and disease among high-risk American Indian children SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID REDUCES OROPHARYNGEAL CARRIAGE; MEMBRANE PROTEIN COMPLEX; CONJUGATE VACCINE; INVASIVE DISEASE; UNITED-STATES; POLYSACCHARIDE; EPIDEMIOLOGY; POPULATION; COLONIZATION; IMPACT AB Objectives. This report describes the epidemiology of Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal among Navajo and White: Mountain Apache children younger than 7 years in an era of wide-spread immunization. Methods. We conducted active surveillance for-invasive H influenzae disease from 1992 to 1999 and an oropharyngeal carriage study from 1997 to 1999. The predominant vaccine used was PedvaxHib. Results. The average annual incidence of invasive Hib disease among children younger:than 24 months was 22 cases per 100 000. Of 381 children younger than 7 years, only 1 (0.3%; 95% confidence interval = 0.0%, 1.3%) was colonized with Hib; 370 (97%) had received 2 or more doses of Hib conjugate vaccine. Conclusions Among Navajo and White Mountain Apache children, Hib conjugate vaccines have led to a sustained reduction in invasive Hib disease and a reduction in oropharyngeal Hib carriage. The disease incidence among children younger than 24 months remains 20 times higher than in the general US population. Hib elimination will require additional characterization of colonization and disease in these high-risk populations. C1 Johns Hopkins Univ, Ctr Amer Indian & Alaskan Native Hlth, Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. NIAID, Resp Dis Branch, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Resp Dis Branch, Atlanta, GA USA. RP O'Brien, KL (reprint author), Johns Hopkins Univ, Ctr Amer Indian & Alaskan Native Hlth, Sch Hyg & Publ Hlth, Dept Int Hlth, 621 N Washington St, Baltimore, MD 21205 USA. NR 19 TC 33 Z9 35 U1 0 U2 1 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 OCT PY 2000 VL 90 IS 10 BP 1550 EP 1554 DI 10.2105/AJPH.90.10.1550 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 358LJ UT WOS:000089559300009 PM 11029987 ER PT J AU Stearns, SC Bernard, SL Fasick, SB Schwartz, R Konrad, TR Ory, MG DeFriese, GH AF Stearns, SC Bernard, SL Fasick, SB Schwartz, R Konrad, TR Ory, MG DeFriese, GH TI The economic implications of self-care: The effect of lifestyle, functional adaptations, and medical self-care among a national sample of medicare beneficiaries SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OLDER ADULTS AB Objectives. Self-care includes actions taken by individuals to promote or ensure their health, to recover from diseases or injuries, or to manage their effects. This study measured associations between self-care practices (lifestyle practices, adaptations to functional limitations, and medical self-care) and Medicare expenditures among a national sample of adults 65 years and older. Methods. Regression models of Medicare use and expenditures were estimated by using the National Survey of Self-Care and Aging and Medicare claims for 4 years following a baseline interview. Results. Lifestyle factors (swimming and walking) and functional adaptations (general home modifications) were associated with reductions in monthly Medicare expenditures over a 12-month follow-up period. Expenditure reductions were found over the 48-month follow-up period for participation in active sports, gardening, and medical self-care. Practices associated with increases in expenditures included smoking, physical exercise (possibly of a more strenuous nature), and specific home modifications. Conclusions. Certain self-care practices appear to have significant implications for Medicare expenditures and presumptively for the health status of older adults. Such practices should be encouraged among older adults as a matter of national health policy. C1 Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC 27599 USA. Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. NIA, Bethesda, MD 20892 USA. RP Stearns, SC (reprint author), Univ N Carolina, Dept Hlth Policy & Adm, CB 7400,114C McGavran Greenberg, Chapel Hill, NC 27599 USA. OI Konrad, Thomas R/0000-0002-5269-0440 FU PHS HHS [A07929-02] NR 14 TC 25 Z9 26 U1 0 U2 1 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 OCT PY 2000 VL 90 IS 10 BP 1608 EP 1612 DI 10.2105/AJPH.90.10.1608 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 358LJ UT WOS:000089559300018 PM 11029996 ER PT J AU Spong, CY McCune, SK Sternberg, EM Gustafsson, JA AF Spong, CY McCune, SK Sternberg, EM Gustafsson, JA TI Maternal estrogen receptor-beta expression during mouse gestation SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE estrogen receptor alpha; estrogen receptor beta; pregnancy ID ALPHA ER-ALPHA; MESSENGER-RNA; TISSUE DISTRIBUTION; RAT-BRAIN; SITES AB PROBLEM: Although estrogen receptor (ER)-alpha has been well characterized, the recently identified novel ER-beta has not. In some tissues, there is overlap of the ERs, which allows for rescue in cases of deficiency; in other tissues, the ERs appear to have opposite effects. The objective of this study was to evaluate the expression of ER-beta during pregnancy. METHOD OF STUDY: Pregnant mouse uteri (embryonic days 6-14, 16,18) were studied. ER-alpha and ER-beta oligonucleotide probes were end-labeled and in situ hybridization histochemistry was performed. RESULTS: ER-beta was strongly expressed in maternal ovaries; there was no other evidence of strong expression during gestation. ER-alpha was expressed in the uterus throughout gestation, with decreasing intensity as gestation progressed, and in maternal ovarian tissue. CONCLUSIONS: Differential expression of the two ERs was apparent during pregnancy, with ER-alpha playing a dominant role. This may have implications for selective drug treatment targeting estrogen receptors. C1 NICHD, Sect Dev & Mol Pharmacol, LDN, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neonatol, Bethesda, MD USA. NIMH, CNE, DIRP, Bethesda, MD 20892 USA. Karolinska Inst, Huddinge, Sweden. RP Spong, CY (reprint author), NICHD, Sect Dev & Mol Pharmacol, LDN, NIH, Bldg 49,5A-38,MSC 4480,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 4 Z9 5 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD OCT PY 2000 VL 44 IS 4 BP 249 EP 252 DI 10.1111/j.8755-8920.2000.440410.x PG 4 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 363GG UT WOS:000089826300010 PM 11076098 ER PT J AU Gauderman, WJ McConnell, R Gilliland, F London, S Thomas, D Avol, E Vora, H Berhane, K Rappaport, EB Lurmann, F Margolis, HG Peters, J AF Gauderman, WJ McConnell, R Gilliland, F London, S Thomas, D Avol, E Vora, H Berhane, K Rappaport, EB Lurmann, F Margolis, HG Peters, J TI Association between air pollution and lung function growth in southern California children SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID OBSTRUCTIVE RESPIRATORY-DISEASE; PULMONARY-FUNCTION GROWTH; NORTH-AMERICAN CHILDREN; PREADOLESCENT CHILDREN; CHRONIC EXPOSURE; UCLA POPULATION; DIFFERING LEVELS; DUTCH CHILDREN; ACID AEROSOLS; HEALTH AB Average growth of lung function over a 4-yr period, in three cohorts of southern California children who were in the fourth, seventh, or tenth grade in 1993, was modeled as a function of average exposure to ambient air pollutants. In the fourth-grade cohort, significant deficits in growth of lung function (FEV1, FVC, maximal midexpiratory flow [MMEF], and FEF75) were associated with exposure to particles with aerodynamic diameter less than 10 mu m (PM10), PM2.5, PM10-PM2.5, NO2, and inorganic acid vapor (p < 0.05). No significant associations were observed with ozone. The estimated growth rate for children in the most polluted of the communities as compared with the least polluted was predicted to result in a cumulative reduction of 3.4% in FEV1 and 5.0% in MMEF over the 4-yr study period. The estimated deficits were generally larger for children spending more time outdoors. In the seventh- and tenth-grade cohorts, the estimated pollutant effects were also negative for most lung function measures, but sample sizes were lower in these groups and none achieved statistical significance. The results suggest that significant negative effects on lung function growth in children occur at current ambient concentrations of particles, NO2 and inorganic acid vapor. C1 Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Sonoma Technol Inc, Petaluma, CA USA. State Calif, Air Resources Board, Sacramento, CA USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Gauderman, WJ (reprint author), Univ So Calif, Sch Med, Dept Prevent Med, 1540 Alcazar St,CHP 220, Los Angeles, CA 90089 USA. OI London, Stephanie/0000-0003-4911-5290 FU NIEHS NIH HHS [SP30ES07048-02] NR 33 TC 200 Z9 210 U1 6 U2 33 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 OCT PY 2000 VL 162 IS 4 BP 1383 EP 1390 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 364RD UT WOS:000089905900033 PM 11029349 ER PT J AU Hong, SH Kadosawa, T Mochizuki, M Matsunaga, S Nishimura, R Sasaki, N AF Hong, SH Kadosawa, T Mochizuki, M Matsunaga, S Nishimura, R Sasaki, N TI Effect of all-trans and 9-cis retinoic acid on growth and metastasis of xenotransplanted canine osteosarcoma cells in athymic mice SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID VITAMIN-A; PROMYELOCYTIC LEUKEMIA; HUMAN-MELANOMA; BREAST-CANCER; CARCINOMA; INTERFERON; LINE; DIFFERENTIATION; COMBINATION; INHIBITION AB Objective-To determine effects of all-trans and 9-cis retinoic acid (RA) on tumor growth and metastatic ability of canine osteosarcoma cells transplanted into athymic (nude) mice. Animals-Forty-five 5-week-old female BALB/c nude mice. Procedure-1 X 10(7) POS osteosarcoma cells were transplanted subcutaneously into the intrascapular region of mice. All-trans RA (3 or 30 mu g/kg of body weight in 0.1 mi of sesame oil), 9-cis RA (3 or 30 mg/kg in 0.1 mi of sesame oil), or sesame oil (0.1 mi, control treatment) were administered intragastrically 5 d/wk for 4 weeks beginning 3 days after transplantation (n = 4 mice/group) or after formation of a palpable tumor (5 mice/group). Tumor weight was estimated weekly by measuring tumor length and width, and retinoid toxic effects were evaluated daily. Two weeks after the final treatment, mice were euthanatized, and number of mice with pulmonary metastases was determined. Results-Adverse treatment effects were not detected. Tumor weight was less in mice treated with either dose of 9-cis RA than in control mice, although this difference was not significant. Treatment with 30 mg of 9-cis RA/kg initiated after tumor formation significantly reduced the incidence of pulmonary metastasis, compared with the control group. Conclusions and Clinical Relevance-9-cis RA decreased the incidence of pulmonary metastasis in nude mice transplanted with canine osteosarcoma cells and may be a potential adjunct therapy for treatment of osteosarcoma in dogs. C1 NCI, Pediat Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Agr & Life Sci, Div Vet Anim Sci, Lab Vet Surg, Tokyo 1138657, Japan. Univ Tokyo, Vet Med Ctr, Tokyo 1138657, Japan. Hokkaido Univ, Grad Sch Vet Med, Dept Vet Clin Sci, Lab Vet Surg, Sapporo, Hokkaido 0600818, Japan. RP Hong, SH (reprint author), NCI, Pediat Oncol Branch, Div Clin Sci, 10-13N240, Bethesda, MD 20892 USA. NR 30 TC 4 Z9 4 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD OCT PY 2000 VL 61 IS 10 BP 1241 EP 1244 DI 10.2460/ajvr.2000.61.1241 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 362RG UT WOS:000089791600014 PM 11039554 ER PT J AU Kar, SR Kingsbury, JS Lewis, MS Laue, TM Schuck, P AF Kar, SR Kingsbury, JS Lewis, MS Laue, TM Schuck, P TI Analysis of transport experiments using pseudo-absorbance data SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE sedimentation velocity; analytical electrophoresis; time-invariant noise; analytical ultracentrifugation; protein interactions ID INTERFERENCE OPTICAL-DATA; SEDIMENTATION EQUILIBRIUM; ULTRACENTRIFUGE; COEFFICIENTS AB The measurement of the concentration distribution of a macromolecule across a solution column by absorption optics usually requires optical transmission profiles of both the sample solution and the buffer, measured under identical conditions, to calculate the absorbance as the logarithm of the ratio of reference to sample intensity. For transport experiments, however, where the changes in the local macromolecule concentration with time are measured, a reference buffer intensity is not necessarily required. We demonstrate that the logarithm of the light transmitted through the sample solution, referred to as pseudoabsorbance, can suffice to determine macromolecular transport parameters of interest, with little loss of precision. Local changes in illumination of the sample column or in the detection efficiency of the transmitted light, as well as temporal fluctuations of the light source intensity can be well-described by consideration of time-invariant and radial-invariant signal components in the pseudo-absorbance data, using the systematic noise decomposition techniques developed recently (Schuck, P., and Demeler, B. (1999) Biophys. J. 76, 2288-2296). The practical use of the method is demonstrated with double-sector and single-sector sedimentation velocity experiments, and with analytical electrophoresis experiments. It is shown that pseudoabsorbance analysis can increase the capacity of a sedimentation velocity experiment in ultracentrifugation, and, in general, can considerably simplify the requirements of optical design. (C) 2000 Academic Press. C1 NIH, ORS, Mol Interact Resource Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. Univ New Hampshire, Ctr Adv Mol Interact Sci, Durham, NH 03824 USA. Univ New Hampshire, Dept Biochem, Durham, NH 03824 USA. RP Schuck, P (reprint author), NIH, ORS, Mol Interact Resource Bioengn & Phys Sci Program, Bldg 13,Room 3N17,13 South Dr, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 24 TC 22 Z9 23 U1 0 U2 4 PU ACADEMIC PRESS INC 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 OCT 1 PY 2000 VL 285 IS 1 BP 135 EP 142 DI 10.1006/abio.2000.4748 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 360VD UT WOS:000089687300016 PM 10998273 ER PT J AU Pettit, GR Lippert, JW Boyd, MR Verdier-Pinard, P Hamel, E AF Pettit, GR Lippert, JW Boyd, MR Verdier-Pinard, P Hamel, E TI Antineoplastic agents 442. Synthesis and biological activities of dioxostatin SO ANTI-CANCER DRUG DESIGN LA English DT Article DE asymmetric dihydroxylation; dioxostatin; dioxostatin prodrug; tubulin binding agent ID COMBRETASTATIN A-4 PHOSPHATE; SOLID TUMOR-THERAPY; ANTIMITOTIC AGENTS; TUBULIN POLYMERIZATION; ANGIOGENESIS INHIBITORS; ASYMMETRIC-SYNTHESIS; SELECTIVE TOXICITY; ANTITUMOR-ACTIVITY; COMBRETUM-CAFFRUM; NATURAL-PRODUCTS AB A high-yield regioselective synthesis of (E)-combretastatin A-1 2b was completed using methoxymethyl (MOM) protection and a Wadsworth-Emmons reaction as key steps. In turn, (E)-stilbene 11 was converted by convenient syntheses to both (S,S)- and (R,R)-1,3-dioxolanes 5a and 6a. A Sharpless asymmetric dihydroxylation reaction was employed for preparation of intermediates (S,S)-12 and (R,R)-13. The (4S,5S)-4-(2 ' ,3 ' dihydroxy-4 ' -methoxyphenyl)-5-(3 " ,4 " ,5 " -trimethoxyphenyl)-1, 3-dioxolane 5a was found to be a highly potent inhibitor of microtubule assembly (IC50 = 0.59 muM) and was designated dioxostatin. Conversion to sodium phosphate 17 (P388 lymphocytic leukemia cell line: ED50 = 0.2 mug/ml) provided a very useful water-soluble prodrug. C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Dev & Screening Technol Branch, DTP DCTD, Frederick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, POB 872404, Tempe, AZ 85287 USA. FU NCI NIH HHS [CA 44344-06-12] NR 54 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD OCT PY 2000 VL 15 IS 5 BP 361 EP 371 PG 11 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA 431HR UT WOS:000168626200007 PM 11354312 ER PT J AU Walsh, TJ Jackson, AJ Lee, JW Amantea, M Sein, T Bacher, J Zech, L AF Walsh, TJ Jackson, AJ Lee, JW Amantea, M Sein, T Bacher, J Zech, L TI Dose-dependent pharmacokinetics of amphotericin B lipid complex in rabbits (vol 44, pg 2068, 2000) SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Correction C1 NCI, Mycol Unit, NIH, Bethesda, MD 20892 USA. NCI, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. NCI, Math Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Resource Program, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Bioequivalence, Rockville, MD 20857 USA. RP Walsh, TJ (reprint author), NCI, Mycol Unit, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 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 OCT PY 2000 VL 44 IS 10 BP 2924 EP 2924 DI 10.1128/AAC.44.10.2924-2924.2000 PG 1 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 355TK UT WOS:000089402300065 ER PT J AU Howard, JC Heinemann, C Thatcher, BJ Martin, B Gan, BS Reid, G AF Howard, JC Heinemann, C Thatcher, BJ Martin, B Gan, BS Reid, G TI Identification of collagen-binding proteins in Lactobacillus spp. with surface-enhanced laser desorption/ionization-time of flight ProteinChip technology SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID BIOSURFACTANTS; STRAINS AB Biosurfactants produced by Lactobacillus fermentum RC-14, L. rhamnosus GR-I and 36, and L, casei Shirota were found to contain proteins that bind to both collagen types III and VI, as determined by surface-enhanced Laser desorption/ionization (SELDI)-time of flight mass spectrometry. Both collagen types III and VI immobilized on SELDI preactivated ProteinChip arrays detected several different sizes (2 to 48 kDa) of collagen-binding proteins. Overall, the RC-14-produced biosurfactant contained the greatest number of collagen-binding proteins (RC-14 > GR-1 > 36 > Shirota), including the mature form of a previously cloned 29-kDa collagen-binding protein (referred to in its mature 26-kDa form). Although biosurfactants isolated from L, casei Shirota and L. rhamnosus 36 and GR-1 also contain several collagen-binding proteins, they do not contain the 26-kDa collagen-binding protein. Together, these results demonstrate the utility of the SELDI system as a means of rapidly characterizing clinically important but complex biosurfactant solutions. C1 Lawson Res Inst, London, ON N6A 4V2, Canada. Hand & Upper Limb Ctr, London, ON, Canada. Ciphergen Biosyst Inc, Palo Alto, CA USA. NIH, Div Clin Neurosci, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Surg, London, ON N6A 3K7, Canada. Univ Western Ontario, Dept Pharmacol & Toxicol, London, ON N6A 3K7, Canada. Univ Western Ontario, Dept Immunol & Microbiol, London, ON N6A 3K7, Canada. Univ Western Ontario, Dept Med Biophys, London, ON N6A 3K7, Canada. RP Reid, G (reprint author), Lawson Res Inst, H414,268 Grosvenor St, London, ON N6A 4V2, Canada. NR 13 TC 40 Z9 47 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2000 VL 66 IS 10 BP 4396 EP 4400 DI 10.1128/AEM.66.10.4396-4400.2000 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 360CW UT WOS:000089649700034 PM 11010889 ER PT J AU Marshall, AD McPhie, P Jakoby, WB AF Marshall, AD McPhie, P Jakoby, WB TI Redox control of aryl sulfotransferase specificity SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID TYROSINE-ESTER SULFOTRANSFERASE; PHENOL SULFOTRANSFERASE; CRYSTAL-STRUCTURE; RAT-LIVER; ESTROGEN SULFOTRANSFERASE; SUBSTRATE-SPECIFICITY; IV; 3'-PHOSPHOADENOSINE-5'-PHOSPHOSULFATE; IDENTIFICATION; SULFATION AB Aryl sulfotransferase IV from rat liver has the very broad substrate range that is characteristic of the enzymes of detoxication. With the conventional assay substrates, 4-nitrophenol and PAPS, sulfation was considered optimal at pH 5.5 whereas the enzyme in the physiological pH range was curiously ineffective. These properties would seem to preclude a physiological function for this cytosolic enzyme. Partial oxidation of the enzyme, however, results not only in a substantial increase in the rate of sulfation of 4-nitrophenol at physiological pH but also in a shift of the pH optimum to this range and radically altered overall substrate specificity. The mechanism for this dependence on redox environment involves oxidation at Cys66, a process previously shown to occur by formation of a mixed disulfide with glutathione or by the formation of an internal disulfide with Cys232, Oxidation at Cys66 acts only as a molecular redox switch and is not directly part of the catalytic mechanism, Underlying the activation process is a change in the nature of the ternary complex formed between enzyme, phenol, and the reaction product, adenosine 3',5'-bisphosphate, The reduced enzyme gives rise to an inhibitory, dead-end ternary complex, the stability of which is dictated by the ionization of the specific phenol substrate. Ternary complex formation impedes the binding of PAPS that is necessary to initiate a further round of the reaction and is manifest as profound, substrate-dependent inhibition, In contrast, the ternary complex formed when the enzyme is in the partially oxidized state allows binding of PAPS and the unhindered completion of the reaction cycle. (C) 2000 Academic Press. C1 NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Genet & Biochem, NIH, Bethesda, MD 20892 USA. RP Jakoby, WB (reprint author), NIDDKD, Biochem & Metab Lab, NIH, Bldg 8,Room 311, Bethesda, MD 20892 USA. NR 35 TC 31 Z9 33 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 1 PY 2000 VL 382 IS 1 BP 95 EP 104 DI 10.1006/abbi.2000.2020 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 360VE UT WOS:000089687400013 PM 11051102 ER PT J AU Spanaki, MV Kopylev, L DeCarli, C Gaillard, WD Liow, K Fazilat, S Fazilat, S Reeves, P Sato, S Kufta, C Theodore, WH AF Spanaki, MV Kopylev, L DeCarli, C Gaillard, WD Liow, K Fazilat, S Fazilat, S Reeves, P Sato, S Kufta, C Theodore, WH TI Postoperative changes in cerebral metabolism in temporal lobe epilepsy SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; COMPLEX PARTIAL SEIZURES; GLUCOSE-METABOLISM; BLOOD-FLOW; PET; VALPROATE; CORTEX; HYPOMETABOLISM; DEPRESSION; EFFERENTS AB Background: Fludeoxyglucose F 18 positron emission tomography (F-18-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. Design: Interictal preoperative and postoperative F-18-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. Setting: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. Patients: Twenty-two patients with refractory TLE. Results: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. Conclusion: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. C1 NINDS, Clin Epilepsy Sect, ERB, NIH, Bethesda, MD 20892 USA. NINDS, Biometry & Field Studies Branch, NIH, Bethesda, MD 20892 USA. NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, ERB, NIH, Bldg 10,Room 5N-250,10 Ctr Dr,Mailstop MSC 1408, Bethesda, MD 20892 USA. RI DeCarli, Charles/B-5541-2009 NR 45 TC 56 Z9 57 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2000 VL 57 IS 10 BP 1447 EP 1452 DI 10.1001/archneur.57.10.1447 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 363EB UT WOS:000089821200006 PM 11030796 ER PT J AU Leppala, JM Virtamo, J Fogelholm, R Albanes, D Taylor, PR Heinonen, OP AF Leppala, JM Virtamo, J Fogelholm, R Albanes, D Taylor, PR Heinonen, OP TI Vitamin E and beta carotene supplementation in high risk for stroke - A subgroup analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID ATHEROSCLEROTIC PLAQUE; PLATELET-FUNCTION; LASER AB Context: High serum or dietary levels of vitamin E and beta carotene appear to he associated with lower risk of stroke, but studies regarding their supplementation have not supported their use in stroke prevention. Objective: To determine if vitamin E (dl-alpha tocopherol) and beta carotene supplementations could be used in prevention of stroke in men at high risk for hemorrhagic or ischemic events. Design: Population-based, randomized, double-blind, placebo-controlled, 2 x 2 factorial design trial (the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study), conducted from April 1985 through April 30, 1993, with median follow-up of 6 years. Interventions: Alpha tocopherol, 50 mg; beta carotene, 20 mg; both; or placebo. Participants: From the total male population aged 50 through 69 years in southwestern Finland (n=290406), 29133 male smokers were randomized to 1 of 4 treatment regimens. We excluded 614 men because of previous stroke at baseline, leaving 28519. Main Outcome Measures: Incident and fatal subarachnoid and intracerebral hemorrhage, cerebral infarction, and unspecified stroke. Results: Stroke occurred in a total of 1057 men: 85 had subarachnoid and 112 had intracerebral hemorrhage, 807 had cerebral infarction, and 53 had unspecified stroke. Within 90 days from onset, 160 men died of stroke. Vitamin E supplementation increased the risk of subarachnoid hemorrhage (relative risk [RR], 2.45; 95% confidence interval [Cl], 1.08-5.55) and decreased risk of cerebral infarction (RR, 0.70; 95% CI, 0.55-0.89) in hypertensive men but had no effect among normotensive men. Furthermore, it decreased the risk of cerebral infarction. without elevating the risk of subarachnoid hemorrhage, among hypertensive men with concurrent diabetes (RR, 0.33; 95% CI, 0.14-0.78). Beta carotene supplementation appeared to increase the risk of intracerebral hemorrhage and modestly decrease that of cerebral infarction among men with greater alcohol consumption. Conclusion: Vitamin E supplementation may prevent ischemic stroke in high-risk hypertensive patients, but further studies are needed. C1 Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland. Univ Helsinki, Cent Hosp, Dept Clin Neurosci, Helsinki, Finland. Natl Publ Hlth Inst, Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Leppala, JM (reprint author), Univ Helsinki, Dept Publ Hlth, POB 41, Helsinki 00014, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 18 TC 30 Z9 32 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2000 VL 57 IS 10 BP 1503 EP 1509 DI 10.1001/archneur.57.10.1503 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 363EB UT WOS:000089821200014 PM 11030804 ER PT J AU Kalmijn, S Foley, D White, L Burchfiel, CM Curb, JD Petrovitch, H Ross, GW Havlik, RJ Launer, LJ AF Kalmijn, S Foley, D White, L Burchfiel, CM Curb, JD Petrovitch, H Ross, GW Havlik, RJ Launer, LJ TI Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men - The Honolulu-Asia Aging Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE Alzheimer's disease; dementia; elderly; epidemiology; insulin resistance syndrome ID CORONARY HEART-DISEASE; INSULIN-RESISTANCE SYNDROME; APOLIPOPROTEIN-E GENOTYPE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; CEREBROSPINAL-FLUID; GLUCOSE-TOLERANCE; ARTERY DISEASE; SCREENING-TEST; STROKE AB Cardiovascular risk factors often cluster into a metabolic syndrome that may increase the risk of dementia. The objective of the present study was to assess the long-term association between clustered metabolic cardiovascular risk factors measured at middle age and the risk of dementia in old age. This prospective cohort study of cardiovascular disease was started in 1965 and was extended to a study of dementia in 1991. The subjects were Japanese-American men with an average age of 52.7+/-4.7 (mean+/-SD) years at baseline. Dementia was diagnosed in 215 men, according to international criteria, and was based on a clinical examination, neuropsychological testing, and an informant interview. The z scores were calculated for 7 risk factors (random postload glucose, diastolic and systolic blood pressures, body mass index, subscapular skinfold thickness, random triglycerides, and total cholesterol). The relative risk (RR [95% CI]) of dementia (subtypes) per 1 SD increase in the sum of the z scores was assessed after adjustment for age, education, occupation, alcohol consumption, cigarette smoking, and years of childhood lived in Japan. The z-score sum was higher in demented subjects than in nondemented subjects, indicating a higher risk factor burden (0.74 versus -0.06, respectively; P=0.008). Per SD increase in the z-score sum, the risk of dementia was increased by 5% (RR 1.05, 95% CI 1.02 to 1.09), The z-score sum was specifically associated with vascular dementia (RR 1.11, 95% CI 1.05 to 1.18) but not with Alzheimer's disease (RR 1.00, 95% CI 0.94 to 1.05). Clustering of metabolic cardiovascular risk factors increases the risk of dementia (mainly, dementia of vascular origin). C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Natl Inst Publ Hlth & Environm, Dept Chrom Dis Epidemiol, NL-3720 BA Bilthoven, Netherlands. Univ Hawaii, John A Burns Sch Med, Div Clin Epidemiol, Manoa, HI USA. NHLBI, Epidemiol & Biometry Program, Jackson, MS USA. Dept Vet Affairs, Honolulu, HI USA. RP Launer, LJ (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, Room 3C,309 Gateway Bldg,7201 Wisonsin Ave, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 43 TC 236 Z9 240 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2000 VL 20 IS 10 BP 2255 EP 2260 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 368GY UT WOS:000090110400016 PM 11031212 ER PT J AU Xu, ASL Ohba, Y Vida, L Labotka, RJ London, RE AF Xu, ASL Ohba, Y Vida, L Labotka, RJ London, RE TI Aspirin acetylation of beta Lys-82 of human hemoglobin - NMR study of acetylated hemoglobin Tsurumai SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE aspirin; hemoglobin; Hb Tsurumai; sickle cell disease; NMR ID 2,3-DIPHOSPHOGLYCERATE BINDING-SITE; SICKLE-CELL HEMOGLOBIN; ACETYLSALICYLIC-ACID; DISEASE; DEOXYHEMOGLOBIN; ERYTHROCYTES; TRANSPORT; PHOSPHATE; MEMBRANE AB Acetylation of hemoglobin by aspirin and other compounds has been of interest for the development of agents useful for the treatment of sickle cell disease. In the present study, we have used 2D NMR methods in combination with [1-C-13-acetyl]salicylic acid to probe the acetylation sites of hemoglobin A and hemoglobin Tsurumai, a mutant human hemoglobin characterized by a beta Lys-82-Gln substitution. In contrast to earlier studies by Klotz and coworkers (e.g. Shamsuddin M, Mason RG, Ritchey JM, Honig GR and Klotz KM, Proc Natl Acad Sci USA 71: 4693-4697, 1974) in which it was concluded that beta Lys-144 is the principal target residue acetylated by aspirin, the present study confirms our previous but less conclusive demonstration (Xu ASL, Macdonald JM, Labotka RJ and London RE, Biochim Biophys Acta 1432: 333-349, 1999) that beta Lys-82 is the primary acetylation site of aspirin and related agents. The present studies also provide conclusive evidence that acetylation of beta Lys-82 produces multiple resonances, probably as a consequence of additional acetylation of other sites, particularly beta Lys-82' on the second beta chain. The present results also resolve the apparent discrepancy between the targets of modification by aspirin and double-headed aspirin analogs, and provide an explanation for the changes in oxygen affinity and aggregation threshold of aspirin-modified hemoglobin previously observed under in vitro conditions. In light of the present identification of the principal site of acetylation, the potential therapeutic benefit of aspirin in the treatment of sickle cell disease is discussed. BIOCHEM PHARMACOL 60;7:917-922, 2000. (C) 2000 Elsevier Science Inc. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Yamaguchi Univ, Sch Med, Dept Clin Lab Sci, Ube, Yamaguchi 7558508, Japan. Univ Illinois, Dept Pediat, Chicago, IL 60612 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, MD MR-01,Box 12233, Res Triangle Pk, NC 27709 USA. FU NHLBI NIH HHS [5R01 HL57604] NR 32 TC 11 Z9 11 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 OCT 1 PY 2000 VL 60 IS 7 BP 917 EP 922 DI 10.1016/S0006-2952(00)00419-6 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 352DN UT WOS:000089199400005 PM 10974199 ER PT J AU Roman, BL Weinstein, BM AF Roman, BL Weinstein, BM TI Building the vertebrate vasculature: research is going swimmingly SO BIOESSAYS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; ZEBRAFISH GENE CLOCHE; HEMATOPOIETIC LINEAGES; CARDIOVASCULAR DEVELOPMENT; DANIO-RERIO; EMBRYONIC ANGIOGENESIS; VESSEL FORMATION; XENOPUS-LAEVIS; BLOOD-VESSELS AB The vertebrate vasculature develops in remarkably similar fashion in all vertebrates. A cohort of unspecified mesodermal cells differentiates into primitive endothelial cells, which migrate to and occupy positions within the stereotypical blueprint of the primitive vasculature, Once in position, these cells coalesce and form cords, which lumenize and become ensheathed by supporting pericytes and smooth muscle cells. This primitive vascular network is extensively remodeled in some places, and expanded by sprouting in others. Various studies using the mouse, quail/chick, and frog have uncovered a number of signals that guide these complex processes but many gaps still exist in our understanding of the mechanisms by which the embryonic vasculature is built. Because many questions will require in vivo studies to be properly addressed, the zebrafish, with its unique accessibility to analysis by combined embryological, molecular, and genetic methods, should prove invaluable in identifying new molecules involved in blood vessel development and integrating pathways that influence embryonic blood vessel formation. Published 2000 John Wiley & Sons, Inc. C1 NICHHD, Mol Genet Lab, Unit Vertebrate Organogenesis, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHHD, Mol Genet Lab, Unit Vertebrate Organogenesis, NIH, Bldg 6B,Room 309, Bethesda, MD 20892 USA. OI Roman, Beth/0000-0002-1250-1705 FU NICHD NIH HHS [ZO1 HD 01011-03] NR 90 TC 39 Z9 39 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD OCT PY 2000 VL 22 IS 10 BP 882 EP 893 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 358MN UT WOS:000089562000003 PM 10984714 ER PT J AU Casey, BJ Giedd, JN Thomas, KM AF Casey, BJ Giedd, JN Thomas, KM TI Structural and functional brain development and its relation to cognitive development SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE brain development; neuroimaging; prefrontal functioning; magnetic resonance imaging ID HUMAN CEREBRAL-CORTEX; WORKING-MEMORY TASK; WHITE-MATTER VOLUMES; MAGNETIC-RESONANCE; PREFRONTAL CORTEX; RHESUS-MONKEY; VISUAL-CORTEX; TEMPORAL-LOBE; GRAY-MATTER; AGES 4-18 AB Despite significant gains in the fields of pediatric neuroimaging and developmental neurobiology, surprisingly little is known about the developing human brain or the neural bases of cognitive development. This paper addresses MRI studies of structural and functional changes in the developing human brain and their relation to changes in cognitive processes over the first few decades of human life. Based on post-mortem and pediatric neuroimaging studies published to date, the prefrontal cortex appears to be one of the last brain regions to mature. Given the prolonged physiological development and organization of the prefrontal cortex during childhood, tasks believed to involve this region are ideal for investigating the neural bases of cognitive development. A number of normative pediatric fMRI studies examining prefrontal cortical activity in children during memory and attention tasks are reported. These studies, while largely limited to the domain of prefrontal functioning and its development, lend support for continued development of attention and memory both behaviorally and physiologically throughout childhood and adolescence. Specifically, the magnitude of activity observed in these studies was greater and more diffuse in children relative to adults. These findings are consistent with the view that increasing cognitive capacity during childhood may coincide with a gradual loss rather than formation of new synapses and presumably a strengthening of remaining synaptic connections. It is clear that innovative methods like fMRI together with MRI-based morphometry and nonhuman primate studies will transform our current understanding of human brain development and its relation to behavioral development. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Cornell Univ, Weill Med Coll, Sackler Inst Dev Psychobiol, Dept Psychiat, New York, NY 10021 USA. NIMH, Child Psychiat Branch, New York, NY 10021 USA. RP Casey, BJ (reprint author), Cornell Univ, Weill Med Coll, Sackler Inst Dev Psychobiol, Dept Psychiat, 525 E 68th St,Box 171, New York, NY 10021 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 FU NIMH NIH HHS [1K01MH01297-01A2] NR 66 TC 686 Z9 702 U1 10 U2 128 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD OCT PY 2000 VL 54 IS 1-3 BP 241 EP 257 DI 10.1016/S0301-0511(00)00058-2 PG 17 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 367RU UT WOS:000090075900009 PM 11035225 ER PT J AU Tsuruta, JK Eddy, EM O'Brien, DA AF Tsuruta, JK Eddy, EM O'Brien, DA TI Insulin-like growth factor-II/cation-independent mannose 6-phosphate receptor mediates paracrine interactions during spermatogonial development SO BIOLOGY OF REPRODUCTION LA English DT Article DE gametogenesis; gene regulation; growth factors; IGF receptor; polypeptide receptors; Sertoli cells; signal transduction; spermatogenesis; testes ID FACTOR-II RECEPTOR; TUBULAR BASOLATERAL MEMBRANES; MAJOR EXCRETED PROTEIN; FOLLICLE-STIMULATING-HORMONE; RAT SERTOLI CELLS; LATENT TGF-BETA; CATHEPSIN-L; NEUROTROPHIC FACTOR; IN-VIVO; INOSITOL TRISPHOSPHATE AB The insulin-like growth factor-II/cation-independent mannose 6-phosphate (IGF-II/M6P) receptor transduces signals after binding IGF-II or M6P-bearing growth factors. We hypothesized that this receptor relays paracrine signals between Sertoli cells and spermatogonia in the basal compartment of the seminiferous epithelium. For these studies spermatogonia were isolated from 8-day-old mice with purity >95% and viability >85% after overnight culture. The IGF-II/M6P receptors were present on the surface of spermatogonia, as detected by indirect immunofluorescence. We determined that both IGF-II and M6P-glycoproteins in Sertoli cell conditioned medium (SCM) modulate gene expression in isolated spermatogonia. The IGF-II produced dose-dependent increases in both rRNA and c-fas mRNA. These effects were mediated specifically by IGF-II/M6P receptors, as shown by studies using IGF-II analogues that are specific agonists for either IGF-I or IGF-II receptors. The SCM treatment also induced dose-dependent increases in rRNA levels, and M6P competition showed that this response required interaction with IGF-II/M6P receptors. The M6P-glycoproteins isolated from SCM by IGF-II/M6P receptor affinity chromatography increased spermatogonial rRNA levels at much lower concentrations than required by SCM treatment, providing further evidence for the paracrine activity of Sertoli M6P-glycoproteins. These results demonstrate that Sertoli cells secrete paracrine factors that modulate spermatogonial gene expression after interacting with cell-surface IGF-II/M6P receptors. C1 Univ N Carolina, Dept Pediat, Labs Reprod Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Tsuruta, JK (reprint author), Univ N Carolina, Dept Pediat, Labs Reprod Biol, CB 7500,377 Med Sci Res Bldg, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA16086]; NICHD NIH HHS [U54 HD35041, R01 HD026485, HD26485] NR 61 TC 18 Z9 19 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD OCT PY 2000 VL 63 IS 4 BP 1006 EP 1013 DI 10.1095/biolreprod63.4.1006 PG 8 WC Reproductive Biology SC Reproductive Biology GA 357GC UT WOS:000089489300008 PM 10993821 ER PT J AU Anantharaman, V Moen, LK AF Anantharaman, V Moen, LK TI Effects of nucleoside analogs on native and site-directed mutants of HTLV type 1 reverse transcriptase SO BIOORGANIC CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL LEUKEMIA; ESCHERICHIA-COLI; DRUG-RESISTANCE; RETROVIRUS HTLV; LYMPHOMA; HIV; COMBINATION; INHIBITION; FOSCARNET AB A bacterial assay was developed for testing HTLV-1 reverse transcriptase sensitivity to common nucleoside analog inhibitors in an Escherichia coli strain characterized by a temperature sensitive PolI/RecA deletion phenotype. This genetic complementation assay exploits the ability of HTLV-1 reverse transcriptase to functionally replace these missing activities at nonpermissive temperatures. The four inhibitors tested, dideoxyinosine, dideoxyadenosine, deoxythymidine, and didehydrodeoxythymidine are well-known inhibitors of HIV reverse transcriptase. All except dideoxyadenosine showed a strong activity against HTLV-1 reverse transcriptase with ICS, in the nanomolar range. Sequence alignments were used to identify amino acid residues in HTLV-I reverse transcriptase, which correspond to those identified as important for drug-resistance in HIV reverse transcriptase. Mutations of some of these HTLV-I residues altered the ICS, for the inhibitors as expected, which suggests that these amino acids have a function in HTLV-1 reverse transcriptase similar to that of their homologs in HIV reverse transcriptase, (C) 2000 Academic Press. C1 Old Dominion Univ, Dept Chem & Biochem, Norfolk, VA 23529 USA. RP Moen, LK (reprint author), NIGMS, Off Sci Review, NIH, Bldg 45 Rm 1AS-13H, Bethesda, MD 20892 USA. OI Anantharaman, Vivek/0000-0001-8395-0009 NR 50 TC 1 Z9 2 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD OCT PY 2000 VL 28 IS 5 BP 293 EP 305 DI 10.1006/bioo.2000.1181 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 392AB UT WOS:000166387500005 ER PT J AU Chen, IJ Neamati, N Nicklaus, MC Orr, A Anderson, L Barchi, JJ Kelley, JA Pommier, Y MacKerell, AD AF Chen, IJ Neamati, N Nicklaus, MC Orr, A Anderson, L Barchi, JJ Kelley, JA Pommier, Y MacKerell, AD TI Identification of HIV-1 integrase inhibitors via three-dimensional database searching using ASV and HIV-1 integrases as targets SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS INTEGRASE; PHOTO-CROSS-LINKING; CATALYTIC DOMAIN; TYPE-1 INTEGRASE; ACTIVE-SITE; DRUG DESIGN; 3-DIMENSIONAL STRUCTURE; REVERSE-TRANSCRIPTASE; FLEXIBLE LIGANDS; 3D DATABASE AB Integration of viral DNA. into the host cell genome is a critical step in the life cycle of HIV. This essential reaction is catalyzed by integrase (IN) through two steps, 3'-processing and DNA strand transfer. Integrase is an attractive target for drug design because there is no known cellular analogue and integration is essential for successful replication of HIV. A computational three-dimensional (3-D) database search was used to identify novel HIV-1 integrase inhibitors. Starting from the previously identified Y3 (4-acetylamino-5-hydroxynaphthalene-2,7-disulfonic acid) binding site on the avian sarcoma virus integrase (ASV IN), a preliminary search of all compounds in the nonproprietary, open part of the National Cancer Institute 3-D database yielded a collection of 3100 compounds. A more rigorous scoring method was used to rescreen the 3100 compounds against both ASV IN and HIV-1 IN. Twenty-two of those compounds were selected for inhibition assays against HIV-1 IN. Thirteen of the 22 showed inhibitory activity against HIV-1 IN at concentrations less than 200 mu M and three of them showed antiviral activities in HIV-1 infected CEM cells with effective concentrations (EC50) ranging from 0.8 to 200 mu M. Analysis of the computer-generated binding modes of the active compounds to HIV-1 IN showed that simultaneous interaction with the Y3 site and the catalytic site is possible. In addition, interactions between the active compounds and the flexible loop involved in the binding of DNA by IN are indicated to occur. The structural details and the unique binding motif between the HIV-1 IN and its inhibitors identified in the present work may contribute to the future development of IN inhibitors. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Bethesda, MD 20892 USA. RP MacKerell, AD (reprint author), Univ So Calif, Sch Pharm, 1985 Zonal Ave,Room PSC 304A, Los Angeles, CA 90089 USA. RI Nicklaus, Marc/N-4183-2014; Barchi Jr., Joseph/N-3784-2014; OI MacKerell, Alex/0000-0001-8287-6804 NR 64 TC 38 Z9 39 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 2000 VL 8 IS 10 BP 2385 EP 2398 DI 10.1016/S0968-0896(00)00180-2 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 359RA UT WOS:000089624800001 PM 11058033 ER PT J AU Pinney, KG Mejia, MP Villalobos, VM Rosenquist, BE Pettit, GR Verdier-Pinard, P Hamel, E AF Pinney, KG Mejia, MP Villalobos, VM Rosenquist, BE Pettit, GR Verdier-Pinard, P Hamel, E TI Synthesis and biological evaluation of aryl azide derivatives of combretastatin A-4 as molecular probes for tubulin SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ANTIMITOTIC NATURAL-PRODUCTS; ANTINEOPLASTIC AGENTS; BETA-TUBULIN; PHOTOAFFINITY LABELS; TUMOR VASCULATURE; COLCHICINE SITE; DOLASTATIN 10; BINDING-SITE; AMINO-ACIDS; MICROTUBULE AB Two new aryl azides, (Z)-1-(3'-azido-4'-methoxyphenyl)-2- (3",4", 5"-trimethoxyphenyl)ethene 9 and (Z)-1-(4'-azido-3'-methoxyphenyl)-2-(3'',4",5"-trimethoxyphenyl)ethene 5, modeled after the potent antitumor, antimitotic agent combretastatin A-4 (CA-4), have been prepared by chemical synthesis as potentially useful photoaffinity labeling reagents for the colchicine site on beta-tubulin. Aryl azide 9, in which the 3'-hydroxyl group of CA-4 is replaced by an azido moiety, demonstrates excellent in vitro cytotoxicity against human cancer cell lines (NCI 60 cell line panel, average GI(50) = 4.07x10(-8) M) and potent inhibition of tubulin polymerization (IC50 = 1.4+/-0.1 mu M). The 4'-azido analogue 5 has lower activity (NCI 60 cell line panel, average GI(50) = 2.28x10(-6) M, and IC50= 5.2 +/-0.2 mu M for inhibition of tubulin polymerization), suggesting the importance of the 4'-methoxy moiety for interaction with the colchicine binding site on tubulin. These CA-4 aryl azide analogues also inhibit binding of colchicine to tubulin, as does the parent CA-4, and therefore these compounds are excellent candidates for photoaffinity labeling studies. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Baylor Univ, Dept Chem & Biochem, Waco, TX 76798 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem, Tempe, AZ 85287 USA. NCI, Screening Technol Branch, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Pinney, KG (reprint author), Baylor Univ, Dept Chem & Biochem, Waco, TX 76798 USA. OI Pinney, Kevin/0000-0003-1262-8631; Verdier-Pinard, Pascal/0000-0002-6149-6578 FU NCI NIH HHS [CA-44344-06-11] NR 52 TC 62 Z9 65 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 2000 VL 8 IS 10 BP 2417 EP 2425 DI 10.1016/S0968-0896(00)00176-0 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 359RA UT WOS:000089624800004 PM 11058036 ER PT J AU Ullrich, T Rice, KC AF Ullrich, T Rice, KC TI A practical synthesis of the serotonin 5-HT2A receptor antagonist MDL 100907, its enantiomer and their 3-phenolic derivatives as precursors for [C-11]labeled PET ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; C-11 MDL-100907; HUMAN-BRAIN; RADIOLIGAND; KETONES; SYSTEM; POTENT; ROUTE AB A practical synthesis of the 3-phenolic precursor of MDL 100907, a selective 5-HT2A receptor antagonist, is described. The route was also applied to the enantiomeric series, thus affording the direct precursors of both 3-[C-11]MDL 100907 and its enantiomer as ligands for positron emission tomography. Similar methodology was developed for the direct synthesis of MDL 100907 and its enantiomer, MDL 100009. The routes utilized classical optical resolution of the N-nor intermediates in at least 98% enantiomeric excess and easily afforded multigram amounts of the chiral precursors of a variety of N- and 3-O-substituted enantiomers. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, NIH, Bldg 8,Room B1,21, Bethesda, MD 20892 USA. NR 22 TC 30 Z9 30 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 2000 VL 8 IS 10 BP 2427 EP 2432 DI 10.1016/S0968-0896(00)00175-9 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 359RA UT WOS:000089624800005 PM 11058037 ER PT J AU Siggia, ED Lippincott-Schwartz, J Bekiranov, S AF Siggia, ED Lippincott-Schwartz, J Bekiranov, S TI Diffusion in inhomogeneous media: Theory and simulations applied to whole cell photobleach recovery SO BIOPHYSICAL JOURNAL LA English DT Article ID GREEN FLUORESCENT PROTEIN; TO-GOLGI TRANSPORT; LIVING CELLS; ENDOPLASMIC-RETICULUM; SCANNING MICROPHOTOLYSIS; LATERAL DIFFUSION; MEMBRANE; VISUALIZATION; ER; MICROTUBULES AB A continuum description for diffusion in a simple model for an inhomogeneous but isotropic media is derived and implemented numerically. The locally averaged density of diffusible marker is input from experiment to define the sample. Then a single additional parameter, the effective diffusion constant, permits the quantitative simulation of diffusive relaxation from any initial condition. Using this simulation, it is possible to model the recovery of a fluorescently tagged protein in the endoplasmic reticulum (ER) after photobleaching a substantial region of a live cell, and fit an effective diffusion constant which is a property both of the geometry of the ER and the marker. Such quantitative measurements permit inferences about the topology and internal organization of this organelle. C1 Rockefeller Univ, Ctr Studies Phys & Biol, New York, NY 10021 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rockefeller Univ, Ctr Studies Phys & Biol, 1230 York Ave, New York, NY 10021 USA. EM siggia@eds1.rockefeller.edu FU NIGMS NIH HHS [GM59018-01] NR 28 TC 93 Z9 95 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2000 VL 79 IS 4 BP 1761 EP 1770 PG 10 WC Biophysics SC Biophysics GA 360VL UT WOS:000089688000009 PM 11023884 ER PT J AU Dong, XX Ehrenstein, D Iwasa, KH AF Dong, XX Ehrenstein, D Iwasa, KH TI Fluctuation of motor charge in the lateral membrane of the cochlear outer hair cell SO BIOPHYSICAL JOURNAL LA English DT Article ID CAPACITANCE; MOTILITY; AMPLIFIER AB Functioning of the membrane motor of the outer hair cell is tightly associated with transfer of charge across the membrane. To obtain further insights into the motor mechanism, we examined kinetics of charge transfer across the membrane in two different modes. One is to monitor charge transfer induced by changes in the membrane potential as an excess membrane capacitance. The other is to measure spontaneous flip-flops of charges across the membrane under voltage-clamp conditions as current noise. The noise spectrum of current was inverse Lorentzian, and the capacitance was Lorentzian, as theoretically expected. The characteristic frequency of the capacitance was similar to 10 kHz, and that for current noise was similar to 30 kHz. The difference in the characteristic frequencies seems to reflect the difference in the modes of mechanical movement associated with the two physical quantities. C1 Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Bldg 9,Room 1E120,9 Ctr Dr,MSC 0922, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 18 TC 11 Z9 11 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2000 VL 79 IS 4 BP 1876 EP 1882 PG 7 WC Biophysics SC Biophysics GA 360VL UT WOS:000089688000018 PM 11023893 ER PT J AU Bolger, G Liuzzi, M Krogsrud, R Scouten, E McCollum, R Welchner, E Kempner, E AF Bolger, G Liuzzi, M Krogsrud, R Scouten, E McCollum, R Welchner, E Kempner, E TI Radiation inactivation of ribonucleotide reductase, an enzyme with a stable free radical SO BIOPHYSICAL JOURNAL LA English DT Article ID SIMPLEX VIRUS TYPE-1; ESCHERICHIA-COLI; LARGE SUBUNIT; ADENOVIRUS VECTOR; TARGET ANALYSIS; PROTEIN; PURIFICATION; EXPRESSION; CELLS; PHENYLALANINE AB Herpes simplex virus ribonucleotide reductase (RR) is a tetrameric enzyme composed of two homodimers of large R1 and small R2 subunits with a tyrosyl free radical located on the small subunit. irradiation of the holoenzyme yielded simple exponential decay curves and an estimated functional target size of 315 kDa. Western blot analysis of irradiated holoenzyme R1 and R2 yielded target sizes of 281 kDa and 57 kDa (approximately twice their expected size). Irradiation of free R1 and analysis by all methods yielded a single exponential decay with target sizes ranging from 128-153 kDa. For free R2, quantitation by enzyme activity and Western blot analyses yielded simple inactivation curves but considerably different target sizes of 223 kDa and 19 kDa, respectively; competition for radioligand binding in irradiated R2 subunits yielded two species, one with a target size of similar to 210 kDa and the other of similar to 20 kDa. These results are consistent with a model in which there is radiation energy transfer between the two monomers of both Fl and R2 only in the holoenzyme, a radiation-induced loss of free radical only in the isolated R2, and an alteration of the tertiary structure of R2. C1 NIH, Phys Biol Lab, Bethesda, MD 20892 USA. Boehringer Ingelheim Canada Ltd, Dept Biol Sci, Biomega Res Div, Laval, PQ H7S 2G5, Canada. RP Kempner, E (reprint author), NIH, Phys Biol Lab, Bldg 6,Room 140, Bethesda, MD 20892 USA. NR 36 TC 4 Z9 4 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2000 VL 79 IS 4 BP 2155 EP 2161 PG 7 WC Biophysics SC Biophysics GA 360VL UT WOS:000089688000044 PM 11023919 ER PT J AU Koch-Paiz, CA Momenan, R Amundson, SA Lamoreaux, E Fornace, AJ AF Koch-Paiz, CA Momenan, R Amundson, SA Lamoreaux, E Fornace, AJ TI Estimation of relative mRNA content by filter hybridization to a polyuridylic probe SO BIOTECHNIQUES LA English DT Article ID RNA C1 NCI, NIH, Gene Response Sect, DBS, Rockville, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. RP Koch-Paiz, CA (reprint author), NCI, NIH, Gene Response Sect, DBS, Bldg 37,Room 5C09,9000, Rockville, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 5 TC 8 Z9 8 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 2000 VL 29 IS 4 BP 706 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363XP UT WOS:000089863200007 PM 11056796 ER PT J AU Agarwal, A Guindo, A Cissoko, Y Taylor, JG Coulibaly, D Kone, A Kayentao, K Djimde, A Plowe, CV Doumbo, O Wellems, TE Diallo, D AF Agarwal, A Guindo, A Cissoko, Y Taylor, JG Coulibaly, D Kone, A Kayentao, K Djimde, A Plowe, CV Doumbo, O Wellems, TE Diallo, D TI Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S SO BLOOD LA English DT Article ID SICKLE-CELL TRAIT; PLASMODIUM-FALCIPARUM MALARIA; ABNORMAL-HEMOGLOBINS; IMMUNE-RESPONSES; SUDAN SAVANNA; P-FALCIPARUM; 2 AREAS; ANTIGENS; CHILDREN; MECHANISM AB The malaria hypothesis proposes a survival advantage for individuals with hemoglobin variants in areas of endemic Plasmodium falciparum malaria. Hemoglobin C (HbC) is a possible example in West Africa, where this hemoglobin has a centric distribution with high frequencies among certain populations including the Dogon ethnic group. To test whether HbC is associated with protection from malaria, we performed a case-control study in the Dogon of Bandiagara, Mali, HbC was present in 68 of 391 (17.4%) of uncomplicated malaria control cases, whereas it was detected in only 3 of 67 cases (4.5%) of severe malaria (odds ratio [OR], 0.22; P = .01). Further, HbC was present in only 1 of 34 cases (2.9%) with cerebral manifestations, the most common presentation of severe malaria in this population (OR, 0.14; P = .03). Episodes of uncomplicated malaria and parasitemias (4800-205 050/mu L) were identified in cases of homozygous HbC (HbCC), which indicates that P falciparum parasites are able to efficiently replicate within HbCC erythrocytes in vivo. These findings suggest that HbC does not protect against infection or uncomplicated malaria but can protect against severe malaria in the Dogon population of Bandiagara, Mali. The data also suggest that the protective effect associated with HbC may be greater than that of HbS in this population. (Blood, 2000;96:2358-2363) (C) 2000 by The American Society of Hematology. C1 NIAID, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Fac Med Pharm & Odontostomatol, Dept Epidemiol & Parasit Dis, Hematol Lab, Bamako, Mali. Fac Med Pharm & Odontostomatol, Dept Epidemiol & Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali. Univ Maryland, Sch Med, Div Geog Med, Baltimore, MD 21201 USA. RP Wellems, TE (reprint author), NIAID, NIH, Bldg 4,Rm 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. OI Taylor, James/0000-0002-4421-1809 NR 45 TC 116 Z9 127 U1 2 U2 14 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 OCT 1 PY 2000 VL 96 IS 7 BP 2358 EP 2363 PG 6 WC Hematology SC Hematology GA 358HL UT WOS:000089552500007 PM 11001883 ER PT J AU Wayne, AS Schoenike, SE Pegelow, CH AF Wayne, AS Schoenike, SE Pegelow, CH TI Financial analysis of chronic transfusion for stroke prevention in sickle cell disease SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; CEREBROVASCULAR ACCIDENTS; RECURRENT STROKE; ANEMIA; CHILDREN; THERAPY; RISK; HYDROXYUREA; TRIAL AB Chronic red blood cell transfusion can prevent many of the manifestations of sickle cell disease. The medical costs of chronic transfusion and management of associated side effects, especially iron overload, are considerable. This study was undertaken to evaluate the financial impact of chronic transfusion for stroke prevention in patients with sickle cell anemia. Outpatient charges pertaining to hospital-based Medicare uniform bill (UB-92) codes, professional fees, and iron chelation were evaluated. Data were collected on 21 patients for a total of 296 patient months (mean, 14; median, 14 months/patient). Charges ranged from $9828 to $50 852 per patient per year. UB-92, chelation, and physician-related charges accounted for 53%, 42%, and 5% of total charges, respectively. Of UB-92 charges, 58% were associated with laboratory fees and 160/u were related to the processing and administration of blood, Charges for patients who required chelation therapy ranged from $31 143 to $50 852 per patient per year (mean, $39 779; median, $38 607). Deferoxamine accounted for 71% of chelation-related charges, which ranged from $12 719 to $24 845 per patient per year (mean, $20 514; median, $21 381), The financial impact of chronic transfusion therapy for sickle cell disease is substantial with charges approaching $400 000 per patient decade for patients who require deferoxamine chelation, These data should be considered in reference to cost and efficacy analyses of alternative therapies for sickle cell disease, such as allogeneic bone marrow transplantation. (Blood, 2000;96:2369-2372) (C) 2000 by The American Society of Hematology. C1 Univ Miami, Sch Med, Jackson Mem Med Ctr,Dept Pediat, Div Pediat Hematol Oncol,Sickle Cell Ctr, Miami, FL USA. Univ Miami, Sch Med, Jackson Mem Med Ctr, Pediat Pharm Dept, Miami, FL USA. RP Wayne, AS (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. NR 29 TC 37 Z9 38 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 OCT 1 PY 2000 VL 96 IS 7 BP 2369 EP 2372 PG 4 WC Hematology SC Hematology GA 358HL UT WOS:000089552500009 PM 11001885 ER PT J AU Foster, CB Lehmbecher, T Samuels, S Stein, S Mol, F Metcalf, JA Wyvill, K Steinberg, SM Kovacs, J Blauvelt, A Yarchoan, R Chanock, SJ AF Foster, CB Lehmbecher, T Samuels, S Stein, S Mol, F Metcalf, JA Wyvill, K Steinberg, SM Kovacs, J Blauvelt, A Yarchoan, R Chanock, SJ TI An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus SO BLOOD LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; GROWTH-FACTOR; GENETIC RESTRICTION; HIV-1 INFECTION; ALPHA PROMOTER; AIDS; CELLS; CYTOKINES; CHEMOKINE; DISEASE AB Kaposi sarcoma (KS) is an angioproliferative inflammatory condition that occurs commonly in patients infected with human immunodeficiency virus (HIV). Inflammatory cytokines and growth factors promote the development of KS. Because physiologically important cytokine polymorphisms modulate host inflammatory responses, we investigated the association between KS and common regulatory polymorphisms in 5 proinflammatory cytokine genes encoding interleukin (IL) IL-1 alpha, IL-1 beta, tumor necrosis factor (TNF) alpha, TNF-beta, and IL-6 and in the IL-1 receptor antagonist (IL1RN). We also examined the contribution of stromal-derived factor 1 and chemokine receptor 5 (Delta 32) polymorphisms to KS development. The population consisted of 115 HIV-infected men with KS and 126 deceased HIV-infected men without KS. The only strong association was observed between an IL6 promoter polymorphism (G-174C) and susceptibility to KS in HIV-infected men (P =.0035), Homozygotes for IL6 allele G, associated with increased IL6 production, were overrepresented among patients with KS (P =.0046), whereas allele C homozygotes were underrepresented (P =.0062). Substantial in vitro evidence indicates that IL-6 contributes to the pathogenesis of KS. Our results show that IL6 promoter genotypes associated with altered gene expression are risk factors for development of KS. Identification of a genetic risk factor for development of KS has important clinical implications for prevention and therapy. (Blood. 2000;96: 2562-2567) (C) 2000 by The American Society of Hematology. C1 NCI, Ctr Adv Technol, Pediat Oncol Branch, Immunocompromised Host Sect, Gaithersburg, MD 20877 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD USA. NCI, AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Ctr Adv Technol, Pediat Oncol Branch, Immunocompromised Host Sect, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. NR 38 TC 95 Z9 100 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 OCT 1 PY 2000 VL 96 IS 7 BP 2562 EP 2567 PG 6 WC Hematology SC Hematology GA 358HL UT WOS:000089552500036 PM 11001912 ER PT J AU Gubin, AN Njoroge, JM Wojda, U Pack, SD Rios, M Reid, ME Miller, JL AF Gubin, AN Njoroge, JM Wojda, U Pack, SD Rios, M Reid, ME Miller, JL TI Identification of the Dombrock blood group glycoprotein as a polymorphic member of the ADP-ribosyltransferase gene family SO BLOOD LA English DT Article ID RED-CELL ANTIGENS; GROUP SYSTEM; ANTI-DO(B); RECEPTOR; PROTEINS; MALARIA; DISEASE; GY(A); HY AB Identification of the 25 known human blood group molecules Is of fundamental importance for the fields of erythroid cell biology and transfusion medicine. Here we provide the first molecular description of the "Dombrock" blood group system. A candidate gene was identified by in silico analyses of approximately 5000 expressed sequence tags (ESTs) from terminally differentiating human erythroid cells. Transfection experiments demonstrated specific binding of anti-Dombrock and confirmed glycosylphosphatidylinositol membrane attachment. Dombrock expression is developmentally regulated during erythroid differentiation and occurs at highest levels in the fetal liver Homology studies suggest that the Dombrock molecule is a member of the adenosine 5'-diphosphate (ADP)-ribosyltransferase ectoenzyme gene family. Genotypic comparisons suggest Do(a) versus Do(b) antigenicity results from a single amino acid substitution within an encoded arginine-glycine-aspartic acid (RGD) motif of the molecule. (Blood. 2000;96: 2621-2627) (C) 2000 by The American Society of Hematology. C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. New York Blood Ctr, Dept Immunochemistry, New York, NY 10021 USA. RP Miller, JL (reprint author), NIDDKD, Biol Chem Lab, NIH, Bldg 10,Rm 9B17, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014; Wojda, Urszula/M-6079-2015 OI Wojda, Urszula/0000-0002-4525-2004 NR 33 TC 58 Z9 62 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2000 VL 96 IS 7 BP 2621 EP 2627 PG 7 WC Hematology SC Hematology GA 358HL UT WOS:000089552500044 PM 11001920 ER PT J AU Bodine, DM Seidel, NE Gallagher, PG Sabatino, DE AF Bodine, DM Seidel, NE Gallagher, PG Sabatino, DE TI Long-term expression of human gamma-globin mRNA at therapeutic levels in mouse erythrocytes from retrovirus vectors containing the gamma-globin gene linked to an ankyrin promoter. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 7 BP 492 EP 492 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500017 ER PT J AU Felsenfeld, G Bell, A Litt, M Pikaart, M Prioleau, MN Recillas-Targa, F Saitoh, N West, A AF Felsenfeld, G Bell, A Litt, M Pikaart, M Prioleau, MN Recillas-Targa, F Saitoh, N West, A TI Establishment and maintenance of chromatin boundaries. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Prioleau, Marie-Noelle/G-9824-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 18 BP 495 EP 495 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500028 ER PT J AU Bulger, M Bender, M Farrell, C Felsenfeld, G Wertman, B Groudine, M Hardison, R AF Bulger, M Bender, M Farrell, C Felsenfeld, G Wertman, B Groudine, M Hardison, R TI Open chromatin domain of mammalian beta-globin genes. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Penn State Univ, University Pk, PA 16802 USA. NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 23 BP 497 EP 497 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500033 ER PT J AU Trainor, C AF Trainor, C TI GATA zinc fingers modulate transactivation. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 53 BP 505 EP 506 PG 2 WC Hematology SC Hematology GA 381WR UT WOS:000165787500062 ER PT J AU Cline, AP Frazer, T Rowland, L Seidel, NE Anderson, SM Garrett, LJ Bodine, DM AF Cline, AP Frazer, T Rowland, L Seidel, NE Anderson, SM Garrett, LJ Bodine, DM TI The mRNA encoding HMG-4, a chromatin binding protein, is expressed in hematopoietic stem cells (HSC) and erythroid progenitor cells. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 66 BP 509 EP 509 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500075 ER PT J AU Burgess-Beusse, B Recillas-Targa, F Felsenfeld, G AF Burgess-Beusse, B Recillas-Targa, F Felsenfeld, G TI Functional analysis of the chicken beta-globin insulator. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Natl Autonomous Univ Mexico, Inst Cellular Physiol, Dept Mol Genet, Mexico City 04510, DF, Mexico. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 70 BP 510 EP 510 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500079 ER PT J AU Ghirlando, R Trainor, CD AF Ghirlando, R Trainor, CD TI GATA-1 bends DNA in a site-independent fashion. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ghirlando, Rodolfo/A-8880-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 88 BP 516 EP 516 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500097 ER PT J AU Gui, CY Dean, A AF Gui, CY Dean, A TI Acetylation of a specific promoter nucleosome accompanies activation of the epsilon-globin gene by beta-globin LCR HS2. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 90 BP 516 EP 516 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500099 ER PT J AU Jackson, DA Dean, A AF Jackson, DA Dean, A TI Dominant interference with beta-globin transcription by beta-globin locus control region HS2. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 94 BP 518 EP 518 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500103 ER PT J AU Miller, JL Gubin, AN Lee, T AF Miller, JL Gubin, AN Lee, T TI Identification of transcription related factors during early and late adult erythroid cell differentiation. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 110 BP 522 EP 522 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500119 ER PT J AU Noguchi, CT Ogilvie, M Yu, X Pudilo, SM Ruegg, U AF Noguchi, CT Ogilvie, M Yu, X Pudilo, SM Ruegg, U TI Erythropoietin stimulates proliferation and blocks differentiation of promyoblasts. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Univ Lausanne, Sch Pharm, Lausanne, Switzerland. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 113 BP 523 EP 523 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500122 ER PT J AU Sabatino, DE Seidel, NE Gallagher, PG Bodine, DM AF Sabatino, DE Seidel, NE Gallagher, PG Bodine, DM TI Long-term expression of human gamma-globin mRNA at therapeutic levels in mouse erythrocytes from retrovirus vectors containing the gamma-globin gene linked to an ankyrin promoter. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 129 BP 527 EP 527 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500138 ER PT J AU Sabatino, DE Gallagher, PG Garrett, LJ Cline, AP Bodine, DM AF Sabatino, DE Gallagher, PG Garrett, LJ Cline, AP Bodine, DM TI Erythroid-specific, copy number-dependent, and position- and enhancer-dependent expression of an ankyrin promoter linked to a human gamma-globin gene in transgenic mice. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 128 BP 527 EP 527 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500137 ER PT J AU Yu, XB Chin, K Noguchi, CT AF Yu, XB Chin, K Noguchi, CT TI Regulation of the erythropoietin receptor by SCL/Tal-1. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 145 BP 532 EP 532 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500154 ER PT J AU Yu, XB Lin, CS Costantini, F Noguchi, CT AF Yu, XB Lin, CS Costantini, F Noguchi, CT TI Rescue of the erythropoietin receptor null mouse by the human erythropoietin receptor gene. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Columbia Univ, Dept Genet & Dev, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 26 IS 5 MA 146 BP 532 EP 532 PG 1 WC Hematology SC Hematology GA 381WR UT WOS:000165787500155 ER PT J AU Ludlow, CL AF Ludlow, CL TI Stuttering: dysfunction in a complex and dynamic system. SO BRAIN LA English DT Editorial Material ID AUDITORY-CORTEX; SPEECH C1 NINDS, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NINDS, Laryngeal & Speech Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 10 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2000 VL 123 BP 1983 EP 1984 DI 10.1093/brain/123.10.1983 PN 10 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 364RU UT WOS:000089907400001 PM 11004116 ER PT J AU Amemiya, K Granger, RP Dalakas, MC AF Amemiya, K Granger, RP Dalakas, MC TI Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time - Studies in repeated muscle biopsies SO BRAIN LA English DT Article DE T-cell receptor; inclusion body myositis; autoimmunity ID MONOCLONAL-ANTIBODY ANALYSIS; BASIC-PROTEIN PEPTIDE; V-GENE USAGE; INFLAMMATORY MYOPATHIES; RHEUMATOID-ARTHRITIS; ADHESION MOLECULES; DUCHENNE DYSTROPHY; MULTIPLE-SCLEROSIS; MONONUCLEAR-CELLS; POLYMYOSITIS AB Inclusion body myositis (IBM) is an inflammatory myopathy characterized immunohistologically by prominent invasion of the non-necrotic, MHC-I class antigen-expressing muscle fibres by CD8+ cytotoxic T cells. If the autoinvasive CD8+ T cells are recruited specifically to the muscle and play a primary pathogenetic role in the disease, a clonal restriction persisting over time should be anticipated. In this study, we analysed the T-cell receptor (TCR) gene usage by endomysial T lymphocytes in three sequential muscle biopsies from three different IBM patients over a 19-22 month period using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis of the complementarity determining region (CDR3) of the amplified TCRs. We found that CD8+ T lymphocytes persist in the endomysial infiltrates in all biopsies during a 19-22 month period. The most frequently detected TCRs were the V beta 3, V beta 5.1, V beta 6.7 and V beta 13 gene families, and several of the autoinvasive CB8+ T cells expressed the TCRs V beta 6.7 and V beta 5.1. A restricted usage of the examined V beta 6 gene family was found to persist in the complementarity CDR3 determining region of the autoinvasive T cells over the 22 month period. Identical V beta 6 CDR3 gene arrangements were also found in the multiple muscle biopsies from two of the three IBM patients. The results indicate that in IBM there is a restricted expression of the TCR gene families among the autoinvasive T lymphocytes with homologies in the CDR3 region that persist over the course of the disease. a continuous, antigen-driven T-cell response is prominent in the muscle of patients with IBM. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 33 TC 63 Z9 65 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2000 VL 123 BP 2030 EP 2039 DI 10.1093/brain/123.10.2030 PN 10 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 364RU UT WOS:000089907400005 PM 11004120 ER PT J AU Torpy, DJ Stratakis, CA Chrousos, GP AF Torpy, DJ Stratakis, CA Chrousos, GP TI Familial hyperaldosteronism SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 1st International Meeting on Adrenal Disease: Basic and Clinical Aspects CY AUG 31-SEP 02, 1999 CL RIBEIRAO PRET, BRAZIL SP Brazilian Physiol Soc DE aldosterone; hyperaldosteronism; genetics; adrenal tumour; hypertension ID GLUCOCORTICOID-REMEDIABLE ALDOSTERONISM; PLASMA-RENIN ACTIVITY; ANGIOTENSIN-II; SUPPRESSIBLE HYPERALDOSTERONISM; CAPTOPRIL TEST; CYP11B2 GENE; DIAGNOSIS; HYPERTENSION; ADENOMA; BIOSYNTHESIS AB Aldosterone, the major circulating mineralocorticoid, participates in blood volume and serum potassium homeostasis, Primary aldosteronism is a disorder characterised by hypertension and hypokalaemia due to autonomous aldosterone secretion from the adrenocortical zona glomerulosa. Improved screening techniques, particularly application of the plasma aldosterone:plasma renin activity ratio, have led to a suggestion that primary aldosteronism may be more common than previously appreciated among adults with hypertension. Glucocorticoid-remediable aldosteronism (GRA) was the first described familial form of hyperaldosteronism. The disorder is characterised by aldosterone secretory function regulated chronically by ACTH. Hence, aldosterone hypersecretion can be suppressed, on a sustained basis, by exogenous glucocorticoids such as dexamethasone in physiologic range doses. This autosomal dominant disorder has been shown to be caused by a hybrid gene mutation formed by a crossover of genetic material between the ACTH-responsive regulatory portion of the 11 beta -hydroxylase (CYP11B1) gene and the coding region of the aldosterone synthase (CYP11B2) gene. Familial hyperaldosteronism type II (FH-II), so named to distinguish the disorder from GRA or familial hyperaldosteronism type I(FH-I), is characterised by autosomal dominant inheritance of autonomous aldosterone hypersecretion which is not suppressible by dexamethasone. Linkage analysis in a single large kindred, and direct mutation screening, has shown that this disorder is unrelated to mutations in the genes for aldosterone synthase or the angiotensin II receptor. The precise genetic cause of FH-U remains to be elucidated. C1 Univ Queensland, Greenslopes Hosp, Dept Med, Brisbane, Qld 4120, Australia. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. NICHD, Pediat & Reprod Branch, NIH, Bethesda, MD USA. RP Torpy, DJ (reprint author), Univ Queensland, Greenslopes Hosp, Dept Med, Newdegate St, Brisbane, Qld 4120, Australia. NR 55 TC 3 Z9 4 U1 0 U2 0 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 OCT PY 2000 VL 33 IS 10 BP 1149 EP 1155 PG 7 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 365NF UT WOS:000089956800005 PM 11004715 ER PT J AU Eisenhofer, G Walther, M Keiser, HR Lenders, JWM Friberg, P Pacak, K AF Eisenhofer, G Walther, M Keiser, HR Lenders, JWM Friberg, P Pacak, K TI Plasma metanephrines: a novel and cost-effective test for pheochromocytoma SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 1st International Meeting on Adrenal Disease: Basic and Clinical Aspects CY AUG 31-SEP 02, 1999 CL RIBEIRAO PRET, BRAZIL SP Brazilian Physiol Soc DE pheochromocytoma; hypertension; sympathetic nervous system; adrenal gland; metanephrines; catecholamines ID CATECHOL-O-METHYLTRANSFERASE; HIPPEL-LINDAU-DISEASE; ENDOCRINE NEOPLASIA TYPE-2; EXTRANEURONAL UPTAKE; MONOAMINE-OXIDASE; NOREPINEPHRINE; METABOLISM; DIHYDROXYPHENYLGLYCOL; NORADRENALINE; DIAGNOSIS AB Pheochromocytomas are rare chromaffin cell tumors that nevertheless must be excluded in large numbers of patients who develop sustained or episodic hypertension as well as in many others with suggestive symptoms or with a familial history of pheochromocytoma. Diagnosis of pheochromocytoma depends importantly on biochemical evidence of excess catecholamine production by a tumor. Imperfect sensitivity and specificity of commonly available biochemical tests and the low incidence of the tumor among the tested population mean that considerable time and effort can be expended in confirming or ruling out pheochromocytoma in patients where the tumor is suspected. Measurements of plasma free metanephrines provide a superior test compared to other available tests for diagnosis of pheochromocytoma. In particular, the high sensitivity of plasma free metanephrines means that a normal test result reliably excludes all but the smallest of pheochromocytomas so that no other tests are necessary. Measurements of plasma free metanephrines, when systematically combined with other diagnostic procedures outlined in this review, provide a more efficient, reliable and cost-effective approach for diagnosis of pheochromocytoma than offend by previously available approaches. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. Univ Nijmegen St Radboud Hosp, Dept Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. Univ Gothenburg, Dept Clin Physiol, Gothenburg, Sweden. RP Eisenhofer, G (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. RI Lenders, J.W.M./L-4487-2015 NR 37 TC 30 Z9 31 U1 0 U2 0 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 OCT PY 2000 VL 33 IS 10 BP 1157 EP 1169 PG 13 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 365NF UT WOS:000089956800006 PM 11004716 ER PT J AU Barrett, J Childs, R AF Barrett, J Childs, R TI Non-myeloablative stem cell transplants SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE non-myeloablative; allogeneic stem cell transplantation; haematological malignancies; renal cell cancer ID MIXED HEMATOPOIETIC CHIMERISM; BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; IDENTICAL LITTERMATE DOGS; CHRONIC MYELOID-LEUKEMIA; TOTAL-BODY IRRADIATION; HOST DISEASE; PHARMACOLOGICAL IMMUNOSUPPRESSION; MOLECULAR REMISSION C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 48 TC 73 Z9 75 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2000 VL 111 IS 1 BP 6 EP 17 DI 10.1046/j.1365-2141.2000.02405.x PG 12 WC Hematology SC Hematology GA 377KA UT WOS:000165511700003 PM 11091178 ER PT J AU Dvir, I Chayoth, R Sod-Moriah, U Shany, S Nyska, A Stark, AH Madar, Z Arad, SM AF Dvir, I Chayoth, R Sod-Moriah, U Shany, S Nyska, A Stark, AH Madar, Z Arad, SM TI Soluble polysaccharide and biomass of red microalga Porphyridium sp alter intestinal morphology and reduce serum cholesterol in rats SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE dietary fibre; red microalga; cholesterol; image analysis ID ACID EPA PRODUCTION; DIETARY FIBER; FOOD-PRODUCTS; LIPIDS; ENZYME; LIVER; FORMS AB The present study investigated the effects of the red microalga Porphyridium sp. on gastrointestinal physiology and lipid metabolism in male Sprague-Dawley rats. Diets containing dietary fibre from pelleted red microalgal cells (biomass) or their sulfated polysaccharide, pectin or cellulose (control) were fed to rats for a period of 30 d. All three fibre-supplemented diets increased the length of both the small intestine and colon, with a significantly greater effect in rats fed the algal polysaccharide. The polysaccharide also increased mucosa and muscularis cross-sectional area of the jejunum, and caused hypertrophy in the muscularis layer. The algal biomass significantly lowered gastrointestinal transit time by 44 % in comparison with the control rats. Serum and mucosal cholecystokinin levels were lower in rats on the pectin and polysaccharide diets, while cholecystokinin levels in rats fed algal biomass were not different from those in the control animals. In comparison with the control diet, all the experimental diets significantly lowered serum cholesterol levels (22-29 %). Feeding of non-fermentable algal polysaccharide or biomass significantly increased faecal weight and bile acid excretion compared with pectin-fed or control rats. The algal polysaccharide and biomass were thus shown to be potent hypocholesterolaemic agents active at low concentrations in the diet. Both metabolic and morphological changes were observed following consumption of algae, suggesting several possible mechanisms by which the alga affects lipid metabolism. The results presented in the present study encourage the use of red microalga as a functional food. C1 Hebrew Univ Jerusalem, Fac Agr Food & Environm Qual Sci, Inst Biochem Food Sci & Nutr, IL-76100 Rehovot, Israel. Ben Gurion Univ Negev, Inst Appl Biosci, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Clin Biochem Unit, IL-84105 Beer Sheva, Israel. Soroka Univ, Hosp Kupat Holim, Toor Inst, IL-84105 Beer Sheva, Israel. NIEHS, Res Triangle Pk, NC 27709 USA. RP Madar, Z (reprint author), Hebrew Univ Jerusalem, Fac Agr Food & Environm Qual Sci, Inst Biochem Food Sci & Nutr, POB 12, IL-76100 Rehovot, Israel. EM madar@agri.huji.ac.il NR 44 TC 48 Z9 57 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD OCT PY 2000 VL 84 IS 4 BP 469 EP 476 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 366QL UT WOS:000090016000009 PM 11103217 ER PT J AU Wood, FB Lyon, B Schell, MB Kitendaugh, P Cid, VH Siegel, ER AF Wood, FB Lyon, B Schell, MB Kitendaugh, P Cid, VH Siegel, ER TI Public library consumer health information pilot project: results of a National Library of Medicine evaluation SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID INTERNET; MEDLINE AB In October 1998, the National Library of Medicine (NLM) launched a pilot project to learn about the role of public libraries in providing health information to the public and to generate information that would assist NLM and the National Network of Libraries of Medicine (NN/LM) in learning how best to work with public libraries in the future. Three regional medical libraries (RMLs), eight resource libraries, and forty-one public libraries or library systems from nine states and the District of Columbia were selected for participation. The pilot project included an evaluation component that was carried out in parallel with project implementation. The evaluation ran through September 1999. The results of the evaluation indicated that participating public librarians were enthusiastic about the training and information materials provided as part of the project and that many public libraries used the materials and conducted their own outreach to local communities and groups. Most libraries applied the modest funds to purchase additional Internet-accessible computers and/or upgrade their health-reference materials. However, few of the participating public libraries had health information centers (although health information was perceived as a top-ten or top-five topic of interest to patrons). Also, the project generated only minimal usage of NLM's consumer health database, known as MEDLINEplus, from the premises of the monitored libraries (patron usage from home or office locations was not tracked). The evaluation results suggested a balanced follow-up by NLM and the NN/LM, with a few carefully selected national activities, complemented by a package of targeted activities that, as of January 2000, are being planned, developed, or implemented. The results also highlighted the importance of building an evaluation component into projects like this one from the outset, to assure that objectives were met and that evaluative information was available on a timely basis, as was the case here. C1 Natl Lib Med, Off Hlth Informat Programs Dev, Bethesda, MD 20894 USA. Natl Lib Med, Div Lib Operat, Bethesda, MD 20894 USA. Natl Lib Med, Off Comp & Commun Syst, Bethesda, MD 20894 USA. RP Wood, FB (reprint author), Natl Lib Med, Off Hlth Informat Programs Dev, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 11 TC 33 Z9 34 U1 1 U2 5 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 2000 VL 88 IS 4 BP 314 EP 322 PG 9 WC Information Science & Library Science SC Information Science & Library Science GA 530JT UT WOS:000174355100003 PM 11055298 ER PT J AU Vriesendorp, HM Quadri, SM AF Vriesendorp, HM Quadri, SM TI Radiolabeled immunoglobulin therapy in patients with Hodgkin's disease SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE radiolabeled immunoglobulin therapy; Hodgkin's disease; yttrium-90; indium-111; ferritin ID B-CELL LYMPHOMA; ANTIBODY THERAPY; ANTIFERRITIN; Y-90; CHEMOTHERAPY; RADIOIMMUNOTHERAPY; RTOG AB Translational research supports the use of radiolabeled antiferritin for recurrent Hodgkin's disease. A 60% tumor response rate is obtained after treatment of out-patients with polyclonal radiolabeled antiferritin, Hodgkin's disease masses shrink after radiolabeled antiferritin treatment due to the radiation delivered by the radioimmunoconjugate. Unlabeled antiferritin does not cause tumor shrinkage. Hodgkin's disease provides unique opportunities for the development and optimization of radiolabeled immunoglobulin therapy for other malignancies as well. Radiolabeled Immunoglobulin Therapy is a useful addition to the cancer treatment armamentarium due to its high therapeutic ratio: high tumor response rates with side effects limited to hematopoetic tissues. C1 Marshfield Clin, Marshfield, WI USA. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Vriesendorp, HM (reprint author), 1000 N Oak Ave, Marshfield, WI 54449 USA. NR 44 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD OCT PY 2000 VL 15 IS 5 BP 431 EP 445 DI 10.1089/cbr.2000.15.431 PG 15 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 376AP UT WOS:000165435900002 PM 11155816 ER PT J AU Behrens, C Travis, LB Wistuba, II Davis, S Maitra, A Clarke, EA Lynch, CF Glimelius, B Wiklund, T Tarone, R Gazdar, AF AF Behrens, C Travis, LB Wistuba, II Davis, S Maitra, A Clarke, EA Lynch, CF Glimelius, B Wiklund, T Tarone, R Gazdar, AF TI Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MICROSATELLITE MUTATOR PHENOTYPE; P53 MUTATIONS; GENOMIC INSTABILITY; MISMATCH REPAIR; MALIGNANT NEOPLASMS; IONIZING-RADIATION; COLORECTAL-CANCER; URANIUM MINERS; CHROMOSOME 3P; RISK AB The risk of lung and breast cancer is significantly increased after therapy for Hodgkin's disease (HD), but there are few data that describe the molecular profiles of these tumors. We investigated the genetic abnormalities in second primary lung (n = 19) and breast cancers (n = 19) that follow therapy for HD ("post-HD cancers") and compared these with changes observed in corresponding tumor types (57 lung and 20 breast cancers) arising in the general population ("sporadic cancers"). DNA obtained from archival tissues was examined using PCR-based analyses for loss of heterozygosity and microsatellite alterations (MAs) at several chromosomal regions, TP53 and K-uas gene mutations, and frameshift mutations at minisatellite sequences at the coding regions of several genes (TGF-beta RII, IGFIIR, BAX, hMSH6, and hMSH3). The occurrence of loss of heterozygosity at all chromosomal regions taken together and frequencies at most individual areas were similar for the post-HD and sporadic cancers for both lung and breast sites, The overall frequency of MAs in the post-HD tumors was substantially greater (lung, 2.4-fold, P = 0.004; breast, 4.2-fold, P = 0.16) than that in the respective sporadic cancers. No differences in the pattern of TP53 and K-ras mutations were detected between post-HD and sporadic cancers. No mutations were detected at the minisatellite sequences examined. MAs, which reflect widespread genomic instability, occur at greatly increased frequency in post-HD lung and breast cancers. Although the mechanisms underlying the development of increased MAs are unknown, they have been associated with immunosuppression and radiation exposure. Future research should address the role that MAs, as well as other influences, may play in the development of neoplasias that occur after therapy for HD. C1 Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Pontificia Univ Catolica Chile, Dept Pathol, Santiago, Chile. Canc Care Ontario, Toronto, ON, Canada. Univ Iowa, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. Univ Uppsala Hosp, S-75175 Uppsala, Sweden. Univ Helsinki, Cent Hosp, Helsinki, Finland. RP Gazdar, AF (reprint author), Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. FU NCI NIH HHS [P50-CA70907] NR 56 TC 33 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2000 VL 9 IS 10 BP 1027 EP 1035 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 364TP UT WOS:000089909300004 PM 11045784 ER PT J AU Decensi, A Torrisi, R Bruno, S Costantini, M Curotto, A Nicolo, G Malcangi, B Baglietto, L Bruttini, GP Gatteschi, B Rondanina, G Varaldo, M Perloff, M Malone, WF Bruzzi, P AF Decensi, A Torrisi, R Bruno, S Costantini, M Curotto, A Nicolo, G Malcangi, B Baglietto, L Bruttini, GP Gatteschi, B Rondanina, G Varaldo, M Perloff, M Malone, WF Bruzzi, P TI Randomized trial of fenretinide in superficial bladder cancer using DNA flow cytometry as an intermediate end point SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SYNTHETIC RETINOID FENRETINIDE; BREAST-CANCER; CLINICAL-TRIALS; VITAMIN-A; CHEMOPREVENTION; CYTOLOGY; PHARMACOKINETICS; HYBRIDIZATION; PROLIFERATION; ETRETINATE AB Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer. We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers, A total of 99 subjects with resected superficial bladder cancer (pTa, pT1) were randomized to either fenretinide (200 mg day p.o. for 24 months) or no intervention. Cystoscopy and bladder washing for DNA flow cytometry end points (proportion of DNA aneuploid histograms, hyperdiploid fraction, and percentage of apoptotic cells) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months. The primary study end point was the proportion of DNA aneuploid histograms after 12 months. This figure was 48.9% in the fenretinide arm and 41.9% in the control arm (odds ratio, 1.16; 95% confidence interval, 0.44-3.07), There was no difference in any other response biomarker between the two groups up to 36 months, nor was any biomarker able to predict recurrence risk. Recurrence-free survival was comparable between the arms (27 events in the fenretinide arm versus 21 in the control arm; P = 0.36), Twelve subjects in the fenretinide arm complained of diminished dark adaptability, and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations. We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings. Recurrence-free survival was comparable between groups. Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer. C1 European Inst Oncol, Chemoprevent Unit, I-20141 Milan, Italy. Natl Canc Inst, Div Med Oncol 2, I-16132 Genoa, Italy. Natl Canc Inst, Unit Clin Epidemiol & Trials, I-16132 Genoa, Italy. Natl Canc Inst, Pathol Serv, I-16132 Genoa, Italy. Natl Canc Inst, Biotechnol Unit, I-16132 Genoa, Italy. Univ Dept Expt Med, Anat Unit, I-16132 Genoa, Italy. Adv Biotechnol Ctr, Cytometry Unit, I-16132 Genoa, Italy. European Inst Oncol, Div Epidemiol & Biostat, I-20141 Milan, Italy. San Martino Hosp, Urol Clin, I-16132 Genoa, Italy. Nervi Hosp, Div Urol, I-16167 Genoa, Italy. Gallino Hosp, Div Urol, I-16164 Genoa, Italy. NCI, Chemoprevent Branch, Bethesda, MD 20832 USA. RP Decensi, A (reprint author), European Inst Oncol, Chemoprevent Unit, Via Ripamonti 435, I-20141 Milan, Italy. RI costantini, massimo/G-1443-2012; Bruno, Silvia/B-8980-2013; OI costantini, massimo/0000-0002-5293-7079; Bruzzi, Paolo/0000-0002-7874-2077 FU NCI NIH HHS [5UO1 CA-56457] NR 48 TC 20 Z9 20 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2000 VL 9 IS 10 BP 1071 EP 1078 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 364TP UT WOS:000089909300010 PM 11045790 ER PT J AU Singletary, E Lieberman, R Atkinson, N Sneige, N Sahin, A Tolley, S Colchin, M Bevers, T Stelling, C Fornage, B Fritsche, H Hittelman, W Kelloff, G Lippman, SM AF Singletary, E Lieberman, R Atkinson, N Sneige, N Sahin, A Tolley, S Colchin, M Bevers, T Stelling, C Fornage, B Fritsche, H Hittelman, W Kelloff, G Lippman, SM TI Novel translational model for breast cancer chemoprevention study: Accrual to a presurgical intervention with tamoxifen and N-[4-hydroxyphenyl] retinamide SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CLINICAL-TRIALS; ELIGIBILITY CRITERIA; PREVENTION; INHIBITION AB Surrogate end point biomarkers for risk assessment and efficacy of potential chemopreventive agents are needed to improve the efficiency and reduce the cost of chemoprevention trials, It is imperative to develop the best clinical breast model for translational surrogate end point biomarker studies, especially with respect to accrual feasibility. We have initiated a prospective study to develop biomarkers for tamoxifen and N-[4-hydroxyphenyl] retinamide by administering either a placebo or both drugs for 2-4 weeks to women with ductal carcinoma in situ or early invasive cancers in the interval between the initial diagnostic core biopsy and definitive surgery, The principle end point is pretreatment versus posttreatment tumor levels of Ki-67; a number of other exploratory markers will also be examined. The planned target sample size is 100 patients. Between February 1997 and February 2000, 4514 women who had either an abnormal mammogram or a diagnosed breast cancer were screened for the study. Of these 4514 screened patients, 52 (1%) were registered on the study. Major factors of nonparticipation in the remaining 4462 women were as follows: (a) no evidence of malignancy (2081 patients; 46%); (b) ineligible per protocol criteria (575 patients; 13%); (c) preoperative chemotherapy/tamoxifen (520 patients; 11%); (d) surgery scheduling conflict (360 patients; 8%); (e) outside needle biopsy (221 patients; 5%); (f) no residual disease after excisional biopsy (345 patients; 8%); and (g) second opinion only (123 patients; 3%), Other nonparticipation factors included fine needle aspiration only, refusal, tumor size >2 cm, and estrogen replacement therapy (35 patients each; 2% each). The protocol was amended in midstudy to allow outside needle biopsy, tumor >2 cm, and estrogen replacement therapy, Accrual to biomarker (nontherapeutic) protocols with delay in definitive cancer surgery is challenging but feasible. Although some accrual problems remain, we have nonetheless succeeded in recruiting 50% of our target sample size in a 3-year period. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. NCI, Chemoprevent Branch, Bethesda, MD 20852 USA. RP Singletary, E (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd,Box 106, Houston, TX 77030 USA. FU NCI NIH HHS [N01-CN-25433-04] NR 18 TC 20 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2000 VL 9 IS 10 BP 1087 EP 1090 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 364TP UT WOS:000089909300012 PM 11045792 ER PT J AU Kauraniemi, P Hedenfalk, I Persson, K Duggan, DJ Tanner, M Johannsson, O Olsson, H Trent, JM Isola, J Borg, A AF Kauraniemi, P Hedenfalk, I Persson, K Duggan, DJ Tanner, M Johannsson, O Olsson, H Trent, JM Isola, J Borg, A TI MYB oncogene amplification in hereditary BRCA1 breast cancer SO CANCER RESEARCH LA English DT Article ID GERM-LINE MUTATIONS; C-MYB; EXPRESSION; GENE; CARCINOMA; ARREST AB Comparative genomic hybridization analysis has demonstrated that breast tumors from BRCA1 and BRCA2 germ-line mutation carriers contain a large number of chromosomal copy number gains and losses. A high regional copy number gain at 6q22-q24 was observed in one BRCA1 tumor, and fluorescence in situ hybridization analysis indicated a strong amplification of the MYB oncogene (15 copies of MYB compared with 1 copy of chromosome 6 centromere). Fluorescence in situ hybridization analysis revealed amplification of MYB in 5 (29%) of 17 BRCA1 breast tumors, whereas none of 8 BRCA2 tumors and 13 breast cancer cell lines, and only 2 of 100 sporadic breast tumors exhibited altered MYB copy numbers, Gene amplification resulted in mRNA overexpression as determined by Northern blot and cDNA microarray analysis, and protein overexpression by immunohistochemical staining. We conclude that MYB amplification is infrequent in sporadic breast cancer but common in breast tumors from BRCA1 mutation carriers, suggesting a role of this cell cycle regulator and transcription factor in the progression of some BRCA1 tumors. However, we cannot rule out the significance of other genes in the 6q22-q24 amplicon. C1 Univ Lund Hosp, Dept Oncol, SE-22185 Lund, Sweden. Tampere Univ Hosp, FIN-33101 Tampere, Finland. Tampere Univ, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Borg, A (reprint author), Univ Lund Hosp, Dept Oncol, SE-22185 Lund, Sweden. NR 25 TC 66 Z9 68 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2000 VL 60 IS 19 BP 5323 EP 5328 PG 6 WC Oncology SC Oncology GA 362HG UT WOS:000089772100002 PM 11034064 ER PT J AU Barlund, M Monni, O Kononen, J Cornelison, R Torhorst, J Sauter, G Kallioniemi, OP Kallioniemi, A AF Barlund, M Monni, O Kononen, J Cornelison, R Torhorst, J Sauter, G Kallioniemi, OP Kallioniemi, A TI Multiple genes at 17q23 undergo amplification and overexpression in breast cancer SO CANCER RESEARCH LA English DT Article ID DNA AMPLIFICATION; COPY-NUMBER; FAMILY; LOCALIZATION; MICROARRAYS; PROTEIN; KINASE; MEMBER; BRCA1; CELLS AB Studies by comparative genomic hybridization imply that amplification of the chromosomal region 17q22-q24 is common in breast cancer. Here, amplification and expression levels of six known genes located at 17q23 were examined in breast cancer cell lines. Four of them (RAD51C, S6K, PAT1, and TBX2) were found to be highly amplified and overexpressed. To investigate the involvement of these genes in vivo, fluorescence irt situ hybridization analysis of a tissue microarray containing 372 primary breast cancers was used. S6K, PAT1, and TBX2 were coamplified in about 10% of tumors, whereas RAD51C amplification was seen in only 3% of tumors. Expression analysis in 12 primary tumors showed that RAD51C and S6K were consistently expressed in all cases in which they were amplified and also in some tumors without amplification. These data suggest that 17q23 amplification results in simultaneous up-regulation of several genes, whose increased biological activity may jointly contribute to the more aggressive clinical course observed in patients with 17q23-amplified tumors. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, FIN-33101 Tampere, Finland. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. RP Kallioniemi, A (reprint author), NHGRI, Canc Genet Branch, NIH, 49 Convent Dr,Room 4B24, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Anne/0000-0003-3552-8158 NR 20 TC 144 Z9 153 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2000 VL 60 IS 19 BP 5340 EP 5344 PG 5 WC Oncology SC Oncology GA 362HG UT WOS:000089772100005 PM 11034067 ER PT J AU Davis, BJ McCurdy, EA Miller, BD Lucier, GW Tritscher, AM AF Davis, BJ McCurdy, EA Miller, BD Lucier, GW Tritscher, AM TI Ovarian tumors in rats induced by chronic 2,3,7,8-tetrachlorodibenzo-p dioxin treatment SO CANCER RESEARCH LA English DT Article ID SPRAGUE-DAWLEY RAT; AH-RECEPTOR; CELL-PROLIFERATION; ESTROGEN-RECEPTOR; TCDD; MICE; EXPRESSION; PROMOTION; LIVER; HEPATOCARCINOGENESIS AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multispecies reproductive toxicant, and it has been recently classified by IARC as a known human carcinogen. Here, we report that TCDD promotes the development of ovarian tumors in an initiation-promotion model in female Sprague Dawley rats. Rats were initiated with diethylnitrosamine (DEN) or vehicle at 70 days of age. Starting 2 or 18 weeks after initiation, rats were exposed biweekly to TCDD at a daily average dose of 125 ng/kg/day for 14, 30, or 60 weeks continuously or for 30 weeks plus withdrawal periods of 16 or 30 weeks. Fifteen of 76 (20%) rats initiated with DEN and promoted with TCDD for various lengths of time developed ovarian sex cord-stromal tumors of Sertoli cell type, whereas no ovarian tumors developed in 86 rats used as vehicle controls or that received DEN alone or TCDD alone. The highest tumor incidence occurred in 6 of 14 rats (43%) after 60 weeks of continuous TCDD after DEN initiation. One of six rats developed a tumor by 30 weeks of exposure. Because most effects of TCDD can be attributed to its activation of the aryl hydrocarbon receptor (AhR), the presence and localization of AhR was determined in the rat ovary and in the ovarian tumors by reverse transcription-PCR, immunohistochemistry, and in situ hybridization, AhR was localized to oocytes, granulosa and thecal cells of growing follicles, surface epithelial cells, and epithelial cells lining single tubules in ovaries from adult control Sprague Dawley rats. Neoplastic cells in the ovarian tumors were also positive for both AhR message and protein. These results indicate that the ability of TCDD to cause ovarian tumors is dependent on initiation, Length of promotion, and age of the animal when exposed and evaluated. The tumor type induced by TCDD in this experimental system is the same histological subtype as that reported from an early study of youngsters exposed during an industrial accident in Seveso, Italy. C1 NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne, Switzerland. RP Davis, BJ (reprint author), NIEHS, Lab Womens Hlth, POB 12233,MD B3-06, Res Triangle Pk, NC 27709 USA. NR 34 TC 44 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2000 VL 60 IS 19 BP 5414 EP 5419 PG 6 WC Oncology SC Oncology GA 362HG UT WOS:000089772100020 PM 11034082 ER PT J AU Yu, F Jensen, RT Lubensky, IA Mahlamaki, EH Zheng, YL Herr, AM Ferrin, LJ AF Yu, F Jensen, RT Lubensky, IA Mahlamaki, EH Zheng, YL Herr, AM Ferrin, LJ TI Survey of genetic alterations in gastrinomas SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; ZOLLINGER-ELLISON-SYNDROME; PANCREATIC ENDOCRINE TUMORS; NEUROENDOCRINE TUMORS; ALLELIC DELETIONS; NEOPLASIA TYPE-1; MICROSATELLITE INSTABILITY; SPORADIC GASTRINOMAS; CHROMOSOME 11Q13; CLINICAL COURSE AB Gastrinomas are rare gastrin-secreting endocrine tumors that usually arise in the duodenum or pancreas and, if untreated, can cause severe peptic ulcers or metastatic disease. Although most tumors are sporadic, they are especially common in patients with multiple endocrine neoplasia type 1 (MEN1), and most studies of these tumors have focused on the role of the MEN1 gene, Although the gene is commonly altered in sporadic tumors, this finding is not universal, and it is highly likely that other genetic defects play a significant role. In the present study, an in-depth analysis of the DNA of eight tumors was carried out in an effort to localize these areas. The experiments consisted of an analysis of 400 microsatellite marker loci distributed evenly throughout the human genome, and the results were confirmed with comparative genomic hybridization, Whereas deletions encompassing the MEN1 gene were seen in two tumors, the most striking result was multiple large rearrangements on chromosome 1 in two of the tumors with hepatic metastases, In several instances, an individual tumor had abnormalities of every informative maker on a given chromosome, presumably as a result of aneuploidy affecting that chromosome. Such defects were only seen in the four large or aggressive tumors, and the total number of chromosomes affected in a tumor ranged from 1 to a high of 13 in a patient who had an unusually aggressive tumor. This tumor also showed microsatellite instability, and this is the first report of such a defect in gastrinomas, This study implicates chromosome 1 defects, aneuploidy, and perhaps mismatch repair defects as important features of gastrinomas; deletions involving the MEN1 gene were confirmed, but the rest of the genome was free of large deletions or amplifications. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Tampere, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Canc Genet Lab, FIN-33101 Tampere, Finland. RP Ferrin, LJ (reprint author), Univ Minnesota, Sch Med, Div Gastroenterol & Hepatol, Box 36,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 46 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2000 VL 60 IS 19 BP 5536 EP 5542 PG 7 WC Oncology SC Oncology GA 362HG UT WOS:000089772100037 PM 11034099 ER PT J AU Kelavkar, UP Cohen, C Kamitani, H Eling, TE Badr, KF AF Kelavkar, UP Cohen, C Kamitani, H Eling, TE Badr, KF TI Concordant induction of 15-lipoxygenase-1 and mutant p53 expression in human prostate adenocarcinoma: correlation with Gleason staging SO CARCINOGENESIS LA English DT Article ID CANCER CELL-GROWTH; TRIGGERED 15-EPI-LIPOXIN A(4); CONJUGATED LINOLEIC-ACID; MESSENGER-RNA EXPRESSION; ATHYMIC NUDE-MICE; BREAST-CANCER; ENDOTHELIAL-CELL; FATTY-ACIDS; 12(S)-HYDROXYEICOSATETRAENOIC ACID; 15-HYDROXYEICOSATETRAENOIC ACID AB We recently reported that the mutant form of the tumor-suppressor gene p53 up-regulates 15-LO-1 gene expression in a murine cell line, Here, we examine the expression of 15-lipoxygenase (LO)-1 and mutant p53 (mtp53) in human prostatic tissues and 15-LO-1 in the human prostate adenocarcinoma cell line PC-3, Reverse transcription-PCR and western analyses conclusively demonstrated expression of 15-LO-1 in PC-3 cells, Western blotting for 15-LO-1 in freshly resected 'normal' and prostate adenocarcinoma specimens showed 15-LO-1 expression in normal tissue, but significantly higher levels were detected in prostate adenocarcinomas, Prostate adenocarcinoma tissues generated chirally pure 13-S-hydroxyoctadecadienoic acid from exogenous linoleic acid, a preferred substrate of 15-LO-1. To study the correlation of 15-LO-1 expression with mtp53 in prostate cancer, we immunostained 48 prostatectomy specimens obtained by transurethral resection of the prostate and needle biopsy (median age 68 years, range 52-93) of different Gleason grades (n = 48), using antibodies specific for 15-LO-1, mtp53 and MIB-1 (a proliferation marker), We compared staining in cancerous foci with adjacent normal appearing prostate tissues, In only 5 of 48 patients did 'normal' tissue adjacent to cancerous foci display staining for 15-LO-1, However, no staining for mtp53 was observed in any of the normal tissues, In cancer foci, robust staining was observed for both 15-LO-1 (36 of 48, 75%) and mtp53 (19 of 48, 39%), Furthermore, the intensities of expression of 15-LO-1 and mtp53 correlated positively with each other (P < 0.001) and with the degree of malignancy, as assessed hy Gleason grading (P < 0.01). By immunohistochemistry, 15-LO-1 was located in secretory cells of peripheral zone glands, prostatic ducts and seminal vesicles, but not in the basal cell layer or stroma, Based on these and other studies, we propose a model describing a possible role for 15-LO-1 expression in influencing the malignant potential and pathobiological behavior of adenocarcinomas. C1 Emory Univ, Sch Med, Div Renal, Ctr Glomerulonephritis, Atlanta, GA 30322 USA. VAMC, Atlanta, GA 30322 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Kelavkar, UP (reprint author), Emory Univ, Sch Med, Div Renal, Ctr Glomerulonephritis, 3304 WMB,1639 Pierce Dr, Atlanta, GA 30322 USA. FU NIDDK NIH HHS [2RO1DK43883] NR 66 TC 78 Z9 81 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2000 VL 21 IS 10 BP 1777 EP 1787 PG 11 WC Oncology SC Oncology GA 365KZ UT WOS:000089951600002 PM 11023533 ER PT J AU Khan, SG Metter, EJ Tarone, RE Bohr, VA Grossman, L Hedayati, M Bale, SJ Emmert, S Kraemer, KH AF Khan, SG Metter, EJ Tarone, RE Bohr, VA Grossman, L Hedayati, M Bale, SJ Emmert, S Kraemer, KH TI A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism SO CARCINOGENESIS LA English DT Article ID DNA-REPAIR GENE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NUCLEOTIDE EXCISION-REPAIR; BASAL-CELL CARCINOMA; TRANSCRIPTION GENE; MOLECULAR DEFECTS; POLYMERASE-BETA; L1 ELEMENT; A PATIENTS; MUTATIONS AB We found a common biallelic polymorphism (PAT) in the xeroderma pigmentosum complementation group C (XPC) DNA repair gene consisting of an insertion of 83 bases of A and T [poly(AT)] and a 5 base deletion within intron 9, We developed a PCR assay to resolve the XPC PAT+ and PAT- alleles and found that the PAT+ allele frequency was 0.44 in 156 cancer-free donors from the Johns Hopkins School of Public Health, 0.41 in 263 cancer-free donors from the Baltimore Longitudinal Study of Aging and 0.36 in samples from 216 unselected donors from NIH, We also found a single nucleotide polymorphism in exon 15 of the XPC gene (A2920C, Lys939-->Gln) that creates a new enzyme restriction site. This XPC exon 15 single nucleotide polymorphism occurred at a frequency of 0.38 in 98 NIH donors and is in linkage disequilibrium with the PAT locus. We developed an allele-specific complementation assay utilizing post-UV host cell reactivation to assess DNA repair capacity of polymorphic alleles, We found similar DNA repair with XPC 2920A and XPC 2920C, These common polymorphisms in the XPC DNA repair gene may be useful for molecular epidemiological studies of cancer susceptibility. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. NCI, NIH, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. NIAMSD, NIH, Baltimore, MD USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. RP Kraemer, KH (reprint author), NCI, Basic Res Lab, NIH, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC004517-31]; PHS HHS [NIH 22846] NR 55 TC 103 Z9 116 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2000 VL 21 IS 10 BP 1821 EP 1825 DI 10.1093/carcin/21.10.1821 PG 5 WC Oncology SC Oncology GA 365KZ UT WOS:000089951600008 PM 11023539 ER PT J AU King, KL Jewell, CM Bortner, CD Cidlowski, JA AF King, KL Jewell, CM Bortner, CD Cidlowski, JA TI 28S ribosome degradation in lymphoid cell apoptosis: evidence for caspase and Bcl-2-dependent and -independent pathways SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; glucocorticoids; RNA degradation; ribosomes ID LYMPHOCYTES INVITRO; DNA FRAGMENTATION; RNA; GLUCOCORTICOIDS; BCL-2; DEATH; ACID; ACTIVATION; INHIBITION; CLEAVAGE AB Apoptosis, a physiological form of cell death, is characterized by the activation of a program that kills cells and recycles their constituents. We have used thymoma cell lines to examine the role of Bcl-2 and caspases in ribosomal destruction during apoptosis, Glucocorticoid and calcium ionophore (A23187)-induced apoptosis of S49 Neo cells resulted in both 28S rRNA and DNA degradation. Interestingly, anisomycin, a potent protein synthesis inhibitor, also induced 28S rRNA and DNA fragmentation suggesting that the responsible nucleases are present in the viable cells and become activated during apoptosis, The anti apoptotic protein, Bcl-2, inhibited both glucocorticoid and anisomycin induced DNA and 28S rRNA degradation but could not protect against A23187 induced nucleic acid degradation. We next examined the role of caspase activation in the generation of 28S rRNA degradation through the use of ZVAD, a general caspase inhibitor. Under conditions where ZVAD substantially decreased 28S rRNA degradation induced by glucocorticoid or anisomycin, no decrease was observed when A23187 was used to induce apoptosis, Surprisingly, RNA degradation, like DNA degradation, occurs exclusively in shrunken lymphocytes but not those with normal cell volume despite equivalent exposure of the cells to the apoptotic signals. Together, these findings indicate the ribosome is a specific target for death effecters during apoptosis and that a caspase/Bcl-2-independent pathway exists to activate its destruction. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ Cincinnati, Raymond Walters Coll, Cincinnati, OH 45236 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,MD E2-02, Res Triangle Pk, NC 27709 USA. NR 33 TC 24 Z9 26 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD OCT PY 2000 VL 7 IS 10 BP 994 EP 1001 DI 10.1038/sj.cdd.4400731 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 360FF UT WOS:000089655200017 PM 11279546 ER PT J AU Standley, S Baudry, M AF Standley, S Baudry, M TI The role of glycosylation in ionotropic glutamate receptor ligand binding, function, and trafficking SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE glutamate; receptors; glycosylation; ionotropic; asparagine-linked ID N-LINKED GLYCOSYLATION; NMDA RECEPTOR; QUISQUALATE RECEPTORS; SURFACE EXPRESSION; BACULOVIRUS SYSTEM; INDUCED INHIBITION; AMPA RECEPTORS; HIGH-AFFINITY; SUBUNIT; DESENSITIZATION AB Members of the ionotropic glutamate receptor (iGluR) family have between 4 and 12 consensus asparagine (N)-linked glycosylation sites. They are localized on the extracellular N-termini, and the loop between the penultimate and last transmembrane domains. These regions also contain the essential elements for formation of the ligand binding site. N-linked glycosylation does not appear to be essential for formation of the ligand binding site per se, but there are demonstrated interactions between glycosylation state and ligand binding affinity, receptor physiology, susceptibility to allosteric modulation and, in some cases, trafficking. There is no indication of a general role for N-linked glycosylation in iGluRs; instead the effects of glycosylation vary among glutamate receptor subtypes and splice variants, with specific effects on structure or function with different subunits. C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Univ So Calif, Neurosci Program, Los Angeles, CA 90089 USA. RP Standley, S (reprint author), NIDCD, Neurochem Lab, NIH, Bldg 36,Rm 5D08, Bethesda, MD 20892 USA. NR 55 TC 28 Z9 30 U1 1 U2 6 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 OCT PY 2000 VL 57 IS 11 BP 1508 EP 1516 DI 10.1007/PL00000635 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 371LE UT WOS:000165179800004 PM 11092445 ER PT J AU Nitkin, RM AF Nitkin, RM TI Dendritic mechanisms in brain function and developmental disabilities SO CEREBRAL CORTEX LA English DT Editorial Material C1 NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. RP Nitkin, RM (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2000 VL 10 IS 10 BP 925 EP 926 DI 10.1093/cercor/10.10.925 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 358HB UT WOS:000089551600001 PM 11007542 ER PT J AU Michejda, CJ Dedon, PC Marnett, LJ AF Michejda, CJ Dedon, PC Marnett, LJ TI Highlights from a symposium on the mechanisms of action of cytotoxic agents SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Editorial Material C1 NCI, SBL, Mol Aspects Drug Design Sect, Bethesda, MD 20892 USA. MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. RP Michejda, CJ (reprint author), NCI, SBL, Mol Aspects Drug Design Sect, Bethesda, MD 20892 USA. OI Dedon, Peter/0000-0003-0011-3067 NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2000 VL 13 IS 10 BP 933 EP 935 DI 10.1021/tx000496y PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 366MK UT WOS:000090009000001 ER PT J AU Glover, RE Germolec, DR Patterson, R Walker, NJ Lucier, GW Mason, RP AF Glover, RE Germolec, DR Patterson, R Walker, NJ Lucier, GW Mason, RP TI Endotoxin (lipopolysaccharide)-induced nitric oxide production in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated Fischer rats: Detection of nitrosyl hemoproteins by EPR spectroscopy SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID NECROSIS-FACTOR INVOLVEMENT; TREATED RATS; TCDD; SUPPRESSION; HEPATOCYTES; HEMOGLOBIN; EXPRESSION; CYTOKINES AB Electron paramagnetic resonance (EPR) spectroscopy was used to study the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on endotoxin (lipopolysaccharide)-induced nitric oxide (NO) production in Fischer rats. We found that rats treated with 50 mug/kg TCDD had increased sensitivity to endotoxin, resulting in an approximately 2-fold increase in the level of NO production detected as nitrosylhemoglobin (HbNO) in venous blood. At lower concentrations (less than or equal to5 mug/kg), TCDD did not affect the endotoxin-induced NO production. The TNF-alpha serum concentration was found to parallel that of NO. TCDD alone did not induce the production of detectable HbNO or TNF-alpha. We found that TCDD induced a dose-dependent increase in the EPR signal intensity of (Fe3+) low-spin methemoprotein complexes found in the liver and kidney. These species with EPR resonance at g = 2.43, 2.26, and 1.92 are attributed to low-spin Fe3+ in cytochromes P450 and P420. Our data confirm previous studies that have shown that TCDD induces a dose-dependent increase in the production of some cytochrome P450 enzymes. However, in rats that were subsequently challenged with endotoxin, a smaller increase in the EPR intensity of these species was observed. The decrease in the low-spin Fe3+ cytochrome P450 EPR signal in endotoxin-challenged rats could be due to one or more of the following occurring: (1) cytochrome destruction, (2) reduction of the ferric to the ESR-silent ferrous oxidation state of cytochromes by nitric oxide, and/or (3) formation of ferrous nitrosyl cytochrome complexes that contribute, in part, to the characteristic five-coordinate nitrosyl hemoprotein triplet also observed in these tissues. Since low concentrations of endotoxin can leak from the gut lumen into the systemic circulation, this investigation explores the possibility that endotoxin interaction with TCDD may be, in part, responsible for the effects of TCDD observed in these tissues. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, NIH, Res Triangle Pk, NC 27709 USA. RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 14 TC 7 Z9 7 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2000 VL 13 IS 10 BP 1051 EP 1055 DI 10.1021/tx000128u PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 366MK UT WOS:000090009000021 PM 11080054 ER PT J AU Hix, S Kadiiska, MB Mason, RP Augusto, O AF Hix, S Kadiiska, MB Mason, RP Augusto, O TI In vivo metabolism of tert-butyl hydroperoxide to methyl radicals. EPR spin-trapping and DNA methylation studies SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MEDIATED PROTEIN OXIDATION; SINGLE-STRAND BREAKAGE; ELECTROCHEMICAL DETECTION; ORGANIC HYDROPEROXIDES; MISCODING SPECIFICITY; CUMENE HYDROPEROXIDE; CARBON-TETRACHLORIDE; ALKOXYL RADICALS; BENZOYL PEROXIDE; BASE ADDUCTS AB Metabolic activation of peroxides and hydroperoxides to free radicals is associated with the tumor promoting activity of these compounds. tert-Butyl hydroperoxide (t-BOOH) metabolism has been extensively studied as a model of peroxide biotransformation. In vivo studies are limited, and the hemoglobin-thiyl radical was the only species thus far identified in the blood of treated rats. Here we further examine t-BOOH metabolism in vivo with regard to free radical and DNA adduct production. Spin-trapping experiments with phenyl-N-tert-butylnitrone (PBN) led to the detection of EPR signals in the blood, bile, and organic extracts of the liver and stomach of rats treated with t-BOOH. Analysis of these signals demonstrated that t-BOOH metabolism in vivo produces alkyl radicals, detected in the bile and organic extracts of liver and stomach, in addition to the previously identified hemoglobin-thiyl radical. To characterize the produced alkyl radicals, experiments were performed with C-13-labeled t-BOOH and two spin traps, PEN and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). The latter was used because the EPR signals obtained with PEN were too weak to be unambiguous. Nevertheless, the EPR signals present in the bile of animals treated with C-13-labeled t-BOOH and PEN or POBN mere consistent with adducts of C-13-labeled methyl radical and an unidentified alkyl radical. The latter is probably derived from lipids oxidized by the metabolically produced primary radicals, methyl and its precursor, tert-butoxyl. The presence of 8-methylguanine and 7-methylguanine in hydrolysates of DNA from liver and stomach of rats treated with t-BOOH was also examined. g-Methylguanine, a typical product of methyl radical attack on DNA, was detectable in both the Liver and stomach of treated rats. The results may be relevant to the understanding of the genotoxic properties of other peroxides, particularly of cumene hydroperoxide. C1 Univ Sao Paulo, Inst Quim, Dept Biochem, BR-05513970 Sao Paulo, Brazil. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Augusto, O (reprint author), Univ Sao Paulo, Inst Quim, Dept Biochem, CP 26077, BR-05513970 Sao Paulo, Brazil. RI Augusto, Ohara/D-3839-2012 OI Augusto, Ohara/0000-0002-7220-4286 NR 59 TC 63 Z9 63 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2000 VL 13 IS 10 BP 1056 EP 1064 DI 10.1021/tx0001301 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 366MK UT WOS:000090009000022 PM 11080055 ER PT J AU Mathew, J Hunsberger, S Fleg, J Mc Sherry, F Williford, W Yusuf, S AF Mathew, J Hunsberger, S Fleg, J Mc Sherry, F Williford, W Yusuf, S CA Digitalis Investigation Grp TI Incidence, predictive factors, and prognostic significance of supraventricular tachyarrhythmias in congestive heart failure SO CHEST LA English DT Article; Proceedings Paper CT 47th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 07, 1998 CL ATLANTA, GEORGIA SP Amer Coll Cardiol DE atrial fibrillation; congestive heart failure; digoxin; stroke; supraventricular arrhythmia ID LEFT-VENTRICULAR DYSFUNCTION; CHRONIC ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; SYSTOLIC DYSFUNCTION; RISK; MORTALITY; PROGRESSION; THERAPY; TRIALS AB Background: The incidence, predictive factors, morbidity, and mortality associated with the development of supraventricular tachyarrhythmias (SVTs) in patients with congestive heart failure (CHF) are poorly defined, Methods: In the Digitalis Investigation Group trial, patients with CHF who were in sinus rhythm were randomly assigned to digoxin (n = 3,889) or placebo (n = 3,899) and followed up for a mean of 37 months, Baseline factors that predicted the occurrence of SVT and the effects of SVT on total mortality, stroke, and hospitalization for worsening CHF were determined. Results: Eight hundred sixty-six patients (11.1%) had SVT during the study period. Older age (odds ratio [OR], 1.029 for each year increase in age; p = 0.0001), male sex (OR, 1.270; p = 0.0075), increasing duration of CHF (OR, 1.003 for each month increase in duration of CHF; p = 0.0021), and a cardiothoracic ratio of > 0.50 (OR, 1.403; p = 0.0001) predicted an increased risk of experiencing SVT, Left ventricular ejection fraction, New York Heart Association functional class, and treatment with digoxin vs placebo were not related to the occurrence of SVT. After adjustment for other risk factors, development of SVT predicted a greater risk of subsequent total mortality (risk ratio [RR] = 2.451; p = 0.0001), stroke (RR = 2.352; p = 0.0001), and hospitalization for worsening CHF (RR = 3.004; p = 0.0001). Conclusion: In CHF patients in sinus rhythm, older age, male sex, longer duration of CHF, and increased cardiothoracic ratio predict an increased risk for experiencing SVT. Development of SVT is a strong independent predictor of mortality, stroke, and hospitalization for CHF in this population. Prevention of SVT may prolong survival and reduce morbidity in CHF patients. C1 Univ Iowa, Coll Med, Dept Med, Iowa City, IA 52242 USA. Galesburg Cottage Hosp, Dept Cardiol, Galesburg, IL 61401 USA. LaSalle Cardiol, Galesburg, IL USA. NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bayview Med Ctr, Div Cardiol, Baltimore, MD USA. Vet Affairs Med Ctr, Perry Point, MD USA. McMaster Univ, Div Cardiol, Hamilton, ON, Canada. RP Mathew, J (reprint author), Galesburg Cottage Hosp, Dept Cardiol, 695 N Kellogg St, Galesburg, IL 61401 USA. NR 27 TC 83 Z9 86 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2000 VL 118 IS 4 BP 914 EP 922 DI 10.1378/chest.118.4.914 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 366MC UT WOS:000090008300009 PM 11035656 ER PT J AU Cederborg, AC Orbach, Y Sternberg, KJ Lamb, ME AF Cederborg, AC Orbach, Y Sternberg, KJ Lamb, ME TI Investigative interviews of child witnesses in Sweden SO CHILD ABUSE & NEGLECT LA English DT Article DE investigative interviews; sexual abuse; victims; interview practices ID SEXUAL ABUSE; UTTERANCE TYPES; QUESTION AB Objective: To evaluate the structure and informativeness of interviews with 4- to 13-year-old alleged victims of sexual abuse in Sweden. Method: Seventy-two alleged victims of sexual abuse were interviewed by six experienced officers from one police district in Sweden. Our evaluation focused on the structure of the interviews, the distribution and timing of the investigators' utterance types. and the quantity and quality of the information provided by the children. Results: Content analysis revealed that the interviewers relied primarily on option-posing and suggestive questions-together. these comprised 53% of their utterances-when interviewing the alleged victims. As a result, most of the details (57%) obtained from the children were elicited by option-posing and suggestive utterances. Only 6% of the interviewers' utterances were open-ended invitations, and these elicited only 8% of the information obtained. Conclusion: The reliance on option-posing and suggestive prompts may have reduced the accuracy of the information obtained, thereby interfering with the investigations, and reducing the forensic admissibility of the children's statements. This suggests a continuing need in Sweden, as in other countries, for interview practices that enhance the quality of information provided by young victims. (C) 2000 Elsevier Science Ltd. C1 Linkoping Univ, Dept Educ & Psychol, Linkoping, Sweden. NICHHD, Bethesda, MD 20892 USA. RP Cederborg, AC (reprint author), Linkoping Univ, Dept Educ & Psychol, Linkoping, Sweden. NR 36 TC 78 Z9 78 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD OCT PY 2000 VL 24 IS 10 BP 1355 EP 1361 DI 10.1016/S0145-2134(00)00183-6 PG 7 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 353YB UT WOS:000089302100009 PM 11075701 ER PT J AU Liu, Y Zhang, JT AF Liu, Y Zhang, JT TI Recent development in NMDA receptors SO CHINESE MEDICAL JOURNAL LA English DT Article DE NMDA receptor; ion-channel; cation; amino acid ID SUBUNIT MESSENGER-RNAS; H-3 MK-801 BINDING; GLUTAMATE-RECEPTOR; MEDIATED NEUROTOXICITY; IN-VIVO; CHANNEL; PROTEIN; FAMILY; MODULATION; POLYAMINES AB Purpose To identify the structure and the function NMDA receptors, to understand the modulatory mechanism of some endogenous and exogenous and to provide new drugs that compounds on NMDA receptors, theoretical basis for developing modulate NMDA receptors. Data sources A total of 24 originally identified articles were selected. Study selection A total of 24 articles were selected from several hundred original articles or reviews. The content of selected articles are in accordance with our purpose and the authors are authorized scientists in the study on NMDA receptors. Data extraction After careful review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria and our experience in the research of NMDA receptors. Results NMDA receptor contains at least five subunits. They were designated as the NR1 (sigma 1), NR2A (epsilon 1), NR2B (epsilon 2), NR2C (epsilon 3), and NR2D (epsilon 4). A unique feature of NMDA receptor is the requirement for both glutamate and the co-agnist glycine for the efficient gating. NMDA receptor is modulated by a number of endogenous and exogenous compounds. Mg2+ not only blocks the NMDA channel in a voltage-dependent manner but also potentiates NMDA-induced responses at positive membrane potentials. Na+, K+ and Ca2+ not only pass through the NMDA receptor channel but also modulate the activity of NMDA receptors. Zn2+ blocks the NMDA current in a noncompetitive and a voltage-independent manner. It has been demonstrated that polyamines do not directly activate NMDA receptors, but instead act to potentiate or inhibit glutamate-mediated responses. The activity of NMDA receptors is also strikingly sensitive to the changes in Hf concentration, and partially inhibited by the ambient concentration of H+ under physiological conditions. Conclusions NMDA receptors are glutamate- regulated by ion channels that are permeable to Ca2+, Na+, K+ and are sensitive to voltage-dependent Mg2+ block. This channel complex contributes to excitatory synaptic transmission at sites throughout the brain and the spinal cord, and is modulated by a number of endogenous and exogenous compounds. NMDA receptors play a key role in wide range of physiologic and pathologic processes. Five NMDA receptor subunits have now been characterized in both rat and mouse brain. C1 NIMH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China. RP Liu, Y (reprint author), NIMH, 36 Convent Dr,MSC 4033,Bldg 36,Rom 1A31, Bethesda, MD 20892 USA. NR 24 TC 31 Z9 48 U1 1 U2 12 PU CHINESE MEDICAL ASSOCIATION PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD OCT PY 2000 VL 113 IS 10 BP 948 EP 956 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 363NE UT WOS:000089840800019 PM 11775847 ER PT J AU Robinson, TJ Wittekindt, O Pasantes, JJ Modi, WS Schempp, W Morris-Rosendahl, DJ AF Robinson, TJ Wittekindt, O Pasantes, JJ Modi, WS Schempp, W Morris-Rosendahl, DJ TI Stable methylation patterns in interspecific antelope hybrids and the characterization and localization of a satellite fraction in the Alcelaphini and Hippotragini SO CHROMOSOME RESEARCH LA English DT Article DE antelope hybrids; FISH; methylation; satellite DNA ID CHROMOSOMAL EVOLUTION; DNA; BOVIDAE; HYBRIDIZATION; HETEROCHROMATIN; ARTIODACTYLA; KARYOTYPE; SEQUENCE; MAMMALIA; SITES AB Conflicting data has recently appeared concerning altered methylation patterns in interspecific mammalian hybrids and the potential this may hold for driving karyotypic evolution. We report no detectable methylation difference in the genomic DNA of different interspecific F1 antelope hybrids (family Bovidae) and their parent species using the methylation-sensitive enzyme HpaII and its methylation insensitive isoschizomer MspI. However, both enzymes released a tandemly repeated satellite array. Characterization of the repeat using Southern blotting and a combination of sequencing, fluorescence in-situ hybridization (FISH) and C-banding, shows some similarity in the family of repeats between the hybridizing antelope species groups, and that the satellite is localized in the centromeric C-band positive regions of the chromosomes. Moreover, although there is little meaningful sequence homology with the well characterized bovine 1.715 satellite DNA, there is 86% sequence similarity with the sheep/goat satellite I, suggesting that they are related and are likely to have originated and evolved separately from the bovine unit. C1 Univ Stellenbosch, Dept Zool, ZA-7602 Stellenbosch, South Africa. Univ Freiburg, Inst Human Genet & Anthropol, Freiburg, Germany. Univ Vigo, Dept Biochem Genet & Immunol, Vigo, Spain. NCI, SAIC Frederick, FCRDC, Frederick, MD 21701 USA. RP Robinson, TJ (reprint author), Univ Stellenbosch, Dept Zool, Private Bag X1, ZA-7602 Stellenbosch, South Africa. OI Pasantes, Juan J/0000-0001-6515-3946 NR 28 TC 14 Z9 15 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD OCT PY 2000 VL 8 IS 7 BP 635 EP 643 DI 10.1023/A:1009294226213 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 365XP UT WOS:000089976000009 PM 11117360 ER PT J AU Goldstein, DS Tack, C AF Goldstein, DS Tack, C TI Noninvasive detection of sympathetic neurocirculatory failure SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE sympathetic; autonomic; orthostatic hypotension; Valsalva maneuver ID HEART-RATE-VARIABILITY; POWER SPECTRAL-ANALYSIS; BETA-HYDROXYLASE DEFICIENCY; AUTONOMIC NERVOUS-SYSTEM; FINGER BLOOD-PRESSURE; VALSALVA MANEUVER; SYNCOPE; DYSAUTONOMIA; RELIABILITY; SUDOMOTOR AB In sympathetic neurocirculatory failure (SNF), reflexive sympathetically mediated cardiovascular stimulation does not compensate for decreased cardiac filling. This explains orthostatic hypotension in chronic primary autonomic failure (CPAF). During phase 2 of the Valsalva maneuver (phase 2_L), blood pressure increases from its peak During phase 4, blood pressure normally "overshoots" the baseline. Because these changes depend on sympathetically mediated cardiovascular stimulation, a progressive decrease in pressure during phase 2 and absence of the overshoot in phase 4 may indicate SNF. Moreover, because beat-to-beat blood pressure can be measured noninvasively using a photoplethysmographic or tonometric device, evaluating reflexive pressure responses might enable noninvasive diagnosis of SNF. This study assessed the relative frequencies of abnormal phase 2_L. and phase 4 blood pressure in patients with CPAF and orthostatic hypotension and whether noninvasive measurement of beat-to-beat blood pressure can be used to diagnose SNF in patients. Twenty patients with chronic primary autonomic failure and orthostatic hypotension and 50 comparison patients, including several with CPAF but lacking orthostatic hypotension, underwent arterial pressure monitoring during performance of the Valsalva maneuver. Of the 20 patients with CPAF and orthostatic hypotension, all had an abnormal phase 2_L or phase 4 pressure response (sensitivity 100%), whereas only 3 of the 50 comparison patients had an abnormal response in either phase (specificity 94%). Seventeen patients with CPAF and orthostatic hypotension had abnormal responses in both phases (sensitivity 85%), but none of the comparison patients had such findings in both phases (specificity 100%). Of 13 patients in whom beat-to-beat blood pressure was recorded simultaneously invasively and noninvasively, all had abnormal blood pressure responses during phase 2_L and phase 4, whereas none of 29 comparison patients had such symptoms. Detection of abnormal blood pressure responses during phase 2_L or phase 4 of the Valsalva maneuver is a highly sensitive test for SNF. Abnormal pressure during these phases appears to identify SNF specifically. Noninvasive measurements can detect both of these abnormalities. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Univ Nijmegen Hosp, Div Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. RI Tack, Cees/A-2368-2014 NR 39 TC 42 Z9 43 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD OCT PY 2000 VL 10 IS 5 BP 285 EP 291 DI 10.1007/BF02281111 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 382XT UT WOS:000165853200003 PM 11198484 ER PT J AU Kardaun, JWPF White, L Resnick, HE Petrovitch, H Marcovina, SM Saunders, AM Foley, DJ Havlik, RJ AF Kardaun, JWPF White, L Resnick, HE Petrovitch, H Marcovina, SM Saunders, AM Foley, DJ Havlik, RJ TI Genotypes and phenotypes for apolipoprotein E and Alzheimer disease in the Honolulu-Asia Aging Study SO CLINICAL CHEMISTRY LA English DT Article ID CORONARY HEART-DISEASE; E ALLELE EPSILON-4; E POLYMORPHISM; COGNITIVE DECLINE; POPULATION-SAMPLE; DIABETES-MELLITUS; PREDICTIVE VALUE; E LOCUS; DEMENTIA; RISK AB Background: The utility of apolipoprotein E (ApoE) type as an indicator of genetic susceptibility to Alzheimer disease (AD) depends on the reliability of typing. Although ApoE protein isoform phenotyping is generally assumed equivalent to genotyping from DNA, phenotype-genotype differences have been reported, Methods: ApoE genotype and phenotype results were examined for 3564 older (ages 71-93 years) Japanese-American male participants of the Honolulu-Asia Aging Study, an ongoing population-based study of aging and dementia. Results: Both methods demonstrated similar associations of ApoE type with AD: a direct association with ApoE4 and a less dramatic inverse association ApoE2. Advanced age did not appear to influence the ApoE4-AD association. The association with AD among ApoE4 homozygotes [odds ratio (OR) = 14.7] was higher than expected based on an observed OR of 2.0 in heterozygotes. Phenotype-genotype nonconcordance was more frequent for ApoE2 than for ApoE4. The ApoE2 phenotype occurred at a frequency of 7.9% vs a genotype frequency of 4.9%, corresponding to a probability of 56% that an individual with ApoE2 phenotype had the same genotype. Conclusions: Whereas E4 and E2 phenotypes and genotypes were comparably associated with AD, neither method would be expected to substantially improve the efficiency of case finding in the context of population screening beyond prediction based on age and education. Nonconcordance of phenotype and genotype was substantial for E2 and modest for E4 in this population. The ApoE4-AD association was independent of age; (C) 2000 American Association for Clinical Chemistry. C1 Pacific Hlth Sci Res Inst, Honolulu, HI 96813 USA. Kuakini Med Ctr, Honolulu, HI 96813 USA. Univ Washington, Sch Med, NW Lipid Labs, Seattle, WA 98103 USA. Duke Univ, Sch Med, Hoseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC 27710 USA. NIA, Bethesda, MD 20892 USA. RP White, L (reprint author), Pacific Hlth Sci Res Inst, Suite 306,846 S Hotel St, Honolulu, HI 96813 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 53 TC 15 Z9 16 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 OCT PY 2000 VL 46 IS 10 BP 1548 EP 1554 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 363PQ UT WOS:000089844100006 PM 11017931 ER PT J AU Pinto, LA Shearer, GM Blazevic, V AF Pinto, LA Shearer, GM Blazevic, V TI Immune-based approaches for control of HIV infection and viral-induced immunopathogenesis SO CLINICAL IMMUNOLOGY LA English DT Review ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTE; CELL-DEFICIENT MICE; HELPER CELL; HIV-1-INFECTED PATIENTS; GENE-EXPRESSION; CRITICAL STEP; RESPONSES; INDIVIDUALS AB Due to the limited efficacy of the current antiretroviral drug regimens in completely eradicating HIV and reconstituting the immune system, AIDS research is turning toward immune-based therapy to complement highly active antiretroviral therapy. Here we review potential mechanisms of protective cellular immunity and current HIV-specific immune-based strategies and discuss the rationale for novel hypothetical immunologic approaches for modulation of host antiviral immunity. One of the mechanisms by which the immune system exerts antiviral effects is via leukocyte generation of anti-HIV factors. Recent observations in this area of research suggest that non-MN antigens can stimulate the in vitro production of anti-HIV activity by leukocytes from healthy uninfected individuals and HIV-infected patients. These findings may provide insights for the design of novel therapeutic or prophylactic approaches, which might contribute to modulating immune system control of HIV infection. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Pinto, LA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 96 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 97 IS 1 BP 1 EP 8 DI 10.1006/clim.2000.4913 PG 8 WC Immunology SC Immunology GA 360YP UT WOS:000089695200001 PM 10998312 ER PT J AU Hewitt, RG Yiannoutsos, CT Higgs, ES Carey, JT Geiseler, PJ Soave, R Rosenberg, R Vazquez, GJ Wheat, LJ Fass, RJ Antoninievic, Z Walawander, AL Flanigan, TP Bender, JF AF Hewitt, RG Yiannoutsos, CT Higgs, ES Carey, JT Geiseler, PJ Soave, R Rosenberg, R Vazquez, GJ Wheat, LJ Fass, RJ Antoninievic, Z Walawander, AL Flanigan, TP Bender, JF CA AIDS Clinical Trials Grp TI Paromomycin: No more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID AIDS PATIENTS; NATURAL-HISTORY; DIARRHEA; TRIAL; EPIDEMIOLOGY; SPECIMENS; NUMBER AB To evaluate the efficacy of paromomycin for the treatment of symptomatic cryptosporidial enteritis in human immunodeficiency virus-infected adults, we conducted a prospective, randomized, double-blind, placebo-controlled trial before the widespread introduction of highly active antiretroviral therapy (HAART). Seven units under the auspices of the AIDS Clinical Trials Group enrolled 35 adults with CD4 cell counts of less than or equal to 150/mm(3). Initially 17 patients received paromomycin (500 mg 4 times daily) and 18 received matching placebo for 21 days. Then all patients received paromomycin (500 mg q.i.d.) for an additional 21 days. Clinical definitions of response were measured by an average number of bowel movements per day in association with concurrent need for antidiarrheal agents that was lower than that before study entry. There was no treatment response during the placebo-controlled phase of the study according to protocol-defined criteria (P = .88). Three paromomycin recipients (17.6%) versus 2 placebo recipients (14.3%) responded completely Rates of combined partial and complete responses in the paromomycin arm (8 out of 17, 47.1%) and the placebo arm (5 out of 14, 35.7%) of the study were also similar (P = .72). The clinical course of cryptosporidiosis was quite variable. Paromomycin was not shown to be more effective than placebo for the treatment of symptomatic cryptosporidial enteritis. However, inadequate statistical power prevents definitive rejection of the usefulness of paromomycin as therapy for this infection. C1 SUNY Buffalo, Buffalo, NY 14260 USA. Cornell Univ, Ithaca, NY USA. Columbia Univ, New York, NY USA. Harvard Univ, Boston, MA 02115 USA. NIAID, Bethesda, MD USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ So Calif, Los Angeles, CA USA. Indiana Univ, Bloomington, IN USA. Frontier Sci Technol & Res Fdn, Amherst, NY USA. Brown Univ, Providence, RI 02912 USA. Warner Lambert Parke Davis, Dept Pharmacol, Ann Arbor, MI 48105 USA. Univ Puerto Rico, San Juan, PR 00936 USA. RP Hewitt, RG (reprint author), Erie Cty Med Ctr & Labs, 462 Grider St, Buffalo, NY 14215 USA. FU NIAID NIH HHS [5 U01AI12765812] NR 35 TC 59 Z9 66 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 2000 VL 31 IS 4 BP 1084 EP 1092 DI 10.1086/318155 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 375EU UT WOS:000165387200033 PM 11049793 ER PT J AU Colbert, LH Hootman, JM Macera, CA AF Colbert, LH Hootman, JM Macera, CA TI Physical activity-related injuries in walkers and runners in the Aerobics Center Longitudinal Study SO CLINICAL JOURNAL OF SPORT MEDICINE LA English DT Article DE physical activity; walking; running ID WALKING; FITNESS AB Objective: To examine the association between physical activity-related injuries and participation in walking versus running. Design: Nested case-control study. Setting: Cooper Clinic Preventive Medicine Center, Dallas, Texas. Participants: 5,327 men and women undergoing exams between 1987 and 1995 and completing follow-up health history questionnaires in 1990 or 1995. Participants were classified as those reporting regular participation in walking or jogging/running at baseline. Those reporting both or neither activity were excluded from the study (n = 1404). Cases (698 men, 169 women) were those reporting physical activity-related injuries requiring physician visits in the previous year on the follow-up questionnaire. Controls (2,358 men, 698 women) were randomly selected from the remaining population. Main Outcome Measures: Logistic regression was used to examine the risk of injury in walkers versus runners and risk of injury by exercise dose while considering age, body mass index, previous injury, and strength training. Results: There was a significantly lower risk of injury for walkers compared with runners in young (<45 years old) (odds ratio [OR] = 0.75, 95% confidence interval [CI] = 0.58-0.97) and older (45 years) men (OR = 0.64, 95% CI = 0.49-0.82), and a nonsignificantly lower risk among young (OR = 0.73, 95% CI = 0.39-1.37) and older women (OR = 0.72, 95% CI = 0.38-1.35). There was no effect of greater amounts of walking on injuries for either gender; however, there was a higher injury risk associated with running 15-30 min/day (OR = 1.36, 95% Ct = 1.07-1.73) and 30+ min/day (OR = 1.52, 95% CI = 1.14-2.04) compared with <15 min/day among men, but not among women. Conclusions: This low risk of musculoskeletal injury suggests that participation in walking can be safely recommended as a way to improve health and fitness. C1 NCI, Div Canc Prevent, Bethesda, MD USA. Ctr Dis Control & Prevent, Div Adult & Community Hlth, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Nutr & Phys Activ, Atlanta, GA USA. RP Colbert, LH (reprint author), 6006 Execut Blvd,Suite 321, Bethesda, MD 20892 USA. FU NIA NIH HHS [AG06945] NR 19 TC 38 Z9 40 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1050-642X J9 CLIN J SPORT MED JI Clin. J. Sport Med. PD OCT PY 2000 VL 10 IS 4 BP 259 EP 263 DI 10.1097/00042752-200010000-00006 PG 5 WC Orthopedics; Physiology; Sport Sciences SC Orthopedics; Physiology; Sport Sciences GA 389HK UT WOS:000166232400006 PM 11086751 ER PT J AU Ballow, M Strober, W AF Ballow, M Strober, W TI Primary immune deficiencies - Introduction SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Editorial Material C1 SUNY Buffalo, Childrens Hosp, Buffalo, NY 14260 USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Ballow, M (reprint author), SUNY Buffalo, Childrens Hosp, Buffalo, NY 14260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD OCT PY 2000 VL 19 IS 2 BP 79 EP 81 DI 10.1385/CRIAI:19:2:79 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 373QU UT WOS:000165301000001 ER PT J AU Strober, W Chua, K AF Strober, W Chua, K TI Common variable immunodeficiency SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Review ID X-LINKED AGAMMAGLOBULINEMIA; INTRAVENOUS GAMMA-GLOBULIN; B-CELLS; VARIED IMMUNODEFICIENCY; SEPTIC ARTHRITIS; IMMUNOGLOBULIN PRODUCTION; GRANULOMATOUS-DISEASE; IL-10 PRODUCTION; GENE-EXPRESSION; IGA DEFICIENCY C1 NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIH, 10 Ctr Dr,MSC 1980,Bldg 10,room 11N238, Bethesda, MD 20892 USA. NR 78 TC 16 Z9 16 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD OCT PY 2000 VL 19 IS 2 BP 157 EP 181 DI 10.1385/CRIAI:19:2:157 PG 25 WC Allergy; Immunology SC Allergy; Immunology GA 373QU UT WOS:000165301000006 PM 11107500 ER PT J AU Anderson, RT Ory, M Cohen, S McBride, JS AF Anderson, RT Ory, M Cohen, S McBride, JS TI Issues of aging and adherence to health interventions SO CONTROLLED CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Conference on Adherence to Behavioral and Pharmaocological Interventions in Clinical Research on Older Adults CY MAY, 1998 CL WAKE FOREST UNIV, SCH MED, WINSTON SALEM, NORTH CAROLINA SP Womens Hlth Ctr Excellence, Claude D Pepper Older Americans Independence Ctr HO WAKE FOREST UNIV, SCH MED DE adherence; aging; older adults; health interventions ID ELDERLY PATIENTS; OLDER ADULTS; NONPHARMACOLOGIC INTERVENTIONS; MEDICATION COMPLIANCE; COGNITIVE FUNCTION; HYPERTENSION; TRIAL; WOMEN; CARE; BEHAVIORS AB This review article describes several processes and considerations that are important to adherence in aging research and potential strategies that could be used to facilitate adherence among older adults. In many large aging trials participants are purposively selected to reduce the risk of suboptimal adherence and retention. This selection often involves screening out those with barriers such as transportation needs, sensory deficits, functional dependence, major diseases limiting life expectancy, or apparent psychological distress. However, trends toward extending interventions to the general population of older adults require specific knowledge about the circumstances and processes that support adherence among older adults or the conditions that make them vulnerable to adherence problems. Addressing the diversity of needs, expectations, and capabilities of older adults that promote adherence is a key consideration in aging research. Control Clin Trials 2000;21:171S-183S (C) Elsevier Science Inc. 2000. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Sec Social Sci & Hlth Policy, Winston Salem, NC 27157 USA. NIA, Social Sci Res Aging Branch, Behav Res Program, Bethesda, MD 20892 USA. RP Anderson, RT (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Sec Social Sci & Hlth Policy, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU BHP HRSA HHS [DHHS 282-97-0025]; NIA NIH HHS [1R13AG16229-01, P60 AG10484] NR 71 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2000 VL 21 IS 5 SU S BP 171S EP 183S DI 10.1016/S0197-2456(00)00075-1 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 361YR UT WOS:000089752300004 PM 11018572 ER PT J AU Ranstam, J Buyse, M George, SL Evans, S Geller, NL Scherrer, B Lesaffre, E Murray, G Edler, L Hutton, JL Colton, T Lachenbruch, P AF Ranstam, J Buyse, M George, SL Evans, S Geller, NL Scherrer, B Lesaffre, E Murray, G Edler, L Hutton, JL Colton, T Lachenbruch, P CA ISCB Subcomm Fraud TI Fraud in medical research: An international survey of biostatisticians SO CONTROLLED CLINICAL TRIALS LA English DT Article AB The characteristics of scientific fraud and its impact on medical research are in general not well known. However, the interest in the phenomenon has increased steadily during the last decade. Biostatisticians routinely work closely with physicians and scientists in many branches of medical research and have therefore unique insight into data. In addition, they have methodological competence to detect fraud and could be expected to have a professional interest in valid results. Biostatisticians therefore are likely to provide reliable information on the characteristics of fraud in medical research. The objective of this survey of biostatisticians, who were members of the International Society for Clinical Biostatistics, was to assess the characteristics of fraud in medical research. The survey was performed between April and July 1998. The participation rate was only 37%. We report the results because a majority (51%) of the participants knew about fraudulent projects, and many did not know whether the organization they work for has a formal system for handling suspected fraud or not. Different forms of fraud (e.g., fabrication and falsification of data, deceptive reporting of results, suppression of data, and deceptive design or analysis) had been observed in fairly similar numbers. We conclude that fraud is not a negligible phenomenon in medical research, and that increased awareness of the forms in which it is expressed seems appropriate. C1 Malmo Univ, Sch Hlth & Soc, SE-20506 Malmo, Sweden. Int Inst Drug Dev, Brussels, Belgium. Duke Univ, Durham, NC 27706 USA. Med Control Agcy, London, England. NHLBI, Bethesda, MD 20892 USA. Inst Rech Jouvenail, Paris, France. Ctr Biostat, Louvain, Belgium. Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. German Canc Res Ctr, D-6900 Heidelberg, Germany. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Boston Univ, Boston, MA 02215 USA. US FDA, Rockville, MD 20857 USA. RP Ranstam, J (reprint author), Malmo Univ, Sch Hlth & Soc, SE-20506 Malmo, Sweden. RI Ranstam, Jonas/A-4386-2009 OI Ranstam, Jonas/0000-0002-8287-7273 NR 9 TC 35 Z9 37 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2000 VL 21 IS 5 BP 415 EP 427 DI 10.1016/S0197-2456(00)00069-6 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 361AH UT WOS:000089699200001 PM 11018560 ER PT J AU Greene, T Beck, GJ Gassman, JJ Gotch, FA Kusek, JW Levey, AS Levin, NW Schulman, G Eknoyan, G AF Greene, T Beck, GJ Gassman, JJ Gotch, FA Kusek, JW Levey, AS Levin, NW Schulman, G Eknoyan, G CA HEMO Study Grp TI Design and statistical issues of the Hemodialysis (HEMO) Study SO CONTROLLED CLINICAL TRIALS LA English DT Article DE dialysis; renal failure; end stage renal disease; urea kinetic modeling; clinical trial ID NATIONAL COOPERATIVE DIALYSIS; STAGE RENAL-DISEASE; PATIENT SURVIVAL; MORTALITY; PREDICTORS; MEMBRANES; SELECTION; MORBIDITY; ADEQUACY; REMOVAL AB The Hemodialysis Study is a multicenter clinical trial of hemodialysis prescriptions for patients with end stage renal disease. Participants from over 65 dialysis facilities associated with 15 clinical centers in the United States are randomized in a 2 X 2 factorial design to dialysis prescriptions targeted to a standard dose (equilibrated Kt/V = 1.05) or a high dose (equilibrated Kt/V = 1.45), and to either low or high flux membranes. The primary outcome variable is mortality; major secondary outcomes are defined based on hospitalizations due to cardiovascular or infectious complications, and on the decline of serum albumin. The Outcome Committee, consisting of study investigators, uses a blinded review system to classify causes of death and hospitalizations related to the major secondary outcomes;The dialysis dose intervention is directed by the Data Coordinating Center using urea kinetic modeling programs that analyze results from dialysis treatments to monitor adherence to the study targets, adjust suggested dialysis prescriptions, and assist in trouble-shooting problems with the delivery of dialysis. The study design has adequate power to detect reductions in mortality rate equal to 25% of the projected baseline mortality rate for both of the interventions. (C) Elsevier Science Inc. 2000. C1 Cleveland Clin Fdn, Dept Biostat & Epidemiol, HEMO Study Data Coordinating Ctr, Cleveland, OH 44195 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIDDKD, Bethesda, MD 20892 USA. New England Med Ctr, Boston, MA 02111 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Vanderbilt Univ, Nashville, TN USA. Baylor Coll Med, Houston, TX 77030 USA. RP Greene, T (reprint author), Cleveland Clin Fdn, Dept Biostat & Epidemiol, HEMO Study Data Coordinating Ctr, 9500 Euclid Ave,Wb4, Cleveland, OH 44195 USA. NR 59 TC 99 Z9 100 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2000 VL 21 IS 5 BP 502 EP 525 DI 10.1016/S0197-2456(00)00062-3 PG 24 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 361AH UT WOS:000089699200009 PM 11018567 ER PT J AU Gladwin, MT AF Gladwin, MT TI Electrocardiographic guidance in placing central venous catheters - Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID PLACEMENT; CANNULATION; POSITION; ECG C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 8 TC 2 Z9 2 U1 0 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 OCT PY 2000 VL 28 IS 10 BP 3577 EP 3578 DI 10.1097/00003246-200010000-00052 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 365CT UT WOS:000089931400042 ER PT J AU Tycko, R AF Tycko, R TI Solid-state NMR as a probe of amyloid fibril structure SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID NUCLEAR-MAGNETIC-RESONANCE; ANGLE-SPINNING NMR; MULTIPLE-QUANTUM NMR; PROTEIN SECONDARY STRUCTURE; ALZHEIMERS-DISEASE; BETA-SHEET; CHEMICAL-SHIFT; EXCHANGE SPECTROSCOPY; ROTATIONAL RESONANCE; 2-DIMENSIONAL NMR AB Amyloid fibrils are intrinsically noncrystalline, insoluble, high-molecular-weight aggregates of peptides and proteins, with considerable biomedical and biophysical significance. Solid-state NMR techniques are uniquely capable of providing high-resolution, site-specific structural constraints for amyloid fibrils, at the level of specific interatomic distances and torsion angles. So far, a relatively small number of solid-state NMR studies of amyloid fibrils have been reported. These have addressed issues about the supramolecular organization of beta-sheets in the fibrils and the peptide conformation in the fibrils, and have concentrated on the beta-amyloid peptide of Alzheimer's disease. Many additional applications of solid-state NMR to amyloid fibrils from a variety of sources are anticipated in the near future, as these systems are ideally suited for the technique and are of widespread current interest. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 84 TC 69 Z9 71 U1 2 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD OCT PY 2000 VL 4 IS 5 BP 500 EP 506 DI 10.1016/S1367-5931(00)00123-X PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 363PB UT WOS:000089842800004 PM 11006536 ER PT J AU Kim, L Kimmel, AR AF Kim, L Kimmel, AR TI GSK3, a master switch regulating cell-fate specification and tumorigenesis SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; WNT SIGNALING PATHWAY; PROTEIN PHOSPHATASE 2A; SEA-URCHIN EMBRYO; BETA-CATENIN; NEGATIVE REGULATOR; XENOPUS EMBRYOS; AXIS FORMATION; CAENORHABDITIS-ELEGANS; MOLECULAR MECHANISM AB Until recently, protein kinase GSK3 (glycogen synthase kinase 3), an essential component for cell-fate specification, had been considered a constitutively activated enzyme subject to developmentally regulated inhibition through hierarchical, linear signaling paths. Data from various systems now indicate more complex scenarios involving activating as well as inhibiting circuits, and the differential formation of multi-protein complexes that antagonistically affect GSK3 function. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, L (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bldg 6-B1-22, Bethesda, MD 20892 USA. NR 67 TC 185 Z9 190 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD OCT PY 2000 VL 10 IS 5 BP 508 EP 514 DI 10.1016/S0959-437X(00)00120-9 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 351VM UT WOS:000089178900007 PM 10980428 ER PT J AU Restifo, NP AF Restifo, NP TI Building better vaccines: how apoptotic cell death can induce inflammation and activate innate and adaptive immunity SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; COLONY-STIMULATING FACTOR; INDUCED PROTEIN-KINASE; GENE GUN IMMUNIZATION; DENDRITIC CELLS; T-LYMPHOCYTES; TNF-ALPHA; FAS LIGAND; IFN-GAMMA; TUMOR AB The immunological consequences of apoptosis have been hotly debated. Apoptosis was originally described as a set of cellular morphological changes that occur in the absence of inflammation but the term has been redefined on the basis of a set of conserved molecular events that include the activation of caspases. Though the apoptosis occurring during normal development is immunologically bland or even tolerizing, the apoptotic death after viral infection or after the ligation of Fas can trigger powerful innate and adaptive immune responses. The molecular machinery at the nexus of apoptosis and inflammation includes caspase-1 - an activator of 1L-1 beta and IL-18 - as well as the double-stranded-RNA-dependent protein kinase pathway and RNaseL pathway, which are key effecters of antiviral immunity. New proapoptotic vaccines induce immune responses that may be able to prevent or treat infectious disease and cancer. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 79 TC 124 Z9 130 U1 1 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2000 VL 12 IS 5 BP 597 EP 603 DI 10.1016/S0952-7915(00)00148-5 PG 7 WC Immunology SC Immunology GA 351EC UT WOS:000089144000018 PM 11007365 ER PT J AU Barrette, S Orlic, D AF Barrette, S Orlic, D TI Alternative viral envelopes for oncoretroviruses to increase gene transfer into hematopoietic stem cells SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE gene therapy; hematopoietic stem cell; receptors; retrovirus ID BLOOD CD34(+) CELLS; AMPHOTROPIC RETROVIRUS RECEPTOR; EXPRESSING HIGH-LEVELS; MURINE LEUKEMIA-VIRUS; BONE-MARROW CELLS; EX-VIVO CULTURE; LONG-TERM; IN-VIVO; PERIPHERAL-BLOOD; REPOPULATING CELLS AB The hemzatopoietic stent cell is the target for gene therapy of human blood disease. Low retroviral receptors for the commonly used vectors and quiescence of hematopoietic stem cells are believed to be major obstacles to the success of gene therapy. The development of new stem cell assays has allowed better understanding of the biology and phenotype of hematopoietic stem cells, leading to selection of highly enriched populations of hematopoietic stem cells. Quantitation of retrovirus receptors on these enriched populations of hematopoietic stem cells has resulted in the identification of subpopulations of cells expressing high levels of retrovirus receptors. New promising retrovirus envelopes are being developed. In this review, we discuss those issues that nay help to resolve the problem of low gene transfer efficiency into human hematopoietic stem cells. C1 NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. RP Barrette, S (reprint author), NHGRI, Hematopoiesis Sect, NIH, Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA. NR 53 TC 7 Z9 7 U1 0 U2 0 PU PHARMAPRESS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD OCT PY 2000 VL 2 IS 5 BP 507 EP 514 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 367XU UT WOS:000090087800004 PM 11249753 ER PT J AU Baudet, C Mikaels, A Westphal, H Johansen, J Johansen, TE Ernfors, P AF Baudet, C Mikaels, A Westphal, H Johansen, J Johansen, TE Ernfors, P TI Positive and negative interactions of GDNF, NTN and ART in developing sensory neuron subpopulations, and their collaboration with neurotrophins SO DEVELOPMENT LA English DT Article DE GDNF; NTN; ART; neurotrophin; DRG; mouse ID NERVE GROWTH-FACTOR; MIDBRAIN DOPAMINERGIC-NEURONS; RECEPTOR TYROSINE KINASE; DORSAL-ROOT GANGLION; MICE LACKING GDNF; CUTANEOUS MECHANORECEPTORS; FUNCTIONAL RECEPTOR; NEURTURIN RECEPTOR; RET PROTOONCOGENE; ENTERIC NEURONS AB Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and neublastin/artemin (ART) are distant members of the transforming growth factor beta family, and have been shown to elicit neurotrophic effects upon several classes of peripheral and central neurons, Limited information from in vitro and expression studies has also substantiated a role for GDNF family ligands in mammalian somatosensory neuron development, Here, we show that although dorsal root ganglion (DRG) sensory neurons express GDNF family receptors embryonically, they do not survive in response to their ligands. The regulation of survival emerges postnatally for all GDNF family ligands, GDNF and NTN support distinct subpopulations that can be separated with respect to their expression of GDNF family receptors, whereas ART supports neurons in populations that are also responsive to GDNF or NTN, Sensory neurons that coexpress GDNF family receptors are medium sized, whereas small-caliber nociceptive cells preferentially express a single receptor, In contrast to brain-derived neurotrophic factor (BDNF)-dependent neurons, embryonic nerve growth factor (NGF)dependent nociceptive neurons switch dependency to GDNF, NTN and ART postnatally, Neurons that survive in the presence of neurotrophin 3 (NT3) or neurotrophin 4 (NT4), including proprioceptive afferents, Merkel end organs and D-hair afferents, are also supported by GDNF family ligands neonatally, although at postnatal stages they lose their dependency on GDNF and NTN, At late postnatal stages, ART prevents survival elicited by GDNF and NTN. These data provide new insights on the roles of GDNF family ligands in sensory neuron development. C1 Karolinska Inst, Lab Mol Neurobiol Med Biochem & Biophys, S-17177 Stockholm, Sweden. NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. NsGene AS, DK-2570 Ballerup, Denmark. RP Ernfors, P (reprint author), Karolinska Inst, Lab Mol Neurobiol Med Biochem & Biophys, S-17177 Stockholm, Sweden. NR 75 TC 62 Z9 66 U1 2 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 OCT PY 2000 VL 127 IS 20 BP 4335 EP 4344 PG 10 WC Developmental Biology SC Developmental Biology GA 372KF UT WOS:000165232300004 PM 11003834 ER PT J AU Lund, LR Bjorn, SF Sternlicht, MD Nielsen, BS Solberg, H Usher, PA Osterby, R Christensen, IJ Stephens, RW Bugge, TH Dano, K Werb, Z AF Lund, LR Bjorn, SF Sternlicht, MD Nielsen, BS Solberg, H Usher, PA Osterby, R Christensen, IJ Stephens, RW Bugge, TH Dano, K Werb, Z TI Lactational competence and involution of the mouse mammary gland require plasminogen SO DEVELOPMENT LA English DT Article DE tissue remodeling; plasminogen deficient mice; mammary gland involution; urokinase; entactin; metalloproteinases ID FIBROBLAST GROWTH-FACTOR; MATRIX METALLOPROTEINASES; GENE-EXPRESSION; CELL-DEATH; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; DEFICIENT MICE; FACTOR-BETA; TISSUE; STROMELYSIN-1 AB Urokinase-type plasminogen activator expression is induced in the mouse mammary gland during development and post-lactational involution, We now show that primiparous plasminogen-deficient (Plg(-/-)) mice have seriously compromised mammary gland development and involution. All mammary glands were underdeveloped and one-quarter of the mice failed to lactate. Although the glands from lactating Plg(-/-) mice were initially smaller, they failed to involute after weaning, and in most cases they failed to support a second litter. Alveolar regression was markedly reduced and a fibrotic stroma accumulated in Plg(-/-) mice. Nevertheless, urokinase and matrix metalloproteinases (MMPs) were upregulated normally in involuting glands of Plg-/- mice, and fibrin did not accumulate in the glands. Heterozygous Plg(+/-) mice exhibited haploinsufficiency, with a definite, but less severe mammary phenotype. These data demonstrate a critical, dose-dependent requirement for Plg in lactational differentiation and mammary gland remodeling during involution. C1 Univ Copenhagen Hosp, Finsen Lab, DK-2100 Copenhagen, Denmark. Herlev Univ Hosp, Dept Gynecol & Obstet, DK-2730 Herlev, Denmark. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Aarhus Cty Hosp, Electron Microscopy Lab, DK-8000 Aarhus C, Denmark. Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH 45229 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. RP Lund, LR (reprint author), Univ Copenhagen Hosp, Finsen Lab, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. RI Stephens, Ross/A-8524-2008 OI Stephens, Ross/0000-0001-6124-0102 FU NCI NIH HHS [CA 57621, CA 57621S1] NR 52 TC 74 Z9 80 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 OCT PY 2000 VL 127 IS 20 BP 4481 EP 4492 PG 12 WC Developmental Biology SC Developmental Biology GA 372KF UT WOS:000165232300016 PM 11003846 ER PT J AU Brody, T Odenwald, WF AF Brody, T Odenwald, WF TI Programmed transformations in neuroblast gene expression during Drosophila CNS lineage development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila; CNS; neuroblast lineage; sublineages; cell culture; transcription factor network ID CENTRAL-NERVOUS-SYSTEM; EMBRYONIC NEUROBLASTS; EGF RECEPTOR; ASYMMETRIC SEGREGATION; EARLY NEUROGENESIS; COLUMN IDENTITY; FINGER PROTEIN; CELL-DIVISION; PROSPERO; SPECIFICATION AB During Drosophila embryonic CNS development, the sequential neuroblast (NB) expression of four proteins, Hunchback (Hb), Pou-homeodomain proteins 1 and 2 (referred to collectively as Pdm), and Castor (Cas), identifies a transcription factor network regulating the temporal development of all ganglia. The Zn-finger proteins Hb and Gas, acting as repressors, confine Pdm expression to a narrow intermediate temporal window; this results in the generation of three panneural domains whose cellular constituents are marked by expression of Hb, Pdm, or Cas (R. Kambadur et al., 1998, Genes DeV. 12, 246-260). Seeking to identify the cellular mechanisms that generate these expression compartments, we studied the lineage development of isolated NBs in culture. We found that the Db, Pdm, and Cas expression domains are generated by transitions in NE gene expression that are followed by gene product perdurance within sequentially produced sublineages. Our results also indicate that following Cas expression, many CNS NBs continue their asymmetric divisions generating additional progeny, which can be identified by the expression of the bHLH transcription factor Grainyhead (Gh). Gh appears to be a terminal embryonic CNS lineage marker. Taken together, these studies indicate that once NBs initiate Lineage development, no additional signaling between NBs and the neuroectoderm and/or mesoderm is required to trigger the temporal progression of Hb --> Pdm --> Cas --> Gh expression during NB outgrowth. C1 NINDS, Neurogenet Unit, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Odenwald, WF (reprint author), NINDS, Neurogenet Unit, Neurochem Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 107 Z9 107 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 1 PY 2000 VL 226 IS 1 BP 34 EP 44 DI 10.1006/dbio.2000.9829 PG 11 WC Developmental Biology SC Developmental Biology GA 361DB UT WOS:000089705800003 PM 10993672 ER PT J AU Tanaka, M Komuro, I Inagaki, H Jenkins, NA Copeland, NG Izumo, S AF Tanaka, M Komuro, I Inagaki, H Jenkins, NA Copeland, NG Izumo, S TI Nkx3.1, a murine homolog of Drosophila bagpipe, regulates epithelial ductal branching and proliferation of the prostate and palatine glands SO DEVELOPMENTAL DYNAMICS LA English DT Article DE homeobox; prostate cancer; prostate hypertrophy; tumor suppressor; NK2 domain ID HOMEOBOX GENE; HEART DEVELOPMENT; EXPRESSION; MICE; CANCER; ROLES; ORGANOGENESIS; MORPHOGENESIS; DISRUPTION; FOREBRAIN AB Nkx3.1 is a homeobox gene related to Drosophila bagpipe. Nkx3.1 is an early marker of the sclerotome and a subset of vascular:smooth muscle cells, and at later stages, this gene is expressed in the prostate, palatine glands, kidney, and restricted regions of the central nervous system. In the present study, we determined the chromosomal localization of Nkx3.1 and examined the function of Nkx3.1 in vivo by using gene targeting technique. Interestingly, Nkx3.1 mapped to the central region of the mouse chromosome 14 and was linked to Nkx2.6, a murine homolog of Drosophila tinman, Homozygous mutant mice for Nkx3.1 were viable and:fertile, and the phenotype was, unexpectedly, confined to the prostate and palatine glands. The homozygous mutant mice exhibited defective branching morphogenesis of the prostate and palatine glands. Moreover, epithelial cells of the mutant prostate and palatine glands showed significant hyperplasia, No abnormalities were detected in the sclerotome, blood vessels, kidney, or brain. These results indicate that Nkx3.1 plays a critical role in epithelial branching and proliferation in the prostate and palatine glands. However, we did not observe prostate cancer in homozygous mutant mice up to 2 years of age. Therefore, involvement of NKX3.1 in carcinogenesis in men needs to be carefully determined by further investigation, Published 2000 Wiley-Liss, Inc.(dagger). C1 Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Tokyo, Fac Med, Dept Cardiovasc Med, Tokyo 113, Japan. Natl Ind Res Inst Nagoya, Dept Chem, Nagoya, Aichi 462, Japan. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Izumo, S (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, SL-201,330 Brookline Ave, Boston, MA 02215 USA. FU NHLBI NIH HHS [R01HL51253] NR 32 TC 61 Z9 63 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 2000 VL 219 IS 2 BP 248 EP 260 DI 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1054>3.3.CO;2-5 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 359TL UT WOS:000089628100013 PM 11002344 ER PT J AU Montagnani, M Quon, MJ AF Montagnani, M Quon, MJ TI Insulin action in vascular endothelium: potential mechanisms linking insulin resistance with hypertension SO DIABETES OBESITY & METABOLISM LA English DT Review DE endothelium; nitric oxide; metabolism ID NITRIC-OXIDE SYNTHASE; MUSCLE BLOOD-FLOW; RAT ADIPOSE-CELLS; POSITRON EMISSION TOMOGRAPHY; CONTRACTING SKELETAL-MUSCLE; STIMULATED GLUCOSE-UPTAKE; FREE FATTY-ACIDS; LIPID-METABOLISM; HUMAN FOREARM; HUMAN-DISEASE C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 8C-218,10 Ctr Dr MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; montagnani, monica/0000-0002-5697-8185; Quon , Michael /0000-0002-5289-3707 NR 75 TC 66 Z9 70 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD OCT PY 2000 VL 2 IS 5 BP 285 EP 292 DI 10.1046/j.1463-1326.2000.00092.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 354KH UT WOS:000089329300003 PM 11225743 ER PT J AU Mott, JL Denniger, G Zullo, SJ Zassenhaus, HP AF Mott, JL Denniger, G Zullo, SJ Zassenhaus, HP TI Genomic structure of murine mitochondrial DNA polymerase-gamma SO DNA AND CELL BIOLOGY LA English DT Article ID NUCLEAR GENES; SEQUENCE; ELEMENTS; REGIONS AB We have sequenced a genomic clone of the gene encoding the mouse mitochondrial DNA polymerase. The gene consists of 23 exons, which span approximately 13.2 kb, with exons ranging in size from 53 to 768 bp, All intron-exon boundaries conform to the GT-AG rule. By comparison with the human genomic sequence, we found remarkable conservation of the gene structure; the intron-exon borders are in almost identical locations for the 22 introns, The 5' upstream region contains approximately 300 bp of homology between the mouse and human sequences that presumably contain the promoter element. This region lacks any obvious TATA domain and is relatively GC rich, consistent with the housekeeping function of the mitochondrial DNA polymerase, Finally, within the 5' flanking region, both mouse and human genes have a region of 73 bp with high homology to the tRNA-Arg gene. C1 St Louis Univ, Hlth Sci Ctr, Dept Mol Microbiol & Immunol, St Louis, MO 63104 USA. NIMH, Biochim Genet Lab, Bethesda, MD 20892 USA. RP Zassenhaus, HP (reprint author), St Louis Univ, Hlth Sci Ctr, Dept Mol Microbiol & Immunol, 1402 S Grand Blvd, St Louis, MO 63104 USA. NR 17 TC 2 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 2000 VL 19 IS 10 BP 601 EP 605 DI 10.1089/104454900750019353 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 368TT UT WOS:000090134200002 PM 11058962 ER PT J AU Rothman, RB Carroll, FI AF Rothman, RB Carroll, FI TI Opportunities for medication development in obesity SO DRUG DEVELOPMENT RESEARCH LA English DT Editorial Material ID CLINICAL IMPLICATIONS; INGESTIVE BEHAVIOR; UNITED-STATES; FENFLURAMINE; WEIGHT; DEXFENFLURAMINE; SIBUTRAMINE; PHENTERMINE; ADDICTION; APPETITE C1 NIDA, NIH, Baltimore, MD 21224 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Rothman, RB (reprint author), NIDA, NIH, Baltimore, MD 21224 USA. NR 28 TC 1 Z9 1 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 2000 VL 51 IS 2 BP 49 EP 51 DI 10.1002/1098-2299(200010)51:2<49::AID-DDR1>3.0.CO;2-0 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 390EA UT WOS:000166281700001 ER PT J AU Rothman, RB Baumann, MH AF Rothman, RB Baumann, MH TI Neurochemical mechanisms of phentermine and fenfluramine: Therapeutic and adverse effects SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE dopamine; serotonin; anorectics; feeding; addiction ID PRIMARY PULMONARY-HYPERTENSION; MONOAMINE-OXIDASE INHIBITORS; APPETITE-SUPPRESSANT DRUGS; IN-VIVO MICRODIALYSIS; SEROTONIN TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS; D-AMPHETAMINE; SUBSTITUTED AMPHETAMINES; DISCRIMINATIVE STIMULUS; PARA-CHLOROAMPHETAMINE AB Most clinically available anorectic medications, such as phentermine and fenfluramine, are thought to interact with monoamine systems in the brain. Preclinical evidence suggests that there is substantial overlap between the neural circuits controlling feeding behavior and those involved in self-administration of abused drugs. Thus, anorectics may be effective treatments for substance use disorders. The purpose of the present article is to review recent findings that address the neurochemical mechanisms of action of phentermine, fenfluramine, the phentermine plus fenfluramine combination, and other selected anorectic medications. We review studies that have examined the effects of phentermine and fenfluramine in a variety of preclinical models of stimulant addiction. The implications of these findings for explaining the therapeutic efficacy and potential adverse actions of these drugs are considered. Finally, the review concludes by discussing the feasibility of developing novel drugs that produce the same neurochemical effects as phentermine plus fenfluramine, without the associated adverse effects of primary pulmonary hypertension (fenfluramine-related), neurotoxicity (fenfluramine-related), and abuse liability (phentermine-related). Such agents would have potential applications in the treatment of obesity, drug dependence, and other psychiatric disorders. Published 2000 Wiley-Liss, Inc.(dagger) C1 NIDA, CPS, IRP, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, CPS, IRP, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 134 TC 16 Z9 16 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 2000 VL 51 IS 2 BP 52 EP 65 DI 10.1002/1098-2299(200010)51:2<52::AID-DDR2>3.0.CO;2-H PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 390EA UT WOS:000166281700002 ER PT J AU Weyer, C de Souza, CJ AF Weyer, C de Souza, CJ TI Development of beta(3)-adrenoceptor agonists as antiobesity and antidiabetes drugs in humans: Current status and future prospects SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE obesity; pharmacotherapy; thermogenic drugs; beta(3)-adrenoceptor; insulin sensitizers ID BETA-ADRENOCEPTOR AGONIST; BROWN ADIPOSE-TISSUE; MITOCHONDRIAL UNCOUPLING PROTEIN; HUMAN BETA-3-ADRENERGIC RECEPTOR; ZUCKER FA/FA RATS; BODY-MASS INDEX; ADRENERGIC-RECEPTOR; OBESE SUBJECTS; SKELETAL-MUSCLE; INSULIN SENSITIVITY AB The discovery of a third P-adrenergic receptor (beta (3)-AR) in the early 1980s and the finding that stimulation of this receptor by selective agonists leads to marked weight loss and glycemic improvements in rodent models of obesity and diabetes, respectively, has led to intensive research efforts to develop beta (3)-AR agonists for the treatment of obesity and Type 2 diabetes in humans. Indeed, the ability of beta (3)-AR agonists to simultaneously increase lipolysis, fat oxidation, energy expenditure, and insulin sensitivity suggests that this class of agents may have promising potential as both antiobesity and antidiabetic agents. Unfortunately, several pharmaceutical problems have hampered their development as therapeutic agents in humans over the past 15 years. Major obstacles have been the pharmacological differences between the rodent and human beta (3)-AR, the lack of selectivity of previous compounds for the beta (3) over beta (1)/ beta (2)-ARs, and unsatisfactory pharmacokinetic properties. More recently, clinical studies with a highly (rodent-) selective beta (3)-AR agonist have provided unequivocal evidence that selective beta (3)-AR stimulation can increase lipolysis, fat oxidation, and insulin sensitivity in humans. Meanwhile, cloning of the human beta (3)-AR has allowed the development of novel compounds that are specifically targeted at the human receptor. This new generation of compounds has shown promising results in nonhuman primates and in Phase 1 studies in humans. Once human beta (3)-AR selective compounds with satisfactory pharmacokinetic properties become available, clinical testing will reveal whether their effects are sufficient and safe in the long term to allow the use of these agonists for the treatment of obesity and diabetes in humans. (C) 2000 Wiley-Liss, Inc. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Novartis Inst Biomed Res, Metab & Cardiovasc Dis, Summit, NJ USA. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 134 TC 14 Z9 15 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 2000 VL 51 IS 2 BP 80 EP 93 DI 10.1002/1098-2299(200010)51:2<80::AID-DDR4>3.0.CO;2-E PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 390EA UT WOS:000166281700004 ER PT J AU Coop, A Rice, KC AF Coop, A Rice, KC TI Role of delta-opioid receptors in biological processes SO DRUG NEWS & PERSPECTIVES LA English DT Article ID DISCRIMINATIVE STIMULUS PROPERTIES; MESSAGE-ADDRESS CONCEPT; ANTAGONIST NALTRINDOLE; MORPHINE-TOLERANCE; (+)-4-<(ALPHA-R)-ALPHA-((2S,5R)-4-ALLYL-2,5-DIMETHYL-1-PIPERAZINYL)-3-ME THOXYBE.; PHARMACOLOGICAL CHARACTERIZATION; PHYSICAL-DEPENDENCE; MEDIATED PHENOMENA; PLACE PREFERENCE; AGONIST BW373U86 AB Agonists at the delta -opioid receptor were initially investigated as potential analgesic agents that may lack the undesired effects (respiratory depression, constipation, dependence) of mu -opioid agonists such as morphine. These studies have, however, uncovered that the delta -opioid system is involved in many biological processes, and thus delta -opioid-based medications have great therapeutic potential for the treatment of a wide variety of disorders. (C) 2000 Prous Science. All rights reserved. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21244 USA. Univ Maryland, Coll Problems Drug Abuse, Drug Evaluat Comm, Baltimore, MD 21244 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 98 TC 28 Z9 33 U1 0 U2 1 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD OCT PY 2000 VL 13 IS 8 BP 481 EP 487 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 389PC UT WOS:000166246100005 PM 12937621 ER PT J AU Bruce-Keller, AJ Keeling, JL Keller, JN Huang, FF Camondola, S Mattson, MP AF Bruce-Keller, AJ Keeling, JL Keller, JN Huang, FF Camondola, S Mattson, MP TI Antiinflammatory effects of estrogen on microglial activation SO ENDOCRINOLOGY LA English DT Article ID NF-KAPPA-B; PROTEIN-KINASE PATHWAYS; NITRIC-OXIDE; ADHESION MOLECULES; GLIAL-CELLS; TRANSCRIPTION FACTOR; GLUTAMATE TOXICITY; ALZHEIMERS-DISEASE; IMMUNE-RESPONSES; MESSENGER-RNA AB In the present study the effects of 17 beta-estradiol on microglial activation are described. Estrogen replacement therapy has been associated with decreased severity of age-related neurodegenerative diseases such as Alzheimer's disease, and estrogens have potent immunosuppressive properties outside of the brain. To determine the role that microglial cells might play in estrogen-mediated neuroprotection, primary rat microglia and N9 microglial cell lines were treated with increasing doses of 17 beta-estradiol before or during immunostimulation by lipopolysaccharide, phorbol ester, or interferon-gamma. Pretreatment with 17 beta-estradiol, but not 17 alpha-estradiol or progesterone, dose dependently attenuated microglial superoxide release and phagocytic activity. Additionally, 17 beta-estradiol attenuated increases in inducible nitric oxide synthase protein expression, but did not alter nuclear factor-kappa B activation. The antiinflammatory effects of 17 beta-estradiol were blocked by the antiestrogen ICI 182,780. Additionally, 17 beta-estradiol induced rapid phosphorylation of the p42/p44 mitogen-activated protein kinase (MAP kinase), and the MAP kinase inhibitor PD 98059 blocked the antiinflammatory effects of 17 beta-estradiol. Overall, these results suggest that estrogen receptor-dependent activation of MAP kinase is involved in estrogen-mediated antiinflammatory pathways in microglial cells. These results describe a novel mechanism by which estrogen may attenuate the progression of neurodegenerative disease and suggest new pathways for therapeutic intervention in clinical settings. C1 Univ Kentucky, Albert B Chandler Med Ctr Mn 210, Dept Neurobiol & Anat, Lexington, KY 40536 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Bruce-Keller, AJ (reprint author), Univ Kentucky, Albert B Chandler Med Ctr Mn 210, Dept Neurobiol & Anat, Lexington, KY 40536 USA. EM abruce@pop.uky.edu RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG16429-01]; NINDS NIH HHS [NS39398-01] NR 58 TC 211 Z9 220 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2000 VL 141 IS 10 BP 3646 EP 3656 DI 10.1210/en.141.10.3646 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 355PV UT WOS:000089394800016 PM 11014219 ER PT J AU Olden, K Newbold, RR AF Olden, K Newbold, RR TI Women's health and the environment in the 21st century SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE autoimmune diseases; breast cancer; endocrine disrupters; endometriosis; environmental estrogens; environmental exposures; gender differences; health disparity; osteoporosis; uterine leiomyoma; women's health ID SUSCEPTIBILITY; BREAST AB For many years, the National Institute of Environmental Health Sciences has been a leader in studying the role of environmental factors in the causation of diseases that are particularly prevalent or unique to women. As we enter the next millennium, we face exciting new possibilities in broadening-our understanding of how the environment impacts women's health. Sophisticated new technology and scientific information are now available to help us more precisely define environmental contributions to disease. Moreover, further development of our information base in environmental health sciences will usher in a new era of informed preventive care for women of all ages. The hallmark of this new era will be our ability to finally address the etiology and prevention of disease, rather than simply focusing on treatment and management of human illness. C1 NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Off Director, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Toxicol Lab, Environm Toxicol Program, MD E4-02,POB 12233, Res Triangle Pk, NC 27709 USA. NR 7 TC 5 Z9 5 U1 0 U2 0 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 OCT PY 2000 VL 108 SU 5 BP 767 EP 768 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366HT UT WOS:000090000500001 PM 11035979 ER PT J AU Newbold, RR DiAugustine, RP Risinger, JI Everitt, JI Walmer, DK Parrott, EC Dixon, D AF Newbold, RR DiAugustine, RP Risinger, JI Everitt, JI Walmer, DK Parrott, EC Dixon, D TI Advances in uterine leiomyoma research: Conference overview, summary, and future research recommendations SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Conference on Womens Health and the Environment CY OCT 07-08, 1999 CL RES TRIANGLE PK, NORTH CAROLINA DE conference summary; overview; research recommendations; uterine leiomyoma ID GROWTH-FACTOR-I; GUINEA-PIG MODEL; FACTOR HMGI-C; ARCHITECTURAL FACTOR; GENE-EXPRESSION; TRANSGENIC MICE; DIETHYLSTILBESTROL; ESTRADIOL; UTERUS; MOUSE AB Uterine leiomyomas (fibroids, myomas) are the most common tumors occurring in the genital tract of women over 30 years of age. These benign uterine smooth-muscle tumors are estimated to be clinically significant in at least 25% of the American female population during their reproductive years. Furthermore, when thorough pathologic examination of hysterectomy specimens has been performed in patients with or without clinical history of myomatous uteri, the incidence of fibroids is 77%. suggesting that these tumors are far more prevalent than estimated by clinical cases. In spite of their high prevalence, little is known concerning the etiology or the molecular basis of their development and growth. It is well known that leiomyoma growth is regulated by ovarian steroid hormones, yet the exact molecular pathway(s) involved in tumor growth and the role of genetic susceptibility/predisposition and the environment are unclear. This article is an overview of some of the topics addressed at the conference on Women's Health and the Environment: The Next Century-Advances in Uterine Leiomyoma Research. A summary of research needs and recommendations for future research directions based on conference discussions are also presented. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. NICHHD, Bethesda, MD 20892 USA. RP Dixon, D (reprint author), NIEHS, POB 12233,111 alexander Dr,Bldg 101, Res Triangle Pk, NC 27709 USA. OI Everitt, Jeffrey/0000-0003-0273-6284 NR 63 TC 27 Z9 28 U1 1 U2 2 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 OCT PY 2000 VL 108 SU 5 BP 769 EP 773 DI 10.2307/3454304 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366HT UT WOS:000090000500002 PM 11035980 ER PT J AU Dixon, D He, H Haseman, JK AF Dixon, D He, H Haseman, JK TI Immunohistochemical localization of growth factors and their receptors in uterine leiomyomas and matched myometrium SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Conference on Womens Health and the Environment CY OCT 07-08, 1999 CL RES TRIANGLE PK, NORTH CAROLINA DE growth factors/receptors; immunohistochemistry; leiomyomas; myometrium; uterus ID MESSENGER-RIBONUCLEIC-ACID; SMOOTH-MUSCLE CELLS; INSULIN-LIKE; FACTOR-I; BREAST-CANCER; FACTOR-BETA; EXPRESSION; BINDING; TISSUES; WOMEN AB Immunolocalization of transforming growth factor alpha (TGF-alpha), epidermal growth factor (EGF), insulinlike growth factor (IGF)-I, vascular endothelial growth factor (VEGF(165,189,121)), basic fibroblast growth factor (FGF)-2, EGF receptor (R), IGF-IR beta, and FGFR-1 was studied in uterine leiomyomas and matched myometrial samples taken from seven women (42-47 years of age) in the proliferative phase of the menstrual cycle. Immunolocalization of growth factor peptides was accomplished with either monoclonal or polyclonal antibodies to the amino or carboxy terminus of growth factor peptides or their respective receptors, or against full-length recombinant growth factor. All reactions were conducted using the avidin-biotin complex method. Immunolocalization of TGF-alpha, EGF, EGF-R, IGF-I, IGF-IR beta, FGF-2, FGFR-1, and VEGF was observed in the cytoplasm of smooth-muscle cells of leiomyomas and matched myometrium. The cytoplasm of vascular smooth-muscle cells expressed TGF-alpha, EGF, EGF-R, IGF-I, IGF-IR beta, FGF-2, FGFR-1, and VEGF, whereas the vascular endothelium was positive for TGF-alpha, EGF, EGF-R, FGF-2, and FGFR-1 in both leiomyomas and matched myometria. Fibroblasts within the fibrous component of some leiomyomas were positive for IGF-I and FGF-2 and minimally positive for FGFR-1. In addition, the extracellular matrix of leiomyomas showed focal localization of FGF-2 and IGF-I in some tumors. When scores of intensity and percent positive staining were compared, IGF-IR beta was significantly increased in the leiomyomas compared to matched myometria, whereas EGF was significantly decreased in the uterine leiomyomas compared to matched myometria. In summary, these data revealed growth factors to be expressed differentially in smooth muscle, vascular and fibroblastic cell types of leiomyomas and matched myometria. Specifically, IGF-IR beta was significantly increased in leiomyomas; although a similar increase was seen with IGF-I peptide, statistical significance was not achieved. The EGF peptide was significantly decreased in the leiomyomas compared to matched myometrium. These data suggest that IGF-IR beta and IGF-I peptide may be one of several growth factor/receptor pathways important in uterine leiomyoma growth during the proliferative phase of the menstrual cycle. In addition, decreased EGF may be secondary to the predominant estrogenic milieu present at time of sampling, as it has been proposed that progesterone, and not estrogen, may regulate EGF. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dixon, D (reprint author), NIEHS, Lab Expt Pathol, POB 12233,MDC2-09,Rm C254,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 31 TC 52 Z9 57 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 OCT PY 2000 VL 108 SU 5 BP 795 EP 802 DI 10.2307/3454309 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366HT UT WOS:000090000500007 PM 11035985 ER PT J AU Cesen-Cummings, K Copland, JA Barrett, JC Walker, CL Davis, BJ AF Cesen-Cummings, K Copland, JA Barrett, JC Walker, CL Davis, BJ TI Pregnancy, parturition, and prostaglandins: Defining uterine leiomyomas SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Conference on Womens Health and the Environment CY OCT 07-08, 1999 CL RES TRIANGLE PK, NORTH CAROLINA DE cyclooxygenase; differentiation; parturition; prostaglandins; uterine leiomyoma ID MESSENGER-RIBONUCLEIC-ACID; REPRODUCTIVE-TRACT LEIOMYOMATA; SMOOTH-MUSCLE CELLS; HUMAN MYOMETRIUM; GENE-EXPRESSION; ESTROUS-CYCLE; RAT UTERUS; OXYTOCIN RECEPTORS; CORPUS-LUTEUM; GROWTH ARREST AB Leiomyomas, benign smooth muscle tumors of the uterus, are the most common gynecologic neoplasm in women. Studies with surgically resected human tissues and primary cultures have revealed that several genes are differentially expressed in leiomyomas compared to matched normal myometrium. An estrogen-driven pattern of gene expression in leiomyomas, similar to that seen in normal myometrium during pregnancy and parturition, is associated with a persistent inappropriate response of neoplastic myometrial smooth muscle cells to ovarian hormones. This is possibly due to aberrant expression levels or signaling via estrogen and progesterone receptors. We propose the hypothesis that uterine leiomyomas mimic a differentiated myometrial cell at pregnancy and exhibit a hypersensitivity to sex steroid hormones that prevents the cells from responding to normal apoptotic or dedifferentiation signals and from returning to a nongravid phenotype. Support of this hypothesis is derived from experimental studies in female Eker rats that develop uterine leiomyomas with many similarities to the human disease. Our hypothesis accounts for the benign nature of these tumors and their high incidence in women during the reproductive years. By identifying the factors that participate in parturition and involution of the pregnant myometrium, we may better define uterine leiomyomas and thus identify novel targets for therapeutic strategies to treat these tumors. C1 NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Davis, BJ (reprint author), NIEHS, Lab Womens Hlth, POB 12233,MD B3-06, Res Triangle Pk, NC 27709 USA. NR 59 TC 17 Z9 17 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 OCT PY 2000 VL 108 SU 5 BP 817 EP 820 DI 10.2307/3454312 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366HT UT WOS:000090000500010 PM 11035988 ER PT J AU Schwartz, SM Marshall, LM Baird, DD AF Schwartz, SM Marshall, LM Baird, DD TI Epidemiologic contributions to understanding the etiology of uterine leiomyomata SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Conference on Womens Health and the Environment CY OCT 07-08, 1999 CL RES TRIANGLE PK, NORTH CAROLINA DE epidemiology; etiology; risk factors; uterine leiomyomata ID REPRODUCTIVE-AGE WOMEN; ORAL-CONTRACEPTIVE USE; PREMENOPAUSAL WOMEN; UNITED-STATES; MENSTRUAL-CYCLE; CIGARETTE-SMOKING; RISK-FACTORS; FIBROIDS; MYOMAS; HYSTERECTOMY AB Uterine leiomyomata are hormonally dependent tumors that are a major source of gynecologic morbidity among women of reproductive age. Relatively few studies have attempted to identify specific risk factors for these neoplasms. In this review of epidemiologic contributions to the etiology of uterine leiomyomata, we begin by outlining methodologic issues in epidemiologic studies that arise from the fact that a large proportion of uterine leiomyomata does not come to medical attention. We then review the major findings from published epidemiologic studies, which to date have focused primarily on menstrual and childbearing history, exogenous hormone use, obesity. cigarette smoking, and other lifestyle and behavioral characteristics that may in part reflect aspects of a woman's hormonal milieu. None of the potential risk factors studied have demonstrated sufficiently consistent associations' to guide decisions on the primary prevention of uterine leiomyomata. Clarifying the etiology and natural history of uterine leiomyomata will require studies designed to address methodologic issues and test hypotheses involving environmental and lifestyle influences on endocrine function, as well as on other possible etiologic mechanisms. Recent advances in molecular genetics present opportunities for epidemiologic studies of uterine leiomyomata to incorporate biomarkers of somatic changes found in these tumors and to examine inherited genetic factors related to possible causal physiologic mechanisms. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Oregon Hlth Div, Portland, OR USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Schwartz, SM (reprint author), 1100 Fairview Ave N MP-381,POB 19024, Seattle, WA 98109 USA. OI Baird, Donna/0000-0002-5544-2653 FU NICHD NIH HHS [R01 HD029819-04, HD 29819, R01 HD029819]; NIEHS NIH HHS [ES 08305] NR 61 TC 79 Z9 84 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2000 VL 108 SU 5 BP 821 EP 827 DI 10.2307/3454313 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366HT UT WOS:000090000500011 PM 11035989 ER PT J AU Kohn, MC AF Kohn, MC TI Current directions in physiological modeling for environmental health sciences: An overview SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID MULTICOMPARTMENT GEOMETRIC MODEL; RISK ASSESSMENT; PHARMACOKINETIC MODELS; METHYLENE-CHLORIDE; MECHANISTIC MODEL; EPOXIDE HYDRASE; GAS UPTAKE; RAT; BUTADIENE; SIMULATION C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Kohn, MC (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233,MD A3-06, Res Triangle Pk, NC 27709 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2000 VL 108 SU 5 BP 857 EP 859 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366HT UT WOS:000090000500017 PM 11035995 ER PT J AU Kohn, MC Melnick, RL AF Kohn, MC Melnick, RL TI The privileged access model of 1,3-butadiene disposition SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE 1,3-butadiene; enzymatic channeling; metabolic mechanisms; PBPK modeling ID SPRAGUE-DAWLEY RATS; LUNG IN-VITRO; INHALATION PHARMACOKINETICS; BUTADIENE MONOXIDE; SPECIES-DIFFERENCES; B6C3F1 MICE; GAS UPTAKE; GLUTATHIONE CONJUGATION; BLOOD-CONCENTRATIONS; TOXICOKINETIC MODEL AB In previous attempts to model disposition of 1,3-butadiene in mice and rats, parameter values for 1,2-epoxybut-3-ene metabolism were optimized to reproduce elimination of this gas from closed chambers. However, each of these models predicted much higher concentrations of circulating epoxybutene than were subsequently measured in animals exposed to butadiene. To account for this discrepancy, a previous physiologically based pharmacokinetic model of butadiene disposition was modified to describe a transient complex between cytochrome P450 and epoxide hydrolase on the endoplasmic reticulum:membrane. In this model the epoxide products are directly transferred from the P450 to the epoxide hydrolase in competition with release of products into the cytosol. The model includes flow-restricted delivery of butadiene and epoxides to gastrointestinal tract, liver, lung, kidney, fat, other rapidly perfused tissues, and other slowly perfused tissues. Blood was distributed among compartments for arterial, venous, and capillary spaces. Oxidation of butadiene and epoxybutene and hydrolysis and glutathione conjugation of epoxides were included in liver, lung, and kidney. The model reproduces observed uptake of butadiene and epoxybutene from closed chambers by mice and rats and steady-state concentrations of butadiene, epoxybutene, and 1,2;3,4-diepoxybutane concentrations in blood of mice and rats exposed by nose only. Successful replication of these observations indicates that the proposed privileged access of epoxides formed in situ to epoxide hydrolase is a plausible mechanistic representation for the metabolic clearance of epoxide-forming chemicals. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Kohn, MC (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233,Mail Drop A3-06, Res Triangle Pk, NC 27709 USA. NR 50 TC 14 Z9 15 U1 0 U2 0 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 OCT PY 2000 VL 108 SU 5 BP 911 EP 917 DI 10.2307/3454324 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366HT UT WOS:000090000500022 PM 11036000 ER PT J AU Andric, SA Kostic, TS Dragisic, SM Andric, NL Stojilkovic, SS Kovacevic, RZ AF Andric, SA Kostic, TS Dragisic, SM Andric, NL Stojilkovic, SS Kovacevic, RZ TI Acute effects of polychlorinated biphenyl-containing and -free transformer fluids on rat testicular steroidogenesis SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE 3 beta-hydroxysteroid dehydrogenase; androgen; P450c17; polychlorinated biphenyls; progesterone ID PREPUBERTAL FEMALE RATS; LEYDIG-CELLS; PCB CONGENERS; AROCLOR 1254; ACUTE STRESS; ADULT-RATS; 3,4,5,3',4',5'-HEXACHLOROBIPHENYL; CYTOCHROME-P-450; REPRODUCTION; INHIBITION AB Polychlorinated biphenyl (PCB)-based transformer fluids belong to a class of environmentally persistent mixtures with known toxic effects. Here, we studied the acute effects of Askarel (which contains Aroclor 1260) and two substitute transformer fluids (the silicone oil-based DC561 and the mineral oil-based ENOL C) on rat testicular steroidogenesis. Single intraperitoneal (ip; 10 mg/kg body weight) or bilateral intratesticular (itt; 25 mug/testis) injections of Askarel markedly decreased serum androgen levels 24 hr after administration. In acute testicular cultures from these animals, chorionic gonadotropin-stimulated progesterone and androgen productions were severely attenuated. When itt was injected or added in vitro, Askarel inhibited 3 beta -hydroxysteroid dehydrogenase (3 beta HSD), stimulated 17 alpha -hydroxylase/lyase (P450c17), and did not affect 17 beta -hydroxysteroid dehydrogenase in testicular postmitochondrial fractions. The ip-injected Askarel did not affect 3 beta HSD, but inhibited P450c17, suggesting that a more intensive metabolism of peripherally injected Askarel reduces the circulating levels of active ingredients below the threshold needed for inhibition of 3 beta HSD and generates a derivative that inhibits P450c17. In contrast to Askarel, itt-injection (25 mug/testis) of DC561 and ENOL C did not affect in vivo and in vitro steroidogenesis. These findings show the acute effects of Askarel, but not silicone and mineral oils, on testicular steroidogenesis. C1 Fac Sci Novi Sad, Inst Biol, YU-21000 Novi Sad, Serbia, Yugoslavia. NICHHD, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Kovacevic, RZ (reprint author), Fac Sci Novi Sad, Inst Biol, 2 Dositeja Obradovica Sq, YU-21000 Novi Sad, Serbia, Yugoslavia. NR 38 TC 28 Z9 31 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2000 VL 108 IS 10 BP 955 EP 959 DI 10.1289/ehp.00108955 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 367ZP UT WOS:000090093000022 PM 11049815 ER PT J AU Blount, BC Silva, MJ Caudill, SP Needham, LL Pirkle, JL Sampson, EJ Lucier, GW Jackson, RJ Brock, JW AF Blount, BC Silva, MJ Caudill, SP Needham, LL Pirkle, JL Sampson, EJ Lucier, GW Jackson, RJ Brock, JW TI Levels of seven urinary phthalate metabolites in a human reference population SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE exposure; glucuronidase; human; metabolism; phthalates; urine ID BUTYL BENZYL PHTHALATE; PLASTICIZER DI(2-ETHYLHEXYL)PHTHALATE; RATS; EXCRETION; EXPOSURE; SAMPLES AB Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 mug/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 mug/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 mug/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate. Women of reproductive age (20-40 years) were found to have significantly higher levels of monobutyl phthalate, a reproductive and developmental toxicant in rodents, than other age/gender groups (p < 0.005). Current scientific and regulatory attention on phthalates has focused almost exclusively on health risks from exposure to only two phthalates, di-(2-ethylhexyl) phthalate and di-isononyl phthalate. Our findings strongly suggest that health-risk assessments for phthalate exposure in humans should include diethyl, dibutyl, and benzyl butyl phthalates. C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Brock, JW (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, 4770 Buford Highway MS F-17, Atlanta, GA 30341 USA. RI Needham, Larry/E-4930-2011 NR 29 TC 355 Z9 383 U1 8 U2 59 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2000 VL 108 IS 10 BP 979 EP 982 DI 10.1289/ehp.00108979 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 367ZP UT WOS:000090093000026 PM 11049818 ER PT J AU Huff, J Chan, P AF Huff, J Chan, P TI Antitumor effects of THC SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID TRANSGENIC MOUSE MODELS; BODY-WEIGHT; CHEMICAL CARCINOGENESIS; TUMOR-INCIDENCE; TOXICITY; MICE; RISK C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2000 VL 108 IS 10 BP A442 EP A443 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 367ZP UT WOS:000090093000004 PM 11097557 ER PT J AU Kohn, MC Parham, F Masten, SA Portier, CJ Shelby, MD Brock, JW Needham, LL AF Kohn, MC Parham, F Masten, SA Portier, CJ Shelby, MD Brock, JW Needham, LL TI Human exposure estimates for phthalates SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID METABOLISM; RAT; PHARMACOKINETICS; IDENTIFICATION C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. RP Kohn, MC (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010; Needham, Larry/E-4930-2011; masten, scott/R-1403-2016 OI Portier, Christopher/0000-0002-0954-0279; masten, scott/0000-0002-7847-181X NR 11 TC 99 Z9 104 U1 1 U2 12 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 OCT PY 2000 VL 108 IS 10 BP A440 EP A442 DI 10.1289/ehp.108-a440b PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 367ZP UT WOS:000090093000003 PM 11097556 ER PT J AU Beja, O Suzuki, MT Koonin, EV Aravind, L Hadd, A Nguyen, LP Villacorta, R Amjadi, M Garrigues, C Jovanovich, SB Feldman, RA DeLong, EF AF Beja, O Suzuki, MT Koonin, EV Aravind, L Hadd, A Nguyen, LP Villacorta, R Amjadi, M Garrigues, C Jovanovich, SB Feldman, RA DeLong, EF TI Construction and analysis of bacterial artificial chromosome libraries from a marine microbial assemblage SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; RIBOSOMAL-RNA GENES; ESCHERICHIA-COLI; PHYLOGENETIC DIVERSITY; CLASS PROTEOBACTERIA; COMPARATIVE GENOMICS; PLANKTONIC ARCHAEA; ALPHA-SUBCLASS; CLONING; DNA AB Cultivation-independent surveys of ribosomal RNA genes have revealed the existence of novel microbial lineages, many with no known cultivated representatives. Ribosomal RNA-based analyses, however, often do not provide significant information beyond phylogenetic affiliation. Analysis of large genome fragments recovered directly from microbial communities represents one promising approach for characterizing uncultivated microbial species better. To assess further the utility of this approach, we constructed large-insert bacterial artificial chromosome (BAC) libraries from the genomic DNA of planktonic marine microbial assemblages. The BAC libraries we prepared had average insert sizes of approximate to 80 kb, with maximal insert sizes >150 kb. A rapid screening method assessing the phylogenetic diversity and representation in the library was developed and applied. In general, representation in the libraries agreed well with previous culture-independent surveys based on polymerase chain reaction (PCR)-amplified rRNA fragments. A significant fraction of the genome fragments in the BAC libraries originated from as yet uncultivated microbial species, thought to be abundant and widely distributed in the marine environment. One entire BAC insert, derived from an uncultivated, surface-dwelling euryarchaeote, was sequenced completely. The planktonic euryarchaeal genome fragment contained some typical archaeal genes, as well as unique open reading frames (ORFs) suggesting novel function. In total, our results verify the utility of BAC libraries for providing access to the genomes of as yet uncultivated microbial species, Further analysis of these BAC libraries has the potential to provide significant insight into the genomic potential and ecological roles of many indigenous microbial species, cultivated or not. C1 Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Mol Dynam, Sunnyvale, CA 94086 USA. RP DeLong, EF (reprint author), Monterey Bay Aquarium Res Inst, POB 628, Moss Landing, CA 95039 USA. RI Suzuki, Marcelino/D-3329-2009 OI Suzuki, Marcelino/0000-0003-3868-6362 NR 57 TC 228 Z9 248 U1 0 U2 22 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD OCT PY 2000 VL 2 IS 5 BP 516 EP 529 DI 10.1046/j.1462-2920.2000.00133.x PG 14 WC Microbiology SC Microbiology GA 374AU UT WOS:000165322900005 PM 11233160 ER PT J AU Hammerschmidt, K Newman, JD Champoux, M Suomi, SJ AF Hammerschmidt, K Newman, JD Champoux, M Suomi, SJ TI Changes in rhesus macaque 'coo' vocalizations during early development SO ETHOLOGY LA English DT Article ID MACACA-MULATTA VOCALIZATIONS AB In order to test whether 'coo' calls of young rhesus macaques, Macaca mulatta, undergo same modifications during early development, and to explore which factors may influence these changes, we studied the ontogeny of their contact call, the 'coo' call. Vocalizations were recorded during brief periods of social separation. Infants were either raised with their mothers and other conspecifics, or separated from their mothers at birth and housed in a nursery with other infants. We recorded calls uttered in the separation context from 20 infants. We digitized the first 50 calls of a given series and subjected them to a Fourier transform. From each frequency-time spectrum, we extracted 65 acoustic parameters using a software program (LMA 5.9). We then used a cluster analysis to separate the 'coo' calls from other call types. With increasing age, the 'coos' dropped in pitch and became more even. The course of amplitude became more constant and the call duration increased slightly. Nevertheless, we found a high intra-individual variation throughout the 5mo. Neither rearing condition nor sex had any apparent influence on age-related changes in 'coo' structure. With one exception, all parameters that correlated with age could be explained by variation in weight. Therefore, we conclude that growth is the main factor accounting for the observed changes. C1 Deutsch Primatenzentrum, Abt Neurobiol, D-37077 Gottingen, Germany. NICHHD, Bethesda, MD 20892 USA. RP Hammerschmidt, K (reprint author), Deutsch Primatenzentrum, Abt Neurobiol, Kellnerweg 4, D-37077 Gottingen, Germany. NR 30 TC 40 Z9 41 U1 0 U2 4 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0179-1613 J9 ETHOLOGY JI Ethology PD OCT PY 2000 VL 106 IS 10 BP 873 EP 886 DI 10.1046/j.1439-0310.2000.00611.x PG 14 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA 366FL UT WOS:000089994100002 ER PT J AU Hendler, RW Drachev, LA Bose, S Joshi, MK AF Hendler, RW Drachev, LA Bose, S Joshi, MK TI On the kinetics of voltage formation in purple membranes of Halobacterium salinarium SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE photocurrents; electrogenicity; energy-transduction; back-pressure; electrometric measurements ID BACTERIORHODOPSIN PHOTOCYCLE; ELECTRIC SIGNALS; CHROMATOPHORES; ABSORPTION; GENERATION; LIGHT AB The kinetics of the bacteriorhodopsin photocycle, measured by voltage changes in a closed membrane system using the direct electrometrical method (DEM) of Drachev, L.A., Jasaitus, A.A., Kaulen, A.D., Kondrashin, A.A., Liberman, E.A., Nemecek, IB., Ostroumov, S.A., Semenov, Yu, A. & Skulachev, V.P. (1974) Nature 249, 321-324 are sixfold slower than the kinetics obtained in optical studies with suspensions of purple membrane patches. in this study, we have investigated the reasons for this discrepancy. In the presence of the uncouplers carbonyl cyanide m-chlorophenylhydrazone or valinomycin, the rates in the DEM system are similar to the rates in suspensions of purple membrane. Two alternative explanations for the effects of uncouplers were evaluated: (a) the 'back-pressure' of the Delta<(mu)over bar>(H+) slows the kinetic steps leading to its formation, and (b) the apparent difference between the two systems is due to slow major electrogenic events that produce little or no change in optical absorbance. In the latter case, the uncouplers would decrease the RC time constant for membrane capacitance leading to a quicker discharge of voltage and concomitant decrease in photocycle turnover time. The experimental results show that the primary cause for the slower kinetics of voltage changes in the DEM system is thermodynamic back-pressure as described by Westerhoff, H.V. & Dancshazy, Z. (1984) Trends Biochem. Sci. 9, 112-117. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hendler, RW (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 20 TC 12 Z9 12 U1 1 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT PY 2000 VL 267 IS 19 BP 5879 EP 5890 DI 10.1046/j.1432-1327.2000.01620.x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361JC UT WOS:000089719100009 PM 10998047 ER PT J AU Leost, M Schultz, C Link, A Wu, YZ Biernat, J Mandelkow, EM Bibb, JA Snyder, GL Greengard, P Zaharevitz, DW Gussio, R Senderowicz, AM Sausville, EA Kunick, C Meijer, L AF Leost, M Schultz, C Link, A Wu, YZ Biernat, J Mandelkow, EM Bibb, JA Snyder, GL Greengard, P Zaharevitz, DW Gussio, R Senderowicz, AM Sausville, EA Kunick, C Meijer, L TI Paullones are potent inhibitors of glycogen synthase kinase-3 beta and cyclin-dependent kinase 5/p25 SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE Alzheimer's disease; cyclin-dependent kinase 5; glycogen synthase kinase-3; paullones; kinase inhibitors ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-2 MESSENGER-RNA; AU-RICH ELEMENTS; 3' UNTRANSLATED REGION; NF-KAPPA-B; FACTOR-ALPHA; TRANSLATIONAL CONTROL; ACTIVATION PATHWAY; GM-CSF; SEQUENCE AB Paullones constitute a new family of benzazepinones with promising antitumoral properties. They were recently described as potent, ATP-competitive, inhibitors of the cell cycle regulating cyclin-dependent kinases (CDKs). We here report that paullones also act as very potent inhibitors of glycogen synthase kinase-3 beta (GSK-3 beta) (IC50: 4-80 nM) and the neuronal CDK5/p25 (IC50: 20-200 nM). These two enzymes are responsible for most of the hyperphosphorylation of the microtubule-binding protein tau, a feature observed in the brains of patients with Alzheimer's disease and other neurodegenerative 'taupathies'. Alsterpaullone, the most active paullone, was demonstrated to act by competing with ATP for binding to GSK-3 beta. Alsterpaullone inhibits the phosphorylation of tau in vivo at sites which are typically phosphorylated by GSK-3 beta in Alzheimer's disease. Alsterpaullone also inhibits the CDK5/p25-dependent phosphorylation of DARPP-32 in mouse striatum slices in vitro. This dual specificity of paullones may turn these compounds into very useful tools for the study and possibly treatment of neurodegenerative and proliferative disorders. C1 CNRS, Biol Stn, Cell Cycle Grp, F-29682 Roscoff, Bretagne, France. Univ Hamburg, Inst Pharm, Hamburg, Germany. DESY, Max Planck Unit Struct Mol Biol, D-2000 Hamburg, Germany. Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD USA. RP Meijer, L (reprint author), CNRS, Biol Stn, Cell Cycle Grp, BP 74, F-29682 Roscoff, Bretagne, France. RI Link, Andreas/H-5067-2013 OI Link, Andreas/0000-0003-1262-6636 NR 102 TC 262 Z9 268 U1 1 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT PY 2000 VL 267 IS 19 BP 5983 EP 5994 DI 10.1046/j.1432-1327.2000.01673.x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361JC UT WOS:000089719100021 PM 10998059 ER PT J AU Tozser, J Zahuczky, G Bagossi, P Louis, JM Copeland, TD Oroszlan, S Harrison, RW Weber, IT AF Tozser, J Zahuczky, G Bagossi, P Louis, JM Copeland, TD Oroszlan, S Harrison, RW Weber, IT TI Comparison of the substrate specificity of the human T-cell leukemia virus and human immunodeficiency virus proteinases SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE HIV-1 proteinase; HTLV-1 proteinase; molecular modeling; oligopeptide substrates; substrate specificity ID HIV-1 PROTEASE; ESCHERICHIA-COLI; CLEAVAGE SITES; I PROTEASE; AMINO-ACID; INHIBITORS; BINDING; REQUIREMENTS; SUBSITES AB Human T-cell leukemia virus type-1 (HTLV-1) is associated with a number of human diseases. Based on the therapeutic success of human immunodeficiency virus type 1 (HIV-1) PR inhibitors, the proteinase (PR) of HTLV-1 is a potential target for chemotherapy. To facilitate the design of potent inhibitors, the subsite specificity of HTLV-1 PR was characterized and compared to that of HIV-1 PR. Two sets of substrates were used that contained single amino-acid substitutions in peptides representing naturally occurring cleavage sites in HIV-1 and HTLV-1. The original HIV-1 matrix/capsid cleavage site substrate and most of its substituted peptides were not hydrolyzed by the HTLV-1 enzyme, except for those with hydrophobic residues at the P4 and P2 positions. On the other hand, most of the peptides representing the HTLV-1 capsid/nucleocapsid cleavage site were substrates of both enzymes. A large difference in the specificity of HTLV-1 and HIV-1 proteinases was demonstrated by kinetic measurements, particularly with regard to the S4 and S2 subsites, whereas the S1 subsite appeared to be more conserved. A molecular model of the HTLV-1 PR in complex with this substrate was built, based on the crystal structure of the S9 mutant of Rous sarcoma virus PR, in order to understand the molecular basis of the enzyme specificity. Based on the kinetics of shortened analogs of the HTLV-1 substrate and on analysis of the modeled complex of HTLV-1 PR with substrate, the substrate binding site of the HTLV-1 PR appeared to be more extended than that of HIV-1 PR. Kinetic results also suggested that the cleavage site between the capsid and nucleocapsid protein of HTLV-1 is evolutionarily optimized for rapid hydrolysis. C1 Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NCI, Program Struct Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. RP Tozser, J (reprint author), Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, POB 6, H-4012 Debrecen, Hungary. EM tozser@indi.biochem.dote.hu RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU FIC NIH HHS [TW01001]; NIAID NIH HHS [AI4380]; NIGMS NIH HHS [R01 GM062920] NR 43 TC 41 Z9 41 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT PY 2000 VL 267 IS 20 BP 6287 EP 6295 DI 10.1046/j.1432-1327.2000.01714.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363VJ UT WOS:000089858100024 PM 11012683 ER PT J AU Egeler, RM Favara, BE Laman, JD Claassen, E AF Egeler, RM Favara, BE Laman, JD Claassen, E TI Abundant expression of CD40 and CD40-ligand (CD154) in paediatric Langerhans cell histiocytosis lesions SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Langerhans cell histiocytosis; co-stimulatory molecules ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; DENDRITIC CELLS; T-CELLS; CD40-CD40 LIGAND; TNF-ALPHA; CYTOKINES; ACTIVATION; DISEASE; INTERLEUKIN-12 AB The pathogenesis of Langerhans cell histiocytosis (LCH) is obscure, partly because the events leading to activation of Langerhans-like lesional cells (LCH cells) and associated T cells, and the excessive cytokine production by these cells are unknown. The interaction between CD40 on antigen-presenting cells (APC) like Langerhans cells and CD40 ligand (CD40L) (CD154) expressed by activated CD4+ T cells, is essential for the activation of both the APC and the T cells and results in upregulation of APC functions and initiation of immunoreactivity. The effects of CD40-CD40L interaction include increased expression of co-stimulatory and adhesion molecules, proliferation, and production of pro-inflammatory cytokines and proteolytic enzymes, all features of LCH. Using immunohistochemistry, we analysed the irt situ presence of the co-stimulatory molecules CD40 and CD40L in 15 fresh frozen biopsies of LCH lesions in children. The cells producing these molecules were identified by double staining for CD1a on LCH cells and CD3 on T cells. Prominent expression of CD40 by LCH cells and CD40L by T cells was found in all 15 specimens regardless of the source of specimen or characteristics of the patient. The findings of high expression of CD40 and CD40L in all specimens imply a key role for the CD40-CD40L adhesion pathway in the pathogenesis of LCH. Since this interaction is an accessible and realistic target for immunotherapy, these findings prompt speculation on the use of blocking antibodies to CD40 or to CD40L in the treatment of LCH. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Calgary, Dept Oncol & Pediat, Childrens Hosp,So Alberta Childrens Canc Program, Tom Baker Canc Ctr, Calgary, AB, Canada. Leiden Univ, Med Ctr, Dept Pediat Immunol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Hematol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Oncol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Bone Marrow Transplantat, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Autoimmune Dis, NL-2300 RC Leiden, Netherlands. Univ Utah, Dept Pathol, Salt Lake City, UT USA. NIH, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT USA. Erasmus Univ, Dept Immunol, NL-3000 DR Rotterdam, Netherlands. Acad Hosp Dijkzigt, NL-3000 DR Rotterdam, Netherlands. ID DLO Inst Anim Sci & Hlth, Dept Immunol, Lelystad, Netherlands. RP Egeler, RM (reprint author), Univ Calgary, Dept Oncol & Pediat, Childrens Hosp,So Alberta Childrens Canc Program, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 28 TC 37 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 2000 VL 36 IS 16 BP 2105 EP 2110 DI 10.1016/S0959-8049(00)00296-3 PG 6 WC Oncology SC Oncology GA 370RT UT WOS:000165136600019 PM 11044648 ER PT J AU Cho, KH Pezzuto, JM Bolton, JL Steele, VE Kelloff, GJ Lee, SK Constantinou, A AF Cho, KH Pezzuto, JM Bolton, JL Steele, VE Kelloff, GJ Lee, SK Constantinou, A TI Selection of cancer chemopreventive agents based on inhibition of topoisomerase II activity SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE topoisomerase I; topoisomerase II; chemoprevention; unknotting assay; relaxation assay; organoselenium; carcinogenesis; selectivity; specificity; predictive value ID ACID PHENETHYL ESTER; MAMMARY-CANCER; CELL-DIFFERENTIATION; LEUKEMIA-CELLS; DNA; GENISTEIN; CARCINOGENESIS; INDUCTION; TUMORIGENICITY; RESVERATROL AB The present study was undertaken to determine if in vitro inhibition of one or both of the two most dominant mammalian DNA topoisomerases (topos) is common among chemopreventive agents. To determine if an agent was a topo I inhibitor, we employed the DNA relaxation and nicking assays. For potential topo II inhibitors, we used the DNA unknotting and linearisation assays. 14 of 30 agents (47%) were ineffective in all four assays (IC50 > 100 mug/ml), and 11 (37%) inhibited topo II catalytic activity. The sensitivity of the topo II assay was 63%, selectivity 93%, positive predictive value 91%. and total accuracy 77%. For chemopreventive efficacy, the positive predictive value of the unknotting assay was 92%, and the total accuracy was 60%. These data suggest that reduced topo II activity is a desirable property of many known chemopreventive agents. We conclude that the unknotting assay could be a valuable addition to the in vitro tests presently used to select chemopreventive agents. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Illinois, Coll Med, Dept Surg Oncol, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. NCI, Chemoprevent Branch, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Pharm, Seodaemun Ku, Seoul 120750, South Korea. RP Constantinou, A (reprint author), Univ Illinois, Coll Med, Dept Surg Oncol, 840 S Wood St, Chicago, IL 60612 USA. OI Constantinou, Andreas/0000-0003-0365-1821 FU NCI NIH HHS [N01-CN-55136, P01 CA48112, R01 CA62184] NR 41 TC 35 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 2000 VL 36 IS 16 BP 2146 EP 2156 DI 10.1016/S0959-8049(00)00300-2 PG 11 WC Oncology SC Oncology GA 370RT UT WOS:000165136600025 PM 11044654 ER PT J AU De Rosa, SC Zaretsky, MD Dubs, JG Roederer, M Anderson, M Green, A Mitra, D Watanabe, N Nakamura, H Tjioe, I Deresinski, SC Moore, WA Ela, SW Parks, D Herzenberg, LA Herzenberg, LA AF De Rosa, SC Zaretsky, MD Dubs, JG Roederer, M Anderson, M Green, A Mitra, D Watanabe, N Nakamura, H Tjioe, I Deresinski, SC Moore, WA Ela, SW Parks, D Herzenberg, LA Herzenberg, LA TI N-acetylcysteine replenishes glutathione in HIV infection SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE glutathione; GSH; GSH deficiency; HIV; N-acetylcysteine; NAC ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACETYL-L-CYSTEINE; OXIDATIVE STRESS; T-CELLS; KAPPA-B; INTRACELLULAR GLUTATHIONE; PARKINSONS-DISEASE; SEROPOSITIVE INDIVIDUALS; CEREBROSPINAL-FLUID; POSITIVE PATIENTS AB Background Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. Design Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks. Subjects HIV-infected, low GSH, CD4 T cells < 500 L-1, no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors. Results Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAG-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and beta2-microglobulin levels, also increased in the NAG-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion. Conclusion. NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes. C1 Stanford Univ, Sch Med, Dept Genet, Beckman Ctr, Stanford, CA 94305 USA. Univ Calif Berkeley, Berkeley, CA USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Univ Tokyo, Tokyo, Japan. Kyoto Univ, Inst Viral Res, Kyoto, Japan. RP De Rosa, SC (reprint author), Stanford Univ, Sch Med, Dept Genet, Beckman Ctr, B007, Stanford, CA 94305 USA. EM leeherz@darwin.stanford.edu RI Roederer, Mario/G-1887-2011 FU NCI NIH HHS [CA42509, CA81543] NR 100 TC 126 Z9 128 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD OCT PY 2000 VL 30 IS 10 BP 915 EP 929 DI 10.1046/j.1365-2362.2000.00736.x PG 15 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 368TG UT WOS:000090133200012 PM 11029607 ER PT J AU Sarantaus, L Huusko, P Eerola, H Launonen, V Vehmanen, P Rapakko, K Gillanders, E Syrjakoski, K Kainu, T Vahteristo, P Krahe, R Paakkonen, K Hartikainen, J Blomqvist, C Lopponen, T Holli, K Ryynanen, M Butzow, R Borg, A Arver, BW Holmberg, E Mannermaa, A Kere, J Kallioniemi, OP Winqvist, R Nevanlinna, H AF Sarantaus, L Huusko, P Eerola, H Launonen, V Vehmanen, P Rapakko, K Gillanders, E Syrjakoski, K Kainu, T Vahteristo, P Krahe, R Paakkonen, K Hartikainen, J Blomqvist, C Lopponen, T Holli, K Ryynanen, M Butzow, R Borg, A Arver, BW Holmberg, E Mannermaa, A Kere, J Kallioniemi, OP Winqvist, R Nevanlinna, H TI Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE BRCA1; BRCA2; haplotype; founder mutations; breast cancer; ovarian cancer ID BREAST-CANCER FAMILIES; GERMLINE MUTATIONS; PHENOTYPE ANALYSIS; LOW PROPORTION; GENE; HAPLOTYPE; MAP; CANDIDATE; DISEASES; LINKAGE AB In the Finnish breast and ovarian cancer families six BRCA1 and five BRCA2 mutations have been found recurrently. Some of these recurrent mutations have also been seen elsewhere in the world, while others are exclusively of Finnish origin. A haplotype analysis of 26 Finnish families carrying a BRCA1 mutation and 20 families with a BRCA2 mutation indicated that the carriers of each recurrent mutation have common ancestors. The common ancestors were estimated to trace back to 7-36 generations (150-800 years). The time estimates and the geographical clustering of these founder mutations in Finland are in concordance with the population history of this country. Analysis of the cancer phenotypes showed differential ovarian cancer expression in families carrying mutations in the 5' and 3' ends of the BRCA1 gene, and earlier age of ovarian cancer onset in families with BRCA1 mutations compared with families with BRCA2 mutations. The identification of prominent and regional BRCA1 and BRCA2 founder mutations in Finland will have significant impact on diagnostics in Finnish breast and ovarian cancer families. An isolated population with known history and multiple local founder effects in multigenic disease may offer distinct advantages also for mapping novel predisposing genes. C1 Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00029 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00029 Helsinki, Finland. Univ Oulu, Dept Clin Genet, Oulu, Finland. Oulu Univ Hosp, Oulu, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Tampere Univ Hosp, Dept Oncol, Tampere, Finland. Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland. Univ Helsinki, Finnish Genome Ctr, FIN-00014 Helsinki, Finland. Kuopio Univ Hosp, Dept Gynecol, Clin Genet Unit, Kuopio, Finland. Univ Kuopio, FIN-70211 Kuopio, Finland. Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. Karolinska Hosp, CMM2, Dept Clin Genet, Stockholm, Sweden. Karolinska Hosp, CMM2, Inst Mol Med, Stockholm, Sweden. Norrland Univ Hosp, Dept Clin Genet, Umea, Sweden. RP Nevanlinna, H (reprint author), Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Haartmaninkatu 2, FIN-00029 Helsinki, Finland. RI Kere, Juha/A-9179-2008; Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; Hartikainen, Jaana/E-6256-2015 OI Kere, Juha/0000-0003-1974-0271; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; NR 32 TC 45 Z9 47 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD OCT PY 2000 VL 8 IS 10 BP 757 EP 763 DI 10.1038/sj.ejhg.5200529 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 365FM UT WOS:000089938600005 PM 11039575 ER PT J AU Saeki, H Wu, MT Olasz, E Hwang, ST AF Saeki, H Wu, MT Olasz, E Hwang, ST TI A migratory population of skin-derived dendritic cells expresses CXCR5, responds to B lymphocyte chemoattractant in vitro, and co-localizes to B cell zones in lymph nodes in vivo SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE chemokine; dendritic cell; lymph node; B cell ID PROTEIN-COUPLED RECEPTOR; IN-VIVO; LANGERHANS CELLS; T-CELLS; CHEMOKINE; MATURE; DIFFERENTIATION; FOLLICLES; CCR7; ORGANS AB Chemokine receptors on dendritic cells (DC) and chemokines within lymph nodes (LN) contribute to trafficking of DC to appropriate sites within the LN. Here we show that DC that have migrated out of skin ex vivo (migratory DC, migDC) express 50-fold more CXCR5 mRNA than fresh Langerhans cells and migrate in response to B lymphocyte chemoattractant (BLC) in vitro. When injected into the footpad of mice, migDC emigrate to regional LN where up to 40 % are found in B cell zones. By contrast, murine bone marrow-derived DC display 14-fold less CXCR5, do not migrate to BLC in vitro, and migrate strictly to T cell zones in LN. We propose that activated skin DC utilize CXCR5 and BLC as a possible mechanism to home to B cell zones of LN. where they may have direct effects on B cells. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, Bldg 10,Rm 12N246,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. NR 28 TC 37 Z9 43 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2000 VL 30 IS 10 BP 2808 EP 2814 DI 10.1002/1521-4141(200010)30:10<2808::AID-IMMU2808>3.0.CO;2-K PG 7 WC Immunology SC Immunology GA 365YN UT WOS:000089978200009 PM 11069061 ER PT J AU Pandeya, SN Yogeeswari, P Stables, JP AF Pandeya, SN Yogeeswari, P Stables, JP TI Synthesis and anticonvulsant activity of 4-bromophenyl substituted aryl semicarbazones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE semicarbazones; electroshock; pentylenetetrazole; strychnine; neurotoxicity; pentobarbitone ID ANTIEPILEPTIC DRUG DEVELOPMENT; MAXIMAL ELECTROSHOCK SCREEN; AGENTS; RATS AB A number of 4-bromophenyl semicarbazones were synthesised and evaluated for anticonvulsant and sedative-hypnotic activities. After intraperitoneal injection to mice, the semicarbazone derivatives were examined in the maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY) and neurotoxicity (NT) screens. All the compounds showed anticonvulsant activity in one or more test models. Compound 12 showed greatest activity, being active in all the screens with very low neurotoxicity and no sedative-hypnotic activity. All the compounds except 7 had lower neurotoxicity compared to phenytoin. Three compounds (6, 11 and 14) showed greater protection than sodium valproate. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 Banaras Hindu Univ, Inst Technol, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India. NIH, Epilepsy Branch, Preclin Pharmacol Branch, Bethesda, MD 20892 USA. RP Pandeya, SN (reprint author), Banaras Hindu Univ, Inst Technol, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India. NR 23 TC 96 Z9 102 U1 0 U2 4 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD OCT PY 2000 VL 35 IS 10 BP 879 EP 886 DI 10.1016/S0223-5234(00)01169-7 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 382CL UT WOS:000165800800001 PM 11121613 ER PT J AU D'Agata, V Grimaldi, M Pascale, A Cavallaro, S AF D'Agata, V Grimaldi, M Pascale, A Cavallaro, S TI Regional and cellular expression of the parkin gene in the rat cerebral cortex SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE autosomal recessive juvenile parkinsonism; cortex; neurons; Parkinson's disease; type I astrocytes ID RECESSIVE JUVENILE PARKINSONISM; HOMOZYGOUS DELETIONS; JAPANESE FAMILIES; EARLY-ONSET; MUTATIONS; DISEASE AB A mutation in the parkin gene has been identified as the cause for an autosomal recessively inherited form of early onset Parkinson's disease. We have recently isolated the mRNA coding for the rat homologue of parkin and showed its widespread expression in the central nervous system (CNS) by in situ hybridization. In the present study we investigated the distribution of parkin in the rat cerebral cortex with a polyclonal antibody that reacts with a single similar to 52-kDa protein, corresponding to the predicted molecular mass of parkin. Conventional light microscopic studies revealed intense parkin immunoreactivity (IR) throughout the cortex. Examination of mixed cortical neuro-glial cultures by indirect immunofluorescence technique coupled to traditional epifluorescence and confocal microscopy analysis demonstrated the expression of parkin in the cytoplasm and neurites of neurons, and its absence in glial fibrillary acidic protein (GFAP)-positive astrocytes. The predominant neuronal parkin-IR and -mRNA expression was confirmed by Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR), respectively, performed on highly enriched neuronal and type I astrocytes cultures. The information gathered in our study about the cellular and subcellular distribution of parkin should facilitate further research on its physiological role in the nervous system. C1 Italian Natl Res Council, Inst Bioimaging & Pathophysiol Cent Vervous Syst, I-95123 Catania, Italy. IRCCS, Oasi Inst Res Mental Retardat & Brian Aging, Troina, Italy. NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Cavallaro, S (reprint author), CNR, Ist Bioimmagini & Fisiopatol Sistema Nervoso Cent, Piazza Roma 2, I-95123 Catania, Italy. RI D'Agata, Velia/F-3622-2010; Cavallaro, Sebastiano/F-3104-2010; OI D'Agata, Velia/0000-0003-1114-8265; Cavallaro, Sebastiano/0000-0001-7590-1792; Grimaldi, Maurizio/0000-0002-7331-7055 NR 18 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2000 VL 12 IS 10 BP 3583 EP 3588 DI 10.1046/j.1460-9568.2000.00244.x PG 6 WC Neurosciences SC Neurosciences & Neurology GA 363XL UT WOS:000089862900015 PM 11029628 ER PT J AU Koch, R Friedman, E Azen, C Hanley, W Levy, H Matalon, R Rouse, B Trefz, F Waisbren, S Michals-Matalon, K Acosta, P Guttler, F Ullrich, K Platt, L de la Cruz, F AF Koch, R Friedman, E Azen, C Hanley, W Levy, H Matalon, R Rouse, B Trefz, F Waisbren, S Michals-Matalon, K Acosta, P Guttler, F Ullrich, K Platt, L de la Cruz, F TI The international collaborative study of maternal phenylketonuria: status report 1998 SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Workshop on PKU Today and Tommorrow - Evidence Based Clinical Practice CY NOV 18-20, 1998 CL FULDA, GERMANY SP SHS, Gesell Klin Ernahrung mbH DE maternal phenylketonuria; phenylalanine; collaborative study AB The Maternal Phenylketonuria Study began in 1984 and during the intervening years, 572 pregnancies in hyperphenylalaninemic women and 99 controls and their outcomes have been evaluated. Among hyperphenylalaninemic women who delivered a live infant, only 15.9% were treated and in metabolic control preconceptually, however, another 18.4% were in control by 10 weeks. Compared to the results reported by Lenke and Levy in 1980, there is a marked improvement in outcome with treatment. Microcephaly was unusual in preconceptually treated pregnancies with well controlled phenylalanine restricted diets. Even in pregnancies that established control after conception but before the 8th week, congenital heart disease did not occur in the offspring, however, it did occur in 12% of pregnancies not achieving control until after 10 weeks of pregnancy. Conclusion The recommended level of blood phenylalanine during pregnancy is 120- 360 mu mol/l. Best results were obtained by close cooperation between the attending obstetrician and a metabolic team experienced in the care of persons with phenylketonuria. C1 Childrens Hosp Los Angeles, Div Med Genet, Los Angeles, CA 90027 USA. Univ So Calif, Dept Pediat, Los Angeles, CA 90027 USA. Hosp Sick Children, PKU Program, Toronto, ON M5G 1X8, Canada. Childrens Hosp & Med Ctr, Boston, MA 02115 USA. Univ Texas, Med Branch, Child Dev Div, Galveston, TX 77550 USA. Childrens Hosp, Reutlingen, Germany. Ross Labs, Columbus, OH 43210 USA. John F Kennedy Inst, DK-2600 Glostrup, Denmark. Univ Hamburg Hosp, Dept Paediat, D-2000 Hamburg, Germany. Univ Calif Los Angeles, Med Ctr, Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Los Angeles, CA 90048 USA. NICHHD, Bethesda, MD 20892 USA. RP Koch, R (reprint author), Childrens Hosp Los Angeles, Div Med Genet, PKU 73,4650 Sunset Blvd, Los Angeles, CA 90027 USA. FU NICHD NIH HHS [N01-HD-2-3149, N01-HD-2-3155, N01-HD-2-3148] NR 9 TC 23 Z9 24 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 OCT PY 2000 VL 159 SU 2 BP S156 EP S160 DI 10.1007/PL00014383 PG 5 WC Pediatrics SC Pediatrics GA 355GL UT WOS:000089377900024 PM 11043164 ER PT J AU Masahiko, N Honkakoski, P AF Masahiko, N Honkakoski, P TI Induction of drug metabolism by nuclear receptor CAR: molecular mechanisms and implications for drug research SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article; Proceedings Paper CT International Symposium on the Induction of Drug Metabolism - From Molecular Mechanisms to Drug Approval CY DEC 09-10, 1999 CL STOCKHOLM, SWEDEN DE drug metabolism; cytochrome P450; induction; gene expression; phenobarbital; nuclear receptor CAR ID PROLIFERATOR-ACTIVATED RECEPTOR; RESPONSIVE ENHANCER MODULE; RAT CYP2B2 GENE; PHENOBARBITAL INDUCTION; X-RECEPTOR; 5'-FLANKING REGION; ENZYME-INDUCTION; TRANSGENIC MICE; IN-VIVO; EXPRESSION AB Recent findings indicate that induction of drug metabolism is regulated by activation of specific members of the nuclear receptor gene family. This minireview deals with the mechanisms by which phenobarbital and phenobarbital-type chemicals induce cytochrome P450 and other genes, and summarises the knowledge on the role of the constitutively active receptor CAR in the induction process. The potential implications of CAR-mediated induction for drug research and possible uses of CAR are also discussed. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland. NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Honkakoski, P (reprint author), Univ Kuopio, Dept Pharmaceut, POB 1627, FIN-70211 Kuopio, Finland. OI Honkakoski, Paavo/0000-0002-4332-3577 NR 42 TC 18 Z9 18 U1 0 U2 1 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 OCT PY 2000 VL 11 IS 4 BP 259 EP 264 DI 10.1016/S0928-0987(00)00112-3 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 368ZD UT WOS:000090146600001 PM 11033069 ER PT J AU Bussey, TJ Dias, R Redhead, ES Pearce, JM Muir, JL Aggleton, JP AF Bussey, TJ Dias, R Redhead, ES Pearce, JM Muir, JL Aggleton, JP TI Intact negative patterning in rats with fornix or combined perirhinal and postrhinal cortex lesions SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE hippocampus; negative patterning; object discrimination; autoshaping; inferotemporal cortex ID CONFIGURAL ASSOCIATION THEORY; HIPPOCAMPAL-FORMATION; OLFACTORY CUES; MEMORY; OBJECT; DISCRIMINATIONS; RECOGNITION; ACQUISITION; TRANSECTION; CHALLENGE AB It has been proposed that the hippocampal formation is necessary for the acquisition of tasks that require the use of configural representations for their solution, including spatial learning and negative patterning. Tests of this influential view have, however, yielded conflicting results. For example fornix or hippocampal lesions, which reliably impair spatial learning, do not reliably impair negative patterning. A problem in interpreting these results has been the lack of controls for factors such as over-responding, excitatory effects of reward, and the possibility of non-configural solutions. At the same time, other studies have pointed to a role in configural learning for parahippocampal regions such as the perirhinal cortex. The present experiments controlled for the above factors and revealed that neither lesions of the fornix nor of the perirhinal/postrhinal cortex in the rat had any effect on negative patterning, although subsequent tests of object and spatial memory demonstrated the functional efficacy of the lesions. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. Univ Wales Coll Cardiff, Sch Psychol, Cardiff CF10 3YG, S Glam, Wales. RP Bussey, TJ (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pearce, John/A-1783-2010; Bussey, Timothy/M-2758-2016; OI Bussey, Timothy/0000-0001-7518-4041; Aggleton, John/0000-0002-5573-1308 NR 38 TC 30 Z9 30 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 2000 VL 134 IS 4 BP 506 EP 519 DI 10.1007/s002210000481 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 366LC UT WOS:000090006000012 PM 11081833 ER PT J AU Lee, JW Chen, QY Rayborn, ME Shadrach, KG Crabb, JW Rodriguez, IR Hollyfield, JG AF Lee, JW Chen, QY Rayborn, ME Shadrach, KG Crabb, JW Rodriguez, IR Hollyfield, JG TI SPACR in the interphotoreceptor matrix of the mouse retina: Molecular, biochemical and immunohistochemical characterization SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retina; interphotorecptor matrix; SPACR; proteoglycan; glycoprotein ID CHONDROITIN-SULFATE PROTEOGLYCAN; EPIDERMAL GROWTH-FACTOR; IMMUNOCYTOCHEMICAL LOCALIZATION; PIGMENT-EPITHELIUM; DERMATAN SULFATE; PROTEINS; DEGENERATION; HYALURONAN; CDNA; PHOTORECEPTORS AB Mouse SPACR cDNA was cloned by screening a mouse retina cDNA library using a PCR probe derived from human SPACR cDNA, Mouse SPACR cDNA comprises 3675 bp containing an open reading frame coding for 742 amino acids. Multitissue Northern blot analysis and in situ hybridization studies indicate that SPACR expression is restricted to retinal photoreceptors. The SPACR core protein was identified with Western blotting following SDS-PAGE with a SPACR C-terminal peptide polyclonal antibody and a chondroitin-6-sulfate Delta disaccharide monoclonal antibody. The 150 kD immunopositive band was isolated, digested with trypsin and the peptides analysed by MALDI mass spectroscopy. Peptide mass mapping confirmed the identity of the 150 kD immunopositive band to be mouse SPACR core protein. Alignment comparisons of the deduced amino acid sequence of mouse and human SPACR show 64 % homology. Like SPACR in the human interphotoreceptor matrix, the mouse orthologue contains a large central mucin-like domain flanked by consensus sites for N-linked oligosaccharide attachment, one EGF-like domain and four hyaluronan-binding motifs. Unlike human SPACR, which contains no conventional consensus sites for glycosaminoglycan attachment, mouse SPACR contains three. Recent biochemical studies of human and mouse SPACR protein indicate that this never interphotoreceptor matrix molecule is a glycoprotein in human and a proteoglycan in the mouse. The presence of consensus sites for glycosaminoglycan attachment in the deduced sequence of mouse SPACR and the absence of these sites in human SPACR provide molecular Verification of our biochemical results, suggesting that differences in post-translational modifications of SPACR may be important in SPACR function in foveate and non-foveate retinas. (C) 2000 Academic Press. C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Hollyfield, JG (reprint author), Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 47 TC 10 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 2000 VL 71 IS 4 BP 341 EP 352 DI 10.1006/exer.2000.0888 PG 12 WC Ophthalmology SC Ophthalmology GA 361KK UT WOS:000089722100002 PM 10995555 ER PT J AU Eberling, JL Pivirotto, P Bringas, J Bankiewicz, KS AF Eberling, JL Pivirotto, P Bringas, J Bankiewicz, KS TI Tremor is associated with PET measures of nigrostriatal dopamine function in MPTP-lesioned monkeys SO EXPERIMENTAL NEUROLOGY LA English DT Article DE MPTP; tremor; Parkinson's disease; PET; primate; dopamine ID POSITRON EMISSION TOMOGRAPHY; PARKINSONS-DISEASE; BRAIN DOPAMINE; REST TREMOR; METABOLISM; SYMPTOMS; PRIMATES; SYSTEM; MODEL AB Unilateral intracarotid artery (ICA) MPTP infusion, along with sequential systemic doses of MPTP, produces near complete degeneration of the nigrostriatal pathway on the side of infusion (ipsilateral) and variable levels of damage in the contralateral hemisphere accompanied by varying levels of parkinsonism (overlesioned hemiparkinsonian model). Positron emission tomography and the dopamine (DA) metabolism tracer [F-18]6-fluoro-L-m-tyrosine (FMT) were used to evaluate the relationship between DA metabolism and clinical features of parkinsonism in 14 overlesioned hemiparkinsonian monkeys. Monkeys were rated on a parkinsonian scale that included ratings of bradykinesia, fine motor skills (FMS), and rest tremor. Because the monkeys tended to show more severe clinical signs on the side of the body contralateral to ICA MPTP infusion, we calculated asymmetry scores for each of the clinical features as well as for FMT uptake (K-i) in the caudate and putamen. Tremor asymmetry was associated with FMT uptake asymmetry in the putamen. No such relationship was observed for FMS or bradykinesia. The overall severity of tremor (mild, moderate/severe) was associated with FMT uptake in the caudate and putamen. Postmortem biochemical analysis for a subset of monkeys showed that the monkeys with moderate/severe tremor had significantly lower DA levels in both caudate and putamen than those with mild tremor. In addition, K-i values were significantly correlated with DA levels in both caudate and putamen. These findings support the idea that nigrostriatal degeneration contributes to rest tremor. (C) 2000 Academic Press. C1 Lawrence Berkeley Lab, Ctr Funct Imaging, Berkeley, CA 94720 USA. Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. NINDS, Mol Therapeut Sect, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Eberling, JL (reprint author), Lawrence Berkeley Lab, Ctr Funct Imaging, 1 Cyclotron Rd,Mail Stop 55-121, Berkeley, CA 94720 USA. NR 24 TC 18 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2000 VL 165 IS 2 BP 342 EP 346 DI 10.1006/exnr.2000.7470 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 358FM UT WOS:000089547800013 PM 10993693 ER PT J AU Borlongan, CV AF Borlongan, CV TI Transplantation therapy for Parkinson's disease SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE clinical trials; immunosuppression; intracerebral grafts; neurodegenerative disorders; Parkinson's disease; trophic factors ID PROMOTES FUNCTIONAL RECOVERY; FETAL MESENCEPHALIC TISSUE; CHROMAFFIN CELL-SURVIVAL; EMBRYONIC NIGRAL GRAFTS; CENTRAL-NERVOUS-SYSTEM; INTRASTRIATAL TRANSPLANTATION; VENTRAL MESENCEPHALON; DOPAMINE NEURONS; CYCLOSPORINE-A; SERTOLI CELLS AB This review paper will provide an overview of the advent of neural transplantation therapy and the milestones achieved over the last 20 years for its use in treating Parkinson's disease. A discussion of technical factors that influence the outcome of neural transplantation is presented, with emphasis given on three sections dealing with immunosuppressants, alternative grafts and trophic factors which have recently been the focus of basic research and development of early phase clinical trials. Some views on the clinical assessment of transplanted Parkinson's disease patients are given at the end of the paper, with a synopsis highlighting the importance of basic research in advancing the potential clinical benefits of neural transplantation therapy in the treatment of Parkinson's disease. C1 NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Borlongan, CV (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 67 TC 13 Z9 15 U1 0 U2 1 PU ASHLEY PUBL LTD PI LONDON PA 1ST FL, THE LIBRARY, 1 SHEPHERDS HILL HIGHGATE, LONDON N6 5QJ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD OCT PY 2000 VL 9 IS 10 BP 2319 EP 2330 DI 10.1517/13543784.9.10.2319 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 361KL UT WOS:000089722200008 PM 11060809 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI p53 from complexity to simplicity: mutant p53 stabilization, gain-of-function, and dominant-negative effect SO FASEB JOURNAL LA English DT Review DE prion; dysfunction; cancer therapy; trans-activating function ID WILD-TYPE P53; TUMOR-SUPPRESSOR P53; CELL-CYCLE ARREST; DNA-DAMAGE; TRANSCRIPTIONAL ACTIVATION; COLORECTAL TUMORIGENESIS; SV40-TRANSFORMED CELLS; APOPTOTIC FUNCTION; CANCER-THERAPY; FEEDBACK LOOP AB Increasing the complexity of their models, p53s are stabilized either in order to function (wt p53) or due to the loss of function (mutant p53) with acquiring a mysterious prion-like ability to drive the normal p53 into the abnormal conformation to gain new functions. As already recognized, the loss of trans-activating function leads to a stabilization of mutant p53 because of the disappearance of the p53-inducible proteins, which otherwise directly (Mdm-2) or indirectly (p21) target p53 for degradation. Simplifying further, I will discuss that the loss of function results in a dominant-negative effect and gain-of-function (a dominant-positive effect). Thus, mutant p53 lacking trans-activation function nevertheless may retain the ability to repress transcription due to its competition with numerous transcription factors for their coactivators. When mutant p53 competes with wt p53, the inhibition of the wt p53-dependent transcription is perceived as a dominant-negative effect. Just like trans-repression, a dominant-negative effect requires an excess of p53 and, therefore, a 'dominant'-negative effect is not dominant. Furthermore, the stabilization of an endogenous mt p53 due to the loss of wt functions cannot occur in the presence of the wt p53 allele. Given the inability of mutant p53 to accumulate in the presence of wt p53, a dominant-negative effect does not naturally occur and, not surprisingly, heterozygous mt/wt cells are rare. The detection of a dominant-negative effect simply indicates that mutant p53 indeed has lost its function. Last, since mutant p53 loses some or most but not all activities and accumulates in the absence of wt allele, gain-of-function can be considered as an exaggeration of the remaining functions. Applications to cancer therapy are discussed. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 13 N 226, Bethesda, MD 20892 USA. NR 91 TC 113 Z9 121 U1 0 U2 12 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 OCT PY 2000 VL 14 IS 13 BP 1901 EP 1907 DI 10.1096/fj.99-1078rev PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 359WE UT WOS:000089634400009 PM 11023974 ER PT J AU Salcedo, R Resau, JH Halverson, D Hudson, EA Dambach, M Powell, D Wasserman, K Oppenheim, JJ AF Salcedo, R Resau, JH Halverson, D Hudson, EA Dambach, M Powell, D Wasserman, K Oppenheim, JJ TI Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells SO FASEB JOURNAL LA English DT Article DE chemokines; angiogenesis ID INTERFERON-BETA; INDUCIBLE PROTEIN-10; GROWTH-FACTOR; IFN-BETA; IN-VIVO; ANGIOGENESIS; INTERLEUKIN-8; METASTASIS; IL-8; TUMORIGENICITY AB The basis for the angiogenic effects of CXC chemokines such as interleukin 8 (IL-8) and for angiostatic chemokines such as interferon-inducible protein 10 (IP-10) has been difficult to assess. We recently reported, based on an RNase protection assay, that human umbilical vein endothelial cells (HUVECs) did not express detectable mRNA for the IL-8 receptors CXCR1 and CXCR2. This raised the possibility of heterogeneity of receptor expression by different endothelial cell (ECs) types. Since systemic angiogenesis induced by IL-8 would more likely involve microvessel ECs, we investigated CXC receptor expression on human microvascular dermal endothelial cells (HMECs). By confocal microscopy and immunofluorescence we observed that HMECs consistently expressed high levels of CXCR1 and CXCR4 (mean fluorescence intensity of 261+/-22.1 and 306.2+/-19, respectively) and intermediate levels of CXCR3 and CXCR2 (173.9+/-30.2 and 156+/-30.9, respectively). In contrast, only a small proportion of HUVEC preparations expressed low levels of CXCR1, -2; and -3 (66+/-19.9; 49+/-15, and 81.4+/-17.9, respectively). However, both HMECs and HUVECs expressed equal levels of CXCR4. As expected, HMECs had more potent chemotactic responses to IL-8 than HUVECs, and this was correlated with the levels of IL-8 receptors on the ECs. Antibodies to CXCR1 and CXCR2 each had inhibitory effects on chemotaxis of HMECs to IL-8, indicating that both IL-8 receptors contributed to the migratory response of these cells toward IL-8. Assessment of the functional capacity of CXCR3 unexpectedly revealed that HMECs migrated in response to relatively higher concentrations (100-500 ng/ml) of each of the 'angiostatic' chemokines IP-10, ITAC, and MIG. Despite this, the 'angiostatic' chemokines inhibited the chemotactic response of HMECs to IL-8. IL-8 and SDF-1 alpha but not IP-10 induced calcium mobilization in adherent ECs, suggesting that signaling events associated with calcium mobilization are separable from those required for chemotaxis. Taken together, our data indicated that functional differences among EC types is dependent on the level of the expression of CXC chemokine receptors. Whether this heterogeneity in receptor expression by ECs reflects distinct differentiation pathways remains to be established. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Data Management Serv Inc, ABL BRP, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Data Management Serv Inc, ABL BRP, Div Basic Sci, Frederick, MD 21702 USA. RP Oppenheim, JJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 21-89A, Frederick, MD 21702 USA. NR 34 TC 187 Z9 193 U1 0 U2 3 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 OCT PY 2000 VL 14 IS 13 BP 2055 EP 2064 DI 10.1096/fj.99-0963com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 359WE UT WOS:000089634400025 PM 11023990 ER PT J AU Nagababu, E Chrest, FJ Rifkind, JM AF Nagababu, E Chrest, FJ Rifkind, JM TI The origin of red cell fluorescence caused by hydrogen peroxide treatment SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE erythrocytes; fluorescence; hydrogen peroxide; heme degradation; lipid peroxidation; flow cytometry; hemoglobin; free radicals ID LIPID-PEROXIDATION; OXIDANT STRESS; BLOOD-CELLS; HEMOGLOBIN; ERYTHROCYTES; AUTOXIDATION; SUPEROXIDE; GENERATION; INITIATION; PRODUCTS AB Fluorescence in red cells following hydrogen peroxide treatment has been attributed to lipid peroxidation of the membrane. The putative relationship between Lipid peroxidation and fluorescence was questioned by the finding that BHT and cu-tocopherol, which are thought to inhibit lipid peroxidation, do not inhibit the fluorescence detected by flow cytometry. Furthermore, lipid peroxidation induced in red cells by the Fe(III)-ADP-ascorbate system did not produce fluorescence. These results require an alternative explanation for the hydrogen peroxide-induced fluorescence. A role for reduced hemoglobin is indicated by the inhibition of fluorescence by pretreatment of cells with CO that binds strongly to ferrohemoglobin and nitrite that oxidizes ferrohemoglobin. Our earlier studies have shown the formation of fluorescent heme degradation products during the reaction of purified hemoglobin with hydrogen peroxide, which was also inhibited by CO and nitrite pretreatment. The fluorescence produced in red cells after the addition of hydrogen peroxide can, therefore, be attributed to fluorescent heme degradation products. (C) 2000 Elsevier Science Inc. C1 NIA, Mol Dynam Sect, Baltimore, MD 21224 USA. NIA, Flow Cytometry Unit, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), LCMB, MDS, GRC Bldg,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 24 TC 28 Z9 28 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD OCT 1 PY 2000 VL 29 IS 7 BP 659 EP 663 DI 10.1016/S0891-5849(00)00348-8 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 367VR UT WOS:000090082600009 PM 11033418 ER PT J AU Usdin, TB Wang, TL Hoare, SRJ Mezey, E Palkovits, M AF Usdin, TB Wang, TL Hoare, SRJ Mezey, E Palkovits, M TI New members of the parathyroid hormone/parathyroid hormone receptor family: The parathyroid hormone 2 receptor and tuberoinfundibular peptide of 39 residues SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE neuropeptide; anatomical distribution; peptide purification; nociception; hypothalamus ID PROTEIN-KINASE-C; CYCLASE-ACTIVATING POLYPEPTIDE; MESSENGER-RIBONUCLEIC-ACID; SMOOTH-MUSCLE CELLS; PTH-RELATED PEPTIDE; MULTIPLE G-PROTEINS; VASOACTIVE INTESTINAL POLYPEPTIDE; MEDIAL BASAL HYPOTHALAMUS; GLUCAGON-LIKE PEPTIDE-1; RENIN-RELEASING FACTOR AB The parathyroid hormone (PTH) family currently includes three peptides and three receptors. PTH regulates calcium homeostasis through bone and kidney PTH1 receptors. PTH-related peptide, probably also through PTH1 receptors, regulates skeletal, pancreatic, epidermal, and mammary gland differentiation and bladder and vascular smooth muscle relaxation and has a CNS role that is under investigation. Tuberoinfundibular peptide of 39 residues (TIP39) was recently purified from bovine hypothalamus based on selective PTH2 receptor activation. PTH2 receptor expression is greatest in the CNS, where it is concentrated in limbic, hypothalamic, and sensory areas, especially hypothalamic periventricular neurons, nerve terminals in the median eminence, superficial layers of the spinal cord dorsal horn, and the caudal part of the sensory trigeminal nucleus. It is also present in a number of endocrine cells. Thus TIP39 and PTH2 receptor-influenced functions may range from pituitary and pancreatic hormone release to pain perception. A third PTH-recognizing receptor has been found in zebrafish. C1 NIMH, Genet Lab, Cell Biol Unit, Bethesda, MD 20892 USA. NIND, Basic Neurosci Program, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Genet Lab, Cell Biol Unit, Bldg 36,Room 3D06,36 Convent Dr MSC4094, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 160 TC 35 Z9 36 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD OCT PY 2000 VL 21 IS 4 BP 349 EP 383 DI 10.1006/frne.2000.0203 PG 35 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 364UT UT WOS:000089911900003 PM 11013069 ER PT J AU Ju, DW Yang, Y Tao, Q Song, WG He, L Chen, G Gu, S Ting, CC Cao, X AF Ju, DW Yang, Y Tao, Q Song, WG He, L Chen, G Gu, S Ting, CC Cao, X TI Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity SO GENE THERAPY LA English DT Article DE interleukin-18; tetramer gene therapy; cytosine deaminase ID CYTOTOXIC T-LYMPHOCYTES; CELL RECEPTOR REPERTOIRE; CYTOSINE DEAMINASE GENE; GM-CSF GENE; IN-VIVO; ESCHERICHIA-COLI; PEPTIDE COMPLEXES; ANTIGEN; TUMOR; IL-18 AB To increase the antitumor effects of cytosine deaminase (AdCD) gene therapy and induce more potent antitumor immunity, Th1 cytokine interleukin-18 encoded adenovirus (AdIL18) was combined with adenovirus encoding CD (AdCD) for the therapy of established murine B16 melanoma. combination therapy of the tumor-bearing mice with AdlL18 and AdCD/SFC inhibited the growth of the subcutaneous 816 tumors more significantly, compared with AdlL18 or AdCD/SFC alone. In vivo depletion analysis with anti-CD4, anti-cog or anti-NK 1. 1 McAb illustrated that both CD8(+) T cells and CD4(+) T cells played key roles in the augmented antitumor response of the combined therapy. Peptide/MHC tetramer represents a powerful and general tool for rapid, highly sensitive, and direct analysis of antigen-specific T cells. In this study, we prepared H-2K(b)/TRP2(180-188) tetramer, which was demonstrated to bind H-2K(b)-restricted, 816 melanoma- specific CD8(+) T cells. B16 specific H-2K(b)/TRP2(180188)tetramer was used to stain the tumor-specific CD8(+) T cells and the results showed that CD8(+) tetramer T cells were about 3-5% of the splenic CD8(+) T cells derived from tumor-bearing mice after combined therapy. The CTL cytotoxicity was markedly induced in mice after combined therapy, suggesting efficient induction of tumor-specific CD8(+) T cells after combined gene therapy with AdCD/5FC/AdIL18. IL-18 gene transfer could significantly augment the cytotoxicity of NK cells and macrophages, and increase the production of interleukin-2 and interferon-gamma, as compared with treatments with AdCD/SFC, AdlacZ/5FC or PBS. These data suggested that in vivo IL-18 gene transfer could augment the antitumor effects of CD suicide gene therapy through efficient induction of antitumor immunity. C1 Second Mil Med Univ, Dept Immunol, Shanghai 200433, Peoples R China. NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Cao, X (reprint author), Second Mil Med Univ, Dept Immunol, 800 Xiang Yin Rd, Shanghai 200433, Peoples R China. NR 43 TC 29 Z9 34 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2000 VL 7 IS 19 BP 1672 EP 1679 DI 10.1038/sj.gt.3301291 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 362GL UT WOS:000089770200008 PM 11083476 ER PT J AU Ahuja, HG Felix, CA Aplan, PD AF Ahuja, HG Felix, CA Aplan, PD TI Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations SO GENES CHROMOSOMES & CANCER LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BREAKPOINT CLUSTER REGION; ACUTE MYELOGENOUS LEUKEMIA; THERAPY-RELATED LEUKEMIA; CHROMOSOME-TRANSLOCATION; SECONDARY LEUKEMIAS; NUCLEOPORIN NUP98; IN-VIVO; GENE; CLEAVAGE AB Chromosomal aberrations are frequently associated with therapy-related myelodysplastic syndromes and acute myelogenous leukemia (t-MDS/AML) and are thought to result from exposure to genotoxic drugs, including alkylating agents and DNA topoisomerase II poisons. The NUP98 gene on chromosome band 11p15 is involved in several different chromosomal aberrations that have been associated with t-MDS/AML. We have cloned the translocation breakpoints from two cases of t-MDS harboring a (11;20)(p15;q11). Sequence analysis of the breakpoints from both cases revealed almost perfectly balanced translocations between NUP98 and TOP1. There were no known recombinogenic sequences identified at or near the breakpoints. However, four bp microduplications present at the translocation crossover points suggested that these translocations may have been initiated by 4 bp staggered double-stranded DNA breaks, which are known to be associated with the action of topoisomerase II. Given the history of patient exposure to topoisomerase II poisons, and the fact that these drugs stabilize staggered breaks with a 4 bp overhang, it seems possible that drug-induced topoisomerase II cleavage and subunit exchange was involved in these translocations. These results suggest that NUP98 is a recurrent target for therapy-related malignancies induced by multiagent chemotherapy, and suggest a role for DNA topoisomerase II poisons in the generation of these translocations. Published 2000 Wiley-Liss, Inc.dagger C1 NCI, Dept Genet, Med Branch, Div Clin Sci, Gaithersburg, MD 20877 USA. Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. RP Aplan, PD (reprint author), NCI, Div Clin Sci, Ctr Adv Technol, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. RI Aplan, Peter/K-9064-2016 FU NCI NIH HHS [CA73773, CA16056, CA66140] NR 38 TC 43 Z9 43 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2000 VL 29 IS 2 BP 96 EP 105 DI 10.1002/1098-2264(2000)9999:9999<::AID-GCC1013>3.0.CO;2-T PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 350UV UT WOS:000089120300002 PM 10959088 ER PT J AU Guan, XY Fang, Y Sham, JST Kwong, DLW Zhang, YQ Liang, QW Li, HM Zhou, H Trent, JM AF Guan, XY Fang, Y Sham, JST Kwong, DLW Zhang, YQ Liang, QW Li, HM Zhou, H Trent, JM TI Recurrent chromosome alterations in hepatocellular carcinoma detected by comparative genomic hybridization SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN PROSTATE-CANCER; BREAST-CANCER; OVARIAN-CANCER; ALLELIC LOSS; ALLELOTYPE; DELETION; DISEASE; TUMOR; P53; MUTATION AB Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and has a very poor prognosis. Fifty primary HCC cases have been analyzed in the present study to explore the association between genomic alteration in primary HCC and clinical features. Several recurrent chromosomal abnormalities were identified in this study. The most frequently detected chromosomal gains involved chromosome arms Iq (33/50 cases, 66%), 8q (24/50 cases, 48%), and 20q (10/50 cases, 20%). High-copy-number amplifications involving Iq (4 cases), 8q (3 cases), and 20q (3 cases) were detected, and a minimum overlapping amplified region at 1q12-q22 was identified. The most frequently detected loss of chromosomal material involved 16q (35/50 cases, 70%), 17p (26/50 cases, 52%), 19p (21/50 cases, 42%), 4q (20/50 cases, 40%), 1p(18/50 cases, 36%), 8p(16/50 cases, 32%), and 22q (14/50 cases, 28%). The associations between genomic alterations detected in the present study and clinical features including clinical stage, tumor size, HBV infection, chronic liver disease, and liver cirrhosis were explored. Our CGH results suggest that the gain of 20q and deletion of 8p are late genetic alterations in HCC, because the incidence of these alterations was obviously increased in the advanced clinical stages. Another finding showed that loss of 8p and gain of 8q and 20q are associated with tumor size. The recurrent gain and loss of chromosomal regions identified in this study provide candidate regions that may contain oncogenes or tumor suppressor genes respectively involved in HCC development and progression. (C) 2000 Wiley-Liss, Inc. C1 Univ Hong Kong, Queen Mary Hosp, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. Sun Yat Sen Univ, Inst Canc, Guangzhou, Peoples R China. Sun Yat Sen Univ, Canc Hosp, Guangzhou, Peoples R China. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Guan, XY (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Clin Oncol, Room 118,Professorial Block,Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China. EM xyguan@hkucc.hku.hk RI Kwong, Dora/C-4295-2009; Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 28 TC 127 Z9 138 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2000 VL 29 IS 2 BP 110 EP 116 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 350UV UT WOS:000089120300004 PM 10959090 ER PT J AU Angeloni, D Danilkovitch-Miagkova, A Ivanov, SV Breathnach, R Johnson, BE Leonard, EJ Lerman, MI AF Angeloni, D Danilkovitch-Miagkova, A Ivanov, SV Breathnach, R Johnson, BE Leonard, EJ Lerman, MI TI Gene structure of the human receptor tyrosine kinase RON and mutation analysis in lung cancer samples SO GENES CHROMOSOMES & CANCER LA English DT Article ID MACROPHAGE STIMULATING PROTEIN; MET PROTOONCOGENE; RET PROTOONCOGENE; SHORT ARM; C-KIT; CELL CARCINOMA; FAMILY; CHROMOSOME-3; TUMORS; DOMAIN AB The human RON gene (MSTIR) maps to 3p21.3, a region frequently altered in lung cancer and other malignancies. It encodes a receptor tyrosine kinase (RTK) closely related to MET, whose mutations are associated with neoplasia. We investigated whether RON might be involved in the development or progression of lung cancer. We first determined the exon-intron structure of the gene by direct sequencing of RON cosmid DNA and PCR products containing intronic sequences, and then developed primers suitable for mutation analysis by the single-strand conformation polymorphism (SSCP) method. Twenty coding exons were characterized, ail but the first one small (average size: 170 bp), a feature shared with other RTK genes. We performed SSCP analysis of RON in small and non-small cell lung cancer samples, upon detection of its expression in a sample of lung cancer cell lines. A mutation (T915C: L296P) was found in an adenocarcinoma specimen. Several single nucleotide polymorphisms were also found. The panel of intron-anchored primers developed in this work will be useful for mutation analysis of the RON gene in different types of human tumors. (C) 2000 Wiley-Liss, Inc. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Frederick, MD 21702 USA. Inst Biol, Nantes, France. NCI, USN, Med Branch, NIH, Bethesda, MD 20892 USA. RP Angeloni, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. RI Breathnach, Richard/K-7599-2015 FU NCI NIH HHS [N01-CO-56000] NR 40 TC 44 Z9 52 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2000 VL 29 IS 2 BP 147 EP 156 DI 10.1002/1098-2264(2000)9999:9999<::AID-GCC1015>3.3.CO;2-E PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 350UV UT WOS:000089120300008 PM 10959094 ER PT J AU Srivatsan, ES Bengtsson, U Manickam, P Benyamini, P Chandrasekharappa, SC Sun, C Stanbridge, EJ Redpath, JL AF Srivatsan, ES Bengtsson, U Manickam, P Benyamini, P Chandrasekharappa, SC Sun, C Stanbridge, EJ Redpath, JL TI Interstitial deletion of 11q13 sequences in HeLa cells SO GENES CHROMOSOMES & CANCER LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; TUMOR-SUPPRESSOR GENE; CHROMOSOME BAND 11Q13; CERVICAL-CARCINOMA; PROXIMAL 11Q13; PHYSICAL MAP; MEN1 GENE; LONG ARM; HETEROZYGOSITY; TUMORIGENICITY AB Previous cytogenetic and molecular genetic studies have shown that the HeLa (cervical carcinoma) cell line D98/AH-2 contains two apparently normal copies of chromosome II and additional 11q13-25 material translocated onto a chromosome 3 marker. To determine the 11q13 breakpoint, we performed fluorescence in situ hybridization (FISH) using 18 different 11q13 specific BAC (bacterial artificial chromosome) and cosmid probes spanning a 5.6 Mb interval. Markers localized to the multiple endocrine neoplasia type I (MEN1) gene (menin) were also included in the analysis. The FISH study identified an interstitial deletion between markers DIIS449 and GSTPI, an interval of 2.3 Mb, in the marker chromosome. This deletion did not include the MEN1 gene. Because point mutations and methylations can inactivate the MEN1 gene, single stranded conformational polymorphism (SSCP) and Northern and Western blot analyses were performed with MEN1 specific probes and antibody. SSCP did not reveal mutations of the MEN1 gene in HeLa or in seven other cervical cancer cell lines. Northern and Western blot studies revealed normal levels of expression of this gene in the cervical cancer cell lines as well as in Hela cell derived tumorigenic hybrids. Because deletions of tumor suppressor genes often occur in cancer progression, we hypothesize that the inactivation of a tumor suppressor gene other than MEN1, localized to the 2.3 Mb interval on 11q13, might play a role in the abnormal growth behavior of HeLa cells in vitro or in vivo. (C) 2000 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, VAGLAHS W Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Irvine, Calif Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Calif Coll Med, Dept Radiat Oncol, Irvine, CA 92717 USA. RP Srivatsan, ES (reprint author), Univ Calif Los Angeles, VAGLAHS W Los Angeles, Sch Med, Dept Surg, 10H2,Bldg 304,Room E2-218,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA 39312, CA 19401] NR 39 TC 7 Z9 8 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2000 VL 29 IS 2 BP 157 EP 165 DI 10.1002/1098-2264(2000)9999:9999<::AID-GCC1024>3.0.CO;2-P PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 350UV UT WOS:000089120300009 PM 10959095 ER PT J AU Procopio, A Strizzi, L Vianale, G Betta, P Puntoni, R Fontana, V Tassi, G Gareri, F Mutti, L AF Procopio, A Strizzi, L Vianale, G Betta, P Puntoni, R Fontana, V Tassi, G Gareri, F Mutti, L TI Simian virus-40 sequences are a negative prognostic cofactor in patients with malignant pleural mesothelioma SO GENES CHROMOSOMES & CANCER LA English DT Article ID LARGE-T-ANTIGEN; 40-LIKE DNA-SEQUENCES; SIMIAN-VIRUS-40; SV40; EXPRESSION; TUMORS; SURVIVAL; TISSUE AB Several biochemical and clinical factors have been shown to correlate with survival in human malignant pleural mesothelioma (MM). Nevertheless, average survival of 4 to 10 months from diagnosis is sometimes not sufficient for full expression of these factors. Several studies have reported SV40 sequences in MM, suggesting a possible pathogenic role. We investigated whether the presence of these sequences had any effect on MM patient survival. For this study, we used polymerase chain reaction and Southern blot analysis to search for and identify SV40 DNA in biopsy samples from 83 MM patients. These cases were divided according to histology: 62/83 (74.7%) had epithelioid morphology (EMM) and 21/83 (25.3%) had either biphasic or sarcomatous morphology (B/SMM). SV40 positivity was significantly associated with B/SMM growth pattern (chi-squared test = 5.03, P = 0.025). Kaplan-Meier univariate analysis confirmed the independent effect of histology on MM survival (log-rank test = 13.9, P < 0.001) and showed a trend for increased survival in SV40-negative patients (log-rank test = 2.83, P = 0.09). Most importantly, Cox's regression model showed that SV40-positive status affected the predictive value of histology on patient survival. In particular, when SV40 expression was added to the B/SMM histotype, Cox's regression model showed a significant increase in hazard ratio (HR) with respect to SV40-negative B/SMM (HR = 4.25, 95% CI = 2.00-9.00, likelihood ratio test = 14.31, P < 0.001). We conclude that SV40 expression is significantly associated with B/SMM histology and represents an important prognostic cofactor when associated with the tumor subtype in MM patients. (C) 2000 Wiley-Liss, Inc. C1 Univ G DAnnunzio, Dept Oncol & Neurosci, Clin Pathol Sect, I-66013 Chieti, Italy. Univ G DAnnunzio, Mesothelioma Res Ctr, I-66013 Chieti, Italy. Alessandria Hosp, Dept Pathol, Alessandria, Italy. Natl Canc Inst, Liguria Canc Registry Sect, Genoa, Italy. Esine Hosp, Dept Resp Dis, Esine, Italy. Salvatore Maugeri Fdn, Inst Res & Care, Vercelli, Italy. Salvatore Maugeri Fdn, Dept Med, Vercelli, Italy. RP Procopio, A (reprint author), Univ G DAnnunzio, Dept Oncol & Neurosci, Clin Pathol Sect, Nuovo Polo Didattico,Via Vestini 31, I-66013 Chieti, Italy. NR 30 TC 42 Z9 43 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2000 VL 29 IS 2 BP 173 EP 179 DI 10.1002/1098-2264(2000)9999:9999<::AID-GCC1019>3.0.CO;2-B PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 350UV UT WOS:000089120300011 PM 10959097 ER PT J AU Asano, K Clayton, J Shalev, A Hinnebusch, AG AF Asano, K Clayton, J Shalev, A Hinnebusch, AG TI A multifactor complex of eukaryotic initiation factors, eIE1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo SO GENES & DEVELOPMENT LA English DT Article DE eukaryotic translation initiation factor (eIF); ribosomal preinitiation complex; GAP; AUG selection; Met-tRNA(i)(Met) binding ID GUANINE-NUCLEOTIDE-EXCHANGE; MAMMALIAN PROTEIN-SYNTHESIS; SACCHAROMYCES-CEREVISIAE; START CODON; FACTOR-II; YEAST; SUBUNIT; GCN4; SELECTION; BINDING AB Translation initiation factor 2 (eIF2) bound to GTP transfers the initiator methionyl tRNA to the 40S ribosomal subunit. The eIF5 stimulates GTP hydrolysis by the eIF2/GTP/Met-tRNA(i)(Met) ternary complex on base-pairing between Met-tRNA(i)(Met) and the start codon. The eIF2, eIF5, and eIF1 all have been implicated in stringent selection of AUG as the start codon. The eIE3 binds to the 40S ribosome and promotes recruitment of the ternary complex; however, physical contact between eIE3 and eIE2 has not been observed. We show that yeast eIE5 can bridge interaction in vitro between eIE3 and eIF2 by binding simultaneously to the amino terminus of eIF3 subunit NIP1 and the amino-terminal half of eIE2 beta, dependent on a conserved bipartite motif in the carboxyl terminus of eIF5. Additionally, the amino terminus of NIP1 can bind concurrently to eIF5 and eIE1. These findings suggest the occurrence of an eIE3/eIE1/eIE5/eIF2 multifactor complex, which was observed in cell extracts free of 40S ribosomes and found to contain stoichiometric amounts of tRNA(i)(Met). The multifactor complex was disrupted by the tif5-7A mutation in the bipartite motif of eIE5. Importantly, the tif5-7A mutant is temperature sensitive and displayed a substantial reduction in translation initiation at the restrictive temperature. We propose that the multifactor complex is an important intermediate in translation initiation in vivo. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. NR 39 TC 181 Z9 187 U1 0 U2 8 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 2000 VL 14 IS 19 BP 2534 EP 2546 DI 10.1101/gad.831800 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 362EJ UT WOS:000089765400012 PM 11018020 ER PT J AU Arudchandran, A Cerritelli, SM Narimatsu, SK Itaya, M Shin, DY Shimada, Y Crouch, RJ AF Arudchandran, A Cerritelli, SM Narimatsu, SK Itaya, M Shin, DY Shimada, Y Crouch, RJ TI The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication and repair SO GENES TO CELLS LA English DT Article ID DOUBLE-STRANDED-RNA; CELL-CYCLE; ESCHERICHIA-COLI; SCHIZOSACCHAROMYCES-POMBE; SUBCELLULAR-LOCALIZATION; SUBSTRATE-SPECIFICITY; CHECKPOINT GENES; XENOPUS-LAEVIS; CALF THYMUS; YEAST AB Background: RNA of RNA-DNA hybrids can be degraded by ribonucleases H present in all organisms including the eukaryote Saccharomyces cerevisiae. Determination of the number and roles of the RNases H in eukaryotes is quite feasible in S. cerevisiae. Results: Two S. cerevisiae RNases H, related to Escherichia coli RNase HI and HII, are not required for growth under normal conditions, yet, compared with wild-type cells, a double-deletion strain has an increased sensitivity to hydroxyurea (HU) and is hypersensitive to caffeine and ethyl methanesulphonate (EMS). In the absence of RNase H1, RNase H2 activity increases, and cells are sensitive to EMS but not HU and are more tolerant of caffeine; the latter requires RNase H2 activity. Cells missing only RNase H2 exhibit increased sensitive to HU and EMS but not caffeine Conclusions: Mutant phenotypes infer that some RNA-DNA hybrids are recognized by both RNases H1 and H2, while other hybrids appear to be recognized only by RNase H2. Undegraded RNA-DNA hybrids have an effect when DNA synthesis is impaired, DNA damage occurs or the cell cycle is perturbed by exposure to caffeine suggesting a role in DNA replication/repair that can be either beneficial or detrimental to cell viability. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM robert_crouch@nih.gov NR 55 TC 79 Z9 83 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-9597 EI 1365-2443 J9 GENES CELLS JI Genes Cells PD OCT PY 2000 VL 5 IS 10 BP 789 EP 802 DI 10.1046/j.1365-2443.2000.00373.x PG 14 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 363WW UT WOS:000089861500002 PM 11029655 ER PT J AU Tsang, M Kim, R de Caestecker, MP Kudoh, T Roberts, AB Dawid, IB AF Tsang, M Kim, R de Caestecker, MP Kudoh, T Roberts, AB Dawid, IB TI Zebrafish nma is involved in TGF beta family signaling SO GENESIS LA English DT Article DE nma; Bambi; BMP; patterning; development ID DORSOVENTRAL PATTERN-FORMATION; GROWTH-FACTOR-BETA; ONE-EYED PINHEAD; XENOPUS-EMBRYOS; SPEMANN ORGANIZER; HOMEOBOX GENE; MESODERM; EXPRESSION; PROTEIN; ANTAGONIST AB Bone morphogenetic proteins (BMP) are members of the TGF beta superfamily of secreted factors with important regulatory functions during embryogenesis, We have isolated the zebrafish gene, nma, that encodes a protein with high sequence similarity to human NMA and Xenopus Bambi, It is also similar to TGF beta type I serine/theronine kinase receptors in the extracellular ligand-binding domain but lacks a cytoplasmic kinase domain. During development, nma expression is similar to that of bmp2b and bmp4, and analysis in the dorsalized and ventralized zebrafish mutants swirl and chordino indicates that nma is regulated by BMP signaling. Overexpression of nma during zebrafish and Xenopus development resulted in phenotypes that appear to be based on inhibition of BMP signaling. Biochemically, NMA can associate with TGF beta type II receptors and bind to TGF beta ligand. We propose that nma is a BMP-regulated gene whose function is to attenuate BMP signaling during development through interactions with type II receptors and ligands. Published 2000 Wiley-Liss, Inc.(dagger) C1 NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, Bldg 6B-420, Bethesda, MD 20892 USA. RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014 OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063 NR 64 TC 45 Z9 46 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD OCT PY 2000 VL 28 IS 2 BP 47 EP 57 DI 10.1002/1526-968X(200010)28:2<47::AID-GENE20>3.0.CO;2-S PG 11 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 376JQ UT WOS:000165454800002 PM 11064421 ER PT J AU Kawahara, A Wilm, T Solnica-Krezel, L Dawid, IB AF Kawahara, A Wilm, T Solnica-Krezel, L Dawid, IB TI Functional interaction of vega2 and goosecoid homeobox genes in zebrafish SO GENESIS LA English DT Article DE vega; bozozok/dharma; goosecoid; organizer formation ID SIGNALING PATHWAY; BETA-CATENIN; XENOPUS; ORGANIZER; BMP-4; SPECIFICATION; GASTRULATION; PREGASTRULA; EXPRESSION; MESODERM AB The gastrula organizer forms in the dorsal region of the zebrafish embryo, where the bozozok/ dharma homeobox gene downregulates expression of the vega1 transcriptional repressor, Here, we describe a novel Vega family homeobox gene, vega2, Expression of vega2 is initiated at the ventral blastoderm margin during blastula stages, and by gastrulation becomes complementary to but partially overlapping with the dorsal expression domain of the homeobox gene goosecoid (gsc), This dorsal exclusion of vega2 expression is not observed in bozozok mutants in which organizer formation is impaired. Both vega2 and vega1 can physically interact with Gsc, Zebrafish embryos injected with vega2 mRNA failed to express gsc and developed a headless phenotype, Conversely, a putative dominant negative form of vega2, VP16-vega2, elicited the expansion of gsc expression and a dorsalized phenotype, We suggest that vega2, in cooperation with vega1, functions as a negative regulator of organizer genes including gsc, and participates in the refinement of the gastrula organizer domain. Published 2000 Wiley-Liss, Inc.(dagger) C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Mol Biol, Nashville, TN 37235 USA. RP Dawid, IB (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NR 32 TC 38 Z9 39 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 1526-954X J9 GENESIS JI Genesis PD OCT PY 2000 VL 28 IS 2 BP 58 EP 67 DI 10.1002/1526-968X(200010)28:2<58::AID-GENE30>3.0.CO;2-N PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 376JQ UT WOS:000165454800003 PM 11064422 ER PT J AU Motoike, T Loughna, S Perens, E Roman, BL Liao, W Chau, TC Richardson, CD Kawate, T Kuno, J Weinstein, BM Stainier, DYR Sato, TN AF Motoike, T Loughna, S Perens, E Roman, BL Liao, W Chau, TC Richardson, CD Kawate, T Kuno, J Weinstein, BM Stainier, DYR Sato, TN TI Universal GFP reporter for the study of vascular development SO GENESIS LA English DT Article ID RECEPTOR TYROSINE KINASE; GREEN FLUORESCENT PROTEIN; ENDOTHELIAL-CELL LINEAGE; GENE-EXPRESSION; ZEBRAFISH EMBRYOS; DNA MICROARRAYS; TRANSGENIC MICE; DROSOPHILA; PROMOTER; MARKER AB We report the generation and characterization of transgenic mouse and zebrafish expressing green fluorescent protein (GFP) specifically in vascular endothelial cells in a relatively uniform fashion. These reporter lines exhibit fluorescent vessels in developing embryos and throughout adulthood, allowing visualization of the general vascular patterns with single cell resolution, Furthermore, we show the ability to purify endothelial cells from whole embryos and adult organs by a single step fluorescence activated cell sorting. We expect that these transgenic reporters will be useful tools for imaging vascular morphogenesis, global gene expression profile analysis of endothelial cells, and high throughput screening for vascular mutations. (C) 2000 Wiley-Liss, Inc. C1 Univ Texas, SW Med Ctr, Dept Internal Med & Mol Biol, Dallas, TX 75235 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. NICHD, Genet Mol Lab, Unit Vertebrate Organogenesis, NIH, Bethesda, MD USA. RP Stainier, DYR (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med & Mol Biol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. NR 28 TC 296 Z9 303 U1 2 U2 16 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD OCT PY 2000 VL 28 IS 2 BP 75 EP 81 DI 10.1002/1526-968X(200010)28:2<75::AID-GENE50>3.0.CO;2-S PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 376JQ UT WOS:000165454800005 PM 11064424 ER PT J AU Jung, G Jones, G Wegrzyn, RD Masison, DC AF Jung, G Jones, G Wegrzyn, RD Masison, DC TI A role for cytosolic Hsp70 in yeast [PSI+] prion propagation and [PSI+] as a cellular stress SO GENETICS LA English DT Article ID HEAT-SHOCK RESPONSE; SACCHAROMYCES-CEREVISIAE; MULTIGENE FAMILY; TRANSLATION TERMINATION; PROTEIN HSP104; SUP35 PROTEIN; IN-VITRO; DETERMINANT; EFFICIENCY; EXPRESSION AB [PSI+] is a prion (infectious protein) of Sup35p, a subunit of the Saccharomyces cerevisiae translation termination factor. We isolated a dominant allele, SSA1-21, of a gene encoding an Hsp70 chaperone that impairs [PSI+] mitotic stability and weakens allosuppression caused by [PSI+]. While [PSI+] stability is normal in strains lacking SSA1, SSA2, or both, SSA1-21 strains with a deletion of SSA2 cannot propagate [PSI+]. SSA1-21 [PSI+] strains are hypersensitive to curing of [PSI+] by guanidine-hydrochloride and partially cured of [PSI+] by rapid induction of the heat-shock response but not by growth at 37 degrees. The number of inheritable [PSI+] particles is significantly reduced in SSA1-21 cells. SSA1-21 effects on [PSI+] appear to be independent of Hsp104, another stress-inducible protein chaperone known to be involved in [PSI+] propagation. We propose that cytosolic Hsp70 is important for the formation of Sup35p polymers characteristic of [PSI+] from preexisting material and that Ssa1-21p both lacks and interferes with this activity. We further demonstrate that the negative effect of heat stress on [PSI+] phenotype directly correlates with solubility of Sup35p and find that in wild-type strains the presence of [PSI+] causes a stress that elevates basal expression of Hsp104 and SSA1. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Rm 407,8 Ctr Dr,MSC 0851, Bethesda, MD 20892 USA. EM masisond@helix.nih.gov NR 44 TC 146 Z9 151 U1 1 U2 4 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD OCT PY 2000 VL 156 IS 2 BP 559 EP 570 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 362EZ UT WOS:000089766800009 PM 11014806 ER PT J AU Picardeau, M Lobry, JR Hinnebusch, BJ AF Picardeau, M Lobry, JR Hinnebusch, BJ TI Analyzing DNA strand compositional asymmetry to identify candidate replication origins of Borrelia burgdorferi linear and circular plasmids SO GENOME RESEARCH LA English DT Article ID BACTERIAL PLASMIDS; BIDIRECTIONAL REPLICATION; SUBSTITUTION PATTERNS; NUCLEOTIDE-SEQUENCE; BACILLUS-SUBTILIS; CHROMOSOME; PARTITION; GENOMES; REGION; ORGANIZATION AB The Lyme disease agent Borrelia burgdorferi has a genome composed of a linear chromosome and a series of linear and circular plasmids. We previously mapped the oriC of the linear chromosome to the center of the molecule, where a pronounced switch in CC skew occurs. In this study, we analyzed B. burgdorferi plasmid sequences for AT and CG skew in an effort to similarly identify plasmid replication origins. Cumulative skew diagrams of the plasmids suggested that they, Like the linear chromosome, replicate bidirectionally from an internal origin. The B. burgdorferi linear chromosome contains homologs to partitioning protein genes soj and spoOJ which are closely linked to oriC at the minimum cumulative skew point of the 1-Mb molecule. A sojl parA homolog also maps to cumulative skew minima of the B. burgdorferi linear and circular plasmids, further suggesting that these regions contain the replication origin. The heterogeneity in these genes and in the nucleotide sequences of the putative origin regions could account for the mutual compatibility of the multiple DNA elements in B. burgdorferi. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Lyon 1, Lab Biometrie, CNRS UMR 5558, F-69622 Villeurbanne, France. RP Hinnebusch, BJ (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. NR 39 TC 49 Z9 51 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2000 VL 10 IS 10 BP 1594 EP 1604 DI 10.1101/gr.124000 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 367WB UT WOS:000090083500016 PM 11042157 ER PT J AU Wang, YL Bryant, S Tatusov, R Tatusova, T AF Wang, YL Bryant, S Tatusov, R Tatusova, T TI Links from genome proteins to known 3-D structures SO GENOME RESEARCH LA English DT Article ID CARBOXYKINASE; SEQUENCES AB We describe a genome annotation service provided by the Entrez browser, http://www.ncbi.nlm.nih.gov/entrez. AII protein products identified in fully sequenced microbial genomes have been compared with proteins with known 3-D structure by use of the BLAST sequence comparison algorithm. For the similar to 20% of genome proteins in which unambiguous sequence similarity is detected, Entrez provides a link From the gene product to its predicted structure. The service uses the Cn3D molecular graphics viewer to present a 3-D view of the known structure, together with an alignment display mapping conserved residues from the genome protein onto the known structure. Using an example from Aeropyrum pernix, we illustrate how mapping to a 3-D structure can confirm predictions of biological function. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Tatusova, T (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 21 TC 9 Z9 9 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2000 VL 10 IS 10 BP 1643 EP 1647 DI 10.1101/gr.143200 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 367WB UT WOS:000090083500020 PM 11042161 ER PT J AU Ostendorff, HP Bossenz, M Mincheva, A Copeland, NG Gilbert, DJ Jenkins, NA Lichter, P Bach, I AF Ostendorff, HP Bossenz, M Mincheva, A Copeland, NG Gilbert, DJ Jenkins, NA Lichter, P Bach, I TI Functional characterization of the gene encoding RLIM, the corepressor of LIM homeodomain factors SO GENOMICS LA English DT Article ID TRANSCRIPTION FACTOR PU.1; WING DEVELOPMENT; BINDING-PROTEIN; DROSOPHILA; DIFFERENTIATION; EXPRESSION; COMPLEX; CELLS; NOTCH; MOUSE AB RLIM is a RING H2 zinc finger protein that acts as a negative coregulator for LIM homeodomain transcription factors. We have isolated genomic A clones that cover the entire mouse RLIM-encoding Rnf12 gene. The Rnf12 gene encompasses 20 kb and consists of at least five exons and four introns. Several transcriptional start sites within a 24-bp region were mapped around 300 nt upstream of the translational start site. Rnf12-specific mRNA can be detected in many tissues as revealed by Northern blot analysis. Transient cotransfections reveal that the proximal Rnf12 promoter can be activated in vitro by ubiquitously and more restrictively expressed transcription factors, some of which are known mediators of signal transduction pathways, e.g., mammalian Kruppel-like transcription factors, Sox and ets-related proteins, and RBP-J. We isolated a cDNA encoding human RLIM, which is highly conserved with mouse and chick RLIM. By fluorescence in situ hybridization and interspecific backcross analysis, we have localized the Rnf12 gene to the central regions of mouse and human chromosome X. (C) 2000 Academic Press. C1 Univ Hamburg, Ctr Mol Neurobiol, D-20251 Hamburg, Germany. German Canc Res Ctr, D-69120 Heidelberg, Germany. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Bach, I (reprint author), Univ Hamburg, Ctr Mol Neurobiol, Martinistr 85, D-20251 Hamburg, Germany. OI Ostendorff, Heather/0000-0002-1481-8263 NR 53 TC 16 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 1 PY 2000 VL 69 IS 1 BP 120 EP 130 DI 10.1006/geno.2000.6311 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 362YH UT WOS:000089805500013 PM 11013082 ER PT J AU Ramakrishnan, B Qasba, PK AF Ramakrishnan, B Qasba, PK TI Crystal structure of Lactose Synthetase: A complex between 1,4-galactosyltransferase and -lactalbumin in the presence of uridinediphosphogalactose, Mn2+ and 4-fluroglucose SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Struct Glycobiol Sect, LECB, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, 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 OCT PY 2000 VL 10 IS 10 MA 79 BP 1098 EP 1098 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 360JN UT WOS:000089664300091 ER PT J AU Kawai, H Wada, R Allende, ML Kono, M Sango, K Miyakawa, T Crawley, JN Bierfreund, UB Sandhoff, K Proia, RL AF Kawai, H Wada, R Allende, ML Kono, M Sango, K Miyakawa, T Crawley, JN Bierfreund, UB Sandhoff, K Proia, RL TI Mice that express only ganglioside GM3 exhibit sudden death and audiogenic seizures SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012; Miyakawa, Tsuyoshi/A-7741-2008 OI Miyakawa, Tsuyoshi/0000-0003-0137-8200 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 OCT PY 2000 VL 10 IS 10 MA 120 BP 1109 EP 1109 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 360JN UT WOS:000089664300132 ER PT J AU Li, Q Ashraf, MF Bekoe, NA Stark, WJ Chan, CC O'Brien, TP AF Li, Q Ashraf, MF Bekoe, NA Stark, WJ Chan, CC O'Brien, TP TI The role of apoptosis in the early corneal wound healing after excimer laser keratectomy in the rat SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID CELL-DEATH; EXPRESSION AB Background: The potential role of apoptosis in corneal wound healing after excimer laser keratectomy was investigated in a rat model. Methods: Lewis rats underwent laser keratectomy using a 193-nm excimer laser. The central corneas were ablated in three depths: group A, epithelium; group B, superficial stroma; group C, deep stroma. Eyes were collected at 1, 12, 24, and 36 h and I week. Cellular markers associated with apoptosis - Fas, Fas ligand (FasL), Bcl-2, and Bax - were examined by immunohistochemistry. Keratocyte depletion and endothelial changes were evaluated histologically. In situ end labeling of double-stranded DNA breaks was used to demonstrate apoptosis in corneal sections. Results: Keratocyte depletion was observed in 6 (50%) of 12 rats (total from groups A, B, and C) at 12 h, 11 (73%) of 15 at 24 h, 3 (20%) of 15 at 36 h, and 2 (15%) of 13 at 1 week after laser surgery. Corneal endothelial edema was observed in the ablation zone. Expression of Fas, FasL, Bcl-2, and Bax in corneal cells showed dynamics similar to that of keratocyte depletion and endothelial changes. There was less expression of apoptotic molecules in newly generated epithelial cells and more in endothelial cells of the stromal ablation groups. Conclusions: Excimer laser keratectomy triggered apoptosis of corneal keratocytes and endothelial cells. More endothelial edema was observed in the stromal ablation than in the epithelial ablation group. The expression of apoptotic molecules coincided with the period of keratocyte depletion and regeneration and of endothelial recovery, suggesting that apoptosis is a dynamic part of corneal wound healing and remodeling after excimer laser keratectomy. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP O'Brien, TP (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St,Woods Bldg,Rm 259, Baltimore, MD 21287 USA. NR 18 TC 8 Z9 8 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD OCT PY 2000 VL 238 IS 10 BP 853 EP 860 DI 10.1007/s004170000182 PG 8 WC Ophthalmology SC Ophthalmology GA 370FU UT WOS:000165113500009 PM 11127573 ER PT J AU Fishman, A Dekel, E Chetrit, A Lerner-Geva, L Bar-Am, A Beck, D Beller, U Ben-Baruch, G Piura, B Friedman, E Struewing, JP Modan, B AF Fishman, A Dekel, E Chetrit, A Lerner-Geva, L Bar-Am, A Beck, D Beller, U Ben-Baruch, G Piura, B Friedman, E Struewing, JP Modan, B TI Patients with double primary tumors in the breast and ovary - Clinical characteristics and BRCA1-2 mutations status SO GYNECOLOGIC ONCOLOGY LA English DT Article DE double primary malignancy; breast cancer; ovarian cancer; BRCA1-2 mutations ID MULTIPLE PRIMARY CANCERS; JEWISH WOMEN; 185DELAG MUTATION; FAMILY HISTORY; ASHKENAZI JEWS; P53 MUTATIONS; FREQUENCY; RISK; MALIGNANCIES; PENETRANCE AB Objective. The aim of this study was to define the prevalence, clinical characteristics, and BRCA1-2 mutation carrier status of ovarian cancer (OvC) patients with a previous primary malignancy in the breast (PPMBr). Methods. The study population comprised 1240 consecutive Jewish Israeli women with pathologically confirmed epithelial OvC diagnosed between March 1, 1994, and December 31, 1997. Demographic and clinical data were obtained from medical files and from a detailed questionnaire taken through a nationwide epidemiological case-control study on OvC. Blood samples and tumor tissues were collected for analysis of the three predominant germline BRCA1-2 Jewish founder mutations (185delAG, 5382insC, and 6174delT). Results. Fifty nine (4.7%) patients with OvC had a PPMBr. The median age at diagnosis of OvC was 60 years. The mean interval between the two diagnoses was 104 months (range 0-363 months). In the majority of the patients (n = 53), the diagnosis of breast cancer (BrC) preceded the OvC by more than 1 year. The ovarian tumors were diagnosed in 47% of the cases following investigation of patients' symptoms. In 41%, diagnosis was made as a consequence of check-up exams performed during the routine follow-up of BrC survivors. Patients with PPMBr were more likely to present with FIGO ovarian stage III-IV, compared to women with solitary OvC (73% vs 60.3%, P < 0.05), and less likely to have borderline tumors (3.4% vs 17.9%, P = 0.007). Family history of OvC/BrC was recorded in 26% of this group of patients compared to 10.5% among patients with solitary OvC (P = 0.003). Patients with PPMBr had an exceptionally high prevalence of BRCA1-2 mutations (57%), irrespective of family history. Conclusions. Patients with PPMBr present with more advanced disease and invasive-type epithelial ovarian tumors when compared to cases associated with solitary OvC. The rate of BRCA1-2 mutations in Jewish women with OvC who had PPMBr is at least twice as high as in Jewish women with OvC as the solitary disease. (C) 2000 Academic Press. C1 Meir Hosp, Sapir Med Ctr, IL-44281 Kefar Sava, Israel. Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Ichilov Hosp, IL-64239 Tel Aviv, Israel. Rambam Med Ctr, Haifa, Israel. Shaare Zedek Med Ctr, Jerusalem, Israel. Soroka Med Ctr, IL-84101 Beer Sheva, Israel. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. RP Fishman, A (reprint author), Meir Hosp, Sapir Med Ctr, IL-44281 Kefar Sava, Israel. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 35 TC 15 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2000 VL 79 IS 1 BP 74 EP 78 DI 10.1006/gyno.2000.5895 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 361FP UT WOS:000089712700016 PM 11006035 ER PT J AU Farley, JH Nycum, LR Birrer, MJ Park, RC Taylor, RR AF Farley, JH Nycum, LR Birrer, MJ Park, RC Taylor, RR TI Age-specific survival of women with endometrioid adenocarcinoma of the uterus SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-Gynecologic-Oncologists CY MAR 20-24, 1999 CL SAN FRANCISCO, CALIFORNIA SP Soc Gynecol Oncologists DE age; survival; endometrial; cancer ID PREMENOPAUSAL WOMEN; CARCINOMA; YOUNGER; HYPERPLASIA; PROGESTIN; CANCER AB Objective. The purpose of this paper was to evaluate the age-specific survival for women diagnosed with endometrioid adenocarcinoma of the uterus. Methods. A retrospective analysis was conducted of 328 patients diagnosed with endometrioid adenocarcinoma of the uterus between January 1990 and December 1997. Patients were followed for 3 to 96 months with a mean of 43 months. The impact of age on survival was assessed using Col proportional hazard regression and multivariate analysis for age, stage, and grade. Stage and grade were analyzed using log-rank tests, and survival curves were generated by the Kaplan-Meier method. Results. A total of 328 patients were evaluated. Multivariate analysis revealed age, stage, and grade were all significant independent predictors of survival (P < 0.0001). Age-specific survival varied from a high of 90% at age 40 to a low of 55% at age 80. interval age-specific survival decreased below 86% at age 50. Subset analysis of patients younger than 50 compared with older patients revealed no difference in surgical stage or grade of tumors among these patients. Patients older than 50, however, were 41% more likely to receive adjuvant radiation therapy. Conclusion. Age is a specific, significant predictor of outcome in endometrioid adenocarcinoma of the uterus. Survival decreases significantly in patients older than 50. This decreased survival associated with age is unrelated to surgical stage or grade of adenocarcinoma, Decreased survival could involve molecular differences in the developing endometrial cancer or an increased risk of death from other non-cancer-related factors, (C) 2000 Academic Press. C1 Tripler Army Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Honolulu, HI 96859 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NCI, Div Clin Sci, Med Branch, Cell & Canc Biol Dept, Rockville, MD 20850 USA. Gynecol Oncol Grp, Philadelphia, PA USA. St Barnabas Med Ctr, Livingston, NJ 07039 USA. RP Farley, JH (reprint author), Tripler Army Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, 1 Jarrett White Rd TAMC, Honolulu, HI 96859 USA. NR 23 TC 28 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2000 VL 79 IS 1 BP 86 EP 89 DI 10.1006/gyno.2000.5934 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 361FP UT WOS:000089712700018 PM 11006037 ER PT J AU Farci, P Chessa, L Peddis, G Strazzera, R Pascariello, E Scioscia, R Lai, ME Mazzoleni, AP Roskams, T Desmet, V Purcell, RH AF Farci, P Chessa, L Peddis, G Strazzera, R Pascariello, E Scioscia, R Lai, ME Mazzoleni, AP Roskams, T Desmet, V Purcell, RH TI Influence of alfa interferon on the natural history of chronic hepatitis D: Dissociation of histologic and virologic response. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Cagliari, Cagliari, Italy. Katholieke Univ Leuven, Louvain, Belgium. NIH, Bethesda, MD 20892 USA. RI Chessa, Luchino/H-7561-2012 OI Chessa, Luchino/0000-0002-9474-0995 NR 0 TC 5 Z9 5 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 OCT PY 2000 VL 32 IS 4 MA 242 BP 222A EP 222A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400237 ER PT J AU Umemura, T Yeo, AE Wang, RY Shih, J Donahue, P Primi, D Alter, HJ AF Umemura, T Yeo, AE Wang, RY Shih, J Donahue, P Primi, D Alter, HJ TI The incidence of SEN virus infection in transfusion-associated hepatitis. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Diasorin, Saluggia, Italy. NR 0 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 OCT PY 2000 VL 32 IS 4 MA 244 BP 222A EP 222A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400238 ER PT J AU Heller, T Thomson, M Koziol, D Mallatt, DB Jeffers, L Schiff, ER Hoofnagle, JH Liang, TJ AF Heller, T Thomson, M Koziol, D Mallatt, DB Jeffers, L Schiff, ER Hoofnagle, JH Liang, TJ TI The role of the E2 envelope protein of hepatitis C virus as a determinant of interferon response. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NIH, Cc, Bethesda, MD 20892 USA. Univ Miami, Miami, FL 33152 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 250 BP 224A EP 224A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400245 ER PT J AU Guardiola, J Xiol, X Sallie, R Botargues, JM Vazquez, S Torras, J Ramos, E Rafecas, A AF Guardiola, J Xiol, X Sallie, R Botargues, JM Vazquez, S Torras, J Ramos, E Rafecas, A TI Vitamin D-receptor genotypes as independent genetic predictors of acute rejection after liver transplantation. SO HEPATOLOGY LA English DT Meeting Abstract C1 Ciutat Sanitaria & Univ Bellvitge, Barcelona, Spain. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 321 BP 241A EP 241A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400316 ER PT J AU Lechmann, MT Vergalla, J Satoi, J Triyatni, M Baumert, TF Liang, JT AF Lechmann, MT Vergalla, J Satoi, J Triyatni, M Baumert, TF Liang, JT TI Immunization with hepatitis C virus-like particles induces protection from HCV-recombinant vaccinia infection in mice. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 428 BP 268A EP 268A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400422 ER PT J AU Thio, CL Carrington, M Goedert, JJ Vlahov, D Nelson, KE Hilgartner, MJ O'Brien, SJ Karacki, P Marti, D Astemborski, J Thomas, DL AF Thio, CL Carrington, M Goedert, JJ Vlahov, D Nelson, KE Hilgartner, MJ O'Brien, SJ Karacki, P Marti, D Astemborski, J Thomas, DL TI The association of HLA-CW04 and hepatitis C virus persistence. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Johns Hopkins Univ, Baltimore, MD USA. New York Acad Med Sci, New York, NY USA. Cornell Univ, New York, NY USA. NCI, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 432 BP 269A EP 269A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400426 ER PT J AU Bukh, J Thimme, R Forns, X Chang, KM Yanagi, M Emerson, SU Chisari, FV Purcell, RH AF Bukh, J Thimme, R Forns, X Chang, KM Yanagi, M Emerson, SU Chisari, FV Purcell, RH TI A chimpanzee with sterilizing immunity against a hepatitis C virus (HCV) homologous polyclonal challenge was not protected against a heterologous challenge. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID, NIH, LID, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. Scripps Res Inst, La Jolla, CA USA. NIAID, NIH, Mol Hepatitis Sect, Bethesda, MD 20892 USA. RI Chisari, Francis/A-3086-2008 NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 436 BP 270A EP 270A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400430 ER PT J AU Satoi, JJ Lechman, M Manickan, E Thomson, M Rhermann, B Liang, TJ AF Satoi, JJ Lechman, M Manickan, E Thomson, M Rhermann, B Liang, TJ TI Induction of HCV-specific immune response in HCV transgenic mice by DNA immunization. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Jikei Univ, Sch Med, Tokyo, Japan. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 439 BP 271A EP 271A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400435 ER PT J AU Dufour, DR Yeh, MM Strader, DB Marino, G Boonpongmanee, S Seeff, LB AF Dufour, DR Yeh, MM Strader, DB Marino, G Boonpongmanee, S Seeff, LB TI HCV genotypes and treatment response among veterans of different ethnic backgrounds. SO HEPATOLOGY LA English DT Meeting Abstract C1 Vet Affairs Med Ctr, Washington, DC 20422 USA. Washington Univ, Med Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Washington, DC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 480 BP 281A EP 281A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400474 ER PT J AU Ghany, MG Kleiner, DE Alter, HJ Doo, E Herion, DW Khokar, F AF Ghany, MG Kleiner, DE Alter, HJ Doo, E Herion, DW Khokar, F TI Progression of fibrosis in early stages of chronic hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 496 BP 285A EP 285A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400490 ER PT J AU Wedemeyer, H Mizukoshi, E Davis, AR Rehermann, B AF Wedemeyer, H Mizukoshi, E Davis, AR Rehermann, B TI Hepatitis C virus NS3 specific cytotoxic T cells can be induced by influenza a virus infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Barbara Rehermann Lds, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 573 BP 303A EP 303A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400560 ER PT J AU Rodrigues, CM Sola, S Brito, MA Brites, D Moura, JG Youle, RJ Steer, CJ AF Rodrigues, CM Sola, S Brito, MA Brites, D Moura, JG Youle, RJ Steer, CJ TI Tauroursodeoxycholate prevents mitochondrial membrane perturbation induced by recombinant Bax protein. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Lisbon, Fac Farm, P-1699 Lisbon, Portugal. Univ Nova Lisboa, FCT, M Caparica, Portugal. NINDS, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RI brito, maria/M-8278-2013; Brites, Dora/M-8293-2013; iMed.ULisboa, iMed.ULisboa/C-6292-2014; Rodrigues, Cecilia/M-3572-2013 OI brito, maria/0000-0002-8493-4649; Brites, Dora/0000-0002-3024-9777; Rodrigues, Cecilia/0000-0002-4829-754X NR 0 TC 1 Z9 1 U1 0 U2 2 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 OCT PY 2000 VL 32 IS 4 MA 582 BP 305A EP 305A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400570 ER PT J AU Edlin, BR Gee, L Kral, AH Seal, KH Lorvick, J Tobler, LH Andrews, WW Phelps, BH Busch, MP O'Brien, TR AF Edlin, BR Gee, L Kral, AH Seal, KH Lorvick, J Tobler, LH Andrews, WW Phelps, BH Busch, MP O'Brien, TR TI Decline of hepatitis C virus transmission among injection drug users, San Francisco, 1977-1998. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Urban Hlth Study, San Francisco, CA 94143 USA. Blood Ctr Pacific, San Francisco, CA USA. Chiron Corp, Emeryville, CA 94608 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 615 BP 313A EP 313A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400601 ER PT J AU Arichi, T Shirai, M Chen, M Arima, K Watanabe, S Berzofsky, JA Nishioka, M AF Arichi, T Shirai, M Chen, M Arima, K Watanabe, S Berzofsky, JA Nishioka, M TI Collaboration of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (TH) in clearing hepatitis C virus (HCV) during and after interferon therapy. SO HEPATOLOGY LA English DT Meeting Abstract C1 Kagawa Med Univ, Kagawa, Japan. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 855 BP 373A EP 373A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400841 ER PT J AU Arichi, T Major, ME Saito, T Nishioka, M Engelhard, VH Feinstone, SM Berzolsky, JA AF Arichi, T Major, ME Saito, T Nishioka, M Engelhard, VH Feinstone, SM Berzolsky, JA TI Application of epitope enhancement to a prophylactic DNA vaccine for hepatitis C virus (HCV) in an HLA-A2.1 transgenic mouse model: Enhanced HCV specific CTL induction and protection from HCV-recombinant vaccinia infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Kagawa Med Univ, Kagawa, Japan. US FDA, Bethesda, MD 20014 USA. Yamagata Univ, Sch Med, Yamagata 99023, Japan. Univ Virginia, Charlottesville, VA 22903 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 853 BP 373A EP 373A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400840 ER PT J AU Ghany, MG Lau, DTY Doo, E Herion, DW Everhart, JE Heller, T Kleiner, DE Park, Y Liand, JT Hoofnagle, JH AF Ghany, MG Lau, DTY Doo, E Herion, DW Everhart, JE Heller, T Kleiner, DE Park, Y Liand, JT Hoofnagle, JH TI Clinical features of viral resistance in patients with chronic hepatitis B maintained on long-term lamivudine therapy. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. NR 0 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 OCT PY 2000 VL 32 IS 4 MA 866 BP 376A EP 376A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400854 ER PT J AU Umemura, T Yeo, AE Shih, Y Matsumoto, A Orii, K Tanaka, E Kiyosawa, K Primi, D AF Umemura, T Yeo, AE Shih, Y Matsumoto, A Orii, K Tanaka, E Kiyosawa, K Primi, D TI The prevalence of SEN virus infection in Japanese patients with viral hepatitis and liver disease. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Shinshu Univ, Matsumoto, Nagano 390, Japan. NR 0 TC 12 Z9 15 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 OCT PY 2000 VL 32 IS 4 MA 885 BP 381A EP 381A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400872 ER PT J AU Thimme, R Bukh, J Pemberton, J Guidotti, LG Sette, A Purcell, RH Chisari, FV AF Thimme, R Bukh, J Pemberton, J Guidotti, LG Sette, A Purcell, RH Chisari, FV TI Clearance of HCV infection is determined by the vigor of the antiviral T cell response and the intrahepatic cytokine profile. SO HEPATOLOGY LA English DT Meeting Abstract C1 Scripps Res Inst, La Jolla, CA USA. NIH, Bethesda, MD 20892 USA. Scripps Res Inst, La Jolla, CA USA. Epimmune, La Jolla, CA USA. NIH, Bethesda, MD 20892 USA. RI Chisari, Francis/A-3086-2008 NR 0 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 OCT PY 2000 VL 32 IS 4 MA 902 BP 385A EP 385A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400890 ER PT J AU Wedemeyer, H Cagneten, S Davis, AR Feinstone, SM Rehermann, B AF Wedemeyer, H Cagneten, S Davis, AR Feinstone, SM Rehermann, B TI Oral immunization with HCV-NS3 encoding salmonella: Long-lasting induction of HCV-specific CTL in an HLA-A2 transgenic mouse model. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 905 BP 386A EP 386A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400892 ER PT J AU Thimme, R Pemberton, J Guidotti, LG Purcell, RH Chisari, FV AF Thimme, R Pemberton, J Guidotti, LG Purcell, RH Chisari, FV TI Analysis of a successful immune response against HBV. SO HEPATOLOGY LA English DT Meeting Abstract C1 Scripps Res Inst, La Jolla, CA USA. NIH, Bethesda, MD 20892 USA. RI Chisari, Francis/A-3086-2008 NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 931 BP 392A EP 392A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400916 ER PT J AU Thurman, RG Yin, M Nakagami, M Hiroshi, K Uesugi, T Goyert, S Holland, SM AF Thurman, RG Yin, M Nakagami, M Hiroshi, K Uesugi, T Goyert, S Holland, SM TI New application of long-term enteral alcohol delivery to study hepatic fibrosis in the mouse. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. N Shore Univ Hosp, Manhasset, NY 11030 USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 997 BP 409A EP 409A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400983 ER PT J AU Hoare, JM Henkler, F Robert, GD Koshy, R McGarvey, MJ AF Hoare, JM Henkler, F Robert, GD Koshy, R McGarvey, MJ TI The subcellular localisation of the X protein in HBV infected hepatocytes. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ London Imperial Coll Sci Technol & Med, London, England. Natl Inst Med Res, London NW7 1AA, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 1153 BP 448A EP 448A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401139 ER PT J AU Momosaki, S Umemura, T Scudamore, CH Kojiro, M Alter, HJ Tabor, E AF Momosaki, S Umemura, T Scudamore, CH Kojiro, M Alter, HJ Tabor, E TI The prevalence of SEN-V infection in patients with hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Surg, Vancouver, BC V6T 1W5, Canada. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. NR 0 TC 4 Z9 7 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 OCT PY 2000 VL 32 IS 4 MA 1155 BP 448A EP 448A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401140 ER PT J AU Lu, T Liu, J LeCluyse, E Mumford, J Cheng, ML Waalkes, MP AF Lu, T Liu, J LeCluyse, E Mumford, J Cheng, ML Waalkes, MP TI Applications of cDNA microarray to the study of arsenic-induced liver injury in the population of Guizhou, China. SO HEPATOLOGY LA English DT Meeting Abstract C1 US EPA, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC USA. Guiyang Med Coll Hosp, Guiyang, Peoples R China. NCI, NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 1241 BP 470A EP 470A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401227 ER PT J AU Li, CX Luo, L Li, L Cheng, ML Huang, NH Waalkes, MP Liu, J AF Li, CX Luo, L Li, L Cheng, ML Huang, NH Waalkes, MP Liu, J TI The collagenolytic effects of traditional Chinese medicine prescriptions, Han-Dan-Gan-Le, on CCL4-induced liver fibrosis in rats. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIEHS, NCI, RTP, NC USA. Guiyang Med Coll, Guiyang, Peoples R China. Guiyang Med Coll Hosp, Guiyang, Peoples R China. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 1357 BP 499A EP 499A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401342 ER PT J AU Lu, T Cheng, ML Wu, J Deng, KS Zhou, YS Waalkes, MP Liu, J AF Lu, T Cheng, ML Wu, J Deng, KS Zhou, YS Waalkes, MP Liu, J TI The therapeutic effects of Chinese medicine, Han-Dan-Gan-Le, on arsenic-induced liver disorders in Guizhou, China. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIEHS, NCI, RTP, NC USA. Xingyi Endem Stn, Xingyi, Peoples R China. Guiyang Med Coll Hosp, Guiyang, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 2 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 OCT PY 2000 VL 32 IS 4 MA 1370 BP 502A EP 502A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401356 ER PT J AU Shrestha, S Kemmer, NM Soloway, R Njoku, DB Pohl, LR Duray, PR Tsokos, M Abu-Asab, MS West, B AF Shrestha, S Kemmer, NM Soloway, R Njoku, DB Pohl, LR Duray, PR Tsokos, M Abu-Asab, MS West, B TI Isoflurane-induced acute hepatitis: Immunohistochemical evidence for the mechanism of hepatotoxicity. SO HEPATOLOGY LA English DT Meeting Abstract C1 NYU, New York, NY USA. NCI, NIH, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 1372 BP 502A EP 502A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401357 ER PT J AU Edlin, BR Gee, L Kral, AH Seal, KH Lorvick, J Tobler, LH Andrews, WW Phelps, BH Busch, MP O'Brien, TR AF Edlin, BR Gee, L Kral, AH Seal, KH Lorvick, J Tobler, LH Andrews, WW Phelps, BH Busch, MP O'Brien, TR TI Duration of injection drug use affects likelihood of hepatitis C virus infection but not viral persistence. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Urban Hlth Study, San Francisco, CA 94143 USA. Blood Ctr Pacific, San Francisco, CA USA. Chiron Corp, Emeryville, CA 94608 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 32 IS 4 MA 1533 BP 543A EP 543A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401518 ER PT J AU Lu, DTY Khokhar, MF Doo, E Ghany, MG Herion, D Park, Y Kleiner, DE Schmid, P Condreay, LD Gauthier, J Kuhns, MC Liang, TJ Hoofnagle, JH AF Lu, DTY Khokhar, MF Doo, E Ghany, MG Herion, D Park, Y Kleiner, DE Schmid, P Condreay, LD Gauthier, J Kuhns, MC Liang, TJ Hoofnagle, JH TI Long-term therapy of chronic hepatitis B with lamivudine SO HEPATOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; VIRAL-HEPATITIS; INTERFERON-ALFA; UNITED-STATES; FOLLOW-UP; VIRUS; MUTATION; TRIAL; SUSCEPTIBILITY; RESISTANCE AB Lamivudine therapy induces improvements in chronic hepatitis B in a high proportion of patients, but prolonged therapy is limited by the development of viral resistance. We analyzed clinical responses and virologic resistance in 27 patients treated continuously with lamivudine for 2 to 4 years. Serum transaminases, hepatitis B virus (HBV) DNA by both branched DNA (bDNA) signal amplification and quantitative polymerase chain reaction were monitored at 4- to 8-week intervals. Virologic resistance to lamivudine was confirmed by the presence of mutations in the YMDD motif of the polymerase gene by restriction fragment-length polymorphism analysis. Serum HBV-DNA levels decreased rapidly in all treated patients, falling by 4 to 5 logs within 1 year. Transaminase levels also decreased and were normal in 70% of patients at 1 year, at which point liver histology had improved in 81% of patients. Viral resistance began to emerge after 8 months of therapy, eventually developing in 14 patients, including 76% of hepatitis B e antigen (HBeAg)-positive patients but only 10% of HBeAg-negative patients. Lamivudine withdrawal led to reappearance of wild-type HBV species, but retreatment led to more rapid reappearance of the mutant virus. Clinical, serum biochemical, and histologic improvements were maintained in the 13 patients who did not develop resistance. Thus, long-term therapy with lamivudine resulted in maintained improvements in virologic, biochemical, and histologic features of disease in most patients with HBeAg-negative chronic hepatitis B and in the subgroup of HBeAg-positive patients with high serum transaminase levels. A high rate of resistance limited efficacy, particularly in patients who remained HBeAg positive on therapy. C1 NIDDKD, Digest Dis Branch, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Genet, Los Angeles, CA USA. Glaxo Wellcome Inc, Dept Virol, Res Triangle Pk, NC 27709 USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Digest Dis Branch, Liver Dis Sect, NIH, Bldg 31,Room 9A23, Bethesda, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 NR 39 TC 10 Z9 12 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 BP 828 EP 834 DI 10.1053/jhep.2000.17912 PN 1 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PF UT WOS:000089618700020 ER PT J AU Sasano, Y Li, HC Zhu, JX Imanaka-Yoshida, K Mizoguchi, I Kagayama, M AF Sasano, Y Li, HC Zhu, JX Imanaka-Yoshida, K Mizoguchi, I Kagayama, M TI Immunohistochemical localization of type I collagen, fibronectin and tenascin C during embryonic osteogenesis in the dentary of mandibles and tibias in rats SO HISTOCHEMICAL JOURNAL LA English DT Article ID CALVARIAL OSTEOBLAST DIFFERENTIATION; EXTRACELLULAR-MATRIX; INTEGRIN RECEPTORS; EXPRESSION; BONE; INVITRO; GROWTH; CHONDROGENESIS; OSSIFICATION; CONDENSATION AB Type I collagen, fibronectin and tenascin C play an important role in regulating early osteoblast differentiation, but the temporal and spatial relationship of their localization during embryonic osteogenesis in vivo is not known. The present study was designed to localize these three molecules in the dentary of mandibles and tibias in rat embryos using immunohistochemistry. Serial paraffin sections were cut and adjacent sections were processed for von Kossa staining or immunohistochemistry for type I collagen, fibronectin and tenascin C. In the dentary, tenascin C was localized within and around the mesenchymal cell condensation in embryos at 14 days in utero. The bone matrix at 15 days showed immunoreactivity for both type I collagen and fibronectin. The immunoreactivity of type I collagen was persistent, whereas that of fibronectin decreased with age of embryos. In tibias, tenascin C was localized in the perichondral mesenchymal tissue at 17 days. Immunoreactivity for type I collagen was persistent in the bone matrix, whereas the tibial bone showed little immunoreactivity for fibronectin at any embryonic age examined. The present study demonstrated characteristic localization of type I collagen, fibronectin and tenascin C during embryonic osteogenesis in the dentary of mandibles and tibias. C1 Tohoku Univ, Sch Dent, Dept Oral Anat 2, Sendai, Miyagi 9808575, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Mie Univ, Sch Med, Dept Pathol, Tsu, Mie 5148507, Japan. Hlth Sci Univ Hokkaido, Sch Dent, Dept Orthodont, Tobetsu, Hokkaido 0610293, Japan. RP Sasano, Y (reprint author), Tohoku Univ, Sch Dent, Dept Oral Anat 2, Sendai, Miyagi 9808575, Japan. NR 34 TC 24 Z9 25 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD OCT PY 2000 VL 32 IS 10 BP 591 EP 598 DI 10.1023/A:1026720003564 PG 8 WC Cell Biology SC Cell Biology GA 379FG UT WOS:000165630700002 PM 11202155 ER PT J AU Koh, CY Welniak, LA Murphy, WJ AF Koh, CY Welniak, LA Murphy, WJ TI Adoptive cellular immunotherapy: NK cells and bone marrow transplantation SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE NK cells; GVHD; GVT; allogeneic BMT ID VERSUS-HOST DISEASE; NATURAL-KILLER-CELLS; COLONY-STIMULATING FACTOR; HIGH-DOSE CHEMOTHERAPY; CYTOTOXIC T-CELLS; INTERFERON-GAMMA; RECOMBINANT INTERLEUKIN-2; PECULIAR IMMUNOBIOLOGY; CYTOKINE PRODUCTION; ANTIBODY-RESPONSES AB Allogeneic bone marrow transplantation (BMT) has been increasingly used for the treatment of both neoplastic and non-neoplastic disorders. However, serious obstacles currently limit the efficacy and thus more extensive use of BMT. These obstacles include: graft-versus-host disease (GVHD), relapse from the original tumor, and susceptibility of patients to opportunistic infections due to the immunosuppressive effects of the conditioning regimen. Overcoming these obstacles is complicated by dual outcome of existing regimens; attempts to reduce GVHD by depleting T cells from the graft, result in increased rates of tumor relapse and failure of engraftment. On the other hand, efforts to increase graft-versus-tumor (GVT) effects of the transplant also promote GVHD. In this review, the use of natural killer (NK) cells to overcome some of these obstacles of allogeneic BMT is evaluated. Adoptive immunotherapy using NK cells after allogeneic BMT has several potential advantages. First, NK cells can promote hematopoiesis and therefore engraftment by production of hematopoietic growth factors. Second, NK cells have been shown to prevent the incidence and severity of GVHD. This has been shown to be at least partially due to TGF-TS, an immunosuppressive cytokine. Third, NK cells have been shown to augment numerous anti-tumor effects in animals after BMT suggesting a vital role of NK cells in mediating GVT effects. Finally, NK cells have been demonstrated to affect B cell recovery and function in mice. Therefore, understanding the mechanisms of beneficial effects of NK cells after BMT may lead to significant increases in the efficacy of this procedure. C1 SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Frederick, MD USA. RP Murphy, WJ (reprint author), SAIC Frederick, Intramural Res Support Program, Bldg 567,Room 210, Frederick, MD 21702 USA. RI Koh, Crystal/D-9986-2013 FU NCI NIH HHS [N01-CO-56000] NR 92 TC 15 Z9 19 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD OCT PY 2000 VL 15 IS 4 BP 1201 EP 1210 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 355NC UT WOS:000089390900023 PM 11005245 ER PT J AU Quintanilla-Martinez, L Jaffe, ES AF Quintanilla-Martinez, L Jaffe, ES TI Aggressive NK cell lymphomas: insights into the spectrum of NK cell derived malignancies SO HISTOPATHOLOGY LA English DT Editorial Material ID GRANULAR LYMPHOCYTE LEUKEMIA; BARR VIRAL-DNA; T-CELL; EXPRESSION; VARIANT; DISEASE; CD3(+); ENTITY; NASAL C1 GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Pathol, Oberschleissheim, Germany. NCI, Hematopathol Sect, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NIH, Bldg 10,Room 2N202,10 Center Dr,MSC 1500, Bethesda, MD 20892 USA. NR 30 TC 21 Z9 22 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2000 VL 37 IS 4 BP 372 EP 374 DI 10.1046/j.1365-2559.2000.01029.x PG 3 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 405MX UT WOS:000167164500011 PM 11012745 ER PT J AU Longui, CA Vottero, A Adamson, PC Cole, DE Kino, T Monte, O Chrousos, GP AF Longui, CA Vottero, A Adamson, PC Cole, DE Kino, T Monte, O Chrousos, GP TI Low glucocorticoid receptor alpha/beta ratio in T-cell lymphoblastic leukemia SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE glucocorticoid receptor; acute leukemia; glucocorticoid sensitivity; glucocorticoid resistance ID INDUCED APOPTOSIS; DOWN-REGULATION; LYMPHOCYTIC-LEUKEMIA; DRUG-RESISTANCE; BETA-ISOFORM; CEM-C1 CELLS; CHILDHOOD; EXPRESSION; CHILDREN; GENE AB Glucocorticoid therapy is pivotal in the treatment of acute lymphoblastic leukemia (ALL); it reduces cell proliferation, promotes cell cycle arrest, and induces cell death by apoptosis, The sensitivity of leukemic cells to glucocorticoids was previously related to the cell concentration of (3)[H]dexamethasone-binding sites. The latter represents the classic glucocorticoid receptor (GR) isoform cr that binds ligand and modulates the transcription rates of glucocorticoid-responsive genes. In ALL, lymphoblasts of T-lineage are less sensitive to glucocorticoids than cells of the B-lineage, The alternatively spliced CR isoform (GR beta), which exerts a dominant negative effect on GR alpha -mediated transcriptional activity, has been proposed as a possible mediator of glucocorticoid resistance. In this study, we determined the amount of GR alpha and GR beta in mononuclear cells from 13 newly diagnosed and untreated children with ALL and 9 controls by quantitative Western analysis. Generally, leukemic patients expressed 6 times less GR alpha (ALL = 0.54 +/- 1.1; controls = 3.1 +/- 0.9; p < 0.01) than controls, but the same amount of GRP (ALL = 3.62 +/- 3.3: controls = 3.6 +/- 3.4). ALL patients with T-cell disease had a much lower GR (0.09 +/- 0.1;p < 0.01) but a similar or slightly higher GR (5.98 +/- 3.9: p = 0.1) expression than controls, with a GR alpha /GR beta ratio 15 times smaller than controls. Mononuclear leukocytes of T-cell lineage expressed significantly lower GR alpha (p = 0.04) and higher CR beta (p < 0.01) than cells of the pre-B immunophenotype, with a 10 times smaller ratio. We conclude that: the combination of low GR and normal-to-high GR beta expression in leukemic lymphoblasts might represent one of the mechanisms responsible for their reduced glucocorticoid sensitivity; this is more pronounced in T-lineage cells. C1 Santa Casa Sao Paulo, Sch Med, Pediat Endocrinol Unit, Dept Pediat, BR-01221020 Sao Paulo, Brazil. Santa Casa Sao Paulo, Sch Med, Pediat Endocrinol Unit, Dept Physiol, BR-01221020 Sao Paulo, Brazil. NICHD, Sect Pediat Endocrinol, DEB, NIH, Bethesda, MD USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Longui, CA (reprint author), Santa Casa Sao Paulo, Sch Med, Pediat Endocrinol Unit, Dept Pediat, Rua Cesareo Motta Jr,112,Vila Buarque, BR-01221020 Sao Paulo, Brazil. RI Monte, Osmar/G-9063-2012; OI Monte, Osmar/0000-0002-2549-9237 NR 44 TC 56 Z9 63 U1 0 U2 3 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 OCT PY 2000 VL 32 IS 10 BP 401 EP 406 DI 10.1055/s-2007-978661 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 368YG UT WOS:000090144600004 PM 11069204 ER PT J AU Singh, GK Hoyert, DL AF Singh, GK Hoyert, DL TI Social epidemiology of chronic liver disease and cirrhosis mortality in the United States, 1935-1997: Trends and differentials by ethnicity, socioeconomic status, and alcohol consumption SO HUMAN BIOLOGY LA English DT Article ID NATIONAL LONGITUDINAL MORTALITY; AMERICAN; MEN AB This study examines trends and ethnic and socioeconomic differentials in chronic liver disease and cirrhosis mortality in the United States. Age-adjusted death rates from the National Vital Statistics System were used to analyze race and sex-specific mortality trends from 1968 through 1997, Age-adjusted liver cirrhosis mortality and per capita alcohol consumption data from 1935 through 1996 were modeled using time-series regression. Moreover, the Cox hazards regression was applied to the National Longitudinal Mortality Study, 1979-1989, to examine socioeconomic differentials at the individual level, whereas multivariate ordinary least squares regression was used to model state-specific cirrhosis mortality from 1990 to 1997 as a function of socioeconomic variables and alcohol consumption at the ecological level. Chronic liver disease and cirrhosis continues to be an important cause of death in the United States, even after three decades of consistently declining mortality rates. For both men and women aged 25 years and older, significant mortality differentials were found by age, race/ethnicity, marital status, family income, and employment status. For men, marked differentials were also found by nativity, rural-urban residence, and education. Unemployment, minority concentration, and alcohol consumption were major predictors of state-specific cirrhosis mortality. Both time-series and cross-sectional data indicate a strong correlation between alcohol consumption and US cirrhosis mortality. Substantial ethnic and socioeconomic differences in cirrhosis mortality suggest the need for social and public health policies and interventions that target such high-risk groups as American Indians, Hispanic Americans, the socially isolated, and the poor. C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Natl Ctr Hlth Stat, Ctr Dis Control & Prevent, Div Vital Stat, Hyattsville, MD 20782 USA. RP Singh, GK (reprint author), NCI, Div Canc Control & Populat Sci, NIH, Execut Plaza N,Suite 343J,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. NR 38 TC 87 Z9 88 U1 2 U2 12 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0018-7143 J9 HUM BIOL JI Hum. Biol. PD OCT PY 2000 VL 72 IS 5 BP 801 EP 820 PG 20 WC Biology; Genetics & Heredity SC Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA 379MY UT WOS:000165647700005 PM 11126726 ER PT J AU Chima, SC Ryschkewitsch, CF Fan, KJ Stoner, GL AF Chima, SC Ryschkewitsch, CF Fan, KJ Stoner, GL TI Polyomavirus JC genotypes in art urban United States population reflect the history of African origin and genetic admixture in modern African Americans SO HUMAN BIOLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SEQUENCE-ANALYSIS; COMPLETE GENOMES; VIRUS-DNA; TRANSMISSION; INFECTION; TISSUE; URINE AB The human polyomavirus JC (JC virus) a small, circular, I double-stranded DNA virus, has a worldwide distribution and is excreted harmlessly in urine by 20% to 70% of adults. DNA sequence analysis has identified seven distinct genotypes that likely coevolved with modern humans, although the mode of virus transmission is unknown. Type 1 is European in its distribution. Types 2 and 7 are Asian, while Types 3 and 6 are African. Type 4, closely related to Type 1, is of uncertain origin, having been found in population groups in parts of Europe and in the United States, but not in Africa. Here we have studied the JCV partial genomic DNA sequences amplified by polymerase chain reaction techniques from urines of an urban, mainly African American population cohort from Washington, D.C, The predominant genotype identified was Type 4 (32/78 JCV strains, 41%), Type 1 strain was found in 32% of African Americans, while JCV Type 3 strain was found in 18% of African Americans. These African strains have persisted in modern African Americans after 200 to 400 years of minority existence and genetic admixture in the New World. An ancient West African genotype, Type 6, was absent in this African American cohort. However, one Type 6 strain was found in a patient from Sierra Leone (West Africa), domiciled in the United States for 20 years. Type 2A, the most common subtype in Native Americans, was seen in only two African-Americans (3%). A Type 7 strain, previously reported only in Taiwan and South China, was identified in a Vietnamese immigrant. These data support the history of African origin, migration, and genetic admixture of modern African Americans. Analysis of JCV strains in the present American populations provides a novel tool for reconstructing human migrations and genetic admixture in the New World. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Pathol, Washington, DC 20059 USA. RP Chima, SC (reprint author), NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. RI Chima, Sylvester Chidi/N-5564-2013 NR 37 TC 16 Z9 16 U1 0 U2 5 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0018-7143 J9 HUM BIOL JI Hum. Biol. PD OCT PY 2000 VL 72 IS 5 BP 837 EP 850 PG 14 WC Biology; Genetics & Heredity SC Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA 379MY UT WOS:000165647700007 PM 11126728 ER PT J AU Bergthorsson, JT Johannesdottir, G Arason, A Benediktsdottir, KR Agnarsson, BA Bailey-Wilson, JE Gillanders, E Smith, J Trent, J Barkardottir, RS AF Bergthorsson, JT Johannesdottir, G Arason, A Benediktsdottir, KR Agnarsson, BA Bailey-Wilson, JE Gillanders, E Smith, J Trent, J Barkardottir, RS TI Analysis of HPC1, HPCX, and PCaP in Icelandic hereditary prostate cancer SO HUMAN GENETICS LA English DT Article ID SUSCEPTIBILITY LOCUS; ALLELIC IMBALANCE; CHROMOSOME; LINKAGE; TUMORS; GENE AB Putative prostate cancer susceptibility loci have recently been identified by genetic linkage analysis on chromosomes 1924-25 (HPC1), 1q44.2-43 (PCaP), and Xq27-28 (HPCX). In order to estimate the genetic linkage in Icelandic prostate cancer families, we genotyped 241 samples from 87 families with eleven markers in the HPC1 region, six markers at PCaP, and eight at HPCX. Concurrently we assessed allelic imbalance at the HPC1 and PCaP loci in selected tumors from the patients. For each of the candidate regions, the combined parametric and non-parametric LOD scores were strongly negative. Evidence for linkage allowing for genetic heterogeneity was also insignificant for all the regions. The results were negative irrespective of whether calculations were performed for the whole material or for a selected set of early age at onset families. The prevalence of allelic imbalance was relatively low in both the HPC1 (0%-9%) and PCaP (5%-20%) regions and was not elevated in tumors from positively linked families. Our studies indicate that the putative cancer susceptibility genes at chromosomes 1q24-25, 1q44.2-43, and Xq27-28 are unlikely to contribute significantly to hereditary prostate cancer in Iceland and that selective loss of the HPC1 and PCaP loci is a relatively ran somatic event in prostate cancers. C1 Univ Hosp Iceland, Dept Pathol, Cell Biol Lab, IS-101 Reykjavik, Iceland. NHGRI, Prostata Canc Invest Grp, NIH, Bethesda, MD 20892 USA. RP Barkardottir, RS (reprint author), Univ Hosp Iceland, Dept Pathol, Cell Biol Lab, House 14, IS-101 Reykjavik, Iceland. RI Smith, Jeff/C-3484-2012; OI Bailey-Wilson, Joan/0000-0002-9153-2920 NR 17 TC 22 Z9 22 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 2000 VL 107 IS 4 BP 372 EP 375 DI 10.1007/s004390000384 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 375UH UT WOS:000165419300011 PM 11129338 ER PT J AU Tayebi, N Park, J Madike, V Sidransky, E AF Tayebi, N Park, J Madike, V Sidransky, E TI Gene rearrangement on 1q21 introducing a duplication of the glucocerebrosidase pseudogene and a metaxin fusion gene SO HUMAN GENETICS LA English DT Article ID GAUCHER-DISEASE; MUTATIONS AB The genes for glucocerebrosidase and metaxin, both located on chromosome 1q21, each have a highly homologous pseudogene sequence nearby. We describe a novel recombinant allele consisting of a duplication of the glucocerebrosidase pseudogene and a fusion between the metaxin gene and its pseudogene, resulting from a crossover between metaxin and pseudometaxin in the region downstream of the glucocerebrosidase gene. We also show that certain individuals have a metaxin-pseudometaxin fusion gene without a duplication, resulting from the same crossover. DNA from patients with Gaucher disease and normal controls were screened for recombinant alleles by Southern blot analyses prepared with the restriction enzymes SspI and HincII and by direct sequencing. Downstream alterations were identified in eight of the 398 patient alleles studied and in seven of the 200 normal control alleles examined, and were encountered more frequently among patients and controls of African-American ancestry. This is the first recognition of a duplicated allele in the glucocerebrosidase gene region, and its presence may contribute to genotype-phenotype studies in Gaucher disease. C1 NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, NIH, 49 Convent Dr,MSC4405, Bethesda, MD 20892 USA. NR 14 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 2000 VL 107 IS 4 BP 400 EP 403 DI 10.1007/s004390000380 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 375UH UT WOS:000165419300016 PM 11129343 ER PT J AU Zipp, F Windemuth, C Pankow, H Dichgans, J Wienker, T Martin, R Muller, C AF Zipp, F Windemuth, C Pankow, H Dichgans, J Wienker, T Martin, R Muller, C TI Multiple sclerosis associated amino acids of polymorphic regions relevant for the HLA antigen binding are confined to HLA-DR2 SO HUMAN IMMUNOLOGY LA English DT Article DE genetic; HLA; antigen binding; multiple sclerosis; autoimmunity ID MYELIN BASIC-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DEPENDENT DIABETES-MELLITUS; CELL SUBSET ACTIVATION; II BETA-CHAIN; HYPERVARIABLE REGION; CYTOKINE PROFILE; PEPTIDE BINDING; GENETIC-FACTORS; MHC CONTROL AB Among the candidate genes for multiple sclerosis (MS), the strongest influence is conferred by human leucocyte antigen (HLA) class II genes, in particular the DR2, DQ6, Dw2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602). Similar to other autoimmune diseases, it is not clear yet how the presence of a specific HLA-DR or -DQ molecule translates into an increased disease susceptibility. Previous observations by us and others imply a HLA-DR2 dependent propensity of antigen-specific T-cell lines to produce increased amounts of TNF-alpha/beta as one mechanism how DR2 could contribute to susceptibility. In this article, we investigated the distribution of polymorphic stretches of the DRB1, DQA1, and DQB1 chains known to be relevant for antigen binding, in 66 unrelated patients with relapsing remitting MS and 210 unrelated controls. We found a significant association with disease for the appearance of proline at position Il, arginine at position 13, and alanine at position 71 of HLA-DR beta1. Surprisingly, we identified only residues preferentially expressed in the MS group that were related to HLA-DR2. Thus, the contribution of HLA class II to the pathogenesis of MS is not mediated by allele-overlapping antigen binding sites, but is confined to the disease associated HLA allele. (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc. C1 Univ Hosp Charite, Div Neuroimmunol, Dept Neurol, D-13353 Berlin, Germany. Univ Bonn, Dept Med Stat, D-5300 Bonn, Germany. Max Delbruck Ctr Mol Med, Dept Genet, Berlin, Germany. Univ Tubingen, Dept Neurol, D-7400 Tubingen, Germany. Univ Tubingen, Dept Internal Med, Div Transplantationsimmunol, D-7400 Tubingen, Germany. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Zipp, F (reprint author), Univ Hosp Charite, Div Neuroimmunol, Dept Neurol, 20G R 535,Augustenburger Pl 1, D-13353 Berlin, Germany. RI Zipp, Frauke/C-9968-2015 OI Zipp, Frauke/0000-0002-1231-1928 NR 43 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 2000 VL 61 IS 10 BP 1021 EP 1030 DI 10.1016/S0198-8859(00)00173-7 PG 10 WC Immunology SC Immunology GA 375UN UT WOS:000165419800008 PM 11082515 ER PT J AU Matsui, K Tatsuguchi, A Valencia, J Yu, ZX Bechtle, J Beasley, MB Avila, N Travis, WD Moss, J Ferrans, VJ AF Matsui, K Tatsuguchi, A Valencia, J Yu, ZX Bechtle, J Beasley, MB Avila, N Travis, WD Moss, J Ferrans, VJ TI Extrapulmonary lymphangioleiomyomatosis (LAM): Clinicopathologic features in 22 cases SO HUMAN PATHOLOGY LA English DT Article DE extrapulmonary; immunohistochemistry; lymphangioleiomyomatosis; lymph node; mediastinum; retroperitoneum ID PULMONARY LYMPHANGIOLEIOMYOMATOSIS; RENAL ANGIOMYOLIPOMA; LYMPHANGIOMYOMATOSIS; RECEPTORS; LUNG AB We describe the lesions of extrapulmonary lymphangioleiomyomatosis (LAM) affecting the lymph nodes of the mediastinun and retroperitoneum in 22 women (mean age +/- SD, 42.4 +/- 10.5 years). In most of these patients, the diagnosis of extrapulmonary LAM preceded that of pulmonary LAM, usually by 1 to 2 years. Eleven patients had distinct symptoms, including chylous pleural effusion and/or ascites, abdominal, pain, and palpable abdominal masses. In the other 11 patients, the masses caused no symptoms. Well-circumscribed, encapsulated masses, measuring up to 20 cm in size, occurred in the mediastinum in 2 patients, the upper retroperitoneum in 15, extensive areas of the retroperitoneun in 2, and the pelvis in 3. The masses exceeding 3 cm in diameter contained large, multiple cysts filled with yellow-tan chylous fluid. Histologically, the masses were characterized by a proliferation of smooth muscle cells (LAM cells) arranged in fascicular, trabecular, and papillary patterns, which were associated with slit-like vascular channels. The LAM cells varied from small, spindle-shaped cells to large epithelioid cells. Immunohistochemical studies showed a strong reactivity of most LAM cells for alpha -smooth muscle actin and smooth muscle myosin heavy chain and a weak to moderate reactivity of a lesser number of cells for desmin and nonmuscle myosin heavy chain II-B. A reaction for HMB-45 and estrogen and progesterone receptors was observed mainly in epithelioid LAM cells. These patterns of reactivity are similar to those observed in pulmonary LAM. However, the chylous cysts are not a feature of pulmonary LAM and are thought to result from obstruction of lymphatics. HUM PATHOL 31:1242-1248. Copyright (C) 2000 by W.B. Saunders Company. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Ferrans, VJ (reprint author), NHLBI, Pathol Sect, NIH, Bldg 10,Room 2N240,10 Ctr Dr,MSC-1518, Bethesda, MD 20892 USA. NR 21 TC 105 Z9 114 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2000 VL 31 IS 10 BP 1242 EP 1248 DI 10.1053/hupa.2000.18500 PG 7 WC Pathology SC Pathology GA 369KB UT WOS:000165063500012 PM 11070117 ER PT J AU Beasley, MB Thunnissen, FBJ Brambilla, E Hasleton, P Steele, R Hammar, SP Colby, TV Sheppard, M Shimosato, Y Koss, MN Falk, R Travis, WD AF Beasley, MB Thunnissen, FBJ Brambilla, E Hasleton, P Steele, R Hammar, SP Colby, TV Sheppard, M Shimosato, Y Koss, MN Falk, R Travis, WD TI Pulmonary atypical carcinoid: Predictors of survival in 106 cases SO HUMAN PATHOLOGY LA English DT Article DE carcinoid; atypical carcinoid; lung; pulmonary; neuroendocrine; mitoses; bronchus; large cell neuroendocrine carcinoma. ID NEUROENDOCRINE LUNG-TUMORS; BRONCHIAL CARCINOIDS; CELL CARCINOMAS; REPRODUCIBILITY; CLASSIFICATION; SPECTRUM; FEATURES; CRITERIA; P53 AB Pulmonary neuroendocrine tumors (NE) include a spectrum of tumors from typical carcinoid (TC) to atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). Little is known about prognostic predictors for AC because of its rarity. Survival analysis was performed on 106 ACs with clinical follow-up from the AFIP and the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). The rumors fulfilled the 1999 WHO/IASLC criteria for AC of a NE tumor with a mitotic rate of 9 to 10 per 2 mm(2) of viable tumor or coagulative necrosis. Multiple clinical and histologic features were analyzed by Kaplan-Meier and Cox regression analysis. Of the clinical features, higher stage (P = .003) and a tumor size of 3.5 cm or greater (P = .003) were associated with a worse prognosis. Features that were histologically unfavorable by univariate analysis were mitotic rate (P = .002), pleomorphism (P = .018), and aerogenous spread (P = .007). Histologically favorable features by univariate analysis were the presence of palisading (P = .008), papillary (P = .039), pseudoglandular (P = .026), and rosette (P = .022) patterns. Female gender showed a trend toward a poorer prognosis (P = .085) and was included in the multivariate model. Multivariate analysis stratified for stage showed mitoses (P < .001), a tumor size of 3.5 cm or greater (P = .017), and female gender (P = .012) to be the only negative independent predictors of prognosis and the presence of rosettes (P = .016) to be the only independent positive predictor. We further divided the AC into subgroups of low (2 to 5 mitoses/2 mm2) and high (6 to 10 mitoses/2 mm2) mitotic rate and compared the survival with TC and with LCNEC. Within the category of AC, the patients with a higher mitotic rate had a significantly worse survival than those with a lower mitotic rate (P < .001) stratified for stage. Five- and 10-year survival rates for AC (61% and 35%, respectively) stratified for stage were significantly worse than for TC and better than that for LCNEC and SCLC. Chemotherapy or radiation therapy was given in 12 of 52 and 14 of 52 cases, respectively, but the data were insufficient to evaluate tumor response. We conclude that AC is an aggressive neuroendocrine neoplasm with survival intermediate between TC and LCNEC and SCLC. Higher mitotic rate, tumor size of 3.5 cm or greater, female gender, and presence of rosettes are the only independent predictors of survival. Surgical resection remains the treatment of choice, and the role of chemotherapy and radiation therapy remains to be proven. HUM PATHOL 31:1255-1265. This is a US Government work. There are no restrictions on its use. C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Canisius Wilhemina Hosp, Nymegen, Netherlands. CHU Grenoble, F-38043 Grenoble, France. Univ Manchester, Sch Med, Manchester, Lancs, England. Princess Alexandra Hosp, Woolloongabba, Qld, Australia. Diagnost Specialties Lab, Bremerton, WA USA. Mayo Clin, Scottsdale, AZ USA. Royal Brompton Hosp, London SW3 6LY, England. Keio Univ, Sch Med, Tokyo, Japan. NCI, Environm Epidemiol Branch, NIH, Rockville, MD USA. RP Beasley, MB (reprint author), Tulane Univ, Med Ctr, Dept Pathol, 5L-79,1430 Tulane Ave, New Orleans, LA 70122 USA. RI Brambilla, Elisabeth/L-8796-2013; OI Thunnissen, Erik/0000-0001-5355-8508 NR 40 TC 124 Z9 133 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2000 VL 31 IS 10 BP 1255 EP 1265 DI 10.1053/hupa.2000.19294 PG 11 WC Pathology SC Pathology GA 369KB UT WOS:000165063500014 PM 11070119 ER PT J AU Levy, D DeStefano, AL Larson, MG O'Donnell, CJ Lifton, RP Gavras, H Cupples, LA Myers, RH AF Levy, D DeStefano, AL Larson, MG O'Donnell, CJ Lifton, RP Gavras, H Cupples, LA Myers, RH TI Evidence for a gene influencing blood pressure on chromosome 17 - Genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the Framingham Heart Study SO HYPERTENSION LA English DT Article DE genetics; genome scan; linkage; epidemiology; hypertension, essential; blood pressure; Framingham Heart Study ID EPITHELIAL SODIUM-CHANNEL; ESSENTIAL-HYPERTENSION; RAT CHROMOSOME-10; RECEPTOR LOCUS; MUTATIONS; ANGIOTENSINOGEN; ASSOCIATION; DISSECTION; SUBUNIT; CELLS AB Hypertension is a leading cause of morbidity and mortality. Efforts to identify hypertension genes have focused on 3 approaches: mendelian disorders, candidate genes, and genome-wide scans. Thus far, these efforts have not identified genes that contribute substantively to overall blood pressure (BP) variation in the community. A 10-centiMorgan (cM) density genome-wide scan was performed in the largest families from 2 generations of Framingham Heart Study participants. Heritability and linkage for long-term mean systolic and diastolic BP phenotypes were analyzed by use of SOLAR software. Heritability estimates were based on BP measurements in 1593 families. Genotyping was performed on 1702 subjects from 332 large families, and BP data were available for 1585 (93%) genotyped subjects who contributed 12 588 longitudinal BP observations. The mean age was 47 years, and mean BP was 127/80 (systolic/diastolic) mm Hg. Long-term systolic and diastolic BP phenotypes had high heritability estimates, 0.57 and 0.56, respectively. For systolic BP, multipoint log-of-the-odds (LOD) scores >2.0 were located on chromosome 17 at 67 cM (LOD 4.7, P=0.0000016) and 94 cM (LOD 2,2). For diastolic BP, LOD scores >2.0 were identified on chromosome 17 (74 cM, LOD 2.1) and chromosome 18 (7 cM, LOD 2.1). Using a genome-wide scan, we found strong evidence for a BP quantitative trait locus on chromosome 17. Follow-up studies are warranted to identify the gene or genes in this quantitative trait locus that influence BP. Such knowledge could extend our understanding of the genetic basis of essential hypertension and have implications for the evaluation and treatment of patients with high BP. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Genet Program, Boston, MA 02118 USA. Boston Univ, Sch Med, Hypertens Sect, Dept Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Div Cardiol, Boston, MA 02114 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Med, New Haven, CT 06510 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038, P50HL55001, P50HL55007] NR 35 TC 415 Z9 433 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 477 EP 483 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900003 PM 11040222 ER PT J AU Weyer, C Pratley, RE Snitker, S Spraul, M Ravussin, E Tataranni, PA AF Weyer, C Pratley, RE Snitker, S Spraul, M Ravussin, E Tataranni, PA TI Ethnic differences in insulinemia and sympathetic tone as links between obesity and blood pressure SO HYPERTENSION LA English DT Article DE adipose tissue; hyperinsulinism; autonomic nervous system; hypertension, obesity; ethnic groups ID BORDERLINE HYPERTENSIVE HUMANS; NERVE ACTIVITY; PIMA-INDIANS; GLUCOSE-INTOLERANCE; HYPERINSULINEMIA; RESISTANCE; OVERACTIVITY; MECHANISMS; CAUCASIANS; HALLMARK AB Hyperinsulinemia and increased sympathetic nervous system (SNS) activity are thought to be pathophysiological links between obesity and hypertension. In the present study, we examined the relation among heart rate (HR), blood pressure (BP), and percent body fat (hydrodensitometry or DEXA), fasting plasma insulin concentration, and muscle sympathetic nerve activity (MSNA, microneurography) in male, normotensive whites (n=42) and Pima Indians (n=77). Pima Indians have a high prevalence of obesity and hyperinsulinemia but a relatively low prevalence of hypertension. Compared with whites, Pima Indian men had a higher percent body fat (28% versus 21%) and higher fasting insulin concentrations (210 versus 132 pmol/L) but lower MSNA (27 versus 33 bursts/min) tall P<0.001). In both ethnic groups, HR and BP were positively related to percent body fat and MSNA, and both were significant independent determinants of HR and BP in multiple regression analyses. However, MSNA was positively related to percent body fat and the fasting insulin concentration in whites (r=0.60 and r=0.47, both P<0.01) but not in Pima Indians (r=0.15 and r=0.03, NS) (P<0.01 for ethnic differences in the slope of the regression lines). These results confirm the physiological importance of the SNS in normal BP regulation but indicate that the roles of hyperinsulinemia and increased SNS activity as mediators for the relation between obesity and hypertension can differ between different ethnic groups. The lack of an increase in SNS activity with increasing adiposity and insulinemia in Pima Indians may contribute to the low prevalence of hypertension in this population. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. Univ Dusseldorf, Dept Metab Dis & Nutr, D-4000 Dusseldorf, Germany. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St,Room 5-41, Phoenix, AZ 85016 USA. NR 37 TC 78 Z9 83 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 531 EP 537 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900012 PM 11040231 ER PT J AU Johansson, M Elam, M Rundqvist, B Eisenhofer, G Herlitz, H Jensen, G Friberg, P AF Johansson, M Elam, M Rundqvist, B Eisenhofer, G Herlitz, H Jensen, G Friberg, P TI Differentiated response of the sympathetic nervous system to angiotensin-converting enzyme inhibition in hypertension SO HYPERTENSION LA English DT Article DE hypertension, renovascular; sympathetic nervous system; renin-angiotensin system ID RENOVASCULAR HYPERTENSION; RENAL-FUNCTION; PLASMA; NORADRENALINE; FAILURE; RELEASE; HUMANS; RABBIT AB Hypertension with renal artery stenosis is associated with both an activated renin-angiotensin system and elevated sympathetic activity. Therefore, in this condition it may be favorable to use a therapeutic modality that does not reflexly increase heart rate, renin secretion, and sympathetic nervous activity. The purpose of the present study was to assess overall, renal, and muscle sympathetic activity after short-term administration of an angiotensin-converting enzyme inhibitor (enalaprilat) and a nonspecific vasodilator (dihydralazine) to hypertensive patients with renal artery stenosis, Forty-eight patients undergoing a clinical investigation for renovascular hypertension were included in the study. An isotope dilution technique for assessing norepinephrine spillover was used to estimate overall and bilateral renal sympathetic nerve activity. In 11 patients simultaneous intraneural recordings renal sympathetic nerve activity. in 11 patients simultaneous intraneural recordings of efferent muscle sympathetic nerve activity were performed. Thirty minutes after dihydralazine administration, mean arterial pressure fell by 15%, whereas plasma angiotensin IT, muscle sympathetic nerve activity, heart rate, and total body norepinephrine spillover increased (P<0.05 for all). In contrast, after enalaprilat administration a fall in arterial pressure similar to that for dihydralazine was followed by decreased angiotensin II levels and unchanged muscle sympathetic nerve activity, heart rate, and total body norepinephrine spillover, whereas renal norepinephrine spillover increased by 44% (P<0.05). Acute blood pressure reduction by an angiotensin-converting enzyme inhibitor provokes a differentiated sympathetic response in patients with hypertension and renal artery stenosis, inasmuch that overall and muscle sympathetic reflex activation are blunted, whereas the reflex renal sympathetic response to blood pressure reduction is preserved. C1 Sahlgrens Univ Hosp, Univ Gothenburg, Dept Clin Physiol, SE-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Univ Gothenburg, Dept Clin Neurophysiol, SE-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Univ Gothenburg, Dept Cardiol, SE-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Univ Gothenburg, Dept Nephrol, SE-41345 Gothenburg, Sweden. NINDS, Bethesda, MD USA. RP Johansson, M (reprint author), Sahlgrens Univ Hosp, Univ Gothenburg, Dept Clin Physiol, SE-41345 Gothenburg, Sweden. NR 31 TC 25 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 543 EP 548 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900014 PM 11040233 ER PT J AU Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Roccella, EJ Levy, D AF Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Roccella, EJ Levy, D TI Differential control of systolic and diastolic blood pressure - Factors associated with lack of blood pressure control in the community SO HYPERTENSION LA English DT Article DE hypertension detection and control; blood pressure; epidemiology; antihypertensive therapy ID CORONARY HEART-DISEASE; PULSE PRESSURE; CARDIOVASCULAR MORTALITY; HYPERTENSION; FRAMINGHAM; POPULATION; RISK; PREVALENCE AB Data from the Third National Health and Nutrition Examination Survey, phase 2 (1991 to 1994), indicate that among hypertensive individuals in the United States, 53.6% are treated and only 27.4% are controlled to goal levels. We sought to determine whether poor hypertension control is due to lack of systolic or diastolic blood pressure control, or both. We studied Framingham Heart Study participants examined between 1990 and 1995 and determined rates of control to systolic goal (<140 mm Hg), diastolic goal (<90 mm Hg), or both (systolic <140 and diastolic <90 mm Hg). Of 1959 hypertensive subjects (mean age 66 years, 54% women), 32.7% were controlled to systolic goal, 82.9% were controlled to diastolic goal, and only 29.0% were controlled to both. Among the 1189 subjects who were receiving antihypertensive therapy (60.7% of all hypertensive subjects), 49.0% were controlled to systolic goal, 89.7% were controlled to diastolic goal, and only 47.8% were controlled to both. Thus, poor systolic blood pressure control was overwhelmingly responsible for poor rates of overall control to goal. Covariates associated with lack of systolic control in treated subjects included older age (OR for age 61 to 75 years, 2.43, 95% CI 1.79 to 3.29; OR for age >75 years, 4.33, 95% CI 3.10 to 6.09), left ventricular hypertrophy (OR 1.63, 95% CI 1.04 to 2.54), and obesity (OR for body mass index greater than or equal to 30 versus <25 kg/m(2), 1.49, 95% CI 1.08 to 2.06). In this community-based sample of middle-aged and older subjects, overall rates of hypertension control were remarkably similar to those in the Third National Health and Nutrition Examination Survey. Poor blood pressure control was overwhelmingly due to lack of systolic control, even among treated subjects. Therefore, clinicians and policymakers should place greater emphasis on the achievement of goal systolic levels in all hypertensive patients, especially those who are older or obese or have target organ damage. C1 NHLBI, Farmingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. NHLBI, Natl High Blood Pressure Educ Program, Bethesda, MD 20892 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. RP Levy, D (reprint author), NHLBI, Farmingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 28 TC 231 Z9 242 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 594 EP 599 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900022 PM 11040241 ER PT J AU Nelson, CR Knapp, DA AF Nelson, CR Knapp, DA TI Trends in antihypertensive drug therapy of ambulatory patients by US office-based physicians SO HYPERTENSION LA English DT Article DE antihypertensive agents; hypertension, essential; drug therapy ID UNITED-STATES AB This study assessed trends from 1980 to 1995 in ambulatory patients' antihypertensive drug therapy by US office-based physicians for visits in which hypertension was the principal diagnosis and compared these trends with the respective guidelines given in 5 Joint National Committee (JNC) Reports on Detection, Evaluation, and Treatment of High Blood Pressure published around the same time period. Data from the National Center for Health Statistics' National Ambulatory Medical Care Surveys for 1980, 1985, 1990, and 1995 were used. From 1980 to 1995, there was no significant trend in the percentage of. hypertension visits that did not mention any antihypertensive drug (20% to 27%). Further analyses focused on those hypertension visits in which at least 1 antihypertensive drug was used. Across the years, antihypertensive drug visits mentioning calcium channel blockers or ACE inhibitors significantly increased; those noting diuretics significantly decreased. However, in 1995, antihypertensive drug visits that included a diuretic and/or a beta -adrenergic blocker equalled 53%; these are the antihypertensive drug classes preferred by the JNC V. Physician antihypertensive drug prescribing was generally consistent with the basic antihypertensive drug guidelines of the JNC reports. C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, Baltimore, MD 21201 USA. RP Nelson, CR (reprint author), NHLBI, Div Epidemiol & Clin Applicat, NIH, 2 Rockledge Ctr,6701 Rockledge Dr,Room 8152, Bethesda, MD 20892 USA. NR 27 TC 55 Z9 55 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 600 EP 603 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900023 PM 11040242 ER PT J AU Turner, PL Masilamani, SME Reyes, I Knepper, MA AF Turner, PL Masilamani, SME Reyes, I Knepper, MA TI Long-term effect of nitric oxide inhibition on Na transporter abundance in kidney: A targeted proteomics approach. SO HYPERTENSION LA English DT Meeting Abstract C1 NHLBI, NIH, Lkem, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 681 EP 681 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900175 ER PT J AU Fedorova, OV Kolodkin, NI Lakatta, EG Bagrov, AY AF Fedorova, OV Kolodkin, NI Lakatta, EG Bagrov, AY TI An endogenous ligand of alpha-1 sodium pump in hypertensive Dahl salt sensitive rats SO HYPERTENSION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 710 EP 711 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900330 ER PT J AU Goldstein, DS Eisenhofer, G Li, ST Pacak, K AF Goldstein, DS Eisenhofer, G Li, ST Pacak, K TI 6-[F-18]Fluorodopamine positron emission tomographic (PET) scanning in the diagnostic localization of pheochromocytoma SO HYPERTENSION LA English DT Meeting Abstract C1 NINDS, 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 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 714 EP 715 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900352 ER PT J AU Masilamani, SME Kim, GH Knepper, MA AF Masilamani, SME Kim, GH Knepper, MA TI Differential regulation of the epithelial sodium channel (ENaC) in rat kidney, lung and distal colon in response to aldosterone. SO HYPERTENSION LA English DT Meeting Abstract C1 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 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 724 EP 724 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900402 ER PT J AU Bek, MJ Asico, L Eisner, GM Sibley, DR Jose, PA AF Bek, MJ Asico, L Eisner, GM Sibley, DR Jose, PA TI Non-N-methyl D-Aspartate receptors are involved in the hypertension of D5 dopamine receptor knockout mice. SO HYPERTENSION LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 726 EP 726 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900417 ER PT J AU Chan, FKM Siegel, RM Lenardo, MJ AF Chan, FKM Siegel, RM Lenardo, MJ TI Signaling by the TNF receptor superfamily and T cell homeostasis SO IMMUNITY LA English DT Review ID NECROSIS-FACTOR RECEPTOR; APOPTOSIS; DOMAINS; ACTIVATION; LYMPHOCYTE; MUTATIONS C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. EM mlenardo@nih.gov RI Siegel, Richard/C-7592-2009; Chan, Francis/E-9647-2014; Chan, Francis K. L./F-4851-2010 OI Siegel, Richard/0000-0001-5953-9893; Chan, Francis/0000-0002-4803-8353; Chan, Francis K. L./0000-0001-7388-2436 NR 18 TC 109 Z9 111 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD OCT PY 2000 VL 13 IS 4 BP 419 EP 422 DI 10.1016/S1074-7613(00)00041-8 PG 4 WC Immunology SC Immunology GA 367UD UT WOS:000090079100001 ER PT J AU Schulz, O Edwards, AD Schito, M Aliberti, J Manickasingham, S Sher, A Sousa, CRE AF Schulz, O Edwards, AD Schito, M Aliberti, J Manickasingham, S Sher, A Sousa, CRE TI CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal SO IMMUNITY LA English DT Article ID IN-VIVO; DIFFERENTIAL EXPRESSION; MOUSE CD40; INTERLEUKIN-12; IMMUNITY; ACTIVATION; INDUCTION; INFECTION; CYTOKINE; ANTIGEN AB CD40 ligation triggers IL-12 production by dendritic cells (DC) in vitro. Here, we demonstrate that CD40 cross-linking alone is not sufficient to induce IL-12 production by DC in vivo. Indeed, resting DC make neither the IL-12 p35 nor IL-12 p40 subunits and express only low levels of CD40. Nevertheless, after DC activation by microbial stimuli that primarily upregulate IL-12 p40 and augment CD40 expression, CD40 ligation induces a significant increase in IL-12 p35 and IL-12 p70 heterodimer production. Similarly, IL-12 p70 is produced during T cell activation in the presence but not in the absence of microbial stimuli. Thus, production of bioactive IL-12 by DC can be amplified by T cell-derived signals but must be initiated by innate signals. C1 Imperial Canc Res Fund, Immunobiol Lab, London WC2A 3PX, England. NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. RP Sousa, CRE (reprint author), Imperial Canc Res Fund, Immunobiol Lab, 44 Lincolns Inn Fields, London WC2A 3PX, England. RI Edwards, Alexander/F-7440-2010; Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Edwards, Alexander/0000-0003-2369-989X; Aliberti, Julio/0000-0003-3420-8478 NR 42 TC 400 Z9 405 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2000 VL 13 IS 4 BP 453 EP 462 DI 10.1016/S1074-7613(00)00045-5 PG 10 WC Immunology SC Immunology GA 367UD UT WOS:000090079100005 PM 11070164 ER PT J AU Baker, BM Gagnon, SJ Biddison, WE Wiley, DC AF Baker, BM Gagnon, SJ Biddison, WE Wiley, DC TI Conversion of a T cell antagonist into an agonist by repairing a defect in the TCR/peptide/MHC interface: Implications for TCR signaling SO IMMUNITY LA English DT Article ID CAVITY-CREATING MUTATIONS; PEPTIDE-MHC COMPLEXES; MULTIVALENT STRUCTURE; DISSOCIATION RATE; RECEPTOR-BINDING; VIRUS TYPE-1; ALPHA-BETA; LIGANDS; RECOGNITION; HLA-A2 AB The structure of the A6 alpha beta TCR/HTLV-1 Tax-peptide/MHC I complex with proline 6 of Tax substituted with alanine (P6A), an antagonist, is nearly identical to the structure with wild-type Tax agonist. Neither the proline in the agonist nor the alanine in the antagonist is contacted by the alpha beta TCR. Here, we demonstrate that antagonist activity of P6A is associated with low affinity of the A6 alpha beta TCR for Tax-P6A/HLA-A2. We show that stepwise repair of a packing defect in the TCR/MHC interface using N-alkylated amino acids results in stepwise increases in TCR affinity and activity. Kinetic and thermodynamic measurements suggest that for some ligands the range of T cell outcomes does not correlate with either their alpha beta TCR affinity or the half-life of the alpha beta TCR/peptide/MHC complex. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Howard Hughes Med Inst, Cambridge, MA 02138 USA. NINDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Wiley, DC (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RI Baker, Brian/B-4584-2009 OI Baker, Brian/0000-0002-0864-0964 NR 45 TC 100 Z9 100 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2000 VL 13 IS 4 BP 475 EP 484 DI 10.1016/S1074-7613(00)00047-9 PG 10 WC Immunology SC Immunology GA 367UD UT WOS:000090079100007 PM 11070166 ER PT J AU Slansky, JE Rattis, FM Boyd, LF Fahmy, T Jaffee, EM Schneck, JP Margulies, DH Pardoll, DM AF Slansky, JE Rattis, FM Boyd, LF Fahmy, T Jaffee, EM Schneck, JP Margulies, DH Pardoll, DM TI Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC-peptide-TCR complex SO IMMUNITY LA English DT Article ID T-CELL-RECEPTOR; SURFACE-PLASMON RESONANCE; TUMOR REJECTION ANTIGEN; CLASS-I MOLECULE; 3-DIMENSIONAL STRUCTURE; MHC/PEPTIDE COMPLEXES; BINDING-SPECIFICITY; DENDRITIC CELLS; HIGH-AFFINITY; LOW AVIDITY AB T cell responsiveness to an epitope is affected both by its affinity for the presenting MHC molecule and the affinity of the MHC-peptide complex for TCR. One limitation of cancer immunotherapy is that natural tumor antigens elicit relatively weak T cell responses, in part because high-affinity T cells are rendered tolerant to these antigens. We report here that amino acid substitutions in a natural MHC class I-restricted tumor antigen that increase the stability of the MHC-peptide-TCR complex are significantly more potent as tumor vaccines. The improved immunity results from enhanced in vivo expansion of T cells specific for the natural tumor epitope. These results indicate peptides that stabilize the MHC-peptide-TCR complex may provide superior antitumor immunity through enhanced stimulation of specific T cells. C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA. NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pathol & Med, Div Immunopathol, Baltimore, MD 21205 USA. RP Pardoll, DM (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NCI NIH HHS [CA57842, CA76669] NR 59 TC 202 Z9 206 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2000 VL 13 IS 4 BP 529 EP 538 DI 10.1016/S1074-7613(00)00052-2 PG 10 WC Immunology SC Immunology GA 367UD UT WOS:000090079100012 PM 11070171 ER PT J AU Chertov, O Yang, D Howard, OMZ Oppenheim, JJ AF Chertov, O Yang, D Howard, OMZ Oppenheim, JJ TI Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses SO IMMUNOLOGICAL REVIEWS LA English DT Review ID HUMAN NEUTROPHIL DEFENSINS; HEPARIN-BINDING PROTEIN; EOSINOPHIL CATIONIC PROTEIN; G-DEFICIENT MICE; CATHEPSIN-G; ANTIMICROBIAL PEPTIDES; MAST-CELL; EPITHELIAL-CELLS; DENDRITIC CELLS; BETA-DEFENSINS AB "...It is likely that the leukocyte granulations are in fact secretory products, which the cell dissolves and spreads to the environment as needed", Paul Ehrlich, 1900. Neutrophil granules have long been recognized as mediators of innate host defense. Newly discovered functions for individual granule proteins suggest that granule constituents may also participate in adaptive immune responses. Neutrophil granule-derived cathepsin G, azurocidin/CAP37 and alpha-defensins have been shown to be chemotactic for mononuclear cells and neutrophils. Analysis of the chemotactic activity of alpha-defensins shows that they induce CD45RA(+) and CD8 T-lymphocyte cell migration at concentrations 10 to 100-fold below that required for direct bactericidal activity. Additionally, alpha and beta defensins form chemotactic gradients for immature dendritic cells. Recruiting immature dendritic cells to sites of infection is one way for neutrophil granule proteins to initiate adaptive immune responses. Granules found in other leukocytes such as mast cells also contain serine proteases, such as chymase, that are known to chemoattract neutrophils and mononuclear cells. Preliminary evidence suggests that exocytosis of granule-derived products from a variety of leukocytes can mobilize inflammatory cells and immunocytes. Thus, leukocyte granule-derived proteins, more rapidly than chemokines, can mobilize cells that mediate innate host defense and adaptive immunity. C1 NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 21-89, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-56000] NR 114 TC 121 Z9 124 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2000 VL 177 BP 68 EP 78 DI 10.1034/j.1600-065X.2000.17702.x PG 11 WC Immunology SC Immunology GA 380EH UT WOS:000165685700007 PM 11138786 ER PT J AU Kinter, A Arthos, J Cicala, C Fauci, AS AF Kinter, A Arthos, J Cicala, C Fauci, AS TI Chemokines, cytokines and HIV: a complex network of interactions that influence HIV pathogenesis SO IMMUNOLOGICAL REVIEWS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; FOCAL ADHESION KINASE; C-C CHEMOKINES; INFLAMMATORY PROTEIN (MIP)-1-ALPHA; EXPOSED-UNINFECTED INDIVIDUALS; MACROPHAGE-TROPIC HIV; BETA-CHEMOKINES; CCR5 EXPRESSION; INFECTED INDIVIDUALS AB The important role of chemokine receptors in HIV pathogenesis is becoming increasingly apparent. The level at which certain chemokine receptors that serve as HIV co-receptors are available influences the susceptibility of a CD4(+) cell to viral infection and to certain HIV envelope-induced alterations in cellular function. Numerous pathogens, including HIV can stimulate the production of chemokines and cytokines from a variety of cell types. Both cytokines and chemokines modulate CCR5 and CXCR4 availability, resulting in differential replication potentials for R5 and X4 HIV strains depending on the milieu in the microenvironment. In addition, differential expression of CCR5 and CXCR4 on activated memory T cells appears to play an important role in preferential replication of R5 HIV strains in vivo. However, expression of HIV co-receptors and CD4 may not be sufficient for effective HIV entry and replication. Intracellular signaling events, triggered by interaction between chemokine receptors and chemokines or HN envelope, are important for efficient entry and completion of early replication events. Envelope proteins of different HN isolates vary in their ability to transduce these signals, a characteristic that may play a role in determining the ability of a virus to productively infect certain cell types. Finally, the interaction between chemokine receptors and chemokines or HIV envelope has significant effects on cellular functions which likely play a role in HIV pathogenesis. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kinter, A (reprint author), Bldg 10,Room 6A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 107 TC 80 Z9 83 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2000 VL 177 BP 88 EP 98 DI 10.1034/j.1600-065X.2000.17708.x PG 11 WC Immunology SC Immunology GA 380EH UT WOS:000165685700009 PM 11138789 ER PT J AU O'Brien, SJ Moore, JP AF O'Brien, SJ Moore, JP TI The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS SO IMMUNOLOGICAL REVIEWS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MACROPHAGE-TROPIC HIV-1; CELL-DERIVED FACTOR-1; CD4(+) T-CELLS; DISEASE PROGRESSION; TYPE-1 INFECTION; CCR5 GENE; ANTIRETROVIRAL THERAPY; GASTROINTESTINAL-TRACT; CD28 COSTIMULATION AB The pivotal discovery that two chemokine receptors, CCR5 and CXCR4, serve along with the T-cell receptor-interacting CD4 molecule as the principal co-receptors for HIV-1 entry stimulated a search for common genetic polymorphism in their genes which might affect the course of AIDS. Four mutational variants, CCR5-Delta 32, CCR5-P1, CCR2-64I and SDF1-3'A were discovered to play a regulatory role in HIV-1 infection, in the rate of progression to AIDS or both. Plausible physiological mechanisms to explain the population genetic association by these alleles have been advanced and are discussed critically here. Genetic ablation of AIDS progression by chemokine receptor and Ligand gene variants has catalyzed development of novel therapies targeting the virus-co-receptor interaction. The functional and therapeutic implications of these AIDS restriction genes for disease progression and intervention are explored in this review. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Cornell Univ, Joan & Sanford I Weill Med Coll, New York, NY USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. NR 132 TC 197 Z9 209 U1 1 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2000 VL 177 BP 99 EP 111 DI 10.1034/j.1600-065X.2000.17710.x PG 13 WC Immunology SC Immunology GA 380EH UT WOS:000165685700010 PM 11138790 ER PT J AU Mahalingam, S Foster, PS Lobigs, M Farber, JM Karupiah, G AF Mahalingam, S Foster, PS Lobigs, M Farber, JM Karupiah, G TI Interferon-inducible chemokines and immunity to poxvirus infections SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-LYMPHOCYTES; ANTIVIRAL ACTIVITY; VIRAL-INFECTIONS; VIRUS-INFECTION; NATURAL-KILLER; NK CELLS; IN-VIVO; CYTOKINES; EXPRESSION; CRG-2 AB The biological roles of two interferon-inducible chemokines, monokine induced by gamma interferon (Mig) and cytokine responsive gene (Crg-2), in the immune response against vaccinia virus (VV) and ectromelia virus (EV) infections are discussed. To investigate their antiviral effects in viva, the expression profiles of these chemokines during the course of VV or EV infections were first established. Mig and Crg-2 were induced in multiple organs at high levels early after infection with VV. Both chemokines were rapidly induced in popliteal lymph nodes of C57BL/6 mice but nor in BALB/c mice following infection with EV Secondly recombinant vaccinia viruses (rVV) encoding Mig or Crg-2 were constructed to investigate the immunobiology of infection in athymic, nude and euthymic, normal mice. Finally the EV model in combination with recombinant Mig and Crg-2 proteins was used to test their effects on viral replication and immune responses in vivo. The results of these investigations demonstrate that the mechanisms of Mig- and Crg-2-induced viral clearance involve natural killer cells and interferons. C1 Australian Natl Univ, John Curtin Sch Med Res, Div Biochem & Mol Biol, Canberra, ACT 2601, Australia. Australian Natl Univ, John Curtin Sch Med Res, Div Cell Biol & Immunol, Canberra, ACT 2601, Australia. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Univ Sydney, Fac Med, Dept Pathol, Sydney, NSW 2006, Australia. RP Mahalingam, S (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Div Biochem & Mol Biol, POB 334, Canberra, ACT 2601, Australia. RI Foster, Paul/G-5057-2013; Karupiah, Gunasegaran/J-4707-2013 NR 33 TC 19 Z9 19 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2000 VL 177 BP 127 EP 133 DI 10.1034/j.1600-065X.2000.17720.x PG 7 WC Immunology SC Immunology GA 380EH UT WOS:000165685700012 PM 11138770 ER PT J AU Le, YY Li, BQ Gong, WH Shen, WP Hu, JY Dunlop, NM Oppenheim, JJ Wang, JM AF Le, YY Li, BQ Gong, WH Shen, WP Hu, JY Dunlop, NM Oppenheim, JJ Wang, JM TI Novel pathophysiological role of classical chemotactic peptide receptors and their communications with chemokine receptors SO IMMUNOLOGICAL REVIEWS LA English DT Review ID N-FORMYL PEPTIDE; SERUM AMYLOID-A; LIPOXIN A(4) RECEPTOR; METHIONYL-LEUCYL-PHENYLALANINE; PROTEIN-COUPLED RECEPTORS; HIV-1 ENVELOPE GP41; PLATELET FACTOR-IV; FORMYLPEPTIDE RECEPTOR; HUMAN-NEUTROPHILS; HUMAN MONOCYTES AB The bacterial N-formylpeptides, such as N-formyl-Met-Leu-Phe (fMLF), are some of the first identified and most potent chemoattractants for phagocytic leukocytes. Two fMLF receptors, the high affinity formyl peptide receptor (FPR) and its low affinity variant FPR-like I (FPRL1), belong to the seven-transmembrane, Gi protein-coupled receptor superfamily which also includes chemokine receptors. Despite their reaction with bacterial chemotactic peptides, the physiological role of these receptors in humans remains unclear Our recent studies have identified novel exogenous as well as host-derived agonists for FPR and FPRL1. Furthermore, activation of these receptors by their agonists results in desensitization of the receptors for other chemoattractants, including two chemokine receptors, CCR5 and CXCR4, which serve as major co-receptors for HIV-1. These results suggest that FPR and FPRL1 may play important roles not only in host defense and immunological responses but also in the fine tuning of cell activation in the presence of multiple stimuli. C1 NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-40, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 100 TC 37 Z9 38 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2000 VL 177 BP 185 EP 194 DI 10.1034/j.1600-065X.2000.17704.x PG 10 WC Immunology SC Immunology GA 380EH UT WOS:000165685700017 PM 11138775 ER PT J AU Nylander-French, LA French, JE AF Nylander-French, LA French, JE TI Comparative in vitro cytotoxicity of ethyl acrylate and tripropylene glycol diacrylate to normal human skin and lung cells SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE acrylates; cytotoxicity; human keratinocytes; fibroblasts; bronchiolar cells ID DERMAL ONCOGENICITY BIOASSAYS; MOUSE LYMPHOMA-CELLS; MULTIFUNCTIONAL ACRYLATES; 344 RATS; TOXICITY; MICE; KERATINOCYTES; FIBROBLASTS; ACID; CARCINOGENICITY AB The potential for occupational exposure to the esters of acrylic acid (acrylates) is considerable: and, thus, requires a greater understanding of the their toxicity. Confluent (70-90%) cultures of normal human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF), or bronchial epithelium (NHBE) were exposed to the monofunctional ethyl acrylate (EA), the multifunctional tripropylene glycol diacrylate (TPGDA), or TPGDA monomer in a radiation curable lacquer (Lacquer A) at equimolar dosages in order to determine human in vitro cytotoxicity. Viability of the cells after 2-24-h exposure to the representative monofunctional or multifunctional acrylate or solvent control was used to calculate an index of acute cytotoxicity (50% inhibitory dose; ID50) and to determine the shape of the dose-response curves. TPGDA, Lacquer A, and EA were equally cytotoxic (ID50 approximate to0.1 mu mol/cm(2)) to NHEK at equimolar doses. TPGDA or Lacquer A were more cytotoxic (approximate to 100X) to NHDF or NHBE than EA. Sequential exposure of UV, and TPGDA to NHEK indicate the potential for a synergistic cytotoxic response. These findings are consistent with observed decreases in free sulfhydryl groups (e.g., glutathione or cysteine) that parallel the dose-response-related decreases in viability. Together, these data suggest possible differences in toxicity between the monofunctional EA and multifunctional TPGDA to NHEK, NHDF, or NHBE, possibly due to the difference in the number of functional acrylate groups and/or physicochemical differences (e.g., vapor pressure) between the acrylates investigated. C1 Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Nylander-French, LA (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, CB 7400,Rosenau Hall, Chapel Hill, NC 27599 USA. NR 44 TC 1 Z9 1 U1 1 U2 4 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD OCT PY 2000 VL 36 IS 9 BP 611 EP 616 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 397AP UT WOS:000166671000009 ER PT J AU Stowers, AW Keister, DB Muratova, O Kaslow, DC AF Stowers, AW Keister, DB Muratova, O Kaslow, DC TI A region of Plasmodium falciparum antigen Pfs25 that is the target of highly potent transmission-blocking antibodies SO INFECTION AND IMMUNITY LA English DT Article ID MULTISTAGE VACCINE CANDIDATE; SACCHAROMYCES-CEREVISIAE; RECOMBINANT PFS25; SURFACE PROTEIN; SEXUAL STAGE; MALARIA; IMMUNOGENICITY; EXPRESSION; MULTIANTIGEN; INDUCTION AB Each of the four epidermal growth factor (EGF)-like domains of the Plasmodium falciparum sexual-stage antigen Pfs25 has been individually expressed as a yeast-secreted recombinant protein (yEGF1 through yEGF4). All four are recognized by the immune sera of animals and humans vaccinated with TBV25H (the corresponding yeast-secreted full-length recombinant form of Pfs25), with antibody titers to yEGF1 and yEGF2 weakly correlating with the ability of the sera to block the transmission of parasites to the mosquito host. All four proteins are poorly immunogenic in mice vaccinated with aluminum hydroxide-absorbed formulations. However, all four successfully primed the mice to mount an effective secondary antibody response after a single boost with TBV25H, Sera from mice vaccinated with yEGF2-TBV25H completely block the development of oocysts in mosquito midguts in membrane-feeding assays. Further, of the four proteins, only the depletion of antibodies to yEGF2 from the sera of rabbits vaccinated with TBV25H consistently abolished the ability of those sera to block oocyst development. Thus, antibodies to the second EGF-like domain of Pfs25 appear to mediate a very potent blocking activity, even at low titers, Vaccination strategies that target antibody response towards this domain may improve the efficacy of future transmission-blocking vaccines. C1 NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. RP Stowers, AW (reprint author), NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Twinbrook 2,Room 103,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 24 TC 29 Z9 32 U1 0 U2 0 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 OCT PY 2000 VL 68 IS 10 BP 5530 EP 5538 DI 10.1128/IAI.68.10.5530-5538.2000 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 355QE UT WOS:000089395700009 PM 10992450 ER PT J AU Potter, MR Noben-Trauth, N Weis, JH Teuscher, G Weis, JJ AF Potter, MR Noben-Trauth, N Weis, JH Teuscher, G Weis, JJ TI Interleukin-4 (IL-4) and IL-13 signaling pathways do not regulate Borrelia burgdorferi-induced arthritis in mice: IgG1 is not required for host control of tissue spirochetes SO INFECTION AND IMMUNITY LA English DT Article ID MURINE LYME-DISEASE; SEVERE COMBINED IMMUNODEFICIENCY; T-CELLS; SCHISTOSOMA-MANSONI; SUSCEPTIBLE MICE; LABORATORY MICE; SCID MICE; B-CELLS; RECEPTOR; RESPONSES AB Previous studies have suggested that interleukin-4 (IL-4) has a protective effect in host defense to Borrelia burgdorferi infection, both in limiting the severity of arthritis and in controlling spirochete numbers in tissues, and a mapping study revealed suggestive linkage to a cluster of genes on mouse chromosome Il, including the genes for IL-4 and IL-13. In contrast, other studies have questioned the importance of IL-4, In this study the involvement of IL-4 in murine Lyme disease was examined in C57BL/6J and BALB/cJ mice with targeted disruptions in the IL-4 gene, the IL-4R alpha chain gene, or both. A spectrum of arthritis severity was seen in BALB/cJ mice, and ablation of IL-4, IL-4R alpha, or both had no effect on the overall severity of arthritis as determined by joint swelling and histopathology, Wild-type C57B/6J mice exhibited mild to moderate arthritis, and ablation of IL-4 again had no effect on arthritis severity. IL-4- and IL-4R alpha-deficient mice produced extremely low levels of immunoglobulin G1 (IgG1) and showed increased production of IgG2b. This shift in immunoglobulin isotype had no effect on the host's ability to control spirochete growth in either strain of mouse, as determined by PCR detection of B. burgdorferi DNA from heart and ankle tissues. In summary, the IL-4-IL-4R alpha pathway, including IL-13 signaling, neither limits arthritis severity nor is required for control of spirochete growth during B, burgdorferi infection of mice. Furthermore, the IgG1 isotype is not required to control B, burgdorferi cell numbers in tissues, These findings suggest the host defense against B, burgdorferi infection is not dependent on the Th1-Th2. paradigm of T-cell responses. C1 Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Vet Pathobiol, Urbana, IL 61802 USA. RP Weis, JJ (reprint author), Univ Utah, Sch Med, Dept Pathol, 50 N Med Dr, Salt Lake City, UT 84132 USA. FU NCI NIH HHS [P30 CA042014, 5P30-CA-42014]; NIAID NIH HHS [AI-32223, R01 AI032223, R56 AI032223]; NIAMS NIH HHS [R01 AR043521, AR-43521]; NIGMS NIH HHS [T32 GM007464] NR 53 TC 22 Z9 22 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2000 VL 68 IS 10 BP 5603 EP 5609 DI 10.1128/IAI.68.10.5603-5609.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 355QE UT WOS:000089395700019 PM 10992460 ER PT J AU Walsh, TJ Roden, M Roilides, E Groll, A AF Walsh, TJ Roden, M Roilides, E Groll, A TI Concepts in design of comparative clinical trials of antifungal therapy in neutropenic patients SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE antifungal therapy; neutropenic patients; cancer ID B COLLOIDAL DISPERSION; UNILAMELLAR LIPOSOMAL FORMULATION; INVASIVE PULMONARY ASPERGILLOSIS; AMPHOTERICIN-B; FUNGAL-INFECTIONS; RISK-FACTORS; MARROW TRANSPLANT; EMPIRICAL THERAPY; LIPID COMPLEX; PHARMACOKINETICS AB Fundamental to the successful implementation of antifungal compounds in neutropenic patients is the appropriate design of comparative clinical trials investigating their safety and efficacy. The key elements of comparative clinical trial design include issues of enrolment, stratification, randomization, blinding, administration of study drugs, monitoring of drug toxicity, definitions, and key statistical elements of end points, sample size, and tools for data analysis. The initial selection of compounds and the timing of initiation of antifungal therapy in comparative clinical trials are predicated to a large degree on the in vitro and in vivo activities, plasma pharmacokinetics, profiles of safety and toxicity of the study drugs. Phase I and II studies have a critical role in designing comparative clinical trials of antifungal therapy by providing data on safety, tolerance, and plasma pharmacokinetics of the investigational agent. As new antifungal agents are developed in response to the challenge of invasive fungal infections in immunocompromised patients with cancer, thoughtfully designed and carefully implemented clinical trials will be essential in determining the future utility of these promising compounds. (C) 2000 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N-240, Bethesda, MD 20892 USA. NR 34 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD OCT PY 2000 VL 16 IS 2 SI SI BP 151 EP 156 DI 10.1016/S0924-8579(00)00242-9 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 368PB UT WOS:000090125600018 PM 11053799 ER PT J AU Martinez-Lacaci, I Kannan, S De Santis, M Bianco, C Kim, N Wallace-Jones, B Ebert, AD Wechselberger, C Salomon, DS AF Martinez-Lacaci, I Kannan, S De Santis, M Bianco, C Kim, N Wallace-Jones, B Ebert, AD Wechselberger, C Salomon, DS TI Ras transformation causes sustained activation of epidermal growth factor receptor and elevation of mitogen-activated protein kinase in human mammary epithelial cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN BREAST-CANCER; HA-RAS; NUCLEAR TRANSLOCATION; INCREASING COMPLEXITY; SIGNALING PATHWAY; EXPRESSION; EGF; PHOSPHORYLATION; SPECIFICITY; ANTIBODIES AB Activation of the ms oncogene is an important step in carcinogenesis. Human MCF-10A mammary epithelial cells were transformed with a point-mutated form of the Ha-ms oncogene, Epidermal growth factor receptor (EGFR) phosphorylation levels were chronically elevated after EGF induction and the EGFR ligand-driven internalization rate was slower in Ha-res transformed MCF-10A cells, Additionally, basal levels of p42/44 mitogen-activated protein kinase (MAPK) expression and enzyme activity were significantly higher in Ha-res transformed cells, localized predominantly in the nucleus. The anti-EGFR monoclonal antibody (MAb) 225 and the EGFR tyrosine kinase inhibitor PD153035 blocked anchorage-independent growth of Ha-ms transformed cells in soft agar and were more effective when used in combination, The MEK inhibitor PD98059 and anti-erbB-2 MAb L26 also suppressed colony formation of Ha-res transformed cells in soft agar, Therefore, Ha-ms transformation leads to an augmentation in signaling through the EGFR as a result of an increase in ligand-dependent phosphorylation, a decrease in its internalization and an up-regulation in basal p44/42 MAPK levels. These effects may contribute to uncontrolled growth of Ha-ms-transformed human mammary epithelial cells. Published 2000 Wiley-Liss, Inc.(dagger) C1 NCI, Tumor Growth Factor Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. McMaster Univ, Hamilton, ON, Canada. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Mol Pathol, Washington, DC 20307 USA. Free Univ Berlin, Benjamin Franklin Med Ctr, Dept Obstet & Gynecol, D-1000 Berlin, Germany. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Tumor Immunol & Biol Lab, NIH, Bldg 10,Rm 5B39, Bethesda, MD 20892 USA. NR 44 TC 26 Z9 27 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 OCT 1 PY 2000 VL 88 IS 1 BP 44 EP 52 DI 10.1002/1097-0215(20001001)88:1<44::AID-IJC7>3.0.CO;2-8 PG 9 WC Oncology SC Oncology GA 349TQ UT WOS:000089062000007 PM 10962438 ER PT J AU Wang, LD Lubin, JH Zhang, SR Metayer, C Xia, Y Brenner, A Shang, B Wang, ZY Kleinerman, RA AF Wang, LD Lubin, JH Zhang, SR Metayer, C Xia, Y Brenner, A Shang, B Wang, ZY Kleinerman, RA TI Lung cancer and environmental tobacco smoke in a non-industrial area of China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PASSIVE SMOKING; RISK-FACTORS; CIGARETTE-SMOKING; NONSMOKING WOMEN; HISTOLOGIC TYPE; SOUTHERN CHINA; AIR-POLLUTION; TIN MINERS; EXPOSURE; METAANALYSIS AB We report results from a population-based case-control study of lung cancer and environmental tobacco smoke (ETS) among never-smokers conducted in 2 rural prefectures of China, including 200 female and 33 male lung cancer cases, and 407 female and 114 male controls, matched on age, sex and prefecture of current residence. The odds ratio (OR) for ever-exposed to ETS was 1.19 (95% CI 0.7-2.0), with a significant trend (p < 0.05) with increasing exposure. ORs were 1.00, 1.04, 1.13 and 1.51 for non-exposed, < 10, 10-19 and greater than or equal to 20 pack-years of ETS exposure, respectively. Excess risks were limited to ETS exposures in childhood (less than or equal to 18 years of age). The OR for ever-exposed to ETS in childhood, adjusting for ETS exposure in adulthood, was 1.52 (95% CI 1.1-2.2), with a significant trend (p < 0.01) with increasing pack-years of childhood exposure, 1.00, 1.43, 1.81 and 2.95, respectively. After adjustment for ETS in childhood, there was no excess risk from adult ETS exposure. The OR for ever-exposed to ETS in adulthood was 0.90 (95% CI 0.-1.4). These results were not affected by adjustment for type of residential dwelling, type or amount of fuel used, perceived indoor smokiness, or measures of socioeconomic status, or omitting next-of-kin respondents. Published 2000 Wiley-Liss, Inc.(dagger) C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, EPS-8042,6120 Execut Blvd, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 51 TC 32 Z9 36 U1 2 U2 6 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 OCT 1 PY 2000 VL 88 IS 1 BP 139 EP 145 DI 10.1002/1097-0215(20001001)88:1<139::AID-IJC22>3.0.CO;2-L PG 7 WC Oncology SC Oncology GA 349TQ UT WOS:000089062000022 PM 10962452 ER PT J AU Damjanovski, S Sachs, LM Shi, YB AF Damjanovski, S Sachs, LM Shi, YB TI Multiple stage-dependent roles for histone deacetylases during amphibian embryogenesis: implications for the involvement of extracellular matrix remodeling SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE Xenopus laevis; matrix metalloproteinase; histone acetylation; chromatin remodeling; morphogenesis ID XENOPUS-LAEVIS; TRICHOSTATIN-A; TRANSCRIPTIONAL REPRESSION; CHROMATIN STRUCTURE; GENE-EXPRESSION; NUCLEOSOMAL DNA; IN-VITRO; ACETYLATION; METAMORPHOSIS; ACTIVATION AB Histone acetylation has long been implicated in the regulation of gene expression. Recently, a number of histone acetyltransferase and histone deacetylase genes have been identified and cloned. Molecular studies have shown that these enzymes influence transcriptional regulation as components of cofactor complexes that interact with diverse transcription factors. However, relatively little is known about their function during development, Here,we make use of the ability to manipulate Xenopus laevis embryos in vitro to study the role of histone deacetylases in development. We first demonstrate that the histone deacetylase Rpd3 and its associated co-repressor Sin3A are coordinately expressed during embryogenesis. Rpd3 and Sin3A are known to be part of at least one large corepressor complex, which is involved in transcriptional regulation by many transcription factors, suggesting that deacetylase activity is important for embryogenesis through transcriptional regulation. Indeed, treating developing embryos with a specific histone deacetylase inhibitor, trichostatin A (TSA), leads to embryonic lethality with severe defects in the head and tail regions. Furthermore, the effects of TSA are stage-dependent with the severity of the defects decreasing when treatment is initiated at later stages. On the other hand, a sharp bend (kink) develops in the tail even when TSA treatment begins at tadpole hatching. We provide evidence that this tail defect may be in part due to the TSA-dependent inhibition of the expression of the matrix metalloproteinase gene stromelysin-3, which has been implicated in tail development through extracellular matrix remodeling. C1 NICHHD, Mol Embryol Lab, Unit Mol Morphogenesis, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Mol Embryol Lab, Unit Mol Morphogenesis, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 34 TC 11 Z9 12 U1 0 U2 2 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD OCT PY 2000 VL 44 IS 7 BP 769 EP 776 PG 8 WC Developmental Biology SC Developmental Biology GA 380NW UT WOS:000165708800003 PM 11128570 ER PT J AU Madigan, MP Troisi, R Potischman, N Brogan, D Gammon, MD Malone, KE Brinton, LA AF Madigan, MP Troisi, R Potischman, N Brogan, D Gammon, MD Malone, KE Brinton, LA TI Characteristics of respondents and non-respondents from a case-control study of breast cancer in younger women SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; epidemiologic study; selection bias; non-response; oral contraceptives; diet; reproductive history; alcohol drinking ID RISK AB Background This study assessed the nature of potential biases by comparing respondents with non-respondents from a case-control study of breast cancer in younger women. Methods The case-control study was conducted in three regions in the US: Atlanta GA, Seattle/Puget Sound WA, and central New Jersey. An abbreviated interview or mailed questionnaire was completed by willing non-respondents, most of whom had refused participation in the main study. Results Respondents and non-respondents appeared similar with respect to age, race, relative weight, smoking, family history of breast cancer, number of births, age at first birth, and several dietary items. Compared to non-respondents, case and control respondents were of shorter stature, and reported less frequent consumption of doughnuts/pastries. Respondent cases, compared with non-respondent cases, were more highly educated and more likely to have consumed alcohol regularly; similar but not statistically significant tendencies were observed for controls. Respondent cases experienced menarche earlier than non-respondents. Respondent controls were more likely to have used oral contraceptives than non-respondents; a similar but not statistically significant tendency was observed in cases. Comparisons of crude and simulated relative risks using available non-respondents' data generally showed a low impact of non-response on relative risks in this study. Conclusions Our results suggest that non-response would not greatly affect relative risk estimates in this study, except possibly regarding height. However, we were limited by the numbers of informative non-respondents and the amount of data collected. Collecting similar information in future studies would be useful, especially since varying methods used to encourage participation may lead to differences in respondents' characteristics. C1 US Natl Canc Inst, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Epidemiol & Biostat Program, Rockville, MD 20852 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Univ N Carolina, Div Epidemiol, Chapel Hill, NC 27515 USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY 10027 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA USA. RP Madigan, MP (reprint author), US Natl Canc Inst, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Epidemiol & Biostat Program, 6120 Execut Blvd,EPS-MSC 7234, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N01-CP-95604, N01-CP-95671, N01-CP-95672] NR 11 TC 44 Z9 44 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 2000 VL 29 IS 5 BP 793 EP 798 DI 10.1093/ije/29.5.793 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 376DX UT WOS:000165443900002 PM 11034958 ER PT J AU Naficy, AB Frenck, RW Abu-Elyazeed, R Kim, YD Rao, MR Savarino, SJ Wierzba, TF Hall, E Clemens, JD AF Naficy, AB Frenck, RW Abu-Elyazeed, R Kim, YD Rao, MR Savarino, SJ Wierzba, TF Hall, E Clemens, JD TI Seroepidemiology of Helicobacter pylori infection in a population of Egyptian children SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE serology; incidence; prevalence; anthropometry; malnutrition; hygiene ID PERUVIAN CHILDREN; BIRTH COHORT; BREATH TEST; ACQUISITION; AGE; SEROPREVALENCE; TRANSMISSION; EPIDEMIOLOGY; CHILDHOOD; COMMUNITY AB Background To describe the seroepidemiology of Helicobacter pylori infection in a population of Egyptian children under 3 years. Methods A cohort of children under 36 months, residing in Abu Homos, Egypt, were visited at home twice weekly. Information regarding the child's breastfeeding status was obtained, and periodic anthropometric and household hygiene surveys were performed. In June 1997, a serosurvey was conducted on 187 study participants over 6 months old. The serosurvey was repeated in October 1997. All sera were tested for IgG antibodies to H. pylori. Results The June prevalence of H. pylori infection was 10%, and the incidence from June to October was 15%. Between June and October, 8 (42%) of 19 children that were positive for H. pylori infection seroreverted to negative. All seroreversions occurred in children 6-17 months. Other than age, no sociodemographic or environmental factor was significantly associated with incident Pi. pylori infection. There was no significant differences in the weight-for-age, weight-for-height, and height-for-age z-scores between children with and without prevalent H. pylori infection. Conclusions Infection with H. pylori is common in Egyptian children under 3 years old and is not associated with malnutrition. No predictors for H. pylori infection were found. Our preliminary evidence for transient H. pylori infections in young children needs to be confirmed in a prospective cohort study, and predictors for persistent infection should be sought, since only these may be relevant to the known sequellae of infection. C1 NICHHD, Epidemiol Branch, Rockville, MD 20852 USA. USN, Med Res Unit 3, Cairo, Egypt. NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. RP Naficy, AB (reprint author), NICHHD, Epidemiol Branch, Room 7B03,6100 Execut Blvd, Rockville, MD 20852 USA. FU NICHD NIH HHS [Y1-HD-7186-02] NR 24 TC 26 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 2000 VL 29 IS 5 BP 928 EP 932 DI 10.1093/ije/29.5.928 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 376DX UT WOS:000165443900024 PM 11034980 ER PT J AU Jenkinson, CP Hanson, R Cray, K Wiedrich, C Knowler, WC Bogardus, C Baier, L AF Jenkinson, CP Hanson, R Cray, K Wiedrich, C Knowler, WC Bogardus, C Baier, L TI Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE DRD2; dopamine; obesity; diabetes; association; single nucleotide polymorphisms ID QUANTITATIVE TRAIT LOCI; BODY-MASS INDEX; STRIATAL DOPAMINE; GENETIC-LINKAGE; CONSCIOUS RATS; ADMIXTURE; VARIANTS; HAMSTERS; RELEASE; DRD2 AB OBJECTIVES: To investigate whether (a) variants within the dopamine D2 receptor gene (DRD2) are associated with obesity and type 2 diabetes in Pima Indians, and (b) whether variation in this gene could be responsible for previously observed linkage to these phenotypes, at chromosome location 11q23 - 24, in this population. DESIGN: Two single nucleotide polymorphisms (SNPs), Ser311Cys and TaqIA, within the DRD2 gene were genotyped by allelic discrimination PCR in subjects who had provided evidence of linkage to diabetes and obesity in an autosome-wide scan. SUBJECTS: A total of 1187 subjects were genotyped, including 947 full heritage Pima Indians (80%). Descriptive statistics for all subjects analyzed, for whom clinical data were available, were (mean+/-s.d.): age at time of last exam=41+/-15 y; birth year=1950+/-14; age-sex-adjusted body mass index (BMI; adjusted to a mean age of 35 y) = 36 +/- 8 kg/m(2); male = 44%; diabetic = 57%. For full heritage Pimas only: age = 43 +/- 15 y; birth year = 1948 +/- 14; sex-age-adjusted BMI = 36 +/- 8 kg/m(2); male = 43%; diabetic = 59%. RESULTS: Neither polymorphism was significantly associated with diabetes in full heritage Pimas. Individuals with a 'CG' genotype at the Ser311Cys SNP had a higher BMI than those with a 'CC' genotype (36.7 vs 35.5 kg/m(2), P = 0.04). Linkage analysis of BMI, adjusted for either polymorphism, resulted in LOD scores that were similar to those obtained without adjustment. CONCLUSION: Heterozygotes at the Ser311Cys DRD2 polymorphism had a slightly higher BMI than homozygotes, however neither the Ser311Cys nor the TaqIA polymorphism accounted for the linkage with BMI on chromosome 11 in Pima Indians. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. RP Jenkinson, CP (reprint author), Univ Texas, Hlth Sci Ctr, Mail Stop 7886,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Baier, Leslie/F-9008-2013; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 37 TC 47 Z9 47 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD OCT PY 2000 VL 24 IS 10 BP 1233 EP 1238 DI 10.1038/sj.ijo.0801381 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 360CH UT WOS:000089648500001 PM 11093282 ER PT J AU Shinohara, H Fan, D Ozawa, S Yano, SJ Van Arsdell, M Viner, JL Beers, R Pastan, I Fidler, IJ AF Shinohara, H Fan, D Ozawa, S Yano, SJ Van Arsdell, M Viner, JL Beers, R Pastan, I Fidler, IJ TI Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE immunotoxins; human transferrin receptor; colon cancer metastasis ID SINGLE-CHAIN IMMUNOTOXINS; PSEUDOMONAS EXOTOXIN-A; NUDE-MICE; CLINICAL RELEVANCE; DIPHTHERIA-TOXIN; LIVER METASTASES; CARCINOMA; BIOLOGY; MODULATION; RESISTANCE AB We determined the efficacy of HB21(Fv)PE40, a single-chain immunotoxin made by fusing the variable regions of a monoclonal antibody directed at the human transferrin receptor (TW) with a truncated mutant of Pseudomonas exotoxin (PE), against metastatic human colon carcinoma KM12L4 cells growing in the liver or subcutis of nude mice. Organ-specific modulation of TfR expression was examined by immunohistochemistry and flow cytometry using anti-human CD71 antibody. KM12L4 cells expressed human TW and were lysed in vitro by HB21(Fv)PE40 but not LMB-7 (a control immunotoxin specific for a Lewis Y-related carbohydrate antigen). KM12L4 cells growing in the liver expressed higher levels of TfR than cells growing s.c. Systemic administration of HB21(Fv)PE40 eliminated KM12L4 liver metastasis, whereas administration of LMB-7 did not. Treatment of mice with HB21(Fv)PE40 only delayed the growth of s.c. tumors. KM12L4 cells recovered from liver metastases, expressed higher levels of TfR, and were more sensitive to lysis by HB21(Fv)PE40 than KM12L4 cells recovered from s.c. tumors. Indeed, collectively, the data show that the expression level of the TfR by human colon cancer cells is modulated by the organ microenvironment which can be advantageous for the use of therapeutic immunotoxins. C1 Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol 173, Houston, TX 77030 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Fidler, IJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol 173, 1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672, R35-CA42107] NR 38 TC 37 Z9 39 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2000 VL 17 IS 4 BP 643 EP 651 PG 9 WC Oncology SC Oncology GA 356TY UT WOS:000089460000002 PM 10995873 ER PT J AU Li, YW Chinni, SR Senderowicz, AM Sarkar, FH AF Li, YW Chinni, SR Senderowicz, AM Sarkar, FH TI Induction of growth inhibition and apoptosis in prostate cancer cells by flavopiridol SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE flavopiridol; apoptosis; prostate cancer cells ID DEPENDENT KINASE INHIBITOR; BREAST-CARCINOMA CELLS; DRUG FLAVOPIRIDOL; CYCLE ARREST; LEUKEMIA; ACTIVATION; LINES; NSC-649890; L86-8275; BCL-2 AB Flavopiridol is an inhibitor of several cyclin-dependent kinases, and exhibits potent growth-inhibitory activity against a number of human tumor cell lines both in vitro, and when grown as xenografts in mice. It has shown promising antineoplastic activity and is currently undergoing clinical phase II testing. Prostate cancer (PCa) remains a leading cause of morbidity and mortality among males in the United States. There are no effective treatments for hormone and/or radiation refractory PCa, suggesting that novel and newer treatment strategy may be useful in the management of PCa. Our previous study showed that flavopiridol induces cell growth inhibition and apoptosis in breast cancer cells. Here, we investigated whether flavopiridol was effective against prostate cancer cells. Flavopiridol was found to inhibit growth of PC3 prostate cancer cells. Induction of apoptosis was also observed in PC3 cells treated with flavopiridol, as measured by DNA laddering and PARP cleavage. We also found a significant down-regulation of Bcl-2 in flavopiridol-treated cells. These findings suggest that down-regulation of Bcl-2 may be one of the molecular mechanisms through which flavopiridol induces apoptosis and inhibits cell growth, suggesting that flavopiridol may be an effective chemotherapeutic agent against prostate cancer. C1 Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48201 USA. Natl Inst Dent & Craniofacial Res, Mol therapeut Unit, Oral & Pharyngeal Branch, NIH, Bethesda, MD USA. RP Sarkar, FH (reprint author), Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, 9374 Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. NR 28 TC 24 Z9 24 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2000 VL 17 IS 4 BP 755 EP 759 PG 5 WC Oncology SC Oncology GA 356TY UT WOS:000089460000017 PM 10995888 ER PT J AU Josyula, S Schut, HAJ Diwan, BA Anver, MR Anderson, LM AF Josyula, S Schut, HAJ Diwan, BA Anver, MR Anderson, LM TI Age-related alterations in (32)P-postlabeled DNA adducts in livers of mice infected with the tumorigenic bacterial pathogen, Helicobacter hepaticus SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE hepatitis; age; disease; indigenous; microbe ID MODIFICATIONS I-COMPOUNDS; MUTAGEN 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE IQ; CHRONIC ACTIVE HEPATITIS; SPRAGUE-DAWLEY RATS; A/JCR MICE; CYTOCHROME-P450; INDUCTION; P450; HEPATOCARCINOGENESIS; OVEREXPRESSION AB Helicobacter hepaticus causes chronic active hepatitis and liver tumors in mice, with associated increase in reactive oxygen species. Indigenous (I)-compounds are bulky DNA adducts present at low levels and detected by (32)P-post- labeling. Some may be caused by reactive oxygen species; others occur normally and decrease during liver tumorigenesis. The identity of most is unknown. We investigated whether mouse liver infection by H. hepaticus and resulting progression of hepatic lesions would be associated with qualitative or quantitative changes in I-compounds. Mice were 3, 6, 9, and 12 months of age; liver disease ranged from minimal through marked. In control A/J mice, up to 20 I-compounds were detected, and the total level of these did not change with age, whereas 11 individual I-compounds showed marked age-related differences. These appeared to be coordinately regulated, as the total of these 11 adducts was constant at 6-12 months. In A/JNCr mice naturally infected with H. hepaticus, up to 12 hepatic I-compounds were found. Total levels varied markedly with age and were high at 6 and 12 months. Neither total adduct levels, nor the amount of any individual adduct, correlated positively with severity of hepatic lesions; in some cases, highest levels were found in livers with least disease. Thus, liver infection and tumorigenesis by H. hepaticus was not associated with an increase in any (32)P-postlabeled DNA adduct. Marked, and distinct, age-related changes in total or individual adducts in control and infected mice suggest a role in the physiological alterations of aging and in host response to infection. C1 NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Pathol Histotechnol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. RP Anderson, LM (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Bldg 538,Rm 205E, Frederick, MD 21702 USA. EM Andersol@mail.ncifcrf.gov NR 43 TC 6 Z9 6 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2000 VL 17 IS 4 BP 811 EP 818 PG 8 WC Oncology SC Oncology GA 356TY UT WOS:000089460000025 PM 10995896 ER PT J AU Soyland, C Hassfjell, SP AF Soyland, C Hassfjell, SP TI Survival of human lung epithelial cells following in vitro alpha-particle irradiation with absolute determination of the number of alpha-particle traversals of individual cells SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID LINEAR-ENERGY-TRANSFER; MAMMALIAN-CELLS; RADIATION; SINGLE; MICROBEAM; SYSTEM; RADIOBIOLOGY; NUCLEI; DESIGN AB Purpose: To throw light on human exposure to domestic radon and radon progeny, the effects of low doses of alpha-particle irradiation on normal human lung epithelial cells has been studied. At such low exposure levels the concept of dose is inadequate due to the stochastic variation in the number of alpha-particle traversals per cell. The objective of the current study was to establish an accurate survival curve for human lung epithelial cells with absolute determination of the exact number of alpha-particle traversals of individual cells. Materials and methods: irradiation of L132 cells growing in track-etch detector-based cell dishes, was performed using a collimated alpha-particle beam from a Po-210 source. The number of alpha-particle traversals through each individual cell was scored by using a technique of retrospective track-etch dosimetry. This technique is based upon image matching and mapping of corresponding cell and alpha-particle track images. The spatial resolution of the hit determination procedure was +/- 0.9 mu m. Results: Surviving fractions of cells (SF) showed strict dependence on the number of nuclear traversals (n), with SF(n) = a exp( - bn), a = 0.957 (+/- 0.046), b = 0.587 (+/- 0.059), R-2 = 98.8%. No significant dependence on the number of nuclear membrane traversals (m) or the number of cytoplasm traversals (c) was observed. C1 Norwegian Radium Hosp, Dept Biophys, N-0310 Oslo, Norway. NCI, ROB, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. RP Soyland, C (reprint author), Norwegian Radium Hosp, Dept Biophys, N-0310 Oslo, Norway. NR 24 TC 33 Z9 33 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD OCT PY 2000 VL 76 IS 10 BP 1315 EP 1322 PG 8 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 361ZN UT WOS:000089754300003 PM 11057739 ER PT J AU Dickerman, RD Pertusi, R Smith, GH AF Dickerman, RD Pertusi, R Smith, GH TI The upper range of lumbar spine bone mineral density? An examination of the current world record holder in the squat lift SO INTERNATIONAL JOURNAL OF SPORTS MEDICINE LA English DT Article DE critical compression force; spine; weight-lifting; strength; bone density; dual energy x-ray absorptometry ID EXERCISE AB Weight-bearing exercise is known to improve bone mineral density, however, excessive forces exerted on the lumbar spine can be pathologic. Cadaveric studies have calculated a hypothetical "critical compression force" at which the lumbar spine would suffer collapse. In addition, recent studies have suggested that bone density correlates with strength. Thus far studies have failed to examine elite power athletes to determine the possible upper range for bone mineral density and critical compression force. Therefore, we recruited the current world record holder in the squat lift, with a record squat lift >469 kg, for an examination of lumbar spine bone mineral density. The subject had dual energy x-ray absorptometry (DEXA) and magnetic resonance imaging (MRI) performed of the lumbar spine. The subject also had serum chemistries, cell blood count and testosterone levels performed. DEXA scan revealed the highest bone mineral density reported to date. MRI revealed normal alignment, no evidence of disc herniation or compressive disc disease. There was no frank or neural foraminal canal stenosis. The estimated compressive force generated on his lumbar spine during the squat lift of > 469 kg doubles the previously reported critical compression force. This case study supports the previously described relationship between strength and bone density and redefines the upper limits of bone density in strength athletes. C1 NIH, Surg Neurol Branch, Bethesda, MD 20892 USA. Univ N Texas, Hlth Sci Ctr, Dept Surg, Ft Worth, TX USA. RP Dickerman, RD (reprint author), Long Isl Jewish Med Ctr, Dept Neurosurg, 270-05 76th Ave, New Hyde Park, NY 11040 USA. NR 12 TC 4 Z9 4 U1 0 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0172-4622 J9 INT J SPORTS MED JI Int. J. Sports Med. PD OCT PY 2000 VL 21 IS 7 BP 469 EP 470 DI 10.1055/s-2000-7417 PG 2 WC Sport Sciences SC Sport Sciences GA 362VE UT WOS:000089798300003 PM 11071047 ER PT J AU Christiansen, SP Sandnas, A Prill, R Youle, RJ McLoon, LK AF Christiansen, SP Sandnas, A Prill, R Youle, RJ McLoon, LK TI Acute effects of the skeletal muscle-specific immunotoxin ricin-mAb 35 on extraocular muscles of rabbits SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ORBICULARIS OCULI MUSCLE; TOXIN TYPE-A; BOTULINUM TOXIN; BUPIVACAINE; REGENERATION; INJECTIONS; DYSTONIA; TENSION; FIBERS; SPASM AB PURPOSE. TO determine the acute histologic and ultrastructural effects of a recently developed muscle-specific immunotoxin, ricin-mAb 35. METHODS. Graduated doses of ricin-mAb 35, composed of ricin conjugated to a monoclonal antibody against the nicotinic acetylcholine receptor of skeletal muscle, were injected into one superior rectus muscle in rabbits. After 3, 7, and 14 days, both superior rectus muscles were removed and prepared for electron microscopy and histologic examination, by using a number of immunohistochemical markers to identify inflammatory cell infiltration, muscle fiber loss, and muscle regeneration. RESULTS. Myotoxicity Of the ricin-mAb 35 was focal and dose related. At the highest dose tested, there was substantial inflammatory cell infiltrate by 3 daps, which largely disappeared by 7 days. Significant muscle loss was apparent by 7 days after ricin-mAb 35 treatment. Both the inflammatory reaction and muscle fiber loss were confined to the immediate injection site. Surrounding; muscle appeared to be normal. Ar 14 days after treatment, early signs of muscle regeneration were evident within the tissue sections. No evidence of orbital or systemic toxicity was seen in any animal. CONCLUSIONS. Direct injection of ricin-mAb 35 into the extraocular muscles of rabbits results in a dose-related focal injury to the muscles, with a self-limited inflammatory component and significant muscle fiber loss. This novel immunotoxin may be useful in the treatment of strabismus if chronic studies show a sustained histologic and electrophysiologic effect. C1 Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. NIH, Bethesda, MD 20892 USA. RP McLoon, LK (reprint author), Univ Minnesota, Dept Ophthalmol, Room 374 LRB,2001 6th St SE, Minneapolis, MN 55455 USA. NR 24 TC 19 Z9 19 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2000 VL 41 IS 11 BP 3402 EP 3409 PG 8 WC Ophthalmology SC Ophthalmology GA 358PZ UT WOS:000089567600023 PM 11006231 ER PT J AU de Smet, MD Dayan, M AF de Smet, MD Dayan, M TI Prospective determination of T-cell responses to S-antigen in Behcet's disease patients and controls SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LIMITING DILUTION ANALYSIS; MYELIN BASIC-PROTEIN; IMMUNE RESPONSIVENESS; LYMPHOCYTE-RESPONSES; MULTIPLE-SCLEROSIS; PERIPHERAL-BLOOD; UVEITIS PATIENTS; RAPID METHOD; INFECTION; MEMORY AB PURPOSE. TO prospectively determine, using two different assays, the lymphocyte proliferative response to a retinal autoantigen (S-antigen) in patients with Behcet's disease who are under treatment for ocular inflammation. METHODS. Patients were evaluated at each visit for signs of ocular inflammation. Peripheral blood leukocytes were harvested and cultured in the presence of bovine S-antigen in a standard culture assay, as well as by limiting dilution using multiple short-term T-cell lines. RESULTS. Five patients were observed for 2 to 10 months. During follow-up, three patients had episodes of ocular inflammation. No consistent change in proliferative response was observed in standard proliferation assays. However, an increase in established T-cell lines was correlated to the presence of ocular inflammation in all three patients. Ocular activity was associated with an increase of 9- to 30-fold in the frequency of short-term T-cell lines. This increase returned to baseline within 1 to 3 months. CONCLUSIONS. An increase in S-antigen-responsive lymphocytes is found in the peripheral blood of patients with Behcet's disease during episodes of ocular inflammation. This increase cannot be measured using standard proliferation assays but requires the use of techniques exploiting the principles of limiting dilution analysis. C1 Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands. NEI, Clin Immunol Sect, Immunol Lab, Bethesda, MD 20892 USA. RP de Smet, MD (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Rm G2-217,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM m.d.desmet@amc.uva.nl OI de Smet, Marc/0000-0002-9217-5603 NR 37 TC 31 Z9 32 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2000 VL 41 IS 11 BP 3480 EP 3484 PG 5 WC Ophthalmology SC Ophthalmology GA 358PZ UT WOS:000089567600034 PM 11006242 ER PT J AU Baffi, J Byrnes, G Chan, CC Csaky, KG AF Baffi, J Byrnes, G Chan, CC Csaky, KG TI Choroidal neovascularization in the rat induced by adenovirus mediated expression of vascular endothelial growth factor SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; SUBFOVEAL FIBROVASCULAR MEMBRANES; MACULAR DEGENERATION; GENE-TRANSFER; IN-VIVO; SUBRETINAL NEOVASCULARIZATION; CLINICOPATHOLOGICAL CORRELATION; BRUCHS MEMBRANE; MULLER CELLS; VECTOR AB PURPOSE. TO determine the effects of an adenovirus vector encoding vascular endothelial growth factor(165) (Ad.VEGF) delivered to the subretinal space in the rat. METHODS. An El-deleted adenoviral vector encoding VEGF was injected into the subretinal space of Long-Evans rats. Immunohistochemistry identified VEGF expression. Histopathologic changes in the retina were determined by light and electron microscopy, immunohistochemistry, fluorescein angiography, and examination of wholemounts of choroid and retina. RESULTS. Increased expression of VEGF only in the retinal pigment epithelium (RPE) was detected after Ad.VEGF injection. Histopathology of these eyes revealed minimal subretinal exudation at 1 week followed by the appearance of vascular structures in the subretinal space by week 2, which persisted up to 4 weeks. Shortening of photoreceptor outer segments and reduction of the outer nuclear layer were present overlying areas of neovascularization. Fluorescein angiography of animals injected with fluorescein-dextran revealed a deep complex of new vessels. Choroidal flatmounts showed new vessel formation, verified by detection of endothelial cells via immunohistochemistry, arising from the choroid with absence of change in the overlying retinal vasculature. Electron microscopy confirmed the presence of sub-RPE endothelial cells and pericytes and the loss of integrity of Bruch's membrane, and serial sectioning demonstrated choroidal vascular growth through Bruch's membrane. CONCLUSIONS. These results support the hypothesis that overexpression of VEGF from RPE cells is capable of inducing choroidal neovascularization in the rat and provide a framework for further examining angiogenic processes in the RPE- choroid complex. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Dept Ophthalmol, Bethesda, MD USA. RP Csaky, KG (reprint author), NEI, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 68 TC 84 Z9 91 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2000 VL 41 IS 11 BP 3582 EP 3589 PG 8 WC Ophthalmology SC Ophthalmology GA 358PZ UT WOS:000089567600048 PM 11006256 ER PT J AU Levine, RL Moskovitz, J Stadtman, ER AF Levine, RL Moskovitz, J Stadtman, ER TI Oxidation of methionine in proteins: Roles in antioxidant defense and cellular regulation SO IUBMB LIFE LA English DT Review DE antioxidants; cellular regulation; methionine; methionine sulfoxide; methionine sulfoxide reductase; redox cycles; reversible covalent modification ID APOLIPOPROTEIN-A-I; HUMAN ALPHA-1-PROTEINASE INHIBITOR; PHAGOCYTE-DERIVED OXIDANTS; ALZHEIMERS-DISEASE BRAIN; SULFOXIDE REDUCTASE; BIOLOGICAL-ACTIVITY; CHLORAMINE-T; CHEMICAL MODIFICATION; GLUTAMINE-SYNTHETASE; SELECTIVE OXIDATION AB The roles of methionine residues in proteins have not been well defined, but a review of available studies leads to the conclusion that methionine, like cysteine, functions as an antioxidant and as a key component of a system for regulation of cellular metabolism. Methionine is readily oxidized to methionine sulfoxide by many reactive species. The oxidation of surface exposed methionines thus serves to protect other functionally essential residues from oxidative damage. Methionine sulfoxide reductases have the potential to reduce the residue back to methionine, increasing the scavenging efficiency of the system. Reversible covalent modification of amino acids in proteins provides the mechanistic basis for most systems of cellular regulation. Interconversion of methionine and methionine sulfoxide can function to regulate the biological activity of proteins, through alteration in catalytic efficiency and through modulation of the surface hydrophobicity of the protein. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 106,MSC 0320, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 98 TC 208 Z9 212 U1 0 U2 15 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD OCT-NOV PY 2000 VL 50 IS 4-5 BP 301 EP 307 DI 10.1080/15216540051081056 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 420JQ UT WOS:000168002200009 PM 11327324 ER PT J AU Khalsa, JH Genser, S Marriott, B Francis, H AF Khalsa, JH Genser, S Marriott, B Francis, H TI Introduction: Metabolic, endocrine, and gastrointestinal (MEG) disorders in drug abuse and HIV/AIDS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material C1 NIDA, Ctr AIDS & Other Med Consequences Drug Abuse, NIH, Bethesda, MD 20892 USA. NIH, Off Dietary Supplements, Off Director, Bethesda, MD USA. RP Khalsa, JH (reprint author), NIDA, Ctr AIDS & Other Med Consequences Drug Abuse, NIH, 6001 Execut Blvd,Room 5198, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD OCT 1 PY 2000 VL 25 SU 1 BP S1 EP S3 DI 10.1097/00126334-200010001-00001 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 377EX UT WOS:000165499900001 ER PT J AU Rogers, AS AF Rogers, AS TI Research and practice in adolescent medicine: "Both-and" not "either-or" for clinicians SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. RP Rogers, AS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD OCT PY 2000 VL 27 IS 4 BP 225 EP 226 DI 10.1016/S1054-139X(00)00175-0 PG 2 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 357ND UT WOS:000089507000001 PM 11008084 ER PT J AU Aarons, SJ Jenkins, RR Raine, TR El-Khorazaty, MN Woodward, KM Williams, RL Clark, MC Wingrove, BK AF Aarons, SJ Jenkins, RR Raine, TR El-Khorazaty, MN Woodward, KM Williams, RL Clark, MC Wingrove, BK TI Postponing sexual intercourse among urban junior high school students - A randomized controlled evaluation SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE abstinence; adolescents; sexuality; gender differences; pregnancy prevention; virginity ID ADOLESCENT PREGNANCY PREVENTION; HEALTH; INVOLVEMENT; PROGRAM; RISK; CURRICULUM; TEENAGERS; PROJECT; IMPACT; DESIGN AB Purpose: To describe a randomized, controlled evaluation of a school-based intervention to delay sexual intercourse among urban junior high school students. Methods: Six Washington, D.C., junior high schools were randomly assigned to the intervention or nonintervention control condition for an educational program. During the first school year, seventh graders (n = 582) from the six schools obtained written parental consent to participate. Three health professionals (one per intervention school) implemented the program, which consisted of reproductive health classes, the Postponing Sexual Involvement Curriculum, health risk screening, and "booster" educational activities during the following (eighth grade) school year. Cross-sectional surveys were administered at baseline, the end of the seventh grade, and the beginning and end of the eighth grade. Intervention and control group differences in virginity, attitudes toward delayed sex and childbearing, and sexual knowledge and behavior were assessed at all four time points. Results: At baseline, 44% of the seventh grade males and 81% of the seventh grade females reported being virgins. At the end of the seventh grade (first follow-up), after controlling for baseline study group differences, intervention-group females were more likely to report virginity, self-efficacy to refuse sex with a boyfriend, and the intention to avoid sexual involvement during the following 6 months. At the end of the eighth grade, significantly more intervention- than control-group females reported virginity, birth control use at last intercourse (for nonvirgins), and knowledge of adolescent reproductive health and confidentiality rights. No changes in virginity, self-efficacy to refuse sex, or sexual intent for the next 6 months were observed among male participants at any time during the study. However, on all three follow-up surveys, intervention-group males scored significantly higher than their control-group counterparts in knowledge of birth control method efficacy. No change in attitudes toward abstinence was observed for either gender at any follow-up point. Conclusions: Gender differences in baseline sexual activity rates and in various study outcomes suggest a possible need for separate, gender-specific intervention activities that can adequately address the social and cognitive needs of both sexes. (C) Society for Adolescent Medicine, 2000. C1 Howard Univ, Coll Med, Dept Obstet & Gynecol, Washington, DC USA. Howard Univ, Coll Med, Dept Pediat & Child Hlth, Washington, DC USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. Res Triangle Inst, Rockville, MD USA. Childrens Natl Med Ctr, Div Adolescent & Young Adult Med, Washington, DC 20010 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. District Columbia Publ Sch, Comprehens Sch Hlth Program, Off Chief Acad Officer, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. RP Jenkins, RR (reprint author), Howard Univ Hosp, Dept Pediat & Child Hlth, 2041 Georgia Ave NW, Washington, DC 20060 USA. FU NICHD NIH HHS [U18-HD31919, U18-HD30447, U18-HD30458] NR 40 TC 44 Z9 46 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD OCT PY 2000 VL 27 IS 4 BP 236 EP 247 DI 10.1016/S1054-139X(00)00102-6 PG 12 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 357ND UT WOS:000089507000003 PM 11008086 ER PT J AU Hauser, P Matochik, J Altshuler, LL Denicoff, KD Conrad, A Li, XM Post, RM AF Hauser, P Matochik, J Altshuler, LL Denicoff, KD Conrad, A Li, XM Post, RM TI MRI-based measurements of temporal lobe and ventricular structures in patients with bipolar I and bipolar II disorders SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE magnetic resonance imaging; bipolar disorder; quantitative neuroanatomy ID MAGNETIC-RESONANCE; SCHIZOPHRENIA; HYPERINTENSITIES; ENLARGEMENT AB Objective: There have been relatively few quantitative MRI studies of temporal lobe structures and the lateral ventricles in bipolar patients and a lack of agreement across studies as to whether these structures differ significantly in size from control subjects. Also there have been no quantitative MRI studies of bipolar II patients. The present study measured temporal lobe and ventricular structures in both bipolar I and bipolar II patients, as well as control subjects, Method: Twenty-five bipolar I patients, 22 bipolar II patients and 19 control subjects underwent MRI brain scans. The 5 mm coronal slices of each subject were coded and measured by a ratel who was blind with respect to subject diagnosis. Volume estimates of the temporal lobe and hippocampus were calculated fur each hemisphere by measuring the area of the structure in each slice in which it appears, multiplying by 5 mm and summing. In addition to these volume estimates, the area of the lateral ventricle and the inferior hum of the lateral ventricle, the lateral ventricle to cerebrum area ratio (LV/C) and the temporal lobe to cerebrum area ratio (TL/C), were calculated fur each hemisphere in one reference slice only. The area of the third ventricle was also measured. Volume estimates and area ratios were then compared among diagnostic groups. Results: There were no significant differences in temporal lobe or hippocampal volume estimates, in the third ventricle and inferior horn of the lateral ventricle area measurements, and in the TL/C area ratio among diagnostic groups. The lateral ventricle area and LV/C area ratio were significantly larger in bipolar I patients than either bipolar TI patients or control subjects only in the Left hemisphere. Furthermore, these measures were approximately twice as large in the bipolar I patients as the other groups. Conclusions. The current study adds to a growing literature that bipolar I disorder, particularly in males, may show different neurobiological alterations compared to bipolar II patients or control subjects. The pathophysiologic implications of this accumulating evidence of increased left ventricular size in bipolar I disorder remains to be further elucidated. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Med Ctr, Dept Psychiat, Baltimore, MD 21201 USA. Vet Adm Med Ctr, Psychiat Serv, Baltimore, MD 21201 USA. NIDA, Brain Imaging Ctr, Baltimore, MD 21224 USA. Univ Calif Los Angeles, Neuropsychiat Hosp, Dept Psychiat & Behav Sci, Los Angeles, CA 90266 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Anat & Cell Biol, Ctr Hlth Sci, Los Angeles, CA 90024 USA. RP Hauser, P (reprint author), Univ Maryland, Med Ctr, Dept Psychiat, 10 N Greene St, Baltimore, MD 21201 USA. NR 14 TC 101 Z9 102 U1 0 U2 2 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 OCT PY 2000 VL 60 IS 1 BP 25 EP 32 DI 10.1016/S0165-0327(99)00154-8 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 349BQ UT WOS:000089024300003 PM 10940444 ER PT J AU Sparber, A Wootton, JC Bauer, L Curt, G Eisenberg, D Levin, T Steinberg, SM AF Sparber, A Wootton, JC Bauer, L Curt, G Eisenberg, D Levin, T Steinberg, SM TI Use of complementary medicine by adult patients participating in HIV/AIDS clinical trials SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ALTERNATIVE THERAPIES; HIV-INFECTION; UNITED-STATES; AIDS; PATTERNS AB Objective: To identify and characterize patterns of use of complementary and alternative (CAM) therapies by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients participating in clinical trials in a research setting. Design: A descriptive survey using a nonrandom sample of 100 patients was conducted over 17 months, using a 99-item interview schedule adapted from a previous study. Setting: National Institutes of Health (NIH) Warren G. Magnuson Clinical Center. Subjects: Patients diagnosed with HIV/AIDS, participating in clinical research protocols at the National Institute of Allergy and Infectious Diseases and the National Cancer institute (NCI) at the NIH. Results: Ninety-one percent (91%) had used at least one CAM therapy, as defined by a 1993 study by Eisenberg et al., sometime in their lives. Postdiagnosis, 84% used at least one CAM therapy with an average of just fewer than 5. The increase in frequency of use from 64% prediagnosis was significant (p(2) = 0.019). Therapies that became significantly more popular postdiagnosis were, imagery (p(2) = 0.00012), high-dose vitamins, (p(2) = 0.000019), weight gain (p(2) 0.000244), massage (p(2) = 0.00091), relaxation (p(2) = 0.0033), herbals (p(2) = 0.013), spiritual (p(2) = 0.024), and acupuncture (p(2) = 0.035). They were primarily used for HIV/AIDS-related problems: dermatological, nausea, depression, insomnia, and weakness. There was a high level of agreement that benefits of CAM use were: feeling better, 51 (98.1%), increased coping, 52 (100%), feeling in control, 44 (88.5%), and enhanced treatment outcome, 49 (94.2%) with 32 (61%) stating CAM was as, or more effective than conventional treatment. Fifty-three percent (53%) were specifically asked by physicians whether they were using adjunct therapies. Conclusions: Subjects used a variety of CAM therapies to cope with their diseases and rigors of treatment and clinical trials. Further research is needed to identify CAM therapies that may be used as adjunct treatments during clinical trials. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Alternat Med Fdn, Bethesda, MD USA. NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Ctr Alternat Med Res, Boston, MA 02215 USA. NIH, HIV Counseling Ctr, Bethesda, MD USA. RP Sparber, A (reprint author), NIH, Ctr Clin, Room 12S 235B,Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 54 Z9 56 U1 0 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD OCT PY 2000 VL 6 IS 5 BP 415 EP 422 DI 10.1089/acm.2000.6.415 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 366WW UT WOS:000090030100007 PM 11059503 ER PT J AU Johnson, EM Wootton, JC Kimzey, R McCullah, L Wesley, R Byrd, DC Singh, KK Rubino, D Pucino, F AF Johnson, EM Wootton, JC Kimzey, R McCullah, L Wesley, R Byrd, DC Singh, KK Rubino, D Pucino, F TI Use of herbal therapies by adults seen in an ambulatory care research setting: An exploratory survey SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article AB Objective: To identify and characterize patterns of use of herbal products among patients participating in selected research clinics. Design: Survey of three National Institutes of Health (NIH) ambulatory care research clinics. Subjects: Convenience sample of 490 adult patients (168 male, 322 female) attending rheumatology, liver, and endocrinology/metabolic research clinics. Results: Of the patients surveyed, 16.7%: (n = 82) reported using herbs. There were no significant sociodemographic differences between herb and nonherb users. Indications for herb use differed among the disease groups; patients in the endocrine and rheumatology clinics were taking herbs predominantly for "energy" or "wellness"; those attending the liver clinic tended to use herbal therapies as treatment for their disease. Mean and median monthly expenditure for herbal products was $30 and $10, respectively. There was a significant positive correlation between number of herbs used and use of other dietary supplements (p < 0.0001). Conclusions: One in six patients in ambulatory clinical research settings may be taking herbal products in addition to prescribed treatment. This figure is lower than in the general population, possibly because the patients may stop using herbs when participating in a research project. Although empirical evidence on the beneficial or adverse effects of herb therapy alone or in combination with drug therapies is limited, clinical researchers should be aware of the potential for confounding clinical trial results. C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Johnson, EM (reprint author), NIH, Warren G Magnuson Clin Ctr, 10S-221,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 15 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD OCT PY 2000 VL 6 IS 5 BP 429 EP 435 DI 10.1089/acm.2000.6.429 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 366WW UT WOS:000090030100009 PM 11059505 ER PT J AU Moolchan, ET Cone, EJ Wstadik, A Huestis, MA Preston, KL AF Moolchan, ET Cone, EJ Wstadik, A Huestis, MA Preston, KL TI Cocaine and metabolite elimination patterns in chronic cocaine users during cessation: Plasma and saliva analysis SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; HUMAN LIVER CARBOXYLESTERASE; HEROIN; URINE; DISPOSITION; PHARMACOKINETICS; SPECIFICITY; INTRANASAL; EXCRETION; SMOKING C1 NIDA, Sect Chem & Drug Metab, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Sect Chem & Drug Metab, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 30 TC 24 Z9 28 U1 1 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2000 VL 24 IS 7 BP 458 EP 466 PG 9 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 361AT UT WOS:000089700100001 PM 11043647 ER PT J AU Jufer, RA Wstadik, A Walsh, SL Levine, BS Cone, EJ AF Jufer, RA Wstadik, A Walsh, SL Levine, BS Cone, EJ TI Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID EXCRETION; PHARMACOKINETICS; DISPOSITION; BIOTRANSFORMATION; BENZOYLECGONINE C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Behav Pharmacol Res Unit, Baltimore, MD 21224 USA. Off Chief Med Examiner, Baltimore, MD 21201 USA. RP Jufer, RA (reprint author), FBI Lab, 935 Penn Ave NW, Washington, DC 20535 USA. FU NIDA NIH HHS [DA10029] NR 24 TC 47 Z9 50 U1 4 U2 13 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2000 VL 24 IS 7 BP 467 EP 477 PG 11 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 361AT UT WOS:000089700100002 PM 11043648 ER PT J AU Ropero-Miller, JD Goldberger, BA Cone, EJ Joseph, RE AF Ropero-Miller, JD Goldberger, BA Cone, EJ Joseph, RE TI The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID ALTERNATIVE MATRICES; STRATUM-CORNEUM; ABUSE; NAIL; DRUGS; METHAMPHETAMINE; PLASMA; TERBINAFINE; AMPHETAMINE; HISTORY C1 Off Chief Med Examiner, Chapel Hill, NC 27511 USA. Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Ropero-Miller, JD (reprint author), Off Chief Med Examiner, Campus Box 7580, Chapel Hill, NC 27511 USA. FU NIDA NIH HHS [DA09096] NR 33 TC 28 Z9 30 U1 1 U2 4 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2000 VL 24 IS 7 BP 496 EP 508 PG 13 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 361AT UT WOS:000089700100006 PM 11043652 ER PT J AU Huestis, MA Cone, EJ Wong, CJ Umbricht, A Preston, KL AF Huestis, MA Cone, EJ Wong, CJ Umbricht, A Preston, KL TI Monitoring opiate use in substance abuse treatment patients with sweat and urine drug testing SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID POPPY SEED CONSUMPTION; QUALITATIVE DETECTION; GC-MS; COCAINE; CODEINE; HAIR; MORPHINE; URINALYSIS; INGESTION; SALIVA C1 NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 39 TC 42 Z9 42 U1 0 U2 6 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2000 VL 24 IS 7 BP 509 EP 521 PG 13 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 361AT UT WOS:000089700100007 PM 11043653 ER PT J AU Smith, ML Shimomura, ET Summers, J Paul, BD Nichols, D Shippee, R Jenkins, AJ Darwin, WD Cone, EJ AF Smith, ML Shimomura, ET Summers, J Paul, BD Nichols, D Shippee, R Jenkins, AJ Darwin, WD Cone, EJ TI Detection times and analytical performance of commercial urine opiate immunoassays following heroin administration SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID MASS-SPECTROMETRY; DRUG; MORPHINE; 6-ACETYLMORPHINE; CHROMATOGRAPHY; CODEINE C1 Armed Forces Inst Pathol, Div Forens Toxicol, Off Armed Forces Med Examiner, Washington, DC 20306 USA. Forens Toxicol Drug Testing Lab, Ft Meade, MD 20755 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Paul, BD (reprint author), Armed Forces Inst Pathol, Div Forens Toxicol, Off Armed Forces Med Examiner, Washington, DC 20306 USA. NR 18 TC 12 Z9 13 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2000 VL 24 IS 7 BP 522 EP 529 PG 8 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 361AT UT WOS:000089700100008 PM 11043654 ER PT J AU Oyler, JM Cone, EJ Joseph, RE Huestis, MA AF Oyler, JM Cone, EJ Joseph, RE Huestis, MA TI Identification of hydrocodone in human urine following controlled codeine administration SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; HUMAN LIVER; MORPHINE; HYDROMORPHONE; METABOLITES; OPIATES; COCAINE C1 NIDA, Chem & Drug Metab Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Oyler, JM (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 17 TC 41 Z9 45 U1 0 U2 5 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2000 VL 24 IS 7 BP 530 EP 535 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 361AT UT WOS:000089700100009 PM 11043655 ER PT J AU Rumsey, JM Vitiello, B Cooper, J Hirtz, D AF Rumsey, JM Vitiello, B Cooper, J Hirtz, D TI Special issue: Treatments for people with autism and other pervasive developmental disorders: Research perspectives - Editorial preface SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. NIDCD, Bethesda, MD 20892 USA. RP Rumsey, JM (reprint author), NIMH, Bethesda, MD 20892 USA. NR 3 TC 4 Z9 4 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD OCT PY 2000 VL 30 IS 5 BP 369 EP 371 DI 10.1023/A:1005595303185 PG 3 WC Psychology, Developmental SC Psychology GA 373EU UT WOS:000165276100001 ER PT J AU Ernst, M AF Ernst, M TI Commentary: Considerations on the characterization and treatment of self-injurious behavior SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Editorial Material ID LESCH-NYHAN SYNDROME; INTRANIGRAL MICROINJECTION; SEROTONIN SYNTHESIS; MUTILATION; DISEASE; MODEL; RATS; CHILDREN C1 NIDA, Brain Imaging Sect, Baltimore, MD 21224 USA. RP Ernst, M (reprint author), NIDA, Brain Imaging Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 30 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD OCT PY 2000 VL 30 IS 5 BP 447 EP 450 DI 10.1023/A:1005507708636 PG 4 WC Psychology, Developmental SC Psychology GA 373EU UT WOS:000165276100013 PM 11098882 ER PT J AU Nicolson, R Castellanos, FX AF Nicolson, R Castellanos, FX TI Commentary: Considerations on the pharmacotherapy of attention deficits and hyperactivity in children with autism and other pervasive developmental disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Editorial Material ID METHYLPHENIDATE C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Nicolson, R (reprint author), 10 Ctr Dr 3N202, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 8 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD OCT PY 2000 VL 30 IS 5 BP 461 EP 462 DI 10.1023/A:1005511809545 PG 2 WC Psychology, Developmental SC Psychology GA 373EU UT WOS:000165276100015 PM 11098884 ER PT J AU Jhee, KH Yoshimura, T Miles, EW Takeda, S Miyahara, I Hirotsu, K Soda, K Kawata, Y Esaki, N AF Jhee, KH Yoshimura, T Miles, EW Takeda, S Miyahara, I Hirotsu, K Soda, K Kawata, Y Esaki, N TI Stereochemistry of the transamination reaction catalyzed by aminodeoxychorismate lyase from Escherichia coli: Close relationship between fold type and stereochemistry SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE aminodeoxychorismate lyase; molecular evolution; pyridoxal 5 '-phosphate; stereochemistry; transamination ID AMINO-ACID AMINOTRANSFERASE; PYRIDOXAL-PHOSPHATE ENZYMES; TRYPTOPHAN SYNTHASE; NUCLEOTIDE-SEQUENCE; 3-DIMENSIONAL STRUCTURE; SALMONELLA-TYPHIMURIUM; CRYSTAL-STRUCTURE; HYDROGEN-TRANSFER; PURIFICATION; GENE AB Aminodeoxychorismate lyase is a pyridoxal 5'-phosphate-dependent enzyme that converts 4-aminodeoxychorismate to pyruvate and p-aminobenzoate, a precursor of folic acid in bacteria The enzyme exhibits significant sequence similarity to two aminotransferases, D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase, In the present study, we have found that aminodeoxychorismate lyase catalyzes the transamination between D-alanine and pyridoxal phosphate to produce pyruvate and pyridoxamine phosphate, L-Alanine and other D- and L-amino acids tested were inert as substrates of transamination. The pro-R hydrogen of C4' of pyridoxamine phosphate was stereospecifically abstracted during the reverse half transamination from pyridoxamine phosphate to pyruvate, Aminodeoxychorismate lyase is identical to D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase in the stereospecificity of the hydrogen abstraction, and differs from all other pyridoxal enzymes that catalyze pro-S hydrogen transfer, Aminodeoxychorismate lyase is the first example of a lyase that catalyzes pro-R-specific hydrogen abstraction. The result is consistent with recent X-ray crystallographic findings showing that the topological relationships between the cofactor and the catalytic residue for hydrogen abstraction are conserved among aminodeoxychorismate lyase, D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase [Nakai, T, Mizutani, H,, Miyahara, I., Hirotsu, K., Takeda, S., Jhee, K-H., Yoshimura, T., and Esaki, N, (2000) J. Biochem. 128, 29-28]. C1 Kyoto Univ, Inst Chem Res, Kyoto 6110011, Japan. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. Osaka City Univ, Grad Sch Sci, Dept Chem, Sumiyoshi Ku, Osaka 5588585, Japan. Kansai Univ, Fac Engn, Dept Biotechnol, Osaka 5648680, Japan. Tottori Univ, Fac Engn, Tottori 6808552, Japan. RP Esaki, N (reprint author), Kyoto Univ, Inst Chem Res, Kyoto 6110011, Japan. NR 36 TC 10 Z9 10 U1 0 U2 2 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-TOKYO JI J. Biochem. (Tokyo) PD OCT PY 2000 VL 128 IS 4 BP 679 EP 686 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362TR UT WOS:000089794800016 PM 11011151 ER PT J AU Kim, S Dougherty, ER Bittner, ML Chen, YD Sivakumar, K Meltzer, P Trent, JM AF Kim, S Dougherty, ER Bittner, ML Chen, YD Sivakumar, K Meltzer, P Trent, JM TI General nonlinear framework for the analysis of gene interaction via multivariate expression arrays SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE cDNA microarray; gene expression; genomic signals; nonlinear prediction ID CDNA MICROARRAY; PATTERNS AB A cDNA microarray is a complex biochemical-optical system whose purpose is the simultaneous measurement of gene expression for thousands of genes. In this paper we propose a general statistical approach to finding associations between the expression patterns of genes via the coefficient of determination. This coefficient measures the degree to which the transcriptional levels of an observed gene set can be used to improve the prediction of the transcriptional state of a target gene relative to the best possible prediction in the absence of observations. The method allows incorporation of knowledge of other conditions relevant to the prediction, such as the application of particular stimuli or the presence of inactivating gene mutations, as predictive elements affecting the expression level of a given gene. Various aspects of the method are discussed: prediction quantification, unconstrained prediction, constrained prediction using ternary perceptrons, and design of predictors given small numbers of replicated microarrays, The method is applied to a set of genes undergoing genotoxic stress for validation according to the manner in which it points toward previously known and unknown relationships, The entire procedure is supported by software that can be applied to large gene sets, has a number of facilities to simplify data analysis, and provides graphics for visualizing experimental data, multiple gene interaction, and prediction logic. (C) 2000 Society of Photo-Optical Instrumentation Engineers. [S1083-3668(00)00204-5]. C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. NHGRI, NIH, Canc Genet Lab, Bethesda, MD USA. Washington State Univ, Dept Elect Engn, Pullman, WA 99163 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Dept Elect Engn, 3128 TAMUS, College Stn, TX 77843 USA. NR 22 TC 67 Z9 71 U1 0 U2 1 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD OCT PY 2000 VL 5 IS 4 BP 411 EP 424 DI 10.1117/1.1289142 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 365ZR UT WOS:000089980800008 PM 11092429 ER PT J AU Chou, JJ Delaglio, F Bax, A AF Chou, JJ Delaglio, F Bax, A TI Measurement of one-bond N-15-C-13 ' dipolar couplings in medium sized proteins SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE calmodulin; dipolar coupling; HNCO; J(NC '); liquid crystal ID TRIPLE-RESONANCE EXPERIMENTS; LIQUID-CRYSTALLINE MEDIUM; NMR-SPECTRA; MACROMOLECULES; RESOLUTION; PHASE; CALMODULIN; (3H)J(NC'); H-1-N-15 AB A simple and accurate method is described for measurement of (1)J(C'N) splittings in isotopically enriched proteins. The method is of the quantitative J correlation type, and the (1)J(C'N) splitting is derived from the relative intensity in two 3D TROSY-HNCO spectra with (1)J(C'N) dephasing intervals of similar to1/(2(1)J(C'N)) (reference intensity) and similar to1/(1)J(C'N) (residual intensity). If the two spectra are recorded under identical conditions and with the same number of scans, the random error in the (1)J(C'N) value extracted in this manner is inversely related to the signal-to-noise (S/N) in the reference spectrum. A S/N of 30:1 in the reference spectrum yields random errors of less than 0.2 Hz in the extracted (1)J(C'N) value. Dipolar couplings obtained from the difference in (1)J(C'N) splitting in the isotropic and liquid crystalline phase for the C-terminal domain of calmodulin are in excellent agreement with its 1.68-Angstrom crystal structure, but agree considerably less with the 2.2-Angstrom structure. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Chou, JJ (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Chou, James/N-9840-2013 NR 33 TC 49 Z9 49 U1 1 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD OCT PY 2000 VL 18 IS 2 BP 101 EP 105 DI 10.1023/A:1008358318863 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 366BN UT WOS:000089985100002 PM 11101214 ER PT J AU Shoaf, SE Carson, RE Herscovitch, P Eckelman, WC AF Shoaf, SE Carson, RE Herscovitch, P Eckelman, WC TI Does labeled alpha-methyl-L-tryptophan image ONLY blood-brain barrier transport of tryptophan? Reply SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Letter C1 NIAAA, DICBR, Clin Studies Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. RP Shoaf, SE (reprint author), NIAAA, DICBR, Clin Studies Lab, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2000 VL 20 IS 10 BP 1511 EP 1511 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 360WN UT WOS:000089690500014 ER PT J AU Calhoun, ME Mouton, PR AF Calhoun, ME Mouton, PR TI Length measurement: new developments in neurostereology and 3D imagery SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE stereology; length; microscopy; morphology; image processing; acetylcholinesterase ID ALZHEIMERS-DISEASE; SECTIONS; MEMORY; THICK AB Quantification of linear biological structures has important applications in neuroscience; for example, the length of neurotransmitter-specific axonal innervation or length of dendritic processes within particular brain structures. Until recently, however, there have been practical limitations in the application of stereological tools for the unbiased estimation of object length on tissue sections. The recent development of efficient new approaches allows for the wider application of theoretically unbiased sampling and estimation techniques that are devoid of the assumptions and models of earlier methods. In this review, we outline the historical background and recent advances in the estimation of total length for biological objects on tissue sections, including a practical method to estimate the length of cholinergic fibers using newly developed methods. These newer methods also take advantage of three-dimensional image datasets and virtual probes, techniques that may have wider application in quantitative morphometry. (C) 2000 Elsevier Science B.V. All rights reserved. C1 CUNY Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Calhoun, ME (reprint author), CUNY Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, Box 1639, New York, NY 10029 USA. FU NIA NIH HHS [AG05146]; NIMH NIH HHS [MH58981]; NINDS NIH HHS [NS16735, NS38377, NS10580] NR 21 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD OCT PY 2000 VL 20 IS 1 BP 61 EP 69 DI 10.1016/S0891-0618(00)00074-0 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 373XZ UT WOS:000165316500007 PM 11074344 ER PT J AU Jacobsen, T Hibbs, E Ziegenhain, U AF Jacobsen, T Hibbs, E Ziegenhain, U TI Maternal expressed emotion related to attachment disorganization in early childhood: A preliminary report SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE Expressed Emotion; mother-child attachment quality; attachment disorganization ID INFANT ATTACHMENT; PSYCHIATRIC-PATIENTS; AFFECTIVE-DISORDER; NORMAL-CHILDREN; BEHAVIOR; MODELS; RELIABILITY; SECURITY; FAMILIES; PATTERNS AB Using a longitudinal sample of children, this study examined the relation between maternal Expressed Emotion (EE) and mother-child attachment disorganization at age 6 years. A nonclinical sample of 33 children (at ages 12 months and 18 months) from Berlin, Germany participated with their mothers in Ainsworth's Strange Situation. Thirty-two children were again observed with their mothers at age 6 years in a standard laboratory attachment observation. At the time of the 6-year assessment, maternal EE was assessed based on a Five-Minute Speech Sample. Mothers also completed the Life Events Questionnaire, a measure of family stress, and the Present State Examination, a measure of maternal depression. Maternal Expressed Emotion was significantly linked to mother-child attachment security at age 6 years. Further analyses revealed that High EE was most closely linked to the disorganized attachment pattern at age 6 years, an at-risk attachment pattern that has been associated with intrusive and hostile maternal behavior. The relationship was upheld when other relevant variables, including infant attachment disorganization and a measure of perceived family stress, were simultaneously considered. The study provides independent validation of Expressed Emotion as a measure of relationship quality in early childhood. It also provides a basis for the further investigation of the nature of the relation between maternal Expressed Emotion and attachment disorganization. C1 Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. NIMH, Rockville, MD 20857 USA. Univ Rostock, Rostock, Germany. RP Jacobsen, T (reprint author), Univ Illinois, Dept Psychiat, 907 S Wolcott, Chicago, IL 60612 USA. NR 44 TC 30 Z9 30 U1 2 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD OCT PY 2000 VL 41 IS 7 BP 899 EP 906 DI 10.1017/S0021963099006162 PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 372KT UT WOS:000165233400009 PM 11079432 ER PT J AU Jensen, RT AF Jensen, RT TI Editorial: Somatostatin receptor-based scintigraphy and antitumor treatment - An expanding vista? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID NEUROENDOCRINE TUMORS; ANALOGS; THERAPY; LOCALIZATION; CELLS C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 21 TC 11 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2000 VL 85 IS 10 BP 3507 EP 3508 DI 10.1210/jc.85.10.3507 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 363DY UT WOS:000089820800003 PM 11061490 ER PT J AU Arioglu, E Gottlieb, NA Koch, CA Doppman, JL Grey, NJ Gorden, P AF Arioglu, E Gottlieb, NA Koch, CA Doppman, JL Grey, NJ Gorden, P TI Natural history of a proinsulin-secreting insulinoma: From symptomatic hypoglycemia to clinical diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MELLITUS; PATIENT C1 NIDDKD, Diabet Branch, Div Intramural Res, Bethesda, MD 20892 USA. NICHHD, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Univ Connecticut, Sch Med, Hartford, CT 06105 USA. RP Gorden, P (reprint author), NIDDK, NIH, Bldg 10,Room 8S235, Bethesda, MD 20892 USA. EM phillip_gorden@nih.gov RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Oral, Elif/0000-0002-9171-1144; Koch, Christian/0000-0003-0678-1242 NR 7 TC 11 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2000 VL 85 IS 10 BP 3628 EP 3630 DI 10.1210/jc.85.10.3628 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 363DY UT WOS:000089820800027 PM 11061513 ER PT J AU Pack, SD Kirschner, LS Pak, E Zhuang, ZP Carney, JA Stratakis, CA AF Pack, SD Kirschner, LS Pak, E Zhuang, ZP Carney, JA Stratakis, CA TI Genetic and histologic studies of somatomammotropic pituitary tumors in patients with the "complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas" (Carney complex) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the Endocrine-Society CY JUN 21-29, 1998 CL NEW ORLEANS, LA SP Endocrine Soc ID COMPARATIVE GENOMIC HYBRIDIZATION; MCCUNE-ALBRIGHT SYNDROME; GROWTH-HORMONE; NEOPLASIA TYPE-1; ACTIVATING MUTATIONS; SOMATOSTATIN ANALOG; CARDIAC MYXOMAS; HYPERPROLACTINEMIA; HYPERPLASIA; PROLACTIN AB Carney complex (CNC) is a familial multiple neoplasia and lentiginosis syndrome with features overlapping those of McCune-Albright syndrome (MAS) and other multiple endocrine neoplasia (MEN) syndromes, MEN type 1 (MEN 1), in particular. GH-producing pituitary tumors have been described in individual reports and in at least two large CNC patient series. It has been suggested that the evolution of acromegaly in CNC resembles that of the other endocrine manifestations of CNC in its chronic, often indolent, progressive nature. However, histologic and molecular evidence has not been presented in support of this hypothesis. In this investigation, the pituitary glands of eight patients with CNC and acromegaly [age, 22.9 +/- 11.6 yr (mean +/- SD)] were studied histologically. Tumor DNA was used for comparative genomic hybridization (CGH) (four tumors). All tumors stained for both GH and prolactin PRL (eight of eight), and some for other hormones, including alpha-subunit. Evidence for somato-mammotroph hyperplasia was present in five of the eight patients in proximity to adenoma tissue; in the remaining three only adenoma tissue was available for study. CGH showed multiple changes involving losses of chromosomal regions 6q, 7q, 11p, and 11q, and gains of 1pter-p32,2q35-qter,9q33-qter,12q24-qter, 16, 17, 19p, 20p, 20q, 22p and 22q in the most aggressive tumor, an invasive macroadenoma; no chromosomal changes were seen in the microadenomas diagnosed prospectively (3 tumors). We conclude that, in at least some patients with CNC, the pituitary gland is characterized by somatotroph hyperplasia, which precedes GH-producing tumor formation, in a pathway similar to that suggested for MAS-related pituitary tumors. Three GH-producing microadenomas showed no genetic changes by CGH, whereas a macroadenoma in a patient, whose advanced acromegaly was not cured by surgery, showed extensive CGH changes. We speculate that these changes represent secondary and tertiary genetic "hits" involved in pituitary oncogenesis. The data (1) underline the need for early investigation for acromegaly in patients with CNC; (2) provide a molecular hypothesis for its clinical progression; and (3) suggest a model for MAS- and, perhaps, MEN 1-related GH-producing tumor formation. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. EM stratakc@cc1.nichd.nih.gov RI Pack, Svetlana/C-2020-2014 NR 43 TC 86 Z9 90 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2000 VL 85 IS 10 BP 3860 EP 3865 DI 10.1210/jc.85.10.3860 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 363DY UT WOS:000089820800064 PM 11061550 ER PT J AU Leveille, SG Gray, S Black, DJ LaCroix, AZ Ferrucci, L Volpato, S Guralnik, JM AF Leveille, SG Gray, S Black, DJ LaCroix, AZ Ferrucci, L Volpato, S Guralnik, JM TI A new method for identifying antibiotic-treated infections using automated pharmacy records SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE infections; aged; antibiotics; epidemiology; methods; validity ID CARE PHYSICIANS; SURVEILLANCE; BRONCHITIS; EXPOSURE; ADULTS; TRENDS; HEALTH; WOMEN AB For research purposes, there are few alternatives to costly surveillance for ascertaining infections in community populations. We propose a new approach based on antibiotic prescription fills in automated pharmacy records of the Group Health Cooperative of Puget Sound, in Seattle, Washington, to identify treated infections in postmenopausal women. After excluding probable antimicrobial prophylaxis and chronic antibiotic use, four intervals between antibiotic fills (30, 45, 60, and 90 days) were tested for their ability to detect new infections. Concordance with outpatient medical record reviews was evaluated in 150 women. The sensitivity of the automated pharmacy records using the four cutpoints for detecting new infections ranged from 88 to 80%, from 30 to 90 days, respectively. Of the 81 women with no infection in the chart reviews, 75% also had no infection using the pharmacy method. Good agreement was found between the two methods for counts of infections per person over the 2-year follow-up, with the 60-day cutpoint showing the greatest overall agreement with chart reviews (kappa = 0.55). The pharmacy method presented here offers a useful new approach for infection ascertainment for epidemiologic research. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. INRCA, Natl Res Inst, Dept Geriatr, Florence, Italy. RP Leveille, SG (reprint author), Hebrew Rehabil Ctr Aged, Res & Training Inst, 1200 Ctr St, Boston, MA 02131 USA. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 NR 20 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD OCT PY 2000 VL 53 IS 10 BP 1069 EP 1075 DI 10.1016/S0895-4356(00)00235-3 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 363XV UT WOS:000089863700014 PM 11027941 ER PT J AU Kono, H Rusyn, I Yin, M Gabele, E Yamashina, S Dikalova, A Kadiiska, MB Connor, HD Mason, RP Segal, BH Bradford, BU Holland, SM Thurman, RG AF Kono, H Rusyn, I Yin, M Gabele, E Yamashina, S Dikalova, A Kadiiska, MB Connor, HD Mason, RP Segal, BH Bradford, BU Holland, SM Thurman, RG TI NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; FACTOR-KAPPA-B; KUPFFER CELLS; INTRAGASTRIC ALCOHOL; NF-KAPPA; RAT; ETHANOL; INJURY; INHIBITION; INSIGHTS AB In North America, Liver disease due to alcohol consumption is an important cause of death in adults, although its pathogenesis remains obscure. Despite the fact that resident hepatic macrophages are known to contribute to early alcohol-induced liver injury via oxidative stress, the exact source of free radicals has remained a mystery. To test the hypothesis that NADPH oxidase is the major source of oxidants due to ethanol, we used p47(phox) knockout mice, which lack a critical subunit of this major source of reactive oxygen species in activated phagocytes. Mice were treated with ethanol chronically, using a Tsukamoto-French protocol, for 4 weeks. In wild-type mice, ethanol caused severe liver injury via a mechanism involving gut-derived endotoxin, CD 14 receptor, production of electron spin resonance-detectable free radicals, activation of the transcription factor NF-kappa B, and release of cytotoxic TNF-alpha from activated Kupffer cells. In NADPH oxidase-deficient mice, neither an increase in free radical production, activation of NF-kappa B, an increase in TNF-alpha mRNA, nor liver pathology was observed. These data strongly support the hypothesis that free radicals from NADPH oxidase in hepatic Kupffer cells play a predominant role in the pathogenesis of early alcohol-induced hepatitis by activating NF-kappa B, which activates production of cytotoxic TNF-alpha. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. RI Rusyn, Ivan/S-2426-2016 NR 40 TC 326 Z9 336 U1 2 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2000 VL 106 IS 7 BP 867 EP 872 DI 10.1172/JCI9020 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 361LX UT WOS:000089725500010 PM 11018074 ER PT J AU Liu, YJ Wada, R Yamashita, T Mi, YD Deng, CX Hobson, JP Rosenfeldt, HM Nava, VE Chae, SS Lee, MJ Liu, CH Hla, T Spiegel, S Proia, RL AF Liu, YJ Wada, R Yamashita, T Mi, YD Deng, CX Hobson, JP Rosenfeldt, HM Nava, VE Chae, SS Lee, MJ Liu, CH Hla, T Spiegel, S Proia, RL TI Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTORS; BLOOD-VESSEL FORMATION; ENDOTHELIAL-CELLS; PDGF-B; BIOACTIVE LYSOPHOSPHOLIPIDS; LYSOPHOSPHATIDIC ACID; TYROSINE KINASE; TGF-BETA; ANGIOGENESIS; MICE AB Sphingolipid signaling pathways have been implicated in many critical cellular events. Sphingosine-1-phosphate (SPP), a sphingolipid metabolite found in high concentrations in platelets and blood, stimulates members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors and triggers diverse effects, including cell growth, survival, migration, and morphogenesis. To determine the in vivo functions of the SPP/Edg signaling pathway, we disrupted the Edg1 gene in mice. Edg1(-/-) mice exhibited embryonic hemorrhage leading to intrauterine death between E12.5 and E14.5. Vasculogenesis and angiogenesis appeared normal in the mutant embryos. However, vascular maturation was incomplete due to a deficiency of vascular smooth muscle cells/pericytes. We also show that Edg-1 mediates an SPP-induced migration response that is defective in mutant cells due to an inability to activate the small GTPase, Rac. Our data reveal Edg-1 to be the first G protein-coupled receptor required for blood vessel formation and show that sphingolipid signaling is essential during mammalian development. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Univ Connecticut, Ctr Hlth, Dept Physiol, Ctr Vasc Biol, Farmington, CT USA. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bldg 10,Room 9N-314,10 Ctr DR MSC 1821, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012; Hla, Timothy/G-5873-2012; deng, chuxia/N-6713-2016 OI Hla, Timothy/0000-0001-8355-4065; NR 61 TC 741 Z9 757 U1 0 U2 14 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2000 VL 106 IS 8 BP 951 EP 961 DI 10.1172/JCI10905 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 364XQ UT WOS:000089919700007 PM 11032855 ER PT J AU Baier, LJ Permana, PA Yang, XL Pratley, RE Hanson, RL Shen, GQ Mott, D Knowler, WC Cox, NJ Horikawa, Y Oda, N Bell, GI Bogardus, C AF Baier, LJ Permana, PA Yang, XL Pratley, RE Hanson, RL Shen, GQ Mott, D Knowler, WC Cox, NJ Horikawa, Y Oda, N Bell, GI Bogardus, C TI A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID AUTOSOMAL GENOMIC SCAN; DEPENDENT DIABETES-MELLITUS; PIMA-INDIANS; OBESITY AB Previous linkage studies in Mexican-Americans localized a major susceptibility locus for type 2 diabetes, NIDDM1, to chromosome 2q. This evidence for linkage to type 2 diabetes was recently found to be associated with a common G->A polymorphism (UCSNP-43) within the CAPN10 gene. The at-risk genotype was homozygous for the UCSNP-43 G allele. In the present study among Pima Indians, the UCSNP-43 GIG genotype was nor associated with an increased prevalence of type 2 diabetes. However, Pima Indians with normal glucose tolerance, who have a G/G genotype at UCSNP-43, were found to have decreased rates of postabsorptive and insulin-stimulated glucose turnover that appear to result from decreased rates of glucose oxidation. In addition, G/G homozygotes were found to have reduced C4PN10 mRNA expression in their skeletal muscle. A decreased rate of insulin-mediated glucose turnover, or insulin resistance, is one mechanism by which the polymorphism in CAPN10 may increase susceptibility to type 2 diabetes mellitus in older persons. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. RP Baier, LJ (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 16 TC 155 Z9 167 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2000 VL 106 IS 7 BP R69 EP R73 DI 10.1172/JCI10665 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 361LX UT WOS:000089725500016 PM 11018080 ER PT J AU Martin, DH Cammarata, C van der Pol, B Jones, RB Quinn, TC Gaydos, CA Crotchfelt, K Schachter, J Moncada, J Jungkind, D Turner, B Peyton, C AF Martin, DH Cammarata, C van der Pol, B Jones, RB Quinn, TC Gaydos, CA Crotchfelt, K Schachter, J Moncada, J Jungkind, D Turner, B Peyton, C TI Multicenter evaluation of AMPLICOR and automated COBAS AMPLICOR CT/NG tests for Neisseria gonorrhoeae SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS INFECTION; ABBOTT LCX; SWAB SPECIMENS; URINE; PCR; ASSAY; WOMEN; AMPLIFICATION; DIAGNOSIS AB The fully automated COBAS AMPLICOR CT/NG and semiautomated AMPLICOR CT/NG; tests were evaluated in a multicenter trial for their ability to detect Neisseria gonorrhoeae infections, Test performance compared to that of culturing was evaluated for 2,192 matched endocervical swab and urine specimens obtained From women and for 1,981 matched urethral swab and urine specimens obtained from men. Culture-negative, PCR-positive specimens that tested positive in a confirmatory PCR test for an alternative target sequence within the N. gonorrhoeae 16S rRNA gene were considered to be true positives. The overall prevalences of gonorrhea were 6.6% in women and 20.1% in men. The COBAS AMPLICOR and AMPLICOR formats yielded concordant results for 98.8% of the specimens and exhibited virtually identical sensitivities and specificities. The results that follow are for the COBAS AMPLICOR format. With the infected patient as the reference standard, the resolved sensitivities of PCR were 92.4% for endocervical swab specimens and 64.8% for female urine specimens. There were no significant differences in these rates between women with and without symptoms, Among symptomatic men, COBAS AMPLICOR sensitivities were 94.1% for urine and 98.1% for urethral swabs; for asymptomatic men, the results were 42.3 and 73.1%, respectively, In comparison, the sensitivities of culturing were 84.8% for endocervical specimens, 92.7% for symptomatic male urethral specimens, and only 46.2% for urethral specimens obtained from asymptomatic men. When PCR results were analyzed as if only a single test had been performed on a single specimen type, the resolved sensitivity,ias always higher. The resolved specificities of PCR were 99.5% for endocervical swab specimens, 99.8% for female urine specimens, 98.9% for male urethral swab specimens, and 99.9% for male urine specimens. The internal control revealed that 2.1% of specimens were inhibitory when initially tested. Nevertheless, valid results were obtained for 99.2% of specimens because 60.0% of the inhibitory specimens were not inhibitory when a second aliquot was tested. The COBAS AMPLICOR CT/NG test for N. gonorrhoeae exhibited high sensitivity and specificity with urethral swab and urine specimens from men and endocervical swab specimens from women and thus is well suited for diagnosing and screening for N, gonorrhoeae infection. C1 Louisiana State Univ, Med Ctr, Dept Internal Med, New Orleans, LA 70118 USA. City New Orleans Delgado Clin, New Orleans, LA USA. Indiana Univ, Sch Med, Indianapolis, IN USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Thomas Jefferson Univ Hosp, Pittsburgh, PA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Martin, DH (reprint author), Louisiana State Univ, Med Ctr, Dept Internal Med, 1542 Tulane Ave, New Orleans, LA 70118 USA. RI Gaydos, Charlotte/E-9937-2010 NR 20 TC 96 Z9 98 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2000 VL 38 IS 10 BP 3544 EP 3549 PG 6 WC Microbiology SC Microbiology GA 361DP UT WOS:000089707600004 PM 11015361 ER PT J AU Porcella, SF Raffel, SJ Schrumpf, ME Schriefer, ME Dennis, DT Schwan, TG AF Porcella, SF Raffel, SJ Schrumpf, ME Schriefer, ME Dennis, DT Schwan, TG TI Serodiagnosis of louse-borne relapsing fever with glycerophosphodiester phosphodiesterase (GlpQ) from Borrelia recurrentis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; IN-VITRO CULTIVATION; D-BINDING PROTEIN; TREPONEMA-PALLIDUM; ESCHERICHIA-COLI; HAEMOPHILUS-INFLUENZAE; SYPHILIS SPIROCHETE; CHAIN-REACTION; DNA INVITRO; SEQUENCE AB Human louse-borne relapsing fever occurs in sporadic outbreaks ih central and eastern Africa that are characterized by significant morbidity and mortality. Isolates of the causative agent, Borrelia recurrentis, were obtained from the blood of four patients during a recent epidemic of the disease in southern Sudan. The glpQ gene, encoding glycerophosphodiester phosphodiesterase, from these isolates was sequenced and compared with the glpQ sequences obtained from other relapsing-fever spirochetes. Previously we showed that GlpQ of Borrelia hermsii is an immunogenic protein with utility as a serological test antigen for discriminating tick borne relapsing fever front Lyme disease. In the present work, we Cloned and expressed the glpQ gene from B. recurrentis and used recombinant GlpQ in serological tests. Acute- and convalescent-phase serum: samples obtained from 42 patients with louse-borne relapsing fever were tested with an indirect immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) that used whole cells of B. recurrentis and with immunoblotting to whole-cell lysates of the spirochete and Escherichia: coli producing recombinant GlpQ. The geometric mean titers of the acute- and Convalescent-phase serum samples measured by IFA were 1:83 and 1:575, respectively. The immunoblot analysis identified a high level of reactivity and seroconversion to GlpQ, and the assay was more sensitive than the whole-cell IFA and ELISA using purified, recombinant histidine-tagged GlpQ. Serum antibodies to GlpQ and other antigens persisted for 27 Sears in one patient. We conclude that assessment of anti-GlpQ antibodies will allow serological confirmation of louse-borne relapsing fever and determination of disease prevalence. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Ft Collins, CO 80522 USA. RP Schwan, TG (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 74 TC 41 Z9 41 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2000 VL 38 IS 10 BP 3561 EP 3571 PG 11 WC Microbiology SC Microbiology GA 361DP UT WOS:000089707600007 PM 11015364 ER PT J AU Baron, P Bremer, J Wasserman, SS Nowicki, M Driscoll, B Polsky, B Kovacs, A Reichelderfer, PS AF Baron, P Bremer, J Wasserman, SS Nowicki, M Driscoll, B Polsky, B Kovacs, A Reichelderfer, PS CA Div AIDS Treatment Res Initiative TI Detection and quantitation of human immunodeficiency virus type 1 in the female genital tract SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CERVICAL SECRETIONS; CERVICOVAGINAL SECRETIONS; INFECTED WOMEN; RNA LEVELS; HIV; BLOOD; RISK; AIDS; ANTIBODIES; NAIROBI AB Human immunodeficieney virus type 1 (HIV-1) was detected in the genital tracts of 59% of 225 women by RNA PCR and in 7% of the women by culture. In a comparison of two sampling methods, endocervical swabs were more sensitive than cervicovaginal lavage for HIV-1 RNA detection by PCR but not by culture and their sensitivity was independent of the concentration of HIV-1 RNA. C1 NICHHD, NIH, Rockville, MD 20852 USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ So Calif, Los Angeles, CA 90033 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. RP Reichelderfer, PS (reprint author), NICHHD, NIH, 6100 Execut Blvd,Room 8B13D, Rockville, MD 20852 USA. FU NIAID NIH HHS [U01 AI031834, U01 AI042590, U01 AI034993, U01-AI-31834, U01 AI035004, U01 AI034989, U01-AI-35004, U01 AI034994]; NICHD NIH HHS [U01 HD032632]; PHS HHS [N01-A1-15123] NR 19 TC 18 Z9 18 U1 0 U2 1 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 OCT PY 2000 VL 38 IS 10 BP 3822 EP 3824 PG 3 WC Microbiology SC Microbiology GA 361DP UT WOS:000089707600052 PM 11015409 ER PT J AU Fahle, GA Fischer, SH AF Fahle, GA Fischer, SH TI Comparison of six commercial DNA extraction kits for recovery of cytomegalovirus DNA from spiked human specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PCR AB We evaluated six commercially available DNA extraction kits for their ability to recover DNA from various dilutions of cytomegalovirus (CMV) added to four different specimens: bronchoalveolar lavage, cerebral spinal fluid, plasma, and whole blood. The kits evaluated included the Puregene DNA isolation kit (PG), Generation Capture Column kit, MasterPure DNA purification kit, IsoQuick nucleic acid extraction kit, QIAamp blood kit, and NucliSens isolation kit (NS), All six kits evaluated effectively removed PCR inhibitors from each of the four specimen types and produced consistently positive results down to a spiked concentration of 200 PFU of whole CMV per mi. However, the NS and PG resulted in the most consistently positive results at the lowest concentrations of spiked CMV (4 and 0.4 PFU/ml) and, in this evaluation, offered the most sensitive methods for extracting CMV DNA from the four different spiked specimens. Processing time and cost were also evaluated. C1 NIH, Microbiol Serv, Warren G Magnuson Clin Ctr, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Fahle, GA (reprint author), NIH, Microbiol Serv, Warren G Magnuson Clin Ctr, Dept Clin Pathol, Bldg 10,Room 2C-385, Bethesda, MD 20892 USA. NR 7 TC 48 Z9 51 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2000 VL 38 IS 10 BP 3860 EP 3863 PG 4 WC Microbiology SC Microbiology GA 361DP UT WOS:000089707600064 PM 11015421 ER PT J AU Straus, SE Engel, LW AF Straus, SE Engel, LW TI Psychopharmacology: An essential discipline for the critical investigation of complementary and alternative medicines SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. RP Straus, SE (reprint author), Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2000 VL 20 IS 5 BP 497 EP 499 DI 10.1097/00004714-200010000-00001 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 355BU UT WOS:000089366400001 PM 11001232 ER PT J AU Schiller, JT Hidesheim, A AF Schiller, JT Hidesheim, A TI Developing HPV virus-like particle vaccines to prevent cervical cancer: a progress report SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article; Proceedings Paper CT HPV Vaccination Workshop on Vaccinating Women again st Premature Death CY JAN 10, 2000 CL HELSINKI, FINLAND SP Acad Finland, Finnish Med Assoc DE virus-like particle; human papillomaviruses; cancer ID HUMAN-PAPILLOMAVIRUS TYPE-16; COTTONTAIL RABBIT PAPILLOMAVIRUS; NEUTRALIZING ANTIBODIES; SERUM IGG; IMMUNIZATION; MUCOSAL; MICE; VACCINATION; PROTECTION; INFECTION AB Background: the knowledge that sexually transmitted infection with one of a limited number of human papillomaviruses (HPVs) is a central cause of almost all cervical cancers affords the opportunity to prevent this common cancer through anti-viral vaccination. Objective: the spectacular success of vaccines in preventing several other viral diseases offers hope that immunoprophylaxis against the relevant HPVs could lead to a major reduction in cervical cancer incidence. Results and conclusion: the results of preclinical studies and early phase clinical trials of virus-like particle (VLP) based subunit vaccines have been very encouraging. However, unique aspects of papillomavirus biology and genital tract infections, and the lack of sexual a transmission model for papillomavirus, make it far from certain that effective prophylactic vaccination against genital HPV infection will be easily achieved. Future clinical efficacy trials will likely test the hypothesis that parenteral injection of VLPs can induce antibody mediated and type specific protection against genital tract HPV infection and subsequent development of premalignant neoplastic disease. (C) 2000 Elsevier Science B.V. All rights reserved. C1 DBS, Cellular Oncol Lab, Bethesda, MD 20892 USA. NCI, Epidemiol & Biostat Program, DCEG, NIH, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), DBS, Cellular Oncol Lab, Bldg 36,Rm 1D32, Bethesda, MD 20892 USA. NR 42 TC 36 Z9 37 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD OCT PY 2000 VL 19 IS 1-2 SI SI BP 67 EP 74 DI 10.1016/S1386-6532(00)00091-3 PG 8 WC Virology SC Virology GA 377VM UT WOS:000165547000008 PM 11091149 ER PT J AU Kholmurodov, K Smith, W Yasuoka, K Darden, T Ebisuzaki, T AF Kholmurodov, K Smith, W Yasuoka, K Darden, T Ebisuzaki, T TI A smooth-particle mesh Ewald method for DL_POLY molecular dynamics simulation package on the Fujitsu VPP700 SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE molecular dynamics; DL_POLY code; smooth-particle mesh Ewald; fast Fourier transforms; Fujitsu vector machine AB An N . log(N) smooth-particle mesh Ewald method has been incorporated into the DL_POLY molecular dynamics simulation package. The performance of the new code has been tested on a Fujitsu VPP700 for several DL_POLY-specific benchmark systems. The new method is highly vectorizable, and makes use of the extremely efficient Fast Fourier Transforms on the Fujitsu vector machine. In calculations of the coulombic forces in periodic systems requiring large reciprocal space vectors, the new code was found to be considerably faster than the conventional Ewald method. (C) 2000 John Wiley & Sons, Inc. C1 RIKEN, Inst Phys & Chem Res, Adv Comp Ctr, Computat Sci Div, Wako, Saitama 3510198, Japan. Daresbury Lab, Warrington WA4 4AD, Cheshire, England. Keio Univ, Dept Mech Engn, Yokohama, Kanagawa 2238522, Japan. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Kholmurodov, K (reprint author), RIKEN, Inst Phys & Chem Res, Adv Comp Ctr, Computat Sci Div, Hirosawa 2-1, Wako, Saitama 3510198, Japan. RI Yasuoka, Kenji/F-7643-2014; Ebisuzaki, Toshikazu/N-6998-2014 OI Ebisuzaki, Toshikazu/0000-0002-3918-1166 NR 8 TC 24 Z9 24 U1 0 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD OCT PY 2000 VL 21 IS 13 BP 1187 EP 1191 DI 10.1002/1096-987X(200010)21:13<1187::AID-JCC7>3.0.CO;2-7 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 360UP UT WOS:000089685900007 ER PT J AU Hoagwood, K Jensen, PS Feil, M Vitiello, B Bhatara, VS AF Hoagwood, K Jensen, PS Feil, M Vitiello, B Bhatara, VS TI Medication management of stimulants in pediatric practice settings: A national perspective SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE stimulants; pediatric practice; ADHD ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; PRIMARY CARE PHYSICIANS; CLINICAL-PRACTICE; CHILDREN; ATTITUDES; PATTERNS; METHYLPHENIDATE; ADOLESCENTS; KNOWLEDGE AB Using a nationally representative sample of office-based physicians, the management practices of pediatricians, psychiatrists, and family practice physicians were investigated. The major aims were to determine (1) what types of services these physicians were providing to children who received stimulants, (2) what factors predicted receipt of stimulants, and (3) whether these practices were concordant or discordant with professional consensus on diagnosis and treatment of attention-deficit hyperactivity disorders (ADHD). Prescribing and management practice data from the 1995 National Ambulatory Medical Care Survey (NAMCS) were analyzed for children ages 0 to 17 years who were seen for psychiatric problems and received stimulant medication. Results indicated that 2 million visits by children were made in 1995 to psychiatrists, pediatricians, or family practitioners in which psychotropic medications were prescribed. In pediatric visits where stimulant medication was prescribed, mental health counseling was provided 47.3% of the time and psychotherapy 21.6%. Follow-up arrangements were made in 79.1% of the visits. Psychiatrists were significantly more likely to provide psychotherapy and to specify follow-up visits than were pediatricians, but less likely to provide other health counseling. Controlling for demographic and physician effects, the factors with the most significant effect on the probability of receiving stimulants were geographic region (living in the South), race (being white), receiving mental health counseling, not receiving psychotherapy, and having health insurance. Less than 50% of pediatric visits for psychiatric reasons involving stimulant medications included any form of psychosocial intervention. In 21% of these visits, no recommendations were made for follow-up care. These practices diverge from National Institutes of Health (NIH) consensus panel recommendations and association-issued practice parameters. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Columbia Univ, Ctr Advancement Childrens Mental Hlth, New York, NY USA. NIMH, Child Treatment & Prevent Intervent Res Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Hoagwood, K (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd, Bethesda, MD 20892 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 47 TC 53 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2000 VL 21 IS 5 BP 322 EP 331 DI 10.1097/00004703-200010000-00002 PG 10 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 363VG UT WOS:000089857900002 PM 11064959 ER PT J AU Atwood, CS Hovey, RC Glover, JP Chepko, G Ginsburg, E Robison, WG Vonderhaar, BK AF Atwood, CS Hovey, RC Glover, JP Chepko, G Ginsburg, E Robison, WG Vonderhaar, BK TI Progesterone induces side-branching of the ductal epithelium in the mammary glands of peripubertal mice SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID DEOXYRIBONUCLEIC-ACID SYNTHESIS; MOUSE; RECEPTORS; GROWTH; ESTROGEN; CELLS; BETA; MORPHOGENESIS; CULTURE; PROLIFERATION AB Development of the functional secretory epithelium in the mammary gland of the female mouse requires the elongation of the anlage through the mammary fat pad to form the primary/secondary ductal network from which tertiary ductal side-branches and lobuloalveoli develop. In this study we examined the hormonal requirements for the spatial development of the primary/secondary epithelial network and tertiary side-branches by quantifying ductal growth and epithelial cell proliferation in normal and hormone-treated BALB/c mice between 21 and 39 days of age. In normal mice, an allometric increase in ductal length commenced at 31 days of age and resulted in completion of the primary/secondary ductal network by 39 days of age. Concurrent with this allometric growth was a significant increase in cellular proliferation in the terminal end-buds (TEBs) of the ductal epithelium from 29 days of age, as determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation. A level of cellular proliferation similar to that in the TEBs of 33-day-old control mice could be induced in the TEBs of 25-day-old mice following treatment for 1 day with estrogen (E), or progesterone (P) or both (E/P), indicating that both E and P were mitogenic for epithelial cells of the peripubertal TEBs. However, die period of allometric ductal growth in untreated mice did not correspond to an increase in serum E or P (which might have been expected during the estrous cycle). In addition, epithelial growth was not observed in mammary glands from 24-day-old mice that were cultured in vitro with E, P or E/P. In contrast to treatment with E, treatment with P promoted a dramatic increase, relative to control mice, in the number of tertiary branch points upon the primary/secondary ductal network. BrdU labeling of mammary glands from 24-33-day-old mice pelleted with cholesterol (C), E, P or E/P confirmed the greater mitogenicity of P on the epithelial cells of the secondary/tertiary ducts as compared with C or E. Concurrent with these changes, localized progesterone receptor (PR) expression in clusters of cells in the ductal epithelium was associated with structures that histologically resembled early branch points from ductules. In conclusion, our results suggest that additional endocrine growth factor(s) other than E and P contribute to the development of the primary/secondary ductal network, and that P is responsible for the formation of tertiary side-branches in the mammary glands of mice during puberty. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Vonderhaar, BK (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B47,10 Ctr Dr, Bethesda, MD 20892 USA. EM bv10W@nih.gov RI Chepko, Gloria/B-2235-2010 OI Chepko, Gloria/0000-0002-4691-9894 NR 42 TC 73 Z9 75 U1 0 U2 5 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2000 VL 167 IS 1 BP 39 EP 52 DI 10.1677/joe.0.1670039 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 406HR UT WOS:000167209300005 PM 11018751 ER PT J AU Ward, MH Mark, SD Cantor, KP Weisenburger, DD Correa-Villasenor, A AF Ward, MH Mark, SD Cantor, KP Weisenburger, DD Correa-Villasenor, A TI Non-Hodgkin's lymphoma and nitrate in drinking water SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Ward, MH (reprint author), NCI, Div Canc Prevent & Genet, 6120 Execut Blvd,EPS 8104, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD OCT PY 2000 VL 54 IS 10 BP 772 EP 773 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 358VZ UT WOS:000089579000017 PM 11203341 ER PT J AU Worzala, K Murabito, JM Hiller, R Sperduto, RD Ferris, R Mutalik, K D'Agostino, RB Moskowitz, MA Wilson, PMF AF Worzala, K Murabito, JM Hiller, R Sperduto, RD Ferris, R Mutalik, K D'Agostino, RB Moskowitz, MA Wilson, PMF TI Does postmenopausal estrogen replacement therapy reduce lens opacities? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Minnesota, NHLBI, Framingham Study, NEI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2000 VL 15 SU 2 BP 11 EP 11 DI 10.1046/j.1525-1497.2000.15200-46.x PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 374CK UT WOS:000165326700047 ER PT J AU Handa, A Brown, KE AF Handa, A Brown, KE TI GB virus C/hepatitis G virus replicates in human haematopoietic cells and vascular endothelial cells (Retracted Article. See vol 82, pg 2837, 2001) SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HEPATITIS-G VIRUS; BLOOD MONONUCLEAR-CELLS; LOW-DENSITY-LIPOPROTEIN; C VIRUS; FULMINANT-HEPATITIS; CLINICAL-IMPLICATIONS; C/HGV-RNA; INFECTION; LIVER; SERUM AB A novel flavivirus, GB virus C (GBV-C)/hepatitis G virus (HGV), has been detected in chronic liver disease patients. It is known that: the viral RNA can be detected in similar to 5% of American blood donors. However, the implications for liver disease and the sites of virus replication remain unknown. Possible sites of virus replication were studied by using cell lines and/or primary cells derived from human lymphoid cells, myeloid cells, hepatocytes and endothelial cells. RNA was detected by virus strand-specific RT-PCR and GBV-C/HGV antigen was detected with a rabbit polyclonal anti-E2 (envelope 2) antibody by Western blot analysis. Negative-strand RNA, representative of replicating virus, was detected in lymphoid and megakaryocytoid cell lines and primary vascular endothelial cells. In addition, an increase in virus titre over time was demonstrated and viral antigen was detected, and virus could be passaged to infect fresh cells. However, viral RNA or antigen could not be detected in any of the hepatocyte lines tested. These results indicate that the replication site of GBV-C/HGV is not primarily in hepatocytes and that detection of replicating virus in hepatic tissue may reflect virus replication in haematopoietic cells and/or vascular endothelial cells present in the liver. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Handa, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. EM handaa@nih.gov NR 42 TC 13 Z9 14 U1 1 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 2000 VL 81 BP 2461 EP 2469 PN 10 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 358KJ UT WOS:000089557000012 PM 10993934 ER PT J AU Hanazono, Y Brown, KE Dunbar, CE AF Hanazono, Y Brown, KE Dunbar, CE TI Primary T lymphocytes as targets for gene therapy SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Review ID PERIPHERAL-BLOOD LYMPHOCYTES; ADENOASSOCIATED VIRUS VECTORS; GREEN FLUORESCENT PROTEIN; HEMATOPOIETIC STEM-CELLS; APE LEUKEMIA-VIRUS; BETA-GLOBIN GENE; INACTIVATING LENTIVIRUS VECTOR; MUCOPOLYSACCHARIDOSIS TYPE-II; SCAFFOLD ATTACHMENT REGION; CATIONIC LIPOSOMES ENHANCE AB Peripheral blood T lymphocytes have been considered an attractive target for gene therapy applications. They can be easily harvested and readily expanded ex vivo. The transduction efficiency of primary human lymphocytes with standard retroviral vectors approaches 50% or more using optimized methods of gene transfer. Other methods of gene transfer, including adenoviral, adeno-associated viral, and lentiviral vectors, or nonviral techniques, have also been used for gene transfer into primary lymphocytes. Despite encouraging results in vitro, human clinical trials using retroviral vectors to transduce primary lymphocytes have been hindered by low expression levels of transgenes and immune responses against transgene products. Strategies to overcome these problems need to be developed. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Jichi Med Sch, Div Genet Therapeut, Ctr Mol Med, Minami Kawachi, Tochigi 3290498, Japan. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 138 TC 9 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD OCT PY 2000 VL 9 IS 5 BP 611 EP 620 DI 10.1089/15258160050196641 PG 10 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 375ZE UT WOS:000165432700004 PM 11091484 ER PT J AU Castagnola, E Paola, D Giacchino, R Viscoli, C AF Castagnola, E Paola, D Giacchino, R Viscoli, C TI Clinical and laboratory features predicting a favorable outcome and allowing early discharge in cancer patients with low-risk febrile neutropenia: A literature review SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Review ID EARLY HOSPITAL DISCHARGE; ANTIBIOTIC-THERAPY; INTRAVENOUS ANTIBIOTICS; ANTIMICROBIAL THERAPY; OUTPATIENT TREATMENT; PEDIATRIC-PATIENTS; PROSPECTIVE TRIAL; FEVER; CHILDREN; DISCONTINUATION AB To value feasibility of early discharge in febrile granulocytopenic patients, 27 original paper published in the last 11 years were analyzed concerning these clinical and therapeutic approaches. A Medline search of English language literature published in the last 11 years (1988-1999) used the key words neutropenia, fever, cancer, home-antibiotic therapy, short course of antibiotic therapy, and early discharge. Twenty-seven original papers fulfilling the study criteria were identified. In these studies, 5208 episodes were evaluated: there were 538 failures with 87 deaths. Features of low-risk patients who developed life-threatening infectious disease were related to general clinical condition, cancer control, bone marrow function, presence of clinical signs of infection, and social features. Careful risk assessment can allow safe recognition of low-risk patients with febrile neutropenia who can be discharged early and can be used to follow outpatient treatment programs to improve patients' quality of life as well as the use of economic resources. C1 G Caslini Childrens Hosp, Infect Dis Unit, I-16147 Genoa, Italy. Univ Genoa, Natl Canc Inst, Unit Infect Immunocompromised Host, Genoa, Italy. RP Castagnola, E (reprint author), G Caslini Childrens Hosp, Infect Dis Unit, Largo G Gaslini 5, I-16147 Genoa, Italy. RI Castagnola, Elio/C-1865-2012; Castagnola, Elio/J-4454-2016 OI Castagnola, Elio/0000-0002-5336-8429; Castagnola, Elio/0000-0002-5336-8429 NR 35 TC 13 Z9 13 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD OCT PY 2000 VL 9 IS 5 BP 645 EP 649 DI 10.1089/15258160050196687 PG 5 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 375ZE UT WOS:000165432700008 PM 11091488 ER PT J AU Enkemann, SA Ward, RD Berger, SL AF Enkemann, SA Ward, RD Berger, SL TI Mobility within the nucleus and neighboring cytosol is a key feature of prothymosin-alpha SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE prothymosin alpha; nucleus; mitosis; charged molecules ID AUG INITIATOR CODON; MAMMALIAN-CELLS; THYMOSIN ALPHA-1; PROTEIN IMPORT; HISTONE H1; RAT THYMUS; IN-VIVO; TRANSPORT; GENE; RNA AB Prothymosin alpha is a small, unfolded, negatively charged, poorly antigenic mammalian protein with a potent nuclear localization signal. Although it is apparently essential for growth, its precise function is unknown. We examined the location and behavior of the protein bearing different epitope tags using in situ immunolocalization in COS-1 and NIH3T3 cells. Tagged prothymosin or appeared to be punctate and widely dispersed throughout the nucleus, with the exception of the nucleolus. A tiny cytoplasmic component, which persisted in the presence of cycloheximide and actinomycin D during interphase, became pronounced immediately before, during, and after mitosis. When nuclear uptake was abrogated, small tagged prothymosin or molecules, but not prothymosin alpha fused to beta-galactosidase, accumulated significantly in the cytoplasm. Tagged prothymosin or shared domains with mobile proteins such as Ran, transportin, and karyopherin beta, which also traverse the nuclear membrane, and co-localized with active RNA polymerase II. Mild digitonin treatment resulted in nuclei devoid of prothymosin alpha. The data do not support tight binding to any nuclear component, Therefore, we propose that prothymosin alpha is a highly diffusible bolus of salt and infer that it facilitates movement of charged molecules in highly charged environments within and near the nucleus. C1 NCI, Sect Genes & Gene Prod, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Berger, SL (reprint author), NCI, Sect Genes & Gene Prod, NIH, Bldg 8,Room 311A, Bethesda, MD 20892 USA. NR 62 TC 20 Z9 22 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD OCT PY 2000 VL 48 IS 10 BP 1341 EP 1355 PG 15 WC Cell Biology SC Cell Biology GA 356DT UT WOS:000089429600005 PM 10990488 ER PT J AU Watzl, C Stebbins, CC Long, EO AF Watzl, C Stebbins, CC Long, EO TI Cutting edge: NK cell inhibitory receptors prevent tyrosine phosphorylation of the activation receptor 2B4 (CD244) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CLASS-I MOLECULES; CYTOTOXIC LYMPHOCYTES; T-CELLS; HLA-C; COMPLEX; SHP-1; IDENTIFICATION; RECOGNITION; RECRUITMENT AB 2B4 is an NK cell activation receptor that can provide a con stimulatory signal to other activation receptors and whose mode of signal transduction is still unknown. We shaw that cross-linking of 2B4 on NK cells results in its rapid tyrosine phosphorylation, implying that this initial step in 2B4 signaling does not require coligation of other receptors. Ligation of 2B4 in the context of an NK cell-target cell interaction leads to 2B4 tyrosine phosphorylation, target cell lysis, and IFN-gamma release, Coligation of 2B4 with the inhibitory receptors killer cell Ig-like receptor (KIR)2DL1 or CD94/NKG2 completely blocks NK cell activation, The rapid tyrosine phosphorylation of 2B4 observed upon contact of NK cells with sensitive target cells is abrogated when KIR2DL1 or CD94/NKG2 are engaged by their cognate MHC class I ligand on resistant target cells. These results demonstrate that NK inhibitory receptors can interfere with a step as proximal as phosphorylation of an activation receptor. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011; Watzl, Carsten/B-4911-2013 OI Long, Eric/0000-0002-7793-3728; Watzl, Carsten/0000-0001-5195-0995 NR 30 TC 82 Z9 82 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2000 VL 165 IS 7 BP 3545 EP 3548 PG 4 WC Immunology SC Immunology GA 357AZ UT WOS:000089477500002 PM 11034353 ER PT J AU Noben-Trauth, N Hu-Li, J Paul, WE AF Noben-Trauth, N Hu-Li, J Paul, WE TI Conventional, naive CD4(+) T cells provide an initial source of IL-4 during Th2 differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HELPER PHENOTYPE DEVELOPMENT; IMMUNOGLOBULIN-E PRODUCTION; ANTI-IGD ANTIBODY; NON-B-CELL; IN-VIVO; IL-4-PRODUCING CELLS; LEISHMANIA-MAJOR; MESSENGER-RNA; CROSS-LINKAGE; MICE REVEAL AB IL-4 is known to promote the differentiation of CD4(+) T cells into IL-4-secreting Th2 cells. However, the cellular source of the early burst of IL-4 that drives Th2 responses in vivo has not been conclusively identified. Mice deficient for the IL-4 receptor alpha-chain (IL-4R alpha(-/-)) retain the capacity to secrete IL-4 and can be used to identify those cell types that produce IL-4 without a requirement for prior IL-4-mediated stimulation. To address whether naive, conventional CD4(+) T cells may act as initial producers of IL-4 in Ag-specific responses, we crossed the BALB/c IL-4R alpha(-/-)mice to DO11.10/scid TCR transgenic mice. Lymph node cells from wild-type and IL-4R alpha(-/-) DO11.10/scid mice secreted similar to 50 pg of IL-4 per 10(6) cells within 48 h after peptide stimulation. This small amount of IL-4 was sufficient to cause the differentiation of wild-type CD4(+) T cells into Th2 cells, particularly if IFN-gamma and IL-12 were neutralized during the priming cultures. CD4(+) cells from the IL-4R alpha(-/-) mice gave rise to a minor proportion (similar to 2%) of IL-4-producing cells upon stimulation in the presence of anti-IFN-gamma and anti-IL-12, These data show that conventional, naive CD4(+) T cells may be considered as initial sources of IL-4 and, in the absence of IFN-gamma and IL-12, this IL-4 can induce Th2 polarization. C1 NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. RP Noben-Trauth, N (reprint author), NIAID, Immunol Lab, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 45 TC 74 Z9 74 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2000 VL 165 IS 7 BP 3620 EP 3625 PG 6 WC Immunology SC Immunology GA 357AZ UT WOS:000089477500013 PM 11034364 ER PT J AU Lyakh, LA Koski, GK Telford, W Gress, RE Cohen, PA Rice, NR AF Lyakh, LA Koski, GK Telford, W Gress, RE Cohen, PA Rice, NR TI Bacterial lipopolysaccharide, TNF-alpha, and calcium ionophore under serum-free conditions promote rapid dendritic cell-like differentiation in CD14(+) monocytes through distinct pathways that activate NF-kappa B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; TRANSCRIPTION FACTORS; NUCLEAR-LOCALIZATION; SIGNALING PATHWAYS; BLOOD MONOCYTES; MESSENGER-RNAS; DEFICIENT MICE; T-CELLS; RELB AB To facilitate the study of signaling pathways involved in myeloid dendritic cell (DC) differentiation, we have developed a serum-free culture system in which human CD14(+) peripheral blood monocytes differentiate rapidly in response to bacterial LPS, TNF-alpha, or calcium ionophore (CI), Within 48-96 h, depending on the inducing agent, the cells acquire many immunophenotypical, morphological, functional, and molecular properties of DC. However, there are significant differences in the signaling pathways used by these agents, because 1) LPS-induced, but not CI-induced, DC differentiation required TNF-alpha production; and 2) cyclosporin A inhibited differentiation induced by CI, but not that induced by LPS, Nevertheless, all three inducing agents activated members of the NF-kappa B family of transcription factors, including Rein, suggesting that despite differences in upstream elements, the signaling pathways all involve NF-kappa B, In this report we also demonstrate and offer an explanation for two observed forms of the RelB protein and show that RelB can be induced in myeloid cells, either directly or indirectly, through a calcium-dependent and cyclosporin A-sensitive pathway. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Frederick, MD 21702 USA. NCI, Med Branch, Bethesda, MD 20814 USA. Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. RP Rice, NR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, POB B, Frederick, MD 21702 USA. NR 46 TC 94 Z9 109 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2000 VL 165 IS 7 BP 3647 EP 3655 PG 9 WC Immunology SC Immunology GA 357AZ UT WOS:000089477500017 PM 11034368 ER PT J AU Domachowske, JB Bonville, CA Rosenberg, HF AF Domachowske, JB Bonville, CA Rosenberg, HF TI Cytokeratin 17 is expressed in cells infected with respiratory syncytial virus via NF-kappa B activation and is associated with the formation of cytopathic syncytia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INTERLEUKIN-8 GENE-EXPRESSION; MEASLES-VIRUS; TRANSCRIPTION FACTOR; MESSENGER-RNA; KERATIN K17; PROTEIN; CYTOSKELETON; EPITHELIUM; PNEUMONIA; ACTIN AB We used differential display to detect enhanced expression of an mRNA fragment encoding cytokeratin 17 (Ck-17) in respiratory syncytial virus (RSV)-infected epithelial cells. Expression increased 12-fold by 96 h after infection but remained unchanged in cells challenged with virus in the presence of neutralizing anti-RSV fusion protein antibody. Immunoblots of RSV-infected cell lysates probed with an anti-keratin antibody demonstrated stable expression of total cytokeratins over time. When probed with an anti-Ck-17 monoclonal antibody, Ck-17 was first detected at 4 days after infection. In situ staining demonstrated that Ck-17 expression localized to regions of syncytia formation. Expression of Ck-17 mRNA also increased in response to intracellular RSV-F protein in the absence of active RSV infection. No increase in Ck-17 mRNA expression and no syncytia were observed in RSV-infected cells grown in the presence of the NF-kappa B inhibitor gliotoxin, These results suggest that RSV-induced transcriptional activation of the Ck-17 gene is dependent on an NF-kappa B-associated signaling pathway. C1 SUNY Upstate Med Univ, Div Infect Dis, Dept Pediat, Syracuse, NY 13210 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Upstate Med Univ, Div Infect Dis, Dept Pediat, 750 E Adams St, Syracuse, NY 13210 USA. NR 35 TC 17 Z9 17 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 2000 VL 182 IS 4 BP 1022 EP 1028 DI 10.1086/315841 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 361FJ UT WOS:000089712100002 PM 10979895 ER PT J AU Kovacs, JA Imamichi, H Vogel, S Metcalf, JA Dewar, RL Baseler, M Stevens, R Adelsberger, J Lambert, L Davey, RT Walker, RE Falloon, J Polis, MA Masur, H Lane, HC AF Kovacs, JA Imamichi, H Vogel, S Metcalf, JA Dewar, RL Baseler, M Stevens, R Adelsberger, J Lambert, L Davey, RT Walker, RE Falloon, J Polis, MA Masur, H Lane, HC TI Effects of intermittent interleukin-2 therapy on plasma and tissue human immunodeficiency virus levels and quasi-species expression SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th Conference on Retroviruses and Opportunistic Infections CY JAN 31-FEB 04, 1999 CL CHICAGO, ILLINOIS ID ACTIVE ANTIRETROVIRAL THERAPY; NECROSIS-FACTOR-ALPHA; CD4(+) T-CELLS; SUBCUTANEOUS INTERLEUKIN-2; INTRAVENOUS INTERLEUKIN-2; CONTROLLED TRIAL; TYPE-1 RNA; HIV-1; REPLICATION; INFECTION AB To characterize the effects of intermittent interleukin (IL)-2 therapy on human immunodeficiency virus (HIV), 11 patients underwent detailed virological evaluation during a year of IL-2 therapy. Six patients showed a >0.5 log increase in plasma HIV during at least 1 IL-2 cycle, with 2 experiencing an increase in >50% of cycles. Three of the remaining 5 patients had a >0.5 log decrease during at least 1 IL-2 cycle, and the remaining patients exhibited <0.5 log changes. No changes in lymphoid (tonsil) levels of HIV were seen during the year. Quasispecies analysis in a separate cohort demonstrated that the virus induced by IL-2 most commonly resembled pre-IL-2 plasma quasi species. Thus, intermittent IL-2 does not result in sustained increases in either plasma or tissue levels of HIV and does not result in sustained expression of a previously silent quasi species. C1 NIAID, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. RP Kovacs, JA (reprint author), Bldg 10,Rm 7D43,MSC 1662, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 FU NCI NIH HHS [N01-CO-56000] NR 31 TC 24 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 2000 VL 182 IS 4 BP 1063 EP 1069 DI 10.1086/315821 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 361FJ UT WOS:000089712100007 PM 10979900 ER PT J AU Cooper, PJ Chico, ME Losonsky, G Sandoval, C Espinel, I Sridhara, R Aguilar, M Guevara, A Guderian, RH Levine, MM Griffin, GE Nutman, TB AF Cooper, PJ Chico, ME Losonsky, G Sandoval, C Espinel, I Sridhara, R Aguilar, M Guevara, A Guderian, RH Levine, MM Griffin, GE Nutman, TB TI Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BLOOD-GROUP ANTIGENS; PARALYTIC POLIOMYELITIS; STRAIN CVD-103-HGR; ROTAVIRUS VACCINE; GLOBAL BURDEN; SWISS ADULTS; IMMUNOGENICITY; SAFETY; TRIAL; INFECTIONS AB Because concurrent infections with geohelminth parasites might impair the immune response to oral vaccines, we studied the vibriocidal antibody response to the oral cholera vaccine CVD 103-HgR in children infected with Ascaris lumbricoides and investigated the effect of albendazole pretreatment on the postvaccination response. Children with ascariasis were randomized to receive either 2 sequential doses of 400 mg of albendazole or placebo. After the second dose, CVD 103-HgR was given, and serum vibriocidal antibody levels were measured before and 10 days after vaccination. Postvaccination rates of seroconversion were greater in the treatment group that received albendazole (P = .06). Significantly greater rates of seroconversion and geometric mean titer were observed in the albendazole group in subjects with non-O ABO blood groups. A significant association was observed between vibriocidal seroconversion rates and treatment group, suggesting that A. lumbricoides infections impair the immune response to oral cholera vaccine, particularly in subjects of non-O blood groups. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Emmes Corp, Potomac, MD 20854 USA. Hosp Vozandes, Dept Clin Invest, Quito, Ecuador. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Minist Publ Hlth, Quito, Ecuador. RP Cooper, PJ (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Rm 4-126,MSC 0425, Bethesda, MD 20892 USA. EM pc102d@hotmail.com FU NIAID NIH HHS [N01-AI-45251] NR 49 TC 95 Z9 97 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 2000 VL 182 IS 4 BP 1199 EP 1206 DI 10.1086/315837 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 361FJ UT WOS:000089712100025 PM 10979918 ER PT J AU Cooper, PJ Chico, ME Sandoval, C Espinel, I Guevara, A Kennedy, MW Urban, JF Griffin, GE Nutman, TB AF Cooper, PJ Chico, ME Sandoval, C Espinel, I Guevara, A Kennedy, MW Urban, JF Griffin, GE Nutman, TB TI Human infection with Ascaris lumbricoides is associated with a polarized cytokine response SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN ONCHOCERCIASIS; NEMATODE INFECTIONS; TETANUS VACCINATION; HELMINTH INFECTIONS; GLOBAL BURDEN; T-CELL; POPULATIONS; IMMUNITY; ANTIBODY; CHILDREN AB To define the cytokine response to Ascaris lumbricoides infection, the cellular immune response to adult and larval-stage Ascaris antigens in young adults with moderate infection intensities (n = 73) was compared with that of a group of uninfected control subjects (n = 40). A. lumbricoides-infected subjects had significantly greater lymphoproliferative responses to adult and larval-stage antigens, compared with uninfected control subjects (P < .01). The frequencies of parasite antigen-stimulated peripheral blood mononuclear cell (PBMC)-expressing interleukin (IL)-4 and IL-5 were significantly greater in the infected group (P < .001), whereas the frequencies of IL-10- and interferon-gamma-expressing PBMC were similar in the 2 groups studied. The ratios of Th2 to Th1 cytokine frequencies were significantly elevated in the infected group, compared with those in uninfected subjects, as was IL-5 protein production by PBMC stimulated with adult (P < .05) and L3/L4 stage (P < .001) antigens, Analysis of these data indicates that A. lumbricoides infections in endemic regions are associated with a highly polarized type 2 cytokine response. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. USDA, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. Hosp Vozandes, Dept Clin Invest, Quito, Ecuador. Univ Glasgow, Inst Biomed & Life Sci, Div Infect & Immun, Glasgow, Lanark, Scotland. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. RP Cooper, PJ (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Rm 4-126,MSC 0425, Bethesda, MD 20892 USA. OI Urban, Joseph/0000-0002-1590-8869 NR 27 TC 149 Z9 155 U1 0 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 2000 VL 182 IS 4 BP 1207 EP 1213 DI 10.1086/315830 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 361FJ UT WOS:000089712100026 PM 10979919 ER PT J AU Pitt, J Henrard, D FitzGerald, G Mofenson, L Lew, J Hillyer, G Mendez, H Cooper, E Hanson, C Rich, KC AF Pitt, J Henrard, D FitzGerald, G Mofenson, L Lew, J Hillyer, G Mendez, H Cooper, E Hanson, C Rich, KC CA Women Infants Transmission Study TI Human immunodeficiency virus (HIV) type I antibodies in perinatal HIV-1 infection: Association with human HIV-1 transmission, infection, and disease progression SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th Conference on Retroviruses and Opportunistic Infections CY JAN 22-31, 1997 CL WASHINGTON, D.C. ID VERTICAL TRANSMISSION; P24 ANTIBODY; VIRAL LOAD; INFANTS; PROTEINS; CHILDREN; ANTIGEN; MARKERS; MOTHERS; RNA AB Anti -human immunodeficiency virus (HIV) type 1 antibodies in 242 pregnant women and 238 infants were measured at birth and at 1, 2, 4, and 6 months after birth, to estimate their association with perinatal transmission and infant disease progression. Maternal anti-p24 (P = .01) and anti-gp120 (P = .04) antibodies were inversely associated with vertical transmission rates, independent of maternal percentage of CD4 cells, hard drug use, duration of ruptured membranes, serum albumin levels, serum vitamin A levels, and quantitative HIV-1 peripheral mononuclear blood cell culture, but not with maternal plasma immune complex dissociated p24 or HIV-1 RNA copy number, both of which were highly correlated with antibodies. From ages 1-2 months, anti-gp120, -gp41, -p31, and -p66 decayed to a greater extent in Infected than in uninfected infants. Infected infants produced anti-p24 antibody by age 2 months, anti-p17 by 4 months, and anti-p41 and anti-gp120 by 6 months. As early as birth, infants with rapid disease progression had lower levels of anti-p24 than did infants whose disease did not rapidly progress, but not independently of HIV-1 RNA levels. C1 Columbia Univ Coll Phys & Surg, Dept Pediat, Div Infect Dis, New York, NY 10032 USA. SUNY Brooklyn, Dept Pediat, Brooklyn, NY USA. Abbott Labs, N Chicago, IL 60064 USA. Univ Illinois, Dept Pediat, Chicago, IL USA. New England Res Inst, Watertown, MA 02172 USA. Boston Med Ctr, Dept Pediat Infect Dis, Boston, MA USA. Natl Inst Child Hlth & Human Dev, Rockville, MD USA. Univ Puerto Rico, San Juan, PR 00936 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Pitt, J (reprint author), Columbia Univ Coll Phys & Surg, Dept Pediat, Div Infect Dis, 622 W 168th St,PH W 4-463, New York, NY 10032 USA. FU NIAID NIH HHS [U01 AI 34840, U01 AI 34841, U01 AI 34842] NR 15 TC 9 Z9 9 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 2000 VL 182 IS 4 BP 1243 EP 1246 DI 10.1086/315809 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 361FJ UT WOS:000089712100033 PM 10979926 ER PT J AU Calista, D Goldstein, AM Landi, MT AF Calista, D Goldstein, AM Landi, MT TI Familial melanoma aggregation in north-eastern Italy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID CUTANEOUS MALIGNANT-MELANOMA; RISK-FACTORS; HISTORY; NEVI C1 NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. M Bufalini Hosp, Dermatol Unit, Cesena, Italy. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, NIH, EPS 7114-6120 Execut Blvd, Bethesda, MD 20892 USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2000 VL 115 IS 4 BP 764 EP 765 DI 10.1046/j.1523-1747.2000.00124-4.x PG 2 WC Dermatology SC Dermatology GA 363CK UT WOS:000089816700031 PM 10998160 ER PT J AU Mason, LH AF Mason, LH TI Recognition of CHO cells by inhibitory and activating Ly-49 receptors SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Ly-49; NK; CHO; IFN-gamma; DAP-12 ID NATURAL-KILLER-CELLS; NK CELLS; SIGNAL-TRANSDUCTION; MULTIGENE FAMILY; MOLECULES; DOMAINS; LOCUS AB Upon Ligand recognition, members of the murine Ly-49 receptor family can transmit inhibitory or activating signals that regulate NK cell function. Ly-49A, G, and D have been shown to recognize the murine class I molecule H-2Da(d) as a potential ligand. Recent studies also have demonstrated also that Ly-49D(+) NK cells can lyse CHO cells, although the ligand responsible for this recognition was not identified. Because allorecognition by NK cells may be important in bone-marrow transplantation and because of the overlapping class I recognition by these receptors, recognition of CHO cells by Ly-49G and A was investigated. Our data suggest that Ly-49G and probably A transmit inhibitory signals in response to CHO cells. Receptor inhibition was assessed by examining NK lytic function, IFN-gamma secretion, and DAP12 phosphorylation in response to CHO cells by sorted subsets of Ly-49D vs. G B6 NK cells. Our results suggest that CHO cells may express a common ligand(s) that is capable of engaging Ly-49D, G, and possibly A in C576BL/6 NK cells, In addition to our findings that Ly-49 inhibitory receptors also recognize CHO cells, activating receptors other than Ly-49D are present in B6 mice that can lyse CHO cells. C1 NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, DBS, Frederick, MD 21702 USA. RP Mason, LH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, DBS, Bldg 560,Rm 31-93, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 15 TC 10 Z9 10 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 OCT PY 2000 VL 68 IS 4 BP 583 EP 586 PG 4 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 361MD UT WOS:000089726100020 PM 11037982 ER PT J AU Kuszewski, J Clore, GM AF Kuszewski, J Clore, GM TI Sources of and solutions to problems in the refinement of protein NMR structures against torsion angle potentials of mean force SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID ACCURACY AB It is often the case that a substantial number of torsion angles (both backbone and sidechain) in structures of proteins and nucleic acids determined by NMR are found in physically unlikely and energetically unfavorable conformations. We have previously proposed a database-derived potential of mean force comprising one-, two-, three-, and four-dimensional potential surfaces which describe the likelihood of various torsion angle combinations to bias conformational sampling during simulated annealing refinement toward those regions that are populated in very high resolution (less than or equal to 1.75 Angstrom) crystal structures. We now note a shortcoming of our original implementation of this approach: namely, the forces it places on atoms are very rough. When the density of experimental restraints is low, this roughness can both hinder convergence to commonly populated regions of torsion angle space and reduce overall conformational sampling, In this paper we describe a modification that completely eliminates these problems by replacing the original potential surfaces by a sum of multidimensional Gaussian functions. Structures refined with the new Gaussian implementation now simultaneously enjoy excellent global sampling and excellent local choices of torsion angles. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 11 TC 81 Z9 82 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD OCT PY 2000 VL 146 IS 2 BP 249 EP 254 DI 10.1006/jmre.2000.2142 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 361FD UT WOS:000089711600001 PM 11001840 ER PT J AU Stone, GA Johnson, BK Druilhet, R Garza, PB Gibbs, CJ AF Stone, GA Johnson, BK Druilhet, R Garza, PB Gibbs, CJ TI Immunophenotyping of peripheral blood, ranges of serum chemistries and clinical hematology values of healthy chimpanzees (Pan troglodytes) SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE chimpanzees; clinical chemistries; hematology; immunophenotyping; normal ranges ID T-LYMPHOTROPIC RETROVIRUSES; AIDS; TRANSMISSION; INFECTION; TRAITS AB This paper presents clinical chemistry, hematology and immunophenotyping data from 102 chimpanzees over a 2-year period. The groupings were: 3 years or less, 4-7 years, and 8+ years. These data are intended to augment formerly published information on these parameters and to serve as a concise reference guide for primate veterinarians and researchers for whom these data may be useful. This study has larger samplings than previously published data and more panel constituents by immunophenotyping. C1 NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD USA. Univ SW Louisiana, New Iberia Res Ctr, New Iberia, LA USA. RP Stone, GA (reprint author), NCI, Div Basic Sci, Basic Res Lab, Mol Cytogenet Sect,NIH, Frederick, MD 21702 USA. NR 15 TC 10 Z9 10 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2000 VL 29 IS 5 BP 324 EP 329 DI 10.1034/j.1600-0684.2000.290503.x PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 388VR UT WOS:000166204200003 PM 11168822 ER PT J AU Eggers, CH Casjens, S Hayes, SF Garon, CF Damman, CJ Oliver, DB Samuels, DS AF Eggers, CH Casjens, S Hayes, SF Garon, CF Damman, CJ Oliver, DB Samuels, DS TI Bacteriophages of spirochetes SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; 32-KILOBASE CIRCULAR PLASMIDS; UPSTREAM HOMOLOGY BOX; BORRELIA-BURGDORFERI; LINEAR PLASMIDS; GENE FAMILY; SUPERCOILED PLASMIDS; NUCLEOTIDE-SEQUENCE; GENOMIC SEQUENCE; IN-VITRO AB Historically, a number of bacteriophage-like particles have been observed in association with members of the bacterial order Spirochetales, the spirochetes. In the last decade, several spirochete bacteriophages have been isolated and characterized at the molecular level. We have recently characterized a bacteriophage of the Lyme disease agent, Borrelia burgdorferi, which we have designated phi BB-1. Here we review the history of the association between the spirochetes and their bacteriophages, with a particular emphasis on phi BB-1 and its prophage, the 32-kb circular plasmid family of B. burgdorferi. C1 Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. Univ Utah, Div Mol Biol & Genet, Dept Oncol Sci, Salt Lake City, UT 84132 USA. NIAID, Rocky Mt Labs, Microscopy Branch, Hamilton, MT 59840 USA. Wesleyan Univ, Dept Mol Biol & Biochem, Middletown, CT 06459 USA. RP Samuels, DS (reprint author), Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. EM samuels@selway.umt.edu RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 FU NIAID NIH HHS [AI41559] NR 87 TC 40 Z9 40 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PD OCT PY 2000 VL 2 IS 4 BP 365 EP 373 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 404JG UT WOS:000167093200005 PM 11075907 ER PT J AU Tilly, K Elias, AF Bono, JL Stewart, P Rosa, P AF Tilly, K Elias, AF Bono, JL Stewart, P Rosa, P TI DNA exchange and insertional inactivation in spirochetes SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; HIGH-VOLTAGE ELECTROPORATION; BORRELIA-BURGDORFERI; SERPULINA-HYODYSENTERIAE; TREPONEMA-DENTICOLA; CIRCULAR PLASMID; SWINE-DYSENTERY; GENETIC-TRANSFORMATION; ESCHERICHIA-COLI; MUTANT AB Spirochetes have complex life cycles and are associated with a number of diseases in humans and animals. Despite their significance as pathogens, spirochete genetics are in their early stages. However, gene inactivation has been achieved in Borrelia burgdorferi, Brachyspira hyodysenteriae, and Treponema denticola. Here, we review methods that have been used in spirochetes for gene inactivation and DNA exchange, with a primary focus on B. burgdorferi. We also describe factors influencing electrotransformation in B. burgdorferi. In summary, optimal transformation frequencies are obtained with log phase bacteria, large amounts of DNA (up to 50 mug per transformation), and high field strength (12.5-37.5 kV/cm). Infectious B, burgdorferi isolates transform with frequencies 100-fold lower than those found for high passage, non-infectious strains. Surface characteristics of the bacteria, which often correlate with infectivity, are among the obstacles to effective transformation by electroporation. C1 NIAID, Lab Human Bacterial Pathogenesis, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Rosa, P (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. NR 72 TC 37 Z9 39 U1 0 U2 0 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PD OCT PY 2000 VL 2 IS 4 BP 433 EP 442 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 404JG UT WOS:000167093200014 PM 11075915 ER PT J AU Garcia-Lara, J Picardeau, M Hinnebusch, BJ Huang, WM Casjens, S AF Garcia-Lara, J Picardeau, M Hinnebusch, BJ Huang, WM Casjens, S TI The role of genomics in approaching the study of Borrelia DNA replication SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; ASYMMETRIC SUBSTITUTION PATTERNS; BURGDORFERI LINEAR CHROMOSOME; BACILLUS-SUBTILIS CHROMOSOME; F-PLASMID PARTITION; ESCHERICHIA-COLI; ORIGIN REGION; CAULOBACTER-CRESCENTUS; NUCLEOTIDE-SEQUENCE; SOPB-PROTEIN AB The identification of chromosomal and episomal origins of replication in the genome of the causative agent of Lyme disease, the spirochete Borrelia burgdorferi, has been greatly facilitated by genomics. Analysis of genome features, including strand compositional asymmetries, organizational similarities to other bacterial origins of replication, and the presence of homologues of genes involved in replication and partitioning, have contributed to the identification of a collection of putative origins of replication within the Borrelia genome. This analysis has provided the basis for the experimental verification of origins in the linear chromosome and in the linear plasmid Ip28-2. Information generated during the study of these origins will significantly contribute to the understanding of the mechanisms of replication and partitioning in Borrelia. C1 Univ Georgia, Dept Microbiol, Athens, GA 30602 USA. Inst Pasteur, Unite Bacteriol Mol & Med, Paris, France. NIAID, NIH, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. Univ Utah, Sch Med, Div Mol Biol & Genet, Dept Oncol Sci, Salt Lake City, UT 84132 USA. RP Garcia-Lara, J (reprint author), Univ Georgia, Dept Microbiol, 546 Biol Sci Bldg, Athens, GA 30602 USA. NR 75 TC 4 Z9 4 U1 0 U2 0 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PD OCT PY 2000 VL 2 IS 4 BP 447 EP 454 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 404JG UT WOS:000167093200016 PM 11075917 ER PT J AU Koonin, EV Wolf, YI Kondrashov, AS Aravind, L AF Koonin, EV Wolf, YI Kondrashov, AS Aravind, L TI Bacterial homologs of the small subunit of eukaryotic DNA primase SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID DOMAIN; PROTEINS; LEF-1 C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 17 TC 16 Z9 17 U1 0 U2 1 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PD OCT PY 2000 VL 2 IS 4 BP 509 EP 512 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 404JG UT WOS:000167093200025 PM 11075926 ER PT J AU Yu, ZF Nikolova-Karakashian, M Zhou, DH Cheng, GJ Schuchman, EH Mattson, MP AF Yu, ZF Nikolova-Karakashian, M Zhou, DH Cheng, GJ Schuchman, EH Mattson, MP TI Pivotal role for acidic sphingomyelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE apoptosis; calcium; excitotoxicity; interleukin; stroke; tumor necrosis factor ID MANGANESE SUPEROXIDE-DISMUTASE; CYTOCHROME-P450 2C11 CYP2C11; PROTECTS HIPPOCAMPAL-NEURONS; NF-KAPPA-B; BRAIN INJURY; PHOSPHOLIPASE-C; PEROXYNITRITE PRODUCTION; SIGNAL-TRANSDUCTION; CELL-SURVIVAL; MICE LACKING AB Stroke is a major cause of long-term disability, the severity of which is directly related to the numbers of neurons that succumb to the ischemic insult. The signaling cascades activated by cerebral ischemia that may either promote or protect against neuronal death are not well-understood. One injury-responsive signaling pathway that has recently been characterized in studies of non-neural cells involves cleavage of membrane sphingomyelin by acidic and/or neutral sphingomyelinase (ASMase) resulting in generation of the second messenger ceramide. We now report that transient focal cerebral ischemia induces large increases in ASMase activity, ceramide levels, and production of inflammatory cytokines in wild-type mice, but not in mice lacking ASMase. The extent of brain tissue damage is decreased and behavioral outcome improved in mice lacking ASMase. Neurons lacking ASMase exhibit decreased vulnerability to excitotoxicity and hypoxia, which is associated with decreased levels of intracellular calcium and oxyradicals. Treatment of mice with a drug that inhibits ASMase activity and ceramide production reduces ischemic neuronal injury and improves behavioral outcome, suggesting that drugs that inhibit this signaling pathway may prove beneficial in stroke patients. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Physiol, Lexington, KY 40536 USA. Univ Kentucky, Dept Med, Lexington, KY 40536 USA. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 50 TC 122 Z9 128 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD OCT PY 2000 VL 15 IS 2 BP 85 EP 97 DI 10.1385/JMN:15:2:85 PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 396BP UT WOS:000166616700003 PM 11220788 ER PT J AU Lee, J Duan, WZ Long, JM Ingram, DK Mattson, MP AF Lee, J Duan, WZ Long, JM Ingram, DK Mattson, MP TI Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE aging; Alzheimer's disease; bromodeoxyuridine; caloric restriction; hippocampus; stem cells; stereology ID PROTECTS HIPPOCAMPAL-NEURONS; NEUROTROPHIC FACTOR; FOOD RESTRICTION; ENRICHED ENVIRONMENT; PARKINSONS-DISEASE; SPATIAL MEMORY; GROWTH-FACTORS; BRAIN-DAMAGE; NEUROGENESIS; NEUROPROTECTION AB The adult brain contains neural stem cells that are capable of proliferating, differentiating into neurons or glia, and then either surviving or dying. This process of neural-cell production (neurogenesis) in the dentate gyrus of the hippocampus is responsive to brain injury, and both mental and physical activity. We now report that neurogenesis in the dentate gyrus can also be modified by diet. Previous studies have shown that dietary restriction (DR) can suppress age-related deficits in learning and memory, and can increase resistance of neurons to degeneration in experimental models of neurodegenerative disorders. We found that maintenance of adult rats on a DR regimen results in a significant increase in the numbers of newly produced neural cells in the dentate gyrus of the hippocampus, as determined by stereologic analysis of cells labeled with the DNA precursor analog bromodeoxyuridine. The increase in neurogenesis in rats maintained on DR appears to result from decreased death of newly produced cells, rather than from increased cell proliferation. We further show that the expression of brain-derived neurotrophic factor, a trophic factor recently associated with neurogenesis, is increased in hippocampal cells of rats maintained on DR. Our data are the first evidence that diet can affect the process of neurogenesis, as well as the first evidence that diet can affect neurotrophic factor production. These findings provide insight into the mechanisms whereby diet impacts on brain plasticity, aging and neurodegenerative disorders. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 40 TC 227 Z9 236 U1 2 U2 13 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD OCT PY 2000 VL 15 IS 2 BP 99 EP 108 DI 10.1385/JMN:15:2:99 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 396BP UT WOS:000166616700004 PM 11220789 ER PT J AU Palmiter, KA Tyska, MJ Haeberle, JR Alpert, NR Fananapazir, L Warshaw, DM AF Palmiter, KA Tyska, MJ Haeberle, JR Alpert, NR Fananapazir, L Warshaw, DM TI R403Q and L908V mutant beta-cardiac myosin from patients with familial hypertrophic cardiomyopathy exhibit enhanced mechanical performance at the single molecule level SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; ALPHA-MHC403/+ MOUSE MODEL; CHAIN GENE-MUTATIONS; HEAVY-CHAIN; SKELETAL-MUSCLE; IN-VITRO; FUNCTIONAL-ANALYSIS; LASER TRAP; HEART-FAILURE; ACTIN AB Familial hypertrophic cardiomyopathy (FHC) is a disease of the sarcomere. In the beta -myosin heavy chain gene, which codes for the mechanical enzyme myosin, greater than 40 point mutations have been found that are causal for this disease. We have studied the effect of two mutations, the R403Q and L908V, on myosin molecular mechanics. In the in vitro motility assay, the mutant myosins produced a 30% greater velocity of actin filament movement (nu (actin)). At the single molecule level, nu (a)ctin similar tod/t(on), where d is the myosin unitary step displacement and t(on) is the step duration. Laser trap studies were performed at 10 muM MgATP to estimate d and t(on) for the normal and mutant myosin molecules. The increase in nu (actin) can be explained by a significant decrease in the average t(on)'s in both the R403Q and L908V mutants (similar to 30 ms) compared to controls (similar to 40 ms), while d was not different for all myosins tested (similar to7 nm). Thus the mutations affect the kinetics of the cross-bridge cycle without any effect on myosin's inherent motion and force generating capacity. Based on these studies, the primary signal for the hypertrophic response appears to be an apparent gain in function of the individual mutant myosin molecules. C1 Univ Vermont, Dept Mol Physiol & Biophys, Burlington, VT 05405 USA. NIH, Div Cardiol, Bethesda, MD 20892 USA. RP Warshaw, DM (reprint author), Univ Vermont, Dept Mol Physiol & Biophys, Burlington, VT 05405 USA. FU NHLBI NIH HHS [HL59408, HL51126] NR 48 TC 76 Z9 76 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD OCT PY 2000 VL 21 IS 7 BP 609 EP 620 DI 10.1023/A:1005678905119 PG 12 WC Cell Biology SC Cell Biology GA 391ND UT WOS:000166361300001 PM 11227787 ER PT J AU Davies-Coleman, MT Cantrell, CL Gustafson, KR Beutler, JA Pannell, LK Boyd, MR AF Davies-Coleman, MT Cantrell, CL Gustafson, KR Beutler, JA Pannell, LK Boyd, MR TI Stolonic acids A and B, new cytotoxic cyclic peroxides from an Indian Ocean ascidian Stolonica species SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID NATURAL-PRODUCTS AB Two new 3,6-epidioxy-7,10-tetrahydrofurano C-26 unsaturated fatty acids, stolonic acids A (1) and B (2), were isolated from a previously undescribed ascidian species, Stolonica sp. collected off the Maldive Islands in the Indian Ocean. The structures and relative stereochemistry of 1 and 2 were determined using conventional spectroscopic methods. Both compounds exhibited antiproliferative activity against selected human melanoma and ovarian tumor cell lines, with IC50 values of approximately 0.05-0.1 mug/mL. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Canc Res & De, Frederick, MD 21702 USA. Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Boyd, MR (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Canc Res & De, Bldg 1052,Room 121, Frederick, MD 21702 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 6 TC 12 Z9 13 U1 0 U2 4 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 OCT PY 2000 VL 63 IS 10 BP 1411 EP 1413 DI 10.1021/np000158x PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 369XW UT WOS:000165093900020 PM 11076564 ER PT J AU Khan, IA Avery, MA Burandt, CL Goins, DK Mikell, JR Nash, TE Azadegan, A Walker, LA AF Khan, IA Avery, MA Burandt, CL Goins, DK Mikell, JR Nash, TE Azadegan, A Walker, LA TI Antigiardial activity of isoflavones from Dalbergia frutescens bark SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID GIARDIA-LAMBLIA; METRONIDAZOLE; FLAVONOIDS; TOXICITY AB Several isoflavones [formononetin (1), castanin (5), odoratin (6), glycitein (7), pseudebaptogenin (8), fujikinetin (9), and cuneatin (10)] were isolated from Dalbergia frutescens, and their antiprotozoal activities were determined against Giardia intestinalis. Among these compounds, formononetin (1) was the most potent antigiardial agent, with an IC50 value of 30 ng/mL (approximately 0.1 muM), as compared to the value for metronidazole, the current drug of choice, of 100 ng/mL (approximately 0.6 muM). Three isoflavones closely related to formononetin [daidzein (2), biochanin A (3) and genistein (4)] were also evaluated, but they were at least 100 times less active than 1. Formononetin (1) may thus be an interesting lead for development of new antigiardial agents eras a probe for a new mechanistic target. C1 Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Natl Ctr Nat Prod Res, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Dept Med Chem & Pharmacol, University, MS 38677 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Director, Bethesda, MD 20892 USA. RP Walker, LA (reprint author), Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Natl Ctr Nat Prod Res, University, MS 38677 USA. NR 19 TC 57 Z9 60 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD OCT PY 2000 VL 63 IS 10 BP 1414 EP 1416 DI 10.1021/np000010d PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 369XW UT WOS:000165093900021 PM 11076565 ER PT J AU Swerdlow, RH Golbe, LI Parks, JK Cassarino, DS Binder, DR Grawey, AE Litvan, I Bennett, JP Wooten, GF Parker, WD AF Swerdlow, RH Golbe, LI Parks, JK Cassarino, DS Binder, DR Grawey, AE Litvan, I Bennett, JP Wooten, GF Parker, WD TI Mitochondrial dysfunction in cybrid lines expressing mitochondrial genes from patients with progressive supranuclear palsy SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE progressive supranuclear palsy; mitochondria; cybrids; oxidative stress ID RICHARDSON-OLSZEWSKI-SYNDROME; PARKINSONS-DISEASE; TAU-GENE; HUMAN-CELLS; DNA; COMPLEMENTATION; ASSOCIATION; MUTATIONS; CRITERIA; FTDP-17 AB Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder of unknown etiology. We hypothesized that mitochondrial DNA (mtDNA) aberration could occur in this disease and contribute to its pathogenesis. To address this we created transmitochondrial cytoplasmic hybrid (cybrid) cell lines expressing mitochondrial genes from persons with PSP. The presence of cybrid mtDNA aberration was screened for by biochemical assay of mitochondrial gene products. Relative to a control cybrid set, complex I activity was reduced in PSP cybrid fines (p < 0.005). Antioxidant enzyme activities were elevated in PSP cybrid lines. These data suggest that mtDNA aberration occurs in PSP, causes electron transport chain pathology, and can produce oxidative stress. Further study of mitochondrial dysfunction in PSP may yield insights into why neurodegeneration occurs in this disease. C1 Univ Virginia, Hlth Syst, Dept Neurol, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Syst, Ctr Study Neurodegenerat Dis, Charlottesville, VA 22908 USA. Univ Med & Dent New Jersey, Dept Neurol, New Brunswick, NJ USA. NIH, Bethesda, MD 20892 USA. RP Swerdlow, RH (reprint author), Univ Virginia, Hlth Syst, Dept Neurol, Box 394, Charlottesville, VA 22908 USA. OI Litvan, Irene/0000-0002-3485-3445 NR 30 TC 53 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2000 VL 75 IS 4 BP 1681 EP 1684 DI 10.1046/j.1471-4159.2000.0751681.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 353EZ UT WOS:000089263000038 PM 10987850 ER PT J AU Tian, H Habecker, B Guidry, G Gurtan, A Rios, M Roffler-Tarlov, S Landis, SC AF Tian, H Habecker, B Guidry, G Gurtan, A Rios, M Roffler-Tarlov, S Landis, SC TI Catecholamines are required for the acquisition of secretory responsiveness by sweat glands SO JOURNAL OF NEUROSCIENCE LA English DT Article DE synapse development; transmitter plasticity; sweat glands; sympathetic neuron; acetylcholine; catecholamines; tyrosinase; tyrosine hydroxylase null ID VESICULAR ACETYLCHOLINE TRANSPORTER; NEUROTRANSMITTER PLASTICITY INVIVO; MUSCARINIC CHOLINERGIC RECEPTORS; SYMPATHETIC NEURONS; TYROSINE-HYDROXYLASE; TARGETED DISRUPTION; INNERVATION; MOUSE; DIFFERENTIATION; EXPRESSION AB The sympathetic innervation of sweat glands undergoes a developmental change in transmitter phenotype from catecholaminergic to cholinergic. Acetylcholine elicits sweating and is necessary for development and maintenance of secretory responsiveness, the ability of glands to produce sweat after nerve stimulation or agonist administration. To determine whether catecholamines play a role in the development or function of this system, we examined the onset of secretory responsiveness in two transgenic mouse lines, one albino and the other pigmented, that lack tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Although both lines lack TH, their catecholamine levels differ because tyrosinase in pigmented mice serves as an alternative source for catecholamine synthesis (Rios et al., 1999). At postnatal day 21 (P21), 28 glands on average are active in interdigital hind footpads of albino TH wild-type mice. In contrast, fewer than one gland is active in albino TH null mice, which lack catecholamines in gland innervation. Treatment of albino TH null mice with DOPA, a catecholamine precursor, from P11 to P21 increases the number of active glands to 14. Pigmented TH null mice, which have faint catecholamine fluorescence in the developing gland innervation, possess 12 active glands at P21, indicating that catecholamines made via tyrosinase, albeit reduced from wild-type levels, support development of responsiveness. Gland formation and the appearance of cholinergic markers occur normally in albino TH null mice, suggesting that catecholamines act directly on gland cells to trigger their final differentiation and to induce responsiveness. Thus, catecholamines, like acetylcholine, are essential for the development of secretory responsiveness. C1 NINDS, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Anat & Cell Biol, Boston, MA 02111 USA. RP Landis, SC (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS35639] NR 52 TC 21 Z9 22 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 2000 VL 20 IS 19 BP 7362 EP 7369 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 358BY UT WOS:000089538400031 PM 11007894 ER PT J AU Studer, L Csete, M Lee, SH Kabbani, N Walikonis, J Wold, B McKay, R AF Studer, L Csete, M Lee, SH Kabbani, N Walikonis, J Wold, B McKay, R TI Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CNS precursors; CNS stem cells; dopaminergic neurons; erythropoietin; oxygen; Parkinson's disease ID HYDROXYLASE MESSENGER-RNA; CENTRAL-NERVOUS-SYSTEM; STEM-CELLS; TYROSINE-HYDROXYLASE; SONIC-HEDGEHOG; PARKINSONS-DISEASE; FLOOR PLATE; IN-VIVO; NEURONS; ERYTHROPOIETIN AB Standard cell culture systems impose environmental oxygen (O-2) levels of 20%, whereas actual tissue O-2 levels in both developing and adult brain are an order of magnitude lower. To address whether proliferation and differentiation of CNS precursors in vitro are influenced by the O-2 environment, we analyzed embryonic day 12 rat mesencephalic precursor cells in traditional cultures with 20% O-2 and in lowered O-2 (3 +/- 2%). Proliferation was promoted and apoptosis was reduced when cells were grown in lowered O-2, yielding greater numbers of precursors. The differentiation of precursor cells into neurons with specific neurotransmitter phenotypes was also significantly altered. The percentage of neurons of dopaminergic phenotype increased to 56% in lowered O-2 compared with 18% in 20% O-2. Together, the increases in total cell number and percentage of dopaminergic neurons resulted in a ninefold net increase in dopamine neuron yield. Differential gene expression analysis revealed more abundant messages for FGF8, engrailed-1, and erythropoietin in lowered O-2. Erythropoietin supplementation of 20% O-2 cultures partially mimicked increased dopaminergic differentiation characteristic of CNS precursors cultured in lowered O-2. These data demonstrate increased proliferation, reduced cell death, and enhanced dopamine neuron generation in lowered O-2, making this method an important advance in the ex vivo generation of specific neurons for brain repair. C1 Univ Michigan, Dept Anesthesiol, Anesthesiol Res Labs, Ann Arbor, MI 48109 USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Mem Sloan Kettering Canc Ctr, Lab Stem Cell & Tumor Biol Neurosurg & Cellular B, New York, NY 10021 USA. Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. Hanyang Univ, Coll Med, Seoul 133791, South Korea. RP Csete, M (reprint author), Univ Michigan, Dept Anesthesiol, Anesthesiol Res Labs, 1150 W Med Ctr Dr,Room 7444, Ann Arbor, MI 48109 USA. FU NIAMS NIH HHS [AR40780-8, AR42671-05] NR 48 TC 487 Z9 527 U1 2 U2 17 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 2000 VL 20 IS 19 BP 7377 EP 7383 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 358BY UT WOS:000089538400033 PM 11007896 ER PT J AU Bruccoleri, A Harry, GJ AF Bruccoleri, A Harry, GJ TI Chemical-induced hippocampal neurodegeneration and elevations in TNF alpha,TNF beta, IL-1 alpha, IP-10, and MCP-1 mRNA in osteopetrotic (op/op) mice SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE astrocyte; microglia; CSF-1; MIP; trimethyltin ID COLONY-STIMULATING FACTOR; CYTOKINE GENE-EXPRESSION; CENTRAL-NERVOUS-SYSTEM; FACTOR-I; MESSENGER-RNA; GROWTH-FACTOR; HEMATOPOIETIC CYTOKINE; ISOLATED MICROGLIA; CELL-LINE; MOUSE AB The osteopetrotic (op/op) mouse, deficient in biologically active colony stimulating factor 1 (CSF-1), was used to examine the role of microglia in chemical-induced trauma. Op/op mice and normal phenotype littermates (non-op/op) received an acute i.p. injection of the hippocampal toxicant, trimethyltin hydroxide (TMT; 1.5 or 2.0 mg/kg). At 2.0 mg/kg, both mice displayed severe degeneration of dentate granule neurons. At 1.5 mg/kg, non-op/op mice showed a limited punctate pattern of neuronal death white op/op mice showed prominent neuronal death. TMT-induced astrocyte reactivity was similar in both groups. RNase protection assays were conducted on hippocampal tissue at 24 hr post-TMT. Elevations were seen in mRNA levels for the host response genes: intercellular cell adhesion molecule (ICAM-1; non-op/op 80%, op/op 85%), the protease inhibitor EB22 (non-op/op 60%, op/op 300%), and glial fibrillary acidic protein (GFAP; non-op/op 300%, op/op 480%) within 24 hr. Macrophage-1 antigen (Mac-1) mRNA levels were lower in all op/op mice and were not induced by TMT exposure. Macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta mRNA revels were elevated in non-op/op mice while mRNA levels for interferon inducible protein (IP-10) and monocyte chemoattractant protein (MCP-IJ were elevated in op/op mice. Tumor necrosis factor alpha (TNF alpha) mRNA levels were significantly elevated in both non-op/op (100%) and op/op (600%) mice. TNF beta mRNA levels in op/op mice were elevated 200% and interleukin 1alpha (IL-1 alpha) 150%, Reverse transcriptase polymerase chain reaction (RT-PCR) showed a TMT-induced elevation in INF alpha. and INF beta mRNA levels and no elevation of INF gamma. mRNA levels of the CSF-1 receptor, c-fms, were unaltered. Published 2000 Wiley-Liss, Inc.(dagger) C1 NIEHS, Neurotoxicol Grp, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, Neurotoxicol Grp, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA. EM Harry@niehs.nih.gov NR 49 TC 27 Z9 28 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 1 PY 2000 VL 62 IS 1 BP 146 EP 155 DI 10.1002/1097-4547(20001001)62:1<146::AID-JNR15>3.0.CO;2-L PG 10 WC Neurosciences SC Neurosciences & Neurology GA 362BR UT WOS:000089759200015 PM 11002296 ER PT J AU Brouwers, P Civitello, L DeCarli, C Wolters, P Sei, S AF Brouwers, P Civitello, L DeCarli, C Wolters, P Sei, S TI Cerebrospinal fluid viral load is related to cortical atrophy and not to intracerebral calcifications in children with symptomatic HIV disease SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT 3rd International Symposium on NeuroVirology CY SEP 14-16, 2000 CL SAN FRANCISCO, CALIFORNIA SP NINDS, NIMH, Penn State Univ, Life Sci Consortium, Integrat Biosci Grad Program, Temple Univ, Coll Sci & Technol, Ctr Neurovirol & Canc Biol, Adv Biosci Resources, Inc, Pharmacia & Upjohn Inc DE pediatric HIV infection; central nervous system disease; computed tomography brain scans; cerebrospinal fluid analysis; viral load; encephalopathy ID IMMUNODEFICIENCY-VIRUS TYPE-1; PEDIATRIC AIDS; BASAL GANGLIA; RNA LEVELS; INFECTED CHILDREN; ENCEPHALOPATHY; ZIDOVUDINE; THERAPY; CT; REPLICATION AB The relationships between viral load in plasma and cerebrospinal fluid (CSF) and computed tomography (CT) brain scan abnormalities were studied in 39 children between 0.5 and 13 years of age with symptomatic HIV-1 disease. Quantitative RNA PCR was used to determine HIV-1 RNA levels and a semiquantitative analog rating technique was used to evaluate non-contrast CT brain scans. CSF HIV-1 RNA copy number correlated significantly with CT brain scan ratings for severity of cortical atrophy (r=0.36; P<0.05) but not with ratings of intracerebral calcifications (r=-12; NS). The difference between these two correlations was significant (P<0.05). Plasma HIV-1 RNA copy number did not correlate significantly with any CT brain scan ratings or with CSF viral load (r=0.05; NS). Severity of cortical atrophy appeared to reflect the level of viral load in the CSF, supporting the notion that active HIV-1 replication in the CNS is at least in part responsible for such brain abnormalities in children. The lack of correlation of intracerebral calcifications with other CT brain scan abnormalities as well as with CSF viral load suggests that this lesion is relatively independent and may reflect a different neuropathologic process. C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Branch, Bethesda, MD 20892 USA. Med Illness Counseling Ctr, Bethesda, MD 20814 USA. Childrens Hosp, Med Ctr, Washington, DC 20010 USA. RP Brouwers, P (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, 6621 Fannin St,MC 3-3320, Houston, TX 77030 USA. RI DeCarli, Charles/B-5541-2009 NR 32 TC 23 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2000 VL 6 IS 5 BP 390 EP 397 DI 10.3109/13550280009018303 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 354BG UT WOS:000089309500004 PM 11031692 ER PT J AU Gibril, F Reynolds, JC Lubensky, IA Roy, PK Peghini, PL Doppman, JL Jensen, RT AF Gibril, F Reynolds, JC Lubensky, IA Roy, PK Peghini, PL Doppman, JL Jensen, RT TI Ability of somatostatin receptor scintigraphy to identify patients with gastric carcinoids: A prospective study SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE somatostatin receptor scintigraphy; Zollinger-Ellison syndrome; carcinoid; gastric carcinoid; neuroendocrine tumor ID ZOLLINGER-ELLISON-SYNDROME; ENTEROCHROMAFFIN-LIKE CELL; LONG-TERM; NEUROENDOCRINE TUMORS; EXPRESSION; OMEPRAZOLE; MANAGEMENT; THERAPY; MUCOSA; GROWTH AB Gastric carcinoids are of increasing clinical concern because they may develop in hypergastrinemic states, especially with the increased chronic use of potent acid suppressants that can cause hypergastrinemia. However, gastric carcinoids are difficult to diagnose. Somatostatin receptor scintigraphy (SRS) has a high sensitivity and specificity for localizing carcinoids in other locations. The purpose of this study was to determine whether SRS could localize gastric carcinoids. Methods: Two groups of patients with Zollinger-Ellison syndrome (ZES) with hypergastrinemia, each having a different increased risk of developing gastric carcinoids, were studied. One hundred sixty-two consecutive patients with ZES were studied prospectively, with 39 having multiple endocrine neoplasia, type 1 (MEN-1) (high increased risk), and 123 not having MEN-1 (low increased risk). Patients were admitted to the hospital initially and then yearly, undergoing SRS with SPECT, upper gastrointestinal endoscopy, and Jumbo Cup biopsies of any gastric abnormalities, as well as random biopsies of the gastric body. Tumor localization studies were also performed. Both the results of the routine SRS interpretation and the results of a masked review, with particular attention to the stomach of high risk MEN-1 patients, were correlated with the gastric biopsy results. Results: Gastric SRS localization was positive in 19 (12%) of 162 patients. Sixteen patients had a gastric carcinoid, and 12 of these patients had SRS localization. The sensitivity of SRS in localizing a gastric carcinoid was 75%, with a specificity of 95%. Positive and negative predictive values were 63% and 97%, respectively. Conclusion: SRS is a noninvasive method that can identify patients with gastric carcinoids with a reasonable sensitivity and a high specificity. SRS should prove useful in the treatment of patients with hypergastrinemic states that have an increased incidence of gastric carcinoids. In patients with MEN-1, one must realize that localization in the upper abdomen on SRS may be caused by a gastric carcinoid and not a pancreatic endocrine tumor. C1 NIDDK, DDB, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD USA. RP Jensen, RT (reprint author), NIDDK, DDB, NIH, Bldg 10,Rm 9c-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 40 TC 46 Z9 48 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2000 VL 41 IS 10 BP 1646 EP 1656 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364JJ UT WOS:000089889000015 PM 11037994 ER PT J AU Dancey, JE Shepherd, FA Paul, K Sniderman, KW Houle, S Gabrys, J Hendler, AL Goin, JE AF Dancey, JE Shepherd, FA Paul, K Sniderman, KW Houle, S Gabrys, J Hendler, AL Goin, JE TI Treatment of nonresectable hepatocellular carcinoma with intrahepatic Y-90-microspheres SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE hepatocellular carcinoma; Y-90; intrahepatic arterial therapy ID Y-90 MICROSPHERES; RADIATION-THERAPY; PARTITION MODEL; HEPATIC-TUMORS; PHASE-II; INTRAARTERIAL; TRIAL; CANCER; CISPLATIN; PROGNOSIS AB Treatment for nonresectable hepatocellular carcinoma (HCC) is palliative, The relatively greater arteriolar density of hepatic tumors compared with normal liver suggests that intrahepatic arterial administration of Y-90-microspheres can be selectively deposited in tumor nodules and results in significantly greater radiation exposure to the tumor than external irradiation. The purpose of this study was to determine the proportion (frequency) and duration of response, survival, and toxicity after intrahepatic arterial injection of Y-90-microspheres in patients with HCC. Methods: Patients with documented HCC, Eastern Cooperative Oncology Group performance status 0-3, adequate bone marrow, and hepatic and pulmonary function were eligible for study. Patients who had significant shunting of blood to the lungs or gastrointestinal (GI) tract or who could not undergo cannulation of the hepatic artery were excluded. Patients received a planned dose of 100 Gy through a catheter placed into the hepatic artery. Results: Twenty-two patients were treated with Y-90-microspheres; 20 of the treated patients (median age, 62.5 y) were evaluated for treatment efficacy. Nine patients were Okuda stage I, and 11 were Okuda stage II. The median dose delivered was 104 Gy (range, 46-145 Gy), All 22 treated patients experienced at least 1 adverse event. Of the 31 (15%) serious adverse events, the most common were elevations in liver enzymes and bilirubin and upper GI ulceration. The response rate was 20%. The median duration of response was 127 wk; the median survival was 54 wk. Multivariable analysis suggested that a dose >104 Gy (P = 0.06), tumor-to-liver activity uptake ratio >2 (P = 0.06), and Okuda stage I (P = 0.07) were associated with longer survival. Conclusion: Significantly higher doses of radiation can be delivered to a HCC tumor by intrahepatic arterial administration of Y-90-microspheres than by external beam radiation. This treatment appears to be beneficial in nonresectable HCC with acceptable toxicity. C1 Univ Toronto, Toronto Gen Hosp, Dept Radiol, Toronto, ON M5G 1L7, Canada. Univ Toronto, Toronto Gen Hosp, Dept Med, Toronto, ON M5G 1L7, Canada. Univ Toronto, Toronto Gen Hosp, Dept Med Imaging, Toronto, ON M5G 1L7, Canada. Univ Toronto, Princess Margaret Hosp, Toronto, ON M5G 1L7, Canada. Ctr Addict & Mental Hlth, Toronto, ON, Canada. DataMedix Corp, Media, PA USA. RP Dancey, JE (reprint author), NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, 6130 Execut Blvd,EPN 715, Rockville, MD 20852 USA. NR 42 TC 188 Z9 189 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2000 VL 41 IS 10 BP 1673 EP 1681 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364JJ UT WOS:000089889000018 PM 11037997 ER PT J AU Preston, KL Bigelow, GE AF Preston, KL Bigelow, GE TI Effects of agonist-antagonist opioids in humans trained in a hydromorphone/not hydromorphone discrimination SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GAMMA-S BINDING; DRUG-DISCRIMINATION; D-AMPHETAMINE; STIMULUS; RECEPTOR; EFFICACY; DIAZEPAM; METHYLPHENIDATE; METHAMPHETAMINE; BUTORPHANOL AB The purpose of this study was to examine the discrimination of agonist-antagonist opioids in humans trained in a two-choice hydromorphone/not hydromorphone discrimination. Eight adult male volunteers with histories of opioid abuse who were not currently physically dependent were trained to discriminate the mu receptor agonist hydromorphone (3 mg/70 kg, i.m.) ("Drug A") from a "Not Drug A" training condition (saline placebo). Volunteers received financial reinforcement for correct responses. After training, generalization dose-effect curves for hydromorphone, butorphanol, pentazocine, nalbuphine, and buprenorphine were determined. Other subjective, behavioral, and physiological measures were concurrently collected in all sessions. In generalization testing hydromorphone and buprenorphine produced dose-related increases in hydromorphone-appropriate responses. Pentazocine produced an inverted U-shaped dose-response curve with complete substitution at 32 mg/70 kg but not at 64 mg/70 kg. Butorphanol and nalbuphine did not completely substitute for hydromorphone at any dose tested. These results differ from an earlier two-choice, Drug A versus Drug B (hydromorphone/saline) discrimination study. After Drug/Not Drug instructions the behavioral discriminations of agonist-antagonist opioids were more consistent with their putative agonist activities at the mu opioid receptor and with their subjective effects profiles than was the case after Drug A versus Drug B instructions. These results suggest that instructions are an important factor in the outcome of human drug discrimination studies. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Pharmacol Res Unit, Baltimore, MD 21205 USA. RP Preston, KL (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [DA-00050, DA-04089] NR 28 TC 24 Z9 24 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 OCT PY 2000 VL 295 IS 1 BP 114 EP 124 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 354AA UT WOS:000089306600016 PM 10991968 ER PT J AU Liu, B Jiang, JW Wilson, BC Du, L Yang, SN Wang, JY Wu, GC Cao, XD Hong, JS AF Liu, B Jiang, JW Wilson, BC Du, L Yang, SN Wang, JY Wu, GC Cao, XD Hong, JS TI Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; INFLAMMATORY REACTION; MICROGLIA; BRAIN; INDUCTION; CNS; BIOSYNTHESIS; EXPRESSION AB A massive degeneration of dopamine-containing neurons in the substantia nigra (SN) in the midbrain is characteristic of Parkinson's disease. Inflammation in the brain has long been speculated to play a role in the pathogenesis of this neurological disorder. Recently, we reported that treatment of primary rat mesencephalic mixed neuron-glia cultures with lipopolysaccharide (LPS) led to the activation of microglia, resident immune cells of the brain, and subsequent death of dopaminergic neurons. The LPS-induced degeneration of dopaminergic neurons was significantly attenuated by the opiate receptor antagonist (-)-naloxone and its inactive isomer (+)- naloxone, with equal potency, through an inhibition of microglial activation and their production of neurotoxic factors. In this study, injection of LPS into the rat SN led to the activation of microglia and degeneration of dopaminergic neurons: microglial activation was observed as early as 6 h and loss of dopaminergic neurons was detected 3 days after the LPS injection. Furthermore, the LPS-induced loss of dopaminergic neurons in the SN was time- and LPS concentration-dependent. Systemic infusion of either (-)-naloxone or (+)-naloxone inhibited the LPS-induced activation of microglia and significantly reduced the LPS-induced loss of dopaminergic neurons in the SN. These in vivo results combined with our cell culture observations confirmed that naloxone protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation and suggest that naloxone would have therapeutic efficacy in the treatment of inflammation-related neurological disorders. In addition, the inflammation-mediated degeneration of dopaminergic neurons in the rat SN resulting from the targeted injection of LPS may serve as a useful model to gain further insights into the pathogenesis of Parkinson's disease. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Shanghai Med Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. Natl Def Med Ctr, Taipei, Taiwan. RP Liu, B (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, MD-F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 42 TC 122 Z9 136 U1 0 U2 6 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 OCT PY 2000 VL 295 IS 1 BP 125 EP 132 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 354AA UT WOS:000089306600017 PM 10991969 ER PT J AU Gasior, M Ungard, JT Witkin, JM AF Gasior, M Ungard, JT Witkin, JM TI Chlormethiazole: Effectiveness against toxic effects of cocaine in mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Meeting of the American-Society-for-Pharmacology-and-Experimental-Therapeutics CY JUN 04-08, 2000 CL BOSTON, MASSACHUSETTS SP Amer Soc Pharmacol & Exptl Therapeut ID ANTIEPILEPTIC DRUGS; CLINICAL EFFICACY; RECEPTORS; GABA; ANTICONVULSANT; PHARMACOLOGY; MECHANISMS; INCREASES; EPILEPSY; DIAZEPAM AB Chlormethiazole positively modulates the gamma-aminobutyric acid (GABA)(A) receptor complex and is primarily used to treat certain life-threatening neurological events (e.g., refractory seizures and ethanol withdrawal syndrome). On account of several experimental and clinical studies reporting effectiveness against the toxic effects of heroin and methamphetamine, chlormethiazole was systematically tested in the present study for its effectiveness against cocaine-induced seizures and lethality in mice. The protective effects of chlormethiazole were evaluated against single, submaximal convulsive (75 mg/kg) or lethal (110 mg/kg) doses of cocaine. Chlormethiazole also was tested against the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine- kindled seizures, and against fully developed kindled seizures. Cocaine-kindled seizures were produced by a total of five daily treatments with 60 mg/kg cocaine. The inverted-screen test was used to assess behavioral side effects of chlormethiazole. Chlormethiazole protected against acute cocaine- induced convulsions (ED50 = 7.0 mg/kg) and lethality (ED50 = 21.8 mg/kg) with a robust separation [protective index (PI) = TD50/ED50 = 22.3 and 7.2, respectively] from doses producing behavioral side effects (TD50 = 156 mg/kg). Chlormethiazole suppressed the behavioral expression of cocaine-kindled seizures and prevented the development of sensitization to the convulsant effects of cocaine. It was also effective in suppressing fully developed kindled seizures. Relative to cocaine seizures in naive mice, chlormethiazole was equieffective, less potent (ED50 = 22.3 mg/kg), and had a reduced protective index (PI = 3.7) against cocaine-induced seizures in kindled mice. The protective profile and protective index of chlormethiazole were superior to those of the benzodiazepines clonazepam and diazepam, which were of limited efficacy and had low protective indices (PI = similar to 1). The results of this study predict the potential utility of chlormethiazole for the treatment of life-threatening complications of cocaine abuse for which no specific treatment has yet been identified. C1 NIDA, Drug Dev Grp, Behav Neurosci Branch, Addict Res Ctr,NIH, Baltimore, MD 21224 USA. Med Univ Sch, Dept Pharmacol, Lublin, Poland. RP Gasior, M (reprint author), Harvard Univ, McLean Hosp, Sch Med,Behav Pharmacol Program, Alcohol & Drug Abuse Res Ctr,Dept Psychiat, 115 Mill St, Belmont, MA 02178 USA. NR 47 TC 13 Z9 13 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 OCT PY 2000 VL 295 IS 1 BP 153 EP 161 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 354AA UT WOS:000089306600021 PM 10991973 ER PT J AU Jeyarasasingam, G Yeluashvili, M Quik, M AF Jeyarasasingam, G Yeluashvili, M Quik, M TI Nitric oxide is involved in acetylcholinesterase inhibitor-induced myopathy in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SKELETAL-MUSCLE; CHOLINESTERASE INHIBITOR; REPERFUSION INJURY; MEDIATED MYOPATHY; ION CHANNEL; SYNTHASE; RECEPTOR; CALCIUM; PHYSOSTIGMINE; MECHANISMS AB Excess activation of muscle nicotinic acetylcholine receptors due to genetic mutations, as seen in slow channel congenital myasthenic syndrome, or acetylcholinesterase (AChE) inhibition results in muscle cell degeneration. Our recent work showed that nitric oxide synthase (NOS) inhibitors prevent nicotine-induced muscle cell death in culture. In the present study, we examined the effects of NOS inhibition on nicotinic receptor-mediated myopathy in vivo. Rats injected with the AChE inhibitor paraoxon demonstrate a 90-fold increase in the number of dying muscle cells compared with control as evidenced histologically by centralized nuclei and the presence of degenerating profiles. Coadministration of the nonspecific NOS inhibitor nitro-L-arginine methyl ester or the neuronal NOS-specific inhibitor 7-nitroindazole dramatically reduced the presence of such degenerating profiles to similar to 20% of that seen with paraoxon alone. These results show that inhibition of NOS, as well as neuronal NOS, significantly reduces AChE inhibitor-induced muscle cell degeneration, suggesting that increased nitric oxide production mediates such myopathy. C1 Parkinsons Inst, Sunnyvale, CA USA. RP Quik, M (reprint author), NIMH, Extramural Review Branch, 6001 Execut Blvd,Room 6154,MSC 9609, Rockville, MD 20857 USA. NR 40 TC 10 Z9 10 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 OCT PY 2000 VL 295 IS 1 BP 314 EP 320 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 354AA UT WOS:000089306600044 PM 10991996 ER PT J AU Chen, JM Rijhwani, K Friedman, FK Hyde, MJ Pincus, MR AF Chen, JM Rijhwani, K Friedman, FK Hyde, MJ Pincus, MR TI Identification, using molecular dynamics, of an effector domain of the ras-binding domain of the raf-p74 protein that is uniquely involved in oncogenic ras-p21 signaling SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE ras-p21-RBD complex; molecular dynamics; average structure; effector domains; 97-110 RBD PNC-13 peptide ID P21 PROTEIN; ACTIVATION; P21(RAS) AB By comparing the average structures, computed using molecular dynamics, of the ras-binding domain of raf (RBD) bound to activated wild-type ras-p21 and its homologous inhibitory protein, rap-1A, we formerly identified three domains of the RED that changed conformation between the two complexes, residues 62-76, 97-110, and 111-121. We found that one synthetic peptide, corresponding to RED residues 97-110, selectively inhibited oncogenic ras-p21-induced oocyte maturation. In this study, we performed molecular dynamics on the Val 12-ras-p21-RBD complex and compared its average structure with that for the wild-type protein. We find that there is a large displacement of a loop involving these residues when the structures of the two complexes are compared. This result corroborates our former finding that the RED 97-110 peptide inhibits only signal transduction by oncogenic ras-p21 and suggests that oncogenic p21 uses this loop to interact with raf in a unique manner. C1 Harbor VA Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Tularik Inc, S San Francisco, CA 94080 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Adv Comp Serv, DeWitt, NY 13214 USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. RP Pincus, MR (reprint author), Harbor VA Med Ctr, Dept Pathol & Lab Med, 800 Doly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 42500] NR 20 TC 2 Z9 2 U1 2 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD OCT PY 2000 VL 19 IS 7 BP 545 EP 551 DI 10.1023/A:1007127700199 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 399WK UT WOS:000166837100001 PM 11233167 ER PT J AU Magnanti, M Giuliani, L Gandini, O Gazzaniga, P Santiemma, V Ciotti, M Saccani, G Frati, L Agliano, AM AF Magnanti, M Giuliani, L Gandini, O Gazzaniga, P Santiemma, V Ciotti, M Saccani, G Frati, L Agliano, AM TI Follicle-stimulating hormone, testosterone, and hypoxia differentially regulate UDP-glucuronosyltransferase 1 isoforms expression in rat Sertoli and peritubular myoid cells SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE UGT1A1; UGT1A2; UGT1B1; testis; hypoxia; FSH ID MESSENGER-RNA; BILIRUBIN; TISSUE; GLUCURONIDATION; IDENTIFICATION; LIVER; LOCUS AB Uridine diphosphoglucuronosyltransferases (UGTs) are detoxifying enzymes responsible for the metabolism of endogenous and xenobiotics compounds. UGT isoforms are widely distributed in rat tissues showing a constitutive acid inducible gene expression. However, little information is available concerning UGTs expression in testis. The UGT1A1, UGT1A2, and UGT1B1 mRNAs expression in whole rat testis, in Sertoli and peritubular myoid cells in basal conditions, and after hormonal and hypoxic stimulation were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). Constitutive expression of each UGT1 isoform was present in rat testis with higher levels of UGT1A2. UGT transcripts were also detected in Sertoli and peritubular myoid cells. After FSH stimulation, Sertoli cells showed an increase in UGT1B1 mRNA expression. whereas the levels of UGT1A1 and UGT1A2? resulted unmodified. The main effect induced by testosterone was a decrease of UGT1B1 mRNA expression in peritubular myoid cells, whereas in Sertoli cells an increase in UGT1A1 and UGT1B1 was observed. In hypoxic conditions, a reduction in UGTs mRNA levels was detected in both cell types. These findings suggest that rat UGT1 isoforms are regulated in testis by hormonal and environmental factors. Thus, it was speculated that alterations in UGTs expression and/or activity may be involved in the pathogenesis of testis injury, (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Rome La Sapienza, Dept Med Sperimentale & Patol, I-00161 Rome, Italy. Univ Rome La Sapienza, Dipartimento Fisiopatol Med, I-00161 Rome, Italy. NICHD, Sect Genet Disorders Drugs Metab, Heritable Dirorders Branch, NIH, Bethesda, MD 20892 USA. Ist Mediterraneo Neurosci, Pozzilli, Italy. RP Agliano, AM (reprint author), Univ Rome La Sapienza, Dept Med Sperimentale & Patol, Viale Regina Elena 324, I-00161 Rome, Italy. NR 26 TC 9 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD OCT PY 2000 VL 74 IS 3 BP 149 EP 155 DI 10.1016/S0960-0760(00)00095-9 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 376TR UT WOS:000165473300009 PM 11086234 ER PT J AU Murphy, LD Zimmerman, SB AF Murphy, LD Zimmerman, SB TI Multiple restraints to the unfolding of spermidine nucleoids from Escherichia coli SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE chloramphenicol; dilatancy assay; DNA; Escherichia coli; lysozyme; microscopy; nucleoid; protease; RNA; RNase; spermidine; urea ID STABILIZE DNA FOLDS; OUTER MEMBRANE; PROTEIN; CHROMOSOME; CELL; PEPTIDOGLYCAN; PURIFICATION; CONDENSATION; HYDROLASES; MECHANISM AB Bacterial DNA is largely localized in compact bodies known as nucleoids. The structure of the bacterial nucleoid and the forces that maintain its DNA in a highly compact yet accessible form are largely unknown. In the present study, we used urea to cause controlled unfolding of spermidine nucleoids isolated from Escherichia coli to determine factors that are involved in nucleoid compaction. Isolated nucleoids unfolded at similar to 3.2 M urea. Addition of pancreatic RNase reduced the urea concentration for unfolding to similar to 1.8 M urea, indicating a role of RNA in nucleoid compaction. The transitions at similar to 3.2 and similar to 1.8 M urea reflected a RNase-sensitive and a RNase-resistant restraint to unfolding, respectively. Removal of the RNase-sensitive restraint allowed us to test for roles of proteins and supercoiling in nucleoid compaction and structure. The remaining (RNase-resistant) restraints were removed by low NaCl concentrations as well as by urea. To determine if stability would be altered by treatments that caused morphological changes in the nucleoids, transitions were also measured on nucleoids from cells exposed to chloramphenicol; the RNase-sensitive restraint in such nucleoids was stabilized to much higher urea concentrations than that in nucleoids from untreated cells, whereas the RNase-resistant transition appeared unchanged. (C) 2000 Academic Press. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zimmerman, SB (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 328W, Bethesda, MD 20892 USA. NR 79 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD OCT PY 2000 VL 132 IS 1 BP 46 EP 62 DI 10.1006/jsbi.2000.4306 PG 17 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 391WM UT WOS:000166379300005 PM 11121306 ER PT J AU Van Hulle, CA Corley, R Zahn-Waxler, C Kagan, J Hewitt, JK AF Van Hulle, CA Corley, R Zahn-Waxler, C Kagan, J Hewitt, JK TI Early childhood heart rate does not predict externalizing behavior problems at age 7 years SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE heart rate; externalizing behavior; Child Behavior Checklist ID GENE; TWIN AB Objective: In previous research, low resting heart rate in childhood and adolescence has been shown to predict aggressive and/or delinquent behavior at subsequent ages. It has been found that heart rate recorded as early as age 3 years could predict externalizing behavior at age 11 years. This study explored the possibility of a similar relationship between heart rate and externalizing behavior problems. Method: Heart rate recorded at ages 14, 20, 24, 36 months and 7 years was used to predict combined parental ratings on the Aggressive and Delinquent Behavior scales of the Child Behavior Checklist (CBCL/4-18) as well as the Externalizing composite scale measured at age 7 years. Subjects consisted of same-sex twin pairs, treated as singletons in the present study, participating in the MacArthur Longitudinal Twin Study. Subjects were grouped into high and low heart rate groups and also into high CBCL/4-18 scoring and low CBCL/4-18 scoring groups. Results: Heart rate was not significantly related to scores on either of the 2 subscales or the Externalizing composite scale at any age. Heart rate group membership did not predict CBCL/4-18 scores. Conversely, CBCL/4-18 group membership did not predict heart rate at any age. Conclusion: In this sample, heart rate does not predict externalizing behavior at age. C1 Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. NIMH, Bethesda, MD 20892 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Van Hulle, CA (reprint author), Univ Colorado, Inst Behav Genet, CB 447, Boulder, CO 80309 USA. EM vanhulle@colorado.edu FU NICHD NIH HHS [HD-07289]; NIDA NIH HHS [P60DA-11015] NR 31 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2000 VL 39 IS 10 BP 1238 EP 1244 DI 10.1097/00004583-200010000-00010 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 358KA UT WOS:000089556200009 PM 11026177 ER PT J AU Nicolson, R Swedo, SE Lenane, M Bedwell, J Wudarsky, M Gochman, P Hamburger, SD Rapoport, JL AF Nicolson, R Swedo, SE Lenane, M Bedwell, J Wudarsky, M Gochman, P Hamburger, SD Rapoport, JL TI An open trial of plasma exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal exacerbations SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article; Proceedings Paper CT 29th Annual Convention of the Society-for-Biological-Psychiatry CY MAY, 1999 CL WASHINGTON, D.C. SP Soc Biol Psychiat DE obsessive-compulsive disorder; streptococcus; autoimmunity ID SCALE; RELIABILITY; VALIDITY AB Patients with childhood-onset obsessive-compulsive disorder (OCD) with symptom exacerbations following streptococcal infections benefit from treatment with plasma exchange. In this study, 5 patients with treatment-refractory OCD without a history of streptococcus-related exacerbations underwent an open 2-week course of therapeutic plasma exchange. Behavioral ratings, completed at baseline and 4 weeks after the initial treatment, included the Clinical Global Impressions Scale and the Yale-Brown Obsessive Compulsive Scale. Ail 5 patients completed the trial with few side effects, but none showed significant improvement. Plasma exchange does not benefit children and adolescents with OCD who do not have streptococcus-related exacerbations. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Nicolson, R (reprint author), 10 Ctr Dr 3N202, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 9 TC 34 Z9 36 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2000 VL 39 IS 10 BP 1313 EP 1315 DI 10.1097/00004583-200010000-00020 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 358KA UT WOS:000089556200019 PM 11026187 ER PT J AU Blauvelt, A Cobb, MW Turner, ML AF Blauvelt, A Cobb, MW Turner, ML TI Widespread cutaneous vascular papules associated with peripheral blood eosinophilia and prominent inguinal lymphadenopathy SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material ID ANGIOLYMPHOID HYPERPLASIA; KIMURAS-DISEASE C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Dept Dermatol, Bethesda, MD USA. RP Blauvelt, A (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 4 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2000 VL 43 IS 4 BP 698 EP 700 DI 10.1067/mjd.2000.108372 PG 3 WC Dermatology SC Dermatology GA 360MM UT WOS:000089671800022 PM 11004630 ER PT J AU Anson, RM Bohr, VA AF Anson, RM Bohr, VA TI Mitochondria, oxidative DNA damage, and aging SO JOURNAL OF THE AMERICAN AGING ASSOCIATION LA English DT Review ID HAMSTER OVARY CELLS; MANGANESE SUPEROXIDE-DISMUTASE; FREE-RADICAL THEORY; HYDROGEN-PEROXIDE TREATMENT; POLYMERASE CHAIN-REACTION; AGE-DEPENDENT INCREASE; MOUSE SKELETAL-MUSCLE; LIGATION-MEDIATED PCR; CYTOCHROME-C-OXIDASE; NUCLEAR-DNA AB Protection from reactive oxygen species (ROS) and from mitochondrial oxidative damage is well known to be necessary to longevity, The relevance of mitochondrial DNA (mtDNA) to aging is suggested by the fact that the two most commonly measured forms of mtDNA damage, deletions and the oxidatively induced lesion 8-oxo-dG, increase with age. The rate of increase is species-specific and correlates with maximum lifespan. It is less clear that failure or inadequacies in the protection from reactive oxygen species (ROS) and from mitochondrial oxidative damage are sufficient to explain senescence. DNA containing 8-oxo-dG is repaired by mitochondria, and the high ratio of mitochondrial to nuclear levels of 8-oxo-dG previously reported are now suspected to be due to methodological difficulties, Furthermore, MnSOD -/+ mice incur higher than wild type levels of oxidative damage, but do not display an aging phenotype. Together, these findings suggest that oxidative damage to mitochondria is lower than previously thought, and that higher levels can be tolerated without physiological consequence. A great deal of work remains before it will be known whether mitochondrial oxidative damage is a "clock" which controls the rate of aging. The increased level of 8-oxo-dG seen with age in isolated mitochondria needs explanation, It could be that a subset of cells lose the ability to protect or repair mitochondria, resulting in their incurring disproportionate levels of damage, Such an uneven distribution could exceed the reserve capacity of these cells and have serious physiological consequences, Measurements of damage need to focus more on distribution, both within tissues and within cells. In addition, study must be given to the incidence and repair of other DNA lesions, and to the possibility that repair varies from species to species, tissue to tissue, and young to old. C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Anson, RM (reprint author), NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. NR 176 TC 10 Z9 12 U1 3 U2 11 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 J AM AGING ASSOC JI J. Am. Aging Assoc. PD OCT PY 2000 VL 23 IS 4 BP 199 EP 218 PG 20 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 425MY UT WOS:000168295800001 PM 23604866 ER PT J AU Bartke, A Brown-Borg, H Kinney, B Mattison, J Wright, C Hauck, S Coschigano, K Kopchick, J AF Bartke, A Brown-Borg, H Kinney, B Mattison, J Wright, C Hauck, S Coschigano, K Kopchick, J TI Growth hormone and aging SO JOURNAL OF THE AMERICAN AGING ASSOCIATION LA English DT Article ID CAENORHABDITIS-ELEGANS; BODY-COMPOSITION; GENE-EXPRESSION; TRANSGENIC MICE; DWARF MICE; FACTOR-I; LONGEVITY; THERAPY; LIFE; AGE AB The potential usefulness of growth hormone (GH) as an anti-aging therapy is of considerable current interest. Secretion of GH normally declines during aging and administration of GH can reverse age-related changes in body composition. However, mutant dwarf mice with congenital GH deficiency and GH resistant GH-R-KO mice live much longer than their normal siblings, while a pathological elevation of GH levels reduces life expectancy in both mice and men. We propose that the actions of GH on growth, development, and adult body size may serve as important determinants of aging and life span, while the age-related decline in GH levels contributes to some of the symptoms of aging. C1 So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. Univ N Dakota, Sch Med, Dept Physiol, Grand Forks, ND 58202 USA. NIA, Mol Physiol & Genet Sect, NIH, Bethesda, MD 20892 USA. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. Ohio Univ, Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA. RP Bartke, A (reprint author), So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X NR 54 TC 10 Z9 10 U1 1 U2 1 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 J AM AGING ASSOC JI J. Am. Aging Assoc. PD OCT PY 2000 VL 23 IS 4 BP 219 EP 225 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 425MY UT WOS:000168295800002 PM 23604867 ER PT J AU Lazarous, DF Unger, EF Epstein, SE Stine, A Arevalo, JL Chew, EY Quyyumi, AA AF Lazarous, DF Unger, EF Epstein, SE Stine, A Arevalo, JL Chew, EY Quyyumi, AA TI Basic fibroblast growth factor in patients with intermittent claudication: Results of a phase I trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; COLLATERAL DEVELOPMENT; HEART; VASODILATORS; CIRCULATION; MYOCARDIUM; FLOW AB OBJECTIVES This phase I study was designed to evaluate the safety, tolerability and pharmacokinetics of intra-arterial basic fibroblast growth factor (bFGF) in patients with atherosclerotic peripheral arterial disease (PVD) and intermittent claudication. We also assessed the effects of basic fibroblast growth factor (bFGF) on calf blood flow as a measure of biologic activity. BACKGROUND Preclinical studies have shown that bFGF, an angiogenic peptide, promotes collateral development in animal models of myocardial and hind limb ischemia. The safety and efficacy of bFGF in patients is unknown, and early clinical trials are underway in coronary and peripheral arterial disease. METHODS A double-blind, placebo-controlled, dose-escalation trial was conducted in patients with claudication demonstrating ankle/brachial index <0.8. Patients were randomly assigned to placebo (n = 6), 10 mu g/kg of bFGF (n = 4), 30 mu g/kg of bFGF once (n = 5) and 30 mu g/kg of bFGF on two consecutive days (n = 4). Study drug was infused into the femoral artery of the ischemic leg. Detailed safety information including retinal photography for neovascularization were obtained through one year. Calf blood flow was measured with strain gauge plethysmography in the two higher dose treatment groups and in four placebo patients at baseline, one month and three to seven months after treatment. RESULTS Intra-arterial bFGF was safe and well-tolerated. The half-life was 46 +/- 21 min. Calf blood flow increased at one month by 66 +/- 26% (mean +/- SEM) and at six months by 153 +/- 51% in bFGF-treated patients (n = 9, p = 0.002). Flow did not change significantly in the placebo group. CONCLUSIONS In this initial randomized, double-blind, placebo-controlled trial in patients with atherosclerotic PVD and claudication, bFGF was well-tolerated. The data suggest a salutary biologic effect, and initiation of phase 2 trials is warranted. (J Am Coil Cardiol 2000;36:1239-44) (C) 2000 by the American College of Cardiology. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Lazarous, DF (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Div Cardiol, A1 East,4940 Eastern Ave, Baltimore, MD 21224 USA. FU Intramural NIH HHS [Z99 EY999999] NR 29 TC 111 Z9 118 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 2000 VL 36 IS 4 BP 1239 EP 1244 DI 10.1016/S0735-1097(00)00882-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 359TA UT WOS:000089627100016 PM 11028477 ER PT J AU Costello, RC AF Costello, RC TI Zinc supplementation - Author's response to Catherine Klein, MS, RD, CNSD SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Letter C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Costello, RC (reprint author), NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 2000 VL 100 IS 10 BP 1138 EP 1138 DI 10.1016/S0002-8223(00)00332-1 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MN UT WOS:000170311500007 ER PT J AU Dwyer, JT Stone, EJ Yang, MH Webber, LS Must, A Feldman, HA Nader, PR Perry, CL Parcel, GS AF Dwyer, JT Stone, EJ Yang, MH Webber, LS Must, A Feldman, HA Nader, PR Perry, CL Parcel, GS CA CATCH Cooperative Res Grp TI Prevalence of marked overweight and obesity in a multiethnic pediatric population: Findings from the Child and Adolescent trial for Cardiovascular Health (CATCH) study SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID BODY-MASS INDEX; NATIONAL-HEALTH; ADIPOSE-TISSUE; RISK-FACTORS; DISEASE; TRENDS AB Objective Determine the prevalence of marked overweight and obesity among children in the Child and Adolescent Trial for Cardiovascular Health (CATCH), identify high risk groups, and compare findings to other recent studies. Design Cohort study. Subjects/setting Five thousand one hundred-six school children who were participants in CATCH at baseline (age approximately 9 years) during 1991 and 4,019 of those children who had follow-up data from 1994 (age approximately 11 years) available. Methods Body mass index (BMI), triceps and subscapular skinfolds, subscapular to triceps skinfold (S/T) ratio, and an estimate of body fat distribution from skinfolds was calculated. Findings were compared to population-based reference data from the First National Health and Nutrition Examination Survey, 1971 to 1973 (NHANES I), to data from the Bogalusa Heart Study, and to data from the Third National Health and Nutrition Examination Survey, 1988 to 1994 (NHANES III). Results Children in CATCH were markedly heavier and fatter than the NHANES I population and more comparable to the NHANES III population, especially those in the upper percentiles. The prevalence of obesity based on BMI and triceps skinfolds >95th percentile among CATCH children was higher in boys than in girls at both baseline (boys 9.1%, girls 8.6%) and follow-up (boys 11.7%, girls 7.2%). It was higher among African-Americans and Hispanics than whites for both sexes. S/T ratios did not differ appreciably from those observed in the NHANES I reference population, suggesting that body fat distribution was more stable over time than BMI and skinfolds. Applications Our findings support other recent reports that American children, especially African-American and Hispanic children, are becoming heavier and fatter. Preventive measures are warranted, especially for high-risk youth. C1 Tufts Univ, New England Med Ctr, Francis Stern Nutr Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ, Sch Nutr Sci & Policy, Boston, MA 02111 USA. NHLBI, NIH, Bethesda, MD 20892 USA. New England Res Inst Inc, Watertown, MA USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat & Epidemiol, New Orleans, LA USA. Tufts Univ, Sch Med, Dept Family Med & Community Hlth, Boston, MA 02111 USA. Univ Calif San Diego, Community Pediat Div, La Jolla, CA 92093 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. RP Dwyer, JT (reprint author), Tufts Univ, New England Med Ctr, Francis Stern Nutr Ctr, Boston, MA 02111 USA. OI Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [U01-HL-39906, U01-HL-39852, U01-HL-39880] NR 30 TC 42 Z9 44 U1 0 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 2000 VL 100 IS 10 BP 1149 EP 1154 DI 10.1016/S0002-8223(00)00337-0 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MN UT WOS:000170311500012 PM 11043699 ER PT J AU Hisasue, M Nishigaki, K Katae, H Yuri, K Mizuno, T Fujino, Y Setoguchi, A Hasegawa, A Watari, T Masuda, K Ohno, K Tsujimoto, H AF Hisasue, M Nishigaki, K Katae, H Yuri, K Mizuno, T Fujino, Y Setoguchi, A Hasegawa, A Watari, T Masuda, K Ohno, K Tsujimoto, H TI Clonality analysis of various hematopoietic disorders in cats naturally infected with feline leukemia virus SO JOURNAL OF VETERINARY MEDICAL SCIENCE LA English DT Article DE clonality; feline; feline leukemia virus; hematological disorder; myelodysplastic syndrome ID RISK MYELODYSPLASTIC SYNDROME; RED-CELL APLASIA; MYELOPROLIFERATIVE DISORDERS; MOLECULAR-CLONING; GENE; APOPTOSIS; CLASSIFICATION; DISEASES; MARROW; ANEMIA AB The clonality analysis of the bone marrow cells was carried out by detecting the integrated proviruses of feline leukemia virus (FeLV) to understand the pathogenesis of FeLV-associated hematopoietic disorders in cats. Bone marrow cells from 4 cases with acute myeloid leukemia (AML), 9 cases with myelodysplastic syndromes (MDS), 2 cases with pure red cell aplasia (PRCA) and 3 healthy carriers infected with FeLV were subjected to Southern blot analyses using an exogenous FeLV probe. Clonal hematopoiesis was found in all the cases with AML and in 6 of the 9 cases with MDS, but not in the cases with both PRCA and healthy carriers infected with FeLV. In the 2 cases with MDS, it was thought that the same clones of the hematopoietic cells might proliferate before and after the progression of the disease irrespective of the changes of the hematological diagnoses by cytological examination. This study indicates that MDS in cats is a disease manifestation as a result of clonal proliferation of hematopoietic cells and can be recognized as a pre-leukemic state of AML. C1 Univ Tokyo, Grad Sch Agr & Life Sci, Dept Vet Internal Med, Bunkyo Ku, Tokyo 1138657, Japan. NCI, Mol Oncol Lab, Frederick, MD USA. Dainippon Pharmaceut Co Ltd, Div Anim Sci, Res Labs, Osaka, Japan. Nihon Univ, Sch Vet Med, Lab Comprehens Vet Clin Studies, Kanagawa, Japan. RP Tsujimoto, H (reprint author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Vet Internal Med, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan. NR 34 TC 16 Z9 16 U1 0 U2 1 PU JAPAN SOC VET SCI PI TOKYO PA UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO, 103, JAPAN SN 0916-7250 J9 J VET MED SCI JI J. Vet. Med. Sci. PD OCT PY 2000 VL 62 IS 10 BP 1059 EP 1065 DI 10.1292/jvms.62.1059 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 371UZ UT WOS:000165198800006 PM 11073076 ER PT J AU Driscoll, MD Hughes, SH AF Driscoll, MD Hughes, SH TI Human immunodeficiency virus type 1 nucleocapsid protein can prevent self-priming of minus-strand strong stop DNA by promoting the annealing of short oligonucleotides to hairpin sequences SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; ACID-CHAPERONE ACTIVITY; PRIMER BINDING-SITE; IN-VITRO; TRANSFER-RNA; AVIAN-MYELOBLASTOSIS; ORDERED AGGREGATION; SECONDARY STRUCTURE; GENOMIC RNA; REPLICATION AB Understanding how viral components collaborate to convert the human immunodeficiency virus type 1 genome from single-stranded RNA into double-stranded DNA is critical to the understanding of viral replication. Not only must the correct reactions be carried out, but unwanted side reactions must be avoided. After minus-strand strong stop DNA (-sssDNA) synthesis, degradation of the RNA template by the RNase Il domain of reverse transcriptase (RT) produces single-stranded DNA that has the potential to self-prime at the imperfectly base paired TAR hairpin, making continued DNA synthesis impossible. Although nucleocapsid protein (NC) interferes with -sssDNA self-priming in reverse transcription reactions in vitro, NC alone did not prevent self-priming of a synthetic -sssDNA oligomer. NC did not influence DNA bending and therefore cannot inhibit self-priming at hairpins by directly blocking hairpin formation. Using DNA oligomers as a model for genomic RNA fragments, we found that a 17-base DNA fragment annealed to the 3' end of the -sssDNA prevented self priming in the presence of NC. This implies that to avoid self-priming, an RNA-DNA hybrid that is more thermodynamically stable than the hairpin must remain within the hairpin region. This suggests that NC prevents self-priming by generating or stabilizing a thermodynamically favored RNA-DNA heteroduplex instead of the kinetically favored TAR hairpin. In support of this idea, sequence changes that increased base pairing in the DNA TAR hairpin resulted in an increase in self-priming in vitro. We present a model describing the role of NC-dependent inhibition of self-priming in first-strand transfer. C1 NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. NR 41 TC 63 Z9 64 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 19 BP 8785 EP 8792 DI 10.1128/JVI.74.19.8785-8792.2000 PG 8 WC Virology SC Virology GA 352XH UT WOS:000089244300001 PM 10982320 ER PT J AU Schmidt, AC McAuliffe, JM Huang, A Surman, SR Bailly, JE Elkins, WR Collins, PL Murphy, BR Skiadopoulos, MH AF Schmidt, AC McAuliffe, JM Huang, A Surman, SR Bailly, JE Elkins, WR Collins, PL Murphy, BR Skiadopoulos, MH TI Bovine parainfluenza virus type 3 (BPIV3) fusion and hemagglutinin-neuraminidase glycoproteins make an important contribution to the restricted replication of BPIV3 in primates SO JOURNAL OF VIROLOGY LA English DT Article ID NEWCASTLE-DISEASE VIRUS; INFLUENZA-A VIRUSES; SENDAI VIRUS; REASSORTANT VIRUS; ADULT VOLUNTEERS; RHESUS-MONKEYS; VACCINE; INFANTS; GENE; H3N2 AB This study examines the contribution of the fusion (f) and hemagglutinin-neuraminidase (HN) glycoprotein genes of bovine parainfluenza virus type 3 (BPIV3) to its restricted replication in the respiratory tract of nonhuman primates.,A chimeric recombinant human parainfluenza type 3 virus (HPIV3) containing BPIV3 F and HN glycoprotein genes in place of its own and the reciprocal recombinant consisting of BPIV3 bearing the HPIV3 F and HN genes (rBPIV3-FHHNH) were generated to assess the effect of glycoprotein substitution on replication of HPIV3 and BPIV3 in the upper and lower respiratory tract of rhesus monkeys. The chimeric viruses were readily recovered and replicated in simian LLC-MK2 cells to a level comparable to that of their parental viruses, suggesting that the heterologous glycoproteins were compatible with the PIV3 internal proteins. HPIV3 bearing the BPIV3 F and HN genes was restricted in replication in rhesus monkeys to a level similar to that of its BPIV3 parent virus, indicating that the glycoprotein genes of BPIV3 are major determinants of its host range restriction of replication in rhesus monkeys. rBPIV3-FHHNH replicated in rhesus monkeys to a level intermediate between that of HPIV3 and BPIV3. This observation indicates that the F and HN genes make a significant contribution to the overall attenuation of BPIV3 for rhesus monkeys. Furthermore, it shows that BPIV3 sequences outside the F and HN region also contribute to the attenuation phenotype in primates, a finding consistent with the previous demonstration that the nucleoprotein coding sequence of BPIV3 is a determinant of its attenuation for primates. Despite its restricted replication in the respiratory tract of rhesus monkeys, rBPIV3-FHHNH conferred a level of protection against challenge with HPIV3 that was indistinguishable from that induced by previous infection with wild-type HPIV3. The usefulness of rBPIV3-FHHNH as a vaccine candidate against HPIV3 and as a vector for other viral antigens is discussed. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Dept Pediat, D-12200 Berlin, Germany. RP Schmidt, AC (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Rm 130,7 Ctr Dr MSC 0720, Bethesda, MD 20892 USA. NR 44 TC 54 Z9 56 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 19 BP 8922 EP 8929 DI 10.1128/JVI.74.19.8922-8929.2000 PG 8 WC Virology SC Virology GA 352XH UT WOS:000089244300016 PM 10982335 ER PT J AU Dettenhofer, M Cen, S Carlson, BA Kleiman, L Yu, XF AF Dettenhofer, M Cen, S Carlson, BA Kleiman, L Yu, XF TI Association of human immunodeficiency virus type 1 vif with RNA and its role in reverse transcription SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL-DNA SYNTHESIS; HTLV-III/LAV; PRIMER TRNA(3)(LYS); BINDING DOMAIN; PROTEIN; CELLS; INITIATION; GENE; VIRIONS; HIV-1 AB The vif gene of human immunodeficiency virus type 1 (HIV-1) is essential for viral replication, although the functional target of Vif remains elusive. HIV-1 vif mutant virions derived from nonpermissive H9 cells displayed no significant differences in the amount, ratio, or integrity of their protein composition relative to an isogenic wild-type virion. The amounts of the virion-associated viral genomic RNA and tRNA(3)(Lys) were additionally present at normal levels in vif mutant virions. We demonstrate that Vif associates with RNA. in vitro as well as with viral genomic RNA in virus-infected cells. A functionally conserved lentivirus Vif motif was found in the double-stranded RNA binding domain of Xenopus laevis, Xlrbpa. The natural intravirion reverse transcriptase products were markedly reduced in vif mutant virions. Moreover, purified vif mutant genomic RNA-primer tRNA complexes displayed severe defects in the initiation of reverse transcription with recombinant reverse transcriptase. These data point to a novel role for Vif in the regulation of efficient reverse transcription through modulation of the virion nucleic acid components. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. McGill Univ, Jewish Gen Hosp, McGill AIDS Ctr, Montreal, PQ H3T 1E2, Canada. McGill Univ, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Immunol, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Microbiol, Montreal, PQ H3T 1E2, Canada. RP Yu, XF (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St, Baltimore, MD 21205 USA. OI Dettenhofer, Markus/0000-0003-1972-7026 NR 44 TC 97 Z9 100 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 19 BP 8938 EP 8945 DI 10.1128/JVI.74.19.8938-8945.2000 PG 8 WC Virology SC Virology GA 352XH UT WOS:000089244300018 PM 10982337 ER PT J AU Guo, JH Wu, TY Anderson, J Kane, BF Johnson, DG Gorelick, RJ Henderson, LE Levin, JG AF Guo, JH Wu, TY Anderson, J Kane, BF Johnson, DG Gorelick, RJ Henderson, LE Levin, JG TI Zinc finger structures in the human immunodeficiency virus type 1 nucleocapsid protein facilitate efficient minus- and plus-strand transfer SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HIV-1 REVERSE-TRANSCRIPTASE; RNASE-H ACTIVITY; PROVIRAL DNA-SYNTHESIS; AMINO-ACID RESIDUES; PRIMER BINDING-SITE; IN-VITRO; GENOMIC RNA; VIRAL REPLICATION; NUCLEIC-ACIDS AB The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) has two zinc fingers, each containing the invariant metal ion binding residues CCHC, Recent reports indicate that mutations In the CCHC motifs are deleterious for reverse transcription in vivo. To identify reverse transcriptase (RT) reactions affected by such changes, cre have probed zinc finger functions in NC-dependent RT-catalyzed HIV-1 minus- and plus-strand transfer model systems. Our approach was to examine the activities of wild-type NC and a mutant in which all six cysteine residues were replaced by serine (SSHS NC); this mutation severely disrupts zinc coordination. We find that the zinc fingers contribute to the role of NC in complete tRNA primer removal from minus-strand DNA during plus-strand transfer, Annealing of the primer binding site sequences in plus-strand strong-stop DNA [(+) SSDNA] to its complement in minus-strand acceptor DNA is not dependent on SC zinc fingers. In contrast, the rate of annealing of the complementary R regions in (-) SSDNA, and 3' viral RNA during minus-strand transfer is approximately eightfold lower when SSHS NC is used in place of wild-type NC. Moreover, unlike wild-type NC, SSHS SC has only a small stimulatory effect on minus-strand transfer and is essentially unable to block TAR-induced self-priming from (-) SSDNA. Our results strongly suggest that NC zinc finger structures are needed to unfold highly structured RNA and DNA strand transfer intermediates. Thus, it appears that in these cases, zinc finger interactions are important components of NC nucleic acid chaperone activity. C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, AIDS Vaccine Program, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Levin, JG (reprint author), NICHD, Mol Genet Lab, NIH, Bldg 6B,Rm 216, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 83 TC 160 Z9 162 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 19 BP 8980 EP 8988 DI 10.1128/JVI.74.19.8980-8988.2000 PG 9 WC Virology SC Virology GA 352XH UT WOS:000089244300023 PM 10982342 ER PT J AU White, CL Weisberg, AS Moss, B AF White, CL Weisberg, AS Moss, B TI A glutaredoxin, encoded by the G4L gene of vaccinia virus, is essential for virion morphogenesis SO JOURNAL OF VIROLOGY LA English DT Article ID GENOME SEQUENCE; REDUCTASE; PROTEINS; STAGE AB Vaccinia virus encodes two glutaredoxins, O2L and G4L, both of which exhibit thioltransferase and dehydroascorbate reductase activities in vitro, Although O2L was previously found to be dispensable for virus replication, we now show that G4L is necessary for virion morphogenesis. RNase protection and Western blotting assays indicated that G4L was expressed at late times after infection and was incorporated into mature virus particles, Attempts to isolate a mutant virus with a deleted G4L gene were unsuccessful, suggesting that the protein was required for virus replication. This interpretation was confirmed by the construction and characterization of a conditional lethal recombinant virus with an inducible copy of the G4L gene replacing the original one. Expression of G4L was proportional to the concentration of inducer, and the amount of glutaredoxin could be varied from barely detectable to greater than normal amounts of protein, Immunogold labeling revealed that the induced G4L protein was associated with immature and mature virions and adjacent cytoplasmic depots. In the absence of inducer, the production of infectious virus was severely inhibited, though viral late protein synthesis appeared unaffected except for decreased maturation-dependent proteolytic processing of certain core components. Electron microscopy of cells infected under nonpermissive conditions revealed an accumulation of crescent membranes on the periphery of electron-dense globular masses but few mature particles. We concluded that the two glutaredoxin homologs encoded by vaccinia virus have different functions and that G4L has a role in virion morphogenesis, perhaps by acting as a redox protein. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 22 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 19 BP 9175 EP 9183 DI 10.1128/JVI.74.19.9175-9183.2000 PG 9 WC Virology SC Virology GA 352XH UT WOS:000089244300045 PM 10982364 ER PT J AU Teng, MN Whitehead, SS Bermingham, A St Claire, M Elkins, WR Murphy, BR Collins, PL AF Teng, MN Whitehead, SS Bermingham, A St Claire, M Elkins, WR Murphy, BR Collins, PL TI Recombinant respiratory syncytial virus that does not express the NS1 or M2-2 protein is highly attenuated and immunogenic in chimpanzees SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION ELONGATION-FACTOR; VACCINE CANDIDATE; SERONEGATIVE CHIMPANZEES; RNA REPLICATION; MESSENGER-RNA; V-PROTEIN; SH GENE; RSV; MUTATIONS; SUBSTITUTION AB Mutant recombinant respiratory syncytial viruses (RSV) which cannot express the NS1 and M2-2 proteins, designated rA2 Delta NS1 and rA2 Delta M2-2, respectively, were evaluated as live-attenuated RSV vaccines. The rA2 Delta NS1 virus contains a large deletion that should have the advantageous property of genetic stability during replication in vitro and in vivo. In vitro, rA2 Delta NS1 replicated approximately 10-fold less well than wild-type recombinant RSV (rA2), while rA2 Delta M2-2 had delayed growth kinetics but reached a final titer similar to that of rA2. Each virus was administered to the respiratory tracts of RSV-seronegative chimpanzees to assess replication, immunogenicity, and protective efficacy. The rA2 Delta NS1 and rA2 Delta M2-2 viruses were 2,200- to 55,000-fold restricted in replication in the upper and lower respiratory tracts but induced a level of RSV-neutralizing antibody in serum that was only slightly reduced compared to the level induced by wild-type RSV. The replication of wild-type RSV in immunized chimpanzees after challenge was reduced more than 10,000 fold at each site. Importantly, rA2 Delta NS1 and rA2 Delta M2-2 were 10-fold more restricted in replication in the upper respiratory tract than was the cpts248/404 virus, a vaccine candidate that retained mild reactogenicity in the upper respiratory tracts of 1-month-old infants. Thus, either rA2 Delta NS1 or rA2 Delta M2-2 might be appropriately attenuated for this age group, which is the major target population for an RSV vaccine. In addition, these results show that neither NS1 nor M2-2 is essential for RSV replication in vivo, although each is important for efficient replication. C1 NIAID, Resp Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. NIAID, Expt Primate Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Collins, PL (reprint author), NIAID, Resp Viruses Sect, Infect Dis Lab, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. RI Teng, Michael/I-5006-2012 OI Teng, Michael/0000-0002-0722-3659 FU NIAID NIH HHS [Z01 AI000099, AI-000087] NR 34 TC 116 Z9 124 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 19 BP 9317 EP 9321 DI 10.1128/JVI.74.19.9317-9321.2000 PG 5 WC Virology SC Virology GA 352XH UT WOS:000089244300061 PM 10982380 ER PT J AU Goldstein, S Brown, CR Dehghani, H Lifson, JD Hirsch, VM AF Goldstein, S Brown, CR Dehghani, H Lifson, JD Hirsch, VM TI Intrinsic susceptibility of rhesus macaque peripheral CD4(+) T cells to simian immunodeficiency virus in vitro is predictive of in vivo viral replication SO JOURNAL OF VIROLOGY LA English DT Article ID DISEASE PROGRESSION; TYPE-1 INFECTION; HIV-1 INFECTION; AIDS PROGRESSION; CLASS-I; MONKEYS; PLASMA; RESPONSES; VIREMIA; LOAD AB Previous studies with simian immunodeficiency virus (SIV) infection of rhesus macaques suggested that the intrinsic susceptibility of peripheral blood mononuclear cells (PBMC) to infection with SIV in vitro was predictive of relative viremia after SIV challenge. The present study was conducted to evaluate this parameter in a well-characterized cohort of six rhesus macaques selected for marked differences in susceptibility to SIV infection in vitro. Rank order relative susceptibility of PBMC to SIVsmE543-3-infection in vitro was maintained over a 1-year period of evaluation. Differential susceptibility of different donors was maintained in CD4(+) T-cell-depleted PBMC, macrophages, and CD4(+) T-cell lines derived by transformation of PBMC with herpesvirus saimiri, suggesting that this phenomenon is an intrinsic property of CD4(+) target cells. Following intravenous infection of these macaques with SIVsmE543-3, we observed a wide range in plasma viremia which followed the same rank order as the relative susceptibility established by in vitro studies. A significant correlation was observed between plasma viremia at 2 and 8 weeks postinoculation and in vitro susceptibility (P < 0.05). The observation that the two most susceptible macaques were seropositive for simian T-lymphotropic virus type 1 may suggests a role for this viral infection in enhancing susceptibility to SIV infection in vitro and in vivo. In summary, intrinsic susceptibility of CD4(+) target cells appears to be an important factor influencing early virus replication patterns in vivo that should be considered in the design and interpretation of vaccine studies using the SIV/macaque model. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. NCI, Lab Retroviral Pathogenesis, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Twinbrook 2 Facil,12441 Parklawn Dr, Rockville, MD 20852 USA. FU NCI NIH HHS [N01-CO-56000] NR 58 TC 37 Z9 37 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 20 BP 9388 EP 9395 DI 10.1128/JVI.74.20.9388-9395.2000 PG 8 WC Virology SC Virology GA 357LP UT WOS:000089503400007 PM 11000207 ER PT J AU Schmidt, M Afione, S Kotin, RM AF Schmidt, M Afione, S Kotin, RM TI Adeno-associated virus type 2 Rep78 induces apoptosis through caspase activation independently of p53 SO JOURNAL OF VIROLOGY LA English DT Article ID PARVOVIRUS MINUTE VIRUS; ADENOASSOCIATED VIRUS; CELL-CYCLE; DNA HELICASE; BIOCHEMICAL-CHARACTERIZATION; NONSTRUCTURAL PROTEINS; REGULATORY PROTEINS; ATPASE ACTIVITIES; FLOW-CYTOMETRY; NS1 PROTEIN AB Adeno-associated virus (AAV) type 2 Rep78 is a multifunctional protein required for AAV DNA replication, integration, and gene regulation. The biochemical activities of Rep78 have been described, but the effects of Rep proteins on the cell have not been characterized. We have analyzed Rep-mediated cytotoxicity. We demonstrated that Rep78 expression is sufficient to induce cell death and disruption of the cell cycle. Cell death was found to be mediated by apoptosis. Rep78 expression resulted in the activation of caspase-3, a terminal caspase directly involved in the execution of cell death. A peptidic inhibitor of caspase-3, Z-Asp-Glu-Val-Asp-fluoromethylketone (Z-DEVD-FMK), abrogated Rep78-induced apoptosis, indicating that Rep78-mediated apoptosis is caspase3 dependent. Rep78 induced apoptosis in wild-type p53-containing human embryonal carcinoma NT-2 cells and in p53-null promyelocytic human HL-60 cells, indicating that at least one pathway of Rep78-induced apoptosis is p53 independent. Apoptosis was shown to occur during the G(1) and early S phases of the cell cycle. By analyzing the effects of Rep78 mutations on cell viability, the cause of cell death was attributed in part to two biochemical activities of Rep78, DNA binding and ATPase/helicase activity. The endonuclease activity of Rep78 did not contribute to apoptosis induction. C1 NHLBI, LBG, NIH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, LBG, NIH, Bldg 10,Rm 7D05, Bethesda, MD 20892 USA. RI kotin, robert/B-8954-2008 NR 68 TC 67 Z9 72 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 20 BP 9441 EP 9450 DI 10.1128/JVI.74.20.9441-9450.2000 PG 10 WC Virology SC Virology GA 357LP UT WOS:000089503400013 PM 11000213 ER PT J AU Cheslock, SR Anderson, JA Hwang, CK Pathak, VK Hu, WS AF Cheslock, SR Anderson, JA Hwang, CK Pathak, VK Hu, WS TI Utilization of nonviral sequences for minus-strand DNA transfer and gene reconstitution during retroviral replication SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HIV-1 REVERSE-TRANSCRIPTASE; 5' NONTRANSLATED REGION; STRONG-STOP DNA; NUCLEOCAPSID PROTEIN; ESCHERICHIA-COLI; INTERNAL ENTRY; RNA; VECTORS; TRANSACTIVATION AB Minus-strand DNA transfer, an essential step in retroviral reverse transcription, is mediated by the two repeat (R) regions in the viral genome. It is unclear whether R simply serves as a homologous sequence to mediate the strand transfer or contains specific sequences to promote strand transfer. To test the hypothesis that the molecular mechanism by which R mediates strand transfer is based on homology rather than specific sequences, we examined whether nonviral sequences can be used to facilitate minus-strand DNA transfer. The green fluorescent protein (GFP) gene was divided into GF and FP fragments, containing the 5' and 3' portions of GFP, respectively, with an overlapping F fragment (85 bp). FP and GF were inserted into the 5' and 3' long terminal repeats, respectively, of a murine leukemia virus-based vector. Utilization of the F fragment to mediate minus-strand DNA transfer should reconstitute GFP during reverse transcription. Flow cytometry analyses demonstrated that GFP was expressed in 73 to 92% of the infected cells, depending on the structure of the viral construct. This indicated that GFP was reconstituted at a high frequency; molecular characterization further confirmed the accurate reconstitution of GFP. These data indicated that nonviral sequences could be used to efficiently mediate minus-strand DNA transfer. Therefore, placement and homology, not specific sequence context, are the important elements in R for minus-strand DNA transfer. In addition, these experiments demonstrate that minus-strand DNA transfer can be used to efficiently reconstitute genes for gene therapy applications. C1 NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA. W Virginia Univ, Dept Microbiol & Immunol, Morgantown, WV 26506 USA. RP Hu, WS (reprint author), NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Rm 336,Bldg 535, Frederick, MD 21702 USA. NR 46 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 20 BP 9571 EP 9579 DI 10.1128/JVI.74.20.9571-9579.2000 PG 9 WC Virology SC Virology GA 357LP UT WOS:000089503400028 PM 11000228 ER PT J AU Yeh, WW Moss, B Wolffe, EJ AF Yeh, WW Moss, B Wolffe, EJ TI The vaccinia virus A9L gene encodes a membrane protein required for an early step in virion morphogenesis SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIN-CONTAINING MICROVILLI; OUTER ENVELOPE PROTEIN; TO-CELL SPREAD; PROTEOLYTIC MATURATION; TRANSCRIPTION FACTOR; CORE PROTEINS; CONSERVED MOTIF; MATURE VIRIONS; FINE-STRUCTURE; F10 KINASE AB The A9L open reading frame of vaccinia virus was predicted to encode a membrane-associated protein. A transcriptional analysis of the A9L gene indicated that it was expressed at late times in vaccinia virus-infected cells. Late expression, as well as virion membrane association, was demonstrated by the construction and use of a recombinant vaccinia virus encoding an A9L protein with a C-terminal epitope tag. Immunoelectron microscopy revealed that the A9L protein was associated with both immature and mature virus particles and was oriented in the membrane with its C terminus exposed on the virion surface. To determine whether the A9L protein functions in viral assembly or infectivity, we made a conditional-lethal inducible recombinant vaccinia virus. In the absence of inducer, A9L expression and virus replication were undetectable. Under nonpermissive conditions, viral late protein synthesis occurred, but maturational proteolytic processing was inhibited, and there was an accumulation of membrane-coated electron-dense bodies, crescents, and immature virus particles, many of which appeared abnormal. We concluded that the product of the A9L gene is a viral membrane-associated protein and functions at an early stage in virion morphogenesis. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 229,4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 75 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 20 BP 9701 EP 9711 DI 10.1128/JVI.74.20.9701-9711.2000 PG 11 WC Virology SC Virology GA 357LP UT WOS:000089503400042 PM 11000242 ER PT J AU Muller, B Tessmer, U Schubert, U Krausslich, HG AF Muller, B Tessmer, U Schubert, U Krausslich, HG TI Human immunodeficiency virus type 1 Vpr protein is incorporated into the virion in significantly smaller amounts than Gag and is phosphorylated in infected cells SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 PREINTEGRATION COMPLEX; NUCLEAR-PORE COMPLEX; OPEN READING FRAME; REGULATORY PROTEIN; VIRAL EXPRESSION; P6 DOMAIN; T-CELLS; CYCLE; PARTICLES; LOCALIZATION AB Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is a small accessory protein involved in the nuclear import of viral DNA and the growth arrest of host cells. Several studies have demonstrated that a significant amount of Vpr is incorporated into the virus particle via interaction with the p6 domain of Gag, and it is generally assumed that Vpr is packaged in equimolar ratio to Gag. We have quantitated the relative amount of Vpr in purified virions following [S-35]cysteine labeling of infected MT-4 cells, as well as by quantitative immunoblotting and found that Vpr is present in a molar ratio of approximately 1:7 compared to capsid. Analysis of isolated core particles showed that Vpr is associated with the mature viral core, despite quantitative loss of p6 from core preparations. Metabolic labeling of infected cells with ortho[P-32]phosphate revealed that a small fraction of Vpr is phosphorylated in virions and infected cells. C1 Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. NIAID, Viral Dis Lab, Bethesda, MD USA. RP Muller, B (reprint author), Univ Heidelberg, Abt Virol, Neuenheimer Feld 324, D-69120 Heidelberg, Germany. NR 48 TC 66 Z9 67 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 20 BP 9727 EP 9731 DI 10.1128/JVI.74.20.9727-9731.2000 PG 5 WC Virology SC Virology GA 357LP UT WOS:000089503400045 PM 11000245 ER PT J AU Cho, MW Lee, MK Chen, CH Matthews, T Martin, MA AF Cho, MW Lee, MK Chen, CH Matthews, T Martin, MA TI Identification of gp120 regions targeted by a highly potent neutralizing antiserum elicited in a chimpanzee inoculated with a primary human immunodeficiency virus type 1 isolate SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; PBL-SCID MICE; HIV-1 ENVELOPE GLYCOPROTEIN; PASSIVE-IMMUNIZATION; RECOMBINANT VACCINIA; INFECTED CHIMPANZEES; MACAQUE MONKEYS; CHIMERIC VIRUS; SUBTYPE-E; T-CELL AB We have previously reported that a chimpanzee infected with a primary human immunodeficiency virus type 1 (HIV-1) isolate (HIV-1(DH12)) developed an extremely potent virus-neutralizing antibody. Immunoglobulin G purified from this animal conferred sterilizing immunity following passive transfer to macaques which were subsequently challenged with simian immunodeficiency virus/HIV-1 chimeric virus strain DH12. In addition to being highly strain specific, the chimpanzee antiserum did not bind to the V3 loop peptide of HIV-1(DH12), nor did it block the interaction of gp120 with the CD4 receptor. When neutralization was examined in the context of virus particles carrying chimeric envelope glycoproteins, the presence of all five hypervariable regions (V1 to V5) was required for optimal neutralization. Virions bearing chimeric gp120 containing the V1-V2 and V4 regions of HIV-1(DH12) could also be neutralized, but larger quantities of the chimpanzee antiserum were needed to block infection. These results indicate that the HIV-1 gp120 epitope(s) targeted by the chimpanzee antiserum is highly conformational, involving surface elements contributed by all of the hypervariable domains of the envelope glycoprotein. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Meharry Med Coll, Dept Microbiol, Nashville, TN 37208 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Cho, MW (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike,Bldg 4,Rm 339, Bethesda, MD 20892 USA. NR 50 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 20 BP 9749 EP 9754 DI 10.1128/JVI.74.20.9749-9754.2000 PG 6 WC Virology SC Virology GA 357LP UT WOS:000089503400049 PM 11000249 ER PT J AU Weng, YK Yang, ZN Weiss, CD AF Weng, YK Yang, ZN Weiss, CD TI Structure-function studies of the self-assembly domain of the human immunodeficiency virus type 1 transmembrane protein gp41 (vol 74, pg 5368, 2000) SO JOURNAL OF VIROLOGY LA English DT Correction C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA. RP Weng, YK (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 20 BP 9811 EP 9811 DI 10.1128/JVI.74.20.9811-9811.2000 PG 1 WC Virology SC Virology GA 357LP UT WOS:000089503400060 ER PT J AU Cu-Uvin, S Wright, DJ Anderson, D Kovacs, A Watts, DH Cohn, J Landay, A Reichelderfer, PS AF Cu-Uvin, S Wright, DJ Anderson, D Kovacs, A Watts, DH Cohn, J Landay, A Reichelderfer, PS CA Womens Hlth Study WHS 001 WHS 001a Study Team TI Hormonal levels among HIV-1-seropositive women compared with high-risk HIV-seronegative women during the menstrual cycle SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLS; TRANSMISSION; PROGESTERONE; PREGNANCY; CONTRACEPTION; INHIBITION; DISEASE; LOAD AB There is a paucity of normative data on hormonal levels among HIV-infected women. Hormonal levels may influence fertility and HIV-related immunological and virological factors. The objective of this study was to determine progesterone and estradiol levels during the menstrual cycle in HIV-seropositive women compared with high-risk seronegative women. The study enrolled 55 HIV-infected and 10 high-risk uninfected women with self-reported regular menstrual cycles (25-30-day cycles). Progesterone and estradiol levels were determined on a weekly basis for 8 weeks. The analysis included evaluations from the first complete menstrual cycle for the 54 HIV-infected and 9 uninfected women who had at least one complete cycle. The median age was 35 years for HIV-infected women and 36 years for uninfected women. The median CD4(+) count for HIV-seropositive women was 210 cells/mm(3). The median menstrual cycle length was 28 days (range 22-49 days) for HIV-infected women and 25 days (range 24-44 days) for uninfected women. The maximum progesterone level during the luteal phase was normal (>3.0 ng/ml) for 52 (96%) of 54 HIV-seropositive women and 7 (78%) of 9 HIV-seronegative women (p = 0.09, Fisher's exact test). The median maximum progesterone level was 12.2 ng/ml in HIV-seropositive women and 7.2 ng/ml in HIV-seronegative women (p = 0.07, Wilcoxon test). The median maximum estradiol value during the follicular phase was 148 pg/ml for HIV-seropositive women and 111 pg/ml for HIV-seronegative women (p = 0.04, Wilcoxon test). Among HIV-infected women, there were no significant differences in progesterone and estradiol levels by antiretroviral therapy, baseline plasma viral load, or median CD4(+) cell count. We conclude that HIV-infected women with self-reported normal menstrual cycles have normal levels of progesterone and estradiol during the menstrual cycle. C1 Brown Univ, Providence, RI 02912 USA. WESTAT Corp, Rockville, MD 20850 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ So Calif, Los Angeles, CA USA. NICHHD, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Detroit, MI USA. Rush Presbyterian St Lukes Hosp, Chicago, IL USA. RP Cu-Uvin, S (reprint author), Miriam Hosp, 164 Summit Ave, Providence, RI 02906 USA. FU NICHD NIH HHS [N01-HD-3-3162] NR 25 TC 18 Z9 18 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD OCT PY 2000 VL 9 IS 8 BP 857 EP 863 DI 10.1089/152460900750020883 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 369NJ UT WOS:000165073500006 PM 11074951 ER PT J AU Castro, CM Yang, YP Zhang, Z Linnoila, RI AF Castro, CM Yang, YP Zhang, Z Linnoila, RI TI Attenuation of pulmonary neuroendocrine differentiation in mice lacking Clara cell secretory protein SO LABORATORY INVESTIGATION LA English DT Article ID LUNG BRANCHING MORPHOGENESIS; MESSENGER-RNA; 10-KDA PROTEIN; CANCER-CELLS; EXPRESSION; OVEREXPRESSION; HYBRIDIZATION; ASSOCIATION; UTEROGLOBIN; BOMBESIN AB During development and injury, pulmonary neuroendocrine (NE) cells may transiently express Clara cell 10 kD protein (CC10), a major product of the nonciliated progenitor cells for normal and neoplastic airway epithelia suggesting a close relationship between the cells. To assess the role of CC10 during NE differentiation, we studied CC10-deficient mouse lungs by immunohistochemistry and digital imaging. The knockout model revealed a lack of the disrupted gene product in the lung. Because NE cells, which occur as solitary cells or in neuroepithelial bodies (NEBS), comprise less than 1% of airway epithelia, we counted foci positive for each of the three NE markers-synaptophysin, calcitonin gene-related peptide (CGRP), and protein gene product (PGP) 9.5-and developed a method to analyze numerous airways in serial sections. Digitized images of slides were segmented with Photoshop imaging software. The length of airway epithelium and total section areas were then measured using MetaMorph image analysis software. A comparable range of NE foci was observed regardless of CC10 expression patterns with all three markers, suggesting that CC10 is not critical for NE ontogenesis. However, discrimination according to size revealed that wild-type lungs harbored 30% to 40% greater synaptophysin- and CGRP-containing NEBs relative to CC10 deficient lungs. We posit that an attenuation of pulmonary NE differentiation afflicts the CC10-deficient state. Our imaging application greatly facilitates the acquisition and analysis of complex structures such as the lung and promises to be a widely applicable technique for assessments of tissue sections. C1 NCI, Med Branch, NIH, Rockville, MD 20850 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Linnoila, RI (reprint author), NCI, Med Branch, NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM ill7h@nih.gov NR 22 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 2000 VL 80 IS 10 BP 1533 EP 1540 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 366DZ UT WOS:000089990700007 PM 11045570 ER PT J AU Rao, CR Gutierrez, MI Bhatia, K Fend, F Franklin, J Appaji, L Gallo, G O'Conor, G Lalitha, N Magrath, I AF Rao, CR Gutierrez, MI Bhatia, K Fend, F Franklin, J Appaji, L Gallo, G O'Conor, G Lalitha, N Magrath, I TI Association of Burkitt's lymphoma with the Epstein-Barr virus in two developing countries SO LEUKEMIA & LYMPHOMA LA English DT Article DE Burkitt's lymphoma; Epstein-Barr virus; India; Argentina; EBV subtype; LMP-1 deletion ID LATENT MEMBRANE PROTEIN-1; 30-BASE PAIR DELETION; NON-HODGKIN-LYMPHOMA; HIGH PREVALENCE; TURKISH CHILDREN; EPIDEMIOLOGIC CORRELATIONS; NASOPHARYNGEAL CARCINOMA; MEMBRANE-PROTEIN-1 GENE; JAPANESE POPULATION; ONCOGENE DELETIONS AB The clinical presentation of Burkitt's lymphoma (BL) and it's association with the Epstein-Barr virus (EBV) varies in different geographic areas, BL in developing countries being "intermediate" between the sporadic and endemic types, both in it's clinical presentation and it's association with EBV, which varies from 25-80%. In this study we have analysed the clinical features, EBV association, subtype and prevalence of the deleted variant of the Latent Membrane Protein-1 (LMP-1) of EBV in forty-two cases from two developing countries- India (n=25) and Argentina (n=17). In both countries the abdomen was the site most commonly involved while jaw involvement was rare. EBV was detected by in-situ hybridization using the EBER-1 RNA probe. 47% of cases from Argentina and 80% of cases from India were EBER positive. EBV typing using EBNA-3C primers showed a predominance of Type A in both countries (India-13/16 and Argentina-7/8). The 30bp deletion of the LMP-1 gene was detected in all evaluated cases from Argentina while the wild type of the gene was seen in all the evaluable Indian cases. Our study highlights the similarities and differences in the clinical presentation and EBV association of BL in two developing countries and also indicates that the subtype of EBV and prevalence of the LMP-1 deletion may reflect the pre dominant subtype in a particular population. C1 NCI, Pediat Branch, Lymphoma Biol Sect, Bethesda, MD 20892 USA. RP Rao, CR (reprint author), Wilson Manor Apartments,11-3,B305,13th Cross,Wils, Bangalore 560027, Karnataka, India. NR 42 TC 17 Z9 17 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2000 VL 39 IS 3-4 BP 329 EP + DI 10.3109/10428190009065832 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 392YL UT WOS:000166440100011 PM 11342313 ER PT J AU Saif, MW Hamilton, JM Allegra, CJ AF Saif, MW Hamilton, JM Allegra, CJ TI Varicella zoster meningitis preceeded by thrombophlebitis in a patient with Hodgkin's disease SO LEUKEMIA & LYMPHOMA LA English DT Article DE Varicella Zoster virus; meningitis; thrombophlebitis; Hodgkin's disease; immunosuppression.; meningoencephalitis; protein S; antiphospholipid antibodies; cerebrospinal fluid ID HERPES-ZOSTER; CEREBROSPINAL-FLUID; VIRUS-INFECTIONS; POPULATION; CANCER; ADULT; THROMBOSIS; DNA AB Varicella tester (V-Z) infections are common among patients with hematological malignancies, particularly Hodgkin's disease (HD), The common denominator in both HD and V-Z infections is immunosuppression. Most of V-Z infections occur in patients with HD during the remission period, who have mixed cellularity sub-type, with stage III disease and who have received combined chemo-radiation therapy. Involvement of the central nervous system usually manifests as post-herpetic neuralgia or encephalitis. Angiitis has also been found in association with V-Z infections. The authors describe a case of HD who developed V-Z meningitis preceeded by superficial thrombophlebitis of upper extremities during the period of active chemotherapy. C1 NCI, Natl Naval Med Ctr, Med Branch, Bethesda, MD 20889 USA. RP Saif, MW (reprint author), NCI, Natl Naval Med Ctr, Med Branch, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2000 VL 39 IS 3-4 BP 421 EP + DI 10.3109/10428190009065843 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 392YL UT WOS:000166440100022 PM 11342324 ER PT J AU Engels, FHC Kreisel, D Faries, MB Bedrosian, I Koski, GK Cohen, PA Czerniecki, BJ AF Engels, FHC Kreisel, D Faries, MB Bedrosian, I Koski, GK Cohen, PA Czerniecki, BJ TI Calcium ionophore activation of chronic myelogenous leukemia progenitor cells into dendritic cells is mediated by calcineurin phosphatase SO LEUKEMIA RESEARCH LA English DT Article DE Ca2+/calmodulin kinase II (281-301); calmodulin/calcineurin pathway; chronic myelogenous leukemia (CML); cyclosporin A (CsA); dendritic cells (DC); inhibitory effect; myeloid progenitor cells; W-7 ID CYCLOSPORINE-A; CALMODULIN ANTAGONISTS; FK-506; TRANSCRIPTION; ACQUISITION; INHIBITION; EXPRESSION; ENZYME AB We have previously demonstrated that Ph + myeloid progenitor cells of patients with chronic myeloid leukemia (CML) can acquire characteristics of mature dendritic cells (DC) following calcium mobilization with calcium ionophore (A23187, CI). In this study we characterize the intracellular signaling pathway by which CI induces the acquisition of DC features in these leukemic cells. CI-induced activation of CML cells is attenuated by the calcineurin phosphatase inhibitor cyclosporin A (CsA) as well as the calmodulin (CaM) antagonist W-7. These cause ablation of both the CI-induced immunophenotypic expression of DC markers and immunostimulatory properties in mixed leukocyte responses (MLR). Minimal blocking effect was observed when Ca2+/CaM kinase II (281-301) inhibitor was added to the cultures. These findings suggest a Ca2+-dependent mechanism for the CI-induced activation of CML cells into antigen-presenting cells (APC), which is primarily mediated through the CaM/calcineurin pathway. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. RP Engels, FHC (reprint author), Univ Penn, Med Ctr, Dept Surg, 4 Silverstein Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. NR 20 TC 10 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD OCT PY 2000 VL 24 IS 10 BP 795 EP 804 DI 10.1016/S0145-2126(00)00047-3 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 355QR UT WOS:000089396800001 PM 10996197 ER PT J AU Landis, CS Li, X Telang, FW Coderre, JA Micca, PL Rooney, WD Latour, LL Vetek, G Palyka, I Springer, CS AF Landis, CS Li, X Telang, FW Coderre, JA Micca, PL Rooney, WD Latour, LL Vetek, G Palyka, I Springer, CS TI Determination of the MRI contrast agent concentration time course in vivo following bolus injection: Effect of equilibrium transcytolemmal water exchange SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE contrast reagent; concentration; bolus-tracking; transcytolemmal water exchange ID IN-VIVO; EXTRACTION FRACTION; MAGNETIC-RESONANCE; PERFUSION RATE; TUMORS; BRAIN; RESOLUTION; RELAXIVITY; DIFFUSION; KINETICS AB For bolus-tracking studies, it is commonly assumed that CR concentration bears a linear relationship with the measured (usually longitudinal) (H2O)-H-1 relaxation rate constant, R-1* =(T-1*)(-1). This requires that equilibrium transcytolemmal water exchange be in the fast exchange limit (FXL). However, though systems remain in fast exchange, the FXL will not usually obtain. Here, the consequences are considered: 1) the measurement of R-1* itself can be affected, 2) the resultant non-linear [CR]-dependence causes significant error by assuming FXL, 3) the thermodynamic [CR] (based on the space in which CR is actually distributed) can be determined, 4) transcytolemmal water permeability may be estimated, and 5) the pharmacokinetic parameters can be factored. For a 30-sec, 0.17 mmol/kg dose of GdDTPA(2-), the FXL assumption underestimates the [CR] maximum in rat thigh muscle by a factor of almost two. Similar results are obtained for a rat brain GS-SL gliosarcoma tumor model. Magn Reson Med 44:563-574, 2000. published 2000 Wiley-Liss, Inc.(dagger) C1 Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. RP Springer, CS (reprint author), Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. OI Springer, Charles/0000-0002-5966-2135 FU NIGMS NIH HHS [R01 GM32125] NR 39 TC 150 Z9 151 U1 2 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD OCT PY 2000 VL 44 IS 4 BP 563 EP 574 DI 10.1002/1522-2594(200010)44:4<563::AID-MRM10>3.0.CO;2-# PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 360MG UT WOS:000089671300010 PM 11025512 ER PT J AU Basser, PJ Pajevic, S Pierpaoli, C Duda, J Aldroubi, A AF Basser, PJ Pajevic, S Pierpaoli, C Duda, J Aldroubi, A TI In vivo fiber tractography using DT-MRI data SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; DTI; DT; diffusion; tensor; human; brain; white matter; fiber; tract; trajectory; artifact; noise; curvature; torsion; bending ID DIFFUSION-TENSOR MRI; HUMAN BRAIN; B-MATRIX; IMAGES; ECHO; SPECTROSCOPY; ARTIFACTS AB Fiber tract trajectories in coherently organized brain white matter pathways were computed from in vivo diffusion tensor magnetic resonance imaging (DT-MRI) data. First, a continuous diffusion tensor field is constructed from this discrete, noisy, measured DT-MRI data. Then a Frenet equation, describing the evolution of a fiber tract, was solved. This approach was validated using synthesized, noisy DT-MRI data. Corpus callosum and pyramidal tract trajectories were constructed and found to be consistent with known anatomy. The method's reliability, however, degrades where the distribution of fiber tract directions is nonuniform. Moreover, background noise in diffusion-weighted MRIs can cause a computed trajectory to hop from tract to tract. Still, this method can provide quantitative information with which to visualize and study connectivity and continuity of neural pathways in the central and peripheral nervous systems in vivo, and holds promise for elucidating architectural features in other fibrous tissues and ordered media. Published 2000 Wiley-Liss, Inc.(dagger) C1 NIH, Bethesda, MD 20892 USA. NICHD, Sect Tissue Biophys & Biomimet, Bethesda, MD USA. CIT, Math & Stat Comp Lab, Bethesda, MD USA. Vanderbilt Univ, Dept Math, Nashville, TN USA. RP Basser, PJ (reprint author), NIH, Bldg 13,Rm 3W16,13 South Dr, Bethesda, MD 20892 USA. RI Pierpaoli, Carlo/E-1672-2011; Aldroubi, Akram/J-7186-2012; Basser, Peter/H-5477-2011 NR 40 TC 1558 Z9 1606 U1 6 U2 68 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD OCT PY 2000 VL 44 IS 4 BP 625 EP 632 DI 10.1002/1522-2594(200010)44:4<625::AID-MRM17>3.0.CO;2-O PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 360MG UT WOS:000089671300017 PM 11025519 ER PT J AU Cavagna, P Menotti, A Stanyon, R AF Cavagna, P Menotti, A Stanyon, R TI Genomic homology of the domestic ferret with cats and humans SO MAMMALIAN GENOME LA English DT Article ID ZOO-FISH ANALYSIS; ANCESTRAL KARYOTYPE; CHROMOSOME; HYBRIDIZATION; CARNIVORES; GENE AB We used chromosome paints from both the domestic cat and humans to directly establish chromosomal homology between the genome of these species and the domestic ferret. The chromosome painting data indicate that the ferret has a highly conserved karyotype closer to the ancestral carnivore karyotype than that of the cat. The cat chromosome paints revealed 22 homologous autosomal regions in the ferret genome: 16 ferret chromosomes were hybridized by a single cat paint, while 3 ferret chromosomes were hybridized by two cat paints. In situ hybridization combined with banding showed that ferret Chromosome (Chr) 1 = cat A2p/C2, Chr 2 = F2/C1q, and Chr 3 = A2q/D2. Five ferret chromosomes are homologous to single arms of cat chromosomes: ferret 4 = A1q, 5 = Big, 6 = Clp, 10 = Alp, and 12 = B1p. The human chromosome paints revealed 32 + XY homologous regions in the ferret genome: 9 ferret chromosomes were each hybridized by a single human paint, 7 by two paints, 3 by three paints. The 10 ferret chromosomes hybridized by multiple human paints produced the following associations: ferret 1 = human 19/3/21, 2 = 8q/2q, 3 = 10/7,5 = 8/4, 8 = 15/14, 9 = 10/12/22, 11 = 20/2, 12 = 8/4, 14 = 12/22/18, 18 = 19/16. We present an index of genomic diversity, Z, based on the relative number of conserved whole chromosome and chromosome segments as a preliminary statistic for rapid comparison between species. The index of diversity between human-ferret (Z = 0.812) is slightly less than human-cat (Z = 0.843). The homology data presented here allow us to transfer gene mapping data from both cats and humans to the ferret. C1 NCI, Mol Cytogenet Sect, Frederick, MD 21702 USA. Univ Genoa, Dept Expt Biol, I-16132 Genoa, Italy. Univ Genoa, Dept Anthropol Sci, Basic Res Lab, I-16132 Genoa, Italy. RP Stanyon, R (reprint author), NCI, Mol Cytogenet Sect, Bldg 560, Frederick, MD 21702 USA. OI Stanyon, Roscoe/0000-0002-7229-1092 NR 36 TC 33 Z9 33 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 2000 VL 11 IS 10 BP 866 EP 870 DI 10.1007/s003350010172 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 358RZ UT WOS:000089572100010 PM 11003701 ER PT J AU Brantley, DM Yull, FE Muraoka, RS Hicks, DJ Cook, CM Kerr, LD AF Brantley, DM Yull, FE Muraoka, RS Hicks, DJ Cook, CM Kerr, LD TI Dynamic expression and activity of NF-kappa B during post-natal mammary gland morphogenesis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE NF-kappa B; p105; p50; RelA; I kappa B alpha; mammary; epithelium; proliferation; differentiation; involution; apoptosis; transgenic ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; BREAST-CANCER; TRANSCRIPTIONAL REGULATION; B/REL EXPRESSION; CELLS; ACTIVATION; PROTEINS; GROWTH; MICE AB The RelNF-kappaB family of transcription factors has been implicated in such diverse cellular processes as proliferation, differentiation, and apoptosis, As each of these processes occurs during post-natal mammary gland morphogenesis, the expression and activity of NF-kappaB factors in the murine mammary gland were examined. Immunohistochemical and immunoblot analyses revealed expression of the p105/p50 and RelA subunits of NF-kappaB, as well as the major inhibitor, I kappaB alpha, in the mammary epithelium during pregnancy, lactation, and involution. Electrophoretic mobility shift assay (EMSA) demonstrated that DNA-binding complexes containing p50 and RelA were abundant during pregnancy and involution, but not during lactation. Activity of an NF-kappaB-dependent luciferase reporter in transgenic mice was highest during pregnancy, decreased to near undetectable levels during lactation, and was elevated during involution. This highly regulated pattern of activity was consistent with the modulated expression of p105/p50, RelA, and I kappaB alpha. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. NIAID, DAIT, Transplantat Sect, NIH, Bethesda, MD 20892 USA. RP Kerr, LD (reprint author), Vanderbilt Univ, Sch Med, Dept Cell Biol, 1161 21st Ave S, Nashville, TN 37232 USA. FU NCI NIH HHS [CA 68485]; NIGMS NIH HHS [R01GM51249] NR 19 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD OCT PY 2000 VL 97 IS 1-2 BP 149 EP 155 DI 10.1016/S0925-4773(00)00405-6 PG 7 WC Developmental Biology SC Developmental Biology GA 367YK UT WOS:000090089900015 PM 11025216 ER PT J AU Kawahara, A Dawid, IB AF Kawahara, A Dawid, IB TI Expression of the Kruppel-like zinc finger gene biklf during zebrafish development SO MECHANISMS OF DEVELOPMENT LA English DT Article DE biklf; Kruppel-like factor; blood islands; BMP signaling ID TRANSCRIPTION FACTOR; IDENTIFICATION; HEMATOPOIESIS; ACTIVATION; PROMOTER; FAMILY; CLOCHE; EKLF AB The zebrafish biklf gene encodes a novel Kruppel-like transcription factor containing three contiguous zinc fingers at the C-terminus. Expression of biklf is detected from the shield stage onward in the developing prechordal plate, and as a 'baseball seam'-like lateral stripe beginning at the end of gastrulation. The latter expression domain is suppressed in the swirl mutant in which bmp2b is disrupted. At the 5-somite stage the lateral expression domain separates into two distinct stripes, one in the ectoderm, the other in blood islands in the lateral plate mesoderm. Blood island staining of biklf continues through somitogenesis as the most prominent area of biklf expression. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 18 TC 25 Z9 25 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD OCT PY 2000 VL 97 IS 1-2 BP 173 EP 176 DI 10.1016/S0925-4773(00)00404-4 PG 4 WC Developmental Biology SC Developmental Biology GA 367YK UT WOS:000090089900019 PM 11025220 ER PT J AU Stivers, C Brody, T Kuzin, A Odenwald, WF AF Stivers, C Brody, T Kuzin, A Odenwald, WF TI Nerfin-1 and -2, novel Drosophila Zn-finger transcription factor genes expressed in the developing nervous system SO MECHANISMS OF DEVELOPMENT LA English DT Article DE neuronal precursor gene; pan-neural expression; neural stem cell; neuroblast; ganglion mother cell; CNS and PNS development; transcription factor; EIN Zn-finger domain subfamily ID PROTEIN; NEUROGENESIS AB To gain insight into the regulatory networks controlling Drosophila neural-identity decisions, we have identified new neuronal precursor genes by performing an in situ hybridization screen of differentially selected embryonic head cDNAs. Here, we describe the molecular characteristics and expression profile of nerfin-1, a novel pan-neural precursor gene. This paper also documents the embryonic expression of another structurally related gene, nerfin-2. During early CNS development, nerfin-1 gene expression is activated in neuroblasts (NBs) prior to lineage formation. However, after early sublineage development, nerfin-1 expression shifts from NBs to ganglion mother cells (GMCs) but is not expressed in neurons or glia. Differing from nerfin-1, nerfin-2 is expressed only in a subset of brain neurons. Possessing a conserved putative DNA-binding domain, the predicted Nerfin-1 and -2 proteins belong to a subfamily of Zn-finger transcription factors with cognates identified in nematode, mouse and man. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NINDS, Neurochem Lab, Neurogenet Unit, NIH, Bethesda, MD 20892 USA. RP Odenwald, WF (reprint author), NINDS, Neurochem Lab, Neurogenet Unit, NIH, Bethesda, MD 20892 USA. NR 11 TC 17 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD OCT PY 2000 VL 97 IS 1-2 BP 205 EP 210 DI 10.1016/S0925-4773(00)00409-3 PG 6 WC Developmental Biology SC Developmental Biology GA 367YK UT WOS:000090089900026 PM 11025227 ER PT J AU Cohen, JI AF Cohen, JI TI A new approach to vaccination: polymorphic vaccines for RNA viruses SO MEDICAL HYPOTHESES LA English DT Article ID DYNAMICS IN-VIVO; HIV; ESCAPE; INFECTION; TRANSMISSION; MUTAGENESIS; POPULATION; STRAIN AB Conventional vaccines consist of a very large number of virtually identical molecules. While these have been extremely effective for prevention against viral diseases, development of vaccines against rapidly changing pathogens such as human immunodeficiency virus (HIV) and hepatitis C virus has proved to be more difficult. We propose a new approach to vaccination against these rapidly mutating pathogens by the use of vaccines consisting of a set of highly polymorphic recombinant molecules. (C) 2000 Harcourt Publishers Ltd. C1 NIH, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Clin Invest Lab, Bldg 10,Room 11N228, Bethesda, MD 20892 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD OCT PY 2000 VL 55 IS 4 BP 353 EP 355 DI 10.1054/mehy.2000.1068 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 368KM UT WOS:000090116200017 PM 11000067 ER PT J AU Ayala-Torres, S Chen, YM Svoboda, T Rosenblatt, J Van Houten, B AF Ayala-Torres, S Chen, YM Svoboda, T Rosenblatt, J Van Houten, B TI Analysis of gene-specific DNA damage and repair using quantitative polymerase chain reaction SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID HUMAN GENOMIC DNA; TRANSCRIBED STRAND; OXIDATIVE STRESS; DHFR GENE; CELLS; AMPLIFICATION; ADDUCTS; LEVEL; PCR; RESOLUTION AB Soon after discovery of the polymerase chain reaction (PCR), various laboratories have attempted to use quantitative PCR (QPCR) to detect DNA damage in specific gene segments. The development of techniques that facilitate long PCR increased the sensitivity of the assay so that biologically relevant doses of DNA-damaging agents could be assessed. QPCR has been used to survey DNA damage induced by different genotoxicants and to establish the repair kinetics of numerous genes. Current work seeks to analyze damage and repair in specific genes from animals exposed to specific DNA-damaging agents such as oxidative stress. (C) 2000 Academic Press. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. Univ Texas, Med Branch, Div Biomath, Galveston, TX 77555 USA. Shriners Burns Inst, Galveston, TX 77555 USA. RP Van Houten, B (reprint author), NIEHS, 111 TW Alexander Dr,Box 12233, Res Triangle Pk, NC 27709 USA. FU NIA NIH HHS [AG10514]; NIEHS NIH HHS [ES07038, ES07218] NR 32 TC 138 Z9 141 U1 0 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD OCT PY 2000 VL 22 IS 2 BP 135 EP 147 DI 10.1006/meth.2000.1054 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366BJ UT WOS:000089984700005 PM 11020328 ER PT J AU Smith, JD Subramanian, G Gamain, B Baruch, DI Miller, LH AF Smith, JD Subramanian, G Gamain, B Baruch, DI Miller, LH TI Classification of adhesive domains in the Plasmodium falciparum Erythrocyte Membrane Protein 1 family SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; antigenic variation; Plasmodium ID CHONDROITIN SULFATE-A; RED-CELL SURFACE; INFECTED ERYTHROCYTES; ANTIGENIC VARIATION; BINDING-PROTEINS; GENE FAMILY; PSI-BLAST; MALARIA; SEQUENCES; RECEPTOR AB The Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family of cytoadherent proteins has a central role in disease from malaria infection. This highly diverse gene family is involved in binding interactions between infected erythrocytes and host cells and is expressed in a clonally variant pattern at the erythrocyte surface. We describe by sequence analysis the structure and domain organization of 20 PfEMP1 from the GenBank database. Four domains comprise the majority of PfEMP1 extracellular sequence: the N-terminal segment (NTS) located at the amino terminus of all PfEMP1, the C2, the Cysteine-rich Interdomain Region (CIDR) and the Duffy Binding-like (DBL) domains. Previous work has shown that CIDR and DBL domains can possess adhesive properties. CIDR domains grouped as three distinct sequence classes (alpha, beta, and gamma) and DBL domains as five sequence classes (alpha, beta, gamma, delta. and epsilon). Consensus motifs are described for the different DBL and CIDR types. Whereas the number of DBL and CIDR domains vary between PfEMP1, PfEMP1 domain architecture is not random in that certain tandem domain associations - such as DBL alpha CIDR alpha, DBL beta CIDR beta, and DBL beta C2 - are preferentially observed. This conservation may have functional significance for PfEMP1 folding, transport, or binding activity. Parasite binding phenotype appears to be a determinant of infected erythrocyte tissue tropism that contributes to parasite survival, transmission, and disease outcome. The sequence classification of DBL and CIDR types may have predictive value for identifying PfEMP1 domains with a particular binding property. This information might be used to develop interventions targeting parasite binding variants that cause disease. (C) 2000 Elsevier science B.V. All rights reserved. C1 Colorado State Univ, Dept Pathol, Ft Collins, CO 80523 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Smith, JD (reprint author), Colorado State Univ, Dept Pathol, Room 309, Ft Collins, CO 80523 USA. NR 48 TC 186 Z9 187 U1 0 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD OCT PY 2000 VL 110 IS 2 BP 293 EP 310 DI 10.1016/S0166-6851(00)00279-6 PG 18 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 360XD UT WOS:000089691900010 PM 11071284 ER PT J AU Taylor, D Cloonan, N Mann, V Cheng, Q Saul, A AF Taylor, D Cloonan, N Mann, V Cheng, Q Saul, A TI Sequence diversity in rodent malaria of the Pfs28 ookinete surface antigen homologs SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE ookinete; synonymous; Plasmodium berghei; Plasmodium vinckei; Plasmodium yoelii; Plasmodium chabaudi ID TRANSMISSION-BLOCKING ANTIBODIES; PARASITE PLASMODIUM-FALCIPARUM; RECOMBINANT PFS25; NATURAL-SELECTION; VACCINE CANDIDATE; MINIMAL VARIATION; SEXUAL STAGE; BERGHEI; PROTEIN; POLYMORPHISM C1 Univ Queensland, PO Royal Melbourne Hosp, Brisbane, Qld 4029, Australia. Queensland Inst Med Res, Malaria & Arbovirus Unit, Brisbane, Qld 4029, Australia. RP Saul, A (reprint author), NIAID, Malaria Vaccine Dev Unit, LPD, NIH, Twinbrook 2 Room 103,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Cloonan, Nicole/B-5272-2008; Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 32 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD OCT PY 2000 VL 110 IS 2 BP 429 EP 434 DI 10.1016/S0166-6851(00)00285-1 PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 360XD UT WOS:000089691900023 PM 11071297 ER PT J AU Rojo, S Stebbins, CC Peterson, ME Dombrowicz, D Wagtmann, N Long, EO AF Rojo, S Stebbins, CC Peterson, ME Dombrowicz, D Wagtmann, N Long, EO TI Natural killer cells and mast cells from gp49B null mutant mice are functional SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INHIBITORY RECEPTORS; NK CELLS; HLA-B; GENE; ANAPHYLAXIS; DISRUPTION; ACTIVATION; PATHWAY AB Immune responses are controlled by a combination of positive and negative cellular signals. Effector cells in the immune system express inhibitory receptors that serve to limit effector cell expansion and to protect the host from autoreactivity. gp49B is a receptor of unknown function that is expressed on activated mast cells and natural killer (NK) cells and whose cytoplasmic tail endows it with inhibitory potential. To gain insight into the function of gp49B in mice, we disrupted the gp49B gene by homologous recombination. gp49B(0) mice were born at expected ratios, were healthy and fertile, and displayed normal long-term survival rates. gp49B(0) mice showed no defect in NK or mast cell development. Furthermore, NK and mast cells from the gp49B(0) mice showed activation properties in vitro similar to those of cells isolated from wild-type mice. Therefore, gp49B is not critical for the development, expansion, and maturation of mast cells and NK cells in vivo. The healthy status of gp49B(0) mice makes them suitable for testing the role of gp49B in immune responses to infectious agents. C1 NIAID, LIG, NIH, Rockville, MD 20852 USA. Inst Pasteur, Ctr Immunol & Biol Parasitaire, F-59019 Lille, France. RP Long, EO (reprint author), NIAID, LIG, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011; Dombrowicz, David/F-7044-2013 OI Long, Eric/0000-0002-7793-3728; Dombrowicz, David/0000-0002-0485-8923 NR 17 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2000 VL 20 IS 19 BP 7178 EP 7182 DI 10.1128/MCB.20.19.7178-7182.2000 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353HL UT WOS:000089268700014 PM 10982834 ER PT J AU Choi, SK Olsen, DS Roll-Mecak, A Martung, A Remo, KL Burley, SK Hinnebusch, AG Dever, TE AF Choi, SK Olsen, DS Roll-Mecak, A Martung, A Remo, KL Burley, SK Hinnebusch, AG Dever, TE TI Physical and functional interaction between the eukaryotic orthologs of prokaryotic translation initiation factors IF1 and IF2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAMMALIAN PROTEIN-SYNTHESIS; ELONGATION-FACTOR-G; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; SHUTTLE VECTORS; COMPLEX-FORMATION; TERNARY COMPLEX; TRANSFER-RNA; FACTOR 1A; P-SITE AB To initiate protein synthesis, a ribosome with bound initiator methionyl-tRNA must be assembled at the start codon of an mRNA. This process requires the coordinated activities of three translation initiation factors (IF) in prokaryotes and at least 12 translation initiation factors in eukaryotes (eIF). The factors eIF1A and eIF5B front eukaryotes show extensive amino acid sequence similarity to the factors IF1 and IF2 from prokaryotes. By a combination of two-hybrid, coimmunoprecipitation, and in vitro binding assays eIF1A and eIF5B were found to interact directly, and the eIF1A binding site was mapped to the C-terminal region of eIF5B. This portion of eIF5B was found to be critical for growth in vivo and for translation in vitro. Overexpression of eIF1A exacerbated the slow-growth phenotype of yeast strains expressing C-terminally truncated eIF5B. These findings indicate that the physical interaction between the evolutionarily conserved factors eIF1A and eIF5B plays an important role in translation initiation, perhaps to direct or stabilize the binding of methionyl-tRNA to the ribosomal P site. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Dever, TE (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, 6 Ctr Dr,Bldg 6A Rm B1A-02, Bethesda, MD 20892 USA. NR 45 TC 62 Z9 64 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2000 VL 20 IS 19 BP 7183 EP 7191 DI 10.1128/MCB.20.19.7183-7191.2000 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353HL UT WOS:000089268700015 PM 10982835 ER PT J AU Chen, SS Chen, JF Johnson, PF Muppala, V Lee, YH AF Chen, SS Chen, JF Johnson, PF Muppala, V Lee, YH TI C/EBP beta, when expressed from the C/ebp alpha gene locus, can functionally replace C/EBP alpha in liver but not in adipose tissue SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ADIPOCYTE DIFFERENTIATION; STRUCTURAL ORGANIZATION; TRANSCRIPTIONAL CONTROL; CYSTEINE DIOXYGENASE; ADIPOGENESIS; PROTEINS; ADIPSIN; OBESITY; FAMILY; CELLS AB Knockout of C/EBP alpha causes a severe loss of liver function and, subsequently, neonatal lethality in mire. By using a gene replacement approach, we generated a new C/EBP alpha-null mouse strain in which C/EBP beta, in addition to its own expression, substituted for C/EBP alpha expression in tissues. The homozygous mutant mice C/ebp alpha(beta/beta) are viable and fertile and show none of the overt liver abnormalities found in the previous C/EBP alpha-null mouse line. Levels of hepatic PEPCK mRNA are not different between C/ebp alpha(beta/beta) and wild-type mice. However, despite their normal growth rate, C/ebp alpha(beta/beta) mice have markedly reduced fat storage in their white adipose tissue (WAT). Expression of two adipocyte-specific factors, adipsin and leptin, is significantly reduced in the WAT of C/ebp alpha(beta/beta) mice. In addition, expression of the non-adipocyte-specific genes for transferrin and cysteine dioxygenase is reduced in WAT but not in liver. Our study demonstrates that when expressed from the C/ebp alpha gene locus, C/EBP beta can act for C/EBP alpha to maintain liver functions during development. Moreover, our studies with the C/ebp alpha(beta/beta) mice provide new insights into the nonredundant functions of C/EBP alpha and C/EBP beta on gene regulation in WAT. C1 Acad Sinica, Inst Mol Biol, Lab Mol Pathol, Taipei 115, Taiwan. NCI, Eukaryot Transcript Regulat Sect, Regulat Cell Growth Lab, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Lee, YH (reprint author), Acad Sinica, Inst Mol Biol, Lab Mol Pathol, Taipei 115, Taiwan. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 26 TC 70 Z9 76 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2000 VL 20 IS 19 BP 7292 EP 7299 DI 10.1128/MCB.20.19.7292-7299.2000 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353HL UT WOS:000089268700026 PM 10982846 ER PT J AU Nemoto, S Takeda, K Yu, ZX Ferrans, VJ Finkel, T AF Nemoto, S Takeda, K Yu, ZX Ferrans, VJ Finkel, T TI Role for mitochondrial oxidants as regulators of cellular metabolism SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; N-TERMINAL KINASE; HYDROGEN-PEROXIDE; SIGNAL-TRANSDUCTION; GLYCOGEN-SYNTHASE; OXYGEN RADICALS; TYROSINE PHOSPHORYLATION; OXIDATIVE STRESS; ANGIOTENSIN-II AB Leakage of mitochondrial oxidants contributes to a variety of harmful conditions ranging from neurodegenerative diseases to cellular senescence. We describe here, however, a physiological and heretofore unrecognized role for mitochondrial oxidant release. Mitochondrial metabolism of pyruvate is demonstrated to activate the c-Jun N-terminal kinase (JNK). This metabolite-induced rise in cytosolic JNK1 activity is shown to be triggered by increased release of mitochondrial H2O2. We further demonstrate that in turn, the redox-dependent activation of JNK1 feeds back and inhibits the activity of the metabolic enzymes glycogen synthase kinase 3 beta and glycogen synthase. As such, these results demonstrate a novel metabolic regulatory pathway activated by mitochondrial oxidants. In addition, they suggest that although chronic oxidant production may have deleterious effects, mitochondrial oxidants can also function acutely as signaling molecules to provide communication between the mitochondria and the cytosol. C1 NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Mol Biol Lab, NIH, Bldg 10-6N-240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 42 TC 248 Z9 254 U1 4 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2000 VL 20 IS 19 BP 7311 EP 7318 DI 10.1128/MCB.20.19.7311-7318.2000 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353HL UT WOS:000089268700028 PM 10982848 ER PT J AU Vitale, N Ferrans, VJ Moss, J Vaughan, M AF Vitale, N Ferrans, VJ Moss, J Vaughan, M TI Identification of lysosomal and Golgi localization signals in GAP and ARF domains of ARF domain protein 1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RIBOSYLATION FACTOR DOMAIN; GTPASE-ACTIVATING PROTEIN; INTEGRAL MEMBRANE-PROTEIN; CHROMAFFIN CELLS; REGULATED EXOCYTOSIS; PLASMA-MEMBRANE; MOLECULAR CHARACTERIZATION; INTRACELLULAR TRAFFICKING; CYTOPLASMIC DOMAIN; NETWORK AB ADP ribosylation factors (ARFs) are similar to 20-kDa guanine nucleotide-binding proteins that activate cholera toxin and phospholipase D and are critical components of vesicular trafficking pathways. ARF domain protein 1 (ARD1), a member of the ARF superfamily, contains a 46-kDa amino-terminal extension, which acts as a GTPase-activating protein (GAP) with activity towards its ARF domain. When overexpressed, ARD1 was associated with lysosomes and the Golgi apparatus. In agreement with this finding, lysosomal and Golgi membranes isolated from human liver by immunoaffinity contained native ARD1, ARD1, expressed as a green fluorescent fusion protein, was initially associated with the Golgi network and subsequently appeared on lysosomes, suggesting that ARD1 might undergo vectorial transport between the two organelles. Here we show by microscopic colocalization that GAP and ARF domains determine lysosomal and Golgi localization, respectively, consistent with the presence of more than one signal motif. Using truncated ARD1 molecules, expressed as green fluorescent fusion proteins, it was found that the signal for lysosomal localization was present in residues 301 to 402 of the GAP domain. Site-specific mutagenesis demonstrated that the sequence (369)KXXXQ(373) in the GAP domain was responsible for lysosomal localization. Association of ARD1 with the Golgi apparatus required tyrosine-based motifs. A green fluorescent fusion protein containing the QKQQQQF motif was partially associated with lysosomes, suggesting that this motif contains the information sufficient for lysosomal targeting. These results suggest that ARD1 is a multidomain protein with ARF and GAP regions, which contain Golgi and lysosomal localization signals, respectively, that could function in vesicular trafficking. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Room 6D03,10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 47 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2000 VL 20 IS 19 BP 7342 EP 7352 DI 10.1128/MCB.20.19.7342-7352.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353HL UT WOS:000089268700031 PM 10982851 ER PT J AU Dang, VD Levin, HL AF Dang, VD Levin, HL TI Nuclear import of the retrotransposon Tf1 is governed by a nuclear localization signal that possesses a unique requirement for the FXFG nuclear pore factor Nup124p SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID VIRAL MATRIX PROTEIN; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; REVERSE TRANSCRIPTION; MACROPHAGE INFECTION; NONDIVIDING CELLS; HIV-1 INFECTION; VPR PROTEIN; COMPLEX; DNA AB Retroviruses, such as human immunodeficiency virus, that infect nondividing cells generate integration precursors that must cross the nuclear envelope to reach the host genome. As a model for retroviruses, we investigated the nuclear entry of Tf1, a long-terminal-repeat-containing retrotransposon of the fission yeast Schizosaccharomyces pombe. Because the nuclear envelope of yeasts remains intact throughout the cell cycle, components of Tf1 must be transported through the envelope before integration can occur. The nuclear localization of the Gag protein of Tf1 is different from that of other proteins tested in that it has a specific requirement for the FXFG nuclear pore factor, Nup124p. Using extensive mutagenesis, we found that Gag contained three nuclear localization signals (NLSs) which, when included individually in a heterologous protein, were sufficient to direct nuclear import. In the context of the intact transposon, mutations in the NLS that mapped to the first 10 amino acid residues of Gag significantly impaired Tf1 retrotransposition and abolished nuclear localization of Gag. Interestingly, this NLS activity in the heterologous protein was specifically dependent upon the presence of Nup124p. Deletion analysis of heterologous proteins revealed the surprising result that the residues in Gag with the NLS activity were independent from the residues that conveyed the requirement for Nup124p. In fact, a fragment of Gag that lacked NLS activity, residues 10 to 30, when fused to a heterologous protein, was sufficient to cause the classical NLS of simian virus 40 to require Nup124p for nuclear import. Within the context of the current understanding of nuclear import, these results represent the novel case of a short amino acid sequence that specifies the need for a particular nuclear pore complex protein. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. EM Henry_Levin@nih.gov NR 53 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2000 VL 20 IS 20 BP 7798 EP 7812 DI 10.1128/MCB.20.20.7798-7812.2000 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 357MB UT WOS:000089504500036 PM 11003674 ER PT J AU Barrientos, A Muller, S Dey, R Wienberg, J Moraes, CT AF Barrientos, A Muller, S Dey, R Wienberg, J Moraes, CT TI Cytochrome c oxidase assembly in primates is sensitive to small evolutionary variations in amino acid sequence SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE mtDNA; mitochondria; COX; hybrids; evolution ID STEADY-STATE LEVELS; MITOCHONDRIAL-DNA; XENOMITOCHONDRIAL CYBRIDS; MOLECULAR EVOLUTION; HUMAN FIBROBLASTS; HYBRID-CELLS; SUBUNIT-II; DISEASE; MUTATION; MTDNA AB Respiring mitochondria require many interactions between nuclear and mitochondrial genomes. Although mitochondrial DNA (mtDNA) from the gorilla and the chimpanzee are able to restore oxidative phosphorylation in a human cell, mtDNAs from more distant primate species are functionally incompatible with human nuclear genes. Using microcell-mediated chromosome and mitochondria transfer, we introduced and maintained a functional orangutan mtDNA in a human nuclear background. However, partial oxidative phosphorylation function was restored only in the presence of most orangutan chromosomes, suggesting that human oxidative phosphorylation-related nuclear-coded genes are not able to replace many orangutan ones. The respiratory capacity of these hybrids was decreased by 65%-80%, and cytochrome c oxidase (COX) activity was decreased by 85%-95%. The function of other respiratory complexes was not significantly altered. The translation of mtDNA-coded COX subunits was normal, but their steady-state levels were similar to 10% of normal ones. Nuclear-coded COX subunits were loosely associated with mitochondrial membranes, a characteristic of COX assembly-defective mutants. Our results suggest that many human nuclear-coded genes not only cannot replace the orangutan counterparts, but also exert a specific interference at the level of COX assembly. This cellular model underscores the precision of COX assembly in mammals and sheds light on the nature of nuclear-mtDNA coevolutionary constraints. C1 Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA. Univ Munich, Inst Anthropol & Humangenet, Munich, Germany. NCI, Lab Genom Divers, Frederick, MD USA. Univ Miami, Sch Med, Dept Cell Biol & Anat, Miami, FL 33136 USA. RP Moraes, CT (reprint author), Univ Miami, Sch Med, Dept Neurol, 1501 NW 9th Ave, Miami, FL 33136 USA. FU NIGMS NIH HHS [GM55766] NR 44 TC 37 Z9 37 U1 1 U2 1 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD OCT PY 2000 VL 17 IS 10 BP 1508 EP 1519 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 360MH UT WOS:000089671400009 PM 11018157 ER PT J AU Wu, KC Bryan, JT Morasso, MI Jang, SI Lee, JH Yang, JM Marekov, LN Parry, DAD Steinert, PM AF Wu, KC Bryan, JT Morasso, MI Jang, SI Lee, JH Yang, JM Marekov, LN Parry, DAD Steinert, PM TI Coiled-coil trigger motifs in the 1B and 2B rod domain segments are required for the stability of keratin intermediate filaments SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID LEUCINE-ZIPPER; CROSS-LINKING; ION-PAIRS; MOLECULES; MECHANISM; VIMENTIN; RESIDUE; SPECIFICITY; PROTEINS; DISEASE AB Many alpha-helical proteins that form two-chain coiled coils possess a 13-residue trigger motif that seems to be required for the stability of the coiled coil. However, as currently defined, the motif is absent from intermediate filament (IF) protein chains, which nevertheless form segmented two-chain coiled coils. Ln the present work, we have searched for and identified two regions in IF chains that are essential for the stability necessary for the formation of coiled-coil molecules and thus may function as trigger motifs. We made a series of point substitutions with the keratin 5/keratin 14 IF system. Combinations of the wild-type and mutant chains were assembled in vitro and in vivo, and the stabilities of two-chain (one-molecule) and two-molecule assemblies were examined with use of a urea disassembly assay. Our new data document that there is a region located between residues 100 and 113 of the 2B rod domain segment that is absolutely required for molecular stability and IF assembly. This potential trigger motif differs slightly from the consensus in having an Asp residue at position 4 (instead of a Glu) and a Thr residue at position 9 (instead of a charged residue), but there is an absolute requirement for a Glu residue at position 6. Because these 13 residues are highly conserved, it seems possible that this motif functions in all IF chains. Likewise, by testing keratin IF with substitutions in both chains, we identified a second potential trigger motif between residues 79 and 91 of the 1B rod domain segment, which may also be conserved in all IF chains. However, we were unable to find a trigger motif in the 1A rod domain segment. In addition, many other point substitutions had little detectable effect on IF assembly, except for the conserved Lys-23 residue of the 2B rod domain segment. Cross-linking and modeling studies revealed that Lys-23 may lie very close to Glu-106 when two molecules are aligned in the A(22) mode. Thus, the Glu-106 residue may have a dual role in IF structure: it may participate in trigger formation to afford special stability to the two-chain coiled-coil molecule, and it may participate in stabilization of the two-molecule hierarchical stage of IF structure. C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Chungnam Natl Univ Hosp, Dept Dermatol, Taejon, South Korea. Sungkyunkwan Univ, Sch Med, Clin Res Ctr, Dept Dermatol,Samsung Biomed Res Inst, Seoul 135710, South Korea. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. RP Steinert, PM (reprint author), NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. EM pemast@helix.nih.gov FU NIAMS NIH HHS [Z01 AR041124-06] NR 37 TC 62 Z9 63 U1 1 U2 10 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2000 VL 11 IS 10 BP 3539 EP 3558 PG 20 WC Cell Biology SC Cell Biology GA 363KL UT WOS:000089834800022 PM 11029054 ER PT J AU Wei, QZ Adelstein, RS AF Wei, QZ Adelstein, RS TI Conditional expression of a truncated fragment of nonmuscle myosin II-A alters cell shape but not cytokinesis in HeLa cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID REGULATORY LIGHT-CHAIN; HEAVY-CHAIN; FOCAL ADHESIONS; MESSENGER-RNAS; CULTURED-CELLS; STRESS FIBERS; PHOSPHORYLATION; ISOFORMS; LOCALIZATION; FIBROBLASTS AB A truncated fragment of the nonmuscle myosin II-A heavy chain (NMHC II-A) lacking amino acids 1-591, Delta N592, was used to examine the cellular functions of this protein. Green fluorescent protein (GFP) was fused to the amino terminus of full-length human NMHC II-A, NMHC II-B, and Delta N592 and the fusion proteins were stably expressed in HeLa cells by using a conditional expression system requiring absence of doxycycline. The HeLa cell line studied normally expressed only NMHC II-A and not NMHC II-B protein. Confocal microscopy indicated that the GFP fusion proteins of full-length NMHC II-A, II-B, and Delta N592 were localized to stress fibers. However, in vitro assays showed that baculovirus-expressed Delta N592 did not bind to actin, suggesting that Delta N592 was localized to actin stress fibers through incorporation into endogenous myosin filaments. There was no evidence for the formation of heterodimers between the full-length endogenous nonmuscle myosin and truncated nonmuscle MHCs. Expression of Delta N592, but not full-length NMHC II-A or NMHC II-B, induced cell rounding with rearrangement of actin filaments and disappearance of focal adhesions. These cells returned to their normal morphology when expression of Delta N592 was repressed by addition of doxycycline. We also show that GFP-tagged full-length NMHC II-A or II-B, but not Delta N592, were localized to the cytokinetic ring during mitosis, indicating that, in vertebrates, the amino-terminus part of mammalian nonmuscle myosin II may be necessary for localization to the cytokinetic ring. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 38 TC 118 Z9 119 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2000 VL 11 IS 10 BP 3617 EP 3627 PG 11 WC Cell Biology SC Cell Biology GA 363KL UT WOS:000089834800027 PM 11029059 ER PT J AU Field, KA Apgar, JR Hong-Geller, E Siraganian, RP Baird, B Holowka, D AF Field, KA Apgar, JR Hong-Geller, E Siraganian, RP Baird, B Holowka, D TI Mutant RBL mast cells defective in Fc epsilon RI signaling and lipid raft biosynthesis are reconstituted by activated Rho-family GTPases SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; PHOSPHOLIPASE-D ACTIVITY; PROTEIN-TYROSINE KINASE; EXCHANGE FACTOR VAV; RBL-2H3 CELLS; IGE RECEPTOR; ADENOSINE RECEPTOR; MEMBRANE DOMAINS; ANTIGEN RECEPTOR; MDCK CELLS AB Characterization of defects in a variant subline of RBL mast cells has revealed a biochemical event proximal to IgE receptor (Fc epsilon RI)-stimulated tyrosine phosphorylation that is required for multiple functional responses. This cell line, designated B6A4C1, is deficient in both Fc epsilon RI-mediated degranulation and biosynthesis of several lipid raft components. Agents that by-pass receptor-mediated Ca2+ influx stimulate strong degranulation responses in these variant cells. Cross linking of IgE-Fc epsilon RI on these cells stimulates robust tyrosine phosphorylation but fails to mobilize a sustained Ca2+ response. Fc epsilon RI-mediated inositol phosphate production is not detectable in these cells, and failure of adenosine receptors to mobilize Ca2+ suggests a general deficiency in stimulated phospholipase C activity. Antigen stimulation of phospholipases A(2) and D is also defective. Infection of B6A4C1 cells with vaccinia virus constructs expressing constitutively active Rho family members Cdc42 and Rac restores antigen-stimulated degranulation, and active Cdc42 (but not active Rac) restores ganglioside and GPI expression, The results support the hypothesis that activation of Cdc42 and/or Rac is critical for Fc epsilon RI-mediated signaling that leads to Ca2+ mobilization and degranulation. Furthermore, they suggest that Cdc42 plays an important role in the biosynthesis and expression of certain components of lipid rafts. C1 Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY USA. Scripps Res Inst, La Jolla, CA 92093 USA. Cornell Univ, Dept Mol Med, Ithaca, NY 14853 USA. NIDCR, NIH, Bethesda, MD 21814 USA. RP Holowka, D (reprint author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY USA. FU NIAID NIH HHS [AI22449, R01 AI022449, AI42244]; NIGMS NIH HHS [GM42388] NR 58 TC 34 Z9 35 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2000 VL 11 IS 10 BP 3661 EP 3673 PG 13 WC Cell Biology SC Cell Biology GA 363KL UT WOS:000089834800030 PM 11029062 ER PT J AU Shen, JC Klein, RD Wei, QY Guan, YL Contois, JH Wang, TTY Chang, S Hursting, SD AF Shen, JC Klein, RD Wei, QY Guan, YL Contois, JH Wang, TTY Chang, S Hursting, SD TI Low-dose genistein induces cyclin-dependent kinase inhibitors and G(1) cell-cycle arrest in human prostate cancer cells SO MOLECULAR CARCINOGENESIS LA English DT Article DE isoflavone; LNCaP; p27(KIP1); p21(WAF1) ID IN-VITRO; PHYTOESTROGEN INTAKE; HUMAN-LYMPHOCYTES; DNA-REPLICATION; JAPANESE MEN; BIOCHANIN-A; GROWTH; PROTEIN; EXPRESSION; APOPTOSIS AB Genistein, a naturally occurring isoflavone found chiefly in soy products, reportedly has antiprostate cancer effects, but the mechanisms underlying these effects are unknown. We studied the antiproliferative and apoptosis-inducing effects of genistein in the androgen-sensitive human prostate cancer cell line LNCaP. Viable cell number was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell-cycle progression and apoptosis were evaluated by flow cytometry; apoptosis was also assessed by a histone enzyme-linked immunosorbent assay; and the expression of several cell-cycle- and apoptosis-related genes and their gene products was determined by northern blot analysis, western blot analysis, and/or assays based on polymerase chain reaction. Physiologic concentrations of genistein (less than or equal to 20 muM) decreased LNCaP viable cell number in a dose-dependent manner, induced a G(1) cell-cycle block, decreased prostate-specific antigen mRNA expression, and increased p27(KIP1) and p21(WAF1) (mRNA and protein) but had no effect on apoptosis or the mRNA expression of the apoptosis- and cell-cycle-related markers bcl-2, bax, Rb, and proliferating cell nuclear antigen. Higher concentrations of genistein (>20 muM) did induce apoptosis. We conclude that genistein (at physiologic concentrations) exerts potent antiproliferative effects on LNCaP cells by inducing a G(1) cell-cycle block. The antiproliferative effects of genistein may be mediated by increased levels of p27(KIP1) and p21(WAF1), which are negative cell-cycle regulators that act as cyclin-dependent kinase inhibitors and that have been recently linked with prostate carcinogenesis. These findings may provide insights into the mechanisms underlying the apparent antiprostate cancer effects of soy consumption observed in epidemiologic studies. Mol. Carcinog. 29:92-102, 2000. (C) 2000 Wiley-Liss. Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Houston, TX 77030 USA. USDA, Phytonutrients Lab, Beltsville, MD 20705 USA. RP Hursting, SD (reprint author), NCI, Off Prevent Oncol, 6130 Execut Blvd,EPS T-41,MSC 7105, Bethesda, MD 20892 USA. FU NCI NIH HHS [P30 CA166720]; NIEHS NIH HHS [P30 ES07784] NR 56 TC 88 Z9 93 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 2000 VL 29 IS 2 BP 92 EP 102 DI 10.1002/1098-2744(200010)29:2<92::AID-MC6>3.0.CO;2-Q PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 371DG UT WOS:000165162300006 PM 11074606 ER PT J AU Kang, Y Mariano, JM Angdisen, J Moody, TW Diwan, BA Wakefield, LM Jakowlew, SB AF Kang, Y Mariano, JM Angdisen, J Moody, TW Diwan, BA Wakefield, LM Jakowlew, SB TI Enhanced tumorigenesis and reduced transforming growth factor-beta type II receptor in lung tumors from mice with reduced gene dosage of transforming growth factor-beta 1 SO MOLECULAR CARCINOGENESIS LA English DT Article DE transforming growth factor-beta; receptor; lung carcinogenesis; mouse; tumor ID STRAIN-A MICE; TGF-BETA; MOUSE LUNG; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; CARCINOMA-CELLS; DECREASED EXPRESSION; PULMONARY NEOPLASMS; SUPPRESSOR GENE; DOWN-REGULATION AB To elucidate the role of transforming growth factor-beta1 (TGF-beta1) and the TGF-beta type II receptor (TGF-beta RII)as tumor-suppressor genes in lung carcinogenesis, we mated C57BL/6 mice heterozygous (HT) for deletion of the TGF-beta1 gene with A/J mice to produce AJBL6 TGF-beta1 HT progeny and their wild-type (WT) littermates. Immunohistochemical staining, in situ hybridization, and northern blot analyses showed lower staining and hybridization for TGF-beta1 protein and mRNA, respectively, in the lungs of normal HT mice versus WT mice. Competitive reverse transcription-polymerase chain reaction (CRT-PCR) amplification showed the level of TGF-beta1 mRNA in the lungs of HT mice to be fourfold lower than the level in WT lung. When challenged with ethyl carbamate, lung adenomas were detected in 55% of HT mice by 4 mo but only in 25% of WT littermates at this time. Whereas all HT mice had adenomas by 6 mo, it was not until 10 mo before all WT mice had adenomas. After 12 mo, the average number of adenomas was fivefold higher in HT lungs than in WT lungs. Most dramatic was the appearance of lung carcinomas in HT mice 8 mo before they were visible in WT mice. Thus, the AJBL6 TGF-beta1 HT mouse provides an excellent model system to examine carcinogen-induced lung tumorigenesis by increasing progressive lesion incidence and multiplicity relative to their WT littermates. Immunohistochemical staining showed expression of the TGF-beta type I receptor (TGF-beta RI) at moderate to strong levels in lung adenomas and carcinomas in HT and WT mice. In contrast, whereas weak immunostaining for TGF-beta RII was detected in 67% of HT carcinomas at 12 mo, only 22% of WT carcinomas showed weak staining for this protein. individual lung carcinomas showing reduced TGF-beta RII expression and adjacent normal bronchioles were excised from HT lungs using laser capture microdissection, and CRT-PCR amplification of the extracted RNA showed 12-fold less TGF-beta RII mRNA in these carcinomas compared with bronchioles. Decreasing TGF-beta RII mRNA levels occurred with increasing tumorigenesis in lung hyperplasias, adenomas, and carcinomas, with carcinomas having fourfold and sevenfold lower levels of TGF-beta RII mRNA than adenomas and hyperplasias, respectively. These data show enhanced ethyl carbamate-induced lung tumorigenesis in AJBL6 HT mice compared with WT mice, suggesting that both TGF-beta1 alleles are necessary for tumor-suppressor activity. Reduction of TGF-beta RII mRNA expression in progressive stages of lung tumorigenesis in HT mice suggests that loss of TGF-beta RII may play an important role in the promotion of lung carcinogenesis in mice with reduced TGF-beta1 gene dosage when challenged with carcinogen. Mol. Carcinog. 29:112-126, 2000. Published 2000 Wiley-Liss. Inc.(dagger). C1 NCI, Med Branch, Dept Cell & Canc Biol, Rockville, MD 20850 USA. Comparat Carcinogenesis Lab, Frederick, MD USA. Lab Cell Regulat & Carcinogenesis, Bethesda, MD USA. RP Jakowlew, SB (reprint author), NCI, Med Branch, Dept Cell & Canc Biol, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 66 TC 21 Z9 22 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 2000 VL 29 IS 2 BP 112 EP 126 DI 10.1002/1098-2744(200010)29:2<112::AID-MC8>3.0.CO;2-9 PG 15 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 371DG UT WOS:000165162300008 PM 11074608 ER PT J AU Dhillon, N Kamakaka, RT AF Dhillon, N Kamakaka, RT TI A histone variant, Htz1p, and a Sir1p-like protein, Esc2p, mediate silencing at HMR SO MOLECULAR CELL LA English DT Article ID ORIGIN RECOGNITION COMPLEX; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONALLY COMPETENT; SHUTTLE VECTORS; DNA-REPLICATION; MATING LOCI; YEAST GENES; CHROMATIN; SIR1; INHERITANCE AB Silencing at HMR requires silencers, and one of the roles of the silencer is to recruit Sir proteins. This work focuses on the function of Sir1p once it is recruited to the silencer. We have generated mutants of Sir1p that are recruited to the silencer but are unable to silence, and we have utilized these mutants to identify four proteins, Sir3p, Sir4p, Esc2p, and Htz1p, that when overexpressed, restored silencing. The isolation of Sir3p and Sir4p validated this screen. Molecular analysis suggested that Esc2p contributed to silencing in a manner similar to Sir1p and probably helped recruit or stabilize the other Sir proteins, while Htz1p present at HMR assembled a specialized chromatin structure necessary for silencing. C1 NICHD, Unit Chromatin & Transcript, NIH, Bethesda, MD 20892 USA. RP NICHD, Unit Chromatin & Transcript, NIH, 18 Lib Dr, Bethesda, MD 20892 USA. EM rohinton@helix.nih.gov NR 50 TC 113 Z9 119 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD OCT PY 2000 VL 6 IS 4 BP 769 EP 780 DI 10.1016/S1097-2765(00)00076-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368UW UT WOS:000090136700002 PM 11090616 ER PT J AU Chastain, PD Makhov, AM Nossal, NG Griffith, JD AF Chastain, PD Makhov, AM Nossal, NG Griffith, JD TI Analysis of the Okazaki fragment distributions along single long DNAs replicated by the bacteriophage T4 proteins SO MOLECULAR CELL LA English DT Article ID COORDINATED LEADING-STRAND; POLYMERASE; FORK; HOLOENZYME; PRIMASE; HELICASE; INVITRO; SYSTEM; SIZE AB Rolling circle replication from M13 DNA circles was previously reconstituted in vitro using purified factors encoded by bacteriophage T4. The products are duplex circles with linear tails >100 kb. When T4 DNA polymerase deficient in 3' to 5' exonuclease activity was employed, electron microscopy revealed short single-stranded DNA "flaps" along the replicated tails. This marked the beginning of each Okazaki fragment, allowing an analysis of the lengths of sequential Okazaki fragments on individual replicating molecules. DNAs containing runs of Okazaki fragments of similar length were found, but most showed large length variations over runs of six or more fragments reflecting the broad population distribution. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Griffith, JD (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA19014, CA70343]; NIGMS NIH HHS [GM31819] NR 29 TC 27 Z9 27 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD OCT PY 2000 VL 6 IS 4 BP 803 EP 814 DI 10.1016/S1097-2765(00)00081-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368UW UT WOS:000090136700005 PM 11090619 ER PT J AU Fidock, DA Nomura, T Talley, AK Cooper, RA Dzekunov, SM Ferdig, MT Ursos, LMB Sidhu, ABS Naude, B Deitsch, KW Su, XZ Wootton, JC Roepe, PD Wellems, TE AF Fidock, DA Nomura, T Talley, AK Cooper, RA Dzekunov, SM Ferdig, MT Ursos, LMB Sidhu, ABS Naude, B Deitsch, KW Su, XZ Wootton, JC Roepe, PD Wellems, TE TI Mutations in the P-falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance SO MOLECULAR CELL LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; HUMAN DIHYDROFOLATE-REDUCTASE; MALARIA PARASITES; PYRIMETHAMINE; REVERSAL; TRANSFORMATION; ANTIMALARIALS; TRANSFECTION; EXPRESSION; PROGUANIL AB The determinant of verapamil-reversible chloroquine resistance (CQR) in a Plasmodium falciparum genetic cross maps to a 36 kb segment of chromosome 7. This segment harbors a 13-exon gene, pfcrt, having point mutations that associate completely with CQR in parasite lines from Asia, Africa, and South America. These data, transfection results, and selection of a CQR line harboring a novel K761 mutation point to a central role for the PfCRT protein in CQR. This transmembrane protein localizes to the parasite digestive vacuole (DV), the site of Co action, where increased compartment acidification associates with PfCRT point mutations. Mutations in PfCRT may result in altered chloroquine flux or reduced drug binding to hematin through an effect on DV pH. C1 NIAID, NIH, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Georgetown Univ, Lombardi Canc Ctr, Dept Chem, Washington, DC 20057 USA. Georgetown Univ, Lombardi Canc Ctr, Program Tumor Biol, Washington, DC 20057 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20984 USA. RP Wellems, TE (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. RI Ferdig, Michael/C-6627-2016; OI Fidock, David/0000-0001-6753-8938; Su, Xinzhuan/0000-0003-3246-3248 FU NIAID NIH HHS [R01 AI050234, R01 AI050234-01] NR 41 TC 867 Z9 899 U1 7 U2 134 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD OCT PY 2000 VL 6 IS 4 BP 861 EP 871 DI 10.1016/S1097-2765(05)00077-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368UW UT WOS:000090136700010 PM 11090624 ER PT J AU Uren, AG O'Rourke, K Aravind, L Pisabarro, MT Seshagiri, S Koonin, EV Dixit, VM AF Uren, AG O'Rourke, K Aravind, L Pisabarro, MT Seshagiri, S Koonin, EV Dixit, VM TI Identification of paracaspases and metacaspases: Two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma SO MOLECULAR CELL LA English DT Article ID B-CELL LYMPHOMA; TISSUE LYMPHOMAS; APOPTOSIS; DEATH; INHIBITOR; CANCER; BCL10; GENE AB Caspases are cysteine proteases essential to apoptosis. We have identified two families of caspase-like proteins, Paracaspases (found in metazoans and Dictyostelium) and metacaspases (found in plants, fungi, and protozoa). Metazoan paracaspase prodomains contain a death domain and immunoglobulin domains. Several plant metacaspase prodomains contain zinc finger motifs resembling those in the plant hypersensitive response/cell death protein Isd-1. The human paracaspase prodomain binds Bcl10, a protein involved in the t(1;14)(p22;q32) translocation of mucosa-associated lymphoid tissue (MALT) lymphoma. Another MALT lymphoma translocation, t(11;18)(q21;q21), fuses the IAP-2 gene to the MLT1/MALT1 locus, which encodes the human paracaspase. We find that this fusion activates NF-kappaB and that the caspase domain is required for this function, since mutation of the conserved catalytic cysteine attenuates NF-kappaB activation. C1 Genentech Inc, S San Francisco, CA 94080 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Dixit, VM (reprint author), Genentech Inc, 1 DNA Way, S San Francisco, CA 94080 USA. RI dixit, vishva/A-4496-2012; Pisabarro, M. Teresa/D-4270-2012 OI dixit, vishva/0000-0001-6983-0326; NR 18 TC 670 Z9 704 U1 8 U2 30 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD OCT PY 2000 VL 6 IS 4 BP 961 EP 967 DI 10.1016/S1097-2765(05)00086-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368UW UT WOS:000090136700020 PM 11090634 ER PT J AU Anderson, TJC Su, XZ Roddam, A Day, KP AF Anderson, TJC Su, XZ Roddam, A Day, KP TI Complex mutations in a high proportion of microsatellite loci from the protozoan parasite Plasmodium falciparum SO MOLECULAR ECOLOGY LA English DT Article DE heterozygosity; malaria; microsatellite; Plasmodium falciparum; stepwise mutation ID DROSOPHILA-MELANOGASTER; ALLELE FREQUENCIES; NATURAL-SELECTION; GENETIC DISTANCES; LENGTH VARIATION; REPEATS; TRINUCLEOTIDE; EVOLUTION; DINUCLEOTIDE; POPULATIONS AB Microsatellite loci are generally assumed to evolve via a stepwise mutational process and a battery of statistical techniques has been developed in recent years based on this or related mutation models. It is therefore important to investigate the appropriateness of these models in a wide variety of taxa. We used two approaches to examine mutation patterns in the malaria parasite Plasmodium falciparum: (i) we examined sequence variation at 12 tri-nucleotide repeat loci; and (ii) we analysed patterns of repeat structure and heterozygosity at 114 loci using data from 12 laboratory parasite lines. The sequencing study revealed complex patterns of mutation in five of the 12 loci studied. Alleles at two loci contain indels of 24 bp and 57 bp in flanking regions, while in the other three loci, blocks of imperfect microsatellites appear to be duplicated or inserted; these loci essentially consist of minisatellite repeats, with each repeat unit containing four to eight microsatellites. The survey of heterozygosity revealed a positive relationship between repeat number and microsatellite variability for both di- and trinucleotides, indicating a higher mutation rate in loci with longer repeat arrays. Comparisons of levels of variation in different repeat types indicate that the mutation rate of dinucleotide-bearing loci is 1.6-2.1 times faster than trinucleotides, consistent with the lower mean number of repeats in trinucleotide-bearing loci. However despite the evidence that microsatellite arrays themselves are evolving in a manner consistent with stepwise mutation model in P. falciparum, the high frequency of complex mutations precludes the use of analytical tools based on this mutation model for many microsatellite-bearing loci in this protozoan. The results call into question the generality of models based on stepwise mutation for analysing microsatellite data, but also demonstrate the ease with which loci that violate model assumptions can be detected using minimal sequencing effort. C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, Dept Zool, Wellcome Trust Ctr Epidemiol Infect Dis, Oxford OX1 3PS, England. RP Anderson, TJC (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. RI Day, Karen/F-3697-2015; OI Day, Karen/0000-0002-6115-6135; Su, Xinzhuan/0000-0003-3246-3248 NR 35 TC 57 Z9 58 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0962-1083 J9 MOL ECOL JI Mol. Ecol. PD OCT PY 2000 VL 9 IS 10 BP 1599 EP 1608 DI 10.1046/j.1365-294x.2000.01057.x PG 10 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 366HC UT WOS:000089998600015 PM 11050555 ER PT J AU Tomita, S Sinal, CJ Yim, SH Gonzalez, FJ AF Tomita, S Sinal, CJ Yim, SH Gonzalez, FJ TI Conditional disruption of the aryl hydrocarbon receptor nuclear translocator (Arnt) gene leads to loss of target gene induction by the aryl hydrocarbon receptor and hypoxia-inducible factor 1 alpha SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; AH RECEPTOR; TRANSCRIPTION FACTOR; MESSENGER-RNA; MICE LACKING; MOUSE; SEQUENCE; PROTEIN; CLONING; CLOCK AB To determine the function of the aryl hydrocarbon receptor nuclear translocator (ARNT), a conditional gene knockout mouse was made using the Cre-loxP system. Exon 6, encoding the conserved basic-helix-loop-helix domain of the protein, was flanked by loxP sites and introduced into the Amt gene by standard gene disruption techniques using embryonic stem cells. Mice homozygous for the flexed allele were viable and had no readily observable phenotype. The Mx1-Cre transgene, in which Cre is under control of the interferon-gamma promoter, was introduced into the Arnt-floxed mouse line. Treatment with polyinosinic-polycytidylic acid to induce expression of Cre resulted in complete disruption of the Amt gene and loss of ARNT messenger RNA (mRNA) expression in liver. To determine the role of ARNT in gene control in the intact animal mouse liver, expression of target genes under control of an ARNT dimerization partner, the aryl hydrocarbon receptor (AHR), was monitored. Induction of CYP1A1, CYP1A2, and UGT1*06 mRNAs by the AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin was absent in livers of Arnt-floxed/Mx1-Cre mice treated with polyinosinic-polycytidylic. These data demonstrate that ARNT is required for AHR function in the intact animal. Partial deletion of the Amt allele was found in kidney, heart, intestine, and lung. Despite more than 80% loss of the ARNT expression in lung, maximal induction of CYP1A1 was found, indicating that the expression level of ARNT is not limiting to AHR signaling. Cobalt chloride induction of the glucose transporter-1 and heme oxygenase-1 mRNAs was also markedly abrogated in mice lacking ARNT expression, suggesting an inhibition of HIF-1 alpha activity. These studies establish a critical role for ARNT in AHR and HIF-1 alpha signal transduction in the intact mouse. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3E-24, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 31 TC 94 Z9 96 U1 2 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 2000 VL 14 IS 10 BP 1674 EP 1681 DI 10.1210/me.14.10.1674 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 359VR UT WOS:000089633200013 PM 11043581 ER PT J AU Leonard, WJ AF Leonard, WJ TI X-linked severe combined immunodeficiency: from molecular cause to gene therapy within seven years SO MOLECULAR MEDICINE TODAY LA English DT Review ID RECEPTOR-GAMMA CHAIN; LYMPHOID DEVELOPMENT; IL-2 RECEPTOR; MICE; PROLIFERATION; RESTORATION; EXPRESSION; MUTATION; JAK3 AB X-linked severe combined immunodeficiency (XSCID) is the most common form of SCID, The discovery of the genetic defect in this disease, namely mutations in the gene encoding the common cytokine receptor gamma chain, gamma(c), was reported just over seven years ago. In the subsequent period, a tremendous amount of knowledge about the biology and function of this protein has been generated. Moreover, gamma(c)-knockout mice have been generated and their immune systems successfully reconstituted by gene therapy, Furthermore, initial attempts at using gene therapy to treat patients with XSCID have been successful for more than ten months, making this disease perhaps the most promising to date for treatment with such a strategy. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 30 TC 17 Z9 17 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD OCT PY 2000 VL 6 IS 10 BP 403 EP 407 DI 10.1016/S1357-4310(00)01782-2 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 362FM UT WOS:000089768000009 PM 11006530 ER PT J AU Yarmolinsky, MB AF Yarmolinsky, MB TI A pot-pourri of plasmid paradoxes: effects of a second copy SO MOLECULAR MICROBIOLOGY LA English DT Review ID PROGRAMMED CELL-DEATH; SITE-SPECIFIC RECOMBINATION; COLE1 DIMER RESOLUTION; ESCHERICHIA-COLI; REPLICATION CONTROL; F-PLASMID; DNA; PROTEIN; NUMBER; ORIGINS AB Bacterial plasmids are exemplary subjects for study, being conveniently isolated, dissected, reassembled, and introduced into Various hosts. Their versatility and power make them eminently worthy of our attention. In what follows I consider some consequences of simply doubling the dosage of particular plasmid genes or of forming a plasmid dimer. These consequences can be perverse, paradoxical, or informative. They bear on questions of cell viability, copy number limitation, clonal homogeneity, checkpoint control, and the recovery of mutants. They have relevance to biotechnology, evolution and medicine. In reviewing these effects, my motivation is largely to share my enthusiasm for certain kinds of biological narratives, the nature of which is best left for the reader to discern. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Yarmolinsky, MB (reprint author), NCI, Biochem Lab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. NR 51 TC 5 Z9 6 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 2000 VL 38 IS 1 BP 1 EP 7 DI 10.1046/j.1365-2958.2000.02127.x PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 364FV UT WOS:000089882100001 PM 11029685 ER PT J AU Scheschonka, A Dessauer, CW Sinnarajah, S Chidiac, P Shi, CS Kehrl, JH AF Scheschonka, A Dessauer, CW Sinnarajah, S Chidiac, P Shi, CS Kehrl, JH TI RGS3 is a GTPase-activating protein for G(i alpha) and G(q alpha) and a potent inhibitor of signaling by GTPase-deficient forms of G(q alpha) and G(11 alpha) SO MOLECULAR PHARMACOLOGY LA English DT Article ID ALPHA-SUBUNITS; TRANSITION-STATE; ADENYLYL-CYCLASE; PHOSPHOLIPASE-C; FAMILY MEMBERS; REGULATOR; RECEPTORS; GAIP; HYDROLYSIS; MECHANISM AB Many Regulators of G protein Signaling (RGS) proteins accelerate the intrinsic GTPase activity of G(ia) and G(q alpha)-subunits [i.e., behave as GTPase-activating proteins (GAPs)] and several act as G(q alpha)-effector antagonists. RGS3, a structurally distinct RGS member with a unique N-terminal domain and a C-terminal RGS domain, and an N-terminally truncated version of RGS3 (RGS3CT) both stimulated the GTPase activity of G(i alpha) (except G(z alpha)) and G(q alpha) but not that of G(s alpha) or G(12 alpha). RGS3 and RGS3CT had G(q alpha) GAP activity similar to that of RGS4. RGS3 impaired signaling through G(q)-linked receptors, although RGS3CT invariably inhibited better than did full-length RGS3. RGS3 potently inhibited G(q alpha)Q209L- and G(11 alpha)Q209L-mediated activation of a cAMP-response element-binding protein reporter gene and G(q alpha)Q209L induced inositol phosphate production, suggesting that RGS3 efficiently blocks G(q alpha) from activating its downstream effector phospholipase C-beta. Whereas RGS2 and to a lesser extent RGS10 also inhibited signaling by these GTPase-deficient G proteins, other RGS proteins including RGS4 did not. Mutation of residues in RGS3 similar to those required for RGS4 G(i alpha) GAP activity, as well as several residues N terminal to its RGS domain impaired RGS3 function. A greater percentage of RGS3CT localized at the cell membrane than the full-length version, potentially explaining why RGS3CT blocked signaling better than did full-length RGS3. Thus, RGS3 can impair Gi- (but not Gz-) and Gq-mediated signaling in hematopoietic and other cell types by acting as a GAP for G(i alpha) and G(q alpha) subfamily members and as a potent G(q alpha) subfamily effector antagonist. C1 NIH, Cell Mol Biol Sect B, Immunoregulat Lab, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA. RP Scheschonka, A (reprint author), NIH, Cell Mol Biol Sect B, Immunoregulat Lab, Bldg 10 Rm 11B13 Ctr Dr MSC 1876, Bethesda, MD 20892 USA. RI Chidiac, Peter/L-5906-2015 NR 36 TC 64 Z9 64 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2000 VL 58 IS 4 BP 719 EP 728 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 357FW UT WOS:000089488700008 PM 10999941 ER PT J AU Tohkin, M Fukuhara, M Elizondo, G Tomita, S Gonzalez, FJ AF Tohkin, M Fukuhara, M Elizondo, G Tomita, S Gonzalez, FJ TI Aryl hydrocarbon receptor is required for p300-mediated induction of DNA synthesis by adenovirus E1A SO MOLECULAR PHARMACOLOGY LA English DT Article ID E2F TRANSCRIPTION FACTOR; AH-RECEPTOR; CELL-CYCLE; RETINOBLASTOMA PROTEIN; BINDING PROTEIN; COACTIVATOR CBP; MICE LACKING; RAT-CELLS; GENE; DIOXIN AB The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the biological responses to environmental contaminants such as 2,3,7,8- tetrachlorodibenzo-p-dioxin. Embryonic fibroblast (EF) isolated from AHR-null mice exhibited slow cell growth compared with wild-type EF. Reintroduction of AHR into AHR-null EF increased cell growth, suggesting that AHR is involved in cell cycle control. The role of the AHR in cell cycle control was examined using the adenovirus oncoprotein E1A. EF, derived from wild-type and AHR-null mice, were transfected with two mutant E1A expression plasmids that inactivate either p300/CBP or retinoblastoma protein (pRb). Although DNA synthesis of wild-type EF was induced by both E1A mutants, DNA synthesis in the AHR-null EF was induced only by the mutant that binds pRb, not by the mutant to p300/CBP. These data show that both pRb and p300/CBP were the target of E1A-induced DNA synthesis in wild-type EF. In AHR-null mice, however, only pRb was the target of E1A-induced DNA synthesis and p300/CBP cannot be inactivated by E1A in the absence of AHR. Immunoprecipitation revealed that AHR directly bound to p300, thus suggesting the intriguing possibility that AHR is involved in control of the cell cycle via interaction with p300. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Natl Inst Publ Hlth, Dept Pharmaceut Sci, Minato Ku, Tokyo 108, Japan. RP Gonzalez, FJ (reprint author), NCI, Mol Carcinogenesis Lab, 9000 Rockville Pike,Bldg 37, Bethesda, MD 20892 USA. NR 63 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2000 VL 58 IS 4 BP 845 EP 851 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 357FW UT WOS:000089488700023 PM 10999956 ER PT J AU Galynker, II Watras-Ganz, S Miner, C Rosenthal, RN Jarlais, DCD Richman, BL London, E AF Galynker, II Watras-Ganz, S Miner, C Rosenthal, RN Jarlais, DCD Richman, BL London, E TI Cerebral metabolism in opiate-dependent subjects: Effects of methadone maintenance SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE cerebral metabolism; opiate dependency; methadone maintenance ID POSITRON EMISSION TOMOGRAPHY; LONGITUDINAL DATA-ANALYSIS; OPIOID DEPENDENCE; HUMAN-BRAIN; BLOOD-FLOW; PAIN; BUPRENORPHINE; WITHDRAWAL; MORPHINE; COCAINE AB Background: The long-term effects of opiate use on human brain are not known. The goal of this preliminary study was to determine whether human subjects with histories of opiate dependence have persistent differences in brain function as compared with individuals without substance use disorders, and whether methadone maintenance reverses or ameliorates the potential abnormality. Methods: Positron emission tomographic (PET) [18F]fluorodeoxyglucose (FDG) method was used to compare the regional cerebral metabolic rate for glucose (rCMRglc) in three groups: four opiate-dependent subjects currently receiving methadone maintenance therapy (MM), four opiate-dependent subjects not receiving methadone maintenance therapy (MW), and a comparison group of five subjects without substance use disorders. Results: A significant difference in rCMRglc in the anterior cingulate gyrus was found between the MW and Control groups (Mann-Whitney U = 2.0, p = 0.05). Generally speaking, rCMRglc's in MM subjects were intermediate between those of MW and Control groups, although the difference did not reach statistical significance. Conclusions: The results of this study suggest that neurobiological abnormalities can persist in the brain of a chronic opiate user several years after detoxification from methadone. Future research is needed to replicate these results and to determine whether the observed rCMRglc differences are related to opiate use or to neurochemical abnormalities that play a role in developing addictive behavior. C1 Albert Einstein Coll Med, Beth Israel Med Ctr, Dept Psychiat, New York, NY 10003 USA. Albert Einstein Coll Med, Beth Israel Med Ctr, Inst Chem Dependency, New York, NY 10003 USA. Natl Inst Drug Abuse, Brain Imaging Ctr, Baltimore, MD 21224 USA. RP Galynker, II (reprint author), Albert Einstein Coll Med, Beth Israel Med Ctr, Dept Psychiat, 6 Karpas,1st Ave & 16th St, New York, NY 10003 USA. FU NIDA NIH HHS [R01 DA09431] NR 38 TC 28 Z9 30 U1 2 U2 3 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD OCT-NOV PY 2000 VL 67 IS 5-6 BP 381 EP 387 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 368KR UT WOS:000090116600006 PM 11064488 ER PT J AU Boroojerdi, B Kopylev, L Battaglia, F Facchini, S Ziemann, U Muellbacher, W Cohen, LG AF Boroojerdi, B Kopylev, L Battaglia, F Facchini, S Ziemann, U Muellbacher, W Cohen, LG TI Reproducibility of intracortical inhibition and facilitation using the paired-pulse paradigm SO MUSCLE & NERVE LA English DT Article DE intracortical excitability; intracortical inhibition; motor cortex; paired-pulse technique; transcranial magnetic stimulation; variability ID HUMAN MOTOR CORTEX; MAGNETIC STIMULATION AB We have evaluated the reproducibility of intracortical inhibition (ICI) and facilitation (ICF) studied with paired-pulse focal transcranial magnetic stimulation. Three investigators studied the same subjects (n = 4) in three different sessions. A high variability was shown across subjects [coefficient of variation, (cv) 67.3% for ICI and 21.2% for ICF]. Intersession variability was up to 37.1% for ICI and 22.7% for ICF. Interinvestigator variability was 17.3% for ICI and negligible for ICF. Our results may have implications for planning future studies. (C) 2000 John Wiley & Sons, Inc.* C1 NINDS, Human Cortical Physiol Sect, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cortical Physiol Sect, Bldg 10,Room 5N 234,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 9 TC 56 Z9 56 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2000 VL 23 IS 10 BP 1594 EP 1597 DI 10.1002/1097-4598(200010)23:10<1594::AID-MUS19>3.0.CO;2-3 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 358TD UT WOS:000089572500019 PM 11003798 ER PT J AU Giannakakou, P Sackett, DL Ward, Y Webster, KR Blagosklonny, MV Fojo, T AF Giannakakou, P Sackett, DL Ward, Y Webster, KR Blagosklonny, MV Fojo, T TI p53 is associated with cellular microtubules and is transported to the nucleus by dynein SO NATURE CELL BIOLOGY LA English DT Article ID WILD-TYPE P53; PROTEIN; CANCER; CELLS; GENE; ONCOPROTEIN; CENTROSOME; DOMAIN; POLYMERIZATION; DEGRADATION AB Here we show that p53 protein is physically associated with tubulin in vivo and in vitro, and that it localizes to cellular microtubules. Treatment with vincristine or paclitaxel before DNA-damage or before leptomycin B treatment reduces nuclear accumulation of p53 and expression of mdm2 and p21. Overexpression of dynamitin or microinjection of anti-dynein antibody before DNA damage abrogates nuclear accumulation of p53. Our results indicate that transport of p53 along microtubules is dynein-dependent. The first 25 amino acids of p53 contain the residues that are essential for binding to microtubules. We propose that functional microtubules and the dynein motor protein participate in transport of p53 and facilitate its accumulation in the nucleus after DNA damage. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Bristol Myers Squibb Pharmaceut Res Inst, Dept Oncol Drug Discovery, Princeton, NJ 08543 USA. RP Giannakakou, P (reprint author), NCI, Med Branch, Div Clin Sci, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 46 TC 252 Z9 259 U1 4 U2 17 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2000 VL 2 IS 10 BP 709 EP 717 DI 10.1038/35036335 PG 9 WC Cell Biology SC Cell Biology GA 360ZJ UT WOS:000089697000016 PM 11025661 ER PT J AU Vousden, KH Vande Woude, GF AF Vousden, KH Vande Woude, GF TI The ins and outs of p53 SO NATURE CELL BIOLOGY LA English DT Article ID APOPTOSIS; PROTEIN; CANCER; SIGNAL AB Moving proteins between cellular locations is proving to be a tightly regulated process, and provides an important mechanism for controlling protein function. The tumour-suppressor protein p53 has been shown to use microtubules to aid nuclear localization, a finding that raises interesting questions about the action of microtubule-disrupting chemotherapeutic drugs. C1 NCI, Frederick, MD 21702 USA. Van Andel Res Inst, Grand Rapids, MI 49503 USA. RP Vousden, KH (reprint author), NCI, Frederick, MD 21702 USA. NR 17 TC 58 Z9 58 U1 0 U2 1 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2000 VL 2 IS 10 BP E178 EP E180 DI 10.1038/35036427 PG 3 WC Cell Biology SC Cell Biology GA 360ZJ UT WOS:000089697000006 PM 11025676 ER PT J AU Horikawa, Y Oda, N Cox, NJ Li, XQ Orho-Melander, M Hara, M Hinokio, Y Lindner, TH Mashima, H Schwarz, PEH del Bosque-Plata, L Horikawa, Y Oda, Y Yoshiuchi, I Colilla, S Polonsky, KS Wei, S Concannon, P Iwasaki, N Schulze, T Baier, LJ Bogardus, C Groop, L Boerwinkle, E Hanis, CL Bell, GI AF Horikawa, Y Oda, N Cox, NJ Li, XQ Orho-Melander, M Hara, M Hinokio, Y Lindner, TH Mashima, H Schwarz, PEH del Bosque-Plata, L Horikawa, Y Oda, Y Yoshiuchi, I Colilla, S Polonsky, KS Wei, S Concannon, P Iwasaki, N Schulze, T Baier, LJ Bogardus, C Groop, L Boerwinkle, E Hanis, CL Bell, GI TI Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus SO NATURE GENETICS LA English DT Article ID MAJOR SUSCEPTIBILITY LOCUS; GENOME-WIDE SEARCH; DROSOPHILA-MELANOGASTER; MEXICAN-AMERICANS; LINKAGE; MUTATIONS; ONSET; CHROMOSOME-2; PROTEASE; NIDDM1 AB Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes. C1 Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Lund, Malmo Univ Hosp, Dept Endocrinol, Malmo, Sweden. Univ Washington, Mol Genet Program, Virginia Mason Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Tokyo Womens Med Univ, Ctr Diabet, Tokyo, Japan. Tech Univ Dresden, Univ Clin Carl Gustav Carus, Dept Internal Med 3, D-8027 Dresden, Germany. NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. RP Bell, GI (reprint author), Univ Chicago, Howard Hughes Med Inst, 5841 S Maryland Ave, Chicago, IL 60637 USA. RI Schwarz, Peter/B-5127-2013; OI Schwarz, Peter/0000-0001-6317-7880; Concannon, Patrick/0000-0002-5801-1859 FU NIDDK NIH HHS [DK-42086, DK-47486, DK-20595, R01 DK047494] NR 50 TC 1001 Z9 1064 U1 1 U2 42 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2000 VL 26 IS 2 BP 163 EP 175 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 359YC UT WOS:000089638800012 PM 11017071 ER PT J AU Dorfman, JR Stefanova, I Yasutomo, K Germain, RN AF Dorfman, JR Stefanova, I Yasutomo, K Germain, RN TI CD4(+) T cell survival is not directly linked to self-MHC-induced TCR signaling SO NATURE IMMUNOLOGY LA English DT Article ID CLASS-II MOLECULES; RECEPTOR TRANSGENIC MICE; POSITIVE SELECTION; MUTANT MICE; TYROSINE PHOSPHORYLATION; PERIPHERAL SELECTION; ANTIGEN PRESENTATION; DEFICIENT MICE; IN-VIVO; THYMOCYTES AB T cell receptor (TCR) signaling triggered by recognition of self-major histocompatibility complex (MHC) ligands has been proposed to maintain the viability of naive T cells and to provoke their proliferation in T cell-deficient hosts. Consistent with this, the partially phosphorylated state of TCR zeta chains in naive CD4(+) and CD8(+) T tells in vivo was found to be actively maintained by TCR interactions with specific peptide-containing MHC molecules,TCR ligand-dependent phosphorylation of TCR zeta was lost within one day of cell transfer into MHC-deficient hosts, yet the survival of transferred CD4(+) lymphocytes was the same in recipients with or without MHC class II expression for one month. Thus, despite clear evidence for TCR signaling in nonactivated naive T cells, these data argue against the concept that such signaling plays a predominant role in determining lymphocyte lifespan. C1 NIH, Lymphocyte Biol Sect, Immunol Lab, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIH, Lymphocyte Biol Sect, Immunol Lab, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. RI Dorfman, Jeffrey/B-4854-2011 OI Dorfman, Jeffrey/0000-0001-9938-8911 NR 64 TC 130 Z9 132 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2000 VL 1 IS 4 BP 329 EP 335 DI 10.1038/79783 PG 7 WC Immunology SC Immunology GA 364AK UT WOS:000089869700016 PM 11017105 ER PT J AU Alter, HJ Houghton, M AF Alter, HJ Houghton, M TI Hepatitis C virus and eliminating post-transfusion hepatitis SO NATURE MEDICINE LA English DT Editorial Material ID NON-B-HEPATITIS; NON-A-HEPATITIS; VIRAL-HEPATITIS; ANTIBODY; BLOOD; CHIMPANZEES; INFECTION; ANTIGEN; AGENTS; TRANSMISSION C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Immunol Sect, Bethesda, MD 20892 USA. Chiron Corp, Emeryville, CA 94608 USA. RP Alter, HJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Immunol Sect, NIH Bldg 10,Room 1C711,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 39 TC 50 Z9 50 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2000 VL 6 IS 10 BP 1082 EP 1086 DI 10.1038/80394 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 360NT UT WOS:000089674700017 PM 11017126 ER PT J AU Hel, Z Venzon, D Poudyal, M Tsai, WP Giuliani, L Woodward, R Chougnet, C Shearer, G Altman, JD Watkins, D Bischofberger, N Abimiku, A Markham, P Tartaglia, J Franchini, G AF Hel, Z Venzon, D Poudyal, M Tsai, WP Giuliani, L Woodward, R Chougnet, C Shearer, G Altman, JD Watkins, D Bischofberger, N Abimiku, A Markham, P Tartaglia, J Franchini, G TI Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; VACCINIA VIRUS; IMMUNE-RESPONSES; CELL RESPONSES; HIV-1 TAT; INDIVIDUALS; APOPTOSIS; MAMU-A-ASTERISK-01; DISCONTINUATION AB Prolonged antiretroviral therapy (ART) is not likely to eradicate human immunodeficiency virus type I (HIV-I) infection. Here we explore the effect of therapeutic immunization in the context of ART during primary infection using the simian immunodeficiency virus (SIV251) macaque model. Vaccination of rhesus macaques with the highly attenuated poxvirus-based NYVAC-SIV vaccine expressing structural genes elicited vigorous virus-specific CD4(+) and CD8(+) T cell responses in macaques that responded effectively to ART. Following discontinuation of a six-month ART regimen, viral rebound occurred in most animals, but was transient in six of eight vaccinated animals. Viral rebound was also transient in four of seven mock-vaccinated control animals. These data establish the importance of antiretroviral treatment during primary infection and demonstrate that virus-specific immune responses in the infected host can be expanded by therapeutic immunization. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Adv BioSci Labs Inc, Kensington, MD 20895 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. Emory Univ, Vaccine Ctr Yerkes, Atlanta, GA 30329 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Gilead Sci Inc, Foster City, CA 94404 USA. Inst Human Virol, Baltimore, MD 21201 USA. Virogenet Corp, Troy, NY 12180 USA. Ave Pasteur Ltd, N York, ON M2R 3T4, Canada. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; OI Hel, Zdenek/0000-0002-4923-4794 NR 42 TC 159 Z9 163 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2000 VL 6 IS 10 BP 1140 EP 1146 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 360NT UT WOS:000089674700039 PM 11017146 ER PT J AU Ashcroft, GS Lei, KJ Jin, WW Longenecker, G Kulkarni, AB Greenwell-Wild, T Hale-Donze, H McGrady, G Song, XY Wahl, SM AF Ashcroft, GS Lei, KJ Jin, WW Longenecker, G Kulkarni, AB Greenwell-Wild, T Hale-Donze, H McGrady, G Song, XY Wahl, SM TI Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing SO NATURE MEDICINE LA English DT Article ID GROWTH-FACTOR-BETA; AMINO-ACID SEQUENCE; LATENT TGF-BETA; INFLAMMATORY RESPONSE; NEUTROPHIL ELASTASE; POTENT INHIBITOR; AGED HUMANS; ANTILEUKOPROTEASE; MATRIX; DEGRADATION AB Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor with anti-microbial properties found in mucosal fluids. It is expressed during cutaneous wound healing. Impaired healing states are characterized by excessive proteolysis and often bacterial infection, leading to the hypothesis that SLPI may have a role in this process. We have generated mice null for the gene encoding SLPI (Slpi), which show impaired cutaneous wound healing with increased inflammation and elastase activity. The altered inflammatory profile involves enhanced activation of local TGF-beta in Slpi-null mice. We propose that SLPI is a pivotal endogenous factor necessary for optimal wound healing. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 45 TC 267 Z9 276 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2000 VL 6 IS 10 BP 1147 EP 1153 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 360NT UT WOS:000089674700040 PM 11017147 ER PT J AU Bielekova, B Goodwin, B Richert, N Cortese, I Kondo, T Afshar, G Gran, B Eaton, J Antel, J Frank, JA McFarland, HF Martin, R AF Bielekova, B Goodwin, B Richert, N Cortese, I Kondo, T Afshar, G Gran, B Eaton, J Antel, J Frank, JA McFarland, HF Martin, R TI Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: Results of a phase II clinical trial with an altered peptide ligand SO NATURE MEDICINE LA English DT Article ID T-CELL RECEPTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IMMUNE INTERVENTION; PROTEOLIPID PROTEIN; LYMPHOCYTES-T; RECOGNITION; DISEASE; NEUROPATHOLOGY; HETEROGENEITY AB Myelin-specific T lymphocytes are considered essential in the pathogenesis of multiple sclerosis. The myelin basic protein peptide (a.a. 83-99) represents one candidate antigen; therefore, it was chosen to design an altered peptide ligand, CGP77116, for specific immunotherapy of multiple sclerosis. A magnetic resonance imaging-controlled phase II clinical trial with this altered peptide ligand documented that it was poorly tolerated at the dose tested, and the trial had therefore to be halted. Improvement or worsening of clinical or magnetic resonance imaging parameters could not be demonstrated in this small group of individuals because of the short treatment duration. Three patients developed exacerbations of multiple sclerosis, and in two this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic protein peptide (a.a. 83-99) in a subgroup of patients. These data raise important considerations for the use of specific immunotherapies in general. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Lab Diagnost Radiol Res, Ctr Clin, NIH, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Dept Neurol, Montreal, PQ H3A 2B4, Canada. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 57 TC 526 Z9 547 U1 2 U2 11 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2000 VL 6 IS 10 BP 1167 EP 1175 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 360NT UT WOS:000089674700043 PM 11017150 ER PT J AU Romansk, LM Tian, B Fritz, JB Mishkin, M Goldman-Rakic, PS Rauschecker, JP AF Romansk, LM Tian, B Fritz, JB Mishkin, M Goldman-Rakic, PS Rauschecker, JP TI 'What', 'where' and 'how' in auditory cortex - Reply SO NATURE NEUROSCIENCE LA English DT Letter ID MONKEY; LOCALIZATION; NEURONS; HUMANS C1 Univ Rochester, Dept Neurobiol & Anat, Rochester, NY 14642 USA. Georgetown Univ, Med Ctr, Georgetown Inst Cognit & Computat Sci, Washington, DC 20007 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Neurobiol Sect, New Haven, CT 06510 USA. RP Romansk, LM (reprint author), Univ Rochester, Dept Neurobiol & Anat, 601 Elmwood Ave,Box 603, Rochester, NY 14642 USA. RI Rauschecker, Josef/A-4120-2013 NR 12 TC 22 Z9 22 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2000 VL 3 IS 10 BP 966 EP 966 DI 10.1038/79892 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 405TW UT WOS:000167177500008 ER PT J AU Robertson, KD Wolffe, AP AF Robertson, KD Wolffe, AP TI DNA methylation in health and disease SO NATURE REVIEWS GENETICS LA English DT Review ID FRAGILE-X-SYNDROME; HISTONE DEACETYLASE COMPLEX; BINDING-PROTEIN MECP2; DE-NOVO METHYLATION; TRINUCLEOTIDE REPEAT; TRANSCRIPTIONAL REPRESSOR; METHYLTRANSFERASE GENE; CYTOSINE METHYLATION; ICF SYNDROME; IMMUNODEFICIENCY SYNDROME AB DNA methylation has recently moved to centre stage in the aetiology of human neurodevelopmental syndromes such as the fragile X, ICF and Rett syndromes. These diseases result from the misregulation of genes that occurs with the toss of appropriate epigenetic controls during neuronal development. Recent advances have connected DNA methylation to chromatin-remodeling enzymes, and understanding this link will be central to the design of new therapeutic tools. C1 Sangamo Biosci, Point Richmond Tech Ctr, Richmond, CA 94804 USA. NCI, Epigenet Gene Regulat & Canc Sect, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), Sangamo Biosci, Point Richmond Tech Ctr, 501 Canal Blvd,Suite A100, Richmond, CA 94804 USA. NR 101 TC 653 Z9 696 U1 4 U2 60 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2000 VL 1 IS 1 BP 11 EP 19 DI 10.1038/35049533 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 381KY UT WOS:000165763000013 PM 11262868 ER PT J AU Liotta, L Petricoin, E AF Liotta, L Petricoin, E TI Molecular profiling of human cancer SO NATURE REVIEWS GENETICS LA English DT Review ID LASER-CAPTURE MICRODISSECTION; GENE-EXPRESSION PATTERNS; IMMUNOSENSOR; MICROARRAYS; CELLS; ARRAY; IMMUNOASSAY; FABRICATION; SYSTEMS; TISSUE AB Traditionally, tumours have been categorized on the basis of histology. However, the staining pattern of cancer cells viewed under the microscope is insufficient to reflect the complicated underlying molecular events that drive the neoplastic process. By surveying thousands of genes at once, using DNA arrays, it is now possible to read the molecular signature of an individual patient's tumour. When the signature is analysed with clustering algorithms, new classes of cancer emerge that transcend distinctions based on histological appearance alone. Using DNA arrays, protein arrays and appropriate experimental models, the ultimate goal is to move beyond correlation and classification to achieve new insights into disease mechanisms and treatment targets. C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Liotta, L (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 51 TC 328 Z9 338 U1 2 U2 26 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2000 VL 1 IS 1 BP 48 EP 56 DI 10.1038/35049567 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 381KY UT WOS:000165763000017 PM 11262874 ER PT J AU Horwitz, B Friston, KJ Taylor, JG AF Horwitz, B Friston, KJ Taylor, JG TI Neural modeling and functional brain imaging: an overview SO NEURAL NETWORKS LA English DT Review DE neural modeling; functional brain imaging; functional integration ID TRANSCRANIAL MAGNETIC STIMULATION; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; HUMAN MOTOR CORTEX; WORKING-MEMORY; NEURONAL-ACTIVITY; ATTENTIONAL MODULATION; INTRAVENOUS (H2O)-O-15; SENSORY STIMULATION; ELECTRICAL-ACTIVITY AB This article gives an overview of the different functional brain imaging methods, the kinds of questions these methods try to address and some of the questions associated with functional neuroimaging data for which neural modeling must be employed to provide reasonable answers. (C) 2000 Published by Elsevier Science Ltd. C1 Natl Inst Deafness & Commun Disorders, Language Sect, NIH, Bethesda, MD 20892 USA. Inst Neurol, Wellcome Dept Cognit Neurol, London WC1N 3BG, England. Kings Coll London, Dept Math, London WC2R 2LS, England. RP Horwitz, B (reprint author), Natl Inst Deafness & Commun Disorders, Language Sect, NIH, Bldg 10,Room 6C414,MSC 1588,9000 Rockville Pike, Bethesda, MD 20892 USA. EM horwitz@helix.nih.gov RI Friston, Karl/D-9230-2011 OI Friston, Karl/0000-0001-7984-8909 NR 153 TC 85 Z9 89 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD OCT-NOV PY 2000 VL 13 IS 8-9 BP 829 EP 846 DI 10.1016/S0893-6080(00)00062-9 PG 18 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 386PF UT WOS:000166070200002 PM 11156195 ER PT J AU Taylor, JG Horwitz, B Shah, NJ Fellenz, WA Mueller-Gaertner, HW Krause, JB AF Taylor, JG Horwitz, B Shah, NJ Fellenz, WA Mueller-Gaertner, HW Krause, JB TI Decomposing memory: functional assignments and brain traffic in paired word associate learning SO NEURAL NETWORKS LA English DT Article DE long-term memory; working memory; brain imaging; structural equation models; controlled encoding ID POSITRON-EMISSION-TOMOGRAPHY; INFERIOR PREFRONTAL CORTEX; WORKING-MEMORY; NETWORK ANALYSIS; EPISODIC MEMORY; FRONTAL-CORTEX; IDENTIFYING OBJECTS; VERBAL INFORMATION; RETRIEVAL SUCCESS; IMAGING COGNITION AB The recent covariance structural equation model for word-pair associate encoding and retrieval (Krause, Horwitz, Taylor, Schmidt, Mottaghy, Halsband et al., 1998; Krause, Horwitz, Taylor, Schmidt, Mottaghy, Herzog et al., 1999) is analysed to deduce possible functional assignments of the various brain modules used by subjects in solving the task. Specific processing aspects are considered, in particular, that of long-term working memory sites and how they are coupled to buffer working memory sites to enable deposition and manipulation of remembered associates. The new concept of 'brain traffc' is introduced as an aid to the assessment of how important are various brain modules. A set of functional assignments is produced for the relevant modules. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Forschungszentrum Julich, Inst Med, D-52425 Julich, Germany. Kings Coll London, Dept Math, London WC2R 2LS, England. Natl Inst Deafness & Commun Disorders, Lanaguage Sect, NIH, Bethesda, MD USA. Univ Dusseldorf, Dept Nucl Med, D-40225 Dusseldorf, Germany. Forschungszentrum Julich, Dept Nucl Med KME, D-52425 Julich, Germany. RP Taylor, JG (reprint author), Forschungszentrum Julich, Inst Med, Postfach 1913, D-52425 Julich, Germany. EM john.g.taylor@kcl.ac.uk RI Shah, N. Jon /H-5849-2013 OI Shah, N. Jon /0000-0002-8151-6169 NR 83 TC 16 Z9 18 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD OCT-NOV PY 2000 VL 13 IS 8-9 BP 923 EP 940 DI 10.1016/S0893-6080(00)00054-X PG 18 WC Computer Science, Artificial Intelligence SC Computer Science GA 386PF UT WOS:000166070200009 PM 11156202 ER PT J AU Tagamets, MA Horwitz, B AF Tagamets, MA Horwitz, B TI A model of working memory: bridging the gap between electrophysiology and human brain imaging SO NEURAL NETWORKS LA English DT Article DE neuroimaging; electrophysiology; working memory; model ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; PRIMATE FRONTAL-CORTEX; CEREBRAL BLOOD-FLOW; PREFRONTAL CORTEX; ENERGY-METABOLISM; NEURAL SYSTEMS; RHESUS-MONKEYS; VISUAL-CORTEX; PET-RCBF AB Human neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging have made possible the study of large-scale distributed networks in the behaving human brain. Although many imaging studies support and extend knowledge gained from other experimental modalities such as animal single-cell recordings, there have also been a substantial number of experiments that appear to contradict the animal studies. Part of the reason for this is that neuroimaging is an indirect measure of neuronal tiring activity, and thus interpretation is difficult. Computational modeling can help to bridge the gap by providing a substrate for making explicit the assumptions and constraints provided from other sources such as anatomy, physiology and behavior. We describe a large-scale model of working memory that we have used to examine a number of issues relating to the interpretation of imaging data. The gating mechanism that regulates engagement and retention of short-term memory is revised to better reflect hypothesized underlying neuromodulatory mechanisms. It is shown that in addition to imparting better performance for the memory circuit, this mechanism also provides a better match to imaging data from working memory studies. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Funct Neuroimaging Lab, Baltimore, MD 21228 USA. Natl Inst Deafness & Commun Disorders, Speech & Language Branch, Language Sect, NIH, Bethesda, MD 20892 USA. RP Tagamets, MA (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Funct Neuroimaging Lab, POB 21247, Baltimore, MD 21228 USA. NR 59 TC 24 Z9 24 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD OCT-NOV PY 2000 VL 13 IS 8-9 BP 941 EP 952 DI 10.1016/S0893-6080(00)00063-0 PG 12 WC Computer Science, Artificial Intelligence SC Computer Science GA 386PF UT WOS:000166070200010 PM 11156203 ER PT J AU Hall, Z Bloom, FE Fischbach, G AF Hall, Z Bloom, FE Fischbach, G TI Special issue: Neuroscience to neurological recovery - Introduction SO NEUROBIOLOGY OF DISEASE LA English DT Editorial Material C1 Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Scripps Res Inst, Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. NINDS, Bethesda, MD 20892 USA. RP Hall, Z (reprint author), Univ Calif San Francisco, Dept Physiol, 513Parnassus Ave, San Francisco, CA 94143 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2000 VL 7 IS 5 BP 495 EP 498 DI 10.1006/nbdi.2000.0337 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 367XE UT WOS:000090086300002 PM 11042061 ER PT J AU Hyman, SE AF Hyman, SE TI Genes, gene expression, and behavior SO NEUROBIOLOGY OF DISEASE LA English DT Article; Proceedings Paper CT Symposium on Neuroscience 2000: a New Era of Discovery CY APR 11-13, 1999 CL WASHINGTON, D.C. SP Soc Neurosci ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ARRAYS; GENOME C1 NIMH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2000 VL 7 IS 5 BP 528 EP 532 DI 10.1006/nbdi.2000.0347 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 367XE UT WOS:000090086300010 PM 11042069 ER PT J AU Horwitz, B Deiber, MP Ibanez, V Sadato, N Hallett, M AF Horwitz, B Deiber, MP Ibanez, V Sadato, N Hallett, M TI Correlations between reaction time and cerebral blood flow during motor preparation SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CORTICAL AREAS; VOLUNTARY MOVEMENTS; FUNCTIONAL-ANATOMY; FINGER MOVEMENTS; WORKING MEMORY; PET; CORTEX; ORGANIZATION; CEREBELLUM AB We show using positron emission tomography in normal volunteers that for four tasks involving motor preparation, regional cerebral blood flow in the ipsilateral cerebellum is negatively correlated with reaction time. Each of the tasks presented subjects with different amounts of advanced information (from none to partial to full information) prior to a signal. to move one of two possible fingers in one of two possible directions. The cerebellum was the only brain area that was correlated with reaction time in all the conditions. These results are compatible with the idea that the cerebellum plays an important role in the preparation and initiation of motion. C1 Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD 20892 USA. NINCDS, Med Neurol Branch, Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD 20892 USA. RI Deiber, Marie-Pierre/M-5949-2014 NR 47 TC 32 Z9 32 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT PY 2000 VL 12 IS 4 BP 434 EP 441 DI 10.1006/nimg.2000.0632 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 361RL UT WOS:000089737000008 PM 10988037 ER PT J AU Chao, LL Martin, A AF Chao, LL Martin, A TI Representation of manipulable man-made objects in the dorsal stream SO NEUROIMAGE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CORTEX AREA F5; PREMOTOR CORTEX; IDEATIONAL APRAXIA; PREFRONTAL CORTEX; GRASPING OBJECTS; VISUAL GUIDANCE; PARIETAL CORTEX; HAND ACTION; MONKEY AB We used fMRI to examine the neural response in frontal and parietal cortices associated with viewing and naming pictures of different categories of objects. Because tools are commonly associated with specific hand movements, we predicted that pictures of tools, but not other categories of objects, would elicit activity in regions of the brain that store information about motor-based properties. We found that viewing and naming pictures of tools selectively activated the left ventral premotor cortex (BA 6). Single-unit recording studies in monkeys have shown that neurons in the rostral part of the ventral premotor cortex (canonical F5 neurons) respond to the visual presentation of graspable objects, even in the absence of any subsequent motor activity. Thus, the left ventral premotor region that responded selectively to tools in the current study may be the human homolog of the monkey canonical F5 area. Viewing and naming tools also selectively activated the left posterior parietal cortex (BA 40). This response is similar to the firing of monkey anterior intraparietal neurons to the visual presentation of graspable objects. In humans and monkeys, there appears to be a close link between manipulable objects and information about the actions associated with their use. The selective activation of the left posterior parietal and left ventral premotor cortices by pictures of tools suggests that the ability to recognize and identify at least one category of objects (tools) may depend on activity in specific sites of the ventral and dorsal visual processing streams. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Chao, LL (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 35 TC 691 Z9 697 U1 6 U2 29 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT PY 2000 VL 12 IS 4 BP 478 EP 484 DI 10.1006/nimg.2000.0635 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 361RL UT WOS:000089737000012 PM 10988041 ER PT J AU Ho, NC AF Ho, NC TI Monozygotic twins with petal akinesia: The importance of clinicopathological work-up in predicting risks of recurrence SO NEUROPEDIATRICS LA English DT Article DE myogenic arthrogryposis; neurogenic arthrogryposis; anoxic-ischemic damage; recurrence risks; fetal akinesia; monozygotic twins ID PENA-SHOKEIR PHENOTYPE; ARTHROGRYPOSIS MULTIPLEX CONGENITA; LINKED MYOTUBULAR MYOPATHY; FACIAL ANOMALIES; DEFORMATION SEQUENCE; PULMONARY HYPOPLASIA; ANKYLOSES; MYASTHENIA; GENE AB Fetal Akinesia Deformation Sequence (FADS) or Pena-Shokeir Sequence is a heterogeneous group of disorders in which prolonged decrease or absence of fetal movements results in a series of deformational anomalies: multiple contractures, pulmonary hypoplasia, craniofacial anomalies, polyhydramnios, intrauterine growth retardation, and short umbilical cord. Three sets of monozygotic twins, and their affected sibs, are presented. Detailed pathological work-up established that the two pairs of twins concordant for FADS were of myogenic etiology while the set discordant was due to anoxic-ischemic damage. In the myogenic cases, the rate of recurrence was high, in agreement with the findings from the study on arthrogryposis multiplex congenita of myogenic origin [22]. In light of these findings, in sporadic cases of myogenic FADS, counselling, a recurrence risk of 25% seems prudent. In neurogenic cases associated with primary cerebral malformations, there are cases cited in the literature that are clearly recessive as indicated by affected sibs, but many reported are isolated occurrences. Therefore, in this scenario, giving a recurrent risk of 10-15% appears appropriate. In light of autosomal recessive spinal muscular atrophy and reports of familiar FADS due to primary anterior horn cell loss, counselling a 25% risk seems prudent. In cases due to anoxic-ischemic damage, offering a low recurrent risk of 1% appears justified. C1 NHGRI, IOCIOI, Med Genet Branch, NIH, Bethesda, MD 20852 USA. RP Ho, NC (reprint author), NHGRI, IOCIOI, Med Genet Branch, NIH, Bethesda, MD 20852 USA. NR 26 TC 11 Z9 12 U1 1 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD OCT PY 2000 VL 31 IS 5 BP 252 EP 256 DI 10.1055/s-2000-9238 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 390GE UT WOS:000166286700004 PM 11204282 ER PT J AU Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Wiseman, E Bridge, P AF Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Wiseman, E Bridge, P TI Increased CSF volumes are associated with diminished subjective responses to cocaine infusion SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cocaine; euphoria; subjective; CSF; ventricles; cortex; frontal ID MAGNETIC-RESONANCE; GRAY-MATTER; BRAIN; ABUSERS; LOBE; HIPPOCAMPUS; DEPENDENCE; PERFUSION; DOPAMINE; USERS AB We evaluated the hypothesis that ventricular and cortical CSF volume increases are associated with reductions in the magnitude of euphoric effects produced by intravenous IV cocaine infusion in cocaine dependent (CD) individuals. Eleven CD patients participating in a cocaine-infusion study and eleven control subjects underwent magnetic resonance imaging (MRI). Two CSF regions of interest (lateral ventricles and frontal cortex CSF) and two comparison regions (third ventricle and posterior cortex CSF) were measured. Self-reported ratings of the intensify of euphoric response ("high") were obtained from the CD subjects at 3, 20, and 30 minutes after IV administration of cocaine. A significant negative correlation was observed between the volume of the lateral ventricles and subjective ratings of the "high" experienced at 3 minutes, but riot at 20 and 30 minutes after cocaine infusion. In contrast, a significant negative correlation between frontal cortex CSF volume and the intensity of euphoric response was observed at 30 minutes after IV cocaine. No significant associations were observed between the volumes of the two comparison regions and ally subjective ratings of "high." No significant volume differences were observed between the CD and control groups in any region. The results suggest larger lateral ventricular volumes are associated with a decrease in immediate euphoria while larger frontal cortex CSF volumes are associated with a decrease in the duration? of the euphoria induced by cocaine infusion. The age-related brain volume reductions underlying the volume increase in these two CSF spaces may be the neurobiological basis of the age-related reduction in the rates of addiction. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Greater Los Angeles VA Healthcare Syst, W Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90074 USA. NIDA, Medicat Dev Div, Rockville, MD 20857 USA. RP Bartzokis, G (reprint author), Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, 2200 Ft Roots Dr,Bldg 170,116A-NLR, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 FU NIDA NIH HHS [1YO1 DA 50038] NR 27 TC 6 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2000 VL 23 IS 4 BP 468 EP 473 DI 10.1016/S0893-133X(00)00122-6 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 355KV UT WOS:000089385600013 PM 10989274 ER PT J AU Devi, LA Brady, LS AF Devi, LA Brady, LS TI Dimerization of G-protein coupled receptors - Introduction SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material C1 NYU, Sch Med, Dept Pharmacol, New York, NY 10012 USA. NIMH, Bethesda, MD 20892 USA. RP Devi, LA (reprint author), NYU, Sch Med, Dept Pharmacol, New York, NY 10012 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2000 VL 23 IS 4 SU S BP S3 EP S4 DI 10.1016/S0893-133X(00)00154-8 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 356AB UT WOS:000089419800002 PM 11008062 ER PT J AU Zeng, FY Wess, J AF Zeng, FY Wess, J TI Molecular aspects of muscarinic receptor dimerization SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-for-Neuroscience CY OCT 23-28, 1999 CL MIAMI BEACH, FLORIDA SP Soc Neurosci DE G-protein-coupled receptors; muscarinic acetylcholine receptors; receptor oligomerization; receptor dimers; disulfide-crosslinking; site-directed mutagenesis ID PROTEIN-COUPLED RECEPTOR; TERMINAL EXTRACELLULAR DOMAIN; V2 VASOPRESSIN RECEPTORS; ACETYLCHOLINE-RECEPTOR; FUNCTIONAL RESCUE; GABA(B) RECEPTOR; LINKED RECEPTORS; CELL-SURFACE; BINDING; IDENTIFICATION AB The five muscarinic acetylcholine receptors (M-1-M-5) are prototypical members of the superfamily of G-protein-coupled receptors (GPCRs). During the past decade, this laboratory has used different members oft his receptor subfamily as model systems to study the molecular mechanisms involved in GPCR function. This article reviews recent investigations dealing with molecular aspects of M-3 muscarinic receptor assembly and dimerization/oligomerization. Studies with coexpressed M-3 receptor/fragments and M-3 muscarinic/alpha(2C)-adrenergic hybrid receptors showed that muscarinic receptors, like other GPCRs, are composed of multiple autonomous folding domains. Moreover, biochemical studies have provided direct evidence for the formation of M-3 receptor dimers/oligomers. These high molecular mass receptor species ave expressed on the cell surface and can bind muscarinic ligands. M-3 receptor dimerization/oligomerization appears to be receptor subtype-selective and involves both noncovalent interactions as well as disulfide-crosslinking of receptor monomers. These studies add to the growing number of reports suggesting the existence of GPCR dimers or multimers. The precise functional characteristics of such receptor aggregates remain to be elucidated. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05, Bethesda, MD 20892 USA. NR 52 TC 45 Z9 46 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2000 VL 23 IS 4 SU S BP S19 EP S31 DI 10.1016/S0893-133X(00)00146-9 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 356AB UT WOS:000089419800004 PM 11008064 ER PT J AU Fields, RD Ozsarac, N AF Fields, RD Ozsarac, N TI Gene chips: Applications to neuroscience SO NEUROSCIENTIST LA English DT Article DE hybridization arrays; gene chips; gene expression profiling; cDNA; mRNA expression ID DIFFERENTIAL DISPLAY; MESSENGER-RNA; EXPRESSION PATTERNS; CDNA MICROARRAYS; GENOME; ARRAYS; CELLS AB A convergence between molecular biological technique and the technology of miniaturization has produced the "gene chip" or microhybridization array. This device multiplies by several thousand fold the power of the northern blot for studying gene expression. Now, it is possible to survey simultaneously a large fraction of all genes in an experimental organism, and within a few years all of the approximately 140,000 human genes will be within reach of the technique. This capability is not only accelerating the rate of research into gene expression and function, it is changing the perspective of inquiry from single genes in isolation to networks of genes operating as a system. Many neurological diseases, from hydrocephalus to schizophrenia, have a genetic component, and individual responses to therapeutic drugs can vary with the genetic background of patients. In neurology and neurobiology, the ability to obtain "gene expression profiles" from nervous tissue promises to illuminate interactions between neuronal genes and the environment, development, disease, aging, and response to drugs and injury. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 35 TC 1 Z9 1 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2000 VL 6 IS 5 BP 310 EP 314 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 356GV UT WOS:000089436300012 ER PT J AU Gaillard, WD Theodore, WH AF Gaillard, WD Theodore, WH TI Mapping language in epilepsy with functional imaging SO NEUROSCIENTIST LA English DT Review DE language; epilepsy; functional magnetic resonance imaging (fMRI); positron emission tomography (PET); Brain; mapping ID TEMPORAL-LOBE EPILEPSY; TRANSCRANIAL MAGNETIC STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; ELECTROCORTICAL STIMULATION; INDIVIDUAL VARIABILITY; AUDITORY COMPREHENSION; CORTICAL LOCALIZATION; DOMINANT HEMISPHERE; PET ACTIVATION AB Surgery is an important therapeutic alternative for patients with uncontrolled epilepsy. Preoperative identification of brain regions important for language is important to reduce the risk of functional impairment after surgery, The Wada test suffers from several technical and clinical disadvantages and provides hemispheric data at best. More invasive methods such as intraoperative or chronic subdural cortical mapping have more limited application. New approaches using neuroimaging methods offer the opportunity to localize, as well as lateralize, language. In addition, normal volunteers can be studied with the same techniques, providing comparative and control data. Although most normal studies have been reported as group data, it is important for individual scans to be available for comparison with patient studies to understand the normal range of interindividual variability. Two techniques, PET with O-15-water-PET and fMRI, have been used. Both detect signal changes associated with increased regional blood flow during neuronal activity. Usually, scans performed during a language task are compared with those obtained during control conditions. It is important to choose activation tasks carefully, to make sure one is imaging activation associated with the particular process of interest. PET has advantages, including a fully diffusible tracer, standardized analytic methods, a more comfortable environment, and less sensitivity to movement artifact. On the other hand, it involves a cyclotron-produced tracer, radiation exposure, and is more difficult to repeat. FMRI over represents the effects of large vascular structures and is very sensitive to movement but uses widely available equipment and has no limitation on the number of studies. For both studies, it is important to understand the potential effects of such factors as attention, fatigue, and familiarity with the material. Several studies comparing O-15-water-PET and fMRI to the Wada test found that the former are at least as accurate for language lateralization. In addition, we compared O-15-water-PET to direct subdural electrode cortical stimulation and found that regions showing increased cerebral blood flow during naming tasks co-registered with subdural electrodes that disrupted language during electrical stimulation. In this and other studies, PET detected more regions than electrical stimulation techniques. The whole brain cannot be covered with electrodes, but some areas participating in a task may not be crucial for it. FMRI is particularly useful for children. We compared cortical activation patterns in normal children, adolescents, and adults. The activation patterns, and laterality of language dominance, in children 8 years and above, were similar to adults, although some differences could reflect maturation and evolving focality of cognitive processes. In children with epilepsy, fMRI successfully identified language laterality and provided data on intrahemispheric localization. Studies also showed the effects of the epileptic focus on normal activation patterns for several tasks. Neuroimaging functional mapping is an important tool, still in the process of development and evolution. Although potentially of great clinical and scientific value, it should be used and interpreted cautiously. C1 NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 62 TC 2 Z9 2 U1 4 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2000 VL 6 IS 5 BP 390 EP 400 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 356GV UT WOS:000089436300020 ER PT J AU Park, CS Krishna, G Ahn, MS Kang, JH Chung, WG Kim, DJ Hwang, HK Lee, JN Paik, SG Cha, YN AF Park, CS Krishna, G Ahn, MS Kang, JH Chung, WG Kim, DJ Hwang, HK Lee, JN Paik, SG Cha, YN TI Differential and constitutive expression of neuronal, inducible, and endothelial nitric oxide synthase mRNAs and proteins in pathologically normal human tissues SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE nitric oxide synthases; mRNA; protein; alternative splicing; human normal tissues ID MESSENGER-RNA; STRUCTURAL DIVERSITY; SKELETAL-MUSCLE; MOLECULAR-CLONING; HUMAN RETINA; L-ARGININE; BRAIN; RAT; ISOFORM; CDNA AB Nitric oxide (NO) is produced by NO synthases (nNOS, iNOS, and eNOS) expressed in various human tissues and depending on the amount of NO produced in each tissue, the physiological function of NO is determined. However, due to the difficulty in obtaining normal human tissues, little is known about the basal levels of each of the three NOS mRNAs and proteins expressed constitutively in various human tissues. Results of the present study indicate that the basal levels of each of the three NOS mRNAs and proteins expressed in various regions of brain and peripheral tissues are different both in their sizes and in their contents. In Northern blot analysis, two different-sized mRNAs were found for each NOS isozymes: for the nNOS, similar to 12 and <12 kb mRNAs; for the iNOS, 4.2 and 4.5 kb mRNAs; for the eNOS, 4.2 and 4.4 kb mRNAs, In the Western blot, several different-sized NOS proteins were detected (160, similar to 140, and similar to 130 kDa for nNOS; similar to 130 kDa for iNOS and eNOS) with tissue-specific expression patterns. These differential expression patterns of NOS mRNAs and proteins were caused by alternative splicing in the open-reading frame, and 5'- and/or 3'-untranslated regions of NOS mRNAs. These results suggest that regulation for differential expression of the three NOS genes in various human tissues may occur by alternative splicing of the NOS mRNAs in tissue-specific patterns. (C) 2000 Academic Press. C1 Inha Univ, Coll Med, Dept Pharmacol & Toxicol, Med Toxicol Res Ctr,Nam Gu, Inchon 402751, South Korea. Inha Univ, Coll Med, Dept Anat, Inchon, South Korea. NHLBI, Sect Chem Pharmacol, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Sejong Gen Hosp, Dept Internal Med, Buchon, South Korea. Gil Med Ctr, Gachon Med Sch, Dept Gen Surg, Inchon, South Korea. Chungnam Natl Univ, Dept Biol, Taejon, South Korea. RP Cha, YN (reprint author), Inha Univ, Coll Med, Dept Pharmacol & Toxicol, Med Toxicol Res Ctr,Nam Gu, 253 Yonghyun Dong, Inchon 402751, South Korea. NR 45 TC 41 Z9 41 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD OCT PY 2000 VL 4 IS 5 BP 459 EP 471 DI 10.1006/niox.200.0300 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 366QP UT WOS:000090016300001 PM 11020335 ER PT J AU Eckelman, WC Tatum, JL Kurdziel, KA Croft, BY AF Eckelman, WC Tatum, JL Kurdziel, KA Croft, BY TI Quantitative analysis of tumor biochemisty using PET and SPECT SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Editorial Material C1 NIH, PET Dept, Bethesda, MD 20892 USA. NCI, Biomed Imaging Program, Rockville, MD USA. RP Eckelman, WC (reprint author), NIH, PET Dept, Bldg 10, Bethesda, MD 20892 USA. RI Croft, Barbara/D-1248-2013 OI Croft, Barbara/0000-0003-2544-150X NR 1 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 2000 VL 27 IS 7 BP 633 EP 635 DI 10.1016/S0969-8051(00)00163-3 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 379AC UT WOS:000165617900001 PM 11091104 ER PT J AU Carson, RE AF Carson, RE TI PET physiological measurements using constant infusion SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Quantitative Analysis of Tumor Biochemistry Using PET and SPECT CY NOV 18-19, 1999 CL BETHESDA, MARYLAND DE constant infusion; equilibrium; receptors; modeling; volume of distribution ID POSITRON EMISSION TOMOGRAPHY; LIVING HUMAN-BRAIN; C-11 RACLOPRIDE; GRAPHICAL ANALYSIS; RECEPTOR; BINDING; MODEL; QUANTIFICATION; MICRODIALYSIS AB A wide range of study designs can be used with positron emission tomography methods to provide quantitative measurements of physiological parameters. While bolus injection of tracer is the conventional approach, use of combined bolus plus constant infusion provides a number of advantages fur receptor binding tracers. Of recent interest is the use of this approach to dynamically follow the displacement of tracer during in vivo changes in neurotransmitter concentrations. This paper provides an overview of the tradeoffs in using bolus/infusion methods versus conventional bolus injection for receptor binding studies. NUCL MED BIOL 27;7:657-660, 2000. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIH, Warren Grant Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIH, Warren Grant Magnuson Clin Ctr, PET Dept, Bldg 10,Room 1C-401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 28 TC 45 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 2000 VL 27 IS 7 BP 657 EP 660 DI 10.1016/S0969-8051(00)00138-4 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 379AC UT WOS:000165617900005 PM 11091108 ER PT J AU Bacharach, SL Libutti, SK Carrasquillo, JA AF Bacharach, SL Libutti, SK Carrasquillo, JA TI Measuring tumor blood flow with (H2O)-O-15: Practical considerations SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Quantitative Analysis of Tumor Biochemistry Using PET and SPECT CY NOV 18-19, 1999 CL BETHESDA, MARYLAND DE tumor blood flow; PET; O-15-water; tumor perfusion ID POSITRON-EMISSION-TOMOGRAPHY; PET; QUANTITATION; WATER; INPUT; METABOLISM; PERFUSION; DELIVERY; MEDICINE; VOLUME AB The ability to measure blood flow to tumors non-invasively may be of importance in monitoring tumor therapies, assessing drug delivery, and understanding tumor physiology. Of all the radiotracer methods that have been proposed to measure tumor blood flow, the method based on labeled water-(H2O)-O-15-may be the most applicable to tumors. It is highly diffusible, does not participate significantly in metabolic processes during the short times involved in the study, and its uptake and clearance can be easily modeled. We present here an analysis of the bolus injection water methodology and how it might best be used to monitor tumor blood flow. Several different formulations of the basic methodology, based on previous applications in the heart and brain, are discussed. Potential problems of adapting these previous methodologies to tumor blood flow are presented. NUCL MED BIOL 27;7:671-676, 2000. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NCI, Ctr Clin, Bethesda, MD 20892 USA. RP Bacharach, SL (reprint author), NCI, Ctr Clin, Room 1C401,10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 40 TC 27 Z9 30 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 2000 VL 27 IS 7 BP 671 EP 676 DI 10.1016/S0969-8051(00)00136-0 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 379AC UT WOS:000165617900007 PM 11091110 ER PT J AU Heinz, A Jones, DW Raedler, T Coppola, R Knable, MB Weinberger, DR AF Heinz, A Jones, DW Raedler, T Coppola, R Knable, MB Weinberger, DR TI Neuropharmacological studies with SPECT in neuropsychiatric disorders SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Quantitative Analysis of Tumor Biochemistry Using PET and SPECT CY NOV 18-19, 1999 CL BETHESDA, MARYLAND DE SPECT; neuropharmacology; neuropsychiatric disorders ID CEREBRAL BLOOD-FLOW; EMISSION COMPUTED-TOMOGRAPHY; I-123 BETA-CIT; MUSCARINIC ACETYLCHOLINE-RECEPTORS; INERT-GAS CONCENTRATIONS; SEROTONIN TRANSPORTER; DOPAMINE-RECEPTORS; NEGATIVE SYMPTOMS; NONHUMAN-PRIMATES; DYNAMIC SPECT AB The last decade saw a rapid development of single photon emission computed tomography (SPECT) from a tool to assess cerebral blood flow to the stud!: of specific neurotransmitter systems. Because of the relatively long half life of SPECT radioisotopes, it is practical to measure the availability of neuroreceptors and transporters in conditions approaching equilibrium. The cost-efficiency of SPECT allowed studies in relatively large samples of patients with various neuropsychiatric disorders, We have applied this approach in studies of dopaminergic, serotonergic, and muscarinergic neurotransmission in patients with dementia, extrapyramidal disorders, schizophrenia, and alcoholism. No simple associations were observed between a single defect in one neurotransmitter system and a certain neuropsychiatric disease. Instead, complex dysfunction of several neurotransmitter systems in multiple, partially connected brain circuits have been implicated. Treatment effects also have been characterized. Microdialysis and neurotransmitter depletion studies showed that most radioligands and endogenous neurotransmitters compete for binding at receptors and transporters. Future research directions include the assessment of endogenous neurotransmitter concentrations measured by depletion studies and of genetic effects on neuroreceptor and transporter expression. NUCL MED BIOL 27;7:677-682, 2000. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIMH, CBDB, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Cent Inst Mental Hlth, D-6800 Mannheim, Germany. Klin Psychiat & Psychotherapie, Hamburg, Germany. Stanley Res Fdn, Bethesda, MD USA. RP Weinberger, DR (reprint author), NIMH, CBDB, Intramural Res Program, NIH, 10 Ctr Dr,Bldg 10,Room 4S235 MSC 1379, Bethesda, MD 20892 USA. NR 44 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 2000 VL 27 IS 7 BP 677 EP 682 DI 10.1016/S0969-8051(00)00135-9 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 379AC UT WOS:000165617900008 PM 11091111 ER PT J AU Stone, EJ AF Stone, EJ TI Overview of TAAG: Multicenter trial to prevent the decline in physical activity among girls during puberty SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA I82 BP 13S EP 13S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100053 ER PT J AU Del Parigi, A Chen, K Gautier, JF Salbe, AD Reiman, EM Tataranni, PA AF Del Parigi, A Chen, K Gautier, JF Salbe, AD Reiman, EM Tataranni, PA TI Gender differences in brain representation of taste in obese humans: a positron emission tomography study. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O8 BP 15S EP 15S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100061 ER PT J AU Salbe, AD Tataranni, PA DelParigi, A Pratley, RE AF Salbe, AD Tataranni, PA DelParigi, A Pratley, RE TI Hedonic responses to fat-sugar mixtures in Pima Indian and Caucasian adults. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, CDNS, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O41 BP 24S EP 24S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100094 ER PT J AU Weyer, C Vozarova, B Gautier, JF Pratley, RE Cizza, G Chrousos, G Ravussin, E Tataranni, PA AF Weyer, C Vozarova, B Gautier, JF Pratley, RE Cizza, G Chrousos, G Ravussin, E Tataranni, PA TI Effect of overnight partial chemical adrenalectomy and subsequent hydrocortisone infusion on muscle sympathetic nerve activity and resting metabolic rate in Caucasians and Pima Indians SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O65 BP 30S EP 30S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100118 ER PT J AU Pratley, RE Yang, XL Adams, SH Yu, XX Pan, GH Permana, P AF Pratley, RE Yang, XL Adams, SH Yu, XX Pan, GH Permana, P TI Skeletal muscle UCP5/BMCP1 mRNA levels are related to plasma insulin, resting metabolic rate and lipid oxidation rate in humans SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O70 BP 31S EP 31S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100124 ER PT J AU Weyer, C Pratley, RE Foley, JE Bogardus, C Tataranni, PA AF Weyer, C Pratley, RE Foley, JE Bogardus, C Tataranni, PA TI Enlarged subcutaneous abdominal adipocytes, but not obesity per se, predict type 2 diabetes independent of insulin resistance and insulin secretory dysfunction in Pima Indians SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O85 BP 35S EP 35S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100137 ER PT J AU Nicholson, JC McDuffie, JR Russell, DL Boyce, KA McCann, S Michael, M Sebring, NG Reynolds, JC Yanovski, JA AF Nicholson, JC McDuffie, JR Russell, DL Boyce, KA McCann, S Michael, M Sebring, NG Reynolds, JC Yanovski, JA TI Body composition by air displacement plethysmography in African American and Caucasian children SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NICHD, UGO, Bethesda, MD USA. NIDDK, DNRC, Bethesda, MD USA. NIH, CC, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O96 BP 37S EP 37S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100148 ER PT J AU Boyce, K Nguyen, T Russell, D McDuffie, J McCann, S Hubbard, V Yanovski, S Avila, N Yanovski, J AF Boyce, K Nguyen, T Russell, D McDuffie, J McCann, S Hubbard, V Yanovski, S Avila, N Yanovski, J TI Differences in the relationship between intra-abdominal adipose tissue and obesity-related comorbid conditions in overweight African American and Caucasian children. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NICHD, UGO, DEB, Bethesda, MD USA. NIDDK, DNRC, Bethesda, MD USA. NIDDK, DDDN, Bethesda, MD USA. NIH, DRD, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O136 BP 47S EP 47S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100188 ER PT J AU Joanisse, DR St-Onge, J Bricault, AM Gavrilova, O Reitman, ML AF Joanisse, DR St-Onge, J Bricault, AM Gavrilova, O Reitman, ML TI Skeletal muscle metabolic profile in white adipose tissue-lacking A-ZIP/F-1 mice. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Univ Laval, Div Kinesiol, Quebec City, PQ, Canada. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O139 BP 48S EP 48S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100190 ER PT J AU Uwaifo, GI Giere, SY Bulan, EJ Commons, G Spear, SL Yanovski, JA AF Uwaifo, GI Giere, SY Bulan, EJ Commons, G Spear, SL Yanovski, JA TI Clinical and metabolic relevance of large volume liposuction SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NICHD, Unit Growth Obes, DEB, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Div Plast Surg, Washington, DC 20007 USA. RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O165 BP 55S EP 55S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100217 ER PT J AU Tanofsky-Kraff, M Nguyen, TT Morgan, C McDuffie, J Russell, D Vue, S Wilfley, DE Yanovski, SZ Yanovski, JA AF Tanofsky-Kraff, M Nguyen, TT Morgan, C McDuffie, J Russell, D Vue, S Wilfley, DE Yanovski, SZ Yanovski, JA TI Eating-disordered pathology, body fat and depression in children and adolescents. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NICHD, UGO, DEB, Bethesda, MD USA. NIDDK, DDDN, NIH, Bethesda, MD USA. San Diego State Univ, UCSD Program Clin Psychol, San Diego, CA 92182 USA. Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O175 BP 57S EP 57S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100226 ER PT J AU McCann, S McDuffie, J Nicholson, J Sastry, L Calis, K Yanovski, J AF McCann, S McDuffie, J Nicholson, J Sastry, L Calis, K Yanovski, J TI A pilot study of the efficacy of orlistat in overweight adolescents. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NICHD, UGO, DEB, Bethesda, MD USA. NIDDK, DNRC, Bethesda, MD USA. NIH, Dept Pharm, CC, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O179 BP 58S EP 58S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100230 ER PT J AU Visser, M Bouter, LM McQuillan, GM Wener, MH Harris, TB AF Visser, M Bouter, LM McQuillan, GM Wener, MH Harris, TB TI Low-grade systemic inflammation in overweight children SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Vrije Univ Amsterdam, EMGO Inst, Amsterdam, Netherlands. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PD5 BP 98S EP 98S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100386 ER PT J AU Mcduffie, J Drinkard, B McCann, S Nicolson, J Yanovski, JA AF Mcduffie, J Drinkard, B McCann, S Nicolson, J Yanovski, JA TI Relationships between functional performance and cardiorespiratory fitness in overweight adolescents SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIH, NICHD, DEB, Unit Growth & Obes, Bethesda, MD 20892 USA. NIH, CC, Dept Rehabil Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PF21 BP 121S EP 121S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100474 ER PT J AU Lindsay, RS Weyer, C Knowler, WC Walker, BR Tataranni, PA AF Lindsay, RS Weyer, C Knowler, WC Walker, BR Tataranni, PA TI The influence of ethnicity and body fat on urinary glucocorticoid metabolites in Pima and Caucasian subjects SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ 85016 USA. Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PF29 BP 123S EP 123S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100482 ER PT J AU Namata, G Weyer, C Pratley, R AF Namata, G Weyer, C Pratley, R TI Acute insulin secretory responses to glucose are higher in African-Americans with normal glucose tolerance than in Caucasians SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PF31 BP 123S EP 123S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100483 ER PT J AU Vozarova, B Weyer, C Bogardus, C Tataranni, PA AF Vozarova, B Weyer, C Bogardus, C Tataranni, PA TI Higher oral temperature in Pima Indians compared to Caucasians is not explained by differences in body shape. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, CDNS, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PF30 BP 123S EP 123S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100484 ER PT J AU Harris, T Visser, M Goodpaster, B Kritchevsky, S Newman, A Simonsick, E Rubin, S Nevitt, M Pahor, M Hubbard, V Everhart, J AF Harris, T Visser, M Goodpaster, B Kritchevsky, S Newman, A Simonsick, E Rubin, S Nevitt, M Pahor, M Hubbard, V Everhart, J TI Visceral and thigh intermuscular fat explain the association of interleukin-6 with BMI: The Health, Aging and Body Composition Study (Health ABC) SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Epidemiol Demography & Biometry Program, NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PF45 BP 127S EP 127S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100498 ER PT J AU Kaufman, RH Adam, E Hatch, EE Noller, K Herbst, AL Palmer, JR Hoover, RN AF Kaufman, RH Adam, E Hatch, EE Noller, K Herbst, AL Palmer, JR Hoover, RN TI Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID GENITAL-TRACT ABNORMALITIES; CERVICAL CERCLAGE; PRETERM DELIVERY; CONTROLLED TRIAL; WOMEN; RISK; MANAGEMENT; UTERO AB Objective: To evaluate long-term pregnancy experiences of women exposed to diethylstilbestrol (DES) in utero compared with unexposed women. Methods: This study was based on diethylstilbestrol-exposed daughters, the National Collaborative Diethylstylbistrol Adenosis cohort and the Chicago cohort, and their respective nonexposed comparison groups. Subjects who could be traced were sent a detailed questionnaire in 1994 that contained questions on health history, including information on pregnancies and their outcomes. We reviewed 3373 questionnaires from exposed daughters and 1036 questionnaires from unexposed women. Results: The response rate was 88% among exposed and unexposed women. Diethylstilbestrol-exposed women were less likely than unexposed women to have had full-term live births and more likely to have had premature births, spontaneous pregnancy losses, or ectopic pregnancies. Full-term infants were delivered in the first pregnancies of 84.5% of unexposed women compared with 64.1% of exposed women identified by record review (relative risk [RR] 0.76, confidence interval [CI] 0.72, 0.80). Preterm delivery of first births occurred in 4.1% of unexposed compared with 11.5% of exposed women, and ectopic pregnancies in 0.77% of unexposed compared with 4.2% of exposed women. Spontaneous abortion was reported in 19.2% of DES-exposed women compared with 10.3% in control women (RR 2.00, CI 1.54, 2.60). According to complete pregnancy histories (many women had more than one pregnancy), preterm births were more common in DES-exposed women (19.4% exposed versus 7.5% unexposed (RR 2.93 CI 2.23, 3.86). Second-trimester spontaneous pregnancy losses were more common in DES-exposed women (6.3% versus 1.6%; RR 4.25, CI 2.36, 7.66). More first-trimester spontaneous abortions occurred in DES-exposed women than in controls (RR 1.31, CI 1.13, 1.53), and DES-exposed women had at least one ectopic pregnancy more often than unexposed women (RR 3.84, CI 2.26, 6.54). Conclusion: Pregnancy outcomes in DES-exposed women were worse than those in unexposed women. (Obstet Gynecol 2000;96:483-9. (C) 2000 by The American College of Obstetricians and Gynecologists.). C1 Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Baylor Coll Med, Dept Epidemiol, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Div Canc Epidemiol, Bethesda, MD USA. Univ Massachusetts, Med Ctr, Dept Obstet & Gynecol, Worcester, MA USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Boston Univ, Sch Publ Hlth, Slone Epidemiol Unit, Boston, MA USA. RP Kaufman, RH (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NCI NIH HHS [N-01CP-50531] NR 18 TC 72 Z9 76 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2000 VL 96 IS 4 BP 483 EP 489 DI 10.1016/S0029-7844(00)00959-5 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 358YM UT WOS:000089584800001 PM 11004345 ER PT J AU Smith, RE Lembersky, BC Wieand, HS Colangelo, L Mamounas, EP AF Smith, RE Lembersky, BC Wieand, HS Colangelo, L Mamounas, EP TI UFT/leucovorin vs 5-FU/leucovorin in colon cancer SO ONCOLOGY-NEW YORK LA English DT Article; Proceedings Paper CT Orzel/UFT Investigators Meeting and Consensus Conference CY OCT 07-10, 1999 CL VANCOUVER, CANADA SP Univ Alabama Birmingham, Comprehens Canc Ctr ID ORAL REGIMEN; URACIL; LEUCOVORIN; 5-FLUOROURACIL; FTORAFUR AB Adjuvant chemotherapy has been shown to alter the natural history of resected colon cancer. Two regimens (fluorouracil [5-FU]plus leucovorin and 5-FU plus levamisole) have been found to prolong disease-free survival and overall survival irt affected patients. Previous comparisons of these two regimens indicate that 5-FU plus leucovorin may offer a small disease-free survival and overall survival advantage. Evidence that UFT (uracil and tegafur) plus oral leucovorin is associated with significant antitumor activity and has an acceptable toxicity profile makes this a logical formulation for the adjuvant treatment of colon cancer, The National Surgical Adjuvant Breast and Bowel Project Protocol C-06 is a randomized comparison of the relative efficacies of 5-FU plus leucovorin vs UFT plus leucovorin. Preliminary analysis of the toxicity findings among 1,530 evaluable patients indicates that both regimens are well tolerated and have similar toxicity profiles. C1 Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA 15212 USA. Natl Surg Adjuvant Breast & Bowel Project, Biostat Operat Ctr, Pittsburgh, PA USA. Mt Sinai Med Ctr, Cleveland, OH 44106 USA. RP Smith, RE (reprint author), Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, E Commons Profess Bldg,4 Allegheny Ctr,5th Floor, Pittsburgh, PA 15212 USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 2000 VL 14 IS 10 SU 9 BP 24 EP 27 PG 4 WC Oncology SC Oncology GA 371KT UT WOS:000165178700003 PM 11098486 ER PT J AU Anders, RF Saul, A AF Anders, RF Saul, A TI Malaria vaccines SO PARASITOLOGY TODAY LA English DT Article ID PLASMODIUM-FALCIPARUM SPOROZOITES; MONOCLONAL-ANTIBODIES; PROTECTIVE EFFICACY; IMMUNE-RESPONSES; IMMUNOGENICITY; IMMUNIZATION; PROTEIN; ERYTHROCYTES; EXPRESSION; ANTIGENS AB Although the possibility of a live attenuated malaria vaccine has been considered, current malaria vaccine development activities are dominated by attempts to develop a subunit vaccine. Hence, it is entirely appropriate that a session of the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, was devoted to vaccine development. The oral presentations in this session and the relevant poster presentations are outlined here by Robin Anders and Allan Saul. C1 La Trobe Univ, Dept Biochem, Bundoora, Vic 3083, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Anders, RF (reprint author), La Trobe Univ, Dept Biochem, Bundoora, Vic 3083, Australia. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 23 TC 25 Z9 28 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD OCT PY 2000 VL 16 IS 10 BP 444 EP 447 DI 10.1016/S0169-4758(00)01784-1 PG 4 WC Parasitology SC Parasitology GA 359YL UT WOS:000089639600010 PM 11006477 ER PT J AU Zhang, J Hattori, N Leroy, E Morris, HR Kubo, SI Kobayashi, T Wood, NW Polymeropoulos, MH Mizuno, Y AF Zhang, J Hattori, N Leroy, E Morris, HR Kubo, SI Kobayashi, T Wood, NW Polymeropoulos, MH Mizuno, Y TI Association between a polymorphism of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene and sporadic Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; ubiquitin carboxy-terminal hydrolase L1 gene; Lewy bodies; polymorphism; association study ID ALPHA-SYNUCLEIN; BODIES AB We found a novel polymorphism (S/Y18) of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene a mutation of which is expected to contribute to the etiology of a form of familial Parkinson's disease (PD). We report the frequency of this polymorphism in 313 patients with sporadic PD and 302 control subjects (Japanese and Caucasians). The frequency of the mutant allele (Y) was significantly higher in Japanese control subjects (51.2%) than in Japanese PD patients (43.4%) (chi(2) = 3.917, p = 0.048 < 0.05). It appears that this polymorphism has a weak protective factor against PD in at least the Japanese population. The frequencies of Y allele and S/Y and Y/Y genotypes in the PD patients and the controls were more significantly higher in Japanese than in Caucasian population (p < 0.0001). It seems that the role of this polymorphism in PD may he different between Caucasian and Japanese populations. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Juntendo Univ, Sch Med, Dept Neurol, Bunkyo Ku, Tokyo 1130033, Japan. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Inst Neurol, Univ Dept Clin Neurol, London WC1N 3BG, England. Novartis Pharmaceut Corp, Pharmacogenet, Gaithersburg, MD 20878 USA. RP Hattori, N (reprint author), Juntendo Univ, Sch Med, Dept Neurol, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1130033, Japan. RI Morris, Huw/B-8527-2008; turton, miranda/F-4682-2011; Wood, Nicholas/C-2505-2009 OI Morris, Huw/0000-0002-5473-3774; Wood, Nicholas/0000-0002-9500-3348 NR 9 TC 48 Z9 50 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD OCT PY 2000 VL 6 IS 4 BP 195 EP 197 DI 10.1016/S1353-8020(00)00015-8 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 354CP UT WOS:000089312500001 ER PT J AU Hori, M Shimazaki, J Inagawa, S Itabashi, M Hori, M AF Hori, M Shimazaki, J Inagawa, S Itabashi, M Hori, M TI Alternatively spliced MDM2 transcripts in human breast cancer in relation to tumor necrosis and lymph node involvement SO PATHOLOGY INTERNATIONAL LA English DT Article DE human breast cancer; MDM2 oncogene; splice variant mRNA; tumor necrosis ID P53 PROTEIN; EXPRESSION; GENE; ASSOCIATION; CARCINOMA; PROGNOSIS; AMPLIFICATION; NEOPLASMS AB Several short forms of alternatively spliced Murine double minute 2 (MDM2) transcripts have recently been shown to correlate with high-grade malignancy in a number of human tumors. We examined the frequency of splice variants and their correlation with clinicopathological features in 60 cases of human breast cancer. Seven short forms coexpressed with wild-type mRNA were detected by nested RT-PCR. Sequencing of all the MDM2 variants demonstrated mRNA splicing which disrupted not only the conserved p53-binding domain but also, further towards the carboxy-terminus, the conserved nuclear localization sequence and/or the acidic and zinc finger domains. There was no significant correlation between the coexpression of splice variants and tumor size, histologic type or hormone (estrogen and progesterone) receptor status. However, cases with spliced MDM2 transcripts tended to be of a more aggressive type with axillary lymph node involvement and extensive necrosis in the tumors. Although the functional significance of MDM2 variants remains obscure, we anticipate that these variants will be confirmed as a novel prognostic marker in human breast cancer. C1 Ibaraki Prefectural Cent Hosp & Canc Ctr, Dept Pathol, Tomobe, Ibaraki 3091703, Japan. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Hori, M (reprint author), Ibaraki Prefectural Cent Hosp & Canc Ctr, Dept Pathol, 6528 Koibuchi, Tomobe, Ibaraki 3091703, Japan. NR 22 TC 21 Z9 22 U1 0 U2 0 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD OCT PY 2000 VL 50 IS 10 BP 786 EP 792 DI 10.1046/j.1440-1827.2000.01119.x PG 7 WC Pathology SC Pathology GA 365PA UT WOS:000089958600005 PM 11107050 ER PT J AU Robbins, JB Schneerson, R Gotschlich, EC AF Robbins, JB Schneerson, R Gotschlich, EC TI A rebuttal: epidemic and endemic meningococcal. meningitis in sub-Saharan Africa can be prevented now by routine immunization with group A meningococcal capsular polysaccharide vaccine SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE epidemic meningitis; meningococcal meningitis; sub-Saharan Africa; Group A meningococcal polysaccharide vaccine; WHO policy for meningococcal meningitis ID A NEISSERIA-MENINGITIDIS; OUTER-MEMBRANE PROTEIN; BACTERIAL-MENINGITIS; MASS VACCINATION; DISEASE; CHILDREN; INFANTS; STRATEGIES; ANTIBODIES; EFFICACY C1 NICHHD, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, New York, NY 10021 USA. RP Robbins, JB (reprint author), NICHHD, NIH, Bldg 6,Room 424, Bethesda, MD 20892 USA. NR 73 TC 25 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 2000 VL 19 IS 10 BP 945 EP 953 DI 10.1097/00006454-200010000-00001 PG 9 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 367PF UT WOS:000090070100001 PM 11055594 ER PT J AU Uzel, G Premkumar, A Malech, HL Holland, SM AF Uzel, G Premkumar, A Malech, HL Holland, SM TI Respiratory syncytial virus infection in patients with phagocyte defects SO PEDIATRICS LA English DT Article DE respiratory syncytial virus; phagocyte; immunodeficiency; pneumonia ID INTERFERON-GAMMA-RECEPTOR; MYCOBACTERIAL INFECTION; SUSCEPTIBILITY; DEFICIENCY; MUTATION; CHILDREN AB Patients with phagocyte defects frequently develop bacterial or fungal pneumonias, but they are not considered to be at increased risk for viral infections. We describe 3 patients with known phagocyte immunodeficiencies who developed lower respiratory tract infections (LRTI) caused by respiratory syncytial virus (RSV). All 3 patients had dense pneumonias as indicated by computed tomography scan of the lungs and RSV was recovered. We conclude that RSV can present as a dense pneumonia in patients with phagocyte defects. Along with common pathogens causing LRTI, RSV should be considered in the differential diagnosis. Viral cultures as well as rapid antigen detection assays for respiratory viruses should be included in the evaluation of LRTI in patients with phagocyte defects. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 15 TC 7 Z9 7 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2000 VL 106 IS 4 BP 835 EP 838 DI 10.1542/peds.106.4.835 PG 5 WC Pediatrics SC Pediatrics GA 359QG UT WOS:000089623100046 PM 11015530 ER PT J AU Nekhai, S Bottaro, DP Woldehawariat, G Spellerberg, A Petryshyn, R AF Nekhai, S Bottaro, DP Woldehawariat, G Spellerberg, A Petryshyn, R TI A cell-permeable peptide inhibits activation of PKR and enhances cell proliferation SO PEPTIDES LA English DT Article DE PKR; cell-permeable peptide; eIF-2 alpha phosphorylation; regulation of cell proliferation ID DOUBLE-STRANDED-RNA; DEPENDENT PROTEIN-KINASE; NUCLEAR-LOCALIZATION SEQUENCE; TRANSLATIONAL CONTROL MECHANISM; NF-KAPPA-B; BINDING DOMAIN; MALIGNANT TRANSFORMATION; CATALYTIC DOMAIN; 3T3 CELLS; INTERFERON AB The double-stranded RNA dependent protein kinase (PKR) is a negative regulator of cell proliferation and thus itself a target for modulation. We show that a cell-permeable peptide (PRI), containing a conserved double-stranded RNA binding motif found in PKR, inhibits activation of the kinase and activity to phosphorylate its substrate. Further, the PRI-peptide localizes to the cytoplasm of murine embryonic fibroblasts and ablates: cellular. PKR activation. The PRI-peptide enhances cell proliferation compared to treatment with a variant control peptide, resulting in cultures with increased cell density. We conclude that peptides that interfere with PKR may be useful tools for regulating cell proliferation. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Ctr Canc & Transplantat Biol, Washington, DC 20010 USA. George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC 20010 USA. RP Petryshyn, R (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Room 8040,6116 Execut Blvd, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU PHS HHS [A42717] NR 35 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD OCT PY 2000 VL 21 IS 10 BP 1449 EP 1456 DI 10.1016/S0196-9781(00)00297-7 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 372FN UT WOS:000165223800001 PM 11068090 ER PT J AU Cartwright, WS AF Cartwright, WS TI Cocaine medications, cocaine consumption and societal costs SO PHARMACOECONOMICS LA English DT Article ID PREVALENCE AB Objective: To estimate the benefits of reduced cocaine consumption in terms of reduced societal costs resulting from the introduction of a medication for cocaine dependence with a small incremental treatment effect. Study design: Cost-benefit analysis is applied to study the implications of reduced cocaine consumption. A modelling approach extrapolates the magnitude of treatment effects. Methods: Epidemiological data on cocaine use and consumption as well as economic methods of cost-benefit analysis are utilised. Estimates of societal costs associated with heavy users of cocaine, who are most likely addicted and in need of immediate treatment, are developed using 1995 data. Main outcome measures and results: In the first analysis, a postulated 1% reduction in consumption of cocaine among heavy users is examined to approximate a small treatment effect, resulting in a minimal consumption benefit. It is estimated that such a reduction would be valued at $US259 million. The cost-benefit analysis indicated that a cocaine medication with a small treatment effect (10 percentage point increase in abstinence rates) would result in a benefit to cost ratio in the range of 1.58 to 5.79, depending on prescribing behaviour and type of patient. Conclusions: Such estimates of the benefits of these small treatment effects are conservative, and they may be biased downwards since the willingness to pay for such a cocaine medication could far exceed the benefit to cost estimation used in this paper. Nevertheless, the substantial benefits found in this paper indicate how important investment in cocaine medication is for public health policy; costs may be reduced with efficient prescribing behaviour. Market and governmental barriers to the utilisation of a cocaine medication could reduce the benefits and increase costs. Clinical trials, cost-effectiveness studies, and cost-benefit studies must be conducted to establish the actual pattern of benefits and costs that could be obtained for an efficacious and effective cocaine medication. C1 NIDA, Bethesda, MD 20892 USA. RP Cartwright, WS (reprint author), NIDA, 6001 Execut Blvd,Room 4222,Msc 9565, Bethesda, MD 20892 USA. NR 17 TC 10 Z9 10 U1 0 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PD OCT PY 2000 VL 18 IS 4 BP 405 EP 413 DI 10.2165/00019053-200018040-00008 PG 9 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 362CH UT WOS:000089760700008 PM 15344308 ER PT J AU Jackson, A Mead, AN Stephens, DN AF Jackson, A Mead, AN Stephens, DN TI Behavioural effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-receptor antagonists and their relevance to substance abuse SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE AMPA receptors; NMDA receptors; substance abuse; plasticity; sensitisation; conditioning ID CONDITIONED PLACE PREFERENCE; EXCITATORY AMINO-ACIDS; VENTRAL TEGMENTAL AREA; AMPA RECEPTOR ANTAGONIST; RAT NUCLEUS-ACCUMBENS; D-ASPARTATE RECEPTORS; AMPHETAMINE ADMINISTRATION ALTERS; INDUCED LOCOMOTOR-ACTIVITY; LOCUS-COERULEUS NEURONS; NMDA RECEPTOR AB This review presents some of the work that has been carried out to investigate the behavioural effects of alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-receptor antagonists in animal models of substance abuse, Many of the studies have been conducted in light of current ideas that emphasise the analogous role of glutamatergic mechanisms in synaptic plasticity and long-term behavioural adaptation to drugs. Experiments on behavioural sensitisation indicate that whereas N-methyl-D-aspartate receptors are involved in induction, AMPA-receptors may mediate expression of the established response. In this regard, an important factor may be the degree of drug-environment conditioning. Thus, studies of the effects of AMPA-receptor antagonists on conditioned behaviours are reviewed here, Relatively few studies on the effects of AMPA-receptor antagonists on primary reinforcement from self-administered drugs and the subjective effects of drugs have been carried out, but a profile that contrasts with that of the N-methyl-D-aspartate antagonists appears to be emerging. Studies of withdrawal from opioids suggest that whilst AMPA-receptor antagonists may not be able to prevent tolerance or dependence from developing, they may ameliorate both the physical and emotional consequences of withdrawal. Overall, the AMPA-receptor antagonists may represent a promising new approach for treating the consequences of drug abuse. However, as results are often complicated by the use of the less-selective compounds, it will be important to use better tools in future studies. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Sussex, Sch Biol Sci, Brighton BN1 9QG, E Sussex, England. NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Jackson, A (reprint author), Univ Sussex, Sch Biol Sci, Brighton BN1 9QG, E Sussex, England. RI Stephens, David/G-2384-2012 NR 182 TC 23 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD OCT PY 2000 VL 88 IS 1 BP 59 EP 76 DI 10.1016/S0163-7258(00)00078-4 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 365QK UT WOS:000089961800004 PM 11033384 ER PT J AU Sreenivasan, G AF Sreenivasan, G TI What is the general will? SO PHILOSOPHICAL REVIEW LA English DT Article C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Sreenivasan, G (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. NR 17 TC 12 Z9 13 U1 0 U2 1 PU CORNELL UNIV SAGE SCHOOL PHILOSOPHY PI ITHACA PA PHILOSOPHICAL REVIEW 220 GOLDWIN SMITH HALL, ITHACA, NY 14853 USA SN 0031-8108 J9 PHILOS REV JI Philos. Rev. PD OCT PY 2000 VL 109 IS 4 BP 545 EP 581 DI 10.2307/2693624 PG 37 WC Philosophy SC Philosophy GA 441PJ UT WOS:000169238500003 ER PT J AU Roberts, JE Wishart, JF Martinez, L Chignell, CF AF Roberts, JE Wishart, JF Martinez, L Chignell, CF TI Photochemical studies on xanthurenic acid SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HUMAN LENS; OXYGEN; EYE; CONSTITUENTS; GLUCOSIDE; PROTEINS; AZIDE AB The tryptophan metabolite xanthurenic acid (Xan) has been isolated from aged human cataractous lenses. The photophysical properties of Xan were examined to determine if it is a potential chromophore for age-related cataractogenesis. We found that Xan produces singlet oxygen (phi (A) = 0.17 in CD3OD) with the same efficiency as the lenticular chromophore N-formyl kynurenine and quenches singlet oxygen at a rate similar (2.1 x 10(7); CD,OD) to other tryptophan metabolites found in the eye. As the mechanisms of induction of cataracts may also involve redox reactions, the interactions of hydrated electrons (e(aq)-), the azide radical (N-3(.)) and hydroxyl radical (OH.) with Xan were studied using the technique of pulse radiolysis. The reaction rate constants of e(aq)(-), N-3(.) and OH. with Xan were found to be of the same order of magnitude as other tryptophan metabolites. The rate constant for reaction of Xan with e(aq)(-) solvated electrons was found to be diffusion controlled (k = 1.43 x 10(10) M-1 s(-1)); the reaction with N-3(.) was very fast (k = 4.0 x 10(9) M-1 s(-1)); and with OH. was also near diffusion controlled (k = 1.0 x 10(10) M-1 s(-1)). Superoxide O-2(.-) production by irradiated Xan in methanol was detected by electron paramagnetic resonance and substantiated by determining that the enhanced rate of oxygen consumption of Xan irradiated in the presence of furfuryl alcohol was lowered by superoxide dismutase. C1 Fordham Univ, New York, NY 10023 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Roberts, JE (reprint author), Fordham Univ, 113 W 60th St, New York, NY 10023 USA. RI Wishart, James/L-6303-2013 OI Wishart, James/0000-0002-0488-7636 NR 22 TC 26 Z9 27 U1 0 U2 4 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 2000 VL 72 IS 4 BP 467 EP 471 DI 10.1562/0031-8655(2000)072<0467:PSOXA>2.0.CO;2 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 366VU UT WOS:000090027600007 PM 11045716 ER PT J AU Beutler, JA McCall, KL Herbert, K Johnson, T Shoemaker, RH Boyd, MR AF Beutler, JA McCall, KL Herbert, K Johnson, T Shoemaker, RH Boyd, MR TI Cytotoxic clerodane diterpene esters from Laetia corymbulosa SO PHYTOCHEMISTRY LA English DT Article DE Laetia corymbulosa; Flacourtiaceae; diterpenoids; corymbulosin A ID LEAVES AB Three cytotoxic cleroodane diterpene esters, corymbulosins A-C, were isolated from an organic extract of the fruit of Laetia corymbulosa (Flacourtiaceae) from Peru. The structures were determined by spectroscopic methods as clerodane diterpenes unsaturated at C-3, C-13(16) and C-14. Corymbulosin A was esterified at C-2 with a decadienoate moiety, while corymbulosins B and C were C-2 epimers esterified at C-6 with a decanoate moiety. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU NCI NIH HHS [N01-CO-56000] NR 8 TC 23 Z9 23 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD OCT PY 2000 VL 55 IS 3 BP 233 EP 236 DI 10.1016/S0031-9422(00)00281-8 PG 4 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 378YK UT WOS:000165613100008 PM 11142848 ER PT J AU Yabroff, KR Kerner, JF Mandelblatt, JS AF Yabroff, KR Kerner, JF Mandelblatt, JS TI Effectiveness of interventions to improve follow-up after abnormal cervical cancer screening SO PREVENTIVE MEDICINE LA English DT Article DE Pap smear; colposcopy; screening; meta-analyses; interventions ID INCREASE MAMMOGRAPHY USE; INCOME MINORITY WOMEN; MEAN SOJOURN TIME; PAPANICOLAOU SMEARS; PAP SMEARS; EDUCATIONAL BROCHURES; PATIENT COMPLIANCE; COLORECTAL-CANCER; BLACK-WOMEN; ADHERENCE AB Objective. The purpose of this study was to determine the effectiveness of interventions designed to improve follow-up after an abnormal Pap smear. Methods. We performed a qualitative meta-analysis of interventions designed to improve follow-up after an abnormal Pap smear and included studies that met the following criteria: randomized or concurrently controlled study design, defined outcomes, and data available for abstraction. Interventions were classified as behavioral, cognitive, sociologic, or combined strategies (e.g,, behavioral and cognitive). Abnormal Pap smears were defined as any test result requiring additional follow-up. Effectiveness was measured by the rate of compliance with recommended follow-up. Results, Twenty-two interventions in 10 studies met the inclusion criteria. Cognitive interventions utilizing interactive telephone counseling were the most effective, improving compliance by 24 to 31%, Behavioral interventions, such as patient reminders, were also effective, increasing follow-up by up to 18%, Not all of these results achieved statistical significance. The single sociologic intervention we identified used videotaped peer discussions to provide a message about abnormal Pap smears and appropriate follow-up. This intervention was not associated with increased followup after an abnormal test. The effectiveness of interventions using multiple types of strategies to improve follow-up was inconsistent. Conclusions, Cognitive strategies led to the greatest improvement in compliance with follow-up of abnormal Pap smear screening tests. Extension of similar interventions to follow-up of abnormal breast and colon cancer screening, development of physician- and system-targeted interventions, and evaluation of the cost-effectiveness of these strategies are important priorities for future research. (C) 2000 American Health Foundation and Academic Press. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Med, Washington, DC 20007 USA. MEDTAP Int, Bethesda, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Mandelblatt, JS (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Med, 2233 Wisconsin Ave,Suite 430, Washington, DC 20007 USA. OI Kerner, Jon/0000-0002-8792-3830; Yabroff, K. Robin/0000-0003-0644-5572 FU AHRQ HHS [HS 08395]; NCI NIH HHS [R01 CA72908, R01CA65881] NR 64 TC 44 Z9 45 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD OCT PY 2000 VL 31 IS 4 BP 429 EP 439 DI 10.1006/pmed.2000.0722 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 358PK UT WOS:000089566300018 PM 11006069 ER PT J AU Castro, R Barlow-Walden, L Woodson, T Kerecman, JD Zhang, GH Martinez, JR AF Castro, R Barlow-Walden, L Woodson, T Kerecman, JD Zhang, GH Martinez, JR TI Ion transport in an immortalized rat submandibular cell line SMG-C6 SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID EPITHELIAL NA+ CHANNEL; TRACHEAL EPITHELIUM; SALIVARY-GLAND; G-PROTEIN; AMILORIDE; EXPRESSION; DUCT; ABSORPTION; SECRETION; CULTURE AB The immortalized rat submandibular epithelial cell line, SMG-C6, cultured on porous tissue culture supports, forms polarized, tight-junction epithelia facilitating bioelectric characterization in Ussing chambers. The SMG-C6 epithelia generated transepithelial resistances of 956+/-84 Ohm.cm(2) and potential differences (PD) of -16.9+/-1.5mV (apical surface negative) with a basal short-circuit current (I-SC) of 23.9 +/- 1.7 mu A/cm(2) (n = 69), P2 nucleotide receptor agonists, ATP or UTP, applied apically or basolaterally induced a transient increase in I,,, followed by a sustained decreased below baseline value, The peak Delta/(SC) increase was partly sensitive to CI- and K+ channel inhibitors, DPC, glibenclamide, and tetraethylammonium (TEA) and was completely abolished following Ca2+ chelation with BAPTA or bilateral substitution of gluconate for CI-. The major component of basal I-SC was sensitive to apical Na+ replacement or amiloride (half-maximal inhibitory concentration 392 nM), Following pretreatment with amiloride, ATP induced a significantly greater I-SC; however, the poststimulatory decline was abolished, suggesting an ATP-induced inhibition of amiloride-sensitive Na+ transport. Consistent with the ion transport properties found in Ussing chambers, SMG-C6 cells express the rat epithelial Na+ channel alpha-subunit (alpha-rENaC). Thus, cultured SMG-C6 cells produce tight polarized epithelia on permeable support with stimulated CI- secretory conductance and an inward I-SC accounted for by amiloride-sensitive Na+ absorption. C1 Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, Dept Pediat, San Antonio, TX 78236 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Castro, R (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pediat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 42 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD OCT PY 2000 VL 225 IS 1 BP 39 EP 48 DI 10.1046/j.1525-1373.2000.22505.x PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 359AV UT WOS:000089590100005 PM 10998197 ER PT J AU Boesen, CC Motyka, SA Patamawenu, A Sun, PD AF Boesen, CC Motyka, SA Patamawenu, A Sun, PD TI Development of a recombinant bacterial expression system for the active form of a human transforming growth factor beta type II receptor ligand binding domain SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID TGF-BETA; CRYSTAL-STRUCTURE; GROWTH-FACTOR-BETA-2; KINASE AB Expression systems have been designed to test the suitability of expressing the high cysteine containing extracellular domain (residues 1-136) of human transforming growth factor beta type II receptor (T beta RII), Receptor expressed using a baculovirus system was functional following both enzymatic deglycosylation and elimination of the N-terminal 22 amino acids by protease degradation. Bacterial expression of a T beta RII lacking the 26 N-terminal amino acids retained the ability to bind its ligand, TGF-beta 1. Receptor expressed in bacteria was sensitive to proteolytic degradation at residue Lys98 but a K98T mutation eliminated degradation and did not disrupt binding. Although several different forms of T beta RII were expressed, only a fusion with glutathione S-transferase gave soluble T beta RII, which was purified at a yield of 0.1 mg/10 L of bacterial growth. N-Terminal truncations of T beta RII (residues 22-136 or 27-136) could be refolded from inclusion bodies and purified to an active form with an efficiency of 10%. (C) 2000 Academic Press. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Sun, PD (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 12 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD OCT PY 2000 VL 20 IS 1 BP 98 EP 104 DI 10.1006/prep.2000.1306 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 364WJ UT WOS:000089916800014 PM 11035957 ER PT J AU Fenton, WS AF Fenton, WS TI Heterogeneity, subtypes, and longitudinal course in schizophrenia SO PSYCHIATRIC ANNALS LA English DT Article ID DEFICIT SYNDROME; NEGATIVE SYMPTOMS; NONDEFICIT FORMS; NATURAL-HISTORY; LONG-TERM; IMPAIRMENTS; ABNORMALITIES; CLOZAPINE; DISORDER; MODEL C1 NIMH, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. RP Fenton, WS (reprint author), 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 49 TC 3 Z9 3 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 2000 VL 30 IS 10 BP 638 EP 644 PG 7 WC Psychiatry SC Psychiatry GA 363XA UT WOS:000089861900005 ER PT J AU Heishman, SJ Henningfield, JE AF Heishman, SJ Henningfield, JE TI Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; human; nonsmoker; tolerance; psychomotor; cognition-mood; cardiovascular effect; plasma nicotine concentration ID SUBCUTANEOUS NICOTINE; PSYCHOMOTOR PERFORMANCE; CIGARETTE-SMOKING; NEVER-SMOKERS; CHEWING GUM; MEMORY; HUMANS; SENSITIZATION; AMPHETAMINE; RATINGS AB Rationale: When administered acutely to nonsmokers, nicotine's effects on performance are inconsistent, perhaps because of suboptimal dosing or initial dysphoria that could interfere with performance. Objective: The purpose of this study was to determine if a range of nicotine doses administered for 8 days to nonsmokers would enhance psychomotor and cognitive abilities and to document the development of nicotine tolerance or sensitization. Methods: Twelve male volunteers, who reported ever smoking five cigarettes or less, participated in 8 consecutive experimental days in which they were administered four doses of nicotine polacrilex gum each day in this order: 0, 2, 1, and 8 mg. Performance, subjective, and physiological measures were assessed before and after each dose. Results: Plasma nicotine concentration ranged from 6.9 to 11.5 ng/ml following the 8 mg dose. Nicotine increased rate of responding and decreased response time on working memory (digit recall); however, accuracy was impaired. Nicotine also de creased accuracy on visual scanning and attention (two-letter search), and the 8 mg dose impaired gross motor coordination (circular lights). Tolerance did not develop to the performance impairing effects of nicotine. Nicotine produced dose-related increases in ratings of dysphoria and negative mood, including tension, anxiety, nervousness, turning of stomach, and sedation. Tolerance developed to some, but not all, of these aversive effects. Tolerance also was not observed to the increased cardiovascular measures. Conclusion: Although tolerance developed to some of the aversive effects of nicotine, performance enhancement was not observed. These data do not support the hypothesis that nicotine-induced performance enhancement contributes to the reinforcing effects of tobacco use during the early stages of dependence development. C1 NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, Baltimore, MD 21224 USA. Pinney Associates, Bethesda, MD 20814 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. RP Heishman, SJ (reprint author), NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 56 TC 58 Z9 58 U1 4 U2 9 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2000 VL 152 IS 3 BP 321 EP 333 DI 10.1007/s002130000541 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 375UD UT WOS:000165418900012 PM 11105943 ER PT J AU Choyke, PL AF Choyke, PL TI Dynamic contrast-enhanced MR imaging of the scrotum: Reality check SO RADIOLOGY LA English DT Editorial Material DE editorials; epididymitis; magnetic resonance (MR), contrast enhancement; magnetic resonance (MR), rapid imaging; magnetic resonance (MR), three-dimensional; scrotum, diseases; scrotum, MR; testis, abnormalities; testis, neoplasms; testis, torsion; testis, undescended; varicocele C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NIH, Dept Radiol, Bldg 10,Rm 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2000 VL 217 IS 1 BP 14 EP 15 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 356PW UT WOS:000089452500006 PM 11012418 ER PT J AU van der Veen, JWC Weinberger, DR Tedeschi, G Frank, JA Duyn, JH AF van der Veen, JWC Weinberger, DR Tedeschi, G Frank, JA Duyn, JH TI Proton MR spectroscopic imaging without water suppression SO RADIOLOGY LA English DT Article DE brain, metabolism; brain, MR; magnetic resonance (MR), pulse sequences; magnetic resonance (MR), reconstruction algorithms; magnetic resonance (MR), spectroscopy ID TIME-DOMAIN; SOLVENT SUPPRESSION; HUMAN-BRAIN; INVIVO; NMR; METABOLITES; SIGNAL; QUANTIFICATION; ECHO AB To improve reproducibility in proton magnetic resonance (MR) spectroscopic imaging in human brain, simultaneous acquisition of the internal water reference and metabolite signals was evaluated. Measurements in healthy volunteers showed that the increase in dynamic range from signal oversampling was sufficient to avoid digitization errors. In addition, use of singular value decomposition techniques and finite impulse response filters proved effective in separating water and metabolite signals and providing estimates of the metabolite concentrations. C1 NIMH, Clin Brain Disorders Branch, NIH, In Vivo NMR Res Ctr, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Res, In Vivo NMR Res Ctr, Bethesda, MD 20892 USA. Univ Naples 2, Inst Neurol Sci, Naples, Italy. RP van der Veen, JWC (reprint author), NIMH, Clin Brain Disorders Branch, NIH, In Vivo NMR Res Ctr, Bldg 10,Room B1D125,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 23 TC 32 Z9 32 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2000 VL 217 IS 1 BP 296 EP 300 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 356PW UT WOS:000089452500046 PM 11012460 ER PT J AU Zeiger, E Margolin, BH AF Zeiger, E Margolin, BH TI The proportions of mutagens among chemicals in commerce SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE mutagenicity; Salmonella test; Ames test; National Toxicology Program; high-production-volume chemicals ID GENETIC TOXICITY TESTS; RODENT CARCINOGENS AB It has been estimated that there are approximately 80,000 chemicals in commerce, Thus, it is not possible to test all these substances for mutagenicity and carcinogenicity; it is possible, however, to test or make estimates from selected subsets of these chemicals. For example, in the U.S. National Toxicology Program (NTP), 35% of the chemicals tested for mutagenicity in Salmonella mere positive, as were 52% of the chemicals tested for carcinogenicity in rodents. In contrast, in the U.S. EPA Gene-Tox database, the proportions of chemicals that are Salmonella mutagens is 56%. These and other databases may be biased toward positive responses because they generally have been developed to look at specific structural or use classes of chemicals or chemicals suspected of genetic or carcinogenic activity. To address the question of the proportions of mutagens among all chemicals in commerce, a database of 100 chemicals was created from a random selection of chemicals in commerce. These chemicals were tested for mutagenicity in Salmonella and 22% were mutagenic. The mutagenicity of the 46 highest U.S. production organic chemicals was also compiled; 20% were mutagenic. These values provide a more accurate estimate of the proportions of mutagens among chemicals in commerce than can be derived from published mutagenicity databases. (C) 2000 Academic Press. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. RP Zeiger, E (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. FU PHS HHS [273-92C-0013] NR 14 TC 21 Z9 23 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 2000 VL 32 IS 2 BP 219 EP 225 DI 10.1006/rtph.2000.1422 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 379DU UT WOS:000165626300009 PM 11067778 ER PT J AU Chen, DY Patton, JT AF Chen, DY Patton, JT TI De novo synthesis of minus strand RNA by the rotavirus RNA polymerase in a cell-free system involves a novel mechanism of initiation SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE RNA elongation; RNA initiation; RNA polymerase; RNA synthesis; rotavirus ID MESSENGER-RNA; GUANYLYLTRANSFERASE ACTIVITY; REPLICASE ACTIVITY; OPEN CORES; PARTICLES; BINDING; PROTEIN; GENOME; VP3; IDENTIFICATION AB The replicase activity of rotavirus open cores has been used to study the synthesis of (-) strand RNA from viral (+) strand RNA in a cell-free replication system. The last 7 nt of the (+) strand RNA, 5'-UGUGACC-3', are highly conserved and are necessary for efficient (-) strand synthesis in vitro, Characterization of the cell-free replication system revealed that the addition of NaCl inhibited (-) strand synthesis. By preincubating open cores with (+) strand RNA and ATP, CTP, and GTP prior to the addition of NaCl and UTP, the salt-sensitive step was overcome. Thus, (-) strand initiation, but not elongation, was a salt-sensitive process in the cell-free system. Further analysis of the requirements for initiation showed that preincubating open cores and the (+) strand RNA with GTP or UTP, but not with ATP or CTP, allowed (-) strand synthesis to occur in the presence of NaCl, Mutagenesis suggested that in the presence of GTP, (-) strand synthesis initiated at the 3'-terminal C residue of the (+) strand template, whereas in the absence of GTP, an aberrant initiation event occurred at the third residue upstream from the 3' end of the (+) strand RNA. During preincubation with GTP, formation of the dinucleotides pGpG and ppGpG was detected; however, no such products were made during preincubation with ATP, CTP, or UTP, Replication assays showed that pGpG, but not GpG, pApG, or ApG, served as a specific primer for (-) strand synthesis and that the synthesis of pGpG may occur by a template-independent process. From these data, we conclude that initiation of rotavirus (-) strand synthesis involves the formation of a ternary complex consisting of the viral RNA-dependent RNA polymerase, viral (+) strand RNA, and possibly a 5'-phosphorylated dinucleotide, that is, pGpG or ppGpG. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Room 117, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014 NR 32 TC 43 Z9 44 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD OCT PY 2000 VL 6 IS 10 BP 1455 EP 1467 DI 10.1017/S1355838200001187 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 367BU UT WOS:000090042400011 PM 11073221 ER PT J AU Miki, T AF Miki, T TI Malignant transformation and regulation of cell division by a Rho exchange factor ECT2 SO SEIKAGAKU LA Japanese DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; SMALL GTPASE; CYTOKINESIS; ONCOGENE; PROTEIN; KINASE; DROSOPHILA; PHOSPHORYLATION; CLONING; TARGET C1 NCI, Mol Tumor Biol Sect, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 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 0037-1017 J9 SEIKAGAKU JI Seikagaku PD OCT PY 2000 VL 72 IS 10 BP 1249 EP 1253 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370PX UT WOS:000165132400005 PM 11215146 ER PT J AU Adya, N Castilla, LH Liu, PP AF Adya, N Castilla, LH Liu, PP TI Function of CBF beta/Bro proteins SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Cbfb; hematopoiesis; Pebp2; Bro; Bgb; translocation; transcription ID ACUTE MYELOID-LEUKEMIA; BINDING-FACTOR-BETA; ACUTE MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; FETAL LIVER HEMATOPOIESIS; MYOSIN HEAVY-CHAIN; TRANSCRIPTION FACTOR; POLYOMAVIRUS ENHANCER; VIRUS ENHANCER; RUNT DOMAIN AB Mammalian core binding factor beta (CBF beta) and Drosophila Brother (Bro) and Big-brother (Bgb) proteins are transcription factors that dimerize with mammalian Runx and Drosophila Runt and Lozenge proteins and augment their DNA binding affinity and transcriptional potency. CBF beta is essential for development and sustenance of definitive hematopoiesis during mouse embryogenesis. Bro and Bgb are required for Runt/Lozenge functions in Drosophila development. CBF beta contributes to leukemogenesis since the CBFB gene is specifically and consistently mutated by a chromosome 16 inversion found in patients with acute myeloid leukemia subtype M4Eo. The ubiquitous expression pattern of the CBFB gene suggests that it may play important roles in many other organ systems. C1 NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Adya, N (reprint author), NHGRI, Genet & Mol Biol Branch, NIH Bldg 49,Room 3B19,49 Convent Dr, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 57 TC 47 Z9 47 U1 2 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD OCT PY 2000 VL 11 IS 5 BP 361 EP 368 DI 10.1006/scdb.2000.0189 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 373LD UT WOS:000165290200006 PM 11105900 ER PT J AU Curt, GA AF Curt, GA TI Impact of fatigue on quality of life in oncology patients SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT Symposium on Anemia - Where are we now; Where are we going, Clinical Consequences and Treatment Benefits CY DEC 03, 1999 CL NEW ORLEANS, LOUISIANA SP Mt Sinai Sch Med ID FUNCTIONAL ASSESSMENT; ANEMIA C1 NCI, NIH, Bethesda, MD 20892 USA. RP Curt, GA (reprint author), NCI, NIH, Bldg 10,Room 12N214,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 83 Z9 85 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2000 VL 37 IS 4 SU 6 BP 14 EP 17 DI 10.1016/S0037-1963(00)90063-5 PG 4 WC Hematology SC Hematology GA 366HN UT WOS:000090000000004 PM 11068951 ER PT J AU Davis, TA AF Davis, TA TI Monoclonal antibody-eased therapy of lymphoid neoplasms: What's on the horizon? SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT Symposium on Monoclonal Antibody Therapy for Hematologic Malignancies - Prospects for an Integrated Therapy Approach CY DEC, 1999 CL NEW ORLEANS, LOUISIANA SP Stanford Univ Dept Med, Div Oncol ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; HUMANIZED ANTI-CD3 ANTIBODY; LOW-GRADE; CTLA-4 BLOCKADE; IN-VITRO; TUMOR; RADIOIMMUNOTHERAPY; IMMUNOTHERAPY; TOLERANCE C1 NCI, Canc Therapy Evaluat Program, NIH, Rockville, MD 20852 USA. RP Davis, TA (reprint author), NCI, Canc Therapy Evaluat Program, NIH, 6130 Execut Blvd,EPN 7000, Rockville, MD 20852 USA. NR 74 TC 2 Z9 2 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2000 VL 37 IS 4 SU 7 BP 34 EP 42 DI 10.1053/shem.2000.18527 PG 9 WC Hematology SC Hematology GA 366HQ UT WOS:000090000300006 ER PT J AU Schrock, E Padilla-Nash, H AF Schrock, E Padilla-Nash, H TI Spectral karyotyping and multicolor fluorescence in situ hybridization reveal new tumor-specific chromosomal aberrations SO SEMINARS IN HEMATOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; ABL-POSITIVE CELLS; MYELOGENOUS LEUKEMIA; CYTOGENETIC ANALYSIS; SUBTELOMERIC PROBES; MULTIPLE-MYELOMA; TYROSINE KINASE; FISH; TRANSLOCATIONS; AMPLIFICATION C1 Inst Mol Biotechnol, Res Grp Tumor Genet & Mol Genet, D-07745 Jena, Germany. Natl Canc Inst, Div Clin Sci, Dept Genet, Bethesda, MD USA. RP Schrock, E (reprint author), Inst Mol Biotechnol, Res Grp Tumor Genet & Mol Genet, Beutenbergstr 11, D-07745 Jena, Germany. NR 68 TC 57 Z9 59 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2000 VL 37 IS 4 BP 334 EP 347 DI 10.1053/shem.2000.16444 PG 14 WC Hematology SC Hematology GA 365TX UT WOS:000089967500003 PM 11071356 ER PT J AU Kirsch, IR Ried, T AF Kirsch, IR Ried, T TI Integration of cytogenetic data with genome maps and available probes: Present status and future promise SO SEMINARS IN HEMATOLOGY LA English DT Article ID YAC CONTIG MAP; HUMAN-CHROMOSOMES; HYBRIDIZATION; SEQUENCE; TUMOR; GENE; HUMAN-CHROMOSOME-22; TRANSLOCATION; MYELOMA; LOCUS C1 Natl Naval Med Ctr, NCI, Dept Genet, Med Branch, Bethesda, MD 20889 USA. RP Kirsch, IR (reprint author), Natl Naval Med Ctr, NCI, Dept Genet, Med Branch, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 24 TC 7 Z9 7 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2000 VL 37 IS 4 BP 420 EP 428 DI 10.1016/S0037-1963(00)90021-0 PG 9 WC Hematology SC Hematology GA 365TX UT WOS:000089967500010 PM 11071363 ER PT J AU Vacchio, MS Ashwell, JD AF Vacchio, MS Ashwell, JD TI Glucocorticoids and thymocyte development SO SEMINARS IN IMMUNOLOGY LA English DT Review DE glucocorticoids; glucocorticoid receptor; negative selection; positive selection; thymocyte development ID T-CELL-RECEPTOR; THYMIC EPITHELIAL-CELLS; PITUITARY-ADRENAL AXIS; SIDE-CHAIN CLEAVAGE; POSITIVE SELECTION; NEGATIVE SELECTION; TRANSGENIC MICE; LYMPHOPROLIFERATIVE DISEASE; FREE CORTICOSTERONE; SIGNALING PATHWAYS C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Vacchio, MS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10 Rm 4B10, Bethesda, MD 20892 USA. NR 83 TC 40 Z9 41 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD OCT PY 2000 VL 12 IS 5 BP 475 EP 485 DI 10.1006/smim.2000.0265 PG 11 WC Immunology SC Immunology GA 368DV UT WOS:000090103200008 PM 11085180 ER PT J AU Cheson, BD Zwiebel, JA Dancey, J Murgo, A AF Cheson, BD Zwiebel, JA Dancey, J Murgo, A TI Novel therapeutic agents for the treatment of myelodysplastic syndromes SO SEMINARS IN ONCOLOGY LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; PROTEIN-KINASE-C; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; HISTONE DEACETYLASE COMPLEX; ACUTE MYELOGENOUS LEUKEMIA; FIBROBLAST GROWTH-FACTOR; ARSENIC TRIOXIDE AS2O3; CELL-CYCLE ARREST C1 NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Cheson, BD (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Execut Plaza N,Room 741, Bethesda, MD 20892 USA. NR 190 TC 40 Z9 43 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2000 VL 27 IS 5 BP 560 EP 577 PG 18 WC Oncology SC Oncology GA 362YB UT WOS:000089804900008 PM 11049023 ER PT J AU Zheng, G Gastwirth, JL AF Zheng, G Gastwirth, JL TI Where is the Fisher information in an ordered sample? SO STATISTICA SINICA LA English DT Article DE decomposition of Fisher information; limiting Pitman efficiency; location-scale family; matrix expression; multiply censored data ID STATISTICS AB Suppose we have a random sample of size n with multiple censoring. The exact Fisher information in the data is derived and expressed in terms of matrices when each block of censored data contains at least two order statistics. The results are applied to determine how much Fisher information about the location (scale) parameter is contained in the middle (two tails) of an ordered sample. The results show that, for Cauchy, Laplace, logistic, and normal distributions, the middle 30% (extreme half) of the ordered data contains more than 80% of the Fisher information about the location (scale) parameter. These results provide insight into the behavior of two well-known robust linear estimators of the location parameter. C1 George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Rockledge 2,6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 29 TC 33 Z9 33 U1 0 U2 0 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD OCT PY 2000 VL 10 IS 4 BP 1267 EP 1280 PG 14 WC Statistics & Probability SC Mathematics GA 381RK UT WOS:000165776800015 ER PT J AU Hewitt, SC Korach, KS AF Hewitt, SC Korach, KS TI Progesterone action and responses in the alpha ERKO mouse SO STEROIDS LA English DT Article; Proceedings Paper CT Symposium on Progesterone, Progestins, and Antiprogestins in the Next Millennium CY AUG 31-SEP 03, 1999 CL JERUSALEM, ISRAEL SP Shaare Zedek Med Ctr, Weizmann Inst Sci, Populat Council, New York, Consortium Ind Collaborat Contracept Res, NV Organon, TAP Pharmaceut Inc, Theramex, Welcome Trust, WHO, Ares Serono Fdn, AstraZeneca, Columbia Labs, Maurice & Gabriela Goldschleger Fdn, Hoechst Marion Roussel, Israel Endorcine Soc, Jenapharm GmbH, RW Johnson Pharmaceut Res Inst, Lapidot Pharmaceut, Leiras Oy, Ligand Pharmaceut, Orentreich Fdn, Schering AG, SmithKline Beecham Pharmaceut, Wyeth Ayerst DE progesterone; estrogen; receptor; ovulation; PRKO mice; alpha ERKO mice ID ESTROGEN-RECEPTOR GENE; TARGETED DISRUPTION; FEMALE MICE; SEXUAL DEVELOPMENT; UTERUS; EXPRESSION; SUPERFAMILY; IMPLANTATION; PHENOTYPES; ROLES AB Ovarian steroids have important inter-related roles in many systems and processes required for mammalian reproduction. The female reproductive tract, ovaries, and mammary glands are all targets for both estrogen and progesterone. In addition, the actions of these hormones are intertwined in that, for example, progesterone attenuates the proliferative effect of estrogen in the uterus, whereas estrogen also induces the progesterone receptor (PR) mRNA and protein, thus enhancing progesterone actions. The generation of mice that lacks the progesterone receptor (PRKO) or the estrogen receptor alpha (alpha ERKO) has provided numerous insights into the interacting roles of these hormones. The mammary glands of the PRKO mice develop with full epithelial ducts that lack side branching and lobular alveolar structures, whereas the alpha ERKO mice develop only an epithelial rudiment. This indicates that estrogen is important for ductal morphogenesis, whereas progesterone is required for ductal branching and alveolar development. Both the alpha ERKO and PRKO mice are also anovulatory, but exhibit different causal pathologies. The alpha ERKO ovary seems to possess follicles up to the preantral stage and shows a polycystic phenotype as a result of chronic hyperstimulation by LH. The PRKO follicles seem to develop to an ovulatory stage, but are unable to rupture, indicating a role for progesterone in ovulation. The uteri of these two strains seem to develop normally; however, the function and hormone responses are abnormal in each. Because estrogen is known to induce PRs in the uterus, the progesterone responsiveness of the alpha ERKO uterus was characterized. PR mRNA was detected but was not up-regulated-by estrogen in the alpha ERKO tissue. PRs are present in the alpha ERKO tissue at 60% of the level in wild-type tissue and show a similar amount of A and B isoforms when measured by R5020 binding and detected by Western blotting. The PRs were able to mediate induction of two progesterone-responsive uterine genes: calcitonin and amphiregulin. The alpha ERKO uterine tissue was also able to undergo a decidual reaction in response to hormonal and intraluminal treatments to mimic implantation: however, unlike normal wild-type uteri, this response was estrogen independent in the alpha ERKO uterine tissue. (C) 2000 Published by Elsevier Science Inc. C1 NIEHS, Receptor Biol Sect, LRDT, NIH, Res Triangle Pk, NC 27709 USA. RP Hewitt, SC (reprint author), NIEHS, Receptor Biol Sect, LRDT, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 41 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-128X J9 STEROIDS JI Steroids PD OCT-NOV PY 2000 VL 65 IS 10-11 BP 551 EP 557 DI 10.1016/S0039-128X(00)00113-6 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 377BX UT WOS:000165493000003 PM 11108859 ER PT J AU Hirvonen, T Virtamo, J Korhonen, P Albanes, D Pietinen, P AF Hirvonen, T Virtamo, J Korhonen, P Albanes, D Pietinen, P TI Intake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokers SO STROKE LA English DT Article DE antioxidants; diet; epidemiology; stroke ID POTENTIALLY ANTICARCINOGENIC FLAVONOIDS; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; BETA-CAROTENE; DIETARY; FRUIT; VEGETABLES; ANTIOXIDANTS; CONSUMPTION; NETHERLANDS AB Background and Purpose-Antioxidants may protect against atherosclerosis and thus prevent cerebrovascular disease. We studied the association between dietary antioxidants and subtypes of stroke. Methods-The study cohort consisted of 26 593 male smokers, aged 50 to 69 years, without a history of stroke. They were participants of the Alpha-Tocopherol. Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases were identified through national registers. Results-During a 6.1-year follow-up, 736 cerebral infarctions, 83 subarachnoid hemorrhages, and 95 intracerebral hemorrhages occurred. Neither dietary flavonols and flavones nor vitamin E were associated with risk for stroke. The dietary intake of p-carotene was inversely associated with the risk for cerebral infarction (relative risk [RR] of highest versus lowest quartile 0.74, 95% CI 0.60 to 0.91), lutein plus zeaxanthin with risk for subarachnoid hemorrhage (RR 0.47, 95% CI 0.24 to 0.93), and lycopene with risks of cerebral infarction (RR 0.74, 95% CI 0.59 to 0.92) and intracerebral hemorrhage (RR 0.45, 95% CI 0.24 to 0.86). Vitamin C intake was inversely associated with the risk for intracerebral hemorrhage (RR 0.39, 95% CI 0.21 to 0.74). After simultaneous modeling of the antioxidants, a significant association remained only between p-carotene intake and risk for cerebral infarction (RR 0.77, 95% CI 0.61 to 0.99). Conclusions-Dietary intake of p-carotene was inversely associated with the risk for cerebral infarction. No association was detected between other dietary antioxidants and risk for stroke. C1 Natl Publ Hlth Inst, Dept Nutr, Helsinki, Finland. NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Hirvonen, T (reprint author), Natl Publ Hlth Inst, Dept Nutr, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 29 TC 130 Z9 135 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2000 VL 31 IS 10 BP 2301 EP 2306 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 360FN UT WOS:000089655900003 PM 11022054 ER PT J AU Broderick, JP Lu, M Kothari, R Levine, SR Lyden, PD Haley, EC Brott, TG Grotta, J Tilley, BC Marler, JR Frankel, M AF Broderick, JP Lu, M Kothari, R Levine, SR Lyden, PD Haley, EC Brott, TG Grotta, J Tilley, BC Marler, JR Frankel, M CA NINDS rtPA Stroke Study Grp TI Finding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA Stroke Trial SO STROKE LA English DT Article DE clinical trials; models, predictive; outcome; stroke; tissue plasminogen activator ID ACUTE ISCHEMIC STROKE; RANDOMIZED CONTROLLED TRIAL; THROMBOLYTIC THERAPY; DOUBLE-BLIND; SCALE; LUBELUZOLE; MRI AB Background and Purpose-We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial, Methods-Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of "early activity" of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures, The second analysis focused on longer-term outcome and "efficacy" and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results. Results-Of the 5 most powerful outcome measures for early activity of tPA, 4 involved the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours or changes in the NIHSS score from baseline to 24 hours. The best overall single outcome measure was an NIHSS score less than or equal to 2 at 24 hours, which provided an odds ratio of 5.4 (95% CI, 2.4 to 12.1) and a projected sample size of 58 per treatment group assuming an alpha of 0.05 (2-sided test) and a power of 80% using part I data. The top 2 and 3 of the top 5 outcome measures for detecting the longer-term efficacy of tPA also involved the NIHSS score. A Rankin score of 0 or 1 at 3 months was the third most powerful outcome measure. Outcome measures identified by CART from part I data were not as sensitive in detecting the effectiveness of tPA when applied to part n data. Conclusions-Measures using the NIHSS and a Rankin score less than or equal to 1 were the most sensitive discriminators of the effectiveness of tPA in the NINDS tPA Stroke Trial compared with the other clinical and radiological measures. The outcome measures identified in this exploratory analysis (eg, NIHSS score less than or equal to 2 at 24 hours) would be best used as an outcome measure in future phase II trials of recanalization begun within the first 3 hours after stroke onset, with inclusion and exclusion criteria similar to those in the NINDS tPA Stroke Trial. C1 Univ Cincinnati, Dept Neurol, Cincinnati, OH 45267 USA. Henry Ford Hlth Sci Ctr, Dept Biostat & Res Epidemiol, Detroit, MI USA. Borgess Res Inst, Kalamazoo, MI USA. Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. Univ Calif San Diego, Stroke Ctr, San Diego, CA 92103 USA. Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. Univ Texas, Dept Neurol, Houston, TX USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. NINDS, Div Stroke & Trauma, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Broderick, JP (reprint author), Univ Cincinnati, Dept Neurol, 231 Bethesda Ave,ML 0525, Cincinnati, OH 45267 USA. FU NINDS NIH HHS [N01-NS-02377, N01-NS-02382, N01-NS-02374] NR 23 TC 85 Z9 86 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2000 VL 31 IS 10 BP 2335 EP 2341 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 360FN UT WOS:000089655900009 PM 11022060 ER PT J AU Nishimura, Y Ito, T Saavedra, JM AF Nishimura, Y Ito, T Saavedra, JM TI Angiotensin II AT(1) blockade normalizes cerebrovascular autoregulation and reduces cerebral ischemia in spontaneously hypertensive rats SO STROKE LA English DT Article DE brain; hypertension; peptides; receptors; stroke ID RECEPTOR ANTAGONIST CV-11974; BLOOD-FLOW AUTOREGULATION; CONVERTING ENZYME; BRAIN; STROKE; INFARCTION; EXPRESSION; ARTERIES; AT2 AB Background and Purpose-Angiotensin II, through stimulation of AT(1) receptors, not only controls blood pressure but also modulates cerebrovascular flow. We sought to determine whether selective AT(1) antagonists could be therapeutically advantageous in brain ischemia during chronic hypertension. Methods-We pretreated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls with the AT(1) antagonist candesartan (CV-11974), 0.5 mg/kg per day, for 3 to 14 days, via subcutaneously implanted osmotic minipumps. We analyzed cerebral blood flow by laser-Doppler flowmetry, cerebral stroke in SHR after occlusion of the middle cerebral artery with reperfusion, and brain AT(1) receptors by quantitative autoradiography. Results-Candesartan treatment normalized blood pressure and the shift toward higher blood pressures at both the upper and lower limits of cerebrovascular autoregulation in SHR. Candesartan pretreatment of SHR for 14 days partially prevented the decrease in blood flow in the marginal zone of ischemia and significantly reduced the volume of total and cortical infarcts after either 1 or 2 hours of middle cerebral artery occlusion with reperfusion, relative to untreated SHR, respectively. This treatment also significantly reduced brain edema after 2 hours of middle cerebral artery occlusion with reperfusion. In SHR, candesartan markedly decreased AT(1) binding in areas inside (nucleus of the solitary tract) and outside (area postrema) the blood-brain barrier and in the middle cerebral artery. Conclusions-Pretreatment with an AT(1) antagonist protected hypertensive rats from brain ischemia by normalizing the cerebral blood flow response, probably through AT(1) receptor blockade in cerebral vessels and in brain areas controlling cerebrovascular flow during stroke. C1 NIMH, Pharmacol Sect, Intramural Res Program, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Intramural Res Program, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. NR 35 TC 186 Z9 189 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2000 VL 31 IS 10 BP 2478 EP 2485 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 360FN UT WOS:000089655900035 PM 11022082 ER PT J AU Allers, KA Kreiss, DS Walters, JR AF Allers, KA Kreiss, DS Walters, JR TI Multisecond oscillations in the subthalamic nucleus: Effects of apomorphine and dopamine cell lesion SO SYNAPSE LA English DT Article DE subthalamic nucleus; basal ganglia; dopamine; apomorphine; multisecond oscillation; oscillation; periodicity; Parkinson's disease; rotation; stereotypy; 6-hydroxydopamine ID GLOBUS-PALLIDUS NEURONS; SUPPLEMENTARY MOTOR AREA; BASAL GANGLIA; FIRING RATE; FUNCTIONAL-ANATOMY; SPECTRAL-ANALYSIS; ATTENTIONAL TASK; TIME-SERIES; PARKINSONISM; MODULATION AB Clinical and preclinical data indicate that the subthalamic nucleus (STN) plays a critical role in mediating the hyper- and hypoactive behavioral states associated with increases and decreases in dopamine receptor stimulation in the basal ganglia. The present study investigates effects of dopamine receptor stimulation on slow multisecond oscillations in firing rates in STN neurons. Extracellular, single-unit recordings were performed in locally anesthetized and immobilized rats which were either intact or had received unilateral 6-OHDA lesions of the medial forebrain bundle. The majority (64%) of spike trains recorded from STN neurons exhibited periodic oscillations in firing rate within the range of 2-60 sec, with an average period of 24 sec. The distribution of these baseline periodicities was not altered by unilateral 6-OHDA lesion, but periods were significantly shortened by systemic administration of the D1/D2 agonist apomorphine. This effect was observed in a greater proportion of neurons recorded from 6-OHDA-lesioned rats as compared to intact rats, was notably diminished in rats systemically anesthetized with chloral hydrate, and did not correlate with drug-induced changes in firing rate. These oscillations are similar to slow periodicities in firing rate recently reported in other basal ganglia nuclei. The possibility that these periodic oscillations in firing rate play a significant role in basal ganglia function was supported by the observation that the time of onset of apomorphine induced alterations in amplitude and periodicity of slow oscillations in STN spike trains is coincident with the onset of behavioral effects of this drug in 6-OHDA-lesioned animals. Synapse 38:38-50, 2000, Published 2000 Wiley-Liss, Inc.(dagger). C1 NINCDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Allers, KA (reprint author), NINCDS, Expt Therapeut Branch, NIH, Bldg 10-5C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM kaallers@helix.nih.gov NR 61 TC 33 Z9 36 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 0887-4476 J9 SYNAPSE JI Synapse PD OCT PY 2000 VL 38 IS 1 BP 38 EP 50 DI 10.1002/1098-2396(200010)38:1<38::AID-SYN5>3.0.CO;2-V PG 13 WC Neurosciences SC Neurosciences & Neurology GA 348FK UT WOS:000088974700005 PM 10941139 ER PT J AU Heindel, J AF Heindel, J TI 1999 NIEHS Symposium Reports on Oxidative Stress, Apoptosis, and Abnormal Development: Introduction SO TERATOLOGY LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Heindel, J (reprint author), NIEHS, MD-EC-23,POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 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 0040-3709 J9 TERATOLOGY JI Teratology PD OCT PY 2000 VL 62 IS 4 BP 233 EP 233 DI 10.1002/1096-9926(200010)62:4<233::AID-TERA9>3.0.CO;2-C PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 362MV UT WOS:000089782500009 PM 10992265 ER PT J AU Kung, AWC Lau, KS Kohn, LD AF Kung, AWC Lau, KS Kohn, LD TI Characterization of thyroid-stimulating blocking antibodies that appeared during transient hypothyroidism after radioactive iodine therapy SO THYROID LA English DT Article ID ANTITHYROID DRUG-TREATMENT; GRAVES-DISEASE PATIENTS; THYROTROPIN RECEPTOR; DEVELOPED HYPOTHYROIDISM; RADIOIODINE THERAPY; TSH RECEPTOR; WILD-TYPE; EPITOPES; AUTOANTIBODIES; IMMUNOGLOBULINS AB Hypothyroidism after radioactive iodine (RAI) therapy for Graves' disease can be transient or permanent. The cause for early transient hypothyroidism is unknown. We evaluated 11 patients who developed transient hypothyroidism within 6 months of RAI and 12 who remained euthyroid after RAI. Approximately equal numbers of patients in each group had thyroid-stimulating antibody (TSAb) that increased cyclic adenosine monophosphate (cAMP) levels in Chinese hamster ovary (CHO) cells transfected with the recombinant human thyrotropin receptor (TSHR) (WT cells). Approximately equal numbers of patients from both groups had an increase in TSAb activity post-RAI. All TSAbs had their dominant functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity because they, but not TSH, completely lost stimulating activity in a receptor chimera, wherein TSHR residues 90-165 were substituted by equivalent residues of the lutropin/choriogonadotropin receptor (LH/CGR). Although equal numbers of patients in both groups had thyrotropin-binding inhibiting immunoglobulin activity (TBII), as measured by radioreceptor assay before RAI, patients with transient hypothyroidism had a surge in TBII activity and all except one became positive for thyroid-stimulating blocking antibodies (TSBAb), as measured by inhibition of TSH-stimulated cAMP from WT cells. When immunoglobulin G (IgGs) were epitope-mapped using TSHR/LH-CGR chimeras with different substitutions, 8 hypothyroid subjects had TSBAbs directed against residues 90-165 of the TSHR, as well as TSHR residues 261-370. Two had functional epitopes directed at residues 9-89 as well as TSHR residues 261-370. None of the euthyroid control patients developed TSBAbs and their TBII activity decreased post-RAI. When patients with transient hypothyroidism reverted to a euthyroid state, TSAb was still detectable in 5; however, TBII was present in all and TSBAb, although decreased, was still positive in 9. In summary, RAI therapy was associated with a change in thyroid antibody characteristics in most patients. Additionally, patients with a surge in TBII and the appearance of TSBAb developed transient hypothyroidism after RAI. C1 Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. NIDDK, Metab Dis Branch, Cell Regulat Sect, Bethesda, MD USA. RP Kung, AWC (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Med, Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China. RI Kung, Annie/C-4294-2009 NR 23 TC 12 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD OCT PY 2000 VL 10 IS 10 BP 909 EP 917 DI 10.1089/thy.2000.10.909 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 370LJ UT WOS:000165124300010 PM 11081257 ER PT J AU George, JD Price, CJ Marr, MC Myers, CB Jahnke, GD AF George, JD Price, CJ Marr, MC Myers, CB Jahnke, GD TI Evaluation of the developmental toxicity of formamide in Sprague-Dawley (CD) rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE formamide; developmental toxicity; teratogenicity; rats; morphological development ID N-METHYLFORMAMIDE; N,N-DIMETHYLFORMAMIDE; DIMETHYLFORMAMIDE; WORKERS; MICE; METABOLITES; RABBITS; CANCER AB Timed-pregnant CD(R) outbred albino Sprague-Dawley rats received formamide (50, 100, or 200 mg/kg/day) or vehicle (5 ml/kg deionized/distilled water, po) on gestational days (gd)6 through 19. Maternal food and water consumption (absolute and relative), body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20), confirmed-pregnant females (21-23 per group) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations and variations. There were no maternal deaths and no dose-related clinical signs. At 200 mg/kg/day, maternal body weight on gd 20, weight gain, and gravid uterine weight were significantly decreased. Maternal weight gain, corrected for gravid uterine weight, liver weight (absolute or relative), and food and water consumption (absolute or relative), were not affected. Formamide did not affect prenatal viability or incidences of fetal malformations or variations. Average fetal body weight/litter was decreased at 100 and 200 mg/kg/day. Fetal body weight was affected at lower daily doses than in previously published studies, possibly due to the longer total exposure period and/or lack of a recovery period between cessation of exposure and termination. In summary, the maternal toxicity no-observed-adverse-effect level (NOAEL) was 100 mg/kg/day and the low observed adverse effect level (LOAEL) was 200 mg/kg/day under the conditions of this study. Similarly, the developmental toxicity NOAEL was 50 mg/kg/day and the LOAEL was 100 mg/kg/day. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, Dev & Reprod Toxicol Grp, Res Triangle Pk, NC 27709 USA. RP George, JD (reprint author), Res Triangle Inst, POB 12194,Hermann Lab Bldg, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-65405] NR 68 TC 4 Z9 4 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2000 VL 57 IS 2 BP 284 EP 291 DI 10.1093/toxsci/57.2.284 PG 8 WC Toxicology SC Toxicology GA 361UG UT WOS:000089742100011 PM 11006358 ER PT J AU Guiney, PD Walker, MK Spitsbergen, JM Peterson, RE AF Guiney, PD Walker, MK Spitsbergen, JM Peterson, RE TI Hemodynamic dysfunction and cytochrome P4501A mRNA expression induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin during embryonic stages of lake trout development SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE lake trout development; TCDD; cardiovascular toxicity; cytochrome P4501A mRNA; histopathology ID EARLY-LIFE STAGES; MEDAKA ORYZIAS-LATIPES; APOPTOTIC CELL-DEATH; SALVELINUS-NAMAYCUSH; RAINBOW-TROUT; AH-RECEPTOR; SALMO-GAIRDNERI; FUNDULUS-HETEROCLITUS; HYDROXYLASE-ACTIVITY; ONCORHYNCHUS-MYKISS AB Lake trout embryos exposed to [H-3]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) manifest toxicity after hatching by subcutaneous edema of the yolk sac, pericardial edema, meningeal edema, subcutaneous hemorrhages, and a marked congestion of blood Row in various vascular beds culminating in death. Our objective was to determine if this syndrome was associated temporally with morphologic lesions in the vascular endothelium, increased vascular permeability, and cytochrome P4501A (CYP1A) mRNA induction. Lake trout embryos exposed as fertilized eggs to TCDD were found to exhibit marked reductions in perfusion of the peripheral vasculature during the early sac fry stage of development (stage F(1)9), which consistently preceded other gross lesions and mortality observed later in sac fry development (stage F(2)10). This reduction in blood flow was manifested as severe capillary congestion and hemoconcentration in certain vascular beds. Transmission electron microscopic (TEM) examination of endothelial cells in these vascular beds failed to reveal cellular necrosis at hatching (stage E(5)8) and throughout sac fry development (stages F(1)9-F(2)10). Rather, only subtle ultrastructural changes in endothelial cells were found consisting of increased vacuolation, separation of intercellular junctions, and cytoplasmic blebbing, consistent with the TCDD dose and time course for developmental cardiovascular toxicity, which began to manifest itself in some embryos approximately 1 week prior to hatching (E58). To assess permeability of yolk sac vasculature to certain constituents in blood, sac fry (stage F(2)10) were analyzed for the presence of plasma proteins, granulocytes, and serum creatine kinase activity in yolk sac subcutaneous edema fluid from control and TCDD-exposed treatment groups. TCDD dose- and time-related increases in yolk sac edema volume, plasma protein content of edema fluid, granulocyte concentration, and creatine kinase activity in the fluid were observed in midstage and late stage of sac fry development (stage F(2)10). Thus, yolk sac subcutaneous edema fluid is an ultrafiltrate of blood and results from increased vascular permeability. In contrast to the changes in vascular blood flow and permeability induced by TCDD during stages F(1)9 and F(2)10 of sac fry development, respectively, CYP1A mRNA levels were induced by TCDD as early as the 10-somite embryo (stage E(2)5). TCDD also caused a dose-related increase in CYP1A mRNA levels in sac fry at hatching (stage E58) and throughout sac fry development (stages F(1)9-F(2)10). We conclude that subtle, ultrastructural changes in vascular endothelial cells consistently precede increases in vascular permeability and sac fry mortality; however, induction of CYP1A mRNA occurs prior to any observable morphological lesions, changes in vascular permeability, or sac fry mortality. (C) 2000 Academic Press. C1 Univ Wisconsin, NIEHS, Aquat Biomed Ctr, Milwaukee, WI 53204 USA. Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97333 USA. Oregon State Univ, Marine Freshwater Biomed Sci Ctr, Corvallis, OR 97333 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. RP Univ Wisconsin, NIEHS, Aquat Biomed Ctr, 600 E Greenfield Ave, Milwaukee, WI 53204 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIEHS NIH HHS [ES03850, ES04184] NR 62 TC 40 Z9 43 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 1 PY 2000 VL 168 IS 1 BP 1 EP 14 DI 10.1006/taap.2000.8999 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 363QC UT WOS:000089845200001 PM 11000095 ER PT J AU Trouba, KJ Wauson, EM Vorce, RL AF Trouba, KJ Wauson, EM Vorce, RL TI Sodium arsenite inhibits terminal differentiation of murine C3H 10T1/2 preadipocytes SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE arsenic; adipocyte; differentiation; proliferation; carcinogenesis ID ACUTE PROMYELOCYTIC LEUKEMIA; C-MYC EXPRESSION; CELL-CYCLE; DRINKING-WATER; GROWTH-ARREST; ADIPOCYTE DIFFERENTIATION; ADIPOSE CONVERSION; C/EBP-ALPHA; BIOLOGICAL MECHANISMS; RECIPROCAL REGULATION AB Cancer represents an imbalance between cell proliferation and differentiation, two processes that are coordinately and antagonistically regulated. Aberrant cell proliferation is considered to be an important etiological factor in the development of arsenic-induced cancer, suggesting that arsenic also dysregulates differentiation. Based on evidence that arsenic modulates mitogenic events that antagonize the process of differentiation, this study addresses the hypothesis that sodium arsenite inhibits insulin/dexamethasone-induced differentiation of C3H 10T1/2 preadipocytes; it was further postulated that arsenic-treated cells retain mitogenic responsiveness under differentiating conditions. To test this hypothesis, the differentiation capacity of C3H 10T1/2 preadipocytes was examined in control cells and cells treated with sodium arsenite. Differentiation was assessed morphologically and quantified by Oil Red-O staining of accumulated Lipids. The effect of long-term arsenic exposure on mitogenic competence was quantified by flow cytometry, [H-3]thymidine incorporation, and cell counting under conditions favorable for adipocyte differentiation. Results indicate that arsenic inhibits morphological differentiation of wild-type C3H 10T1/2 preadipocytes, Short-term arsenic exposure inhibits differentiation in a dose-dependent manner, with arsenic concentrations greater than or equal to 3 mu M producing a significant inhibition of dexamethasone/insulin-induced lipid accumulation. Furthermore, arsenic-treated cells exhibit an accentuated response to mitogenic stimulation under differentiating conditions. These data suggest that arsenic exposure results in the inhibition of cellular programming required for terminal differentiation of C3H 10T1/2 preadipocytes and that cells acquire mitogenic hyperresponsiveness, The ability of arsenic to dysregulate the balance between proliferation and differentiation is proposed to be one mechanism by which this metalloid causes cancer in humans. (C) 2000 Academic Press. C1 Univ Nebraska, Med Ctr, Dept Pharmacol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Ctr Environm Toxicol, Omaha, NE 68198 USA. RP Trouba, KJ (reprint author), NIEHS, Environm Immunol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [R01 ES07505] NR 74 TC 35 Z9 35 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 1 PY 2000 VL 168 IS 1 BP 25 EP 35 DI 10.1006/taap.2000.9012 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 363QC UT WOS:000089845200003 PM 11000097 ER PT J AU Gubin, AN Reid, ME Miller, JL AF Gubin, AN Reid, ME Miller, JL TI The Dombrock blood group glycoprotein is encoded by a member of the ADP-ribosyltransferase gene family SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. New York Blood Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2000 VL 40 IS 10 SU S BP 1S EP 1S PG 1 WC Hematology SC Hematology GA 364CN UT WOS:000089874600005 ER PT J AU Williams, AE Wu, Y Kleinman, SH Schreiber, GB Wright, D Busch, MP Gilcher, RO Ownby, HE Murphy, EL Zuck, T Nemo, GJ AF Williams, AE Wu, Y Kleinman, SH Schreiber, GB Wright, D Busch, MP Gilcher, RO Ownby, HE Murphy, EL Zuck, T Nemo, GJ CA Nhibi Reds Study TI The declining use and comparative seroprevalence of directed whole blood donations SO TRANSFUSION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Ohio Enterprises Int, Cincinnati, OH USA. UCSF, San Francisco, CA USA. ARC SE Michigan Region, Detroit, MI USA. Oklahoma Blood Inst, Oklahoma City, OK USA. BCP Irwin, San Francisco, CA USA. Westat Inc, Rockville, MD USA. ARC Holland Lab, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2000 VL 40 IS 10 SU S BP 5S EP 5S PG 1 WC Hematology SC Hematology GA 364CN UT WOS:000089874600020 ER EF