FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Giatzakis, C Taymans, SE Stratakis, CA AF Giatzakis, C Taymans, SE Stratakis, CA TI Expression profile of the adrenal gland from patients with primary bilateral adrenocortical diseases: Primary pigmented adrenocortical disease (PPNAD) (associated with Carney Complex) and massive macronodular adrenocortical disease (MMAD). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, UGEN, DEB, NIH, 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 1999 VL 65 IS 4 SU S MA 680 BP A127 EP A127 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800681 ER PT J AU Gill, SP Leyne, M Mull, J Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Axelrod, FB Blumenfeld, A Brownstein, M Chadwick, BP Slaugenhaupt, SA AF Gill, SP Leyne, M Mull, J Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Axelrod, FB Blumenfeld, A Brownstein, M Chadwick, BP Slaugenhaupt, SA TI Genomic structure and localization of the IKBKAP gene to the Familial Dysautonomia candidate region on 9q31. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Inst Human Genet, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. NYU Med Ctr, New York, NY 10016 USA. RI Brownstein, Michael/B-8609-2009 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 1999 VL 65 IS 4 SU S MA 1023 BP A186 EP A186 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801024 ER PT J AU Glenn, GM Walther, MM Toro, JR Hewitt, S Duray, P Choyke, PL Weirich, G Turner, M Linehan, WM Zbar, B AF Glenn, GM Walther, MM Toro, JR Hewitt, S Duray, P Choyke, PL Weirich, G Turner, M Linehan, WM Zbar, B TI Renal neoplasms in a familial multisystem syndrome with fibrofolliculomas as a cutaneous marker. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 329 BP A63 EP A63 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800331 ER PT J AU Goker-Alpan, O Blancato, J Smith, ACM Gahl, WA AF Goker-Alpan, O Blancato, J Smith, ACM Gahl, WA TI Expression of cholesterol biosynthetic enzymes is upregulated in Smith Magenis syndrome fibroblasts. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Bethesda, MD USA. NHGRI, NIH, Bethesda, MD USA. Georgetown Univ, Washington, DC USA. RI SMITH, ANN C.M./C-1122-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 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 1999 VL 65 IS 4 SU S MA 360 BP A69 EP A69 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800361 ER PT J AU Goldfarb, LG Park, KY Semino-Mora, C Lee, HS Litvak, S Sivakumar, K Dalakas, MC AF Goldfarb, LG Park, KY Semino-Mora, C Lee, HS Litvak, S Sivakumar, K Dalakas, MC TI Desmin gene mutations in myofibrillar myopathy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINDS, Clin Neurogenet Unit, MNB, NIH, Bethesda, MD 20892 USA. NINDS, Neuromuscular Dis Sect, MNB, NIH, 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 1999 VL 65 IS 4 SU S MA 573 BP A109 EP A109 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800574 ER PT J AU Goldstein, AM Struewing, JP Chidambaram, A Fraser, MC Tucker, MA AF Goldstein, AM Struewing, JP Chidambaram, A Fraser, MC Tucker, MA TI Genotype-phenotype relationships in American melanoma-prone families with CDKN2A and CDK4 mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 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 1999 VL 65 IS 4 SU S MA 682 BP A128 EP A128 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800685 ER PT J AU Gropman, AL Wolters, P Solomon, B Smith, ACM AF Gropman, AL Wolters, P Solomon, B Smith, ACM TI Neurodevelopmental assessment and functioning in five young children with Smith-Magenis Syndrome (SMS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Dept Genet, Med Genet Br, Bethesda, MD USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NIH, Med Illness Counseling Ctr, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 3 Z9 3 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 1999 VL 65 IS 4 SU S MA 816 BP A151 EP A151 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800817 ER PT J AU Guan, XY Quin, LX Tang, ZY Sham, JST Ma, ZC Ye, SL Zhou, XD Wu, ZQ Trent, JM AF Guan, XY Quin, LX Tang, ZY Sham, JST Ma, ZC Ye, SL Zhou, XD Wu, ZQ Trent, JM TI The association of chromosome 8p deletion and tumor metastasis in human hepatocellular carcinoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Hong Kong, Hong Kong, Peoples R China. Shanghai Med Univ, Liver Canc Inst, Shanghai 200032, Peoples R China. NHGRI, Liver Canc Inst, 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 1999 VL 65 IS 4 SU S MA 686 BP A128 EP A128 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800687 ER PT J AU Hacia, JG Novotny, EA Mayer, RA Woski, SA Ashlock, MA Collins, FS AF Hacia, JG Novotny, EA Mayer, RA Woski, SA Ashlock, MA Collins, FS TI Design of modified oligonucleotide probes to detect telomere repeat sequences in FISH assays. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, GMMB, NHGI, Bethesda, MD 20892 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 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 1999 VL 65 IS 4 SU S MA 894 BP A164 EP A164 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800895 ER PT J AU Hanson, RL Imperatore, G Kobes, S Knowler, WC AF Hanson, RL Imperatore, G Kobes, S Knowler, WC TI An autosomal genomic scan for loci linked to indices of insulin sensitivity and secretion in nondiabetic Pima Indians. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, DAES, Phoenix, AZ 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 1999 VL 65 IS 4 SU S MA 1409 BP A253 EP A253 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801409 ER PT J AU Hedenfalk, IA Duggan, DJ Chen, Y Bittner, M Borg, A Trent, JM AF Hedenfalk, IA Duggan, DJ Chen, Y Bittner, M Borg, A Trent, JM TI Microarray analysis discriminates BRCA2 mutation-positive breast cancer biopsies from BRCA1 mutation-positive and sporadic breast tumors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Lund, Dept Oncol, SE-22185 Lund, Sweden. Natl Human Genome Res Inst, Canc Genet Branch, 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 1999 VL 65 IS 4 SU S MA 42 BP A10 EP A10 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800043 ER PT J AU Ho, N Jia, L King, L Driscoll, C Gutter, E Anderson, M Francomano, C AF Ho, N Jia, L King, L Driscoll, C Gutter, E Anderson, M Francomano, C TI Identification of a novel gene expressed in human bone marrow stromal cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, 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 1999 VL 65 IS 4 SU S MA 1029 BP A187 EP A187 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801030 ER PT J AU Hsieh, PC Kimber, W Chen, A Hirotsuni, S Paylor, R Wynshaw-Boris, A AF Hsieh, PC Kimber, W Chen, A Hirotsuni, S Paylor, R Wynshaw-Boris, A TI Creating a mouse model for DiGeorge(DGS)/velocardiofacial syndromes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, HHMI Res Scholars Program, HHMI, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Univ Calif San Diego, Sch Med, Dept Pediat, San Diego, CA 92103 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 1999 VL 65 IS 4 SU S MA 361 BP A69 EP A69 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800364 ER PT J AU Huizing, M Shotelersuk, V Dell'Angelica, EC Bonifacino, JS Gahl, WA AF Huizing, M Shotelersuk, V Dell'Angelica, EC Bonifacino, JS Gahl, WA TI Screening candidate genes in patients with Hermansky-Pudlak syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Bethesda, MD USA. NICHD, CBMB, 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 1999 VL 65 IS 4 SU S MA 494 BP A94 EP A94 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800495 ER PT J AU Imperatore, G Knowler, WC Roumain, J Hanson, RL AF Imperatore, G Knowler, WC Roumain, J Hanson, RL TI Are the familiar determinants of lipid levels the same in diabetic and non-diabetic individuals? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ 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 1999 VL 65 IS 4 SU S MA 1135 BP A206 EP A206 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801135 ER PT J AU Iwata, T Che, L Li, C Francomano, CA Deng, C AF Iwata, T Che, L Li, C Francomano, CA Deng, C TI Generation and analysis of a mouse model of a lethal dwarfism, Thanatophoric Dysplasia type II. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. RI deng, chuxia/N-6713-2016 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 1999 VL 65 IS 4 SU S MA 248 BP A47 EP A47 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800247 ER PT J AU Jackson, CE Wang, J Fischer, RE Hsu, AP Niemela, J Dale, JK Fleisher, TA Jaffe, ES Lenardo, MJ Straus, SE Puck, JM AF Jackson, CE Wang, J Fischer, RE Hsu, AP Niemela, J Dale, JK Fleisher, TA Jaffe, ES Lenardo, MJ Straus, SE Puck, JM TI Autoimmune lymphoproliferative syndrome (ALPS): an inherited disorder of apoptosis with predisposition to development of diverse lymphomas. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Genet Mol Biol Branch, Bethesda, MD USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, 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 1999 VL 65 IS 4 SU S MA 252 BP A48 EP A48 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800252 ER PT J AU Jain, PK Rao, VK Fojo, T Bates, S Dean, M AF Jain, PK Rao, VK Fojo, T Bates, S Dean, M TI Identification of new mouse ABC Transporter gene related to ABCP, Mapping to chromosome 5. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD USA. NCI, DCS, NIH, 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 1999 VL 65 IS 4 SU S MA 1035 BP A188 EP A188 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801036 ER PT J AU Jenkinson, CP Cray, K Hanson, R Wiedrich, C Bogardus, C Baier, L AF Jenkinson, CP Cray, K Hanson, R Wiedrich, C Bogardus, C Baier, L TI DRD2 not associated with obesity in Pima Indians. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, PECRB, NIH, Phoenix, AZ 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 1999 VL 65 IS 4 SU S MA 1545 BP A276 EP A276 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801546 ER PT J AU Jia, L Ho, N Powell, J Yang, L Robey, P Young, M Francomano, C AF Jia, L Ho, N Powell, J Yang, L Robey, P Young, M Francomano, C TI Digital gene localization of bone-related ESTs. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD USA. Ctr Informat Technol, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 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 1999 VL 65 IS 4 SU S MA 480 BP A92 EP A92 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800483 ER PT J AU Joe, B Remmers, EF Griffiths, MM Wilder, RL AF Joe, B Remmers, EF Griffiths, MM Wilder, RL TI Multiple autoimmune disease regulatory loci cluster on rat chromosome 10 and homologous mouse and human chromosomes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Utah, Vet Affairs Med Ctr, Res Serv, Salt Lake City, UT 84132 USA. Univ Utah, Dept Med Rheumatol, Salt Lake City, UT 84132 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 1999 VL 65 IS 4 SU S MA 1548 BP A277 EP A277 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801548 ER PT J AU Johnston, JJ Kelley, RI Morton, DH Crawford, TO Biesecker, LG Francomano, CA AF Johnston, JJ Kelley, RI Morton, DH Crawford, TO Biesecker, LG Francomano, CA TI Haplotype analysis of markers on chromosome 2q21.2-q22 in nemaline myopathy in the Amish: Evidence for genetic heterogeneity. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Clin Special Children, Strasbourg, PA USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. NHGRI, NIH, Bethesda, MD USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 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 1999 VL 65 IS 4 SU S MA 1430 BP A256 EP A256 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801431 ER PT J AU Jugessur, A Lie, RT Wilcox, A Abyholm, F Vindenes, H Murray, JC AF Jugessur, A Lie, RT Wilcox, A Abyholm, F Vindenes, H Murray, JC TI Allelic variants of candidate genes TGFA, TGFB3, and MSX1 and orofacial clefting in Norway: A case-parent triad approach. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Haukeland Hosp, Ctr Mol Med, N-5021 Bergen, Norway. Univ Bergen, Div Med Stat, Bergen, Norway. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Norwegian Radium Hosp, Oslo, Norway. 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 1999 VL 65 IS 4 SU S MA 1550 BP A277 EP A277 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801549 ER PT J AU Kamnasaran, D Muenke, M O'Brien, PCM Ferguson-Smith, MA Cox, DW AF Kamnasaran, D Muenke, M O'Brien, PCM Ferguson-Smith, MA Cox, DW TI Agenesis of the corpus callosum associated with a chromosome (4;14) translocation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Alberta, Edmonton, AB, Canada. NHGGI, MBG, NIH, Bethesda, MD USA. Childrens Hosp Philadelphia, Philadelphia, PA USA. Ctr Vet Sci, Cambridge, 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 1999 VL 65 IS 4 SU S MA 1551 BP A277 EP A277 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801552 ER PT J AU Kargul, GJ Waeltz, P Ma, P Chen, EY Ko, MSH Nagaraja, R AF Kargul, GJ Waeltz, P Ma, P Chen, EY Ko, MSH Nagaraja, R TI Genomic sequence analysis in mouse t-complex region. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, Genet Lab, Baltimore, MD 21224 USA. Celera Genomics, Foster City, CA 94404 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 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 1999 VL 65 IS 4 SU S MA 1259 BP A227 EP A227 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801260 ER PT J AU Kaufman, DJ Beaty, TH Bailey-Wilson, JE Struewing, JP AF Kaufman, DJ Beaty, TH Bailey-Wilson, JE Struewing, JP TI Breast cancer penetrance estimates for BRCA 1/2 from a segregation analysis of the pedigrees of mutation positive probands. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RI Beaty, Terri/A-6032-2008 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 1999 VL 65 IS 4 SU S MA 444 BP A84 EP A84 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800443 ER PT J AU Kaur, GP Reddy, DE Keck, CL Popescu, N Athwal, RS AF Kaur, GP Reddy, DE Keck, CL Popescu, N Athwal, RS TI Identification of a YAC carrying cell senescence gene for breast cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Temple Univ, Fels Inst Canc Res & Mol Biol, Sch Med, Philadelphia, PA 19140 USA. NCI, Expt Carcinogenesis Lab, 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 1999 VL 65 IS 4 SU S MA 334 BP A64 EP A64 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800334 ER PT J AU Killoran, CE Abbott, M McKusick, VA Biesecker, LG AF Killoran, CE Abbott, M McKusick, VA Biesecker, LG TI Molecular and clinical analyses of the PIV (polydactyly-imperforate anus vertebral anomalies) syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Genet Dis Res Branc, NIH, Bethesda, MD USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Univ, Ctr Med Genet, Baltimore, 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 1999 VL 65 IS 4 SU S MA 24 BP A6 EP A6 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800023 ER PT J AU King, LM Iwata, T Francomano, CA AF King, LM Iwata, T Francomano, CA TI Characterization of a gene encoding an E-rich protein (ERP) expressed in human hone marrow stromal cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, 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 1999 VL 65 IS 4 SU S MA 1040 BP A189 EP A189 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801039 ER PT J AU Kononen, J Rohwer-Nutter, D Leighton, S Pohida, T Kakareka, J Sauter, G Kallioniemi, OP AF Kononen, J Rohwer-Nutter, D Leighton, S Pohida, T Kakareka, J Sauter, G Kallioniemi, OP TI Genome-scale translational research with tissue and cellular microarrays: Identifying and prioritization of targets for diagnostics and therapeutics. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Canc Genet Lab, NIH, Bethesda, MD USA. Univ Basel, Inst Pathol, Basel, Switzerland. NIH, Dept Engn, Bethesda, MD USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 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 1999 VL 65 IS 4 SU S MA 144 BP A28 EP A28 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800143 ER PT J AU Krasnewich, D Orvisky, E Goker, O Introne, W Peters, K Dietrich, K Ginns, E Sidransky, E AF Krasnewich, D Orvisky, E Goker, O Introne, W Peters, K Dietrich, K Ginns, E Sidransky, E TI Clinical manifestations in three American adult patients with carbohydrate-deficient glycoprotein syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, MGB, NIH, Bethesda, MD USA. NIMH, NSB, Bethesda, MD 20892 USA. NICHD, HCB, 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 1999 VL 65 IS 4 SU S MA 2402 BP A424 EP A424 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802402 ER PT J AU Lacbawan, FL Tifft, CJ Amaya, M Pennybacker, M Weinstein, S Wong, LC AF Lacbawan, FL Tifft, CJ Amaya, M Pennybacker, M Weinstein, S Wong, LC TI A novel 4.4kb mtDNA deletion underscores clinical heterogeneity in mitochondrial DNA deletion disorders. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. NHGRI, NIH, Bethesda, MD USA. Georgetown Univ, Inst Mol & Human Genet, Washington, DC USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 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 1999 VL 65 IS 4 SU S MA 1560 BP A279 EP A279 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801560 ER PT J AU Landi, MT Grassman, J Masten, S Bell, D Consonni, D Mocarelli, P Lucier, G Needham, L Bertazzi, PA Caporaso, NE AF Landi, MT Grassman, J Masten, S Bell, D Consonni, D Mocarelli, P Lucier, G Needham, L Bertazzi, PA Caporaso, NE TI Dioxin-related gene expression and activity in Seveso. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Milan, Milan, Italy. CDC, Atlanta, GA 30333 USA. RI Needham, Larry/E-4930-2011; masten, scott/R-1403-2016 OI masten, scott/0000-0002-7847-181X 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 1999 VL 65 IS 4 SU S MA 52 BP A11 EP A11 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800051 ER PT J AU Lattig, MC Morell, R Friedman, TB Tamayo, G Uribe, JI Bernal, JE Plaza, SL Tamayo, ML AF Lattig, MC Morell, R Friedman, TB Tamayo, G Uribe, JI Bernal, JE Plaza, SL Tamayo, ML TI Etiologic diversity for deafness on the island of Providencia - Colombia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Javeriana, Inst Genet Humana, Bogota, Colombia. Fdn Oftalmol Nacl, Bogota, Colombia. Univ Javeriana, Hosp San Ignacio, Bogota, Colombia. NIDCD, NIH, Rockville, 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 1999 VL 65 IS 4 SU S MA 2691 BP A474 EP A474 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802692 ER PT J AU Lee, MH Yi, S Carpten, JD Cohen, J Salen, G Gerhardt, GT Patel, S AF Lee, MH Yi, S Carpten, JD Cohen, J Salen, G Gerhardt, GT Patel, S TI Fine-mapping and mutational analyses of cerebrotendinous xanthomatosis in US pedigrees. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NHGRI, Prostate Canc Invest Grp, Canc Genet Lab, NIH, Bethesda, MD USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Med & Dent New Jersey, VA Hosp, E Orange, NJ USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 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 1999 VL 65 IS 4 SU S MA 1445 BP A259 EP A259 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801445 ER PT J AU Leonard, JC Toji, LH Bender, PK Beiswanger, CM Beck, JC Johnson, RT AF Leonard, JC Toji, LH Bender, PK Beiswanger, CM Beck, JC Johnson, RT TI Regional mapping panels for human chromosomes 1, 2, and 7. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Coriell Inst Med Res, NIGMS Human Genet Cell Repository, Coriell Cell Respositories, Camden, NJ 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 1999 VL 65 IS 4 SU S MA 1266 BP A229 EP A229 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801267 ER PT J AU Levy, HP Mayoral, W Collier, K Tio, TL Francomano, CA AF Levy, HP Mayoral, W Collier, K Tio, TL Francomano, CA TI Gastroesophageal reflux and irritable bowel syndrome in classical and hypermobile Ehlers Danlos syndrome (EDS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 2 Z9 3 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 1999 VL 65 IS 4 SU S MA 362 BP A69 EP A69 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800362 ER PT J AU Leyne, M Mull, J Gill, SP Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Chadwick, BP Gusella, JF Slaugenhaupt, SA AF Leyne, M Mull, J Gill, SP Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Chadwick, BP Gusella, JF Slaugenhaupt, SA TI Complete genomic sequence of the 471 kb Familial Dysautonomia candidate region on chromosome 9q31. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Inst Human Genet, Boston, MA USA. NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. NYU, Med Ctr, New York, NY 10016 USA. RI Brownstein, Michael/B-8609-2009 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 1999 VL 65 IS 4 SU S MA 481 BP A92 EP A92 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800481 ER PT J AU Li, XC Angeli, S Friedman, TB Friedman, RA AF Li, XC Angeli, S Friedman, TB Friedman, RA TI Identification of a novel locus for non-syndromic autosomal dominant hearing loss. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 House Ear Inst, CMB, Los Angeles, CA USA. Hosp San Juan de Dios, Fdn Venezolana Otol, Dept Otorhinolaryngol, Caracas, Venezuela. NIDCD, LMG, NIH, Rockville, 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 1999 VL 65 IS 4 SU S MA 1453 BP A260 EP A260 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801452 ER PT J AU Lieberman, AP Friedlich, DL Fischbeck, KH AF Lieberman, AP Friedlich, DL Fischbeck, KH TI Mammalian orthologs of invertebrate sex differentiation genes are androgen-responsive in motor neurons. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. HHMI, Res Scholars Program, 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 1999 VL 65 IS 4 SU S MA 406 BP A77 EP A77 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800409 ER PT J AU Lin, B Hiraiwa, H Pan, CJ Chou, JY AF Lin, B Hiraiwa, H Pan, CJ Chou, JY TI Deficiencies in the glucose-6-phosphate transporter cause glycogen storage disease type 1b but not 1c. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Heritable Disorders Branch, 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 1999 VL 65 IS 4 SU S MA 2411 BP A425 EP A425 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802412 ER PT J AU Lin, T Lacbawan, FL Davis, J Muenke, M Wong, LC Francomano, CA AF Lin, T Lacbawan, FL Davis, J Muenke, M Wong, LC Francomano, CA TI Deletion of Col2A1 IVS7 5donor splice site in stickler syndrome with SEMD: An expansion of Type II collagenopathy phenotypic spectrum. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Inst Mol Human Genet, Washington, DC 20007 USA. Natl Human Genome Res Inst, 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 1999 VL 65 IS 4 SU S MA 2702 BP A475 EP A475 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802703 ER PT J AU Loi, A Pilia, G Crisponi, L Delana, M Gasparini, P Bisceglia, L Amati, P Bonneau, D Rocchi, M MacMillan, S Ma, P Chen, E Schlessinger, D Cao, A AF Loi, A Pilia, G Crisponi, L Delana, M Gasparini, P Bisceglia, L Amati, P Bonneau, D Rocchi, M MacMillan, S Ma, P Chen, E Schlessinger, D Cao, A TI High resolution mapping of the Blepharophimosis, Ptosis, and Epicanthus inversus Syndrome (BPES) locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CNR, IRTAM, Cagliari, Italy. NIA, NIH, Bethesda, MD 20892 USA. IRCCS, San Giovanni Rotondo, Italy. CHU, Poitiers, France. Univ Bari, Bari, Italy. Perkin Elmer Co, Foster City, CA USA. Washington Univ, St Louis, MO USA. RI Bonneau, Dominique/K-6110-2015; Bisceglia, Luigi/B-8720-2017 OI Bisceglia, Luigi/0000-0001-5367-8518 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 1999 VL 65 IS 4 SU S MA 1459 BP A261 EP A261 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801458 ER PT J AU Mandal, A Yuan, CJ Zhang, Z Mukherjee, A AF Mandal, A Yuan, CJ Zhang, Z Mukherjee, A TI Transcriptional regulation of cyclooxygenase-2 gene expression: Novel effects of non-steroidal antiinflammatory drugs. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, SDG, HDB, 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 1999 VL 65 IS 4 SU S MA 732 BP A136 EP A136 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800734 ER PT J AU Mansoura, MK Henning, KA Novotny, EA Compton, ST Chetty, AP Ashlock, MA AF Mansoura, MK Henning, KA Novotny, EA Compton, ST Chetty, AP Ashlock, MA TI Extrachromosomal amplification of a CFTR YAC in a cystic fibrosis airway epithelial cell line. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Genet & Mol Biol Branch, 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 1999 VL 65 IS 4 SU S MA 2716 BP A478 EP A478 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802719 ER PT J AU Marcelino, J Carpten, JD Suwairi, WM Schwartz, S Robbins, C Sood, R Makalowska, I Baxevanis, A Laxer, RM Johnstone, B Zemel, L Kim, CA Herd, JK Ihle, J Williams, C Johnson, M Raman, V Bahabri, SA Trent, JM Warman, ML AF Marcelino, J Carpten, JD Suwairi, WM Schwartz, S Robbins, C Sood, R Makalowska, I Baxevanis, A Laxer, RM Johnstone, B Zemel, L Kim, CA Herd, JK Ihle, J Williams, C Johnson, M Raman, V Bahabri, SA Trent, JM Warman, ML TI The gene for the camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) encodes a secreted proteoglycan that is essential to normal joint function. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CWRU, Cleveland, OH USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. NHGRI, Bethesda, MD USA. KFSHRC, Riyadh, Saudi Arabia. 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 1999 VL 65 IS 4 SU S MA 246 BP A47 EP A47 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800246 ER PT J AU Marini, JC Bouma, P Cole, WG Sidbury, JB AF Marini, JC Bouma, P Cole, WG Sidbury, JB TI A null alpha 1(V) collagen allele in a family with type II Ehlers-Danlos Syndrome causes variation in type I collagen fibril diameter. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Sect Connect Tissues Disord, HDB, NIH, Bethesda, MD USA. Hosp Sick Children, Div Orthopaed, Toronto, ON M5G 1X8, Canada. 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 1999 VL 65 IS 4 SU S MA 2720 BP A478 EP A478 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802721 ER PT J AU Martin, ER Monks, SA Kaplan, NL AF Martin, ER Monks, SA Kaplan, NL TI A weighted sibship disequilibrium test for linkage and association in discordant sibships. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. Univ Washington, NIEHS, Biostat Branch, Seattle, WA 98195 USA. NR 0 TC 5 Z9 5 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 1999 VL 65 IS 4 SU S MA 2462 BP A434 EP A434 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802463 ER PT J AU Martin-Touaux, E Azibi, K Puech, JP Chateau, D Kremer, E Raben, N Fardeau, M Kahn, A Poenaru, L AF Martin-Touaux, E Azibi, K Puech, JP Chateau, D Kremer, E Raben, N Fardeau, M Kahn, A Poenaru, L TI In vivo gene therapy of Pompe disease using an adenoviral vector. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CHU Cochin Port Royal, Genet Lab, INSERM U129, Paris, France. Pitie Salpetriere, U153, Paris, France. Genethon, Evry, France. NIH, Bethesda, MD 20892 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 1999 VL 65 IS 4 SU S MA 1744 BP A310 EP A310 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801743 ER PT J AU Matikainen, MP Sankila, R Schleutker, J Koivisto, P Tammela, T Pukkala, E Kallioniemi, O AF Matikainen, MP Sankila, R Schleutker, J Koivisto, P Tammela, T Pukkala, E Kallioniemi, O TI A population-based study of cancer incidence in relatives of prostate cancer patients in Finland: High risk of late-onset prostate cancer and association with stomach cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Tampere, IMT, Canc Genet Lab, FIN-33101 Tampere, Finland. TAUH, Tampere, Finland. Finnish Canc Registry, FIN-00170 Helsinki, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 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 1999 VL 65 IS 4 SU S MA 210 BP A40 EP A40 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800209 ER PT J AU Mc Inerney, AM Donnai, D Calveri, M Bitner-Glindzicz, M AF Mc Inerney, AM Donnai, D Calveri, M Bitner-Glindzicz, M TI Multiple etiologies for hemifacial microsomia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. St Marys Hosp, MGB, Manchester M13 0JH, Lancs, England. Great Ormond St Hosp Children, Dept Dent, London WC1N 3JH, England. MGB, Inst Child Hlth, London, England. NR 3 TC 0 Z9 0 U1 1 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 1999 VL 65 IS 4 SU S MA 1882 BP A334 EP A334 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801882 ER PT J AU McAndrew, PE Keppen, LA Kaler, SG AF McAndrew, PE Keppen, LA Kaler, SG TI Rapid mutational screening of the Menkes/Occipital Horn Syndrome locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Med Genet Res Ctr, Childrens Res Inst, Washington, DC USA. Univ S Dakota, Sioux Falls, SD USA. NINDS, Clin Neurocardiol Sect, NIH, 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 1999 VL 65 IS 4 SU S MA 2291 BP A405 EP A405 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802293 ER PT J AU McDermott, M Aksentijevich, I Aganna, E Karenko, L McDermott, EM Hoepelman, AI Phelan, M Teppo, AM Pettersson, T Quane, KA Powell, RJ Molloy, MG Ogunkolade, BW Zweers, EJ Kastner, DL Hitman, GA AF McDermott, M Aksentijevich, I Aganna, E Karenko, L McDermott, EM Hoepelman, AI Phelan, M Teppo, AM Pettersson, T Quane, KA Powell, RJ Molloy, MG Ogunkolade, BW Zweers, EJ Kastner, DL Hitman, GA TI Screening of autosomal dominant recurrent fever families for TNFR1 mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Royal London Hosp, Med Unit, London E1 1BB, England. NIAMS, ARB, NIH, Bethesda, MD USA. Univ Helsinki Hosp, Dept Dermatol, Helsinki, Finland. Univ Helsinki Hosp, Dept Int Med, Helsinki, Finland. Queens Med Ctr, Clin Immunol Unit, Nottingham NG7 2UH, England. Bronovo Ziekenhuis, The Hague, Netherlands. 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 1999 VL 65 IS 4 SU S MA 2724 BP A479 EP A479 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802726 ER PT J AU McGuirt, WT Prasad, SD Griffith, AJ Kunst, DH Shpargel, KB Mueller, RF Brunner, HG Cremers, CWRJ Camp, GV Smith, RJH AF McGuirt, WT Prasad, SD Griffith, AJ Kunst, DH Shpargel, KB Mueller, RF Brunner, HG Cremers, CWRJ Camp, GV Smith, RJH TI Mutations in COL11A2 alter the structure of the tectorial membrane causing nonsyndromic hearing loss at the DFNA13 locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. Univ Hosp, Dept Otorhinolaryngol, Nijmegen, Netherlands. St James Hosp, Dept Clin Genet, Leeds LS9 7TF, W Yorkshire, England. Univ Antwerp, Dept Genet, B-2020 Antwerp, Belgium. Univ Iowa, Dept Otolaryngol, Mol Otolaryngol Rse Lab, Iowa City, IA 52242 USA. RI Brunner, Han/C-9928-2013; Cremers, C.W.R.J./L-4254-2015 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 1999 VL 65 IS 4 SU S MA 579 BP A110 EP A110 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800580 ER PT J AU McKinnon, WC Guttmacher, AE Jacoby, LB MacCollin, M AF McKinnon, WC Guttmacher, AE Jacoby, LB MacCollin, M TI Multiple schwannomas in identical twins. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Vermont, Coll Med, Dept Pediat, Burlington, VT USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 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 1999 VL 65 IS 4 SU S MA 1884 BP A334 EP A334 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801883 ER PT J AU Mendelsohn, NJ Ludowese, C Kriel, R Schirripa, OA Manchester, DK Biesecker, LG AF Mendelsohn, NJ Ludowese, C Kriel, R Schirripa, OA Manchester, DK Biesecker, LG TI Pallister Hall syndrome: early diagnosis and natural history. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Hennepin Cty Med Ctr, Dept Pediat Med Genet, Minneapolis, MN 55415 USA. Univ Minnesota, Minneapolis, MN USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. NIH, Natl Ctr Human Genome Res, GDRB, 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 1999 VL 65 IS 4 SU S MA 1886 BP A335 EP A335 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801887 ER PT J AU Mendoza-Londono, R Arguello, T Prieto, JC Biesecker, LG Warman, M AF Mendoza-Londono, R Arguello, T Prieto, JC Biesecker, LG Warman, M TI Identification of a new mutation in the gene CDMP-1 causing brachydactyly type C in an extensive Colombian pedigree. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 SUNY Brooklyn, Brooklyn, NY USA. Univ Javeriana, Inst Human Genet, Bogota, Colombia. NHGRI, NIH, Bethesda, MD USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr Human Genet, Cleveland, OH 44106 USA. UHC, Cleveland, OH 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 1999 VL 65 IS 4 SU S MA 247 BP A47 EP A47 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800249 ER PT J AU Merry, DE Woods, J Walcott, J Bish, L Fischbeck, KH Abel, A AF Merry, DE Woods, J Walcott, J Bish, L Fischbeck, KH Abel, A TI Characterization of a transgenic model for SBMA. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Penn, Sch Med, Program Pharmacol, Philadelphia, PA 19104 USA. NIH, Neurogenet Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 1999 VL 65 IS 4 SU S MA 153 BP A30 EP A30 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800153 ER PT J AU Miller, JL Gubin, AN Njoroge, JM Lee, T Mitchell, LB AF Miller, JL Gubin, AN Njoroge, JM Lee, T Mitchell, LB TI Genomic studies of human erythropoiesis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, NIH, Biol Chem Lab, 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 1999 VL 65 IS 4 SU S MA 142 BP A28 EP A28 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800142 ER PT J AU Monks, SA Kaplan, NL AF Monks, SA Kaplan, NL TI Extensions of transmission/disequilibrium tests for correlated data or how to use your entire dataset for a test of linkage and association. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Natl Inst Environm Hlth Sci, Dept Biostat, Res Triangle Pk, NC 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 1999 VL 65 IS 4 SU S MA 449 BP A85 EP A85 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800451 ER PT J AU Mononen, N Koivisto, PA Schleutker, J Matikainen, M Tammela, T Trapman, J Kallioniemi, OP AF Mononen, N Koivisto, PA Schleutker, J Matikainen, M Tammela, T Trapman, J Kallioniemi, OP TI Androgen receptor gene mutation R726L is associated with prostate cancer in Finland. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Inst Med Technol, Canc Genet Lab, Tampere, Finland. Erasmus Univ, Dept Pathol, NL-3000 DR Rotterdam, Netherlands. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 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 1999 VL 65 IS 4 SU S MA 1749 BP A311 EP A311 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801748 ER PT J AU Mull, J Leyne, M Gill, SP Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Chadwick, BP Slaugenhaupt, SA AF Mull, J Leyne, M Gill, SP Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Chadwick, BP Slaugenhaupt, SA TI Isolation and characterization of a novel human transcript in the Familial Dysautonomia candidate region on human chromosome 9q31. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. NYU, Sch Med, New York, NY USA. RI Brownstein, Michael/B-8609-2009 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 1999 VL 65 IS 4 SU S MA 2129 BP A377 EP A377 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802131 ER PT J AU Nowak, NJ Conroy, JM Caldwell, GP Catanese, JJ Schuler, G Trask, B Bentley, DR Shen, G de Jong, PJ AF Nowak, NJ Conroy, JM Caldwell, GP Catanese, JJ Schuler, G Trask, B Bentley, DR Shen, G de Jong, PJ TI A resource of mapped BAC clones for cancer chromosome aberrations identification. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. Natl Lib Med, NIH, Bethesda, MD USA. NIH, Natl Lib Med, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Sanger Ctr, Cambridge, England. NCI, DCB, 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 1999 VL 65 IS 4 SU S MA 390 BP A74 EP A74 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800392 ER PT J AU Olivos-Glander, IM Blancato, J Meck, J Biesecker, LG AF Olivos-Glander, IM Blancato, J Meck, J Biesecker, LG TI Molecular analysis of Greig cephalopolysyndactyly syndrome shows a high frequency of deletions. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Georgetown Univ, Inst Mol Human Genet, Washington, DC USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC 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 1999 VL 65 IS 4 SU S MA 2745 BP A483 EP A483 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802746 ER PT J AU Orrison, BM Cabin, DE Gispert, S Chen, A Garrett, L Nussbaum, RL AF Orrison, BM Cabin, DE Gispert, S Chen, A Garrett, L Nussbaum, RL TI Towards mouse models for Parkinson's disease: humanizing the alpha-synuclein locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Genet Dis Res Br, 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 1999 VL 65 IS 4 SU S MA 2746 BP A483 EP A483 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802749 ER PT J AU Orvisky, E Ginns, EI Sidransky, E AF Orvisky, E Ginns, EI Sidransky, E TI Glucosylsphingosine accumulation in patients with Gaucher disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, DHHS, PHS, NIH, Bethesda, MD USA. NR 0 TC 3 Z9 3 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 1999 VL 65 IS 4 SU S MA 2421 BP A427 EP A427 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802423 ER PT J AU Pandya, A Morell, R Oelrich, K Amos, KS Xia, XJ Liu, XZ English, J Blanton, SH Griffith, A Friedman, T Nance, WE AF Pandya, A Morell, R Oelrich, K Amos, KS Xia, XJ Liu, XZ English, J Blanton, SH Griffith, A Friedman, T Nance, WE TI Estimate on the frequency of Connexin 26 mutations in the deaf population in the USA. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Virginia Commonwealth Univ, Richmond, VA 23284 USA. Gallaudet Univ, Washington, DC 20002 USA. NIDCD, Rockville, MD USA. Univ Virginia, Charlottesville, VA 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 1999 VL 65 IS 4 SU S MA 2753 BP A484 EP A484 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802753 ER PT J AU Parry, DM Bromley, CM Courcoutsakis, N Katzman, GL MacCollin, M Patronas, N AF Parry, DM Bromley, CM Courcoutsakis, N Katzman, GL MacCollin, M Patronas, N TI Spinal magnetic resonance (MR) imaging findings In neurofibromatosis 2 (NF2) and correlations with NF2 germline mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 1999 VL 65 IS 4 SU S MA 1768 BP A314 EP A314 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801769 ER PT J AU Peterson, RJ Clark, VJ Smith, MW Dean, M AF Peterson, RJ Clark, VJ Smith, MW Dean, M TI 5' nuclease assay as a tool for SNP haplotype studies of cancer genes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genomic Divers, Frederick, MD 21701 USA. SAIC, Frederick, MD USA. Penn State Univ, Grad Program Genet, University Pk, PA 16802 USA. RI Smith, Michael/B-5341-2012 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 1999 VL 65 IS 4 SU S MA 2357 BP A416 EP A416 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802358 ER PT J AU Porter, FD Richert, N Frank, J Nwokoro, N AF Porter, FD Richert, N Frank, J Nwokoro, N TI Magnetic transfer imaging in Smith-Lemli-Opitz Syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HDB, Bethesda, MD USA. NIH, LDRR, CC, 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 1999 VL 65 IS 4 SU S MA 368 BP A70 EP A70 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800368 ER PT J AU Presciuttini, S Casarino, L Verdiani, S Mannucci, A Peirano, L De Stefano, F Bailey-Wilson, JE AF Presciuttini, S Casarino, L Verdiani, S Mannucci, A Peirano, L De Stefano, F Bailey-Wilson, JE TI Inference on relationships by IBS allele sharing: the mean number of loci per individual needed to discriminate full sibs from non-relatives in a sequential test. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Pisa, Dept Uomo & Ambiente, Pisa, Italy. NHGRI, NIH, Baltimore, MD USA. Univ Genoa, Ist Med Legale, Genoa, Italy. 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 1999 VL 65 IS 4 SU S MA 2227 BP A394 EP A394 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802227 ER PT J AU Pruitt, K Maglott, D Sicotte, H Katz, K Schuler, G AF Pruitt, K Maglott, D Sicotte, H Katz, K Schuler, G TI RefSeq and LocusLink: NCBI's new curated resources for human genes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCBI, NIH, Bethesda, 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 1999 VL 65 IS 4 SU S MA 136 BP A27 EP A27 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800136 ER PT J AU Puck, JM Fanos, JH Davis, J AF Puck, JM Fanos, JH Davis, J TI Sibling knowledge and attitudes toward carrier testing for X-linked severe combined immunodeficiency. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Calif Pacific Med Ctr, Res Inst, San Francisco, 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 1999 VL 65 IS 4 SU S MA 2187 BP A387 EP A387 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802187 ER PT J AU Raben, N Nagaraju, K Lee, E Plotz, P AF Raben, N Nagaraju, K Lee, E Plotz, P TI Increased glycogen load accelerates the course of the disease in the acid alpha-glucosidase knockout mice SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMSD, NIH, Arthritis & Rheumatism Branch, 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 1999 VL 65 IS 4 SU S MA 2765 BP A486 EP A486 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802765 ER PT J AU Radel, M Aragon, R Mazzanti, C Kolachana, B Vanakoski, J Rudolph, J Goldman, D AF Radel, M Aragon, R Mazzanti, C Kolachana, B Vanakoski, J Rudolph, J Goldman, D TI Denaturing high-performance liquid chromatography (dHPLC) analysis of pooled PCR samples for high-throughput screening for DNA sequence variants of human populations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 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 1999 VL 65 IS 4 SU S MA 2360 BP A417 EP A417 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802360 ER PT J AU Reddy, PH Das, MK Das, K Reddy, PA Malik, N Sachdeva, MP Mastana, SS AF Reddy, PH Das, MK Das, K Reddy, PA Malik, N Sachdeva, MP Mastana, SS TI Panorama of Alu insertion polymorphisms in Indian populations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. ISI, Anthropometry & Human Genet Unit, Calcutta, W Bengal, India. Ravi Shankar Univ, Dept Anthropol, Raipur, Madhya Pradesh, India. Univ Delhi, Dept Anthropol, Delhi 110007, India. Univ Loughborough, Dept Human Sci, Loughborough, Leics, 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 1999 VL 65 IS 4 SU S MA 2234 BP A395 EP A395 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802236 ER PT J AU Ren, Z Li, A Shastry, BS Padma, T Ayyagari, R Scott, MH Kaiser-Kupfer, MI Hejtmancik, JF AF Ren, Z Li, A Shastry, BS Padma, T Ayyagari, R Scott, MH Kaiser-Kupfer, MI Hejtmancik, JF TI Mutation identified in crystallin gene in a family with zonular pulverulent cataract. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Oakland Univ, Eye Res Inst, Rochester, MI 48309 USA. Osmania Univ, Dept Genet, Hyderabad 500007, Andhra Pradesh, India. Univ Michigan, Dept Ophthalmol, Ann Arbor, MI 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 1999 VL 65 IS 4 SU S MA 2771 BP A487 EP A487 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802771 ER PT J AU Ringpfeil, F Raus, A Uitto, JJ DiGiovanna, JJ Bale, SJ Richard, G AF Ringpfeil, F Raus, A Uitto, JJ DiGiovanna, JJ Bale, SJ Richard, G TI Darier disease - Novel mutations and a silent polymorphism in ATP2A2. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, NIH, Gen Stud Sect, Bethesda, MD USA. Brown Univ, Dept Derm, Providence, RI USA. Thomas Jefferson Univ, Philadelphia, PA 19107 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 1999 VL 65 IS 4 SU S MA 2773 BP A487 EP A487 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802772 ER PT J AU Rokman, A Schleutker, J Koivisto, P Matikainen, M Karhu, R Kallioniemi, O AF Rokman, A Schleutker, J Koivisto, P Matikainen, M Karhu, R Kallioniemi, O TI Genetic changes in hereditary prostate cancers by comparative genomic hybridization. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Tampere, TAUH, IMT, Canc Genet Lab, FIN-33101 Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 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 1999 VL 65 IS 4 SU S MA 1793 BP A319 EP A319 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801794 ER PT J AU Roschke, AV Tonon, C Nakahara, K Scudiero, DA Kirsch, IR AF Roschke, AV Tonon, C Nakahara, K Scudiero, DA Kirsch, IR TI Using spectral karyotyping (SKY) for analysis of structural instability of chromosomes in human ovarian carcinoma cell lines. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Gen Dept, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, 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 1999 VL 65 IS 4 SU S MA 1795 BP A319 EP A319 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801795 ER PT J AU Rosenberg, M Agarwala, R Hilliard, MS Weber, J Morton, DH Schaffer, AA Kelley, RI Biesecker, LG AF Rosenberg, M Agarwala, R Hilliard, MS Weber, J Morton, DH Schaffer, AA Kelley, RI Biesecker, LG TI Genetic mapping of a locus for Amish microcephaly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, GDRB, Bethesda, MD USA. Kennedy Krieger Inst, Baltimore, MD USA. Clin Special Children, Strasbourg, France. Natl Lib Med, NCBI, NIH, Bethesda, MD USA. Marshfield Clin, Marshfield, WI USA. RI Schaffer, Alejandro/F-2902-2012 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 1999 VL 65 IS 4 SU S MA 2512 BP A443 EP A443 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802515 ER PT J AU Rosenthal, E Biesecker, B Biesecker, LG AF Rosenthal, E Biesecker, B Biesecker, LG TI Parental attitudes towards a diagnosis in children with unidentified multiple congenital anomaly syndromes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. NHGRI, NIH, Lab Genet Dis, Bethesda, 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 1999 VL 65 IS 4 SU S MA 2190 BP A387 EP A387 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802191 ER PT J AU Rust, S Rosier, M Funke, H Real, J Amoura, Z Piette, JC Deleuze, JF Brewer, HB Duverger, N Denefle, P Assmann, G AF Rust, S Rosier, M Funke, H Real, J Amoura, Z Piette, JC Deleuze, JF Brewer, HB Duverger, N Denefle, P Assmann, G TI A defective gene associated with atherosclerosis: Tangier disease is caused by mutations in the ATP binding cassette transporter 1 (ABC1). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Inst Arteriosclerosis Res, Muenster, NRW, Germany. Rhone Poulenc Rorer, Core Genomics Dept, F-91006 Evry, France. Rhone Poulenc Rorer, Cardiovasc Dept, F-91006 Evry, France. Univ Valencia, Dept Med, Hosp Clin Univ, Valencia 46010, Spain. Hop La Pitie Salpetriere, Serv Med Interne, Paris, France. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1999 VL 65 IS 4 SU S MA 172 BP A33 EP A33 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800173 ER PT J AU Saarela, J Riise, HMF Pastinen, T Fejzo, MS Chen, D Kuokkanen, S Peltonen, L AF Saarela, J Riise, HMF Pastinen, T Fejzo, MS Chen, D Kuokkanen, S Peltonen, L TI Candidate regions in MS monitored using SNP microarray. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Helsinki, Helsinki, Finland. Natl Publ Hlth Inst, Dept Mol Genet, Helsinki, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. 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 1999 VL 65 IS 4 SU S MA 2513 BP A443 EP A443 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802513 ER PT J AU Sahoo, T Thomas, JW Lee-Lin, SQ Kuehl, PM Dokken, C Johnson, EW Green, ED Marchuk, DA AF Sahoo, T Thomas, JW Lee-Lin, SQ Kuehl, PM Dokken, C Johnson, EW Green, ED Marchuk, DA TI Physical and transcript map of CCM1 candidate interval on chromosome 7q. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Genet, Durham, NC USA. NHGRI, NIH, Bethesda, MD USA. Barrow Neurol Inst, Phoenix, AZ 85013 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 1999 VL 65 IS 4 SU S MA 2367 BP A418 EP A418 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802369 ER PT J AU Salstrom, J Furuya, T Cannon, GW Remmers, EF Griffiths, MM Wilder, RL AF Salstrom, J Furuya, T Cannon, GW Remmers, EF Griffiths, MM Wilder, RL TI Rat models of autoimmune diseases: The genetic dissection of complex traits. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, Arthritis & Rheumatism Branch, NIH, Bethesda, MD USA. Univ Utah, Res Serv, Vet Affairs Med Ctr, Salt Lake City, UT USA. Univ Utah, Dept Med Rheumatol, Salt Lake City, UT 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 1999 VL 65 IS 4 SU S MA 2653 BP A467 EP A467 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802655 ER PT J AU Sarantaus, L Huusko, P Eerola, H Launonen, V Vehmanen, P Rapakko, K Gillanders, E Syrjakoski, K Kainu, T Vahteristo, P Paakkonen, K Hartikainen, J Blomqvist, C Lopponen, T Holli, K 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 Paakkonen, K Hartikainen, J Blomqvist, C Lopponen, T Holli, K Mannermaa, A Kere, J Kallioniemi, OP Winqvist, R Nevanlinna, H TI BRCA1 and BRCA2 families in Finland: haplotype and phenotype analysis and predominance of founder mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Helsinki, Ctr Hosp, Dept Obstet Gynecol & Oncol, Helsinki, Finland. Univ Oulu Hosp, Dept Clin Genet, Oulu, Finland. Tampere Univ, Canc Genet Lab, FIN-33101 Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. Univ Helsinki, Dept Med Genet, Helsinki, Finland. Univ Helsinki, Finnish Genome Ctr, Helsinki, Finland. Kuopio Univ Hosp, Dept Gynecol, Clin Genet Unit, SF-70210 Kuopio, Finland. RI Kere, Juha/A-9179-2008; Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kere, Juha/0000-0003-1974-0271; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 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 1999 VL 65 IS 4 SU S MA 1802 BP A320 EP A320 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801804 ER PT J AU Sawa, A Wiegand, GW Cooper, J Margolis, RL Sharp, AH Greenamyre, JT Ross, CA Snyder, SH AF Sawa, A Wiegand, GW Cooper, J Margolis, RL Sharp, AH Greenamyre, JT Ross, CA Snyder, SH TI Increased apoptosis of huntingtons disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA. NCI, Frederick, MD 21701 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 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 1999 VL 65 IS 4 SU S MA 2654 BP A467 EP A467 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802653 ER PT J AU Scachen, PC Gillanders, EM Subramony, S Vedanarayayanan, V Crowe, CA Bingier, M Hoffman, EP AF Scachen, PC Gillanders, EM Subramony, S Vedanarayayanan, V Crowe, CA Bingier, M Hoffman, EP TI New mutations in collagen VI alpha 1, alpha 2 genes cause autosomal dominant muscular dystrophy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. NHGRI, NIH, Bethesda, MD USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Metrohlth Med Ctr, Cleveland, OH USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 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 1999 VL 65 IS 4 SU S MA 591 BP A112 EP A112 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800592 ER PT J AU Schaffer, AA Desper, R Jiang, F Kallioniemi, OP Papadimitriou, CH AF Schaffer, AA Desper, R Jiang, F Kallioniemi, OP Papadimitriou, CH TI Using comparative genomic hybridization data to infer tree models of oncogenesis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Univ Basel, Inst Pathol, Basel, Switzerland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. RI Schaffer, Alejandro/F-2902-2012; Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 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 1999 VL 65 IS 4 SU S MA 1804 BP A320 EP A320 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801805 ER PT J AU Schleutker, J Matikainen, M Baffoe-Bonnie, A Xu, J Koivisto, P Tammela, T Smith, J Stephan, D Isaacs, WB Trent, JM Bailey-Wilson, J Kallioniemi, OP AF Schleutker, J Matikainen, M Baffoe-Bonnie, A Xu, J Koivisto, P Tammela, T Smith, J Stephan, D Isaacs, WB Trent, JM Bailey-Wilson, J Kallioniemi, OP TI HPCX (Xq27-26) linkage is common among Finnish prostate cancer families: Strong association with late onset disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. Univ Tampere, TAUH, IMT, Canc Genet Lab, FIN-33101 Tampere, Finland. Univ Maryland, Ctr Genet Asthma & Complex Dis, Baltimore, MD 21201 USA. Johns Hopkins Med Inst, Dept Urol & Oncol, Baltimore, MD 21205 USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 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 1999 VL 65 IS 4 SU S MA 453 BP A86 EP A86 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800456 ER PT J AU Schoenberg-Fejzo, M Saarela, J Chen, D Parkkonen, M Kuokkanen, S Palotie, A Peltonen, L AF Schoenberg-Fejzo, M Saarela, J Chen, D Parkkonen, M Kuokkanen, S Palotie, A Peltonen, L TI Integrated map of chromosome 17q critical region in multiple sclerosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. NHGRI, Canc Genet Branch, NIH, 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 1999 VL 65 IS 4 SU S MA 2521 BP A444 EP A444 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802520 ER PT J AU Sgambati, MT Stolle, C Choyke, PL Walther, MM Zbar, B Linehan, WM Glenn, GM AF Sgambati, MT Stolle, C Choyke, PL Walther, MM Zbar, B Linehan, WM Glenn, GM TI Mosaicism in von Hippel-Lindau disease: Two kindreds each with an affected mosaic parent whose offspring carry germline mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Penn, Genet Diagnost Lab, Philadelphia, PA 19104 USA. NIH, 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 1999 VL 65 IS 4 SU S MA 1809 BP A321 EP A321 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801808 ER PT J AU Shearman, AM Ordovas, JM Cupples, LA Schaefer, EJ Harmon, MD Joost, O DeStefano, AL Keen, D Wilson, PWF Housman, DE Myers, RH AF Shearman, AM Ordovas, JM Cupples, LA Schaefer, EJ Harmon, MD Joost, O DeStefano, AL Keen, D Wilson, PWF Housman, DE Myers, RH TI A genome-wide scan for quantitative trait loci for lipid levels: The Framingham Study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 MIT, Canc Res Ctr, Cambridge, MA 02139 USA. Tufts Univ, Lipid Metab Lab, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA 01701 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 1999 VL 65 IS 4 SU S MA 2655 BP A467 EP A467 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802656 ER PT J AU Sherry, ST Ward, M Sirotkin, K AF Sherry, ST Ward, M Sirotkin, K TI The NCBI dbSNP database for Single Nucleotide Polymorphisms and other classes of minor genetic variation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCBI, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 1999 VL 65 IS 4 SU S MA 532 BP A101 EP A101 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800531 ER PT J AU Shevchenko, YO Compton, JG Toro, JR DiGiovanna, JJ Bale, SJ AF Shevchenko, YO Compton, JG Toro, JR DiGiovanna, JJ Bale, SJ TI Common mutation in transglutaminase 1 in lamellar ichthyosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, Genet Studies Sect, 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 1999 VL 65 IS 4 SU S MA 2794 BP A491 EP A491 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802797 ER PT J AU Shin, HD Winkler, C Stephens, JC Bream, J Young, H Goedert, JJ O'Brien, TR Vlahov, D Buchbinder, S Giorgi, J Rianaldo, C Donfield, S Willoughby, A O'Brien, SJ Smith, MW AF Shin, HD Winkler, C Stephens, JC Bream, J Young, H Goedert, JJ O'Brien, TR Vlahov, D Buchbinder, S Giorgi, J Rianaldo, C Donfield, S Willoughby, A O'Brien, SJ Smith, MW TI Genetic restriction of HIV-1 infection and AIDS progression by promoter alleles of interleukin 10. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, IRSP, SAIC, Lab Genomic Divers, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. NCI, Viral Epidemiol Branch, Baltimore, MD 20852 USA. Johns Hopkins Sch Hyg & Publ Hlth AIDS Link Intrav, Baltimore, MD 21205 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, CIC, Los Angeles, CA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Rho Inc, Chapel Hill, NC USA. NICHD, Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. RI Smith, Michael/B-5341-2012 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 1999 VL 65 IS 4 SU S MA 71 BP A15 EP A15 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800074 ER PT J AU Shugart, YY Hemminki, K Vaittinen, P Dong, C O'Connell, JR Kingman, A AF Shugart, YY Hemminki, K Vaittinen, P Dong, C O'Connell, JR Kingman, A TI A Genetic study of Hodgkin's lymphoma: An estimate of heritability and anticipation using the Familial Cancer Database in Sweden. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Pediat CIDR, Baltimore, MD USA. Karolinska Inst, Dept Biosci, Huddinge, Sweden. Natl Dent & Craniofacial Inst, Bethesda, MD USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Natl Board Hlth & Welf, Ctr Epidemiol, Stockholm, Sweden. 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 1999 VL 65 IS 4 SU S MA 1818 BP A323 EP A323 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801821 ER PT J AU Sidransky, E Tayebi, N Callahan, M Stone, D Madike, V Filiano, JJ Bembi, B Tylki-Szymanska, A Ginns, EI AF Sidransky, E Tayebi, N Callahan, M Stone, D Madike, V Filiano, JJ Bembi, B Tylki-Szymanska, A Ginns, EI TI Are genes contiguous to glucocerebrosidase involved in patients with Gaucher disease who have parkinsonian symptoms? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, DHHS, PHS, NSB,NIH, Bethesda, MD 20892 USA. Childrens Hosp Dartmouth, Dept Pediat Neurol, Lebanon, NH USA. Gaucher Ctr, Trieste, Italy. Childrens Mem Hlth Inst, Warsaw, Poland. 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 1999 VL 65 IS 4 SU S MA 594 BP A112 EP A112 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800596 ER PT J AU Slaugenhaupt, SA Acierno, JS Helbling, LA Bove, C Bach, G Ashworth, L Goldin, E Schiffmann, R AF Slaugenhaupt, SA Acierno, JS Helbling, LA Bove, C Bach, G Ashworth, L Goldin, E Schiffmann, R TI Minimization of the Mucolipidosis Type IV candidate region on human chromosome 19 by haplotype analysis and detailed physical mapping. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, 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 1999 VL 65 IS 4 SU S MA 533 BP A101 EP A101 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800534 ER PT J AU Slavotinek, AM Durrani, S Gorospe, R Maygari, T Schrander-Stumpel, CTRM Biesecker, LG AF Slavotinek, AM Durrani, S Gorospe, R Maygari, T Schrander-Stumpel, CTRM Biesecker, LG TI McKusick-Kaufman syndrome - phenotypic overlap with Bardet-Biedl syndrome necessitates modification of diagnostic criteria management and genetic counseling. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Univ Maastricht, Dept Clin Genet, Maastricht, Netherlands. NR 0 TC 1 Z9 1 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 1999 VL 65 IS 4 SU S MA 186 BP A36 EP A36 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800186 ER PT J AU Smith, MW Lautenberger, JA Stephens, JC O'Brien, SJ AF Smith, MW Lautenberger, JA Stephens, JC O'Brien, SJ TI Significant admixture linkage disequilibrium in African Americans across 30 cM around the FY locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, IRSP, SAIC, Lab Genom Divers, Frederick, MD 21702 USA. Genaissance Pharmaceut Inc, Populat Genom Dept, New Haven, CT 06511 USA. RI Smith, Michael/B-5341-2012 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 1999 VL 65 IS 4 SU S MA 2253 BP A398 EP A398 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802252 ER PT J AU Stacey, MW McAninch, T Santi, L Osgood, C Byrd, RL Liu, JM Young, N Kearns, WG AF Stacey, MW McAninch, T Santi, L Osgood, C Byrd, RL Liu, JM Young, N Kearns, WG TI Increased frequency of glutathione-S transferase (GSTT1) null genotype in patients with aplastic anemia and myelodysplastic syndromes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Ctr Pediat Res, Norfolk, VA USA. Childrens Hosp King Daughters, Div Hematol Oncol, Norfolk, VA USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, 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 1999 VL 65 IS 4 SU S MA 1825 BP A324 EP A324 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801825 ER PT J AU Stephan, DA Malechek, L Gildea, D Smith, J Heiskanen, M Quesenberry, MI Schleutker, J Sood, R Pinket, H Robbins, CM Scott, N Carpten, JD Meltzer, P Kallioniemi, O Isaacs, WB Trent, JM AF Stephan, DA Malechek, L Gildea, D Smith, J Heiskanen, M Quesenberry, MI Schleutker, J Sood, R Pinket, H Robbins, CM Scott, N Carpten, JD Meltzer, P Kallioniemi, O Isaacs, WB Trent, JM TI Physical/transcript map of the hereditary prostate cancer locus at Xq27.3q28. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Canc Genet Lab, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 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 1999 VL 65 IS 4 SU S MA 2378 BP A420 EP A420 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802378 ER PT J AU Stratakis, CA Kirschner, LS Taymans, SE Vaughan, CJ Hatcher, CJ Casey, M Carney, JA Basson, CT AF Stratakis, CA Kirschner, LS Taymans, SE Vaughan, CJ Hatcher, CJ Casey, M Carney, JA Basson, CT TI Genetic Heterogeneity in Carney Complex (OMIM 160980): Contributions of loci at chromosomes 2 and 17 in its genetics. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Unit Genet & Endocrinol, NIH, Bethesda, MD USA. Cornell Univ, Coll Med, New York Hosp, Div Cardiol,Dept Med, New York, NY USA. Mayo Clin, Rochester, MN USA. NR 0 TC 7 Z9 7 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 1999 VL 65 IS 4 SU S MA 2537 BP A447 EP A447 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802537 ER PT J AU Sun, M Schiffmann, R Goldin, E AF Sun, M Schiffmann, R Goldin, E TI Investigating the pathogenesis of mucolipidosis IV using subtractive hybridization. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINDS, Dev & Metab Neurol Branch, NIH, 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 1999 VL 65 IS 4 SU S MA 2438 BP A430 EP A430 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802438 ER PT J AU Tayebi, N Stubblefield, B Stone, D Callahan, M Madike, V Sidransky, E AF Tayebi, N Stubblefield, B Stone, D Callahan, M Madike, V Sidransky, E TI Homologous and non-homologous recombinations at the glucocerebrosidase locus: Implications for Gaucher disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, NSB, NIH, Bethesda, MD USA. US PHS, DHHS, 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 1999 VL 65 IS 4 SU S MA 2807 BP A493 EP A493 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802807 ER PT J AU Taymans, SE Kirschner, LS Pack, S Giatzakis, C Stratakis, CA AF Taymans, SE Kirschner, LS Pack, S Giatzakis, C Stratakis, CA TI YAC-BAC contig of the Carney complex (CNC) critical region on 2p16 and copy number gain of 2p16 in CNC tumors: evidence for a novel oncogene? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, DEB, NIH, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 5 Z9 5 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 1999 VL 65 IS 4 SU S MA 1835 BP A326 EP A326 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801836 ER PT J AU Tonon, G Roschke, A Kuehl, WM Kirsch, IR AF Tonon, G Roschke, A Kuehl, WM Kirsch, IR TI Spectral karyotyping (SKY) in combination with locus-specific FISH, a technique to simultaneously define genes and chromosomes involved in chromosomal translocations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Dept Genet, Med Branch, 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 1999 VL 65 IS 4 SU S MA 396 BP A75 EP A75 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800398 ER PT J AU Toro, JR Bale, SJ King, RA White, JG Gahl, WA AF Toro, JR Bale, SJ King, RA White, JG Gahl, WA TI A novel type of Hermansky-Pudlak Syndrome in Puerto Rico. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, Genet Studies Sect, NIH, Bethesda, MD USA. NICHD, NIH, Bethesda, MD USA. Univ Minnesota, Minneapolis, MN 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 1999 VL 65 IS 4 SU S MA 258 BP A49 EP A49 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800257 ER PT J AU Torosyan, Y Aksentijevich, I Sarkisian, T Astvatsatryan, V Ayvazyan, A Centola, M Chae, JJ Kastner, DL AF Torosyan, Y Aksentijevich, I Sarkisian, T Astvatsatryan, V Ayvazyan, A Centola, M Chae, JJ Kastner, DL TI A population-based survey reveals an extremely high FMF carrier frequency in Armenia, suggesting heterozygote advantage. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, Dept Arthrit & Rheumatism, NIH, Bethesda, MD USA. Yerevan State Univ, Dept Genet, Yerevan 375049, Armenia. Yerevan Med Univ, Dept Pediat, Yerevan, Armenia. Erebuni Med Ctr, Yerevan, Armenia. NR 0 TC 1 Z9 1 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 1999 VL 65 IS 4 SU S MA 2266 BP A400 EP A400 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802267 ER PT J AU Tseng, TL Goldstein, AM Struewing, JP AF Tseng, TL Goldstein, AM Struewing, JP TI Investigating the influence of sequence diversity in the CDKN2A gene on its expression and melanoma susceptibility. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, 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 1999 VL 65 IS 4 SU S MA 2157 BP A382 EP A382 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802160 ER PT J AU Vacha, SJ Shin, SH Meltzer, PS Cohen, MM Biesecker, LG AF Vacha, SJ Shin, SH Meltzer, PS Cohen, MM Biesecker, LG TI The use of cDNA-representational difference analysis (cDNA-RDA) to characterize expression differences between Proteus Syndrome paired tissue samples. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD USA. Dalhousie Univ, Halifax, NS, Canada. NHGRI, Canc Genet Branch, 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 1999 VL 65 IS 4 SU S MA 2671 BP A470 EP A470 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802673 ER PT J AU Vanier, MT Millat, G Marcais, C Rafi, T Yamamoto, T Morris, JA Pentchev, PG Nanba, E Wenger, DA AF Vanier, MT Millat, G Marcais, C Rafi, T Yamamoto, T Morris, JA Pentchev, PG Nanba, E Wenger, DA TI Niemann-Pick C disease: mutational spectrum in NPC1 gene and genotype/phenotype correlations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Lyon Sud Med Sch, INSERM U189, Oullins, France. Thomas Jefferson Univ, Jefferson Med Coll, Dept Neurol, Philadelphia, PA 19107 USA. Tottori Univ, Sch Med, Ctr Gene Res, Yonago, Tottori 683, Japan. NINDS, DMNB, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 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 1999 VL 65 IS 4 SU S MA 2819 BP A495 EP A495 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802819 ER PT J AU Voltz, AK Cassidy, A Cleverly, K Edmonson, M Gandolph, M Harkins, E Hu, Y Kelley, J Michielli, R Scherpbier-Heddema, T Buetow, KH AF Voltz, AK Cassidy, A Cleverly, K Edmonson, M Gandolph, M Harkins, E Hu, Y Kelley, J Michielli, R Scherpbier-Heddema, T Buetow, KH TI Discovery of single nucleotide polymorphisms (SNPs) in biochemical pathway genes as risk factors for cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Populat Genet, DCEG, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 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 1999 VL 65 IS 4 SU S MA 2391 BP A422 EP A422 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802393 ER PT J AU Wada, R Norflus, F Tifft, CJ Proia, RL AF Wada, R Norflus, F Tifft, CJ Proia, RL TI Microglial activation in Sandhoff disease and suppression after bone marrow transplantation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. RI Proia, Richard/A-7908-2012 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 1999 VL 65 IS 4 SU S MA 129 BP A26 EP A26 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800130 ER PT J AU Walker, SJ Price, JA Wright, JT Hart, TC AF Walker, SJ Price, JA Wright, JT Hart, TC TI Genomic structure of the human DLX4/7 gene: evidence for alternative splicing SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Wake Forest Univ, Baptist Med Ctr, Dept Pediat Med Genet, Winston Salem, NC 27109 USA. NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC 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 1999 VL 65 IS 4 SU S MA 2161 BP A382 EP A382 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802162 ER PT J AU Wallace, MR Trimpert, R Nwokoro, N Arn, P Williams, C Keppen, L Elias, E Abuelo, D Kelley, R AF Wallace, MR Trimpert, R Nwokoro, N Arn, P Williams, C Keppen, L Elias, E Abuelo, D Kelley, R TI DHCR7 mutation analysis in Smith-Lemli-Opitz syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Florida, Jacksonville, FL USA. Nemours Childrens Clin, Jacksonville, FL USA. NICHD, NIH, Bethesda, MD USA. Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD USA. Univ S Dakota, Sioux Falls, SD USA. Harvard Univ, Boston, MA 02115 USA. Brown Univ, Providence, RI 02912 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 1999 VL 65 IS 4 SU S MA 2831 BP A497 EP A497 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802831 ER PT J AU Wang, W Tucker, MA Doody, MM Tarone, RE Struewing, JP AF Wang, W Tucker, MA Doody, MM Tarone, RE Struewing, JP TI A single nucleotide polymorphism in the 5'UTR of RAD51 is associated with the risk of breast cancer among BRCA1/2 mutation carriers. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 2 Z9 2 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 1999 VL 65 IS 4 SU S MA 108 BP A22 EP A22 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800111 ER PT J AU Wassif, CA Krakowiak, PA Nwokoro, N Tsokos, M Connor, WE Maslen, CM Steiner, RD Porter, FD AF Wassif, CA Krakowiak, PA Nwokoro, N Tsokos, M Connor, WE Maslen, CM Steiner, RD Porter, FD TI Cellular and molecular studies of Smith-Lemli-Opitz syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HBD, NIH, Bethesda, MD USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NCI, NIH, 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 1999 VL 65 IS 4 SU S MA 2451 BP A432 EP A432 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802453 ER PT J AU Watanabe, RM Langefeld, CD Epstein, M Valle, T Ghosh, S Collins, FS Bergman, RN Boehnke, M AF Watanabe, RM Langefeld, CD Epstein, M Valle, T Ghosh, S Collins, FS Bergman, RN Boehnke, M CA The FUSION Study Investigators TI Genome-wide linkage analysis of type 2 diabetes-related quantitative traits in the FUSION study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Natl Publ Hlth Inst, Helsinki, Finland. Natl Human Genome Res Inst, Bethesda, MD USA. Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA 90089 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 1999 VL 65 IS 4 SU S MA 2565 BP A452 EP A452 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802566 ER PT J AU Weaver, ZA Xu, X Larson, D Wynshaw-Boris, A Deng, CX Ried, T AF Weaver, ZA Xu, X Larson, D Wynshaw-Boris, A Deng, CX Ried, T TI Chromosome aberrations, aneuploidy, and abnormal cell division in Brca1-deficient mice and in the mammary tumors of Brca1 conditional mutants. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Dept Genet, Div Clin Sci, NIH, Bethesda, MD USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, 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 1999 VL 65 IS 4 SU S MA 193 BP A37 EP A37 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800192 ER PT J AU Wilson, AF Sorant, AJM Keats, BJB Bailey-Wilson, JE AF Wilson, AF Sorant, AJM Keats, BJB Bailey-Wilson, JE TI Comparison of the Type I error rate of model-dependent linkage analysis for quantitative traits under random ascertainment. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 LSU, Med Ctr, New Orleans, LA USA. Natl Human Genome Res Inst, NIH, Baltimore, 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 1999 VL 65 IS 4 SU S MA 2198 BP A389 EP A389 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802200 ER PT J AU Witt, MP Wyszynski, DF Wang, YF Miller-Chisholm, A Pawlik, J Khoshnevisan, MH Sun, C Wang, S Zhang, YJ Rutkiewica, E Zebrak, J Kapelerova, A Diehl, SR AF Witt, MP Wyszynski, DF Wang, YF Miller-Chisholm, A Pawlik, J Khoshnevisan, MH Sun, C Wang, S Zhang, YJ Rutkiewica, E Zebrak, J Kapelerova, A Diehl, SR TI Linkage of a gene for Kartagener syndrome to chromosome 15q. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland. Inst TB & Lung Dis, Bronchol & Cyst Fibrosis Clin, Rabka, Poland. Univ Hosp, Clin Pediat 2, Bratislava, Slovakia. Natl Inst Dent & Craniofacial Res, Craniofacial Epidemiol & Genet Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 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 1999 VL 65 IS 4 SU S MA 156 BP A31 EP A31 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800157 ER PT J AU Wolford, JK Hanson, RL Bogardus, C Permana, P Prochazka, M AF Wolford, JK Hanson, RL Bogardus, C Permana, P Prochazka, M TI Single nucleotide polymorphism (SNP) mapping of a type 2 diabetes-linked region on human chromosome 1q21-q23. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, PECRB, NIH, Phoenix, AZ 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 1999 VL 65 IS 4 SU S MA 2396 BP A423 EP A423 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802396 ER PT J AU Wood, JD Duan, K Nucifora, FC Wang, J Kim, Y Schilling, G Lui, J Ross, CA AF Wood, JD Duan, K Nucifora, FC Wang, J Kim, Y Schilling, G Lui, J Ross, CA TI Atrophin-1, the DRPLA gene product, interacts with a component of nuclear care presser complexes, and associates with the nuclear matrix. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Div Neurobiol, Dept Psychiat, Baltimore, MD 21205 USA. NHLBI, Hematol Branch, NIH, 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 1999 VL 65 IS 4 SU S MA 2685 BP A472 EP A472 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802686 ER PT J AU Wyszynski, DF Wu, T Khoshnevisan, MH Miller-Chisholm, AJ Diehl, SR AF Wyszynski, DF Wu, T Khoshnevisan, MH Miller-Chisholm, AJ Diehl, SR TI Evaluation of maternal genotypic effects in the etiology of nonsyndromic cleft lip and palate. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCR, CEGB, 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 1999 VL 65 IS 4 SU S MA 2686 BP A473 EP A473 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802687 ER PT J AU Xu, Z Dutra, A Piatigorsky, J AF Xu, Z Dutra, A Piatigorsky, J TI Functional and structural dissection of a novel human BETA3 gene, a bHLH transcription factor. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Rockville, MD 20852 USA. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 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 1999 VL 65 IS 4 SU S MA 2110 BP A373 EP A373 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802109 ER PT J AU Yan, B Raben, N Nagaraju, K Nichols, R Plotz, P AF Yan, B Raben, N Nagaraju, K Nichols, R Plotz, P TI Hes-1 binds to an E box within intron 1 (IVS I) of the human acid alpha-glucosidase gene and acts as a transcriptional repressor. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, ARB, NIH, Bethesda, MD USA. Dartmouth Med Sch, Dept Med, Hanover, NH 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 1999 VL 65 IS 4 SU S MA 427 BP A81 EP A81 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800428 ER PT J AU Yu, P Chen, A Schwarcz, R Tagle, D AF Yu, P Chen, A Schwarcz, R Tagle, D TI Disruption of mouse kynurenine aminotransferase II gene, a possible factor in the pathophysiology of Huntington's Disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. NR 0 TC 2 Z9 2 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 1999 VL 65 IS 4 SU S MA 2850 BP A500 EP A500 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802852 ER PT J AU Zhang, K Garibaldi, DC Kniazeva, M Hutchinson, A Han, M Dean, M Allikmets, R AF Zhang, K Garibaldi, DC Kniazeva, M Hutchinson, A Han, M Dean, M Allikmets, R TI The ABCR gene recessive and dominant Stargardt diseases: A genetic pathway in macular degeneration. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Wilmer Eye Inst, Baltimore, MD 21205 USA. Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genomic Divers, Frederick, MD 21701 USA. Columbia Univ, Dept Ophthalmol & Pathol, New York, NY USA. RI Kniazeva, Marina/D-4085-2012 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 1999 VL 65 IS 4 SU S MA 609 BP A115 EP A115 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800610 ER PT J AU Bartzokis, G Goldstein, IB Hance, DB Beckson, M Shapiro, D Lu, PH Edwards, N Mintz, J Bridge, P AF Bartzokis, G Goldstein, IB Hance, DB Beckson, M Shapiro, D Lu, PH Edwards, N Mintz, J Bridge, P TI The incidence of T2-weighted MR imaging signal abnormalities in the brain of cocaine-dependent patients is age-related and region-specific SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 149th Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NEW YORK SP Amer Psychiat Assoc ID MIDDLE CEREBRAL-ARTERY; POSITRON EMISSION TOMOGRAPHY; NEUROVASCULAR COMPLICATIONS; SUBCORTICAL LESIONS; ALKALOIDAL COCAINE; LACUNAR INFARCTS; CRACK COCAINE; YOUNG-ADULTS; BLOOD-FLOW; STROKE AB BACKGROUND AND PURPOSE: Cocaine and its metabolites can produce vasospasm, and cocaine-dependent patients are at increased risk for stroke. Based on previous case reports. we hypothesized that the incidence of hyperintense brain lesions observed on T2-weighted MR images would also be increased in asymptomatic cocaine-dependent individuals. METHODS: Sixty-two male "crack" (smoked) cocaine-dependent participants ranging in age from 25 to 66 years were compared with 116 normal male control participants ranging in age from 25 to 80 years. Those with histories of neurologic symptoms or illnesses were excluded. The severity of hyperintense lesions was rated on a 0- to 3-point scale. and ratings of 3 were used in the data analysis as an indicator of a probable pathologic process. Three regions were separately rated: the cerebral white matter. insular subcortex white matter, and subcortical gray matter (basal ganglia and thalamus region). RESULTS: Significantly increased risk of severe lesions was observed in the two white matter regions of the cocaine-dependent group (odds ratio of 16.7 and 20.3) but not in the subcortial gray matter region (odds ratio of 1.4). In the insula subcortex white matter. the risk of lesions increased with age in the cocaine-dependant sample. but remained essentially absent among normal controls through the age of 80 years. In the cerebral white matter, the relationship of age and risk of lesion among normal participants was similar in shape to that in cocaine-dependent participants. but equivalent risk was seen 20 years earlier among cocaine-dependent participants. CONCLUSIONS: Cocaine-dependent participants had a significantly increased age-related risk of white matter damage. The possible clinical implications of this damage are discussed. C1 Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. VA Greater Los Angeles Healthcare Syst, W Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. NIDA, Div Medicat Dev, Rockville, MD USA. RP Bartzokis, G (reprint author), N Little Rock VA Med Ctr, 2200 Ft Roots Dr,Bldg 170,116A NLR, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [AG-11595]; NIDA NIH HHS [1YO1 DA 50038] NR 74 TC 42 Z9 42 U1 1 U2 2 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 1999 VL 20 IS 9 BP 1628 EP 1635 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 250ER UT WOS:000083376500012 PM 10543632 ER PT J AU Longo, LD McClure, ME Jaffe, RB AF Longo, LD McClure, ME Jaffe, RB TI Reproductive physician-scientists for the twenty-first century SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE gynecology; obstetrics; research; academic career ID CLINICAL INVESTIGATOR; OBSTETRICS; GYNECOLOGY; MANPOWER; CRISIS; TRENDS AB As we enter a new century, departments of obstetrics and gynecology in American medical schools face a number of challenges. A primary concern is the relative dearth of physician-scientists to explore basic mechanisms of cell function and relate these to the diseases of women. The question arises, what can we do to revitalize the spirit of investigation in many of our academic departments? This report reviews three programs designed to develop academic investigators: the Reproductive Scientist Development Program, the American Gynecological and Obstetrical Society/American Association of Obstetricians and Gynecologists Foundation Fellowship Program, and the Women's Reproductive Health Research Career Development Centers. On the basis of a decade of experience with the first two of these programs, the prospects for the third are promising. Clearly, the opportunities for obstetrician-gynecologist basic and clinical scientists are considerable. The question remains: Will leaders in the specialty work together to meet the challenge? C1 Loma Linda Univ, Sch Med, Ctr Perinatal Biol, Dept Obstet & Gynecol, Loma Linda, CA 92350 USA. Loma Linda Univ, Sch Med, Ctr Perinatal Biol, Dept Physiol, Loma Linda, CA 92350 USA. NIEHS, Organs & Syst Toxicol Branch, NIH, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Ctr Reprod Endocrinol, San Francisco, CA 94143 USA. RP Longo, LD (reprint author), Loma Linda Univ, Sch Med, Ctr Perinatal Biol, Dept Obstet & Gynecol, Loma Linda, CA 92350 USA. FU NHLBI NIH HHS [HL 03708]; NICHD NIH HHS [K12 HD 00849] NR 24 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-YEAR BOOK 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 1999 VL 181 IS 4 BP 934 EP 939 DI 10.1016/S0002-9378(99)70328-5 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 247EX UT WOS:000083208600031 PM 10521757 ER PT J AU Athayde, N Romero, R Maymon, E Gomez, R Pacora, P Araneda, H Yoon, BH AF Athayde, N Romero, R Maymon, E Gomez, R Pacora, P Araneda, H Yoon, BH TI A role for the novel cytokine RANTES in pregnancy and parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 02-07, 1998 CL MIAMI, FL SP Soc Perinatal Obstetricians DE RANTES; preterm labor; intraamniotic infection ID ACTIVATING PEPTIDE-1 INTERLEUKIN-8; PRETERM PARTURITION; INFLAMMATORY MEDIATORS; ENDOTHELIAL-CELLS; TNF-ALPHA; EXPRESSION; LYMPHOCYTES; FETAL; TERM; CONTRACTILITY AB OBJECTIVE: RANTES (regulated on activation, normal T cell expressed and secreted), a potent and versatile chemokine, is capable of attracting monocytes, lymphocytes, basophils, and eosinophils. This cytokine has been implicated in the regulation of the inflammatory response and in the recruitment of macrophages to the implantation site in early pregnancy. RANTES messenger ribonucleic acid and protein have been detected in fetal tissue and first-trimester trophoblast in response to bacterial endotoxin. The purpose of this study was to determine whether intrauterine infection, parturition (preterm and term), and gestational age affect the amniotic fluid concentrations of RANTES in human pregnancy. STUDY DESIGN: A cross-sectional study was designed to examine the relationship between labor, microbial invasion of the amniotic cavity, gestational age, and RANTES expression in amniotic fluid. Amniotic fluid was obtained from 214 women in the following groups: (1) midtrimester (n = 22), (2) preterm labor with intact membranes in the presence (n = 20) or absence (n = 74) of microbial invasion of the amniotic cavity, (3) term, not in labor (n = 44) and term, in labor in the presence (n = 27) and absence (n = 27) of microbial invasion of the amniotic cavity. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. RANTES concentrations were determined by use of a sensitive and specific immunoassay. RESULTS: (1) Amniotic fluid RANTES concentrations decrease with advancing gestational age (r = 0.43; P < .01). (2) Labor at term was associated with an increase in median concentrations of RANTES (labor-median, 8.4 pg/mL; range, <1.3-94.4 vs no labor-median, <1.3 pg/mL; range, <1.3-230.3; P < .01). (3) Women with preterm labor who delivered preterm (no microbial invasion of the amniotic cavity) had a higher median concentration of amniotic fluid RANTES than those who delivered at term (median, 12.7 pg/mL; range, <1.3-928 vs median, <1.3 pg/mL; range, <1.3-127.5; P < .001). (4) Microbial invasion of the amniotic cavity was associated with a significant increase in median amniotic fluid RANTES in both preterm and term labor (preterm labor with microbial invasion of the amniotic cavity-median, 51.6 pg/mL; range, <1.3-2290 vs preterm labor without microbial invasion of the amniotic cavity-median, 12.7 pg/mL; range, <1.3-928 and vs preterm labor with delivery at term-median, <1.3 pg/mL; range, <1.3-127.5; P < .001 for each; term labor with microbial invasion of the amniotic cavity-median, 16.8 pg/mL; range, <1.3-171.4 vs term labor without microbial invasion of the amniotic cavity-median, 8.4 pg/mL; range, <1.3-94.4; P < .05 and vs no labor and no microbial invasion of the amniotic cavity-median, 1.4 pg/mL; range, <1.3-230.3; P < .001 and P < .05, respectively). CONCLUSION: These results support a role for RANTES in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHD,Perinatol Res Branch, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. Univ Concepcion, Concepcion, Chile. Seoul Natl Univ, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHD,Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011 NR 24 TC 63 Z9 66 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 1999 VL 181 IS 4 BP 989 EP 994 DI 10.1016/S0002-9378(99)70337-6 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 247EX UT WOS:000083208600040 PM 10521766 ER PT J AU Hiller, R Podgor, MJ Sperduto, RD Wilson, PWF Chew, EY D'Agostino, RB AF Hiller, R Podgor, MJ Sperduto, RD Wilson, PWF Chew, EY D'Agostino, RB TI High intraocular pressure and survival: The Framingham studies SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; BEAVER DAM EYE; LENS CHANGES; POPULATION AB PURPOSE: To examine whether high intraocular pressure (greater than or equal to 25 mm Hg) or a history of treatment for glaucoma is associated with decreased survival and, if so, how such ocular markers might be explained. METHODS: Eye examinations, including applanation tonometry, were conducted on members of the Framingham Eye Study cohort from February 1, 1973, to February 1, 1975. Participants who reported a history of treatment for glaucoma were identified. Survival data, including information on the date of death, were available from the time of the Eye Study through March 31, 1990. RESULTS: Of the 1,764 persons under the age of 70 years at the baseline eye examination, 1,421 persons had low intraocular pressure (less than or equal to 20 mm Hg), 264 persons had medium intraocular pressure levels (20 to 24 mm Hg), and 79 persons had high intraocular pressure (greater than or equal to 25 mm Hg) or history of glaucoma treatment. During the follow-up period, 29%, 30%, and 47% died in the groups with low, medium, and high intraocular pressure (or history of glaucoma treatment), respectively. In an age-and-sex adjusted Cox proportional hazards analysis, the death rate ratio for the group with medium intraocular pressure relative to the group with low intraocular pressure was 1.04. The corresponding death rate ratio for the group with high intraocular pressure was 1.56 with a 95% confidence interval of 1.11 to 2.19 (P < .001). After adjustment for age, sex, hypertension, diabetes, cigarette smoking, and body mass index, a positive relationship remained, but at a borderline level of significance (P = .075). CONCLUSIONS: High intraocular pressure or the presence of glaucoma is a marker for decreased life expectancy in the Framingham Eye Study cohort. The relationship is present even after adjustment for risk factors known to be associated with higher mortality such as age, sex, hypertension, diabetes, cigarette smoking, and body mass index. Special attention to the general health status of patients with high intraocular pressure or glaucoma seems warranted. (Am J Ophthalmol 1999; 128:440-445. (C) 1999 by Elsevier Science Inc. All rights reserved.). C1 NEI, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. NHLBI, Framingham, MA USA. Boston Univ, Dept Math, Boston, MA USA. RP Hiller, R (reprint author), NEI, Div Biometry & Epidemiol, Bldg 31,Rm 6A52,31 Ctr Dr MSC 2510, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 EY999999]; NEI NIH HHS [N01-EY-2-2112] NR 22 TC 32 Z9 32 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 1999 VL 128 IS 4 BP 440 EP 445 DI 10.1016/S0002-9394(99)00187-7 PG 6 WC Ophthalmology SC Ophthalmology GA 243NE UT WOS:000083003500006 PM 10577585 ER PT J AU Bisgaard, HC Muller, S Nagy, P Rasmussen, LJ Thorgeirsson, SS AF Bisgaard, HC Muller, S Nagy, P Rasmussen, LJ Thorgeirsson, SS TI Modulation of the gene network connected to interferon-gamma in liver regeneration from oval cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; HEPATIC TRANSCRIPTION FACTORS; ACTIVATOR PLASMIN SYSTEM; FACTOR-ALPHA; STEM-CELLS; RAT-LIVER; ADULT-RAT; EXPRESSION; DIFFERENTIATION; PROLIFERATION AB Suppression subtractive hybridization was used to clone genes associated with proliferation of oval cells in rat liver regenerating after a 70% partial hepatectomy combined with the feeding of 2-acetylaminofluorene, A subset of the identified genes comprised interferon-gamma receptor alpha subunit (IFN-gamma R alpha), gp91phox, interleukin-1 beta (IL-1 beta), lymphocyte function-associated molecule-1 alpha (LFA-1), eukaryotic initiation factor-2-associated 67-kd protein (eIF-2-associated 67-kd protein), and alpha-fetoprotein, which constitute part of the cellular program modulated by IFN-gamma, Therefore, expression analysis performed by Northern blotting and immunohistochemistry were extended to include IFN-gamma, the IFN-gamma receptor beta subunit (IFN-gamma R beta), three secondary response genes induced by interaction of IFN-gamma with IFN-gamma receptor complexes, ie, IL-1 beta-converting enzyme (ICE), intercellular adhesion molecule-1 (ICAM-1), and urokinase-type plasminogen activator receptor (uPAR), and a cytokine inducing IFN-gamma expression, ie, interleukin-18 (IL-18). The Northern blot analysis showed that all examined genes were modulated when progenitor-like oval cells were activated and recruited for liver regeneration. Immunohistochemistry localized the subunits of the IFN-gamma receptor complex, IFN-gamma R alpha and IFN-gamma R beta, the secondary response genes uPAR and ICAM-1, the IFN-gamma-inducing factor IL-18, and ICE to the ductular structures of oval cells. In contrast, during liver regeneration after a 70% partial hepatectomy, only modulation of IL-1 beta and ICE was observed. Our results, therefore, indicate that IFN-gamma-mediated events may be particularly important when cells in the bile ductules must respond to liver damage by production of ductular oval cells. C1 Roskilde Univ Ctr, Dept Chem & Life Sci, DK-4000 Roskilde, Denmark. Semmelweis Univ Med, Inst Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Bisgaard, HC (reprint author), Roskilde Univ Ctr, Dept Chem & Life Sci, Bldg 16-1,Univ Vej 1, DK-4000 Roskilde, Denmark. NR 37 TC 53 Z9 56 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1999 VL 155 IS 4 BP 1075 EP 1085 DI 10.1016/S0002-9440(10)65210-8 PG 11 WC Pathology SC Pathology GA 246UU UT WOS:000083183600011 PM 10514390 ER PT J AU Ashcroft, GS Greenwell-Wild, T Horan, MA Wahl, SM Ferguson, MWJ AF Ashcroft, GS Greenwell-Wild, T Horan, MA Wahl, SM Ferguson, MWJ TI Topical estrogen accelerates cutaneous wound healing in aged humans associated with an altered inflammatory response SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-LEUKOCYTE ELASTASE; ENDOTHELIAL-CELLS; DEGRADATION; FIBRONECTIN; SKIN; METALLOPROTEINASES; NEUTROPHILS; DEPOSITION; INHIBITOR; COLLAGEN AB The effects of intrinsic aging on the cutaneous wound healing process are profound, and the resulting acute and chronic wound morbidity imposes a substantial burden on health services. We have investigated the effects of topical estrogen on cutaneous wound healing in healthy elderly men and women, and related these effects to the inflammatory response and local elastase levels, an enzyme known to be up-regulated in impaired wound healing states. Eighteen health status-defined females (mean age, 74.4 years) and eighteen males (mean age, 70.7 years) were randomized in a double-blind study to either active estrogen patch or identical placebo patch attached for 24 hours to the upper inner arm, through which two 4-mm punch biopsies were made. The wounds were excised at either day 7 or day 80 post-wounding. Compared to placebo, estrogen treatment increased the extent of wound healing in both males and females with a decrease in wound size at day 7, increased collagen levels at both days 7 and 80, and increased day 7 fibronectin levels. In addition, estrogen enhanced the strength of day 80 wounds. Estrogen treatment was associated with a decrease in wound elastase levels secondary to reduced neutrophil numbers, and decreased fibronectin degradation. In vitro studies using isolated human neutrophils indicate that one mechanism underlying the altered inflammatory response involves both a direct inhibition of neutrophil chemotaxis by estrogen and an altered expression of neutrophil adhesion molecules. These data demonstrate that delays in wound healing in the elderly can be significantly diminished by topical estrogen in both male and female subjects, C1 Natl Ins Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Univ Manchester, Sch Biol Sci, Cells Immunol & Dev Div, Manchester, Lancs, England. Hope Hosp, Dept Geriatr Med, Salford M6 8HD, Lancs, England. RP Ashcroft, GS (reprint author), Natl Ins Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Room 327,Bldg 30, Bethesda, MD 20892 USA. NR 28 TC 225 Z9 235 U1 0 U2 10 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1999 VL 155 IS 4 BP 1137 EP 1146 DI 10.1016/S0002-9440(10)65217-0 PG 10 WC Pathology SC Pathology GA 246UU UT WOS:000083183600018 PM 10514397 ER PT J AU Smith, ME Eller, NL McFarland, HF Racke, MK Raine, CS AF Smith, ME Eller, NL McFarland, HF Racke, MK Raine, CS TI Age dependence of clinical and pathological manifestations of autoimmune demyelination - Implications for multiple sclerosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; VASCULAR ENDOTHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; BRITISH-ISLES SURVEY; INBRED GUINEA-PIGS; T-LYMPHOCYTES; ANTIGEN EXPRESSION; OPTIC NEURITIS AB A prominent feature of the clinical spectrum of multiple sclerosis (MS) is its high incidence of onset in the third decade of life and the relative rarity of clinical manifestations during childhood and adolescence, features suggestive of age-related restriction of clinical expression. Experimental allergic encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune demyelination with many similarities to MS, has a uniform rapid onset and a high incidence of clinical and pathological disease in adult (mature) animals. Like MS, EAE is most commonly seen and studied in female adults. In this study, age-related resistance to clinical EAE has been examined with the adoptive transfer model of EAE in SJL mice that received myelin basic protein-sensitized cells from animals 10 days (sucklings) to 12 weeks (young adults) of age. A variable delay before expression of clinical EAE was observed between the different age groups, The preclinical period was longest in the younger (<14 days of age) animals, and shortest in animals 6 to 8 weeks old at time of transfer. Young animals initially resistant to EAE eventually expressed well-developed clinical signs by 6 to 7 weeks of age. This was followed by a remitting, relapsing clinical course. For each age at time of sensitization, increased susceptibility of females compared to males was observed. Examination of the CNS of younger animal groups during the preclinical period showed lesions of acute EAE. Older age groups developed onset of signs coincident with acute CNS lesions. This age-related resistance to clinical EAE in developing mice is reminiscent of an age-related characteristic of MS previously difficult to study in vivo. The associated subclinical CNS pathology and age-related immune functions found in young animals may be relevant to the increasing clinical expression of MS with maturation, and may allow study of factors associated with the known occasional poor correlation of CNS inflammation and demyelination and clinical changes in this disease. C1 NIAID, Div Acquired Immunodeficiency Syndrome, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA. RP Smith, ME (reprint author), NIAID, Div Acquired Immunodeficiency Syndrome, Bldg 6700B,Room 5105,Rockledge Dr, Bethesda, MD 20892 USA. FU NINDS NIH HHS [R01 NS008952, NS 11920, NS 07098, P50 NS011920, NS 08952, T32 NS007098] NR 71 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1999 VL 155 IS 4 BP 1147 EP 1161 DI 10.1016/S0002-9440(10)65218-2 PG 15 WC Pathology SC Pathology GA 246UU UT WOS:000083183600019 PM 10514398 ER PT J AU Gbadegesin, M Vicini, S Hewett, SJ Wink, DA Espey, M Pluta, RM Colton, CA AF Gbadegesin, M Vicini, S Hewett, SJ Wink, DA Espey, M Pluta, RM Colton, CA TI Hypoxia modulates nitric oxide-induced regulation of NMDA receptor currents and neuronal cell death SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE N-methyl-d-aspartate; oxygen-glucose deprivation; PAPA-NO ID D-ASPARTATE RECEPTORS; LONG-TERM POTENTIATION; CEREBRAL-ISCHEMIA; GLUTAMATE-RECEPTOR; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; INDUCED BLOCKADE; BRAIN ISCHEMIA; FREE-RADICALS; RAT-BRAIN AB Nitric oxide (NO) released from a new chemical class of donors enhances N-methyl-D-aspartate (NMDA) channel activity. Using whole cell and single-channel patch-clamp techniques, we have shown that (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]-NO -NO (PAPA-NO) and diethylamine NO, commonly termed NONOates, potentiate the glutamate-mediated response of recombinant rat NMDA receptors (NR1/NR2A) expressed in KEK-293 cells. The overall effect is an increase in both peak and steady-state whole cell currents induced by glutamate. Single-channel studies demonstrate a significant increase in open probability but no change in the mean single-channel open time or mean channel conductance. Reduction in oxygen levels increased and prolonged the PAPA-NO-induced change in both peak and steady-state glutamate currents in transfected HEK cells. PAPA-NO also enhanced cell death in primary cultures of rodent cortical neurons deprived of oxygen and glucose. This potentiation of neuronal injury was blocked by MK-801, indicating a critical involvement of NMDA receptor activation. The NO-induced increase in NMDA channel activity as well as NMDA receptor-mediated cell death provide firm evidence that NO modulates the NMDA channel in a manner consistent with both a physiological role under normoxic conditions and a pathophysiological role under hypoxic conditions. C1 Georgetown Univ, Sch Med, Dept Physiol, Interdisciplinary Program Neurosci, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. Univ Connecticut, Ctr Hlth, Dept Pharmacol, Farmington, CT 06030 USA. NCI, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Colton, CA (reprint author), Georgetown Univ, Sch Med, Dept Physiol, Interdisciplinary Program Neurosci, 3900 Reservoir Rd NW, Washington, DC 20007 USA. FU NIA NIH HHS [AG-16026-01]; NINDS NIH HHS [NS-36812-01] NR 67 TC 35 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 1999 VL 277 IS 4 BP C673 EP C683 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 259XK UT WOS:000083919100010 PM 10516097 ER PT J AU Ballatori, N Hager, DN Nundy, S Miller, DS Boyer, JL AF Ballatori, N Hager, DN Nundy, S Miller, DS Boyer, JL TI Carrier-mediated uptake of lucifer yellow in skate and rat hepatocytes: a fluid-phase marker revisited SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE fluid-phase endocytosis; organic anion transporters; skate and rat liver; isolated hepatocytes ID ASIALOGLYCOPROTEIN RECEPTOR ENDOCYTOSIS; TAURINE TRANSPORT; ORGANIC ANION; INTERNALIZATION; GLUTATHIONE; EFFLUX; LIVER; CELLS; FLOW; HYPEROSMOLARITY AB Uptake of lucifer yellow (LY), a fluorescent disulfonic acid anionic dye, was studied in isolated skate (Raja erinacea) perfused livers and primary hepatocytes to evaluate its utility as a fluid-phase marker in these cells. However, our findings demonstrated that LY is transported across the plasma membrane of skate hepatocytes largely via carrier-mediated mechanisms. Isolated perfused skate livers cleared 50% of the LY from the recirculating perfusate within 1 h of addition of either 22 or 220 mu M LY, with only 4.5 and 9% of the LY remaining in the perfusate after 7 h, respectively. Most of the LY was excreted into bile, resulting in high biliary LY concentrations (1 and 10 mM at the two doses, respectively), indicating concentrative transport into bile canalicular lumen. LY uptake by freshly isolated skate hepatocytes was temperature sensitive, exhibited saturation kinetics, and was inhibited by other organic anions. Uptake was mediated by both sodium-dependent [Michaelis-Menten constant (K-m()), 125 +/- 57 mu M; maximal velocity (V-max), 1.5 +/- 0.2 pmol . mn(-1). mg cells(-1)] and sodium-independent (K-m, 207 +/- 55 mu M; V-max, 1.7 +/- 0.2 pmol min-l mg cells-l) mechanisms. Both of these uptake mechanisms were inhibited by various organic anions and transport inhibitors, including furosemide, bumetanide, sulfobromophthalein, rose bengal, probenecid, N-ethylmaleimide, taurocholate, and p-aminohippuric acid. Fluorescent imaging techniques showed intracellular vesicular compartmentation of LY in skate hepatocyte clusters. Studies in perfused rat livers also indicated that LY is taken up against a concentration gradient and concentrated in bile. LY uptake in isolated rat hepatocytes was saturable, but only at high concentrations, and demonstrated a K-m of 3.7 +/- 1.0 mM and a V-max of 1.75 +/- 0.16 nmol . min(-1). mg wet wt(-1). These results indicate that LY is transported into skate and rat hepatocytes and bile largely by carrier-mediated mechanisms, rather than by fluid-phase endocytosis. C1 Univ Rochester, Sch Med, Dept Environm Med, Rochester, NY 14642 USA. Cornell Univ, Coll Med, New York, NY 10021 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Ctr Liver, New Haven, CT 06520 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RP Ballatori, N (reprint author), Univ Rochester, Sch Med, Dept Environm Med, Box EHSC, Rochester, NY 14642 USA. FU NIDDK NIH HHS [DK-48823]; NIEHS NIH HHS [ES-06484, ES-01247] NR 37 TC 14 Z9 15 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 1999 VL 277 IS 4 BP G896 EP G904 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 259XH UT WOS:000083918900019 PM 10516157 ER PT J AU Morrison, PF Chen, MY Chadwick, RS Lonser, RR Oldfield, EH AF Morrison, PF Chen, MY Chadwick, RS Lonser, RR Oldfield, EH TI Focal delivery during direct infusion to brain: role of flow rate, catheter diameter, and tissue mechanics SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE mathematical model; intracerebral drug delivery ID DRUG INFUSION; MICRODIALYSIS; HYDROCEPHALUS; PRESSURE AB Direct interstitial infusion is a technique capable of delivering agents over both small and large dimensions of brain tissue. However, at a sufficiently high volumetric inflow rate, backflow along the catheter shaft may occur and compromise delivery. A scaling relationship for the finite backflow distance along this catheter in pure gray matter (x(m)) has been determined from a mathematical model based on Stokes flow, Darcy flow in porous media, and elastic deformation of the brain tissue: x(m) = constant Q(o)(3)R(4)r(c)(4)G(-3)mu(-1) (Q(o) = volumetric inflow rate, R = tissue hydraulic resistance, r(c) = catheter radius, G = shear modulus, and mu = viscosity). This implies that backflow is minimized by the use of small diameter catheters and that a fixed (minimal) backflow distance may be maintained by offsetting an increase in flow rate with a similar decrease in catheter radius. Generally, backflow is avoided in rat gray matter with a 32-gauge catheter operating below 0.5 mu l/min. An extension of the scaling relationship to include brain size in the resistance term leads to the finding that absolute backflow distance obtained with a given catheter and inflow rate is weakly affected by the depth of catheter tip placement and, thus, brain size. Finally, an extension of the model to describe catheter passage through a white matter layer before terminating in the gray has been shown to account for observed percentages of albumin in the col pus callosum after a 4-mu l infusion of the compound to rat striatum over a range of volumetric inflow rates. C1 NINDS, Bioengn & Phys Sci Program, Off Res Serv, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Communicat Disorders, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Morrison, PF (reprint author), NINDS, Bioengn & Phys Sci Program, Off Res Serv, NIH, ORS Bldg 13,Rm 3N17, Bethesda, MD 20892 USA. NR 30 TC 115 Z9 119 U1 1 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 1999 VL 277 IS 4 BP R1218 EP R1229 PG 12 WC Physiology SC Physiology GA 259XR UT WOS:000083919700037 PM 10516265 ER PT J AU Norcross, JL Newman, JD Cofrancesco, LM AF Norcross, JL Newman, JD Cofrancesco, LM TI Context and sex differences exist in the acoustic structure of phee calls by newly-paired common marmosets (Callithrix jacchus) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE common marmosets; Callithrix jacchus; acoustic structure; vocalizations; sex differences; social environment ID MACACA-NEMESTRINA; LONG CALLS; CEBUELLA-PYGMAEA; VOCAL STRUCTURE; SOCIAL-CONTEXT; VOCALIZATIONS; COMMUNICATION; STABILITY; RESPONSES; ONTOGENY AB Captive common marmosets of all ages robustly produce a "separation" phee call during brief separations from their group. In contrast, a second structural variant, which may function as an intergroup call, is produced in the home cage primarily by the reproductive adults. A previous study found that postpubertal but nonreproductive offspring rarely produce phee calls when in the home cage with the natal group, yet these marmosets call frequently after pairing with an opposite-sex partner. The sudden increase in home cage phee calls may indicate the rapid onset of intergroup calling. Alternatively, marmosets may be producing the separation phee variant as a result of separation from the natal group. The present study investigated whether phee calls produced by recently paired individuals in the home cage were structurally distinguishable from their calls recorded in a separation paradigm. We also tested whether sex differences, known to exist in the calls of mature adults, could be found in calls recorded from younger, nonreproductive animals separated from their natal groups. We analyzed 18 acoustic parameters of phee calls produced in the home cage after pairing and of calls produced during separation both from the natal group and from a new mate. Discriminant function analyses found that home cage calls were clearly discriminable from separation calls (average 91.7% correctly classified), indicating that the rapid increase in home cage phee call production shortly after pairing is not a consequence of separation from the family group. Postpubertal marmosets appear to show a rapid behavioral adjustment to separation from their natal groups. Additionally, sex was clearly discriminable in calls recorded both before and after pairing (average 86.8% correctly classified). Like calls recorded from well-established paired marmosets, phee calls produced by recently paired, postpubertal marmosets are discriminable by context and sex. (C) 1999 Wiley-Liss, Inc.(dagger). C1 NICHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Newman, JD (reprint author), NICHD, Comparat Ethol Lab, NIH, POB 529, Poolesville, MD 20837 USA. NR 41 TC 23 Z9 24 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD OCT PY 1999 VL 49 IS 2 BP 165 EP 181 DI 10.1002/(SICI)1098-2345(199910)49:2<165::AID-AJP7>3.0.CO;2-S PG 17 WC Zoology SC Zoology GA 226CQ UT WOS:000082003100004 PM 10466575 ER PT J AU Nicolson, R Giedd, JN Lenane, M Hamburger, S Singaracharlu, S Bedwell, J Fernandez, T Thaker, GK Malaspina, D Rapoport, JL AF Nicolson, R Giedd, JN Lenane, M Hamburger, S Singaracharlu, S Bedwell, J Fernandez, T Thaker, GK Malaspina, D Rapoport, JL TI Clinical and neurobiological correlates of cytogenetic abnormalities in childhood-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 28-30, 1998 CL TORONTO, CANADA SP Soc Biol Psychiat ID SEX-CHROMOSOME ANOMALIES; BRAIN; DISORDERS; GENETICS; DELETION; CHILDREN; 22Q11; AGE AB Objective: Cytogenetic abnormalities are increased in schizophrenia, suggesting a possible etiologic contribution. However, their clinical and pathophysiologic roles in the disorder are unknown. To investigate this, a group of children and adolescents participating in a comprehensive study of childhood-onset schizophrenia were screened for chromosomal abnormalities, and their clinical and neurobiological correlates were examined. Method: Cytogenetic screening with the use of high-resolution banding, fluorescent in situ hybridization for chromosome 22q11 deletions, and molecular fragile X testing was undertaken in a group of 47 children and adolescents with very early onset of schizophrenia. Clinical, neurobiological (including brain morphometry), and risk factor measures of the subjects with cytogenetic abnormalities were compared with those of the remaining patients without cytogenetic anomalies. Results: Five patients had previously undiagnosed cytogenetic abnormalities. Lower performance IQ and more pronounced premorbid developmental impairments were seen in this subgroup. Rates of obstetric complications, familial schizophrenia spectrum disorders, and familial eye tracking dysfunction were similar for the patients with and without cytogenetic abnormalities. Conclusions: Cytogenetic abnormalities appear to be increased in childhood-onset schizophrenia, suggesting an association with a very early age at onset. The data from the subgroup of patients with cytogenetic anomalies are consistent with a model in which a childhood onset of schizophrenia is due to a greater impairment of neurodevelopment secondary to the interaction of a number of factors, particularly genetic ones. C1 Yale Univ, New Haven, CT USA. NIMH, Child Psychiat Branch, Baltimore, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Columbia Univ, New York, NY 10027 USA. RP Nicolson, R (reprint author), Bldg 10,Rm 3N202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Fernandez, Thomas/D-4295-2009 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Fernandez, Thomas/0000-0003-0830-022X NR 43 TC 33 Z9 36 U1 5 U2 7 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 1999 VL 156 IS 10 BP 1575 EP 1579 PG 5 WC Psychiatry SC Psychiatry GA 241RN UT WOS:000082896500017 PM 10518169 ER PT J AU Ben-Zion, IZ Meiri, G Greenberg, BD Murphy, DL Benjamin, J AF Ben-Zion, IZ Meiri, G Greenberg, BD Murphy, DL Benjamin, J TI Enhancement of CO2-induced anxiety in healthy volunteers with the serotonin antagonist metergoline SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CARBON-DIOXIDE CHALLENGE; PANIC DISORDER; TRYPTOPHAN DEPLETION AB Objective: The mechanism of action of CO2-induced anxiety is unknown and has been little studied. The authors studied healthy volunteers for the possible influence of serotonin (5-HT) on CO2-induced anxiety. Method: Fourteen healthy volunteers received two vital capacity inhalations each of 35% CO2 and of air, preceded once by placebo and once by the 5-HT antagonist metergoline in a double-blind, randomized crossover design. Results: Mean National Institute of Mental Health self-rating anxiety subscale scores increased nonsignificantly after CO2 inhalation; this effect was significantly enhanced by the administration of metergoline. Conclusions: The authors hypothesize that 5-HT may inhibit CO2-induced anxiety, a function that is lessened by metergoline. C1 Soroka Med Ctr, Div Psychiat, IL-84101 Beer Sheva, Israel. Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Benjamin, J (reprint author), Soroka Med Ctr, Div Psychiat, POB 151, IL-84101 Beer Sheva, Israel. NR 11 TC 27 Z9 28 U1 0 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 1999 VL 156 IS 10 BP 1635 EP 1637 PG 3 WC Psychiatry SC Psychiatry GA 241RN UT WOS:000082896500025 PM 10518177 ER PT J AU Adler, CM Malhotra, AK Elman, I Goldberg, T Egan, M Pickar, D Breier, A AF Adler, CM Malhotra, AK Elman, I Goldberg, T Egan, M Pickar, D Breier, A TI Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FACTORIAL STRUCTURE; CLINICAL SYMPTOMS; COMMUNICATION; SCALE; LANGUAGE; RECEPTOR AB Objective: This study sought to determine whether thought disorder induced in healthy volunteers by the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine resembles the thought disorder found in patients with schizophrenia. Method: The Scale for the Assessment of Thought, Language, and Communication was used to assess thought disorder in healthy volunteers (N=10) who received subanesthetic doses of ketamine and in a group of clinically stable inpatients with schizophrenia (N=15) who did not receive ketamine. Results: Mean scores on the Scale for the Assessment of Thought, Language, and Communication for patients with schizophrenia and healthy volunteers receiving ketamine did not differ significantly. Moreover, three of the four highest rated test items in both groups were the same. Conclusions: These data suggest that ketamine-induced thought disorder in healthy volunteers is not dissimilar to the thought disorder in patients with schizophrenia and provide support for the involvement of the NMDA receptor in a cardinal symptom of schizophrenia. C1 NIMH, Expt Therapeut Branch, Bethesda, MD USA. RP Adler, CM (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 231 Bethesda Ave, Cincinnati, OH 45267 USA. NR 28 TC 185 Z9 192 U1 2 U2 9 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 1999 VL 156 IS 10 BP 1646 EP 1649 PG 4 WC Psychiatry SC Psychiatry GA 241RN UT WOS:000082896500029 PM 10518181 ER PT J AU Nicolson, R Malaspina, D Giedd, JN Hamburger, S Lenane, M Bedwell, J Fernandez, T Berman, A Susser, E Rapoport, JL AF Nicolson, R Malaspina, D Giedd, JN Hamburger, S Lenane, M Bedwell, J Fernandez, T Berman, A Susser, E Rapoport, JL TI Obstetrical complications and childhood-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PREGNANCY; DELIVERY; RISK; AGE AB Objective: Increased obstetrical complications have been reported in individuals with adult-onset schizophrenia, with several studies finding an association between such complications and an earlier age at onset. Consequently, obstetrical records were examined for individuals with childhood-onset schizophrenia to determine if birth complications were more prevalent. Method: The birth records of 36 patients with childhood-onset schizophrenia and 35 sibling comparison subjects were rated for birth complications by two psychiatrists who were unaware of group membership. Results: There were no significant differences between the groups in rates of obstetrical complications. Patients with such complications did not have a relatively earlier age at onset of schizophrenia. Conclusions: A very early age at onset of schizophrenia is probably not due to birth complications. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Columbia Univ, New York, NY 10027 USA. RP Nicolson, R (reprint author), Bldg 10,Rm 3N202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/J-9644-2015; Fernandez, Thomas/D-4295-2009 OI Giedd, Jay/0000-0003-2002-8978; Fernandez, Thomas/0000-0003-0830-022X NR 10 TC 18 Z9 18 U1 6 U2 7 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 1999 VL 156 IS 10 BP 1650 EP 1652 PG 3 WC Psychiatry SC Psychiatry GA 241RN UT WOS:000082896500030 PM 10518182 ER PT J AU Marcus, CL England, S Annett, RD Brooks, LJ Brouillette, RT Carroll, JL Givan, D Gozal, D Kiley, J Redline, S Rosen, CL Rosen, G Tunkel, D AF Marcus, CL England, S Annett, RD Brooks, LJ Brouillette, RT Carroll, JL Givan, D Gozal, D Kiley, J Redline, S Rosen, CL Rosen, G Tunkel, D CA ATS Board Directors TI Cardiorespiratory sleep studies in children - Establishment of normative data and polysomnographic predictors of morbidity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID UPPER AIRWAY-OBSTRUCTION; GROWTH-HORMONE SECRETION; APNEA SYNDROME; RESPIRATORY COMPROMISE; NOCTURNAL HYPOXEMIA; NATURAL-HISTORY; COR-PULMONALE; HEART-RATE; ADENOTONSILLECTOMY; INFANTS C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. McGill Univ, Montreal, PQ, Canada. Indiana Univ, Sch Med, Indianapolis, IN USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. NHLBI, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. RP Marcus, CL (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 69 TC 147 Z9 150 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 1999 VL 160 IS 4 BP 1381 EP 1387 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 244VG UT WOS:000083071000043 ER PT J AU Quintanilla-Martinez, L Fend, F Moguel, LR Spilove, L Beaty, MW Kingma, DW Raffeld, M Jaffe, ES AF Quintanilla-Martinez, L Fend, F Moguel, LR Spilove, L Beaty, MW Kingma, DW Raffeld, M Jaffe, ES TI Peripheral T-cell lymphoma with Reed-Sternberg-like cells of B-cell phenotype and genotype associated with Epstein-Barr virus infection SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Epstein-Barr virus; Hodgkin's disease; T-cell lymphomas; angioimmunoblastic T-cell lymphoma; microdissection; polymerase chain reaction; immunophenotype ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMAS; LASER CAPTURE MICRODISSECTION; GENE REARRANGEMENTS; DISEASE; EXPRESSION; TRANSFORMATION; ORIGIN; CLONE AB We report three cases of nodal peripheral T-cell lymphoma (PTCL) with Reed-Sternberg-like (RS-Like) cells of B-cell pheno- and/or genotype. Histologic analysis in all cases revealed diffuse nodal effacement by atypical lymphoid cells of variable size. Two of the three cases had features of angioimmunoblastic T-cell lymphoma (AILT). Large mononuclear and binucleated cells with prominent eosinophilic nucleoli and abundant cytoplasm resembling classic RS cells and mononuclear variants were scattered throughout all biopsies. The lymphoma cells in the three cases were of T-cell lineage (CD3+, CD43+, and CD45RO+). The RS-like cells from all cases were CD30 and CD15 positive. In contrast to the neoplastic T cells, the RS-like cells lacked all T-cell markers and in two cases were positive for CD20. Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) and EBER 1 (2/2) were detected in the RS-like cells in all cases. The neoplastic T cells were negative for EBV. Polymerase chain reaction (PCR) analysis demonstrated clonal rearrangements of the T-cell receptor gamma chain gene in the three cases. PCR analysis of microdissected RS-like cells for immunoglobulin heavy chain gene rearrangements in cases 1 and 3 showed an oligoclonal pattern. The presence of RS-like cells in PTCL represents a diagnostic pitfall, because in one case this observation led to a misdiagnosis of Hodgkin's disease (HD), The oligoclonal expansion of EBV-infected cells may be related to underlying immunodeficiency associated with T-cell lymphomas and AILT in particular. This phenomenon may provide the basis for some cases of Hodgkin's disease after T-cell lymphomas and suggests that they are clonally unrelated neoplasms. The expression of LMP1 appears to be crucial for the immunophenotype and probably for the morphology of the RS and RS-like cells appearing in diverse lymphoid malignancies, including HD, chronic lymphocytic leukemia, and PTCL. C1 NCI, NIH, Hematopathol Sect, Bethesda, MD 20892 USA. Inst Mexicano Seguro Social, Dept Pathol, Merida, Yucatan, Mexico. Danbury Hosp, Dept Pathol, Danbury, CT USA. RP Jaffe, ES (reprint author), NCI, NIH, Hematopathol Sect, Bldg 10,Room 2N202,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 40 TC 83 Z9 87 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1999 VL 23 IS 10 BP 1233 EP 1240 DI 10.1097/00000478-199910000-00008 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 244NH UT WOS:000083057300008 PM 10524524 ER PT J AU Clark, R Anderson, NB Clark, VR Williams, DR AF Clark, R Anderson, NB Clark, VR Williams, DR TI Racism as a stressor for African Americans - A biopsychosocial model SO AMERICAN PSYCHOLOGIST LA English DT Review ID BLOOD-PRESSURE; SKIN COLOR; SOCIOECONOMIC-STATUS; ANGER EXPRESSION; BLACK-AMERICANS; CARDIOVASCULAR-RESPONSE; PSYCHOLOGICAL STRESS; JOHN-HENRYISM; UNITED-STATES; COMMON COLD AB Various authors have noted that interethnic group and intraethnic group racism are significant stressors for many African Americans. As such, intergroup and intragroup racism may play a role in the high rates of morbidity and mortality in this population. Yet, although scientific examinations of the effects of stress have proliferated few researchers have explored the psychological, social, and physiological effects of perceived racism among African Americans. The purpose of this article was to outline a biopsychosocial model for perceived racism as a guide for future research. The first section of this article provides a brief overview of how racism has been conceptualized in the scientific literature. The second section reviews research exploring the existence of intergroup and intragroup racism. A contextual model for systematic studies of the biopsychosocial effects of perceived racism is then presented, along with recommendations for future research. C1 Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. Morehouse Coll, Dept Psychol, Atlanta, GA 30314 USA. Univ Michigan, Dept Sociol, Ann Arbor, MI 48109 USA. RP Clark, R (reprint author), Wayne State Univ, Dept Psychol, 71 W Warren Ave, Detroit, MI 48202 USA. NR 126 TC 979 Z9 984 U1 10 U2 89 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD OCT PY 1999 VL 54 IS 10 BP 805 EP 816 DI 10.1037/0003-066X.54.10.805 PG 12 WC Psychology, Multidisciplinary SC Psychology GA 245MJ UT WOS:000083112500001 PM 10540593 ER PT J AU Tsarfaty, I Alvord, WG Resau, JH Altstock, RT Lidereau, R Bieche, I Bertrand, F Horev, J Klabansky, RL Keydar, I Vande Woude, GF AF Tsarfaty, I Alvord, WG Resau, JH Altstock, RT Lidereau, R Bieche, I Bertrand, F Horev, J Klabansky, RL Keydar, I Vande Woude, GF TI Alteration of Met protooncogene product expression and prognosis in breast carcinomas SO ANALYTICAL AND QUANTITATIVE CYTOLOGY AND HISTOLOGY LA English DT Article DE Met; breast cancer; confocal microscopy; image analysis; node-negative ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; C-MET; EPITHELIAL-CELLS; MAMMARY-GLAND; FACTOR RECEPTOR; FACTOR-HGF; CANCER; IDENTIFICATION; TUMORIGENICITY AB OBJECTIVE: To objectively quantify the expression and prognostic implications of the met protooncogene product (Met) in human breast cancer. STUDY DESIGN: One hundred eighty-two cases of primary human breast cancer were collected. Both the normal and tumor portions of the original surgical pathology specimen were immunostained for Met and imaged using laser scanning confocal microscopy. Then the cases were ranked according to relative concentrations of normal and tumor Met expression. Subsequently, they were quantified using image analysis and the results correlated with clinical outcome to determine the prognostic value of relative levels of Met. RESULTS: Using a quantitative index to evaluate the relative levels of Met expression, high levels of Met expression in the tumor as compared with the adjacent normal ducts predicted poor prognosis for overall survival and metastasis-ree survival. The risk ratio for elevated Met rxprrssion teas 3.94 (P = .0009). This new method also allows determination of the clinical relevance of low levels of Met in the tumor. The overall survival between the patient population with higher, lower and unchanged levels of Met in normal tissue as compared to tumor were significantly different (P =.0020). CONCLUSION: Our studies suggest that in a subpopulation of node-negative breast cancer patients, either high or low levels of Met in tremor tissue relative to normal tissue is an indicator of poor overall survival (P=.0068). Thus, Met expression could be useful for identifying node-negative patients who could benefit from adjuvant therapy. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Frederick, MD 21701 USA. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel. Data Management Serv Inc, ABL Basic Res Program, Frederick, MD USA. Ctr Rene Huguenin, St Cloud, France. RP Vande Woude, GF (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Bldg 469,POB B, Frederick, MD 21701 USA. NR 50 TC 32 Z9 34 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0884-6812 J9 ANAL QUANT CYTOL JI Anal. Quant. Cytol. Histol. PD OCT PY 1999 VL 21 IS 5 BP 397 EP 408 PG 12 WC Cell Biology SC Cell Biology GA 246AN UT WOS:000083141100005 PM 10560522 ER PT J AU Radko, SP Stastna, M Buzas, Z Kingsley, D Chrambach, A AF Radko, SP Stastna, M Buzas, Z Kingsley, D Chrambach, A TI Charge heterogeneity of commercial, red-shifted recombinant green fluorescent protein, revealed by capillary zone electrophoresis under nondenaturing conditions SO ANALYTICAL BIOCHEMISTRY LA English DT Article C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Membrane & Cellular Biophys, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Russian Acad Med Sci, Med Genet Res Ctr, Moscow, Russia. Agr Biotechnol Ctr, Dept Biochem, H-2101 Godollo, Hungary. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RI Stastna, Miroslava/G-9266-2014 NR 4 TC 7 Z9 7 U1 0 U2 1 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 1999 VL 274 IS 1 BP 146 EP 148 DI 10.1006/abio.1999.4240 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 243XG UT WOS:000083022300021 PM 10527510 ER PT J AU Sharp, DS Everhart, JE Benowitz, NL AF Sharp, DS Everhart, JE Benowitz, NL TI Coffee, alcohol, and the liver SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material ID GAMMA-GLUTAMYL-TRANSFERASE; CHOLESTEROL-RAISING FACTOR; SERUM-LIPIDS; POPULATION DETERMINANTS; DITERPENES CAFESTOL; KAHWEOL; CONSUMPTION; ENZYMES; TROMSO; AMINOTRANSFERASES C1 NIOSH, Biostat Branch, Hlth Effects Lab Div, BB, Morgantown, WV 26505 USA. NIDDKD, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. Univ Calif San Francisco, Div Clin Pharmacol & Expt Therapeut, San Francisco, CA 94143 USA. RP Sharp, DS (reprint author), NIOSH, Biostat Branch, Hlth Effects Lab Div, BB, 1095 Willowdale Rd MS4020, Morgantown, WV 26505 USA. NR 25 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 1999 VL 9 IS 7 BP 391 EP 393 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 239CZ UT WOS:000082752400001 PM 10501405 ER PT J AU Pettinger, MB Waclawiw, MA Davis, KB Thomason, T Garg, R Griffin, B Egan, DA AF Pettinger, MB Waclawiw, MA Davis, KB Thomason, T Garg, R Griffin, B Egan, DA TI Compliance to multiple interventions in a high risk population SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE patient compliance; clinical trials; peripheral vascular diseases ID IMPROVING MEDICATION COMPLIANCE; PERIPHERAL VASCULAR-DISEASE; CARDIOVASCULAR-DISEASE; HYPERCHOLESTEROLEMIA; LIPOPROTEIN; MEN AB PURPOSE: Assess compliance with study medications and examine reasons for noncompliance. Individuals with peripheral arterial disease present the clinician with a unique combination of symptoms and therapeutic needs; the treatment of this population has not been adequately studied. METHODS: The Arterial Disease Multiple Intervention Trial was a randomized double-blind placebo-controlled trial that randomized 468 participants to a combination of antioxidants, niacin and warfarin or matching placebos. Men and women (mean age 65 yrs) with peripheral arterial disease and low density lipoprotein (LDL) < 190 mg/dl were enrolled and followed for one year. Compliance to the study medications was measured by pill count for each medication. An overall measure of compliance was determined by combining pill counts from all study visits. RESULTS: Mean overall pill counts ranged from 88 to 94% in the right treatment groups. No statistically significant differences were found in mean pill counts over time or between active and placebo groups. History of coronary artery disease and number of follow-up visits were associated with higher overall pill counts while low compliance during screening was associated with lower counts during follow up. Participants with an overall mean pill count < 800% had more adverse events compared to those with a higher count. Side effects were reported as the reason for missing pills significantly more often in the active versus placebo niacin group. CONCLUSIONS: Individuals with peripheral arterial disease were able to comply with the complex drug regimen. The ability of this drug combination to reduce cardiovascular events-and improve quality of life warrants study. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Stat & Epidemiol Res Corp, Seattle, WA USA. NHLBI, Bethesda, MD 20892 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. Univ Tennessee, Memphis, TN USA. RP Pettinger, MB (reprint author), FHCRC, 1100 Fairview Ave N,MP 1002, Seattle, WA 98109 USA. FU NHLBI NIH HHS [N01-HC-25110, N01-HC-25112, N01-HC-25111] NR 21 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 1999 VL 9 IS 7 BP 408 EP 418 DI 10.1016/S1047-2797(99)00010-1 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 239CZ UT WOS:000082752400004 PM 10501408 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Overweight, but not high dietary fat intake, increases risk of gastroesophageal reflux disease hospitalization: The NHANES I epidemiologic followup study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE gastroesophageal reflux disease; GERD; esophagitis; hiatal hernia; epidemiology; overweight ID LOWER ESOPHAGEAL SPHINCTER; ACID EXPOSURE; RANDOM-POPULATION; GRADED-EXERCISE; GASTRIC CARDIA; OBESE PATIENTS; HIATUS-HERNIA; PREVALENCE; SYMPTOMS; MOTILITY AB PURPOSE: Gastroesophageal reflux disease is an important and increasingly common condition. Both overweight and high fat food consumption have been implicated as causes of reflux disease. We examined the relationship of overweight, high dietary fat intake, and other factors with reflux disease hospitalization. METHODS: We studied participants in the first National Health and Nutrition Examination Survey, a population-based sample examined in 1971-75 and followed through 1992-93. Persons with a physician diagnosed hiatal hernia at baseline or reflux disease hospitalization within the first five years of study were excluded. A second analysis included follow-up of 9851 participants free of reflux disease in 1982-84. Ninety-six percent of the: baseline cohort were recontacted. Reflux disease cases were persons hospitalized with a diagnosis of esophagitis or uncomplicated hiatal hernia. Hazard race ratios for reflux disease hospitalization according to body mass index (BMI) (kg/m(2)), total daily servings of high fat foods and other factors were calculated using Cox proportional hazards analysis. RESULTS: A total of 12,349 persons were followed for a median of 18.5 years (range 5.0-22.1). Cumulative incidence of reflux disease hospitalization was 5.2% at 20 years. Multivariate survival analysis revealed higher reflux disease hospitalization rates with higher BMI (5 kg/m(2)) [hazard ratio (HR) = 1.22, 95% confidence interval (CI) = 1.13-1.32]. No relationship was found between higher fat intake and reflux disease hospitalization. Other factors associated with reflux disease hospitalization included age, low recreational activity, and history of doctor-diagnosed arthritis. CONCLUSIONS: Overweight, but not high dietary fat intake, increases risk of gastroesophageal reflux disease hospitalization. Published by Elsevier Science Inc. C1 Soc & Sci Syst Inc, Bethesda, MD 20814 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Soc & Sci Syst Inc, 7101 Wisconsin Ave,Suite 1300, Bethesda, MD 20814 USA. FU NIDDK NIH HHS [N01-DK-6-2220] NR 77 TC 114 Z9 118 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 1999 VL 9 IS 7 BP 424 EP 435 DI 10.1016/S1047-2797(99)00020-4 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 239CZ UT WOS:000082752400006 PM 10501410 ER PT J AU Jin, SJ Gu, XX Rhim, JS Lim, DJ AF Jin, SJ Gu, XX Rhim, JS Lim, DJ TI Immortalization of chinchilla middle ear epithelial cells by adenovirus 12-simian virus 40 hybrid virus SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE adenovirus 12-simian virus 40; cell culture; cell line; chinchilla middle ear epithelial cell; immortalization ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; EXPERIMENTAL OTITIS-MEDIA; MONOCLONAL-ANTIBODIES; CYTOKERATIN PATTERNS; EXPRESSION; CULTURE; TISSUES; TRANSFORMATION; CHOLESTEATOMA; PATHOGENESIS AB In order to study the cellular and molecular mechanisms of the pathogenesis of otitis media, a chinchilla middle ear epithelial cell tine (CMEE-I) with differentiated cell characteristics was established by infection of a primary culture with the adenovirus 12-simian virus 40 (Ad12-SV40) hybrid. This cell line has been in continuous culture for 42 passages, whereas the parent cells underwent senescence and died at the 8th passage. The cell line also retains epithelial morphology and expresses cytokeratin polypeptides 4, 7, and 18, characteristic markers for epithelia. In Western blots of cell proteins, bands at 94 and 53 kd were labeled after binding antibodies against SV40 large T antigen and p53, respectively. Karyotype analysis showed that the cell line is derived from chinchilla epithelial cells. These findings confirm that the cell line is a chinchilla epithelial cell immortalized by the hybrid virus. C1 House Ear Inst, Dept Cell & Mol Biol, Los Angeles, CA 90057 USA. NIDOCD, Lab Cellular Biol, NIH, Rockville, MD USA. NCI, Lab Biochem Physiol, NIH, Frederick, MD 21701 USA. RP Lim, DJ (reprint author), House Ear Inst, Dept Cell & Mol Biol, 2100 W 3rd St, Los Angeles, CA 90057 USA. NR 39 TC 9 Z9 9 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 1999 VL 108 IS 10 BP 934 EP 943 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 243QP UT WOS:000083009000003 PM 10526847 ER PT J AU Wu, PC McCart, A Hewitt, SM Turner, E Libutti, SK Bartlett, DL Alexander, HR AF Wu, PC McCart, A Hewitt, SM Turner, E Libutti, SK Bartlett, DL Alexander, HR TI Isolated organ perfusion does not result in systemic microembolization of tumor cells SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 04-07, 1999 CL ORLANDO, FLORIDA SP Soc Surg Oncol DE isolated organ perfusion; RT-PCR; carcinoembryonic antigen; tyrosinase; tumor microembolization ID POLYMERASE CHAIN-REACTION; NECROSIS-FACTOR-ALPHA; ISOLATED LIMB PERFUSION; ISOLATED HEPATIC PERFUSION; SOFT-TISSUE SARCOMAS; PERIPHERAL-BLOOD; REVERSE-TRANSCRIPTASE; INTERFERON-GAMMA; MELANOMA-CELLS; MALIGNANT-MELANOMA AB Background: Isolated organ perfusion with hyperthermia and melphalan with or without tumor necrosis factor-alpha has been effectively used to treat regionally confined, unresectable malignancies of both the limb and liver. Many patients, however, will eventually relapse at distant sites. We used reverse transcription-polymerase chain reaction (RT-PCR) to determine whether significant tumor microembolization occurs in patients undergoing isolated limb perfusion (ILP), isolated hepatic perfusion (MP), of hepatic resection, Methods: Primers specific for the human tyrosinase gene or carcinoembryonic antigen gene were designed for RT-PCR to screen melanoma or colon adenocarcinoma, respectively. RNA from human melanoma lines (Pmel and 1286) and human colon adenocarcinoma lines (H508 and HT29) were used to generate positive control cDNA, Normal human blood was inoculated with tumor cells at concentrations that ranged from 10(-2) to 10(5) tumor cells/ml of blood to define the sensitivity. Systemic and perfusate blood samples were drawn from 15 patients (8 patients underwent IHP, 5 patients underwent ILP, and 2 patients underwent resection) before the start of the operation, immediately before and during the perfusion, and postoperatively. Mononuclear cell fractions were separated from the blood samples and RNA was extracted fur the RT-PCR assay. Standard primers for human beta-actin were used to confirm that cDNA was generated after the RT reaction. Results: RT-PCR assay sensitivity was determined to be 10 tumor cells/ml of whole blood. Of the 8 IHP patients, 6 had colon metastases and 2 had ocular melanoma metastases to the liver. All 5 ILP patients had in transit melanoma of the extremity. Two patients with colon metastases to the liver were found to have resectable disease. There were no detectable circulating tumor cells in the systemic circulation either preoperatively or postoperatively in all 15 patients that were screened. Conclusions: RT-PCR is a highly sensitive method of detecting tumor cells in perfusate or blood. Manipulation of the Limb or liver followed by resection or isolated hyperthermic perfusion does not cause detectable release of circulating tumor cells. The late development of distant metastases observed in many of these patients does not correlate with the ability to measure circulating tumor cells during regional therapy. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Surg, Farmington, CT USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 25 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT-NOV PY 1999 VL 6 IS 7 BP 658 EP 663 DI 10.1007/s10434-999-0658-3 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 258XK UT WOS:000083864800010 PM 10560851 ER PT J AU Groll, AH Petraitis, V Petraitiene, R Field-Ridley, A Calendario, M Bacher, J Piscitelli, SC Walsh, TJ AF Groll, AH Petraitis, V Petraitiene, R Field-Ridley, A Calendario, M Bacher, J Piscitelli, SC Walsh, TJ TI Safety and efficacy of multilamellar liposomal nystatin against disseminated candidiasis in persistently neutropenic rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FUNGAL-INFECTIONS; MARROW TRANSPLANTATION; ENCAPSULATED NYSTATIN; RISK-FACTORS; FLUCONAZOLE; CHILDREN; FUNGEMIA; ALBICANS; LEUKEMIA; TOXICITY AB The activity of liposomal nystatin (L-Nys) against subacute disseminated candidiasis was investigated in persistently neutropenic rabbits. Antifungal therapy was administered for 10 days starting 24 h after intravenous inoculation of 10(3) blastoconidia of Candida albicans, Responses to treatment were assessed by the quantitative clearance of the organism from blood and tissues. Treatments consisted of L-Nys at dosages of 2 and 4 mg/kg of body weight/day (L-Nys2 and L-Nys4, respectively) amphotericin B deoxycholate at 1 mg/kg/day (D-AmB), and fluconazole at 10 mg/kg/day (Flu).;ill treatments were given intravenously once daily. Compared to the results for untreated but infected control animals, treatment with L-Nys2, L-Nys4, D-AmB, and Flu resulted in a significant clearance of the residual burden of C. albicans from the kidney, liver, spleen, lung, and brain (P < 0.0001 by analysis of variance). When the proportion of animals infected at at least one of the five tissue sites studied was evaluated, a dose-dependent response to treatment with L-Nys was found (P < 0.05). Compared to D-AmB-treated rabbits, mean serum creatinine and blood urea nitrogen levels at the end of therapy were significantly lower in animals treated with L-Nys2 (P < 0.001) and L-Nys4 (P < 0.001 and P < 0.01, respectively). L-Nys was less nephrotoxic than conventional amphotericin B and had dose-dependent activity comparable to that of amphotericin B for the early treatment of subacute disseminated candidiasis in persistently neutropenic rabbits. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. Natl Ctr Res Resources, Vet Resources Serv, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Pharmacokinet Res Lab, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 35 TC 21 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1999 VL 43 IS 10 BP 2463 EP 2467 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 242RF UT WOS:000082954900023 PM 10508025 ER PT J AU Yoshimura, K Feldman, R Kodama, E Kavlick, MF Qiu, YL Zemlicka, J Mitsuya, H AF Yoshimura, K Feldman, R Kodama, E Kavlick, MF Qiu, YL Zemlicka, J Mitsuya, H TI In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIGH-LEVEL RESISTANCE; POL GENE-MUTATIONS; REVERSE-TRANSCRIPTASE; DRUG-SENSITIVITY; IN-VITRO; THERAPY; 2',3'-DIDEOXYCYTIDINE; COMPLEX AB Two methylenecyclopropane nucleoside analogues with a phenylphosphoralaninate moiety, QYL-685 and QYL-609, exert potent and specific activities against human immunodeficiency virus type 1 strain LAI (HIV-1(LAI)) and HIV-2 in vitro. In this study, we induced HIV-1 variants resistant to QYL-685 by exposing HIV-1(LAI) to increasing concentrations of QYL-685, After 16 passages, the virus (HIV-1(P16)) was less sensitive to QYL-685 (104-fold), QYL-609 (>41-fold), and (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC) (>1,100-fold) than was HIV-1, and contained an M184I mutation. Two infectious clones, HIV-1(M184I) and HIV-1(M184V) were resistant to QYL-685, QYL-609, and 3TC, confirming that the M184I mutation was responsible for the observed resistance. Viral-fitness analyses (competitive HIV-1 replication assays) revealed that in the absence of drugs, R M184I and M184V conferred a replication disadvantage on the virus compared to the replication efficiency of the wild-type infectious clone (HIV-1(wt)). However, in the presence of QYL-685 (4 mu M), HIV-1(M184I) and HIV-1(M184V) showed greater fitness than HIV-1,. These data may provide structural and virological relevance with regard to the emergence of M184I and M184V substitutions in HIV-1. C1 NCI, Med Branch, Experimental Retrovirol Sect, Div Clin Sci,NIH, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Chem, Detroit, MI 48201 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Dev Therapeut Program,HIV Clin Interface Lab, Frederick, MD 21702 USA. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan. RP Mitsuya, H (reprint author), NCI, Med Branch, Experimental Retrovirol Sect, Div Clin Sci,NIH, Bldg 10,Room 5A11,9000 Rockville Pk, Bethesda, MD 20892 USA. RI Kodama, Eiichi /C-4032-2009 OI Kodama, Eiichi /0000-0002-6622-2752 NR 26 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1999 VL 43 IS 10 BP 2479 EP 2483 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 242RF UT WOS:000082954900026 PM 10508028 ER PT J AU Alvarez-Salas, LM Arpawong, TE DiPaolo, JA AF Alvarez-Salas, LM Arpawong, TE DiPaolo, JA TI Growth inhibition of cervical tumor cells by antisense oligodeoxynucleotides directed to the human papillomavirus type 16 E6 gene SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO; CANCER CELLS; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; PROTOONCOGENE EXPRESSION; HUMAN KERATINOCYTES; SUPPRESSOR PROTEIN; FACTOR RECEPTOR; HUMAN-MELANOMA; E7 GENES AB Human papillomavirus type 16 (HPV-16) is the HPV type most frequently associated with cervical carcinomas. Based on our previous research with anti-HPV ribozymes, we developed a 16-nucleotide antisense oligodeoxynucleotide (AntiE6) able to direct RNase H activity on full-length HPV-16 E6/E7 mRNA. Although the precise mechanism is not completely understood, addition of 50 mu M AntiE6 oligodeoxynucleotide in sterile water caused a significant decrease in the growth rate of CaSki and QGU cervical tumor cell lines. In contrast, addition of a mismatched mutant oligodeoxynucleotide (M7) did not affect cell growth after 72 hours. Treatment with AntiE6 resulted in down-regulation of E6/E7 mRNA and an increase in p53 levels in QGU cells. AntiE6 was also able to (>70%) inhibit significantly growth of transplanted cervical tumors in nude mice after 2 weeks treatment using constant delivery by osmotic pumps. These results indicate that the AntiE6 antisense oligodeoxynucleotides can act as a therapeutic agent against cervical carcinomas. C1 NCI, Dept Hlth & Human Serv, NIH, Lab Biol,Div Basic Sci, Bethesda, MD 20892 USA. RP DiPaolo, JA (reprint author), NCI, Dept Hlth & Human Serv, NIH, Lab Biol,Div Basic Sci, Bldg 37,Room 2A19, Bethesda, MD 20892 USA. NR 61 TC 32 Z9 33 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD OCT PY 1999 VL 9 IS 5 BP 441 EP 450 DI 10.1089/oli.1.1999.9.441 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 250EZ UT WOS:000083377200002 PM 10555151 ER PT J AU Verdier-Pinard, P Sitachitta, N Rossi, JV Sackett, DL Gerwick, WH Hamel, E AF Verdier-Pinard, P Sitachitta, N Rossi, JV Sackett, DL Gerwick, WH Hamel, E TI Biosynthesis of radiolabeled curacin A and its rapid and apparently irreversible binding to the colchicine site of tubulin SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE antimitotic drugs; colchicine site; curacin A; Lyngbya majuscula; microtubule inhibitor ID ANTIMITOTIC NATURAL-PRODUCTS; BRAIN TUBULIN; B-RING; INHIBITION; ANALOGS; POLYMERIZATION; FLUORESCENCE; AGENTS AB Curacin A is a potent competitive inhibitor of colchicine binding to tubulin, and it inhibits the growth of tumor cells. We prepared [C-14]curacin A biosynthetically to investigate its interaction with tubulin. Binding was rapid, even at 0 degrees C, with a minimum k(f) of 4.4 x 10(3) M-1 s(-1). We were unable to demonstrate any dissociation of the [C-14]curacin A from tubulin. Consistent with these observations, the K-a value was so high that an accurate determination by Scatchard analysis was not possible. The [C-14]curacin A was released from tubulin following urea treatment, indicating that covalent bond formation does not occur. We concluded that curacin A binds more tightly to tubulin than does colchicine. Besides high-affinity binding to the colchicine site, we observed significant superstoichiometric amounts of the [C-14]curacin A bound to tubulin, and Scatchard analysis confirmed the presence of two binding sites of relatively low affinity with a K-a of 3.2 x 10(-5) M-1. (C) 1999 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Frederick, MD 21702 USA. Oregon State Univ, Coll Pharm, Corvallis, OR 97331 USA. RP Hamel, E (reprint author), NIH, Bldg 37,Room 5D02, Bethesda, MD 20892 USA. OI Verdier-Pinard, Pascal/0000-0002-6149-6578 NR 28 TC 27 Z9 29 U1 0 U2 2 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 1999 VL 370 IS 1 BP 51 EP 58 DI 10.1006/abbi.1999.1363 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 243XE UT WOS:000083022100007 PM 10496976 ER PT J AU Toro, JR Glenn, G Duray, P Darling, T Weirich, G Zbar, B Linehan, M Turner, ML AF Toro, JR Glenn, G Duray, P Darling, T Weirich, G Zbar, B Linehan, M Turner, ML TI Birt-Hogg-Dube syndrome - A novel marker of kidney neoplasia SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the American-Academy-of-Dermatology CY MAR 19-23, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Acad Dermatol ID HEREDITARY MULTIPLE FIBROFOLLICULOMAS; TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; INTESTINAL POLYPOSIS; SKIN TAGS; ACROCHORDONS; TRICHODISCOMAS; TRANSLOCATION; IDENTIFICATION; MUTATIONS AB Background: Birt-Hogg-Dube syndrome (BHD) is a dominantly inherited predisposition for development of fibrofolliculomas, trichodiscomas, and acrochordons. Concurrent internal tumors, such as colonic polyps and renal carcinoma, have been described in patients with BHD. Objective: To evaluate kindreds with familial renal tumors for cutaneous manifestations of BHD. Design: One hundred fifty-two patients from 49 families underwent complete oral and skin examination. Skin lesions were identified by their clinical appearance. and the diagnosis was confirmed by results of histologic examination. Individuals underwent screening for familial renal neoplasms. Setting: A tertiary referral research hospital. Patients: Individuals with familial renal tumors and their asymptomatic at-risk relatives. Main Outcome Measure: Wt determined whether any form of renal cancer is associated BHD. Results: We identified 3 extended kindreds in whom renal neoplasms and BHD appeared to segregate together. Two kindreds had renal oncocytomas and a third had a variant of papillary renal cell carcinoma. Thirteen patients exhibited BHD. Seven individuals, including a set of identical twins, had renal neoplasms and BHD. An additional 4 patients (3 deceased and nor examined) in these families had renal neoplasms but not BHD. Birt-Hogg-Dube syndrome without renal neoplasms was present in 6 individuals. Thirteen patients with fibrofolliculomas and trichodiscomas presented clinically with multiple smooth skin-colored to grayish-white papules located on the face, auricles, neck, and upper trunk. Oral papules were present in 9 of 28 and achrochordons in 11 of 28 patients. Features of BHD not previously appreciated included deforming lipomas in 5, collagenomas in 4, and pulmonary cysts in 4 of 28 patients. Families with BHD did not display germline mutations in the von Hippel-Lindau gene or in the tyrosine kinase domain of the MET proto-oncogene. Conclusions: Birt-Hogg-Dube syndrome may be associated with familial renal tumors. Birt-Hogg-Dube and renal tumors segregate together in an autosomal dominant fashion, Patients with BHD and their relatives are at risk for development of renal tumors. Therefore, patients with BHD and their relatives should undergo abdominal computed tomography and renal ultrasound screening for renal tumors. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Toro, JR (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N-238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. OI Darling, Thomas/0000-0002-5161-1974 NR 32 TC 195 Z9 197 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 1999 VL 135 IS 10 BP 1195 EP 1202 DI 10.1001/archderm.135.10.1195 PG 8 WC Dermatology SC Dermatology GA 244DK UT WOS:000083036400005 PM 10522666 ER PT J AU Lovell, DJ Lindsley, CB Rennebohm, RM Ballinger, SH Bowyer, SL Giannini, EH Hicks, JE Levinson, JE Mier, R Pachman, LM Passo, MH Perez, MD Reed, AM Schikler, KN Smith, M Zemel, LS Rider, LG AF Lovell, DJ Lindsley, CB Rennebohm, RM Ballinger, SH Bowyer, SL Giannini, EH Hicks, JE Levinson, JE Mier, R Pachman, LM Passo, MH Perez, MD Reed, AM Schikler, KN Smith, M Zemel, LS Rider, LG CA Juvenile Dermatomyositis Dis Activity Collabora TI Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies - II. The Childhood Myositis Assessment Scale (CMAS): A quantitative tool for the evaluation of muscle function SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DERMATOMYOSITIS; POLYMYOSITIS; DISABILITY; STRENGTH AB Objective. To develop, validate, and determine the measurement characteristics of a quantitative tool for assessing the severity of muscle involvement in children with idiopathic inflammatory myopathies. Methods. The Childhood Myositis: Assessment Scale (CMAS) was developed from 2 existing observational functional assessment tools to assess Hnuscle function in the areas of strength and endurance across a wide range of ability and ages. The 14 ordinal items included were chosen to assess primarily axial and proximal muscle groups and are ranked with standard performance and scoring methods. Following the development of the CMAS, a training video and written instructions were developed and reviewed by the physicians participating in this study. Subsequently, utilizing a randomized block design, 12 physicians independently scored 10 children (9 with dermatomyositis, 1 with polymyositis; ages 4-15 years) twice in one day (morning and afternoon) on the CMAS, A pediatric physical therapist performed quantitative manual muscle strength testing (MMT) twice on each child (morning and afternoon), including the neck, trunk, and proximal and distal extremity muscle groups. Results. The CMAS has a potential range of 0-51, with higher scores indicating greater muscle strength and endurance. The observed mean for the 10 patients was 36.4 (median 44, SD 14.1, observed range 5-51), The total score for the CMAS correlated with the physician's global assessment (by visual analog scale) of disease activity, the MMT score, serum creatine kinase level, and the Juvenile Arthritis Functional Assessment Report score, The score on the CMAS was not correlated with patient age. Interrater reliability (Kendall's coefficient of concordance) ranged from 0.77 to 1.0 for individual items (all P < 0.001), and overall, it was 0.95 (P < 0.001). Intrarater reliability for the individual physicians was measured by correlation of the CMAS scores for each patient on 2 separate evaluations and ranged from 0.97 to 0.99, with an overall correlation for all physicians of 0.98 (all P < 0.001), Conclusion. The CMAS demonstrated an acceptable range of observed scores, excellent convergent validity, and excellent inter- and intrarater reliability. The CMAS is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies, It can be used in routine clinical care as well as therapeutic trials. C1 Childrens Hosp, Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Ohio State Univ, Med Ctr, Childrens Hosp, Columbus, OH 43210 USA. Indiana Univ, James Whitcomb Riley Hosp, Med Ctr, Indianapolis, IN 46204 USA. NIH, Bethesda, MD 20892 USA. Univ Kentucky, Lexington, KY USA. Shriners Hosp Children, Lexington, KY USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Louisville, Kosair Childrens Hosp, Sch Med, Louisville, KY 40292 USA. Childrens Med Ctr, Hartford, CT USA. RP Lovell, DJ (reprint author), Childrens Hosp, Med Ctr, Div Rheumatol, Pavil Bldg 2-129,3333 Burnet Ave, Cincinnati, OH 45229 USA. OI Rider, Lisa/0000-0002-6912-2458 FU NIAMS NIH HHS [AR-42632, AR-44059] NR 14 TC 116 Z9 119 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1999 VL 42 IS 10 BP 2213 EP 2219 DI 10.1002/1529-0131(199910)42:10<2213::AID-ANR25>3.0.CO;2-8 PG 7 WC Rheumatology SC Rheumatology GA 246FH UT WOS:000083153400025 PM 10524696 ER PT J AU Alaupovic, P Fesmire, JD Hunnighake, D Domanski, M Forman, S Knatterud, GL Forrester, J Herd, JA Hoogwerf, B Campeau, L Gobel, FL AF Alaupovic, P Fesmire, JD Hunnighake, D Domanski, M Forman, S Knatterud, GL Forrester, J Herd, JA Hoogwerf, B Campeau, L Gobel, FL TI The effect of aggressive and moderate lowering of LDL-cholesterol and low dose anticoagulation on plasma lipids, apolipoproteins and lipoprotein families in post coronary artery bypass graft trial SO ATHEROSCLEROSIS LA English DT Article DE atherosclerosis; saphenous vein grafts; lovastatin; warfarin; lipids; apolipoproteins; lipoprotein families ID HIGH-DENSITY LIPOPROTEINS; PRIMARY HYPERCHOLESTEROLEMIA; ENTEROHEPATIC CIRCULATION; CLINICAL-SIGNIFICANCE; BILE-ACIDS; LOVASTATIN; PARTICLES; EFFICACY; THERAPY; SERUM AB The reported results (The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. New Engl J Med 1997;336:153-162) of the Post Coronary Artery Bypass Graft (Post CABG) trial have shown that aggressive lowering was more effective than moderate lowering of low density lipoprotein (LDL) cholesterol in reducing the progression of atherosclerosis in saphenous-vein grafts (27 vs. 39%; P < 0.001); low dose warfarin had no effect on the progression of atherosclerosis. The present report describes the effect of long-term (an average of 4.3 years) aggressive treatment with high (40-80 mg/day) and moderate treatment with low (2.5-5 mg/day) doses of lovastatin on lipids, apolipoproteins (apo) and apoA-and apoB-containing lipoprotein families. To achieve the target LDL-cholesterol levels (60-85 mg/dl for aggressive group and 134-140 mg/dl for moderate group), cholestyramine (8 g/day) was given to 25% of subjects on aggressive and 5% of subjects on moderate treatment. Although with both treatment strategies there were significant decreases (P < 0.001) in the levels of total cholesterol, LDL-cholesterol, apoB, LDL-apoB and cholesterol-rich Lp-B family, percent changes in the levels of these variables were greater in the aggressive- than in the moderate-treatment groups. These treatments had only marginal effects in increasing the levels of high density lipoprotein cholesterol, apoA-I and Lp-A-I and Lp-A-I:A-II families. The long-term aggressive treatment exerted no effect on the concentrations of triglycerides, apoC-III, apoC-III in VLDL + LDL and triglyceride-rich Lp-B, families. Neither treatment affected the levels of Lp(a). The potentially modifying influence of warfarin and apoE phenotypes on lovastatin-induced changes in lipoprotein variables was found to be of little significance. It is likely that the beneficial effect of lovastatin in reducing the progression of atherosclerosis in grafts is mediated through its specific lowering effect on cholesterol-rich Lp-B particles, (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Maryland Med Res Inst, Baltimore, MD 21210 USA. Oklahoma Med Res Fdn, Lipid & Lipoprot Lab, Oklahoma City, OK 73104 USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Baylor Coll Med, Houston, TX 77030 USA. Cleveland Clin, Cleveland, OH 44106 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Minneapolis Heart Inst, Minneapolis, MN USA. RP Knatterud, GL (reprint author), Maryland Med Res Inst, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. NR 44 TC 23 Z9 25 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 1999 VL 146 IS 2 BP 369 EP 379 DI 10.1016/S0021-9150(99)00151-3 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 240MQ UT WOS:000082830100019 PM 10532693 ER PT J AU Horwitz, B AF Horwitz, B TI Neuron doctrine: Trivial versus radical versus do not dichotomize SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID MODEL AB Gold & Stoljar argue that there are two (often confused) neuron doctrines, one trivial and the other radical, with only the latter having the consequence that non-neuroscientific sciences of the mind will be discarded. They also attempt to show that there is no evidence supporting the radical doctrine. It is argued here that their dichotomy is artificial and misrepresents modem approaches to understanding the neuroscientific cor relates of cognition and behavior. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD OCT PY 1999 VL 22 IS 5 BP 839 EP + DI 10.1017/S0140525X99332192 PG 6 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 274QX UT WOS:000084777500054 ER PT J AU Schooler, C AF Schooler, C TI Psychology and sociology: Beyond neither determinism nor science SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB While agreeing with Rose's reasoning about why the causes of organisms' behaviors cannot be reduced to the solely biological and molecular; this review questions Rose's uses of the terms "determinism" and "contingency"; his occasional seemingly cavalier acceptance as fact of unproven hypotheses about social and psychological phenomena; and his general disdain for the psychometric tradition and its causal modeling extensions. C1 NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. RP Schooler, C (reprint author), NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD OCT PY 1999 VL 22 IS 5 BP 903 EP + DI 10.1017/S0140525X99432200 PG 6 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 274QX UT WOS:000084777500097 ER PT J AU Ching, LM Young, HA Eberly, K Yu, CR AF Ching, LM Young, HA Eberly, K Yu, CR TI Induction of STAT and NF kappa B activation by the antitumor agents 5,6-dimethylxanthenone-4-acetic acid and flavone acetic acid in a murine macrophage cell line SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE antitumor; xanthenones; NF kappa B; STAT; transcription factors ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; TRANSCRIPTION FACTOR; SIGNALING PATHWAYS; COLON-38 TUMORS; BINDING-PROTEIN; MESSENGER-RNA; BLOOD-FLOW; GENE; INTERFERON AB The antitumor agents flavone-8-acetic acid (FAA) and its dose-potent analogue 5,6-dimethyl-xanthenone di-acetic acid (DMXAA), currently in clinical trials, have a novel mechanism of action that is mediated through their ability to induce a spectrum of cytokines. Since NF kappa B and STAT transcription factors participate in the regulation of a number of genes involved in immune and cytokine responses, we investigated whether these transcription factors were activated in the ANA-1 murine macrophage cell line by DMXAA and FAA compared with lipopolysaccharide (LPS), a bacterial component that induces an overlapping spectrum of cytokines. Activation of STAT1 and STAT3 was observed distinctly 4 hr after DMXAA and FAA stimulation. DMXAA and FAA, induced NF kappa B translocation with slower kinetics of activation compared with LPS. STAT activation by DMXAA and FAA was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis. The ANA-1 cells produced high titres of interferons (IFNs) in the culture supernatant after stimulation with DMXAA and FAA, and the addition of antibodies to IFN alpha/beta inhibited STAT activation, indicating that IFNs mediated STAT activation. NF kappa B activation, on the other hand, was not inhibitable with cycloheximide or with antibodies to IFN alpha/beta. NF kappa B activation appeared to be a direct action of the anticancer agents, whereas activation of the STAT proteins was due, in part, to the high titres of IFNs induced. These results demonstrate the significance of the IFN response in initiating the cascade of secondary events that may contribute to the overall antitumor efficacy of DMXAA and FAA in murine models. (C) 1999 Elsevier Science Inc. C1 Univ Auckland, Sch Med, Auckland Canc Soc Res Ctr, Fac Med & Hlth Sci, Auckland, New Zealand. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. RP Ching, LM (reprint author), Univ Auckland, Sch Med, Auckland Canc Soc Res Ctr, Fac Med & Hlth Sci, Private Bag 92019, Auckland, New Zealand. RI Young, Howard/A-6350-2008; Ching, Lai-Ming/H-6735-2016 OI Young, Howard/0000-0002-3118-5111; Ching, Lai-Ming/0000-0002-9745-2868 NR 42 TC 20 Z9 21 U1 0 U2 3 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 1999 VL 58 IS 7 BP 1173 EP 1181 DI 10.1016/S0006-2952(99)00194-X PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 232AK UT WOS:000082343400011 PM 10484075 ER PT J AU Clay, JR Kuzirian, AM AF Clay, JR Kuzirian, AM TI Fluorescence localization of K+ channels in the membrane of squid giant axons SO BIOLOGICAL BULLETIN LA English DT Article; Proceedings Paper CT General Scientific Meeting of the Marine Biological Laboratory CY AUG 16-18, 1999 CL WOODS HOLE, MA SP Marine Biol Lab ID LOLIGO-OPALESCENS; NA+ CHANNELS C1 Marine Biol Lab, Woods Hole, MA 02543 USA. RP NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 10 TC 4 Z9 4 U1 0 U2 1 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 USA SN 0006-3185 EI 1939-8697 J9 BIOL BULL-US JI Biol. Bull. PD OCT PY 1999 VL 197 IS 2 BP 231 EP 232 DI 10.2307/1542620 PG 2 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA 251AC UT WOS:000083421600014 PM 10733271 ER PT J AU Wedel, A Frankenberger, M Sulski, G Petersmann, I Kuprash, D Nedospasov, S Ziegler-Heitbrock, HWL AF Wedel, A Frankenberger, M Sulski, G Petersmann, I Kuprash, D Nedospasov, S Ziegler-Heitbrock, HWL TI Role of p52 (NF-kappa B2) in LPS tolerance in a human B cell line SO BIOLOGICAL CHEMISTRY LA English DT Article DE endotoxin; lipopolysaccharide; NF-kappaB; tolerance ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; BINDING-PROTEIN; ENDOTOXIN TOLERANCE; FACTOR EXPRESSION; MESSENGER-RNA; TRANSCRIPTIONAL ACTIVATION; PERITONEAL-MACROPHAGES; LIPOPOLYSACCHARIDE LPS; DOWN-REGULATION AB Cells of the weakly CD14 positive human B cell line RPMI 8226, clone 1, will mobilize NF-kappa B (p50/p65 and p50/p50) proteins and produce TNF mRNA when stimulated with lipopolysaccharide (LPS), When such cells are precultured with a low amount of LPS (50 - 250 ng/ml) for 3 - 4 days followed by a secondary stimulation with a high dose of LPS (1 mu g/ml) then the cytokine expression is strongly reduced, i.e, the cells have become tolerant. Western blot analysis of proteins of the NF-kappa B/rel family demonstrates cytoplasmic p50 and p65 for naive B cells plus a low level of p52. While with tolerance induction the pattern of p50 and p65 proteins remains essentially unchanged, the LPS tolerant 8226 cells show a dramatic increase of both p52 protein and its p100 precursor in the cytosol. This p52 is found strongly upregulated in Western blots of extracts from purified nuclei of tolerant cells, Also, gelshift analysis with the -605 kappa B motif Of the human TNF 5'-region shows an additional high mobility complex in LPS tolerant cells - a complex that is supershifted with an anti-p52 antibody, Functional analysis with the -1064 TNF 5'-region in front of the luciferase reporter gene demonstrates that transactivation of the TNF promoter is strongly reduced in tolerant cells, Also, overexpression of p52 will suppress activity of TNF promoter reporter gene constructs. Taken together these data show that tolerance to LPS in the human RPM1 8226 a cell line involves upregulation of the p52 (NF-kappa B2) gene, which appears to be instrumental in the blockade of TNF gene expression. C1 Univ Munich, Inst Immunol, D-80336 Munich, Germany. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. RP Ziegler-Heitbrock, HWL (reprint author), Univ Munich, Inst Immunol, Goethestr 31, D-80336 Munich, Germany. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-56000] NR 52 TC 16 Z9 16 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD OCT PY 1999 VL 380 IS 10 BP 1193 EP 1199 DI 10.1515/BC.1999.151 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254KX UT WOS:000083611400009 PM 10595582 ER PT J AU Giedd, JN Jeffries, NO Blumenthal, J Castellanos, FX Vaituzis, AC Fernandez, T Hamburger, SD Liu, H Nelson, J Bedwell, J Tran, L Lenane, M Nicolson, R Rapoport, JL AF Giedd, JN Jeffries, NO Blumenthal, J Castellanos, FX Vaituzis, AC Fernandez, T Hamburger, SD Liu, H Nelson, J Bedwell, J Tran, L Lenane, M Nicolson, R Rapoport, JL TI Childhood-onset schizophrenia: Progressive brain changes during adolescence SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on the State of the Art of Schizophrenia Research CY OCT 08, 1998 CL SANTA FE, NEW MEXICO DE brain; MRI; longitudinal; child; adolescence; schizophrenia ID POSTTRAUMATIC-STRESS-DISORDER; TEMPORAL-LOBE STRUCTURES; HIPPOCAMPAL VOLUME; NEUROANATOMICAL CHANGES; AGES 4-18; RESONANCE; POSTMORTEM; REDUCTION; AMYGDALA; MRI AB Background: Previous NIMH childhood onset schizophrenia (COS) anatomic brain MRI studies found progression of ventricular volume and other structural brain anomalies at 2-year follow up across meals ages 14 to 16 years. However, studies in adult patients generally do not show progression of ventricular volume or correlation of ventricular volume with duration of illness. To address issues of progression of brain anomalies in schizophrenia, this report extends previous studies to include a third longitudinal scan, uses a larger sample size, and includes measures of the amygdala and hippocampus. Methods: Volumes of the total cerebrum, lateral ventricles, hippocampus, and amygdala were quantified on 208 brain magnetic resonance imaging scans from 42 adolescents with COS (23 with one or more repeat scan) and 74 age- and gender-matched controls (36 with one or more repeat scan), A statistical technique permitting combined use of cross-sectional and longitudinal data was used to assess age-related changes, linearity, and diagnostic group differences. Results: Differential nonlinear progression of brain anomalies was seen during adolescence with the total cerebrum and hippocampus decreasing and lateral ventricles increasing in the COS group. The developmental curves for these structures reached art asymptote by early adulthood for the COS group and did not significantly change with age in the control group. Conclusions: These findings reconcile less striking progression of anatomic brain images usually seen for adult schizophrenia and complement other data consistent with time-limited diagnostic-specific decreases in brain tissue. Adolescence appears to be a unique period of differential brain development in schizophrenia. Biol Psychiatry 1999; 46:892-898 (C) 1999 Society of Biological Psychiatry. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr MSC 1367, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Fernandez, Thomas/D-4295-2009 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Fernandez, Thomas/0000-0003-0830-022X NR 45 TC 151 Z9 151 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 1999 VL 46 IS 7 BP 892 EP 898 DI 10.1016/S0006-3223(99)00072-4 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 239RE UT WOS:000082782800004 PM 10509172 ER PT J AU Marchetti, F Lowe, X Bishop, J Wyrobek, AJ AF Marchetti, F Lowe, X Bishop, J Wyrobek, AJ TI Absence of selection against aneuploid mouse sperm at fertilization SO BIOLOGY OF REPRODUCTION LA English DT Article ID IN-SITU HYBRIDIZATION; FLUORESCENCE INSITU HYBRIDIZATION; 2 RECIPROCAL TRANSLOCATIONS; MEIOTIC SEGREGATION; PATERNAL AGE; AUTOSOMAL ANEUPLOIDY; CHROMOSOME; NUCLEI; TRISOMY; MICE AB Is there selection against aneuploid sperm during spermatogenesis and fertilization? To address this question, we used male mice doubly heterozygous for the Robertsonian (Rb) translocations Rb(6.16)24Lub and Rb(16.17)7Bnr, which produce high levels of sperm aneuploid for chromosome 16, the mouse counterpart of human chromosome 21. The frequencies of aneuploid male gametes before and after fertilization were compared by analyzing similar to 500 meiosis II spermatocytes and similar to 500 first-cleavage zygotes using fluorescence in situ hybridization with a DNA painting probe mixture containing three biotin-labeled probes specific for chromosomes 8, 16, and 17 plus a digoxigenin-labeled probe specific for chromosome Y. Hyperhaploidy for chromosome 16 occurred in 20.0% of spermatocytes and in 21.8% of zygotes. Hypohaploidy for chromosome 16 occurred in 17.0% and 16.7% of spermatocytes and zygotes, respectively. In addition, there was no preferential association between chromosome 16 aneuploidy and either of the sex chromosomes, nor was there an elevation in aneuploidy for chromosomes not involved in the Rb translocations. These findings provide direct evidence that there is no selection against aneuploid sperm during spermiogenesis, fertilization, and the first cell cycle of zygotic development. C1 Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Marchetti, F (reprint author), Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, L-452,7000 East Ave,POB 808, Livermore, CA 94550 USA. OI Marchetti, Francesco/0000-0002-9435-4867 FU NIEHS NIH HHS [Y01-ES-10203-00] NR 54 TC 28 Z9 29 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 1999 VL 61 IS 4 BP 948 EP 954 DI 10.1095/biolreprod61.4.948 PG 7 WC Reproductive Biology SC Reproductive Biology GA 240JE UT WOS:000082821500014 PM 10491629 ER PT J AU Chanturiya, A Leikina, E Zimmerberg, J Chernomordik, LV AF Chanturiya, A Leikina, E Zimmerberg, J Chernomordik, LV TI Short-chain alcohols promote an early stage of membrane hemifusion SO BIOPHYSICAL JOURNAL LA English DT Article ID PLANAR BILAYER-MEMBRANES; POLYMORPHIC PHASE-BEHAVIOR; LARGE UNILAMELLAR VESICLES; INFLUENZA HEMAGGLUTININ; PHOSPHOLIPID-VESICLES; COMPLETE FUSION; CELL; PERMEABILITY; TRANSITION; HYDRATION AB Hemifusion, the linkage of contacting lipid monolayers of two membranes before the opening of a fusion pore, is hypothesized to proceed through the formation of a stalk intermediate, a local and strongly bent connection between membranes, When the monolayers' propensity to bend does not support the stalk (e.g., as it is when lysophosphatidylcholine is added), hemifusion is inhibited. In contrast, short-chain alcohols, reported to affect monolayer bending in a manner similar to that of lysophosphatidylcholine, were here found to promote hemifusion between fluorescently labeled liposomes and planar lipid bilayers, Single hemifusion events were detected by fluorescence microscopy. Methanol or ethanol (1.2-1.6 w/w %) added to the same compartment of the planar bilayer chamber as liposomes caused a 5-50 times increase in the number of hemifusion events. Alcohol-induced hemifusion was inhibited by lysophosphatidylcholine. Promotion of membrane hemifusion by short-chain alcohol was also observed for cell-cell fusion mediated by influenza virus hemagglutinin (HA). Alcohol promoted a fusion stage subsequent to the low pH-dependent activation of HA. We propose that binding of short-chain alcohol to the surface of membranes promotes hemifusion by facilitating the transient breakage of the continuity of each of the contacting monolayers, which is required for their subsequent merger in the stalk intermediate. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chernomordik, LV (reprint author), NICHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 10D-04,10 Ctr Dr, Bethesda, MD 20892 USA. NR 68 TC 31 Z9 31 U1 1 U2 5 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 1999 VL 77 IS 4 BP 2035 EP 2045 PG 11 WC Biophysics SC Biophysics GA 244PK UT WOS:000083059800023 PM 10512823 ER PT J AU Kumari, D Usdin, K AF Kumari, D Usdin, K TI Sequencing errors in reactions using labeled terminators SO BIOTECHNIQUES LA English DT Article ID DNA-POLYMERASE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, NIH, Bldg 8,Room 202,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1999 VL 27 IS 4 BP 648 EP + PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253LE UT WOS:000083557400002 PM 10524297 ER PT J AU Curtis, RE Travis, LB Rowlings, PA Socie, G Kingma, DW Banks, PM Jaffe, WS Sale, GE Horowitz, MM Witherspoon, RP Shriner, DA Weisdorf, DJ Kolb, HJ Sullivan, KM Sobcinski, KA Gale, RP Hoover, RN Fraumeni, JF Deeg, HJ AF Curtis, RE Travis, LB Rowlings, PA Socie, G Kingma, DW Banks, PM Jaffe, WS Sale, GE Horowitz, MM Witherspoon, RP Shriner, DA Weisdorf, DJ Kolb, HJ Sullivan, KM Sobcinski, KA Gale, RP Hoover, RN Fraumeni, JF Deeg, HJ TI Risk of lymphoproliferative disorders after bone marrow transplantation: A multi-institutional study SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; VERSUS-HOST DISEASE; STEM-CELL TRANSPLANTATION; MONOCLONAL-ANTIBODIES; HODGKINS-DISEASE; DEPLETED MARROW; RECIPIENTS; LYMPHOMA; LYMPHOCYTES; LEUKEMIA AB We evaluated 18,014 patients who underwent allogeneic hone marrow transplantation (BMT) at 235 centers worldwide to examine the incidence of and risk factors for posttransplant lymphoproliferative disorders ( PTLD). PTLD developed in 78 recipients, with 64 cases occurring less than 1 year after transplantation. The cumulative incidence of PTLD was 1.0% +/- 0.3% at 10 years. incidence was highest 1 to 5 months posttransplant (120 cases/10,000 patients/yr) followed by a steep decline to less than 5/10,000/yr among greater than or equal to 1-year survivors. In multivariate analyses, risk of early-onset PTLD (<1 year) was strongly associated (P < .0001) with unrelated or human leukocyte antigen (HLA) mismatched related donor (relative risk [RR] = 4.1), T-cell depletion of donor marrow (RR = 12.7), and use of antithymocyte globulin (RR = 6.4) or anti-CD3 monoclonal antibody (RR = 43.2) for prophylaxis or treatment of acute graft-versus-host disease (GVHD). There was a weaker association with the occurrence of acute GVHD grades II to IV (RR = 1.9, P = .02) and with conditioning regimens that included radiation (RR = 2.9, P = .02). Methods of T-cell depletion that selectively targeted T cells or T plus natural killer (NK) cells were associated with markedly higher risks of PTLD than methods that removed both T and B cells, such as the CAMPATH-1 monoclonal antibody or elutriation (P = .009). The only risk factor identified for late-onset PTLD was extensive chronic GVHD (RR = 4.0, P = .01). Rates of PTLD among patients with 2 or greater than or equal to 3 major risk factors were 8.0% +/- 2.9% and 22% +/- 17.9%, respectively. We conclude that factors associated with altered immunity and T-cell regulatory mechanisms are predictors of both early- and late-onset PTLD. This is a US government work. There are no restrictions on its use. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Biol & Diag, Pathol Lab, Bethesda, MD 20892 USA. Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Milwaukee, WI 53226 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Hop St Louis, Paris, France. Carolinas Med Ctr, Charlotte, NC 28203 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Salick Hlth Care Inc, Los Angeles, CA USA. Univ Munich, Munich, Germany. RP Curtis, RE (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Room 7042, Bethesda, MD 20892 USA. FU NCI NIH HHS [P01-CA-40053, P01-CA 18029, P01-CA-18221] NR 56 TC 383 Z9 410 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1999 VL 94 IS 7 BP 2208 EP 2216 PG 9 WC Hematology SC Hematology GA 242HT UT WOS:000082935000006 PM 10498590 ER PT J AU Hanazono, Y Brown, KE Handa, A Metzger, ME Heim, D Kurtzman, GJ Donahue, RE Dunbar, CE AF Hanazono, Y Brown, KE Handa, A Metzger, ME Heim, D Kurtzman, GJ Donahue, RE Dunbar, CE TI In vivo marking of rhesus monkey lymphocytes by adeno-associated viral vectors: Direct comparison with retroviral vectors SO BLOOD LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; GENE-THERAPY; IN-VIVO; NONDIVIDING CELLS; INFECTED PATIENTS; HIV-1 INFECTION; T-LYMPHOCYTES; EXPRESSION; INTEGRATION; TITER AB We have compared adeno-associated virus (AAV)-based and retrovirus-based vectors for their ability to transduce primary T lymphocytes in vitro and then tracked the persistence of these genetically marked lymphocytes in vivo, using the rhesus monkey model. To avoid the complication of immune rejection of lymphocytes transduced with xenogeneic genes in tracking studies primarily designed to investigate transduction efficiency and in vivo kinetics, the vectors were designed without expressed genes. All vectors contained identically mutated beta-galactosidase gene (beta-gal) and neomycin resistance gene (neo) DNA sequences separated by different length polylinkers, allowing simple differentiation by polymerase chain reaction (PCR), Each of 2 aliquots of peripheral blood lymphocytes from 4 rhesus monkeys were transduced with either AAV or retroviral vectors. The in vitro transduction efficiency (mean vector copy number/cell) after the ex vivo culture was estimated by PCR at 0.015 to 3.0 for AAV, varying depending on the multiplicity of infection (MOI) used for transduction, and 0.13 to 0.19 for the retroviral transductions. Seven days after transduction, Southern blot analysis of AAV-transduced lymphocytes showed double-stranded and head-to-tail concatemer forms but failed to show integration of the AAV vector. AAV and retroviral aliquots were reinfused concurrently into each animal. Although the retrovirally marked lymphocytes could be detected for much longer after infusion, AAV transduction resulted in higher short-term in vivo marking efficiency compared with retroviral vectors, suggesting possible clinical applications of AAV vectors in lymphocyte gene therapy when longterm vector persistence is not required or desired. This is a US government work. There are no restrictions on its use. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Avigen Inc, Alameda, CA USA. RP Dunbar, CE (reprint author), Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 32 Z9 35 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1999 VL 94 IS 7 BP 2263 EP 2270 PG 8 WC Hematology SC Hematology GA 242HT UT WOS:000082935000014 PM 10498598 ER PT J AU Rosenzweig, M MacVittie, TJ Harper, D Hempel, D Glickman, RL Johnson, RP Farese, AM Whiting-Theobald, N Linton, GF Yamasaki, G Jordan, CT Malech, HL AF Rosenzweig, M MacVittie, TJ Harper, D Hempel, D Glickman, RL Johnson, RP Farese, AM Whiting-Theobald, N Linton, GF Yamasaki, G Jordan, CT Malech, HL TI Efficient and durable gene marking of hematopoietic progenitor cells in nonhuman primates after nonablative conditioning SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; RETROVIRAL-MEDIATED TRANSDUCTION; CHRONIC GRANULOMATOUS-DISEASE; LONG-TERM HEMATOPOIESIS; RHESUS PERIPHERAL-BLOOD; IMMUNE-DEFICIENT MICE; STEM-CELLS; IN-VIVO; FLT-3 LIGAND; NEGATIVE REGULATION AB Optimization of mobilization, harvest, and transduction of hematopoietic stem cells is critical to successful stem cell gene therapy. We evaluated the utility of a novel protocol involving Flt3-ligand (Flt3-L) and granulocyte colony-stimulating factor (G-CSF) mobilization of peripheral blood stem cells and retrovirus transduction using hematopoietic growth factors to introduce a reporter gene, murine CD24 (mCD24), into hematopoietic stem cells in nonhuman primates. Rhesus macaques were treated with Flt3-L (200 mu g/kg) and G-CSF (20 mu g/kg) for 7 days and autologous CD34(+) peripheral blood stem cells harvested by leukapheresis. CD34(+) cells were transduced with an MFGS-based retrovirus vector encoding mCD24 using 4 daily transductions with centrifugations in the presence of Flt3-L (100 ng/mL), human stem cell factor (50 ng/mL), and PIXY321 (50 ng/mL) in serum-free medium. An important and novel feature of this study is that enhanced in vivo engraftment of transduced stem cells was achieved by conditioning the animals with a low-morbidity regimen of sublethal irradiation (320 to 400 cGy) on the day of transplantation. Engraftment was monitored sequentially in the bone marrow and blood using both multiparameter flow cytometry and semi-quantitative DNA polymerase chain reaction (PCR). Our data show successful and persistent engraftment of transduced primitive progenitors capable of giving rise to marked cells of multiple hematopoietic lineages, including granulocytes, monocytes, and B and T lymphocytes. At 4 to 6 weeks posttransplantation, 47% +/- 32% (n = 4) of granulocytes expressed mCD24 antigen at the cell surface. Peak in vivo levels of genetically modified peripheral blood lymphocytes approached 35% +/- 22% (n = 4) as assessed both by flow cytometry and PCR 6 to 10 weeks posttransplantation. In addition, naiive (CD45RA(+) and CD62L(+)) CD4(+) and CD8(+) cells were the predominant phenotype of the marked CD3(+) T cells detected at early time points. A high level of marking persisted at between 10% and 15% of peripheral blood leukocytes for 4 months and at lower levels past 6 months in some animals. A cytotoxic T-lymphocyte response against mCD24 was detected in only 1 animal. This degree of persistent long-lived, high-level gene marking of multiple hematopoietic lineages, including naiive T cells, using a nonablative marrow conditioning regimen represents an important step toward the ultimate goal of high-level permanent transduced gene expression in stem cells. This is a US government work. There are no restrictions on its use. C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Kentucky, Med Ctr, Lucille P Markey Canc Ctr, Lexington, KY USA. Cell Genesys, Foster City, CA USA. RP Malech, HL (reprint author), NIAID, Host Def Lab, Bldg 10 Room 11N113,10 Ctr Dr MSC 1886, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA73473]; NCRR NIH HHS [RR0168]; NIAID NIH HHS [AI39423] NR 64 TC 86 Z9 87 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1999 VL 94 IS 7 BP 2271 EP 2286 PG 16 WC Hematology SC Hematology GA 242HT UT WOS:000082935000015 PM 10498599 ER PT J AU Kirshenbaum, AS Goff, JP Semere, T Foster, B Scott, LM Metcalfe, DD AF Kirshenbaum, AS Goff, JP Semere, T Foster, B Scott, LM Metcalfe, DD TI Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13) SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; BLOOD MONONUCLEAR-CELLS; BONE-MARROW; HUMAN BASOPHILS; IMMUNOPHENOTYPIC ANALYSIS; PERIPHERAL-BLOOD; DIFFERENTIATION; DISEASE; GROWTH AB Human mast cells are known to arise from a CD34(+)/c-kit(+) progenitor cell population that also gives rise to neutrophils, eosinophils, basophils, and monocytes. To further characterize cells within the CD34(+)/c-kit(+) population that yield mast cells, this progenitor was additionally sorted for CD13, a myeloid marker known to appear early on rodent mast cells and cultured human mast cells, but not expressed or expressed at low levels on human tissue mast cells; and cultured in recombinant human (rh) stem cell factor (rhSCF), rh interleukin-1 (rhIL-8; first week only), and rhIL-6. Initial sorts revealed that although the majority of cells in culture arose from the CD34(+)/c-kit(+)/CD13(-) cell population, mast cells arose from a CD34(+)/c-kit(+)/CD13(+) progenitor cell that also gave rise to a population of monocytes. Sequential sorting confirmed that CD34(+)/c-kit(+)/CD13(+) cells in CD34(+)/c-kit(+)/CD13(-) sorts gave rise to the few mast cells observed in CD13(-) sorted cells. CD34(+)/c-kit(+)/CD13(+) cells plated as single cells in the presence of various cytokine combinations gave rise to pure mast cell, monocyte, or mixed mast cell/monocyte progeny. Addition of either rh granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or rhIL-5 to the CD34(+)/c-kit(+)/CD13(+) progenitor cell population cultured in rhSCF, rhIL-3, and rhIL-6 did increase the number of total cells cultured and in the case of rhIL-5, did increase total mast cell numbers. Neither rhGM-CSF or rhIL-5 led to additional cell populations, ie, even with the addition of rhGM-CSF or rhIL-5, only mast cells and monocytes grew from CD34(+)/c-kit(+)/CD13(+) cells. Thus, human mast cells and a population of monocytes arise from precursor cells that express CD34, c-kit, and CD13; and within which, are mast cell, monocyte, and mast/monocyte (bipotential) precursors. (C) 1999 by The American Society of Hematology. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Pittsburgh, PA USA. RP Kirshenbaum, AS (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C208,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 36 TC 260 Z9 267 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1999 VL 94 IS 7 BP 2333 EP 2342 PG 10 WC Hematology SC Hematology GA 242HT UT WOS:000082935000021 PM 10498605 ER PT J AU Pike, SE Yao, L Setsuda, J Jones, KD Cherney, B Appella, E Sakaguchi, K Nakhasi, H Atreya, CD Teruya-Feldstein, J Wirth, P Gupta, G Tosato, G AF Pike, SE Yao, L Setsuda, J Jones, KD Cherney, B Appella, E Sakaguchi, K Nakhasi, H Atreya, CD Teruya-Feldstein, J Wirth, P Gupta, G Tosato, G TI Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth SO BLOOD LA English DT Article ID INTERFERON-INDUCIBLE PROTEIN-10; ANGIOGENESIS IN-VIVO; NITRIC-OXIDE; POTENT INHIBITOR; BINDING PROTEIN; RECEPTOR; THERAPY; CANCER; THROMBOSPONDIN-1; IDENTIFICATION AB Several angiogenesis inhibitors are fragments of larger proteins that are themselves not active as angiogenesis inhibitors. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is an angiogenesis inhibitor that exerts antitumor effects in vivo. In the present study, we examined whether the full-length calreticulin molecule shares the antiangiogenic and antitumor activities of vasostatin. Similar to vasostatin, calreticulin selectively inhibited endothelial cell proliferation in vitro, but not cells of other lineages, and suppressed angiogenesis in vivo. When inoculated into athymic mice, calreticulin inhibited Burkitt tumor growth comparably with vasostatin. Calreticulin lacking the N-terminal 1-120 amino acids inhibited endothelial cell proliferation in vitro and Burkitt tumor growth in vivo comparably with vasostatin. An internal calreticulin fragment encompassing amino acids 120-180 also inhibited endothelial cell proliferation in vitro and angiogenesis in vivo comparably with calreticulin and vasostatin. These results suggest that the antiangiogenic activities of vasostatin reside in a domain that is accessible from the full-length calreticulin molecule and localize to calreticulin N-terminal amino acids 120-180, Thus, calreticulin and calreticulin fragments are inhibitors of angiogenesis that directly target endothelial cells, inhibit angiogenesis, and suppress tumor growth. This information may be critical in designing targeted inhibitors of pathological angiogenesis that underlies cancer and other diseases. This is a US government work. There are no restrictions on its use. C1 Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, DBS, Cell Biol Lab, Bethesda, MD USA. NCI, DCS, Pathol Lab, Bethesda, MD USA. NCI, DBS, Expt Carcinogenesis Lab, Bethesda, MD USA. RP Tosato, G (reprint author), Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 41 TC 131 Z9 146 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1999 VL 94 IS 7 BP 2461 EP 2468 PG 8 WC Hematology SC Hematology GA 242HT UT WOS:000082935000035 PM 10498619 ER PT J AU Vieira, NE Marini, JC Hopkins, E Abrams, SA Yergey, AL AF Vieira, NE Marini, JC Hopkins, E Abrams, SA Yergey, AL TI Effect of growth hormone treatment on calcium kinetics in patients with osteogenesis imperfecta type III and IV SO BONE LA English DT Article DE stable isotopes; bone; calcium; metabolism; children; osteogenesis imperfecta (OI) ID ENDOGENOUS FECAL CALCIUM; BIRTH-WEIGHT INFANTS; BONE TURNOVER; URINARY CALCIUM; FRACTIONAL ABSORPTION; ISOTOPIC TRACERS; STABLE ISOTOPES; SHORT CHILDREN; ELDERLY WOMEN; EXCRETION AB Using a dual stable isotope technique, the effect of growth hormone (GH) on whole body calcium (Ca) metabolism was studied in children (ages 5-14 years) with type III (n = 9) and IV (n = 8) osteogenesis imperfecta, Each subject was studied twice: at baseline and following a GH (0.1-0.2 U/kg per day) treatment period of 1-1.5 years. Subjects were given Ca-42 intravenously and Ca-44 orally. The sera and urine Ca-42 and Ca-44 isotopic enrichments were followed over 7 days using thermal ionization mass spectrometry, The SAAM program was used to fit a three-compartment model to the tracer data. No significant differences were observed between: (1) children with type III and IV disease; or (2) baseline studies of boys and girls within each disease type. However, GH treatment significantly increased: (1) the exchangeable calcium pool (EP) in type III patients (2086 vs. 4422 mg/day, p 0.02); and (2) the parameter associated with bone calcium accretion in type IV patients (Vo(+): 973 vs. 1560 mg/day, p = 0.03) with boys responding with a significantly greater increase than girls (p = 0.008). Although not statistically significant, a trend toward an increase in Vo(+) in type III patients and in EP in type IV was observed following treatment. Our observations imply that more Ca was available for bone mineralization following GH treatment in these subjects. (C) 1999 by Elsevier Science Inc. All rights reserved. C1 NICHD, LCMB, SMAMS, NIH, Bethesda, MD 20892 USA. NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. USDA ARS, Baylor Coll Med, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX USA. RP Vieira, NE (reprint author), NICHD, LCMB, SMAMS, NIH, Bldg 10,Room 9D52,10 Ctr Dr,MSC 1580, Bethesda, MD 20892 USA. OI Abrams, Steven/0000-0003-4972-9233 NR 34 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD OCT PY 1999 VL 25 IS 4 BP 501 EP 505 DI 10.1016/S8756-3282(99)00186-6 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237MW UT WOS:000082661000016 PM 10511119 ER PT J AU Raptis, A Mavroudis, D Suffredini, AF Molldrem, J Van Rhee, F Childs, R Phang, S Barrett, AJ AF Raptis, A Mavroudis, D Suffredini, AF Molldrem, J Van Rhee, F Childs, R Phang, S Barrett, AJ TI High-dose corticosteroid therapy for diffuse alveolar hemorrhage in allogeneic bone marrow stem cell transplant recipients SO BONE MARROW TRANSPLANTATION LA English DT Article DE diffuse alveolar hemorrhage; corticosteroids ID PULMONARY COMPLICATIONS AB In a series of 74 patients with hematological malignancies undergoing allogeneic bone marrow or peripheral blood stem cell transplants from an HLA-identical sibling donor, four developed diffuse alveolar hemorrhage (DAH) between days 0 and 23 post transplant. Diagnosis was made by the radiographic finding of diffuse bilateral lung opacities, and bloody lavage fluid on bronchoscopy, Two patients required mechanical ventilatory support. They were treated with methyl-prednisolone 0.25-1.5 g/day for at least 4 days with slow tapering thereafter. All patients showed an immediate response and two became long-term survivors with normal respiratory function, Two had a relapse of DAH, developed acute respiratory distress syndrome (ARDS) and died with multi-organ failure. Risk factors for DAH were one or more courses of intensive chemotherapy pretransplant vs no treatment or low-dose chemotherapy (4/4 DAH vs 23/70 no DAH; P = 0.015), and second transplants (2/2 DAH vs 1/70 with no DAH; P = 0.006), These results indicate that DAH is life-threatening but is potentially reversible by prompt treatment with high doses of steroids. C1 NHLBI, Bone Marrow Transplantat Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Bone Marrow Transplantat Unit, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 37 Z9 39 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1999 VL 24 IS 8 BP 879 EP 883 DI 10.1038/sj.bmt.1701995 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 249ME UT WOS:000083336200011 PM 10516700 ER PT J AU Rapoport, SI AF Rapoport, SI TI How did the human brain evolve? A proposal based on new evidence from in vivo brain imaging during attention and ideation SO BRAIN RESEARCH BULLETIN LA English DT Review DE evolution; primate; cognition; positron emission tomography; genetics; synapse; pruning; brain; dreaming; neurodevelopment; neocortex; chimpanzee; humans; imaging; attention; ideation; schizophrenia; fragile x; magnetic resonance; visuoconstruction ID POSITRON-EMISSION-TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL BLOOD-FLOW; HUMAN EXTRASTRIATE CORTEX; GLUCOSE METABOLIC-RATE; PRIMARY VISUAL-CORTEX; EYE-MOVEMENT SLEEP; ALZHEIMERS-DISEASE; CORTICOCORTICAL CONNECTIONS; FUNCTIONAL-ORGANIZATION AB It is proposed that brain evolution in nonhuman primates and humans was facilitated by heritable differences in neuroplasticity and in the number of neurons and synapses available during childhood and adolescence, therefore, in differences in modifiability and elaboration of neuronal networks in brains of immature primate genotypes. These differences were exploited when a primate population was forced to adapt to a new cognitively or behaviorally demanding milieu, to select more cognitively and brain competent adults who could best compete and reproduce in this new milieu, extending their genes within the population. Two recently solidified concepts suggest a mechanism for this evolutionary process: (1) "Association" neocortex can be activated by attention and ideation in the absence of sensory or motor contributions, as demonstrated by in vivo imaging and direct brain recording. (2) Activation of the immature brain can promote and stabilize neuronal networks that would disappear or otherwise lose their function by adulthood. Taking these two ideas together, it is proposed that the "thought" processes of attention and ideation, when used by immature primates to adapt to new cognitive or behavioral stresses, led by the repeated selection of genotype to more cognitively able, larger-brained species with more extensive "association" cortex and related regions. (C) 1999 Elsevier Science Inc. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Room 6C103, Bethesda, MD 20892 USA. NR 225 TC 24 Z9 27 U1 25 U2 29 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD OCT PY 1999 VL 50 IS 3 BP 149 EP 165 DI 10.1016/S0361-9230(99)00095-7 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 252EM UT WOS:000083489200001 PM 10566976 ER PT J AU Zujewski, J Pai, L Wakefield, L Giusti, R Dorr, FA Flanders, C Caruso, R Kaiser, M Goodman, L Merino, M Gossard, M Noone, MA Denicoff, A Venzon, D Cowan, KH O'Shaughnessy, JA AF Zujewski, J Pai, L Wakefield, L Giusti, R Dorr, FA Flanders, C Caruso, R Kaiser, M Goodman, L Merino, M Gossard, M Noone, MA Denicoff, A Venzon, D Cowan, KH O'Shaughnessy, JA TI Tamoxifen and fenretinide in women with metastatic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; dark adaptation; fenretinide; lipids; tamoxifen; transforming growth factor-beta ID GROWTH-FACTOR-BETA; THERAPEUTIC ANTICANCER AGENTS; DARK-ADAPTATION; MAMMARY-CANCER; PLASMA; RETINOIDS; 4-HPR; RAT; N-(4-HYDROXYPHENYL)RETINAMIDE; FACTOR-BETA(1) AB Background: Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor-beta (TGF-beta) levels and serum lipids was also examined. Patientsand Methods: Thirty-one patients were treated with tamoxifen (20mg po daily), and fenretinide (400mg po daily with a 3-day drug holiday each month). Plasma TGF-beta testing was performed using isoform specific sandwich ELISA. Results: Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER-negative patients, and three hormone therapy naive ER-positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of -13.5 mg/dl; p = 0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p = 0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-beta 1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated. Conclusions: Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies. C1 NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Zujewski, J (reprint author), Bldg 10 Rm 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 31 TC 24 Z9 26 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 1999 VL 57 IS 3 BP 277 EP 283 DI 10.1023/A:1006216409688 PG 7 WC Oncology SC Oncology GA 257ZD UT WOS:000083812500005 PM 10617304 ER PT J AU Leung, LK Wang, TTY AF Leung, LK Wang, TTY TI Paradoxical regulation of Bcl-2 family proteins by 17 beta-oestradiol in human breast cancer cells MCF-7 SO BRITISH JOURNAL OF CANCER LA English DT Article DE apoptosis; breast cancer; Bcl-2; Bcl-x(L); 17 beta-oestradiol ID CARCINOMA CELLS; X-L; DEATH; APOPTOSIS; ESTROGEN; EXPRESSION; GROWTH; CARCINOGENESIS; ANTIESTROGENS; RECEPTORS AB Tumorigenesis is related to the dysregulation of cell growth or cell death pathways. Hence, elucidation of the mechanisms involved in the modulation of pro- or anti-apoptotic proteins is important in furthering understanding of breast cancer aetiology and may aid in designing prevention and treatment strategies. In the present study, we examined the role of 17 beta-oestradiol on the regulation of apoptosis in the breast cancer cell line MCF-7. Using multi-probe RNAase protection assays, we found changes in the mRNA levels of several Bcl-2 family proteins upon treatment of MCF-7 cells with 17 beta-oestradiol. Unexpectedly, we found a paradoxical effects of 17 beta-oestradiol on two anti-apoptotic proteins Bcl-2 and Bcl-x. Treatment with 17 beta-oestradiol resulted in up-regulation of Bcl-2 mRNA and protein, but down-regulated Bcl-x(L) mRNA and protein. The effect of 17 beta-oestradiol on Bcl-x(L) occurred at concentration-dependent fashion. The effect was specific to 17 beta-oestradiol since other steroid hormones exert no effect on Bcl-x(L). Tamoxifen, an anti-oestrogen, blocked the down-regulation of Bcl-x(L) by 17 beta-oestradiol demonstrating this effect is oestrogen receptor-dependent. We speculate that different members of the Bcl-2 family proteins may be regulated through different pathway and these pathways may be modulated by 17 beta-oestradiol. (C) 1999 Cancer Research Campaign. C1 NCI, Basic Res Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Wang, TTY (reprint author), NCI, Basic Res Lab, Div Basic Sci, Bldg 560-12-05 NCI-FCRDC,POB B, Frederick, MD 21702 USA. RI Leung, Lai/C-6511-2013; LEUNG, Lai K./E-6314-2011 OI Leung, Lai/0000-0002-7781-3099; LEUNG, Lai K./0000-0002-7781-3099 NR 35 TC 45 Z9 48 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT PY 1999 VL 81 IS 3 BP 387 EP 392 DI 10.1038/sj.bjc.6690706 PG 6 WC Oncology SC Oncology GA 240DD UT WOS:000082809800003 PM 10507761 ER PT J AU Phillip, A Bates, S Kubbutat, M Ludwig, R Clarke, P Stott, F Peters, G Vousden, K AF Phillip, A Bates, S Kubbutat, M Ludwig, R Clarke, P Stott, F Peters, G Vousden, K TI Regulation of p53 function SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Imperial Canc Res Fund, London WC2A 3PX, England. NR 0 TC 0 Z9 0 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 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT PY 1999 VL 81 IS 4 MA S3 BP 565 EP 566 PG 2 WC Oncology SC Oncology GA 240YM UT WOS:000082844000004 ER PT J AU Shields, PG AF Shields, PG TI Gene-environment interactions for cancer risk and behaviour SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Mol Epidemiol Sect, Human Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT PY 1999 VL 81 IS 4 MA S8 BP 567 EP 567 PG 1 WC Oncology SC Oncology GA 240YM UT WOS:000082844000009 ER PT J AU Williams, JF Petrus, MJ Wright, JA Husebekk, A Fellowes, V Read, EJ Gress, RE Fowler, DH AF Williams, JF Petrus, MJ Wright, JA Husebekk, A Fellowes, V Read, EJ Gress, RE Fowler, DH TI Fas-mediated lysis of chronic lymphocytic leukaemia cells: role of type I versus type II cytokines and autologous FasL-expressing T cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; fas; Th1/Th2 cytokines; IL-4; apoptosis ID CD8 EFFECTOR POPULATIONS; B-CELLS; TUMOR-REGRESSION; LIGAND; APOPTOSIS; LEUKEMIA; ANTIGEN; ANTIBODY; DEATH; IL-12 AB Given the known role of the fas cytolytic pathway in B-cell regulation, we evaluated whether fas-fasL interactions might induce chronic lymphocytic leukaemia (CLL) cell death. De novo CLL cells expressed a low level of surface fas, and were not lysed by fasL-bearing cells. CLL cells cultured in media containing the type I cytokines interleukin (IL)-12 or interferon (IFN)-alpha had increased fas expression, and were readily lysed by fasL-bearing cells. In contrast, the type II cytokine IL-4 did not increase CLL cell fas, and abrogated type I cytokine-induced fas up-regulation, With prolonged culture, IL-4 exposed CLL cells expressed an intermediate level of fas; however, such CLL cells were resistant to fas-mediated lysis. These results indicate that IL-4 inhibits fas-mediated killing of CLL cells at the level of both fas receptor expression and post-receptor events. Additionally, we have defined in vitro culture conditions which generate fasL-bearing T cells from CLL patients; such T cells efficiently mediated fas-based lysis of autologous fas-positive CLL cells. We therefore conclude that type I and type II cytokines differentially regulate the fas pathway in CLL cells, and that a combination of type I cytokines and fasL-expressing T cells may represent a new approach to the immunotherapy of CLL. C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Transplantat Therapy Sect, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NIH, Dept Transfus Med, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 31 TC 19 Z9 20 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 1999 VL 107 IS 1 BP 99 EP 105 DI 10.1046/j.1365-2141.1999.01670.x PG 7 WC Hematology SC Hematology GA 250MG UT WOS:000083391700011 PM 10520029 ER PT J AU Ambati, J Wynne, KB Angerame, MC Robinson, MR AF Ambati, J Wynne, KB Angerame, MC Robinson, MR TI Anterior uveitis associated with intravenous cidofovir use in patients with cytomegalovirus retinitis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-PRESSURE; AUTOIMMUNE UVEITIS; AQUEOUS-HUMOR; VISUAL-ACUITY; AIDS; HPMPC; RIFABUTIN; HYPOTONY; DISEASE; ANTIGEN AB Aim-Intravenous cidofovir is used to treat cytomegalovirus (CMV) retinitis, and has been reported to cause anterior uveitis. Relations were sought between this complication and patient characteristics that might help predict its occurrence. Methods-17 patients with AIDS and CMV retinitis who were treated with intravenous cidofovir were identified, and the following data collected in a retrospective chart review: demographic characteristics, duration of CMV retinitis, retinal lesion characteristics, dose and duration of cidofovir therapy, tests of renal function, CD4+ T lymphocyte counts, visual acuity, intraocular pressure, iris colour, history of diabetes mellitus, and use of concomitant medications. Case-control analyses were performed to determine risk factors for developing cidofovir associated uveitis. Results-Anterior uveitis characterised by pain, ciliary injection, and decreased visual acuity occurred in 10 patients (59%). Median interval to development of uveitis was II doses of cidofovir. Symptoms developed 4.4 (SD 2.5) days (median 3.5) after an infusion of cidofovir. Patients who developed uveitis had a significantly greater rise in CD4+ T lymphocyte count while receiving cidofovir (68.4 (75.7) x10(6)/l versus 5.0 (0.6) x10(6)/l, (p = 0.04)). By stepwise linear regression, this factor accounted for 33% (p = 0.03) of the effect of developing uveitis. Mean follow up time, intraocular pressure decline during cidofovir therapy, serum creatinine and urine protein concentrations, and rates of protease inhibitor use were not significantly different between patients who developed uveitis and those who did not. Uveitis responded to topical corticosteroids and cycloplegia. Conclusion-Anterior uveitis in patients receiving intravenous cidofovir therapy may be related to improving immune function. The uveitis responds to treatment and may not preclude continuation of cidofovir. C1 Univ Rochester, Sch Med & Dent, Dept Ophthalmol, Rochester, NY USA. Univ Rochester, Sch Med & Dent, Dept Nursing, Rochester, NY USA. RP Robinson, MR (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Room 10N112, Bethesda, MD 20892 USA. NR 35 TC 20 Z9 21 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD OCT PY 1999 VL 83 IS 10 BP 1153 EP 1158 DI 10.1136/bjo.83.10.1153 PG 6 WC Ophthalmology SC Ophthalmology GA 242UX UT WOS:000082961000021 PM 10502577 ER PT J AU Boroojerdi, B Topper, R Foltys, H Meincke, U AF Boroojerdi, B Topper, R Foltys, H Meincke, U TI Transcallosal inhibition and motor conduction studies in patients with schizophrenia using transcranial magnetic stimulation SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID CORPUS-CALLOSUM SIZE; INTERHEMISPHERIC INHIBITION; EVOKED-POTENTIALS; CORTEX; BRAIN; ABNORMALITIES AB Background Transcranial magnetic stimulation of the motor cortex may not only elicit excitatory responses in hand muscles contralateral to the stimulated hemisphere, but may also suppress tonic voluntary electromyogram activity in muscles ipsilateral to the stimulation. This inhibition is mediated between the motor cortices via the corpus callosum. Aims To investigate motor excitability and interhemispheric (transcallosal) connections in patients with schizophrenia. Method Transcallosal inhibition and motor conduction parameters were investigated in ten patients with schizophrenia and in ten age- and gender-matched healthy subjects. Results Transcallosal conduction time (TCT) and duration of the inhibition were significantly longer in patients with schizophrenia (mean (s.d.)):TCT, 12.4 (2.9) ms in normal subjects and 15.3 (2.6) ms in patients(P=0.03); mean duration, 34.1 (4.9) ms in normal subjects and 51.9 (16.8) ms inpatients (P=0.01). Conclusions Magnetic motor conduction parameters are unaltered in schizophrenia, but transcallosal inhibition is significantly delayed and prolonged. This may indicate abnormal function of the corpus callosum in these patients. Declaration of interest Grants received from the Deutsche Forschungsgemeinschaft and the University Hospital, Aachen, Germany. C1 Univ Hosp, Rhein Westfal TH Aachen, Dept Neurol, Aachen, Germany. Univ Hosp, Rhein Westfal TH Aachen, Dept Psychiat & Psychotherapy, Aachen, Germany. RP Boroojerdi, B (reprint author), NINDS, NIH, Bldg 10,Room 5N234,10 Ctr Dr, Bethesda, MD 20892 USA. NR 29 TC 57 Z9 58 U1 2 U2 2 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD OCT PY 1999 VL 175 BP 375 EP 379 DI 10.1192/bjp.175.4.375 PG 5 WC Psychiatry SC Psychiatry GA 245JX UT WOS:000083104500016 PM 10789306 ER PT J AU Goebel, SU Serrano, J Jensen, RT AF Goebel, SU Serrano, J Jensen, RT TI Prospective study of the value of serum chromogranin A or serum gastrin levels in the assessment of the presence, extent, or growth of gastrinomas - Reply SO CANCER LA English DT Letter ID ENDOCRINE NEOPLASIA TYPE-1 C1 NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA. RP Goebel, SU (reprint author), NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA. NR 3 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 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1999 VL 86 IS 7 BP 1378 EP 1379 DI 10.1002/(SICI)1097-0142(19991001)86:7<1378::AID-CNCR39>3.0.CO;2-1 PG 2 WC Oncology SC Oncology GA 239BP UT WOS:000082749200039 ER PT J AU Freudenheim, JL Ambrosone, CB Moysich, KB Vena, JE Graham, S Marshall Jr Muti, P Laughlin, R Nemoto, T Harty, LC Crits, GA Chan, AWK Shields, PG AF Freudenheim, JL Ambrosone, CB Moysich, KB Vena, JE Graham, S Marshall, JR Muti, P Laughlin, R Nemoto, T Harty, LC Crits, GA Chan, AWK Shields, PG TI Alcohol dehydrogenase 3 genotype modification of the association of alcohol consumption with breast cancer risk SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; alcohol dehydrogenase; breast neoplasms; epidemiology; genetic polymorphisms ID HUMAN-LIVER ALCOHOL; ALDEHYDE DEHYDROGENASES; POSTMENOPAUSAL WOMEN; GENETIC-POLYMORPHISM; PREMENOPAUSAL WOMEN; HUMAN STOMACH; ACETALDEHYDE; ESTROGENS; ETHANOL; PLASMA AB Objectives: Because alcohol dehydrogenase 3 (ADH(3)) is rate-limiting in alcohol oxidation and is polymorphic, we examined ADH(3) genotype in relation to alcohol intake and breast cancer risk. Methods: We conducted a case-control study among Caucasian women aged 40-85 with incident, pathologically confirmed breast cancer and controls, frequency-matched on age and county. Queries included alcohol intake in the past 20 years. Genomic DNA was genotyped for the exon VIII ADH polymorphism by PCR followed by restriction enzyme digestion. Computation of odds ratios (OR) and 95% confidence intervals (CI) was by unconditional logistic regression. Results: We found increased risk among pre- (OR 2.3, 95%, CI 1.2-4.3) but not postmenopausal women (OR 1.1, 95% CI 0.7-1.7) associated with ADH(3)(1-1) compared to ADH(3)(1-2) and ADH(3)(2-2) genotypes. Risk was increased for premenopausal women with the ADH(3)(1-1) genotype and alcohol intake above the median (OR 3.6, 95% CI 1.5-8.8) compared to lighter drinkers with the ADH(3)(2-2) or ADH(3)(1-2) genotypes. ORs were close to null for premenopausal women in other drinking and genotype groups and for postmenopausal women categorized by genotype and alcohol consumption. Conclusion: Among premenopausal women there may be a group more genetically susceptible to an alcohol consumption effect on breast cancer risk. C1 SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Roswell Pk Canc Inst, Buffalo, NY USA. Arizona Canc Ctr, Tucson, AZ USA. SUNY Buffalo, Dept Surg, Buffalo, NY 14260 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Res Inst Addict, Buffalo, NY USA. RP Freudenheim, JL (reprint author), SUNY Buffalo, Dept Social & Prevent Med, 270 Farber Hall, Buffalo, NY 14214 USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA/ES 62995, CA11535] NR 56 TC 63 Z9 64 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 1999 VL 10 IS 5 BP 369 EP 377 DI 10.1023/A:1008950717205 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 237VE UT WOS:000082676100007 PM 10530606 ER PT J AU Pietinen, P Malila, N Virtanen, M Hartman, TJ Tangrea, JA Albanes, D Virtamo, J AF Pietinen, P Malila, N Virtanen, M Hartman, TJ Tangrea, JA Albanes, D Virtamo, J TI Diet and risk of colorectal cancer in a cohort of Finnish men SO CANCER CAUSES & CONTROL LA English DT Article DE calcium; colorectal cancer; diet; fat; fiber; meat ID IOWA WOMENS HEALTH; COLON-CANCER; VITAMIN-D; FIBER INTAKE; FAT INTAKE; CALCIUM; DAIRY; MEAT; CONSUMPTION; ALCOHOL AB Objectives: Based on previous epidemiological studies, high fat and meat consumption may increase and fiber, calcium, and vegetable consumption may decrease the risk of colorectal cancer. We sought to address these hypotheses in a male Finnish cohort. Methods: We analyzed data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) where 27, 111 male smokers completed a validated dietary questionnaire at baseline. After an average of 8 years of follow-up, we documented 185 cases of colorectal cancer. The analyses were carried out using the Cox proportional hazards model. Results: The relative risk (RR) for men in the highest quartile of calcium intake compared with men in the lowest quartile was 0.6 (95% CI 0.4-0.9, p for trend 0.04). Likewise, the intake of milk protein and the consumption of milk products was inversely associated with risk of colorectal cancer. However, intake of dietary fiber was not associated with risk, nor was fat intake. Consumption of meat or different types of meat, and fried meat, fruits or vegetables were not associated with risk. Conclusions: In this cohort of men consuming a diet high in fat, meat, and fiber and low in vegetables, high calcium intake was associated with lowered risk of colorectal cancer. C1 Natl Publ Hlth Inst, Dept Nutr, SF-00300 Helsinki, Finland. NCI, Div Clin Sci, CIH, Bethesda, MD 20892 USA. RP Pietinen, P (reprint author), Natl Publ Hlth Inst, Dept Nutr, Mannerheimintie 166, SF-00300 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 46 TC 207 Z9 210 U1 1 U2 13 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 1999 VL 10 IS 5 BP 387 EP 396 DI 10.1023/A:1008962219408 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 237VE UT WOS:000082676100009 PM 10530608 ER PT J AU Cooper, GS Schildkraut, JM Whittemore, AS Marchbanks, PA AF Cooper, GS Schildkraut, JM Whittemore, AS Marchbanks, PA TI Pregnancy recency and risk of ovarian cancer SO CANCER CAUSES & CONTROL LA English DT Article DE epidemiology; ovarian cancer; pregnancy; risk factors ID STATES CASE-CONTROL; COLLABORATIVE ANALYSIS; REPRODUCTIVE FACTORS; INCESSANT OVULATION; APOPTOSIS; DETERMINANTS; PATHOGENESIS; COLON; MICE AB Objective: A recent analysis suggested that ovarian cancer risk increased with time since last birth, possibly because of some aspect of pregnancy that affects the clearance of cells that have undergone malignant transformation. We analyzed data from four case-control studies pertaining to ovarian cancer risk in relation to age at first pregnancy, age at last pregnancy, and years since last pregnancy: 628 cases and 3432 neighborhood or population controls, ages 18-79, were included. Methods: We used logistic regression to analyze associations between ovarian cancer risk, controlling for study, age (at diagnosis or corresponding reference age for controls), race, parity, oral contraceptive use, tubal ligation, family history of ovarian or breast cancer, and excluding women with a history of infertility. Results: An early age at first pregnancy was associated with an increased risk of ovarian cancer (odds ratio 1.4, 95% confidence interval (1.1-1.8) for ages less than or equal to 19 compared to greater than or equal to 25). Years since last pregnancy was also associated with increased ovarian cancer risk, with odds ratios of 1.4, 1.4, 1.8, and 2.1 for 10-14, 15-19, 20-24, and greater than or equal to 25 years compared to 0-9 years (trend test p = 0.004), respectively. Conclusion: These observations support the results from the previous study, and raise additional questions about the role of pregnancy in the etiology of ovarian cancer. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27706 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 20 TC 21 Z9 26 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 1999 VL 10 IS 5 BP 397 EP 402 DI 10.1023/A:1008960520316 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 237VE UT WOS:000082676100010 PM 10530609 ER PT J AU Moradi, T Adami, HO Bergstrom, R Gridley, G Wolk, A Gerhardsson, M Dosemeci, M Nyren, O AF Moradi, T Adami, HO Bergstrom, R Gridley, G Wolk, A Gerhardsson, M Dosemeci, M Nyren, O TI Occupational physical activity and risk for breast cancer in a nationwide cohort study in Sweden SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; physical activity ID POSTMENOPAUSAL WOMEN; UNITED-STATES; YOUNG-WOMEN; SOCIOECONOMIC-STATUS; ENDOMETRIAL CANCER; EXERCISE; ASSOCIATION; HISTORIES; PATTERNS AB Objective: Our purpose was to investigate effects of physical activity on risk for breast cancer. Methods: From the Swedish nationwide censuses in 1960 and 1970 we defined three partly overlapping cohorts of women whose occupational titles allowed reproducible classification of physical demands at work in 1960 (n=704,904), in 1970 (n=982,270), or with the same demands in both 1960 and 1970 (n=253,336). The incidence of breast cancer during 1971-89 was ascertained through record linkage to the Swedish Cancer Register. We used Poisson regression to estimate relative risks (RR). Results: A total of 20,419, 22,840, and 8261 breast cancers, respectively, were detected in the three cohorts. In all three cohorts the risk for breast cancer increased monotonically with decreasing level of occupational physical activity and with increasing socioeconomic status. Among women with the same estimated physical activity level in 1960 and 1970 the RR was 1.3 for sedentary as compared with high/very high activity level (95% CI 1.2-1.4; p for trend < 0.001). Adjustment for socioeconomic status virtually eliminated this association (RR 1.1; 95% CI 0.9-1.2; p for trend 0.12) leaving a statistically significant 30% gradient only among women aged 50-59 years at follow-up. The association between socioeconomic status and breast cancer risk was largely unchanged after adjustment for occupational physical activity. Conclusion: The protective effect of occupational physical activity on breast cancer risk, if any, appears to be confined to certain age groups. C1 Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden. NCI, Div Epidemiol & Genet, Rockville, MD USA. Astro Draco AB, Clin Drug Safety & Epidemiol, Lund, Sweden. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Canc Prevent, Boston, MA 02115 USA. Uppsala Univ, Dept Stat, Uppsala, Sweden. RP Moradi, T (reprint author), Karolinska Inst, Dept Med Epidemiol, POB 281, SE-17177 Stockholm, Sweden. EM tahereh.moradi@mep.ki.se FU NCI NIH HHS [MA N02-CP-7100] NR 57 TC 28 Z9 28 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 1999 VL 10 IS 5 BP 423 EP 430 DI 10.1023/A:1008922205665 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 237VE UT WOS:000082676100014 PM 10530613 ER PT J AU Kiessling, R Wasserman, K Horiguchi, S Kono, K Sjoberg, J Pisa, P Petersson, M AF Kiessling, R Wasserman, K Horiguchi, S Kono, K Sjoberg, J Pisa, P Petersson, M TI Tumor-induced immune dysfunction SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE immunosuppression; cancer; tolerance zeta chains; CTL; NK cells ID T-CELL RECEPTOR; NATURAL-KILLER-CELLS; RHEUMATOID-ARTHRITIS PATIENTS; IMPAIRED CYTOKINE PRODUCTION; SIGNAL-TRANSDUCING MOLECULES; PRIMARY INTRACRANIAL TUMORS; COLONY-STIMULATING FACTOR; PERIPHERAL-BLOOD; INFILTRATING LYMPHOCYTES; SYNOVIAL-FLUID AB Immune system-based approaches for the treatment of malignant disease over the past decades have often focused on cytolytic effector cells such as cytotoxic T lymphocytes (CTL), and natural killer (NK) cells. It has also been demonstrated that tumor-bearing mice can be cured using a wide variety of approaches, some of which involve cytokine-mediated enhancement of CTL and NK cell activity. However, the apparent success in mice stands in contrast to the current situation in the clinic, wherein only a minority of patients have thus far benefited from CTL- or NK cell-based antitumor approaches. The underlying causes of tumor-associated immune suppression of CTL and NK cell activity are discussed, and features of interest shared with HIV infection, leprosy, and rheumatoid arthritis are also be mentioned. Remarkable and very recent observations have shed more light upon the causes of dysfunctional alterations in CTL and NK cells often associated with these diseases, that in turn have suggested new immunotherapeutic approaches for cancer and infectious disease. C1 NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Frederick, MD 21702 USA. Yamanashi Univ, Sch Med, Dept Surg, Tamaho, Yamanashi 40938, Japan. Karolinska Hosp, Canc Ctr Karolinska, Immune & Genetherapy Lab, S-17176 Stockholm, Sweden. Karolinska Hosp, Dept Hematol & Infect Dis, S-17176 Stockholm, Sweden. RP Kiessling, R (reprint author), Karolinska Hosp, Canc Ctr Karolinska, Immune & Genetherapy Lab, KS Ringen R8 01, S-17176 Stockholm, Sweden. NR 91 TC 194 Z9 201 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 1999 VL 48 IS 7 BP 353 EP 362 DI 10.1007/s002620050586 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA 242BW UT WOS:000082919200003 PM 10501847 ER PT J AU Alberts, DS Colvin, GM Conney, AH Ernster, VL Garber, JE Greenwald, P Gudas, LJ Hong, WK Kelloff, GJ Kramer, RA Lerman, CE Mangelsdorf, DJ Matter, A Minna, JD Nelson, WG Pezzuto, JM Prendergast, F Rusch, VW Sporn, MB Wattenberg, LW Weinstein, IB AF Alberts, DS Colvin, GM Conney, AH Ernster, VL Garber, JE Greenwald, P Gudas, LJ Hong, WK Kelloff, GJ Kramer, RA Lerman, CE Mangelsdorf, DJ Matter, A Minna, JD Nelson, WG Pezzuto, JM Prendergast, F Rusch, VW Sporn, MB Wattenberg, LW Weinstein, IB TI Prevention of cancer in the next millennium: Report of the Chemoprevention Working Group to the American Association for Cancer Research SO CANCER RESEARCH LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; HEPATITIS-B VIRUS; REPUBLIC-OF-CHINA; NONSTEROIDAL ANTIINFLAMMATORY DRUG; RANDOMIZED CONTROLLED TRIAL; ORAL PREMALIGNANT LESIONS; ACID RECEPTOR-BETA; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; VITAMIN-A C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Rutgers State Univ, Coll Pharm, Dept Biol Chem, Piscataway, NJ 08854 USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, Dept Pharmacol, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Chemotherapy Branch, Div Canc Prevent & Control, Rockville, MD 20852 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75235 USA. Novartis Pharma AG, Oncol & Virol Dept, CH-4002 Basel, Switzerland. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75235 USA. Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Mayo Clin & Mayo Fdn, Mayo Canc Ctr, Rochester, MN 55905 USA. Mem Sloan Kettering Canc Ctr, Thorac Serv, New York, NY 10021 USA. Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03755 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Columbia Univ Coll Phys & Surg, Columbia Presbyterian Canc Ctr, New York, NY 10032 USA. RP Sporn, MB (reprint author), Dartmouth Med Sch, Dept Pharmacol, Remsen 524, Hanover, NH 03755 USA. NR 134 TC 133 Z9 138 U1 0 U2 1 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 1999 VL 59 IS 19 BP 4743 EP 4758 PG 16 WC Oncology SC Oncology GA 244AC UT WOS:000083028800002 ER PT J AU Afshari, CA Nuwaysir, EF Barrett, JC AF Afshari, CA Nuwaysir, EF Barrett, JC TI Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation SO CANCER RESEARCH LA English DT Article AB One major challenge facing today's cancer researchers and toxicologists is the development of new approaches for the identification of carcinogens and other environmental hazards. Here, we describe the potential impact of emerging technologies for measuring gene expression profiles on carcinogen identification and on the general field of toxicology. An example of one of these technologies is the use of cDNA microarray chips. We provide an overview to the key questions that are confronting investigators charged with determining the relative safety of natural or synthetic chemicals to which humans are exposed, followed by a discussion of how cDNA microarray technology may be applied to these questions. Gene chip technology is still a relatively new technology, and only a handful of studies have demonstrated its utility. However, as the technical hurdles to development are passed, the use of this methodology in addressing the questions raised here will be critical to increase the sensitivity of detection of the potential toxic effects of environmental chemicals and to understand their risks to humans. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 11 TC 153 Z9 165 U1 0 U2 8 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 1999 VL 59 IS 19 BP 4759 EP 4760 PG 2 WC Oncology SC Oncology GA 244AC UT WOS:000083028800003 PM 10519378 ER PT J AU Turker, MS Gage, BM Rose, JA Ponomareva, ON Tischfield, JA Stambrook, PJ Barlow, C Wynshaw-Boris, A AF Turker, MS Gage, BM Rose, JA Ponomareva, ON Tischfield, JA Stambrook, PJ Barlow, C Wynshaw-Boris, A TI Solid tissues removed from Atm homozygous deficient mice do not exhibit a mutator phenotype for second-step autosomal mutations SO CANCER RESEARCH LA English DT Article ID ATAXIA-TELANGIECTASIA PATIENTS; FREQUENCY; LYMPHOCYTES; CANCER; APRT AB The presence of increased frequencies of blood-derived and solid tumors in ataxia-telangiectasia (A-T) patients, coupled with a role for the ATM (A-T mutation) protein in detecting specific forms of DNA damage, has led to the assumption of a mutator phenotype in ATM-deficient cells. Supporting this assumption are observations of increased rates of chromosomal aberrations and iutrachromosomal homologous recombinational events in the cells of A-T patients. We have bred mice with knockout mutations for the selectable Aprt (adenine phosphoribosyltransferase) locus and the Atm locus to examine the frequency of second-step autosomal mutations in Atm-deficient cells, Two solid tissues were examined: (a) the ear, which yields predominately mesenchymal cells; and (b) the kidney which yields predominately epithelial cells. We report here the lack of a mutator phenotype for inactivating autosomal mutations in solid tissues of the Atm-deficient mice. C1 Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH 45267 USA. Natl Human Genome Res Inst, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Turker, MS (reprint author), Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, L606,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Tischfield, Jay/0000-0003-3217-8287 FU NCI NIH HHS [CA56383]; NIDDK NIH HHS [DK38185]; NIEHS NIH HHS [P0 1 ES05652] NR 18 TC 20 Z9 20 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 1999 VL 59 IS 19 BP 4781 EP 4783 PG 3 WC Oncology SC Oncology GA 244AC UT WOS:000083028800008 PM 10519383 ER PT J AU Divi, RL Osborne, MR Hewer, A Phillips, DH Poirier, MC AF Divi, RL Osborne, MR Hewer, A Phillips, DH Poirier, MC TI Tamoxifen-DNA adduct formation in rat liver determined by immunoassay and P-32-postlabeling SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER PATIENTS; SPRAGUE-DAWLEY RATS; IN-VIVO; ENDOMETRIAL SAMPLES; HEPATIC ANEUPLOIDY; CARCINOGEN; MICE; 4-HYDROXYTAMOXIFEN; TOREMIFENE; LEUKOCYTES AB Tamoxifen (TAM), a nonsteroidal antiestrogen used as a chemotherapeutic and chemopreventive agent for breast cancer, induces liver tumors in rodents and covalent DNA adduct formation in hepatic DNA. Here, we report the development and validation of highly sensitive and specific immunoassays for the determination of TAM-DNA adducts. Rabbits were immunized with calf thymus DNA, chemically modified with alpha-acetoxytamoxifen to 2.4 adducts per 100 nucleotides, and the resulting antisera were characterized by competitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) and chemiluminescence immunoassay (CIA). Compared with DELFIA, the CIA has a much lower background and a 20-fold increase in sensitivity. For the immnnogen TAM-DNA, 50% inhibition was at 2.0 +/- 0.11 (mean +/- SE, n = 18) fmol of (E)-alpha-(N-2-deoxyguanosinyl)tamoxifen (TAM-dG) adduct in TAM-DNA by DELFIA. For TAM-DNA modified to 4.8 adducts in 10(6) nucleotides, 50% inhibition was at 20.6 +/- 6.6 (mean +/- SE, n = 8) fmol of TAM-dG in TAM-DNA by DELFIA and at 0.92 +/- 0.11 (mean +/- SE, n = 10) fmol of TAM-dG in TAM-DNA by CIA. No inhibition was observed in either assay with up to 20 mu g (62.5 nmol of nucleotides) of unmodified DNA. The individual adducts TAM-dG and (Z)-alpha-(N-2-deoxyguanosinyl)tamoxifen and the individual compounds TAM and 4-OH-TAM gave DELFIA 50% inhibitions at 828, 2229, 5440,and 8250 fmol, respectively. For assay validation, TAM-dG levels were determined by DELFIA, CIA, and P-32-postlabeling in TAM-DNA samples modified in vitro to different levels, and comparable values were obtained in all three assays. Further validation was obtained in vivo in rat liver. DNA adducts of TAM mere measurable in rat liver 24 h after a single i.p. dose of 45 mg TAM/kg body weight and after daily p.o. dosing for 7 days with 5.0, 10.0, and 20.0 mg TAM/kg body weight. In addition, TAM-DNA adducts disappeared slowly over 21 days in rats on a control diet that were first given p.o. TAM at 45 mg/kg/day for 4 days. In the rat experiments, TAM-DNA adduct levels determined by CIA compared well with those determined by P-32-postlabeling, although the CIA gave an underestimation at the highest doses. For rat liver samples, the detection limit by CIA was 3 adducts per 10(9) nucleotides (0.2 fmol of adducts per 20 mu g of DNA). C1 NCI, NIH, Carcinogens DNA Interact Sect, Bethesda, MD 20892 USA. Inst Canc Res, Sutton SM2 5NG, Surrey, England. RP Poirier, MC (reprint author), NCI, NIH, Carcinogens DNA Interact Sect, Bldg 37,Room 2A05,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 40 TC 34 Z9 36 U1 0 U2 1 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 1999 VL 59 IS 19 BP 4829 EP 4833 PG 5 WC Oncology SC Oncology GA 244AC UT WOS:000083028800017 PM 10519392 ER PT J AU Tang, BW de Castro, K Barnes, HE Parks, WT Stewart, L Bottinger, EP Danielpour, D Wakefield, LM AF Tang, BW de Castro, K Barnes, HE Parks, WT Stewart, L Bottinger, EP Danielpour, D Wakefield, LM TI Loss of responsiveness to transforming growth factor beta induces malignant transformation of nontumorigenic rat prostate epithelial cells SO CANCER RESEARCH LA English DT Article ID BONE MORPHOGENETIC PROTEIN-2; II RECEPTOR; CANCER CELLS; VENTRAL PROSTATE; MUTANT MICE; IN-VIVO; EXPRESSION; GROWTH-FACTOR-BETA-1; TGF-BETA-1; LINES AB Transforming growth factor (TGF)-beta s are multifunctional growth factors, the properties of which include the potent inhibition of epithelial cell growth. Expression patterns of TGF-beta s and TGF-beta receptors in the normal prostate indicate that these growth regulators play key roles in prostatic development and proliferative homeostasis. Importantly, TGF-beta receptor levels are frequently diminished in malignant human prostate tissue. To test the hypothesis that loss of TGF-beta responsiveness is causally involved in the tumorigenic process, we have used retroviral transduction to introduce a dominant-negative mutant type II TGF-beta receptor (DNR) into the premalignant rat prostatic epithelial cell line, NRP-152. High-level expression of the DNR abolished the ability of TGF-beta to inhibit cell growth, to promote cell differentiation, and to induce apoptosis, and it partially blocked the induction of extracellular matrix gene expression, When injected into nude mice, NRP-152-DXR cells formed carcinomas at 13 of 34 sites, compared with 0 of 30 sites for parental and control cells (P = 0.0001). We conclude that the type II TGF-beta receptor is an important tumor suppressor in the prostate, and furthermore, that loss of TGF-beta responsiveness can contribute early in the tumorigenic process by causing the malignant transformation of preneoplastic cells. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Wakefield, LM (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 55 TC 66 Z9 69 U1 0 U2 1 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 1999 VL 59 IS 19 BP 4834 EP 4842 PG 9 WC Oncology SC Oncology GA 244AC UT WOS:000083028800018 PM 10519393 ER PT J AU Ciotti, M Lakshmi, VM Basu, N Davis, BB Owens, IS Zenser, TV AF Ciotti, M Lakshmi, VM Basu, N Davis, BB Owens, IS Zenser, TV TI Glucuronidation of benzidine and its metabolites by cDNA-expressed human UDP-glucuronosyltransferases and pH stability of glucuronides SO CARCINOGENESIS LA English DT Article ID URINARY-BLADDER CARCINOGENESIS; N-HYDROXY METABOLITES; HUMAN UGT1.4 PROTEIN; HUMAN LIVER; DNA-ADDUCTS; RAT-LIVER; EXPOSED WORKERS; COMPLEX LOCUS; GENE-COMPLEX; COS-1 CELLS AB Although glucuronidation is considered a necessary step in aromatic amine-induced bladder cancer, the specific enzymes involved are not known. This study assessed the capacity of five different human recombinant UDP-glucuronosyltransferases expressed in COS-1 cells to glucuronidate benzidine, its metabolites and 4-aminobiphenyl. [C-14]UDP-glucuronic acid was used as co-substrate, UGT1A1, UGT1A4 and UGT1A9 each metabolized all of the aromatic amines, UGT1A9 exhibited the highest relative rates of metabolism with preference for the two hydroxamic acids, N-hydroxy-N-acetylbenzidine and N-hydroxy-N,N'-diacetylbenzidine, UGT1A9 metabolized 4-aminobiphenyl similar to 50% faster than benzidine or N-acetylbenzidine. UGT1A4 N-glucuronidated N'-hydroxy-N-acetylbenzidine at the highest relative rate compared with the other transferases, UGT1A6 was effective in metabolizing only four of the eight aromatic amines tested. UGT1A1 demonstrated more extensive metabolism of the hydroxamic acid, N-hydroxy-N,N'-diacetylbenzidine, and the ring oxidation product, 3-OH-N,N'-diacetylbenzidine, than it did for the other six amines, UGT2B7 was the only product of the UGT2 gene family examined and it metabolized all the aromatic amines at similar low relative levels compared with a preferred substrate, 4-OH-estrone, The K-m values for N-acetylbenzidine metabolism by UGT1A1 and UGT1A4 were 0.37 +/- 0.14 and 1.8 +/- 0.4 mM, respectively, The O-glucuronide of 3-OH-N,N'-diacetylbenzidine was not hydrolyzed during a 24 h 37 degrees C incubation at either pH 5.5 or 7.4, Likewise, the O-glucuronide of 3-OH-benzidine was stable at pH 7.4, with 52% remaining at pH 5.5 after 24 h, These results suggest the following relative ranking of transferase metabolism: UGT1A9 > UGT1A4 much greater than UGT2B7 > UGT1A6 approximate to UGT1A1, The relative pH stability of O-glucuronides is consistent with a role in detoxification and excretion of aromatic amines, while the acid lability of N-glucuronides is consistent with delivery of these amines to the bladder epithelium for activation, resulting in DNA adducts which may lead to mutations. C1 VA Med Ctr, St Louis, MO 63125 USA. NICHHD, Heritable Disorders Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. St Louis Univ, Sch Med, Dept Biochem, St Louis, MO 63125 USA. St Louis Univ, Sch Med, Div Geriatr Med, St Louis, MO 63125 USA. RP Zenser, TV (reprint author), VA Med Ctr, 11G-JB, St Louis, MO 63125 USA. FU NCI NIH HHS [CA-72613] NR 55 TC 45 Z9 46 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 1999 VL 20 IS 10 BP 1963 EP 1969 DI 10.1093/carcin/20.10.1963 PG 7 WC Oncology SC Oncology GA 243PH UT WOS:000083006100013 PM 10506112 ER PT J AU Popescu, NC Greiner, JW AF Popescu, NC Greiner, JW TI Recurrent alterations of the short arm of chromosome 3 define a tumor suppressor region in rat mammary tumor cells SO CARCINOGENESIS LA English DT Article ID CANCER; TRANSFORMATION; LINE; MAP; CYTOGENETICS; PROGRESSION; METHYLUREA; ACTIVATION; INVIVO; MODEL AB Cytogenetic alterations associated with different stages in carcinogenesis can be distinguished in cultured human or rodent cells transformed by carcinogenic agents. Three tumorigenic rat mammary epithelial cell lines transformed in vitro with 7,12,-dimethylbenz[a]anthracene alone or in combination with 12-O-tetradecanoylphorbol-13-acetate were examined cytogenetically. Non-random alterations consisting of translocations involving the short arm of chromosome 3 and trisomy of chromosomes 14 and X were identified in all three lines. Deletion and inversion of chromosome 1 with the breakpoint at band 1q22 and a duplication Iq 32-43 and trisomy of chromosome 2 were observed in two cell lines. The accumulation of structural alterations and chromosome imbalances during the process of cell immortalization and acquisition of tumorigenicity are required for normal rat mammary cells to become malignant. Unbalanced translocations of chromosome 3 resulting in loss of the short arm had the breakpoint at 3p11. This site is a hotspot of breakage and recombination in various rat tumors and may represent a region of tumor suppressor gene critical to the development of rat mammary tumors, as well as other types of tumors. C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 33 TC 4 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1999 VL 20 IS 10 BP 2033 EP 2036 DI 10.1093/carcin/20.10.2033 PG 4 WC Oncology SC Oncology GA 243PH UT WOS:000083006100022 PM 10506121 ER PT J AU Yao, JA Jiang, M Fan, JS Zhou, YY Tseng, GN AF Yao, JA Jiang, M Fan, JS Zhou, YY Tseng, GN TI Heterogeneous changes in K currents in rat ventricles three days after myocardial infarction SO CARDIOVASCULAR RESEARCH LA English DT Article DE rat; Kv4 subunits; transient outward current; myocardial infarction; K channel; gene expression; arrhythmias ID TRANSIENT OUTWARD CURRENT; EPICARDIAL BORDER ZONE; SUBENDOCARDIAL PURKINJE MYOCYTES; POTASSIUM CHANNEL; DIFFERENTIAL EXPRESSION; SUBTHRESHOLD POTENTIALS; ENDOCARDIAL MYOCYTES; REGIONAL DIFFERENCES; REENTRANT CIRCUITS; CANINE INFARCTS AB Objective: After coronary artery occlusion, surviving myocardium in and around the infarct zone plays an important role in arrhythmogenesis. Understanding the mechanisms for derangements in cardiac electrical activity at the cellular and molecular levels is important for the design of effective therapeutic strategies. Methods: To provide part of that understanding, we studied changes in K channel function and expression in rat ventricular myocardium three days after occluding the left major coronary artery. The epicardium and endocardium of infarcted region in the left ventricle and the free wall of right ventricle were separated for myocyte isolation, followed by whole-cell voltage clamp studies. Myocytes were also isolated from corresponding regions of control and sham-operated hearts and studied under the same conditions. Results: We found that the transient outward (I-to), delayed rectifier (I-K) and inward rectifier (I-K1) currents have different distribution patterns in normal rat ventricular myocardium. Sham-operation did not affect any of these K currents in left ventricular myocytes, but coronary artery occlusion caused a reduction of all three. For I-to and I-K1 the reduction was greater in epicardial than in endocardial myocytes, but I-K was reduced equally in these two cell groups. Unexpectedly, I-to and I-K as well as cell capacitance were increased in right ventricular myocytes from infarcted as well as sham-operated hearts. Western blot analysis indicated that the level of Kv4 channel proteins (Kv4.2 + Kv4.3) was reduced in infarcted left ventricular myocardium, consistent with the reduction in I-to. Conclusion: Our data suggest that the distribution of K channels and changes in them induced by coronary artery occlusion are heterogeneous in ventricular myocardium. Understanding the molecular mechanisms for this heterogeneity and its implications in arrhythmogenesis poses a challenge in designing effective antiarrhythmic therapy for myocardial infarction patients. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77555 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Tseng, GN (reprint author), Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. FU NHLBI NIH HHS [HL-30557, HL-46451] NR 41 TC 43 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD OCT PY 1999 VL 44 IS 1 BP 132 EP 145 DI 10.1016/S0008-6363(99)00154-6 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243CR UT WOS:000082980000016 PM 10615397 ER PT J AU Putney, JW AF Putney, JW TI "Kissin' cousins": Intimate plasma membrane-ER interactions underlie capacitative calcium entry SO CELL LA English DT Review ID FUSION; MECHANISM; RECEPTORS; PROTEINS; RELEASE C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 19 TC 118 Z9 120 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 1 PY 1999 VL 99 IS 1 BP 5 EP 8 DI 10.1016/S0092-8674(00)80056-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 243DK UT WOS:000082981600002 PM 10520988 ER PT J AU Holmbeck, K Bianco, P Caterina, J Yamada, S Kromer, M Kuznetsov, SA Mankani, M Robey, PG Poole, AR Pidoux, I Ward, JM Birkedal-Hansen, H AF Holmbeck, K Bianco, P Caterina, J Yamada, S Kromer, M Kuznetsov, SA Mankani, M Robey, PG Poole, AR Pidoux, I Ward, JM Birkedal-Hansen, H TI MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover SO CELL LA English DT Article ID TYPE-1 MATRIX METALLOPROTEINASE; PRO-GELATINASE-A; EXTRACELLULAR-MATRIX; OSTEOBLAST DIFFERENTIATION; HYPERTROPHIC CHONDROCYTES; INTERSTITIAL COLLAGENASE; RHEUMATOID-ARTHRITIS; MOUSE EMBRYOGENESIS; BONE-RESORPTION; IN-VIVO AB MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components. MT1-MMP is therefore thought to be an important molecular tool for cellular remodeling of the surrounding matrix. To establish the biological role of this membrane proteinase we generated MT1-MMP-deficient mice by gene targeting. MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues. Our findings demonstrate the pivotal function of MT1-MMP in connective tissue metabolism, and illustrate that modeling of the soft connective tissue matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton. C1 Natl Inst Dent & Craniofacial Res, MMP Unit, Bethesda, MD 20892 USA. Univ Rome La Sapienza, I-00161 Rome, Italy. Univ Aquila, I-67100 Laquila, Italy. McGill Univ, Shriners Hosp Children, Canadian Unit, Joint Dis Lab, Montreal, PQ H3G 1A6, Canada. NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Div Basic Sci, Frederick, MD 21702 USA. RP Birkedal-Hansen, H (reprint author), Natl Inst Dent & Craniofacial Res, MMP Unit, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 53 TC 857 Z9 881 U1 2 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 1 PY 1999 VL 99 IS 1 BP 81 EP 92 DI 10.1016/S0092-8674(00)80064-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 243DK UT WOS:000082981600010 PM 10520996 ER PT J AU Arai, R Jacobowitz, DM Hida, T AF Arai, R Jacobowitz, DM Hida, T TI Calbindin D28k and calretinin in oxytocin and vasopressin neurons of the rat supraoptic nucleus - A triple-labeling immunofluorescence study SO CELL AND TISSUE RESEARCH LA English DT Article DE calcium-binding protein; calcium buffering; calbindin D28k; calretinin; oxytocin; vasopressin; supraoptic nucleus; rat (Sprague Dawley) ID MAMMALIAN NEUROENDOCRINE CELLS; CALCIUM-BINDING PROTEINS; IMMUNOHISTOCHEMICAL LOCALIZATION; INTRACELLULAR CALCIUM; NERVOUS-SYSTEM; SPINAL-CORD; PARVALBUMIN; HYPOTHALAMUS; NEUROTRANSMITTERS; COLOCALIZATION AB The aim of the present study was to examine quantitatively whether two calcium-binding proteins, calbindin D28k and calretinin, are localized in oxytocin and vasopressin neurons of the supraoptic nucleus of the male rat. We used a triple-labeling immunofluorescence method with a confocal laser scanning microscope. Of the oxytocin-labeled cells, 70% were stained for both calbindin D28k and calretinin, 15% were stained for only calbindin D28k, 13% were stained for only calretinin, and 2% were stained for neither protein. Of the vasopressin-labeled cells, 73% were stained for neither calbindin D28k nor calretinin, 21% were stained for only calbindin D28k, 4% were stained for only calretinin, and 2% were stained for both proteins. Calbindin D28k and calretinin :have been shown previously to contribute to calcium homeostasis by buffering [Ca2+](i). Therefore, these findings suggest that most of the oxytocin neurons may have a higher Ca2+-buffering capacity than most of the vasopressin neurons. C1 Fujita Hlth Univ, Sch Med, Dept Anat, Aichi 4701192, Japan. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Arai, R (reprint author), Fujita Hlth Univ, Sch Med, Dept Anat, Aichi 4701192, Japan. NR 43 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD OCT PY 1999 VL 298 IS 1 BP 11 EP 19 DI 10.1007/PL00008808 PG 9 WC Cell Biology SC Cell Biology GA 245EQ UT WOS:000083093600002 PM 10555535 ER PT J AU Humphreys, RC Hennighausen, L AF Humphreys, RC Hennighausen, L TI Signal transducer and activator of transcription 5a influences mammary epithelial cell survival and tumorigenesis SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MYC-INDUCED TUMORIGENESIS; TRANSGENIC MICE; TYROSINE PHOSPHORYLATION; GLAND INVOLUTION; CONSTITUTIVE ACTIVATION; FACTOR-ALPHA; STAT ACTIVATION; GENE-EXPRESSION; FACTOR RECEPTOR AB The mammary gland undergoes extensive tissue remodeling and cell death at the end of lactation in a process known as involution. We present evidence that the prolactin-activated transcription factor signal transducer and activator of transcription 5a (Stat5a) has a crucial role in the regulation of cell death during mammary gland involution. In a transforming growth factor-alpha transgenic mouse model that exhibited delayed mammary gland involution, the absence of Stat5a facilitated involution-associated changes in morphology of the gland and the extent and timing of programmed cell death. These Stat5a-dependent changes also affected epidermal growth factor receptor-initiated mammary gland tumorigenesis. Overexpression of the transforming growth factor alpha transgene in the mammary epithelium reproducibly generated mammary hyperplasia and tumors. In the presence of the activated epidermal growth factor receptor, deletion of Stat5a delayed initial hyperplasia and mammary tumor development by 6 weeks. These observations demonstrate that Stat5a is a survival factor, and its presence is required for the epithelium of the mammary gland to resist regression and involution-mediated apoptosis. We also suggest that Stat5a is one of the antecedent, locally acting molecules that initiate the process of epithelial regression and reorganization during involution. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Humphreys, RC (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 111, Bethesda, MD 20892 USA. NR 63 TC 87 Z9 87 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1999 VL 10 IS 10 BP 685 EP 694 PG 10 WC Cell Biology SC Cell Biology GA 249XB UT WOS:000083357500003 PM 10547072 ER PT J AU Saavedra, JM Nishimura, Y AF Saavedra, JM Nishimura, Y TI Angiotensin and cerebral blood flow SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE renin angiotensin system; cerebral blood flow; autoregulation; stroke; brain ischemia ID SPONTANEOUSLY HYPERTENSIVE RATS; CONVERTING-ENZYME-INHIBITOR; II RECEPTOR SUBTYPES; ATRIAL-NATRIURETIC-PEPTIDE; RABBIT BRAIN ARTERIOLES; BINDING-SITES; ANTIHYPERTENSIVE TREATMENT; PARAVENTRICULAR NUCLEUS; CEREBROSPINAL-FLUID; SUBFORNICAL ORGAN AB 1. General properties of the cerebral circulation. 2. Cerebral blood how autoregulation in hypertension, in stroke, and during the aging process. 3. The Angiotensin system. 4. Angiotensin receptor subtypes. 5. Angiotensin receptors and actions of Angiotensin II in the brain: interactions between the brain and circulating Angiotensin II. 6. The cerebrovascular Angiotensin system. 7. Effects of Angiotensin II on cerebrovascular reactivity. 8. Angiotensin and cerebrovascular flow. 9. Effects of therapeutic modulation of the Angiotensin II system on cerebrovascular regulation in health and disease. 10. Conclusions. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, 10 Ctr Dr,Bldg 10-2D57, Bethesda, MD 20892 USA. EM Saavedrj@irp.nimh.nih.gov NR 109 TC 37 Z9 38 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD OCT PY 1999 VL 19 IS 5 BP 553 EP 573 DI 10.1023/A:1006995016403 PG 21 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 206PE UT WOS:000080887600001 PM 10384255 ER PT J AU Barlow, T Dipple, A AF Barlow, T Dipple, A TI Formation of deaminated products in styrene oxide reactions with deoxycytidine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID EXPOSED LAMINATION WORKERS; DNA-ADDUCTS; HYDROLYTIC DEAMINATION; DIMROTH REARRANGEMENT; ALKYLATION PRODUCTS; DIFFERENT SITES; GUANOSINE; ARALKYLATION; 1-POSITION AB The reaction of racemic styrene oxide with deoxycytidine under aqueous conditions was studied. The four principal products isolated were a pair of diastereomeric N-4-(2-hydroxy-1-phenylethyl)deoxycytidines (similar to 20% of the products) and a pair of diastereomeric 3-(2-hydroxy-2-phenylethyl)deoxyuridines (similar to 80% of the products). Reactions with optically active styrene oxides allowed the configurations of the 3-(2-hydroxy-2-phenylethyl)deoxyuridines to be assigned, and these structures were confirmed by an independent synthesis from deoxyuridine. Also, it was possible to tentatively assign the configurations of the N-4-(2-hydroxy-1-phenylethyl)deoxycytidines that had undergone some racemization during the reaction (the ratio of the retained to inverted configuration of the products was similar to 1:7). C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. RP Barlow, T (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England. NR 26 TC 13 Z9 13 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 1999 VL 12 IS 10 BP 883 EP 886 DI 10.1021/tx990070n PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 248DF UT WOS:000083259500003 PM 10525262 ER PT J AU Glover, RE Corbett, JT Burka, LT Mason, RP AF Glover, RE Corbett, JT Burka, LT Mason, RP TI In vivo production of nitric oxide after administration of cyclohexanone oxime SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID TREATED RATS; HYDROXYLAMINE; TOXICITY; EPR AB Cyclohexanone oxime (CHOX), an intermediate used in the synthesis of polycaprolactam (Nylon-6), has been reported to be hematotoxic in Fischer rats. The in vivo metabolism of CHOX was found to release nitric oxide, which was detected in venous blood by electron paramagnetic resonance spectroscopy as the nitrosylhemoglobin complex. In vitro incubation of CHOX with venous blood resulted in the formation of the characteristic nitrosylhemoglobin complex, suggesting that the blood was a possible site for metabolism. Excessive nitric oxide production may, in part, contribute to the observed toxicity of CHOX. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Glover, RE (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 16 TC 12 Z9 12 U1 0 U2 4 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 1999 VL 12 IS 10 BP 952 EP 957 DI 10.1021/tx990058v PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 248DF UT WOS:000083259500012 PM 10525271 ER PT J AU Schmidt, DK Fulwood, R Lenfant, C AF Schmidt, DK Fulwood, R Lenfant, C TI The National Asthma Education and Prevention Program - Partnering with local asthma coalitions to implement the guidelines SO CHEST LA English DT Editorial Material C1 NHLBI, Natl Asthma Educ & Prevent Program, Off Prevent Educ & Control, NIH, Bethesda, MD 20892 USA. RP Schmidt, DK (reprint author), NHLBI, Natl Asthma Educ & Prevent Program, Off Prevent Educ & Control, NIH, Bldg 31,Room 4A16,31 Ctr Dr MSC 2480, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 9 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 1999 VL 116 IS 4 SU 1 BP 235S EP 236S DI 10.1378/chest.116.suppl_2.235S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 247ED UT WOS:000083206900030 PM 10532500 ER PT J AU Buchsbaum, DJ Rogers, BE Khazaeli, MB Mayo, MS Milenic, DE Kashmiri, SVS Anderson, CJ Chappell, LL Brechbiel, MW Curiel, DT AF Buchsbaum, DJ Rogers, BE Khazaeli, MB Mayo, MS Milenic, DE Kashmiri, SVS Anderson, CJ Chappell, LL Brechbiel, MW Curiel, DT TI Targeting strategies for cancer radiotherapy SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 7th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 15-17, 1998 CL PRINCETON, NEW JERSEY SP NCI, NIH, Coulter Pharmaceut, Garden State Canc Ctr, Ctr Mol Med & Immunol, Genetech Inc, IDEC Pharmaceut Corp, Immunomed Inc, Schering Oncol Biotech ID MONOCLONAL-ANTIBODY; GENE DELIVERY; IN-VIVO; TUMOR-LOCALIZATION; PEPTIDE RECEPTOR; IMMUNE-RESPONSE; ADENOVIRAL VECTORS; BOMBESIN ANALOG; CELLS; EXPRESS AB Novel strategies to increase the therapeutic ratio in clinical radioimmunotherapy studies are needed. Limitations to radioimmunotherapy include bone marrow suppression due to the long circulating half-life of radiolabeled monoclonal antibodies (mAbs) and heterogeneous tumor penetration of the high-molecular-weight mAb. An approach to overcome these problems is the use of genetically engineered mAbs. The engineered mAb discussed in this paper contains a deletion in the constant region of the mAb that increases its tumor penetration and blood clearance compared with the intact mAb. Radiolabeling of this mAb should lead to a similar radiation-absorbed dose to tumor compared with the intact mAb, but reduce the radiation absorbed dose to bone marrow. In addition, low or variable expression of tumor-associated target antigens or receptors may lead to low or heterogeneous tumor uptake of radiolabeled mAbs. This report also discusses a novel approach toward systemic radiotherapy that combines gene transfer techniques (to increase tumor receptor expression) with radiolabeled peptides that target the induced receptor, The radiolabeled peptides achieve good tumor uptake, rapid tumor penetration, and rapid blood clearance. A humanized construct of the CC49 (HuCC49) high-affinity anti-TAG-72 mAb, as well as a construct with the CH2 region deleted (HuCC49 Delta CH2), were labeled with I-131 and (LU)-L-177. Biodistribution of the radiolabeled constructs was evaluated 24 h after regional i.p. injection in athymic nude mice bearing i.p. LS174T human colon cancer xenografts. The I-131-HuCC49 Delta CH2 showed a median tumor uptake of 5.5% ID/g which was similar to that of I-131-HuCC49 at 5.2% ID/g. However, the median blood concentration of I-131-HuCC49 Delta CH2 was 0.2% ID/g which was significantly lower than 0.8% ID/g for I-131-HuCC49. The uptake of the constructs in other normal tissues were similar. The Lu-177-HuCC49 Delta CH2 showed a median tumor uptake of 9.4% ID/g, which was slightly higher than that of Lu-177-HuCC49 at 7.9% ID/g. The median blood concentration of Lu-177-HuCC49 Delta CH2 was 0.2% ID/g, which was significantly lower than 0.4% ID/g for 177Lu-HuCC49. The uptake of the antibody constructs in other normal tissues were similar except for the kidney, The tumor:blood ratios of 177Lu-HuCC49 and Lu-177-HuCC49 Delta CH2 were 19.4 and 60.2, respectively, at 24 h after injection. The purpose of the second aspect of the study was to determine the biodistribution of Cu-64-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA)-octreotide in a human ovarian cancer model induced to express human somatostatin receptor subtype 2 (SSTr2) using gene transfer techniques as a prelude to future therapy studies, Mice bearing i.p. SKOV3.ip1 tumors transduced with an adenoviral vector encoding the cDNA for SSTr2 (AdSSTr2) and injected i.p. with Cu-64-TETA-octreotide showed a median uptake of 24.3% ID/g in tumor at 4 h postinjection compared with 4.9% ID/g at 18 h after injection. Also, tumor uptake of 64Cu-TETA-octreotide at 4 h was not significantly different when administered either 2 or 4 days after injection of AdSSTr2 2 (P = 0.076). Cu-64-TETA-octreotide should be useful for targeted radiotherapy against tumors that are genetically induced to express high levels of SSTr. These two novel targeting strategies show promise for improved cancer radioimmunotherapy. C1 Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35233 USA. Univ Alabama, Dept Med, Birmingham, AL 35233 USA. Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35233 USA. Univ Kansas, Med Ctr, Dept Prevent Med, Kansas City, KS 66160 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. RP Buchsbaum, DJ (reprint author), Univ Alabama, Dept Radiat Oncol, 1824 6th Ave S,WTI 674, Birmingham, AL 35294 USA. RI Mayo, Matthew/E-3774-2015 FU NCI NIH HHS [R01 CA 62550, R01 CA 73636, R01 CA 78505] NR 37 TC 29 Z9 30 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1999 VL 5 IS 10 SU S BP 3048S EP 3055S PG 8 WC Oncology SC Oncology GA 308CJ UT WOS:000086691600012 PM 10541342 ER PT J AU Santos, AD Kashmiri, SVS Hand, PH Schlom, J Padlan, EA AF Santos, AD Kashmiri, SVS Hand, PH Schlom, J Padlan, EA TI Generation and characterization of a single gene-encoded single-chain-tetravalent antitumor antibody SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 7th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 15-17, 1998 CL PRINCETON, NEW JERSEY SP NCI, NIH, Coulter Pharmaceut, Garden State Canc Ctr, Ctr Mol Med & Immunol, Genetech Inc, IDEC Pharmaceut Corp, Immunomed Inc, Schering Oncol Biotech ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; IN-VIVO; CC49; ANTIGEN; FRAGMENTS; BIVALENT; AFFINITY; DIABODY; VARIANT; PROTEIN AB Monoclonal antibody (mAb) CC49, a murine IgG1, reacts with the tumor-associated glycoprotein-72 expressed on a variety of carcinomas. In clinical trials, radiolabeled CC49 has shown excellent tumor localization to a variety of carcinomas. To minimize the immunogenicity of CC49 mAb in patients, a humanized CC49 (HuCC49) was generated by complementarity-determining region (CDR) grafting. The relative affinity of HuCC49 was 2-3-fold less than that of the murine mAb. With the aim of improving tumor targeting, attempts have been made to enhance the avidity of the HuCC49 mAb. Previous research has yielded a single gene-encoded immunoglobulin, SCIgcCC49 Delta CH1, which is a dimer of a single chain consisting of CC49 single-chain Fv linked to the NH2 terminus of the human gamma 1 Fc through the hinge region, This molecule is comparable to the mouse-human chimeric CC49 in terms of in vitro antigen binding properties, cytolytic activity, and rate of plasma clearance in athymic mice bearing human tumor xenografts. Recently, a single gene encoding a single-chain immunoglobulin consisting of a HuCC49 diabody attached to human gamma 1 Fe via the hinge region was constructed. The diabody, a bivalent antigen-binding structure, is made up of variable heavy (V-H)/ variable light (V-L) domains and V-L/V-H domains. In each of the variable domain pairs, the V-H and V-L domains are linked through a short linker peptide. Meanwhile, the two pairs are linked via a 30-residue Gly-Ser linker peptide to yield two antigen-binding sites by lateral and noncovalent association of the V-L of one pair with the V-H of the other. Transfectomas expressing the single-gene immunoglobulin secrete a homodimer of about M-r 160,000 that reacts to tumor-associated glycoprotein-72, This tetravalent humanized antitumor immunoglobulin molecule may potentially be an efficacious therapeutic and diagnostic reagent against a wide range of human carcinomas. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Santos, AD (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 24 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1999 VL 5 IS 10 SU S BP 3118S EP 3123S PG 6 WC Oncology SC Oncology GA 308CJ UT WOS:000086691600022 PM 10541352 ER PT J AU Meredith, RF Khazaeli, MB Macey, DJ Grizzle, WE Mayo, M Schlom, J Russell, CD LoBuglio, AF AF Meredith, RF Khazaeli, MB Macey, DJ Grizzle, WE Mayo, M Schlom, J Russell, CD LoBuglio, AF TI Phase II study of interferon-enhanced I-131-labeled high affinity CC49 monoclonal antibody therapy in patients with metastatic prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 7th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 15-17, 1998 CL PRINCETON, NEW JERSEY SP NCI, NIH, Coulter Pharmaceut, Garden State Canc Ctr, Ctr Mol Med & Immunol, Genetech Inc, IDEC Pharmaceut Corp, Immunomed Inc, Schering Oncol Biotech ID TUMOR-ASSOCIATED GLYCOPROTEIN-72; IMMUNE-RESPONSE; CARCINOEMBRYONIC ANTIGEN; CARCINOMA AB Adjuvant Interferon (IFN) was given to increase tumor antigen expression and enhance localization with I-131-labeled CC49 radioimmunotherapy in a Phase II trial for hormone resistant metastatic prostate cancer. Patients received four doses of alpha-IFN (3 x 10(6) IU) s.c. on alternate days, from day -5 to day +1 of 75 mCi/m(2) I-131-CC49 treatment. Toxicity was well tolerated, with the majority of patients experiencing transient grade 3 or 4 neutropenia and/or thrombocytopenia (maximal at 4-6 weeks). The absorbed dose was >25 Gy in four of eight tumors visualized, which represents an increase of > 20 fold over whole body radiation dose. Two patients had radiographic minor responses by 6 weeks post-therapy, whereas five of six patients experiencing pain had symptom relief without radiographic changes. The protocol provided modest antitumor effects (pain relief in five of six patients and two minor radiographic responses). This study suggests that the addition of IFN enhanced tumor uptake and antitumor effects as compared to a prior Phase II trial of I-131-CC49 alone. C1 Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Nucl Med, Birmingham, AL 35294 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Meredith, RF (reprint author), Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35294 USA. RI Mayo, Matthew/E-3774-2015 FU NCI NIH HHS [CM 87215]; NCRR NIH HHS [M01-RR-00032] NR 18 TC 48 Z9 49 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1999 VL 5 IS 10 SU S BP 3254S EP 3258S PG 5 WC Oncology SC Oncology GA 308CJ UT WOS:000086691600042 PM 10541372 ER PT J AU Lai, J Quadri, SM Borchardt, PE Harris, L Wucher, R Askew, E Schweichler, L Vriesendorp, HM AF Lai, J Quadri, SM Borchardt, PE Harris, L Wucher, R Askew, E Schweichler, L Vriesendorp, HM TI Pharmacokinetics of radiolabeled polyclonal antiferritin in patients with Hodgkin's disease SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 7th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 15-17, 1998 CL PRINCETON, NEW JERSEY SP NCI, NIH, Coulter Pharmaceut, Garden State Canc Ctr, Ctr Mol Med & Immunol, Genetech Inc, IDEC Pharmaceut Corp, Immunomed Inc, Schering Oncol Biotech ID LABELED ANTIFERRITIN; THERAPY; IMMUNOGLOBULIN AB The objective was to identify pharmacokinetic parameters predictive for tumor response and normal tissue side effects after i.v. administered radiolabeled rabbit antihuman ferritin IgG. Twenty-eight patients with recurrent Hodgkin's disease received 2 mg of rabbit antihuman ferritin i.v., labeled with 4-7 mCi of In-111 followed by two doses of 0.25, one dose of 0.3, or one dose of 0.4 mCi of Y-90-labeled antiferritin per kg of body weight 1 week later. Radioactivity and HPLC measurements of blood and urine samples and liver and tumor volumes identified on sequential whole-body scans provided the data for a pharmacokinetic analysis covering the first 6 days after the administration of the radioimmunoconjugate. Side effects and tumor response were recorded. Temporary hematological toxicity was noted in all patients. Sixteen patients showed a tumor response. The Y-90 blood level at 1 h after administration correlated with the severity of subsequent hematological toxicity. The rapid blood elimination half-life of radioactivity was 4.4 h, Less than 5% of the administered radioactivity was eliminated in the first 24 h urine. The slow blood elimination half-life was 44 and 37 h for In-111 and Y-90, respectively. One of 12 retreated patients produced anti-rabbit IgG antibodies. The volume of distribution was larger for Y-90 than for In-111-labeled antiferritin (160 versus 110% of estimated blood volume). Accidentally extravasated rabbit IgG was rapidly catabolized in perivascular tissues,vith an effective half-life of less than 35 h. Slower catabolism was noted for rabbit IgG in blood (t(1/2) = 40 h), liver (t(1/2) = 62 h) or tumor (t(1/2) = 40-80 h). Twelve of 13 patients with an effective tumor half-life > 57 h showed a tumor response. i.v. administered polyclonal rabbit antihuman ferritin, labeled with In-111 or Y-90 is stable in vivo and targets Hodgkin's disease. Intravascular Y-90 causes a vascular leak and a larger volume of distribution for antiferritin. Elevated Y-90 blood levels at 1 h and a tumor half-life of >57 h predict for hematological toxicity and tumor response, respectively. C1 Arlington Canc Ctr, Arlington, TX 76012 USA. NIH, Ctr Sci Rev, Bethesda, MD 20892 USA. RP Lai, J (reprint author), Intl Isotopes Inc, 3100 Jim Christal Rd, Denton, TX 76207 USA. NR 21 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1999 VL 5 IS 10 SU S BP 3315S EP 3323S PG 9 WC Oncology SC Oncology GA 308CJ UT WOS:000086691600050 PM 10541380 ER PT J AU Vriesendorp, HM Quadri, SM Wyllie, CT Lai, J Borchardt, PE Harris, L Wucher, R Askew, E Schweichler, L AF Vriesendorp, HM Quadri, SM Wyllie, CT Lai, J Borchardt, PE Harris, L Wucher, R Askew, E Schweichler, L TI Fractionated radiolabeled antiferritin therapy for patients with recurrent Hodgkin's disease SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 7th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 15-17, 1998 CL PRINCETON, NEW JERSEY SP NCI, NIH, Coulter Pharmaceut, Garden State Canc Ctr, Ctr Mol Med & Immunol, Genetech Inc, IDEC Pharmaceut Corp, Immunomed Inc, Schering Oncol Biotech ID LYMPHOMA AB The objective of this study was to determine the therapeutic ratio of fractionated radiolabeled immunoglobulin therapy (RIT) for patients with recurrent Hodgkin's disease. Ninety patients with recurrent Hodgkin's disease received 2 mg of yttrium-90-labeled polyclonal rabbit antihuman ferritin IgG i.v. Fifty-seven patients received a single (unfractionated) administration per treatment cycle; 11 of them were treated with 0.3 mCi/kg body weight, 39 were treated with 0.4 mCi/kg body weight, and 7 received 0.5 mCi/kg body weight per treatment cycle. Thirty-three patients had their radiolabeled immunoglobulin administration separated (fractionated) in 2 x 0.25 mCi/kg body weight (total activity, 0.5 mCi/kg), The interval between fractions was 1 week. Radioimmunoconjugates did not cause serious acute side effects. In vivo radioimmunoconjugates were stable. Human antirabbit IgG antibodies were found in 2 of 50 retreated patients (<5%). Hematological toxicity was the only side effect noted in all patients, and it was usually temporary. Response rates (RRs) were 20%, 61%, and 86% after 0.3, 0.4, or 0.5 mCi/kg unfractionated yttrium-90-labeled antiferritin. The RR for patients treated with fractionated RIT was 42%. In the fractionated RIT group, complete responses were decreased, and progressive disease increased (P < 0.05). Complete responses had a medium duration of 6 months. Median survival times were 390 days for 1 x 0.4 mCi/kg and 300 days for the 2 x 0.25 mCi/kg patient group. Fractionation did not provide the expected decrease in hematological toxicity or the expected increase in tumor RRs. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NIH, Ctr Sci Rev, Bethesda, MD 20892 USA. Arlington Canc Ctr, Arlington, TX 76012 USA. RP Vriesendorp, HM (reprint author), 6641 Westchester, Houston, TX 77005 USA. NR 22 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1999 VL 5 IS 10 SU S BP 3324S EP 3329S PG 6 WC Oncology SC Oncology GA 308CJ UT WOS:000086691600051 PM 10541381 ER PT J AU Slavotinek, A Clayton-Smith, J AF Slavotinek, A Clayton-Smith, J TI A girl with ectodermal dysplasia, choanal atresia and polysyndactyly SO CLINICAL DYSMORPHOLOGY LA English DT Letter DE ectodermal; dysplasia; choanal atresia AB We present a 3-year-old child with clinical features of ectodermal dysplasia comprising sparse hair, dystrophic and ridged nails and bilateral obstruction of the nasolacrimal ducts. Additional findings were unilateral choanal atresia, bilateral syndactyly of the feet and polydactyly. We discuss the differential diagnosis of these clinical findings. Clin Dysmorphol 8: 287-289 (C) 1999 Lippincott Williams & Wilkins. C1 Univ Manchester, St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. Univ Manchester, St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. RP Slavotinek, A (reprint author), NIH, Genet Dis Res Branch, Natl Human Genome Res Inst, 49 Convent Dr MSC4472,Bldg 49 Room 4B75, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0962-8827 J9 CLIN DYSMORPHOL JI Clin. Dysmorphol. PD OCT PY 1999 VL 8 IS 4 BP 287 EP 289 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 245XD UT WOS:000083132700010 PM 10532179 ER PT J AU Kastelein, JJP Ordovas, JM Wittekoek, ME Pimstone, SN Wilson, PWF Gagne, SE Larson, MG Schaefer, EJ Boer, JMA Gerdes, C Hayden, MR AF Kastelein, JJP Ordovas, JM Wittekoek, ME Pimstone, SN Wilson, PWF Gagne, SE Larson, MG Schaefer, EJ Boer, JMA Gerdes, C Hayden, MR TI Two common mutations (D9N, N291S) in lipoprotein lipase: a cumulative analysis of their influence on plasma lipids and lipoproteins in men and women SO CLINICAL GENETICS LA English DT Article DE genetics; lipids; lipoprotein lipase; lipoproteins; mutation ID FAMILIAL COMBINED HYPERLIPIDEMIA; HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION SURVIVORS; FREQUENTLY OCCURRING MUTATION; ISCHEMIC-HEART-DISEASE; HEPATIC LIPASE; INCREASED RISK; GENE; ATHEROSCLEROSIS AB We assessed the effect of two common mutations in the lipoprotein lipase gene (LPL), D9N and N291S, which have been shown to modulate plasma lipids in a wide spectrum of patients. A total of 1114 men and 1144 women from the Framingham Offspring Study (FOS) were analyzed for these two LPL variants. Subsequently, the association with fasting plasma lipids and risk of coronary artery disease (CHD) was determined. We extended our study by calculating weighed means of lipids and lipoproteins in carriers and non-carriers for these LPL mutations in patients with genetic dyslipidemias, CHD patients and healthy controls. In the FOS sample, the D9N and N291S alleles were associated with lower high-density lipoprotein-cholesterol (HDL-C) (Delta = -0.07 mmol/l, p = 0.03) and a trend towards increased triglycerides (Delta = 0.25 mmol/l, p = 0.07). In women, a trend towards the high triglyceride, low HDL-C phenotype was evident (Delta = -0.02 mmol/l for HDL-C and Delta = 0.14 mmol/l for triglycerides, respectively). Cumulative analysis of other studies of male carriers of the D9N and N291S revealed higher levels of triglycerides (D291N; 2.60(1.85) mmol/l vs. 1.62(1.18) mmol/l: p < 0.0001) (D9N; 1.94 (1.19) mmol/l vs. 1.74(1.17) mmol/l: p < 0.001) and lower HDL-C (N291S; 1.04(0.32) mmol/l vs. 1.15(0.28) mmol/l: p < 0.0001) (D9N; 1.08(0.24) mmol/l vs. 1.16(0.28) mmol/l: p < 0.0001). In females, results differed with higher TG levels (N291S; 1.70(0.99) mmol/l vs. 1.10(0.63) mmol/l: p < 0.001) (D9N; 1.08(0.76) mmol/l vs. 0.96(0.51) mmol/l: p < 0.01) and lower HDL-C levels (N291S; 1.27(0.33) mmol/l vs. 1.51(0.32) mmol/l: p < 0.0001); however, the HDL-C levels for D9N carriers were similar to non-carriers (D9N; 1.52(0.29) mmol/l vs. 1.53(0.35) mmol/l: p = 0.83). Our data provide evidence that common variants of the LPL gene are significant modulators of lipid and lipoprotein levels in both men and women. C1 Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA 02111 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. NHLBI, Framingham Heart Study, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. Natl Inst Publ Hlth & Environm, Dept Chron Dis & Environm Epidemiol, NL-3720 BA Bilthoven, Netherlands. Aarhus Univ Hosp, Dept Med & Cardiol, DK-8000 Aarhus, Denmark. RP Kastelein, JJP (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, Meibergdreef 9,G1-146, NL-1105 AZ Amsterdam, Netherlands. RI Hayden, Michael/D-8581-2011; OI Hayden, Michael/0000-0001-5159-1419; Ordovas, Jose/0000-0002-7581-5680 NR 53 TC 39 Z9 41 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD OCT PY 1999 VL 56 IS 4 BP 297 EP 305 DI 10.1034/j.1399-0004.1999.560407.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 264EZ UT WOS:000084168800009 PM 10636448 ER PT J AU Choi, Y Ramnath, VR Eaton, AS Chen, A Simon-Stoos, KL Kleiner, DE Erikson, J Puck, JM AF Choi, Y Ramnath, VR Eaton, AS Chen, A Simon-Stoos, KL Kleiner, DE Erikson, J Puck, JM TI Expression in transgenic mice of dominant interfering Fas mutations: A model for human autoimmune lymphoproliferative syndrome SO CLINICAL IMMUNOLOGY LA English DT Article DE apoptosis; autoimmunity; in vivo animal models; T lymphocytes; transgenic mice ID DIABETIC NOD MICE; MUTANT-GENE LPR; LYMPHOCYTE APOPTOSIS; HETEROZYGOUS STATE; IPR GENE; T-CELLS; B-CELLS; INDUCTION; AUTOANTIBODIES; STRAINS AB Most humans with autoimmune lymphoproliferative syndrome (ALPS) carry heterozygous dominant mutations in one allele of the gene encoding Fas/APO-1/ CD95. ALPS patients, like Fas-deficient MRL lpr/lpr mice, have lymphoproliferation, autoimmunity, increased CD4(-)/CD8(-) T lymphocytes, and apoptosis defects. Consistent with the phenotypic variability of lpr/lpr mice of different background strains, human genetic studies indicate that a Fas mutation is insufficient to induce ALPS in all mutation carriers, To investigate the dominant function of human Fas mutations and the additional genetic factor(s) involved in the development of ALPS, we generated transgenic mice expressing, in addition to endogenous Fas, mouse Fas molecules bearing mutations in the intracellular death domain corresponding to mutations identified in ALPS patients. Transgenic mice developed mild features of ALPS, including hepatosplenomegaly, elevated proportions of lymphocytes in spleen and lymph nodes, apoptotic defects, and hepatic lymphocytic infiltrates. Therefore defective murine Fas proteins act in a dominant manner to impair apoptosis of activated lymphocytes and disrupt lymphocyte homeostasis, The influence of genetic background on phenotype was studied by comparing transgenic mice on FVB/N and (FVB/N x MRL) backgrounds with syngenetic control mice and with MRL and MRL lpr/lpr mice. While expression of transgenic mutant Fas contributed mainly to hepatosplenomegaly and accumulation of lymphocytes, MRL background genes played a major role in the production of autoantibodies and elevated serum immunoglobulin levels. Moreover, compared to FVB/N (+/+) mice, a substantial Fas-specific apoptotic defect was found in MRL (+/+) mice, suggesting a mechanism for the known tendency of this strain to develop autoimmunity. (C) 1999 Academic Press. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Wistar Inst, Philadelphia, PA 19104 USA. RP Choi, Y (reprint author), Kangnung Natl Univ, Coll Dent, San 1, Kangnung, Kang Won Do, South Korea. OI Kleiner, David/0000-0003-3442-4453 FU NIAID NIH HHS [R01-AI32137] NR 40 TC 12 Z9 12 U1 0 U2 0 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 1999 VL 93 IS 1 BP 34 EP 45 DI 10.1006/clim.1999.4767 PG 12 WC Immunology SC Immunology GA 243QY UT WOS:000083009800005 PM 10497009 ER PT J AU El-Sadr, WM Luskin-Hawk, R Yurik, TM Walker, J Abrams, D John, SL Sherer, R Crane, L Labriola, A Caras, S Pulling, C Hafner, R AF El-Sadr, WM Luskin-Hawk, R Yurik, TM Walker, J Abrams, D John, SL Sherer, R Crane, L Labriola, A Caras, S Pulling, C Hafner, R CA CPCRA TI A randomized trial of daily and thrice-weekly trimethoprim-sulfamethoxazole for the prevention of Pneumocystic carinii pneumonia in human immunodeficiency virus-infected persons SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID AEROSOLIZED PENTAMIDINE; PRIMARY PROPHYLAXIS; AIDS; METAANALYSIS; ENCEPHALITIS; INTOLERANT; SURVIVAL; EFFICACY; TOXICITY; REGIMENS AB We enrolled 2,625 human immunodeficiency virus-infected patients into a randomized trial to assess the efficacy and tolerability of daily vs. thrice-weekly trimethoprim-sulfamethoxazole (160 mg/800 mg) for prophylaxis of Pneumocystis carinii pneumonia (PCP), The rate of PCP was 3.5 and 4.1 per 100 person-years in the daily and thrice-weekly groups, respectively, with a relative risk (RR) of 0.82 (95% confidence interval [CI], 0.61-1.09; P =.16) (RR of < 1.0 favors daily trimethoprimsulfamethoxazole), The RR for PCP determined by on-treatment analysis was 0.59 (P =.03). The RR for death was 0.91 (P =.12); for bacterial pneumonia, 0.82 (P =.06); and for combined PCP and bacterial pneumonia, 0.84 (P =.04), Discontinuation due to adverse events occurred more commonly in the daily trimethoprim-sulfamethoxazole group (RR, 2.14; 95% CI, 1.73-2.66; P <,001), Overall estimates for efficacy end points favored daily trimethoprim-sulfamethoxazole, although rates of intolerance were higher among patients receiving that dose. Daily trimethoprim-sulfamethoxazole may offer advantages as a first choice for PCP prophylaxis; thrice-weekly dosing is an appropriate option for patients intolerant of the daily dose. C1 Harlem Hosp Ctr, Div Infect Dis, New York, NY 10037 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. St Joseph Hosp, Chicago, IL USA. Univ Minnesota, Sch Publ Hlth, Div Biostat, CPCRA Stat Ctr, Minneapolis, MN 55455 USA. Community Consortium, San Francisco, CA USA. Addict Res & Treatment Corp, Brooklyn, NY USA. Cook Cty Hosp, Chicago, IL 60612 USA. Wayne State Univ, Detroit, MI USA. Dept Vet Affairs Med Ctr, Washington, DC USA. Georgetown Univ, Washington, DC USA. NIAID, Div Aids, Bethesda, MD 20892 USA. RP El-Sadr, WM (reprint author), Harlem Hosp Ctr, Div Infect Dis, Room 3107,506 Lenox Ave, New York, NY 10037 USA. NR 24 TC 42 Z9 44 U1 0 U2 1 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 1999 VL 29 IS 4 BP 775 EP 783 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 248RQ UT WOS:000083289500014 PM 10589887 ER PT J AU Slavkin, HC Panagis, JS Kousvelari, E AF Slavkin, HC Panagis, JS Kousvelari, E TI Future opportunities for bioengineering research at the National Institutes of Health SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Workshop of the Association-of-Bone-and-Joint-Surgeons CY NOV 12-15, 1998 CL TAMPA, FLORIDA SP Assoc Bone & Joint Surgeons ID CELLS AB Bioengineering integrates physical, chemical, and mathematical sciences with engineering principles for the study of biology, medicine, dentistry, behavior, or health. It advances fundamental concepts, translates knowledge from molecular to organ system levels of understanding, and designs and fabricates innovative biologics, biomaterials, processes, medical and dental implants, devices, and bioinformatics for health promotion, disease prevention, diagnosis, treatment, and therapeutics to improve the health of all people, The National Institutes of Health in recent years has made numerous decisions to coordinate bioengineering activities across the various institutes and centers comprising the National Institutes of Health to increase efforts to support research and research training in bioengineering. This paper will focus on innovations from 1995 to the present that have catalyzed increased activities and opportunities in bioengineering across the National Institutes of Health and will highlight current activities related to tissue engineering at the National Institute of Dental and Craniofacial Research and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. C1 NIAMSD, Orthopaed Program, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Panagis, JS (reprint author), NIAMSD, Orthopaed Program, Natl Inst Dent & Craniofacial Res, NIH, 6500 Ctr Dr,Room 5AS-37K, Bethesda, MD 20892 USA. NR 30 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1999 IS 367 SU S BP S17 EP S30 PG 14 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 247RR UT WOS:000083234200004 PM 10546633 ER PT J AU Nussinov, R Wolfson, HJ AF Nussinov, R Wolfson, HJ TI Efficient computational algorithms for docking and for generating and matching a library of functional epitopes - I. Rigid and flexible hinge-bending docking algorithms SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Review ID PROTEIN-PROTEIN INTERFACES; MOLECULAR-SURFACE; SHAPE COMPLEMENTARITY; AUTOMATED DOCKING; RECOGNITION; SITES; LIGANDS; SPARSE; POINTS; SEARCH AB In this, and the next review article (1), we present highly efficient, computer-vision and robotics based algorithms for docking and for the generation and matching of epitopes on molecular surfaces. We start with descriptions of molecular surfaces, and proceed to utilize these in both rigid-body and flexible matching routines. These algorithms originate in the computer Vision and robotics disciplines. Frequently used approaches, both in searches for molecular similarity and for docking, i.e., molecular complementarity, strive to obtain highly accurate correspondence of respective molecular surfaces. However, owing to molecular surface variability in solution, to mutational events, and to the need to use modeled structures in addition to high resolution ones, utilization of epitopes might prove to be a judicious approach to follow. Furthermore, through the deployment of libraries of epitopes which represent recurring features, or motifs in a given family of receptors or of enzymes, in principle we a priori focus on the more critical groups of atoms, or amino acids, essential for the binding of the two molecules. Utilization of recurring motifs may prove more robust than single molecule matchings. In addition, via utilization of epitopes one can make use of information derived from evolutionary related molecules. All of the above combine to represent an approach which may be highly advantageous. Combinatorial approaches have proven their immense utility in the wet laboratory. The combination of efficient computational approaches and the utilization of such libraries may well be particularly profitable. Our highly efficient techniques are amenable to such a task. In this review we focus on rigid and flexible docking algorithms. In the second review (1) we address the generation of epitopes in families of molecules. These may be used by the docking algorithms to identify the more likely bound interfaces. C1 NCI, Intramural Res Support Program, SAIC,Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sch Math Sci, Dept Comp Sci, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC,Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, Bldg 469,Rm 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-56000] NR 47 TC 5 Z9 5 U1 0 U2 1 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD OCT PY 1999 VL 2 IS 5 BP 249 EP 259 PG 11 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 256BR UT WOS:000083705800001 PM 10539986 ER PT J AU Nussinov, R Wolfson, HJ AF Nussinov, R Wolfson, HJ TI Efficient computational algorithms for docking and for generating and matching a library of functional epitopes - II. Computer vision-based techniques for the generation and utilization of functional epitopes SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Review ID LIGAND-BINDING-SITES; MOLECULAR-SURFACE; PROTEIN-STRUCTURE; ACTIVE-SITE; DATA-BANK; RECOGNITION; INTERFACES; ANTIBODY; COMPLEMENTARITY; MACROMOLECULES AB This is the second review in a two-part series. In the first review (1) we described the computational complexity involved in the docking of a ligand onto a receptor surface. in particular, we focused on efficient algorithms designed to handle this computational task. Such a procedure results in a large number of potential, geometrically feasible solutions. The difficulty is to pinpoint which of these is the more likely candidate. While there exists a number of approaches to rank these solutions according to different criteria, such as the size of the interface or some approximation of their binding energetics, none of the existing methods has been shown to be consistently successful in this endeavor. If the binding site is unknown a priori, the magnitude of the task is awesome. Here we propose one way of addressing this problem, i.e., via derivation and utilization of binding epitopes. If a library of such epitopes is available, particularly for a large number of protein families, it may be used to predict more likely binding sites for a given ligand. We describe an efficient, computer-vision based method to construct binding epitopes focusing on two ways through which such a library can be generated, (i) molecular surface-based, or (ii) residue-based. Alternatively, the two can be combined. We further describe how such a library may be used efficiently in the matching/docking procedure. C1 NCI, Intramural Res Support Program, SAIC,Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sch Math Sci, Dept Comp Sci, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC,Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 50 TC 4 Z9 4 U1 0 U2 0 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD OCT PY 1999 VL 2 IS 5 BP 261 EP 269 PG 9 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 256BR UT WOS:000083705800002 PM 10539987 ER PT J AU Freidlin, B Korn, EL George, SL AF Freidlin, B Korn, EL George, SL TI Data monitoring committees and interim monitoring guidelines SO CONTROLLED CLINICAL TRIALS LA English DT Article DE Bayesian methods; clinical trials; group sequential trials; interim analysis; stochastic curtailment ID RANDOMIZED CLINICAL-TRIALS; SEQUENTIAL-METHODS; DESIGN; BOUNDARIES; TESTS AB Most large randomized clinical trials have a data monitoring committee that periodically examines efficacy and safety results. A typical data monitoring committee meets every 6 months, but the interim monitoring guidelines for many trials specify formal analyses that are years apart. In this article we argue that study protocols should include monitoring guidelines with formal looks at each data monitoring committee meeting. Such guidelines are shown to reduce the average duration of a trial with negligible effect on power and estimation bias. Some of the common statistical monitoring guidelines require extreme evidence to stop a trial early and do not distinguish between stopping a trial during active accrual and follow-up stages. We propose practical solutions for these issues. (C) Elsevier Science Inc. 1999. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Div Biometry, Durham, NC USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, EPN-739, Bethesda, MD 20892 USA. NR 29 TC 30 Z9 32 U1 0 U2 5 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 1999 VL 20 IS 5 BP 395 EP 407 DI 10.1016/S0197-2456(99)00017-3 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 237LZ UT WOS:000082659000001 PM 10503800 ER PT J AU Slonim, AD Pollack, MM AF Slonim, AD Pollack, MM TI An approach to costs in critical care: Macro- versus microeconomics SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE cost; intensive care; macroeconomics; microeconomics; resource consumption; quality; outcome ID INTENSIVE-CARE; UNITS C1 NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Crit Care Med, Washington, DC 20010 USA. RP Pollack, MM (reprint author), 111 Michigan Ave, Washington, DC USA. NR 9 TC 3 Z9 3 U1 0 U2 0 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 1999 VL 27 IS 10 BP 2286 EP 2287 DI 10.1097/00003246-199910000-00037 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 250DT UT WOS:000083374300037 PM 10548222 ER PT J AU Murphy, WJ Blazar, BR AF Murphy, WJ Blazar, BR TI New strategies for preventing graft-versus-host disease SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; TOTAL-BODY IRRADIATION; FAS-LIGAND; T-CELLS; ACUTE GVHD; LEUKEMIA; MICE; LYMPHOCYTES; RESPONSES AB Graft-versus-host disease (GVHD) is a complex condition that can occur after allogeneic bone marrow transplantation and remains a significant cause of morbidity. GVHD occurs when donor immunocompetent T cells react to and attack the genetically disparate host. The etiology of GVHD is complex, with numerous Variables affecting its incidence and severity. Recent work has focused upon blunting the initial interactions between the donor T cell and the host. Because GVHD is linked with the beneficial graft-versus-tumor (GVT) effect that occurs after allogenic bone marrow transplantation, previous attempts to circumvent GVHD (i.e. by depletion of T cells from the donor graft) also resulted in increased relapse rates from the original tumor. The ideal scenario involves the tolerization or anergy of the donor T cell that attacks the host while allowing donor cells to mediate GVT effects. Recent work has attempted to address several pivotal features of GVHD: the variables that affect its induction and severity; the effector mechanisms; and whether GVHD can be suppressed yet GVT effects be maintained. Questions about these features need answers to enable us to design successful approaches for intervention. C1 Sci Applicat Int Corp, Natl Canc Inst, Cancer Res & Dev Ctr, Intramural Res Support Program, Frederick, MD 21702 USA. Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. RP Murphy, WJ (reprint author), Sci Applicat Int Corp, Natl Canc Inst, Cancer Res & Dev Ctr, Intramural Res Support Program, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NHLBI NIH HHS [2 R37 HL56067]; NIAID NIH HHS [R01 AI 34495] NR 53 TC 64 Z9 67 U1 0 U2 1 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 1999 VL 11 IS 5 BP 509 EP 515 DI 10.1016/S0952-7915(99)00002-3 PG 7 WC Immunology SC Immunology GA 241BP UT WOS:000082862400006 PM 10508701 ER PT J AU Segal, DM Weiner, GJ Weiner, LM AF Segal, DM Weiner, GJ Weiner, LM TI Bispecific antibodies in cancer therapy SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL ACTIVATION; ANTI-TARGET CELL; MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; INTRAPERITONEAL TREATMENT; OVARIAN-CARCINOMA; PHASE-I; FRAGMENTS; LYMPHOCYTES; RECEPTOR AB Based upon in vitro and animal studies, a number of Phase I and ii clinical trials have been initiated to test whether bispecific antibodies could redirect immune effecters against tumor cells in cancer patients. Recently, results from those trials showed beneficial effects in some patients but it is clear many problems remain to be solved. in addition, molecular engineering approaches are providing new and improved sources of clinically relevant bispecific antibodies. C1 NCI, Expt Immunol Branch, Immune Targeting Sect, NIH, Bethesda, MD 20892 USA. Univ Iowa, Ctr Canc, Iowa City, IA 52242 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. RP Segal, DM (reprint author), NCI, Expt Immunol Branch, Immune Targeting Sect, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 43 TC 117 Z9 121 U1 0 U2 8 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 1999 VL 11 IS 5 BP 558 EP 562 DI 10.1016/S0952-7915(99)00015-1 PG 5 WC Immunology SC Immunology GA 241BP UT WOS:000082862400014 PM 10508714 ER PT J AU Kreitman, RJ AF Kreitman, RJ TI Immunotoxins in cancer therapy SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID RICIN-A-CHAIN; VASCULAR LEAK SYNDROME; PHASE-I TRIAL; T-CELL LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; DIPHTHERIA-TOXIN RECEPTOR; HUMAN ENDOTHELIAL-CELLS; GROWTH-FACTOR RECEPTOR; NON-HODGKINS-LYMPHOMA; VERSUS-HOST DISEASE AB Immunotoxins are composed of a protein toxin connected to a binding ligand such as an antibody or growth factor. These molecules hind to surface antigens (which internalize) and kill cells by catalytic inhibition of protein synthesis within the cell cytosol. Immunotoxins have recently been tested clinically in hematologic malignancies and solid tumors and have demonstrated potent clinical efficacy in patients with malignant diseases that are refractory to surgery, radiation therapy and chemotherapy - the traditional modalities of cancer treatment. This therapy is thus evolving into a separate modality of cancer treatment. capable of rationally targeting cells on the basis of surface markers. Efforts are underway to obviate impediments to clinical efficacy, including immunogenicity and toxicity to normal tissues. Immunotoxins are now being developed to new antigens for the treatment of cancer. C1 NCI, Div Canc Biol, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Div Canc Biol, Mol Biol Lab, NIH, 37-4B27,9000 Rockville Pike,4255, Bethesda, MD 20892 USA. NR 97 TC 159 Z9 177 U1 0 U2 2 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 1999 VL 11 IS 5 BP 570 EP 578 DI 10.1016/S0952-7915(99)00005-9 PG 9 WC Immunology SC Immunology GA 241BP UT WOS:000082862400016 PM 10508704 ER PT J AU Rossouw, JE AF Rossouw, JE TI Hormone replacement therapy and cardiovascular disease SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review ID POSTMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; HEART-DISEASE; MYOCARDIAL-ISCHEMIA; SERUM-LIPIDS; PREVENTION; LIPOPROTEIN(A); RALOXIFENE; RISK AB A large amount of research continues to be conducted on the mechanisms of hormone replacement therapy (HRT) effects, and the first of the large clinical trials published its results during the past year, In addition to the well known effects on LDL-cholesterol, HDL-cholesterol, and triglycerides, recent studies confirmed that estrogen with or without a progestin lowers lipoprotein (a) concentrations in women (but not in men). In men, estrogen appears to have a similar effect on other lipids and lipoproteins and on plasminogen activator inhibitor-1 as in women. A comparison of estrogen with simvastatin indicated that simvastatin is better at lowering LDL-cholesterol while estrogen is better at raising HDL-cholesterol; when given in combination the additional effects were modest. Estrogen and simvastatin had similar beneficial effects on endothelial function. The estrogen effect on endothelial function may be blocked by medroxyprogesterone, but the data are inconsistent. These studies of intermediate outcomes were put in perspective by the results of a landmark secondary prevention trial of coronary heart disease (CHD). This randomized placebo-controlled trial (Heart and Estrogen/Progestin Replacement Study) of conjugated equine estrogens plus medroxyprogesterone failed to show the anticipated reduction in CHD, and at the same time the threefold increase in venous thromboembolism confirmed that HRT is procoagulant. Therefore, it is still not known whether HRT is a viable option for the prevention of CHD. The preliminary data on selective estrogen receptor modulators are not overly promising, but a definitive trial to test whether raloxifene will reduce CHD is ongoing. Curr Opin Lipidol 10:429-434. (C) 1999 Lippincott Williams & Wilkins. C1 NHLBI, Womens Hlth Initiat, Bethesda, MD 20817 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat, 1 Rockledge Ctr MS 7966,6705 Rockledge Dr, Bethesda, MD 20817 USA. NR 25 TC 27 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD OCT PY 1999 VL 10 IS 5 BP 429 EP 434 DI 10.1097/00041433-199910000-00007 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 250PQ UT WOS:000083397100007 PM 10554705 ER PT J AU Priola, SA Caughey, B Caughey, WS AF Priola, SA Caughey, B Caughey, WS TI Novel therapeutic uses for porphyrins and phthalocyanines in the transmissible spongiform encephalopathies - Commentary SO CURRENT OPINION IN MICROBIOLOGY LA English DT Editorial Material ID RESISTANT PRION PROTEIN; PRP ACCUMULATION; CONGO RED; AGENT REPLICATION; INCUBATION PERIOD; VARIANT CJD; SCRAPIE; INHIBITION; POLYANIONS; INFECTION C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Priola, SA (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 25 TC 23 Z9 24 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD OCT PY 1999 VL 2 IS 5 BP 563 EP 566 DI 10.1016/S1369-5274(99)00020-X PG 4 WC Microbiology SC Microbiology GA 247GA UT WOS:000083211700018 PM 10617376 ER PT J AU Ford, BD Loeb, JA Fischbach, GD AF Ford, BD Loeb, JA Fischbach, GD TI Neuregulin stimulates DNA synthesis in embryonic chick heart cells SO DEVELOPMENTAL BIOLOGY LA English DT Article DE acetylcholine receptor-inducing activity (ARIA); endocardial cushion; mesenchyme; erbB receptor ID RECEPTOR-INDUCING ACTIVITY; GLIAL GROWTH-FACTORS; CARDIAC DEVELOPMENT; ENDOTHELIAL-CELLS; MESENCHYMAL CELLS; ARIA ISOFORMS; SCHWANN-CELLS; FACTOR BETA-3; IN-VITRO; MUSCLE AB Neuregulins are a family of growth factors that have been shown to promote the growth or differentiation of various cell. types. Recently, targeted mutations of the genes for neuregulins or their putative receptors by homologous recombination resulted in embryonic lethality characterized by cardiac malformation. Here we investigate a role for neuregulin in the growth of cultured chick heart cells. Neuregulin induced the tyrosine phosphorylation of a 185-kDa protein in cultured heart cells, and it also stimulated an increase in [H-3]thymidine incorporation and BrDU labeling in the cell cultures. Immunocytochemistry revealed that the increased DNA synthesis was primarily in mesenchymal cells and not detected in myocytes or endocardial cells. These data suggest that neuregulin may function as a paracrine signal in mesenchymal-endothelial interactions during cardiac development. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Ford, BD (reprint author), NIMH, NIH, 9600 Rockville Pike, Bethesda, MD 20892 USA. NR 46 TC 12 Z9 12 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 1999 VL 214 IS 1 BP 139 EP 150 DI 10.1006/dbio.1999.9394 PG 12 WC Developmental Biology SC Developmental Biology GA 244FT UT WOS:000083041700012 PM 10491263 ER PT J AU Saillan-Barreau, C Dufresne, M Clerc, P Sanchez, D Corominola, H Moriscot, C Guy-Crotte, O Escrieut, C Vaysse, N Gomis, R Tarasova, N Fourmy, D AF Saillan-Barreau, C Dufresne, M Clerc, P Sanchez, D Corominola, H Moriscot, C Guy-Crotte, O Escrieut, C Vaysse, N Gomis, R Tarasova, N Fourmy, D TI Evidence for a functional role of the cholecystokinin-B/gastrin receptor in the human fetal and adult pancreas SO DIABETES LA English DT Article ID GROWTH-FACTOR-ALPHA; INSULIN-SECRETION; HUMAN BRAIN; DIFFERENTIAL EXPRESSION; PHYSIOLOGICAL-ROLE; HORMONE-SECRETION; GASTRIN; GLUCAGON; CCK; LOCALIZATION AB Gastrin (G) and cholecystokinin (CCK) are gastrointestinal neuropeptides that are released into circulation during a meal. G is also transiently expressed during embryogenic and early ontogenic development of the pancreas and is believed to act on islet-cell. development. Both peptides act on pancreatic endocrine function; however, the effects are dependent on the species and on cellular and molecular underlying mechanisms that remain poorly characterized. Since CCK-B/G subtype receptor is predominant over the CCK-A subtype in the human pancreas, me hypothesized that it could be expressed by islet cells. Here we present reverse transcription-polymerase chain reaction and immunohistochemistry data demonstrating that the CCK-B/G receptor is expressed in islet cells and that islet glucagon-producing cells are the major site of CCK-B/G receptor expression in adult and fetal pancreas, Moreover, G immunoreactivity was detected in the fetal human pancreas at embryogenic week 22, G- and CCK-stimulated glucagon are released from purified human islets, Concentration of CCK and G eliciting a half-maximal level of glucagon secretion were 13 +/- 6 and 8 +/- 5 pmol/l, respectively, Maximal glucagon secretion was achieved in the presence of 30 pmol/l peptides and was similar to that obtained in the presence of 10 mmol/l L-arginine (1.6 pmol.ml(-1).90 min(-1)). The nonpeptide antagonist of the CCK-B/G receptor, RPR-101048, fully inhibited CCK- and G-stimulated glucagon secretion at 100 nmol/l concentration. These data are consistent with the view that the CCK-B/G receptor is involved in glucose homeostasis in adult humans and mediates the autocrine effects of G on islet differentiation and growth in the fetal pancreas. C1 CHU Rangueil, INSERM, U151, Inst Louis Bugnard, F-31403 Toulouse 4, France. Fac Med, Grp Rech Glandes Exocrines, Marseille, France. Hosp Clin, Sch Med, Endocrinol & Diabet Unit, Barcelona, Spain. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Fourmy, D (reprint author), CHU Rangueil, INSERM, U151, Inst Louis Bugnard, Bat L3, F-31403 Toulouse 4, France. RI Dufresne, Marlene/M-6332-2014 OI Dufresne, Marlene/0000-0002-8654-963X NR 42 TC 63 Z9 64 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1999 VL 48 IS 10 BP 2015 EP 2021 DI 10.2337/diabetes.48.10.2015 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240FJ UT WOS:000082815000016 PM 10512367 ER PT J AU Harris, MI AF Harris, MI TI Racial and ethnic differences in health insurance coverage for adults with diabetes SO DIABETES CARE LA English DT Article ID IDDM AB OBJECTIVE - To evaluate the extent and types of health insurance coverage in a representative sample of adults with diabetes in the U.S. RESEARCH DESIGN AND METHODS - The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans aged greater than or equal to 20 years. Information on medical history and treatment of diabetes was obtained to determine subjects who had been diagnosed with diabetes by a physician before the survey (n = 1,503) and subjects without diagnosed diabetes (n = 17,319). Information on health insurance coverage was obtained via a structured questionnaire for 96% of participants. RESULTS - A total of 93% of all adults with diabetes had some form of health insurance. Of these subjects, 73% had private insurance, 48% had Medicare coverage, 15% had Medicaid coverage, and 5% had Champus/Veterans Affairs coverage. Approximately 52% of adults with diabetes had multiple types of health insurance, and 54% had health care coverage through one or more government-sponsored programs. A greater proportion of non-Hispanic whites (91%) and non-Hispanic blacks (89%) than Mexican-Americans (66%) had health insurance among subjects aged 20-64 years. For those aged greater than or equal to 65 years, coverage was virtually 100% or all racial and ethnic groups. Non-Hispanic whites had the highest rate of coverage through private insurance (81%), with non-Hispanic blacks having an intermediate rate (56%) and Mexican-Americans having the lowest rate (45%). Rates of coverage were similar for adults with and without diabetes in each racial and ethnic group for any type of insurance and for private insurance. CONCLUSIONS - There are marked racial and ethnic differences in health insurance coverage for adults with diabetes, although these differences are similar to those for adults without diabetes. Whether these racial and ethnic disparities influence access to care, quality of care, or health outcomes for people with diabetes remains to be determined. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Harris, MI (reprint author), NIDDK, NIH, Bldg 45,Room 5AN24, Bethesda, MD 20892 USA. NR 7 TC 58 Z9 60 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1999 VL 22 IS 10 BP 1679 EP 1682 DI 10.2337/diacare.22.10.1679 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240EJ UT WOS:000082812700014 PM 10526734 ER PT J AU Kahn, R Knowler, WC AF Kahn, R Knowler, WC TI Further data on the comparison between World Health Organization and American Diabetes Association Diagnostic Criteria - Response SO DIABETES CARE LA English DT Letter ID IMPAIRED GLUCOSE-TOLERANCE C1 Amer Diabet Assoc, Alexandria, VA 22311 USA. NIDDKD, Phoenix, AZ USA. RP Kahn, R (reprint author), Amer Diabet Assoc, 1701 N Beauregard St, Alexandria, VA 22311 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1999 VL 22 IS 10 BP 1756 EP 1757 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240EJ UT WOS:000082812700038 ER PT J CA DPP Res Grp TI The Diabetes Prevention Program evaluation and management of diabetes - Response SO DIABETES CARE LA English DT Letter C1 NIDDKD, Diabet Prevent Program, Phoenix, AZ USA. RP George Washington Univ, Ctr Biostat, Coordinating Ctr, 6110 Execut Blvd,750, Rockville, MD 20852 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1999 VL 22 IS 10 BP 1757 EP 1758 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240EJ UT WOS:000082812700040 ER PT J AU Dabelea, D Palmer, JP Bennett, PH Pettitt, DJ Knowler, WC AF Dabelea, D Palmer, JP Bennett, PH Pettitt, DJ Knowler, WC TI Absence of glutamic acid decarboxylase antibodies in Pima Indian children with diabetes mellitus SO DIABETOLOGIA LA English DT Letter C1 NIDDKD, Diabet & Arthrit Epidemiol Sect, NIH, Phoenix, AZ 85014 USA. RP Knowler, WC (reprint author), NIDDKD, Diabet & Arthrit Epidemiol Sect, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. FU NIDDK NIH HHS [DK17047, DK53004] NR 5 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1999 VL 42 IS 10 BP 1265 EP 1266 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 242HY UT WOS:000082935500018 PM 10525671 ER PT J AU Wu, CJ Qian, XL O'Rourke, DM AF Wu, CJ Qian, XL O'Rourke, DM TI Sustained mitogen-activated protein kinase activation is induced by transforming erbB receptor complexes SO DNA AND CELL BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; HUMAN GLIOBLASTOMA CELLS; MAP-KINASE; EGF RECEPTOR; SIGNAL-TRANSDUCTION; TYROSINE KINASE; CYCLE PROGRESSION; GENE-EXPRESSION; TERMINAL KINASE; ADAPTER PROTEIN AB We used a genetic approach to characterize features of mitogen-activated protein kinase (MAPK) activation occurring as a consequence of expression of distinct erbB receptor combinations in transformed human cells. Kinase-deficient erbB proteins reduced epidermal growth factor (EGF)-induced tyrosine phosphorylation of endogenous Shc proteins and also reduced immediate and sustained EGF-induced ERK MAPK activities in human glioblastoma cells, although basal ERK MAPK activities were unaffected. Basal and EGF-induced JNK and p38 MAPK kinase activities were equivalent in parental cancer cells and EGFR-inhibited subclones, When ectopically overexpressed in murine fibroblasts and human glioblastoma cells, a constitutively activated human EGF receptor oncoprotein (Delta EGFR) induced EGF-independent elevation of basal ERK MAPK activity. Basal JNK MAPK kinase activity was also specifically induced by Delta EGFR, which correlated with increased phosphorylation of a 54-kDa JNK2 protein observed in Delta EGFR-containing cells. The JNK activities in response to DNA damage were comparably increased in cells containing wildtype EGFR or Delta EGFR. Consistent with the notion that transforming erbB complexes induce sustained and unregulated MAPK activities, coexpression of p185(neu) and EGFR proteins to levels sufficient to transform murine fibroblasts also resulted in prolonged EGF-induced ERK in vitro kinase activation. Transforming erbB complexes, including EGFR homodimers, Delta EGFR homodimers, and p185(neu)/EGFR heterodimers, appear to induce sustained, unattenuated activation of MARK activities that may contribute to increased transformation and resistance to apoptosis in primary human glioblastoma cells. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Canc, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Surg Neurosurg, Philadelphia, PA 19104 USA. Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP O'Rourke, DM (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Room 288,John Morgan Bldg,36th & Hamilton Walk, Philadelphia, PA 19104 USA. NR 72 TC 29 Z9 30 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 1999 VL 18 IS 10 BP 731 EP 741 DI 10.1089/104454999314872 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 249EV UT WOS:000083320700001 PM 10541432 ER PT J AU Umbricht, A Montoya, ID Hoover, DR Demuth, KL Chiang, CT Preston, KL AF Umbricht, A Montoya, ID Hoover, DR Demuth, KL Chiang, CT Preston, KL TI Naltrexone shortened opioid detoxification with buprenorphine SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE naltrexone; buprenorphine; opioid detoxification; treatment; opioid dependence ID OPIATE WITHDRAWAL; CLONIDINE; ANTAGONISTS; DEPENDENCE AB This double-blind, randomized, placebo-controlled clinical trial evaluated the impact on withdrawal symptoms of (i) combining naltrexone with a 4-day buprenorphine taper for short opioid detoxification (NB Group), compared to (ii) using a 4-day buprenorphine taper alone, followed by naltrexone on day 8 (PB Group). Sublingual buprenorphine was administered on days 1-4 (26 mg total). For the NE Group (n = 32) escalating doses of oral naltrexone were given on days 2-8 (placebo day i). For the PB Group (n = 28) placebo was given on days 1-7 and naltrexone on day 8. Main outcome measures were Observed Opioid Withdrawal scores (OOW, 0-30) and use of medications to treat opioid withdrawal. Of 32 patients in the NE group, 59% experienced clinically relevant withdrawal (defined as OOW greater than or equal to 5) on day 2, but, after day 5, none experienced withdrawal. In the PB group, the number of patients experiencing withdrawal increased over time. The first naltrexone dose induced comparable withdrawal in both groups: peak OOW scores were (mean +/- SD) 5.2 +/- 3.3 on day 2 for the NE group, and 4.0 +/- 3.9 on day 8 for the PB group (NS), though, on day 2, 7 patients dropped out in the NE group and none in the PB group, while only one patient dropped out in the PB group on day 8. Throughout the 8-day study, patients in both groups received similar amount of adjunct medication: 0.64 +/- 0.07 mg (NB group) of clonidine vs 0.73 +/- 0.15 mg (PB group; NS). Only 25% of patients required use of sedatives (up to 20 mg diazepam). Starting naltrexone on day 2 appeared to abolish withdrawal symptoms after day 5 and, thus, to shorten the duration of withdrawal symptoms. Peak withdrawal symptoms after naltrexone were of moderate intensity, suggesting that naltrexone combined with buprenorphine is an acceptable and safe treatment for shortened opioid detoxification and induction of naltrexone maintenance. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NIDA, Intramural Res Program, Addict Res Ctr, Baltimore, MD 21224 USA. RP Umbricht, A (reprint author), NIDA, Intramural Res Program, Addict Res Ctr, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA. EM aumbri@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 32 TC 48 Z9 51 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 1999 VL 56 IS 3 BP 181 EP 190 DI 10.1016/S0376-8716(99)00033-2 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 238GP UT WOS:000082702800002 PM 10529020 ER PT J AU Roth, JS McCully, CM Balis, FM Poplack, DG Kelley, JA AF Roth, JS McCully, CM Balis, FM Poplack, DG Kelley, JA TI 2 '-beta-fluoro-2 ',3 '-dideoxyadenosine, lodenosine, in rhesus monkeys: Plasma and cerebrospinal fluid pharmacokinetics and urinary disposition SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID PURINE METABOLIZING ENZYMES; MACAQUES MACACA-NEMESTRINA; HIV; RATS; 2'-FLUORO-2',3'-DIDEOXYARABINOSYLADENINE; DIDEOXYNUCLEOSIDES; DIDEOXYINOSINE; AGENTS AB 2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA, lodenosine) is a nucleoside analog that was rationally designed as a more chemically and enzymatically stable anti-AIDS drug than its parent compound 2',3'-dideoxyadenosine or didanosine. Plasma and cerebrospinal fluid (CSF) pharmacokinetics of this compound and its major metabolite, 2'-beta-fluoro-2',3'-dideoxyinosine (F-ddI), were studied in three rhesus monkeys after a single 20 mg/kg dose administered as an i.v. push. F-ddA exhibited a mean residence time of 0.17 h in plasma and its plasma concentration time profile appeared to be biexponential. The majority of plasma exposure was from F-ddI, with a mean parent drug area under the curve (AUC) to metabolite AUC ratio of 0.16. CSF levels were low, with a mean CSF AUC to plasma AUC ratio of 0.068, with approximately one-quarter of this exposure in CSF due to unchanged drug. Urinary excretion accounted for half of the drug administered with the majority recovered as the metabolite, F-ddI. In a separate experiment, one monkey received a 20 mg/kg i.v. dose of F-ddI. The total dideoxynucleoside plasma exposure was greater than it was after administration of F-ddA; however, the CSF AUC to plasma AUC ratio was a factor of 4 lower (0.017). Thus, F-ddA central nervous system penetration is at least comparable to that of didanosine, indicating that this experimental drug has potential as an addition to currently approved AIDS therapies. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Texas Childrens Hosp, Hematol Oncol Serv, Houston, TX 77030 USA. RP Roth, JS (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Room 5C-02,37 Convent Dr, Bethesda, MD 20892 USA. NR 25 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD OCT PY 1999 VL 27 IS 10 BP 1128 EP 1132 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 241BG UT WOS:000082861700005 PM 10497138 ER PT J AU Stastna, M Radko, SP Chrambach, A AF Stastna, M Radko, SP Chrambach, A TI Capillary zone electrophoresis of proteins in semidilute polymer solutions: Inter- and intra-polymer predictability of size-dependent retardation SO ELECTROPHORESIS LA English DT Article DE proteins; polymer solutions; electrophoresis; retardation; predictability ID POLYACRYLAMIDE SOLUTIONS; PARTICLES; SEPARATION; DYNAMICS; DIAMETER AB The retardation of three "spherical" proteins with Stokes' radii of 2.0, 2.4, and 3.0 nm (35-104 kDa) was studied in capillary zone electrophoresis (CZE), using semidilute solutions of polyethylene glycol (PEG), linear polyacrylamide (PA), and polyvinyl alcohol (PVA). The purpose was to test the models predicting that the ratio of particle radius, R, to the mesh size of polymer network (the correlation or screening length of a semidilute polymer solution), xi, directly governs the size-dependent retardation in the form: mu/mu(o) = exp (-R/xi). Here xi = kc(0.75), where c is polymer concentration and the numerical factor k can be calculated based on polymer molecular weight. In application to polymers in a "good solvent" (PA and PEG in the aqueous buffer) and to proteins of 2.4 and 3.0 nm radius, that relation between relative mobility and R/xi was found to be obeyed for PA, while for PEG the value of k derived from retardation experiments significantly exceeded that which was theoretically calculated. Thus, the retardation appears to be polymer-specific, rather than universal, even for polymers in a "good solvent". It is suggested that, in that case, retardation of proteins of R > 2 nm be quantitatively described in the form mu/mu(o) = exp[-p(R/xi], where p is a parameter depending on monomer type and/or polymer polydispersity. For PVA, the logarithm of mu/mu(o) was found to be linearly related to c (in line with the prediction that the aqueous buffer is a "poor solvent" for this polymer) and to be near-independent of R. C1 NICHHD, Lab Cellular & Mol Biophys, Macromol Anal Sect, NIH, Bethesda, MD 20892 USA. Russian Acad Med Sci, Med Genet Res Ctr, Moscow, Russia. RP Chrambach, A (reprint author), NICHHD, Lab Cellular & Mol Biophys, Macromol Anal Sect, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. RI Stastna, Miroslava/G-9266-2014 NR 27 TC 6 Z9 6 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1999 VL 20 IS 14 BP 2884 EP 2890 DI 10.1002/(SICI)1522-2683(19991001)20:14<2884::AID-ELPS2884>3.0.CO;2-5 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 279LA UT WOS:000085044200015 PM 10546824 ER PT J AU Issaq, HJ AF Issaq, HJ TI Capillary electrophoresis of natural products-II SO ELECTROPHORESIS LA English DT Review DE natural products; capillary electrophoresis; micellar electrokinetic capillary chromatography; Chinese herbal preparations; alkaloids; toxins; illicit drugs; cells; review ID MICELLAR ELECTROKINETIC CHROMATOGRAPHY; ZONE-ELECTROPHORESIS; BIOGENIC-AMINES; ERGOT ALKALOIDS; SEPARATION; ACID; PHARMACEUTICALS; EXTRACTION; FLAVONOIDS; PROTEINS AB Capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) were used for the separation of widely different compounds from natural materials including compounds from tea, acids from different matrices, flavonoids and alkaloids, toxins and toxicological compounds, proteins and polypeptides, biogenic amines, phenolic compounds in alcoholic beverages, Chinese medicinal drugs, compounds in cells and cell extracts, and micellaneous other applications. A section dealing with recent reviews related to natural products is also included. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Chem Synth & Anal Lab, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Chem Synth & Anal Lab, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 52 TC 65 Z9 70 U1 2 U2 13 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1999 VL 20 IS 15-16 BP 3190 EP 3202 DI 10.1002/(SICI)1522-2683(19991001)20:15/16<3190::AID-ELPS3190>3.0.CO;2-K PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 279LC UT WOS:000085044400015 PM 10596825 ER PT J AU Mongiovi, AM Romano, PR Panni, S Mendoza, M Wong, WT Musacchio, A Cesareni, G Di Fiore, PP AF Mongiovi, AM Romano, PR Panni, S Mendoza, M Wong, WT Musacchio, A Cesareni, G Di Fiore, PP TI A novel peptide-SH3 interaction SO EMBO JOURNAL LA English DT Article DE Eps8; SH3; signal transduction ID TERMINAL SH3 DOMAIN; PROLINE-RICH PEPTIDES; PROTEIN-BINDING DOMAIN; STRUCTURAL BASIS; EPS8; GROWTH; KINASE; SUBSTRATE; SEQUENCE; GRB2 AB SH3 domains constitute a family of protein-protein interaction modules that bind to peptides displaying an X-proline-X-X-proline (XPXXP) consensus. We report that the SH3 domain of Eps8, a substrate of receptor and non-receptor tyrosine kinases, displays a novel and unique binding preference. By a combination of approaches including (i) screening of phage-displayed random peptide libraries, (ii) mapping of the binding regions on three physiological interactors of Eps8, (iii) alanine scanning of binding peptides and (iv) in vitro cross-linking, me demonstrate that a proline-X-X-aspartate-tyrosine (PXXDY) consensus is indispensable for binding to the SH3 domain of Eps8, Screening of the Expressed Sequence Tags database allowed the identification of three Eps8-related genes, whose SH3s also display unusual binding preferences and constitute a phylogenetically distinct subfamily within the SH3 family, Thus, Eps8 identifies a novel family of SH3-containing proteins that do not bind to canonical XPXXP-containing peptides, and that establish distinct interactions in the signaling network. C1 Ist Europeo Oncol, Dept Expt Oncol, I-20141 Milan, Italy. Univ Roma Tor Vergata, Dept Biol, Enrico Calef, I-00133 Rome, Italy. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Bari, Ist Microbiol, Bari, Italy. RP Di Fiore, PP (reprint author), Ist Europeo Oncol, Dept Expt Oncol, Via Ripamonti 435, I-20141 Milan, Italy. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 26 TC 138 Z9 139 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 1 PY 1999 VL 18 IS 19 BP 5300 EP 5309 DI 10.1093/emboj/18.19.5300 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 246AK UT WOS:000083140800015 PM 10508163 ER PT J AU Sasaki, S Lesoon-Wood, LA Dey, A Kuwata, T Weintraub, BD Humphrey, G Yang, WM Seto, E Yen, PM Howard, BH Ozato, K AF Sasaki, S Lesoon-Wood, LA Dey, A Kuwata, T Weintraub, BD Humphrey, G Yang, WM Seto, E Yen, PM Howard, BH Ozato, K TI Ligand-induced recruitment of a histone deacetylase in the negative-feedback regulation of the thyrotropin beta gene SO EMBO JOURNAL LA English DT Article DE histone deacetylases; negative feedback; thyroid hormone; thyrotropin ID THYROID-HORMONE RECEPTOR; TRANSCRIPTION FACTOR PIT-1/GHF-1; EMBRYONAL CARCINOMA-CELLS; RETINOIC ACID RECEPTOR; SUBUNIT GENE; REPRESS TRANSCRIPTION; CHROMATIN STRUCTURE; RESPONSE ELEMENT; NUCLEAR RECEPTORS; TRICHOSTATIN-A AB We have investigated ligand-dependent negative regulation of the thyroid-stimulating hormone beta (TSH beta) gene. Thyroid hormone (T3) markedly repressed activity of the TSH beta promoter that had been stably integrated into GH(3) pituitary cells, through the conserved negative regulatory element (NRE) in the promoter. By DNA affinity binding assay, we show that the NRE constitutively binds to the histone deacetylase 1 (HDAC1) present in GH3 cells. Significantly, upon addition of T3, the NRE further recruited the thyroid hormone receptor (TR beta) and another deacetylase, HDAC2, This recruitment coincided with an alteration of in vivo chromatin structure, as revealed by changes in restriction site accessibility. Supporting the direct interaction between TR and HDAC, in vitro assays showed that TR, through its DNA binding domain, strongly bound to HDAC2, Consistent with the role for HDACs in negative regulation, an inhibitor of the enzymes, trichostatin A, attenuated T3-dependent promoter repression. We suggest that ligand-dependent histone deacetylase recruitment is a mechanism of the negative-feedback regulation, a critical function of the pituitary-thyroid axis. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Maryland, Inst Human Virol, Mol Endocrinol Lab, Baltimore, MD 21201 USA. Univ S Florida, Dept Med Microbiol & Immunol, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NR 64 TC 86 Z9 87 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 1 PY 1999 VL 18 IS 19 BP 5389 EP 5398 DI 10.1093/emboj/18.19.5389 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 246AK UT WOS:000083140800023 PM 10508171 ER PT J AU Hoare, SRJ Bonner, TI Usdin, TB AF Hoare, SRJ Bonner, TI Usdin, TB TI Comparison of rat and human parathyroid hormone 2 (PTH2) receptor activation: PTH is a low potency partial agonist at the rat PTH2 receptor SO ENDOCRINOLOGY LA English DT Article ID MOLECULAR-CLONING; EXPRESSION; BINDING; PEPTIDE; LIGAND; CELLS; POLYPEPTIDE; CALCITONIN; ANALOGS; ORGANS AB The human PTH2 receptor, expressed in tissue culture cells, is selectively activated by PTH. Detailed investigation of its anatomical and cellular distribution has been performed in the rat. It is expressed by neurons in a number of brain nuclei; by endocrine cells that include pancreatic islet somatostatin cells, thyroid parafollicular cells, and peptide secreting cells in the gastrointestinal tract; and by cells in the vasculature and heart. The physiological role of the PTH2 receptor expressed by these cells remains to be determined. All pharmacological studies performed to date have used the human receptor. We have now isolated a complementary DNA including the entire coding sequence of the rat PTH2 receptor and compared its pharmacological profile with that of the human PTH2 receptor when each is expressed in COS-7 cells. PTH-based peptides, including rat PTH(1-84), rat PTH(1-34), and human PTH(1-34), have low potency at the rat PTH2 receptor for stimulation of adenylyl cyclase (EC50 = 19-140 nM). When compared with the effect of a bovine hypothalamic extract, PTH-based peptides are partial agonists at the rat PTH2 receptor. This suggests that PTH is unlikely to be a physiologically important endogenous ligand for the PTH2 receptor. A peptide homologous to an activity detected in a bovine hypothalamic extract is a good candidate for the endogenous PTH2 receptor ligand. C1 NIMH, Cell Biol Unit, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Cell Biol Unit, Genet Lab, NIH, Room 3D06,Bldg 36,36 Convent Dr,MSC4094, Bethesda, MD 20892 USA. EM usdin@codon.nih.gov NR 25 TC 39 Z9 39 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1999 VL 140 IS 10 BP 4419 EP 4425 DI 10.1210/en.140.10.4419 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237RC UT WOS:000082669000007 PM 10499494 ER PT J AU Xi, D Kusano, K Gainer, H AF Xi, D Kusano, K Gainer, H TI Quantitative analysis of oxytocin and vasopressin messenger ribonucleic acids in single magnocellular neurons isolated from supraoptic nucleus of rat hypothalamus SO ENDOCRINOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION; RT-PCR; HYBRIDIZATION HISTOCHEMISTRY; BRATTLEBORO RAT; RNA; COEXPRESSION; PITUITARY; TISSUES; CELLS AB Oxytocin (OT) and vasopressin (VP) are peptide hormones that are derived from genes predominantly expressed in distinct magnocellular neurons in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Recent evidence suggests that some magnocellular neurons coexpress both peptides. Our qualitative RT-PCR experiments on single cells show that the majority of magnocellular neurons coexpress both peptide messenger RNAs (mRNAs) in varying amounts. Using a competitive RT-PCR method combined with a standard calibration curve, we quantitatively determined OT and VP mRNA in single magnocellular neurons from the normal female rat SON, with a detection sensitivity of less than 30 mRNA molecules/cell. We defined the phenotypes of the single magnocellular neurons according to their ratios of these two peptide mRNAs. Using this approach, we identified three major phenotypes: oxytocin neurons, where the average OT to VP mRNA ratio is about 256; vasopressin neurons, where the average VP to OT mRNA ratio is about 182; and one oxytocin/vasopressin coexisting neuron, where the OT/VP mRNA ratio is 2. Thus, there is some OT and VP mRNA coexpression in virtually all of the magnocellular neurons in supraoptic nuclei of hypothalamus. However, clear phenotypes are identifiable by considering quantitative as opposed to qualitative differences. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Room 4D-20, Bethesda, MD 20892 USA. NR 31 TC 65 Z9 66 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1999 VL 140 IS 10 BP 4677 EP 4682 DI 10.1210/en.140.10.4677 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237RC UT WOS:000082669000038 PM 10499525 ER PT J AU Grey, A Mitnick, MA Masiukiewicz, U Sun, BH Rudikoff, S Jilka, RL Manolagas, SC Insogna, K AF Grey, A Mitnick, MA Masiukiewicz, U Sun, BH Rudikoff, S Jilka, RL Manolagas, SC Insogna, K TI A role for interleukin-6 in parathyroid hormone-induced bone resorption in vivo SO ENDOCRINOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; OSTEOCLAST DIFFERENTIATION FACTOR; LEUKEMIA INHIBITORY FACTOR; PRIMARY HYPERPARATHYROIDISM; SOLUBLE INTERLEUKIN-6; POSTMENOPAUSAL WOMEN; OSTEOBLASTIC CELLS; STROMAL CELLS; ESTROGEN LOSS; FACTOR-ALPHA AB Parathyroid hormone (PTH) exerts its regulatory effects on calcium homeostasis in part by stimulating the release of calcium from the skeleton. PTH stimulates bone resorption indirectly, by inducing the production by stromal/osteoblastic cells of paracrine agents which recruit and activate the bone-resorbing cell, the osteoclast. The identity of the stromal cell/osteoblast-derived paracrine factor(s) responsible for mediating the effects of PTH on osteoclasts is uncertain. Recently, it has been demonstrated that the cytokine interleukin-g (IL-6), which potently induces osteoclastogenesis, is produced by osteoblastic cells in response to PTH. Further, we have reported that circulating levels of IL-6 are elevated in patients with primary hyperparathyroidism, and correlate with biochemical markers of bone resorption. Thus, IL-6 may play a permissive role in; PTH-induced bone resorption. In the current studies, we demonstrate that low-dose PTH infusion in rodents increased serum levels of IL-6, coincident with a rise in biochemical markers of bone resorption. In mice, both acute neutralization and chronic deficiency of IL-6 were associated with markedly lower levels of biochemical markers of bone resorption in response to PTH infusion than were observed in animals with normal IL-6 production. Acute neutralization of IL-6 did not affect PTH-induced changes in markers of bone formation. These findings demonstrate that PTH regulates systemic levels of IL-6 in experimental animals, that IL-6 is an important mediator of the bone-resorbing actions of PTH in vivo and suggest that IL-6 plays a role in coupling PTH-induced bone resorption and formation. C1 Yale Univ, Sch Med, Endocrinol Sect, New Haven, CT 06520 USA. NCI, Genet Lab, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Insogna, K (reprint author), Yale Univ, Sch Med, Endocrinol Sect, 333 Cedar St,POB 208020, New Haven, CT 06520 USA. EM karl.insogna@yale.edu NR 40 TC 111 Z9 112 U1 0 U2 2 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 1999 VL 140 IS 10 BP 4683 EP 4690 DI 10.1210/en.140.10.4683 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237RC UT WOS:000082669000039 PM 10499526 ER PT J AU Gothilf, Y Coon, SL Toyama, R Chitnis, A Namboodiri, MAA Klein, DC AF Gothilf, Y Coon, SL Toyama, R Chitnis, A Namboodiri, MAA Klein, DC TI Zebrafish serotonin N-acetyltransferase-2: Marker for development of pineal photoreceptors and circadian clock function SO ENDOCRINOLOGY LA English DT Article ID ACETYLTRANSFERASE MESSENGER-RNA; N-ACETYLTRANSFERASE; MELATONIN SYNTHESIS; CATALYTIC MECHANISM; FLOATING HEAD; RETINA; ORGAN; EXPRESSION; RHYTHM; GLAND AB Serotonin N-acetyltransferase (AANAT), the penultimate enzyme in melatonin synthesis, is typically found only at significant levels in the pineal gland and retina. Large changes in the activity of this enzyme drive the circadian rhythm in circulating melatonin seen in all vertebrates. In this study, we examined the utility of using AANAT messenger RNA (mRNA) as a marker to monitor the very early development of pineal photoreceptors and circadian clock function in zebrafish. Zebrafish AANAT-2 (zfAANAT-2) cDNA was isolated and used for in situ hybridization. In the adult, zfAANAT-2 mRNA is expressed exclusively in pineal cells and retinal photoreceptors, Developmental analysis, using whole mount in, situ hybridization, indicated that pineal zfAANAT-2 mRNA expression is first detected at 22 h post fertilization. Retinal zfAANAT-2 mRNA was first detected on day 3 post fertilization and appears to be associated with development of the retinal photoreceptors. Time-of-day analysis of 2- to 5-day-old zebrafish larvae indicated that zfAANAT-2 mRNA abundance exhibits a dramatic 24-h rhythm in a 14-h light, 10-h dark cycle, with high levels at night. This rhythm persists in constant darkness, indicating that the zfAANAT-2 mRNA rhythm is driven by a circadian clock at this stage. The techniques described in this report were also used to determine that zfAANAT-2 expression is altered in two well characterized genetic mutants, mindbomb and floating head. The observations described here suggest that zfAANAT-2 mRNA may be a useful marker to study development of the pineal gland and of circadian clock mechanisms in zebrafish. C1 Uniformed Serv Univ Hlth Sci, Dept Physiol, NICHHD, Sect Neuroendocrinol,Lab Dev Neurobiol,NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Physiol, NICHHD, Lab Mol Genet,NIH, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), Uniformed Serv Univ Hlth Sci, Dept Physiol, NICHHD, Sect Neuroendocrinol,Lab Dev Neurobiol,NIH, 49-5A38,49 Convent Dr, Bethesda, MD 20892 USA. EM klein@helix.nih.gov NR 40 TC 99 Z9 107 U1 2 U2 9 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 1999 VL 140 IS 10 BP 4895 EP 4903 DI 10.1210/en.140.10.4895 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237RC UT WOS:000082669000063 PM 10499549 ER PT J AU Wang, XL Cahill, CM Pineyro, MA Zhou, J Doyle, ME Egan, JM AF Wang, XL Cahill, CM Pineyro, MA Zhou, J Doyle, ME Egan, JM TI Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells SO ENDOCRINOLOGY LA English DT Article ID GENE-TRANSCRIPTION; TRANSLOCATION; EXPRESSION; PANCREAS; STF-1 AB Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. The latter are also regulated by the PDX-1 homeoprotein. We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10nM) in RIN 1046-38 insulinoma cells. Under these experimental conditions, there was also a 1.6-fold increase in the expression of PDX-1 protein in whole cell and nuclear extracts. Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the A1 element of the rat insulin II promoter was also increased 2h post treatment with GLP-1. In summary, we have uncovered a previously unknown aspect to the regulation of PDX-1 in beta cells. This has important implications in the physiology of adult beta cells and the treatment of type 2 diabetes mellitus with GLP-1 or its analogs. C1 NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Wang, XL (reprint author), NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. NR 13 TC 93 Z9 97 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 1999 VL 140 IS 10 BP 4904 EP 4907 DI 10.1210/en.140.10.4904 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237RC UT WOS:000082669000064 PM 10499550 ER PT J AU Elsasser, TH Kahl, S Martinez, A Montuenga, LM Pio, R Cuttitta, F AF Elsasser, TH Kahl, S Martinez, A Montuenga, LM Pio, R Cuttitta, F TI Adrenomedullin binding protein in the plasma of multiple species: Characterization by radioligand blotting SO ENDOCRINOLOGY LA English DT Article ID SOMATOMEDIN-C; RADIOIMMUNOASSAY AB Frequently, peptide hormones circulate in plasma associated with specific binding proteins that modify the clearance and biochemical activities of the peptide. Our experimental approach was to use I-125-ligand blotting procedures to probe for the presence of specific adrenomedullin (AM) binding proteins (AMBPs). Plasma proteins from chick, calf, dog, goat, guinea pig, human, mouse, pig rabbit and sheep blood were separated electrophoretically in 10% nonreducing SDS-polyacrylamide gels and transferred to nitrocellulose. Nonspecific binding of tracer was blocked on the nitrocellulose with a hydrolyzed casein matrix. Blots were probed with synthetic human I-125-AM. Autoradiogram scanning of blots revealed a mixture of 140- and/or 120- kD protein complexes that bound I-125-AM in all species tested. Binding of the ligand was specific as judged by a linear competitive displacement of the tracer binding from human, bovine and pig plasma AMBP bands with increasing concentrations of nonlabelled AM in the binding buffer. A series of peptide fragments of AM representing amino- and carboxyterminal regions of the hormone, or amylin, calcitonin gene-related peptide (CGRP), or insulin failed to displace intact I-125-AM from ligand blot bands. Bovine plasma proteins from healthy and parasitized calves with an infection-related stunting syndrom were separated electrophoretically, transferred to nitrocellulose and probed with I-125-AM; phosphoimage densitometry analysis revealed a 67% decrease in AMBP band intensity in the 120 and 140 kD proteins from infected calves. We conclude that a specific binding protein(s) for AM exists in mammalian and avian blood that might impact on the bioactivity and function of AM in health and disease. C1 USDA ARS, Growth Biol Lab, Beltsville, MD 20705 USA. NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. RP Elsasser, TH (reprint author), USDA ARS, Growth Biol Lab, Beltsville, MD 20705 USA. RI Martinez, Alfredo/A-3077-2013; Pio, Ruben/F-5353-2017 OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111 NR 12 TC 61 Z9 63 U1 0 U2 2 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 1999 VL 140 IS 10 BP 4908 EP 4911 DI 10.1210/en.140.10.4908 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237RC UT WOS:000082669000065 PM 10499551 ER PT J AU Cooper, GS Germolec, D Heindel, J Selgrade, MJ AF Cooper, GS Germolec, D Heindel, J Selgrade, MJ TI Linking environmental agents and autoimmune diseases - Introduction SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. US EPA, Immunotoxicol Branch, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NR 4 TC 10 Z9 10 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 1999 VL 107 SU 5 BP 659 EP 660 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246XP UT WOS:000083190400001 PM 10502527 ER PT J AU Smith, DA Germolec, DR AF Smith, DA Germolec, DR TI Introduction to immunology and autoimmunity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Linking Environmental Agents to Autoimmune Diseases CY SEP 01-03, 1998 CL RES TRIANGLE PK, NORTH CAROLINA SP NIH, Off Rare Dis, NIH, Off Res Womens Hlth, NIH, NIEHS, NIH, NIAID, NIH, NIDDK, NIH, NIAMS, US EPA, Amer Autoimmune Related Dis Assoc Inc, Juvenile Diaabetes Fdn Int DE autoantibodies; autoimmune disease; autoimmunity; autoreactive immunity; immunity; mechanisms; tolerance ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ARTHRITIDIS-DERIVED SUPERANTIGEN; SYSTEMIC LUPUS-ERYTHEMATOSUS; HEAT-SHOCK PROTEIN-65; B-CELL ACTIVATION; MULTIPLE-SCLEROSIS; YERSINIA-ENTEROCOLITICA; SERUM ANTIBODIES; IMMUNE-RESPONSE; DISEASE AB Autoimmune disease occurs when the immune system attacks self-molecules as a result of a breakdown of immunologic tolerance to autoreactive immune cells. Many autoimmune disorders have been strongly associated with genetic, infectious, and/or environmental predisposing factors. Comprising multiple disorders and symptoms ranging from organ-specific to systemic, autoimmune diseases include insulin-dependent diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, thyroiditis, and multiple sclerosis. There are also implications of autoimmune pathology in such common health problems as arteriosclerosis, inflammatory bowel disease, schizophrenia, and certain types of infertility. Largely of unknown etiology, autoimmune disorders affect approximately 3% of the North American and European populations, > 75% of those affected being women. This discussion provides a brief introduction to the immune system and tolerance maintenance, an overview of selected autoimmune diseases and possible mechanisms of immune autoreactivity, and a review of experimental autoimmune models. C1 NIEHS, Toxicol Lab, Res Triangle Pk, NC USA. RP Germolec, DR (reprint author), POB 12233, Res Triangle Pk, NC 27709 USA. NR 68 TC 13 Z9 14 U1 1 U2 5 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 1999 VL 107 SU 5 BP 661 EP 665 DI 10.2307/3434323 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246XP UT WOS:000083190400002 PM 10502528 ER PT J AU Cooper, GS Miller, FW Pandey, JP AF Cooper, GS Miller, FW Pandey, JP TI The role of genetic factors in autoimmune disease: Implications for environmental research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Linking Environmental Agents to Autoimmune Diseases CY SEP 01-03, 1998 CL RES TRIANGLE PK, NORTH CAROLINA SP NIH, Off Rare Dis, NIH, Off Res Womens Hlth, NIH, NIEHS, NIH, NIAID, NIH, NIDDK, NIH, NIAMS, US EPA, Amer Autoimmune Related Dis Assoc Inc, Juvenile Diaabetes Fdn Int DE autoimmune diseases; gene-environment interactions; genetics; major histocompatibility complex; multiple sclerosis; rheumatoid arthritis; systemic lupus erythematosus; type I diabetes mellitus ID SYSTEMIC LUPUS-ERYTHEMATOSUS; DEPENDENT DIABETES-MELLITUS; EOSINOPHILIA-MYALGIA-SYNDROME; MAJOR HISTOCOMPATIBILITY COMPLEX; PRIMARY SJOGRENS-SYNDROME; DRUG-INDUCED LUPUS; 3 ETHNIC-GROUPS; HLA CLASS-II; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS AB Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. US FDA, Lab Mol & Dev Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 117 TC 69 Z9 71 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 1999 VL 107 SU 5 BP 693 EP 700 DI 10.2307/3434329 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246XP UT WOS:000083190400008 PM 10502533 ER PT J AU Ligier, S Sternberg, EM AF Ligier, S Sternberg, EM TI Neuroendocrine host factors and inflammatory disease susceptibility SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Linking Environmental Agents to Autoimmune Diseases CY SEP 01-03, 1998 CL RES TRIANGLE PK, NORTH CAROLINA SP NIH, Off Rare Dis, NIH, Off Res Womens Hlth, NIH, NIEHS, NIH, NIAID, NIH, NIDDK, NIH, NIAMS, US EPA, Amer Autoimmune Related Dis Assoc Inc, Juvenile Diaabetes Fdn Int DE autoimmunity; eosinophilia myalgia syndrome; Fischer rats; hypothalamic-pituitary-adrenal axis; Lewis rats inflammation; neuroendocrine system; rheumatoid arthritis; Sjogren syndrome; systemic lupus erythematosus ID PITUITARY-ADRENAL AXIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; CORTICOTROPIN-RELEASING HORMONE; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EOSINOPHILIA-MYALGIA-SYNDROME; WALL-INDUCED ARTHRITIS; ACID MESSENGER-RNA; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; IMMUNE-SYSTEM AB The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures. C1 NIMH, Sect Neuroendocrine Immunol & Behav, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, Clin Neuroendocrinol Branch, NIH, Bldg 10,Rm 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 95 TC 11 Z9 12 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 1999 VL 107 SU 5 BP 701 EP 707 DI 10.2307/3434330 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246XP UT WOS:000083190400009 PM 10502534 ER PT J AU Matthews, HB Lucier, GW Fisher, KD AF Matthews, HB Lucier, GW Fisher, KD TI Medicinal herbs in the United States: Research needs SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE medicinal herbs; dietary supplements ID ALTERNATIVE MEDICINE AB Virtually all cultures have, throughout history, used a variety of plants or materials derived from plants for the prevention and treatment of disease. Evidence of the beneficial therapeutic effects of these medicinal herbs is seen in their continued use. Additionally, the development of modern chemistry permitted the isolation of chemicals from medicinal herbs that have served as drugs or starting materials for the synthesis of many important drugs used today. Many more modern drugs have been synthesized as a result of knowledge gained from studies of mechanisms of actions of chemicals first isolated from medicinal herbs. Thus, medicinal herbs have played a major role in the development of modern medicine and continue to be widely used in their original form. Whereas it is generally agreed that most medicinal herbs are safe under the conditions used, some are toxic and should be avoided even though they are readily available, and others have significant adverse side effects when misused. Also, little has been done to investigate potential adverse effects that may be associated with extended or high-dose use of medicinal herbs. Thus, concern has been expressed that the lack of quality control used in the preparation of medicinal herbs, plus their unregulated sale and uninformed use, pose potential adverse health effects for consumers. There is also concern regarding potential herb/herb or herb/drug interactions and possible untoward health effects of medicinal herbs in sensitive subpopulations such as the young and the elderly and certain genetically predisposed individuals. In this paper, we discuss these concerns at some length and make recommendations for additional research and education discussed in the recent International Workshop to Evaluate Research Needs on the Use and Safety of Medicinal Herbs. C1 NIEHS, Res Triangle Pk, NC 27709 USA. US Dept HHS, Off Dis Prevent & Hlth Promot, Washington, DC 20201 USA. RP Matthews, HB (reprint author), NIEHS, B3-10,POB 12233, Res Triangle Pk, NC 27709 USA. NR 22 TC 46 Z9 48 U1 0 U2 8 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 1999 VL 107 IS 10 BP 773 EP 778 DI 10.2307/3454572 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246BR UT WOS:000083143700018 PM 10504141 ER PT J AU Parks, CG Conrad, K Cooper, GS AF Parks, CG Conrad, K Cooper, GS TI Occupational exposure to crystalline silica and autoimmune disease SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Linking Environmental Agents to Autoimmune Diseases CY SEP 01-03, 1998 CL RES TRIANGLE PK, NORTH CAROLINA SP NIH, Off Rare Dis, NIH, Off Res Womens Hlth, NIH, NIEHS, NIH, NIAID, NIH, NIDDK, NIH, NIAMS, US EPA, Amer Autoimmune Related Dis Assoc Inc, Juvenile Diaabetes Fdn Int DE antineutrophil cytoplasmic antibodies; antinuclear antibodies; nephritis; rheumatoid arthritis; scleroderma; systemic lupus erythematosus; Wegener granulomatosis ID SYSTEMIC LUPUS-ERYTHEMATOSUS; STAGE RENAL-DISEASE; RHEUMATOID-ARTHRITIS; SEROLOGICAL CHARACTERISTICS; WEGENER GRANULOMATOSIS; GRANITE WORKERS; IN-VITRO; DUST; SCLERODERMA; EPIDEMIOLOGY AB Occupational exposure to silica dust has been examined as a possible risk factor with respect to several systemic autoimmune diseases, including scleroderma. rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline silica, or quartz, is an abundant mineral found in sand, rock, and soil. High-level exposure to respirable silica dust can cause chronic inflammation and fibrosis in the lung and other organs. Studies of specific occupational groups with high-level silica exposure (e.g., miners) have shown increased rates of autoimmune diseases compared to the expected rates in the general population. However, some clinic- and population-based studies have not demonstrated an association between silica exposure and risk of autoimmune diseases. This lack of effect may be due to the limited statistical power of these studies to examine this association or because the lower- or moderate-level exposures that may be more common in the general population were not considered. Experimental studies demonstrate that silica can act as an adjuvant to nonspecifically enhance the immune response. This is one mechanism by which silica might be involved in the development of autoimmune diseases. Given that several different autoimmune diseases may be associated with silica dust exposure, silica dust may act to promote or accelerate disease development, requiring some other factor to break immune tolerance or initiate autoimmunity The specific manifestation of this effect may depend on underlying differences in genetic susceptibility or other environmental exposures. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Tech Univ Dresden, Inst Immunol, Fak Med, D-8027 Dresden, Germany. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. OI Parks, Christine/0000-0002-5734-3456 NR 124 TC 155 Z9 162 U1 4 U2 8 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 1999 VL 107 SU 5 BP 793 EP 802 DI 10.2307/3434342 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246XP UT WOS:000083190400021 PM 10970168 ER PT J AU Selgrade, MK Cooper, GS Germolec, DR Heindel, JJ AF Selgrade, MK Cooper, GS Germolec, DR Heindel, JJ TI Linking environmental agents and autoimmune disease: An agenda for future research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Linking Environmental Agents to Autoimmune Diseases CY SEP 01-03, 1998 CL RES TRIANGLE PK, NORTH CAROLINA SP NIH, Off Rare Dis, NIH, Off Res Womens Hlth, NIH, NIEHS, NIH, NIAID, NIH, NIDDK, NIH, NIAMS, US EPA, Amer Autoimmune Related Dis Assoc Inc, Juvenile Diaabetes Fdn Int DE autoimmune disease; epidemiology; hazard identification; research needs ID MICE AB Autoimmune diseases are influenced by multiple factors including genetics, age, gender, reproductive status, hormones, and potential environmental contaminants. A workshop, "Linking Environmental Agents and Autoimmune Diseases," was convened at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 1-3 September 1998, to review current knowledge about links between environmental exposures and autoimmune disease, to identify and prioritize research needs, and to develop an integrated, multidisciplinary research agenda. Participatants spent the last half-day of the workshop in small group discussions for the purpose of developing consensus on research needs. Research needs identified were a) develop research tools needed to explore links between environmental agents and autoimmune disease; b) establish a disease registry or surveillance system; c) develop and validate strategies for screening chemicals for the potential to induce or exacerbate autoimmune disease; d) develop an emergency response strategy to gain information from accidental exposures; and e) conduct hypothesis-driven research in occupationally exposed groups and/or in experimental animals. There was consensus that meetings like this workshop and projects that facilitate interactions between specialties should be encouraged. A multidisciplinary approach is needed to address this problem. C1 NIEHS, Div Extramural Res & Testing, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Heindel, JJ (reprint author), NIEHS, Div Extramural Res & Testing, POB 12233 EC-23, Res Triangle Pk, NC 27709 USA. NR 9 TC 13 Z9 13 U1 0 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 1999 VL 107 SU 5 BP 811 EP 813 DI 10.2307/3434345 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246XP UT WOS:000083190400024 PM 10502548 ER PT J AU Fort, DJ Propst, TL Stover, EL Helgen, JC Levey, RB Gallagher, K Burkhart, JG AF Fort, DJ Propst, TL Stover, EL Helgen, JC Levey, RB Gallagher, K Burkhart, JG TI Effects of pond water, sediment, and sediment extracts from Minnesota and Vermont, USA, on early development and metamorphosis of Xenopus SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE Xenopus; frog; malformation; thyroid; deformities ID EMBRYO TERATOGENESIS ASSAY; METABOLIC-ACTIVATION SYSTEM; 3 CARRIER SOLVENTS; THYROID-HORMONE; TAIL RESORPTION; RETINOIC ACID; FETAX; TOXICITY; LAEVIS; VALIDATION AB In recent studies, a high incidence of amphibian mortality and malformation has been reported in the field, suggesting that toxic and/or bioactive agents are present in the environment of the affected amphibians. This study provides evidence for this hypothesis, because it applies to several affected ponds in Minnesota and Vermont, USA. Three developmental bioassays were carried our on samples from three reference and three test sites in Minnesota and one reference and three test sites, in Vermont. The bioassays utilized Xenopus as a model system, measuring altered developmental patterns during the first 4 d of development (frog embryo teratogenesis assay-Xenopus [FETAX]), hind-limb development over a 30-d period, and tail length resorption over a 14-d period. Strong correlations were observed among the results for all three in vitro bioassays, as well as between adverse developmental effects in vitro and in the field. C1 Stover Grp, Stillwater, OK 74076 USA. Minnesota Pollut Control Agcy, St Paul, MN 55155 USA. Vermont Dept Agr & Environm Labs, Waterbury, VT 05671 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Fort, DJ (reprint author), Stover Grp, POB 2056, Stillwater, OK 74076 USA. NR 40 TC 56 Z9 62 U1 2 U2 6 PU SETAC PRESS PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3370 USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD OCT PY 1999 VL 18 IS 10 BP 2305 EP 2315 DI 10.1897/1551-5028(1999)018<2305:EOPWSA>2.3.CO;2 PG 11 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 240FD UT WOS:000082814500027 ER PT J AU Fort, DJ Rogers, RL Copley, HF Bruning, LA Stover, EL Helgen, JC Burkhart, JG AF Fort, DJ Rogers, RL Copley, HF Bruning, LA Stover, EL Helgen, JC Burkhart, JG TI Progress toward identifying causes of maldevelopment induced in Xenopus by pond water and sediment extracts from Minnesota, USA SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE amphibian malformation; frog embryo teratogenesis assay; limb development; chemical fractionation; Minnesota, USA ID EMBRYO TERATOGENESIS ASSAY; METABOLIC-ACTIVATION SYSTEM; DEVELOPMENTAL TOXICITY; THYROID-HORMONE; RESPONSE ELEMENTS; FETAX; TOXICANTS; RECEPTORS AB In previously conducted laboratory studies with the South African clawed frog (Xenopus laevis), pond water and sediment samples collected from various sites in Minnesota, USA, were demonstrated to have the potential to induce a variety of developmental abnormalities, including early embryo-larval maldevelopment, abnormal limb development, and disruption of metamorphosis. The results of exposure of X. laevis to suspect pond water and sediment samples supported the hypothesis that these samples were capable of inducing these abnormalities as the result of either the presence of developmental toxicants or the absence of essential micronutrients. Physicochemical characterization of the causes of abnormal frog embryo-larval and limb development were performed using the frog embryo teratogenesis assay-Xenopus (FETAX). Specific compounds were subsequently identified within the complex mixture fractions and tested by dilution in a control solution and native reference water using both the 4- and 30-d treatment protocols. Results from these studies suggested that a complex mixture of both naturally occurring and man-made compounds was primarily responsible for the effects observed in X. laevis. The potency of several compounds was also enhanced by the site water, thus indicating that the water matrix deserves consideration as a contributing factor for both laboratory and field studies. C1 Stover Grp, Stillwater, OK 74076 USA. Minnesota Pollut Control Agcy, St Paul, MN 55155 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Fort, DJ (reprint author), Stover Grp, POB 2056, Stillwater, OK 74076 USA. NR 38 TC 43 Z9 46 U1 0 U2 5 PU SETAC PRESS PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3370 USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD OCT PY 1999 VL 18 IS 10 BP 2316 EP 2324 DI 10.1897/1551-5028(1999)018<2316:PTICOM>2.3.CO;2 PG 9 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 240FD UT WOS:000082814500028 ER PT J AU Tozser, J Bagossi, P Boross, P Louis, JM Majerova, E Oroszlan, S Copeland, TD AF Tozser, J Bagossi, P Boross, P Louis, JM Majerova, E Oroszlan, S Copeland, TD TI Effect of serine and tyrosine phosphorylation on retroviral proteinase substrates SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE HIV proteinase; AMV proteinase; retropepsins; phosphorylation; substrate specificity ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERMEDIATE FILAMENT PROTEINS; NUCLEOCAPSID PROTEIN; HIV-2 PROTEINASES; AVIAN-SARCOMA; GAG PROTEINS; WILD-TYPE; KINASE-C; VIMENTIN; SPECIFICITY AB Vimentin, a cellular substrate of HN type 1 (HIV-1) proteinase, contains a protein kinase C (PKC) phosphorylation site at one of its cleavage sites. Peptides representing this site were synthesized in P2 Ser-phosphorylated and nonphosphorylated forms. While the nonphosphorylated peptide was a fairly good substrate of the enzyme, phosphorylation prevented hydrolysis. Phosphorylation of human recombinant vimentin by PKC prevented its processing within the head domain, where the phosphorylation occurred, Oligopeptides representing naturally occurring cleavage sites at the C-terminus of the Rous sarcoma virus integrase were assayed as substrates of the avian proteinase. Unlike the nonphosphorylated peptides, a Ser-phosphorylated peptide was not hydrolyzed by the enzyme ar the Ser-Pro bond. suggesting the role of previously established phosphorylation in processing at this site. Ser-phosphorylated and Tyr-phosphorylated forms of model substrates were also tested as substrates of the HIV-1 and the avian retroviral proteinases. In contrast to the moderate effect of P4 Ser phosphorylation, phosphorylation of P1 Tyr prevented substrate hydrolysis by HIV-1 proteinase, Substrate phosphorylation had substantially smaller effects on the hydrolysis by the avian retroviral proteinase. As the active retroviral proteinase as well as various protein kinases are incorporated into mature virions, substrate phosphorylation resulting in attenuation or prevention of proteolytic processing may have important consequences in the regulation of the retroviral life cycle as well as in virus-host cell interactions. C1 Debrecen Univ Med, Sch Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Mol Virol & Carcinogenesis, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Special Program Prot Chem, Frederick, MD USA. SAIC Frederick, Frederick, MD USA. RP Tozser, J (reprint author), Debrecen Univ Med, Sch 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 NR 44 TC 11 Z9 12 U1 0 U2 2 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 1999 VL 265 IS 1 BP 423 EP 429 DI 10.1046/j.1432-1327.1999.00756.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241QA UT WOS:000082893000049 PM 10491200 ER PT J AU Plouzek, CA Ciolino, HP Clarke, R Yeh, GC AF Plouzek, CA Ciolino, HP Clarke, R Yeh, GC TI Inhibition of P-glycoprotein activity and reversal of multidrug resistance in vitro by rosemary extract SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE rosemary; P-glycoprotein; multidrug resistance; breast cancer; doxorubicin ID NATURAL ANTIOXIDANTS; BREAST-CANCER; CELLS; TUMORIGENESIS; MODULATION; CARNOSOL; EFFLUX AB The transmembrane transport pump P-glycoprotein (Pgp) causes the efflux of chemotherapeutic agents from cells and is believed to be an important mechanism in multidrug resistance (MDR) in mammary tumours. In the present study we demonstrate that an extract of the common dietary herb rosemary (Rosemarinus officinalis Labiatae), increases the intracellular accumulation of commonly used chemotherapeutic agents, including doxorubicin (DOX) and vinblastine (VIN), in drug-resistant MCF-7 human breast cancer cells which express Pgp. Rosemary extract (RE) inhibits the efflux of DOX and VIN, which are known to be substrates of Pgp, but does not affect accumulation or efflux of DOX in wild type MCF-7 cells, which lack Pgp. Treatment of drug-resistant cells with RE increases their sensitivity to DOX, which is consistent with an increased intracellular accumulation of the drug. RE blocks the binding of the VIN analogue azidopine to Pgp. Thus, it appears that RE directly inhibits Pgp activity by inhibiting the binding of drugs to Pgp. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Cellular Def & Carcinogenesis Sect, Div Basic Sci,Basic Res Lab,NIH, Frederick, MD 21701 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Yeh, GC (reprint author), NCI, Frederick Canc Res & Dev Ctr, Cellular Def & Carcinogenesis Sect, Div Basic Sci,Basic Res Lab,NIH, Frederick, MD 21701 USA. EM yeh@mail.ncifcrf.gov RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 NR 19 TC 51 Z9 56 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 1999 VL 35 IS 10 BP 1541 EP 1545 DI 10.1016/S0959-8049(99)00180-X PG 5 WC Oncology SC Oncology GA 244FX UT WOS:000083042100022 PM 10673984 ER PT J AU Mages, J Handschuh, G Kremmer, E Wang, QC Pastan, I Hofler, H Becker, KF AF Mages, J Handschuh, G Kremmer, E Wang, QC Pastan, I Hofler, H Becker, KF TI Mutations of E-cadherin: A novel target for cancer specific immunotherapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 GSF, Forschungszentrum, Pathol, D-85764 Neuherberg, Germany. GSF, Forschungszentrum, Mol Immunol, D-85764 Neuherberg, Germany. NCI, NIH, Bethesda, MD 20892 USA. Tech Univ Munich, D-81675 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 1999 VL 35 SU 5 MA 24 BP S15 EP S15 PG 1 WC Oncology SC Oncology GA 251GE UT WOS:000083435600027 ER PT J AU Marincola, FM Rosenberg, SA AF Marincola, FM Rosenberg, SA TI "Surgery branch experience with melanoma vaccines" SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 1999 VL 35 SU 5 MA 6 BP S8 EP S8 PG 1 WC Oncology SC Oncology GA 251GE UT WOS:000083435600009 ER PT J AU Pastan, I Waldman, TA Kreitman, RJ AF Pastan, I Waldman, TA Kreitman, RJ TI Antitumor activity of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients. SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Kreitman Lab, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 1999 VL 35 SU 5 MA 95 BP S51 EP S51 PG 1 WC Oncology SC Oncology GA 251GE UT WOS:000083435600095 ER PT J AU Ballard-Barbash, R Klabunde, C Paci, E Broeders, M Coleman, EA Frachebond, J Bouchard, F Rennert, G Shapiro, S AF Ballard-Barbash, R Klabunde, C Paci, E Broeders, M Coleman, EA Frachebond, J Bouchard, F Rennert, G Shapiro, S TI Breast cancer screening in 21 countries: delivery of services, notification of results and outcomes ascertainment SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE breast cancer; delivery of services; mammography; population-based database; screening ID MAMMOGRAPHY; GUIDELINES; REDUCTION; MORTALITY; PROGRAMS; PROJECT AB Following clinical trial evidence of mammography screening's efficacy and effectiveness, data are needed from organized population-based programmes to determine whether screening in these programmes results in breast cancer mortality reductions comparable to those demonstrated in controlled settings. The International Breast Cancer Screening Network (IBSN) conducted two international programme assessments: in 1990 among nine countries and in 1995 among 22 countries, obtaining information on the organization and process for screening within breast cancer screening programmes, This manuscript describes procedures for recruitment, service delivery, interpretation and communication of results, case ascertainment, and quality assurance. Practices in more established programmes are compared with pilot programmes, Each IBSN country defined a unique programme of population-based breast cancer screening. Some programmes were sub-national rather than national in scope, while others were in pilot stages of development, Screening took place in dedicated centres in established programmes and in both dedicated and general radiology centres in pilot programmes. Although most countries used personal invitation systems to recruit women to screening, other recruitment mechanisms were used. Most countries used two-view mammography in their screening programmes. About half had implemented independent double reading of mammograms, considering it a key component of high-quality mammography screening. In conclusion, diversity exists in the organization and delivery of screening mammography internationally. Quality assurance activities are a priority and are being evaluated in the IBSN, (C) 1999 Lippincott Williams & Wilkins. C1 NCI, Bethesda, MD 20892 USA. Ctr Studio & Prevenz Oncol, Florence, Italy. Univ Nijmegen Hosp, EUREF, Nijmegen, Netherlands. Univ Arkansas Med Sci, Little Rock, AR USA. Erasmus Univ, Rotterdam, Netherlands. Hlth Canada, Ottawa, ON, Canada. Carmel Med Ctr, Haifa, Israel. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Ballard-Barbash, R (reprint author), NCI, Execut Plaza N,Room 313,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. RI Broeders, Mireille/C-8820-2015 NR 17 TC 48 Z9 48 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD OCT PY 1999 VL 8 IS 5 BP 417 EP 426 DI 10.1097/00008469-199910000-00007 PG 10 WC Oncology SC Oncology GA 252WQ UT WOS:000083525600007 PM 10548397 ER PT J AU Woodson, K Ratnasinghe, D Bhat, NK Stewart, C Tangrea, JA Hartman, TJ Stolzenberg-Solomon, R Virtamo, J Taylor, PR Albanes, D AF Woodson, K Ratnasinghe, D Bhat, NK Stewart, C Tangrea, JA Hartman, TJ Stolzenberg-Solomon, R Virtamo, J Taylor, PR Albanes, D TI Prevalence of disease-related DNA polymorphisms among participants in a large cancer prevention trial SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE ATBC study; cancer; genotype; polymorphism ID METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; ANDROGEN RECEPTOR GENE; LUNG-CANCER; COLORECTAL-CANCER; VASCULAR-DISEASE; PROSTATE-CANCER; RISK; SUSCEPTIBILITY; POPULATION; FINNISH AB Genetic susceptibility polymorphisms may be of substantial importance in the modulation of cancer risk. The prevalence for an array of polymorphic genes was determined in a cohort of male smokers who participated in a cancer prevention trial in Finland, A random sample of 120 individuals was selected from the trial cohort and the prevalence of variant alleles for nine genes was determined using a polymerase chain reaction-based approach. The prevalence values from this study were also compared with those of other populations derived from previous studies. Our results show that, with the exception of cytochrome P450-1A1 (CW1A1) and cytochrome P450-2E1 (CYP2E1), all genes tested were sufficiently polymorphic to warrant an investigation of gene-environment studies. Most of the variant alleles, including alcohol dehydrogenase 3 (ADH(3)), glutathiones-transferase (GSTM1), methionine synthase (MS), methylene tetrahydofolater reductase (MHTFR), CYP2E1 and CYP1A1, exhibited similar frequencies to other Caucasian populations, Interestingly, the prevalence of androgen receptor-GAG repeat (AR-CAG) and vitamin D receptor (VDR) polymorphisms differed significantly between the alpha-trocopherol, beta-carotene (ATBC) Study and other Caucasian populations. We present herein results from this survey and conclude that the ATBG study population in Finland is sufficiently heterogeneous to facilitate analysis of genetic polymorphisms and disease associations. (C) 1999 Lippincott Williams & Wilkins. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. Natl Inst Publ Hlth, Helsinki, Finland. RP Woodson, K (reprint author), NCI, Canc Prevent Studies Branch, Div Clin Sci, 6006 Execut Blvd MSC 7058, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-43045] NR 28 TC 23 Z9 23 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD OCT PY 1999 VL 8 IS 5 BP 441 EP 447 DI 10.1097/00008469-199910000-00010 PG 7 WC Oncology SC Oncology GA 252WQ UT WOS:000083525600010 PM 10548400 ER PT J AU Allen, J Sillanaukee, P AF Allen, J Sillanaukee, P TI Carbohydrate-deficient transferrin is a useful marker for the detection of chronic alcohol abuse SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Letter ID CONSUMPTION; SERUM; DRINKING; RELAPSE C1 NIAAA, Treatment Studies Div Clin & Prevent Res, Bethesda, MD 20892 USA. Tampere Univ, FIN-33101 Tampere, Finland. RP Allen, J (reprint author), NIAAA, Treatment Studies Div Clin & Prevent Res, Willco Bldg,Suite 505,6000 Execut Blvd MSC 7003, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD OCT PY 1999 VL 29 IS 10 BP 899 EP 900 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 251RP UT WOS:000083458900013 PM 10583432 ER PT J AU Shalev, A AF Shalev, A TI The crucial role of a phosphatase in insulin resistance and obesity SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PROTEIN C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Shalev, A (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 4 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD OCT PY 1999 VL 141 IS 4 BP 323 EP 324 DI 10.1530/eje.0.1410323 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 251YU UT WOS:000083474600002 PM 10526242 ER PT J AU Burke, RE AF Burke, RE TI The use of state-dependent modulation of spinal reflexes as a tool to investigate the organization of spinal interneurons SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE spinal cord; motoneurons; DOPA locomotion; scratching; spatial facilitation ID BACKWARD QUADRUPEDAL WALKING; LATENCY CUTANEOUS EXCITATION; FLEXOR DIGITORUM LONGUS; FICTIVE LOCOMOTION; PRIMARY AFFERENTS; HINDLIMB MOTONEURONS; ADAPTIVE-CONTROL; MOTOR PATTERNS; CAT HINDLIMB; GROUP-IA AB This review examines the proposition that state-dependent modulation of transmission through spinal reflex pathways can be used as an investigative tool to reveal details about the organization of spinal interneurons into functional circuits. The first set of examples includes the use of spinal and supraspinal lesions, as well as the administration of the drug l-dihydroxyphenylalanine (l-DOPA), to produce different, relatively stable "states" of the central nervous system (CNS), revealing previously unsuspected spinal pathways activated by the flexor reflex afferents (FRA). The second set of examples deals with the use of fictive locomotion and scratching to investigate the organization of oligosynaptic excitatory and inhibitory reflex pathways from cutaneous and muscle afferents. As in the first set of examples, several hitherto unknown reflex pathways have been found only during the flexion or extension phases of rhythmic locomotion, which are regarded as different CNS states. Differences in the patterns of control can be used to infer the existence of distinct sets of reflex pathway interneurons that have remarkably precise input/output relations. C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Burke, RE (reprint author), NINDS, Neural Control Lab, NIH, Bldg 49,Rm 3A50, Bethesda, MD 20892 USA. NR 81 TC 94 Z9 96 U1 0 U2 2 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 1999 VL 128 IS 3 BP 263 EP 277 DI 10.1007/s002210050847 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 242NM UT WOS:000082947200001 PM 10501799 ER PT J AU Weeks, RA Gerloff, C Dalakas, M Hallett, M AF Weeks, RA Gerloff, C Dalakas, M Hallett, M TI PET study of visually and non-visually guided finger movements in patients with severe pan-sensory neuropathies and healthy controls SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE functional imaging; plasticity; motor control; deafferentation; premotor; somatosensory ID POSITRON EMISSION TOMOGRAPHY; SUPERIOR PARIETAL LOBULE; CEREBRAL BLOOD-FLOW; MOTOR CORTEX; FUNCTIONAL-ANATOMY; MACAQUE MONKEY; SOMATOSENSORY CORTEX; REACHING MOVEMENTS; HUMAN BRAIN; AREA AB Although patients with sensory neuropathies and normal muscle power are rare, they have been extensively studied because they are a model for dissociating the sensory and motor components of movement. We have examined these patients to determine the cerebral functional anatomy of movement in the absence of proprioceptive input. In addition, the disabling symptoms of these patients can be substantially improved by visually monitoring their movements. We hypothesized that, during visually guided movements, these patients would show overactivity of regions specialized for visuomotor control with the possible additional involvement of areas that normally process somatosensory information. We used positron emission tomography (PET) and the tracer (H2O)-O-15 to determine the functional anatomy of visually and non-visually guided finger movements in three patients with long-standing pan-sensory neuropathies and normal muscle power and six healthy controls. Five conditions were performed with the right hand: a sequential finger movement task under visual guidance, the same motor task without observation of the hand, monitoring a video of the same sequential finger movement, a passive visual task observing a reversing checkerboard, and an unconstrained rest condition. Data were analyzed using conventional subtraction techniques with a statistical threshold of z>2.33 with corrections for multiple comparisons. When compared with the control group, activation was not deficient in any brain areas of the patient cohort in any of the contrasts tested. In particular, in the non-visually guided movement task, in which meaningful visual and proprioceptive input was absent, the patient group activated primary motor, premotor, and cerebellar regions. This suggests that these areas are involved in motor processing independent of sensory input. In all conditions involving visual observation of hand movements, there was highly significant overactivity of the left parietal operculum (SII) and right parieto-occipital cortex (PO) in the patient group. Recent non-human primate studies have suggested that the PO region contains a visual representation of hand movements. Overactivity of this area and the activation of SII by visual input appear to indicate that compensatory overactivity of visual areas and cross-modal plasticity of somatosensory areas occur in deafferented patients. These processes may underlie their ability to compensate for their proprioceptive deficits. C1 NINDS, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. NR 52 TC 14 Z9 14 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 1999 VL 128 IS 3 BP 291 EP 302 DI 10.1007/s002210050849 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 242NM UT WOS:000082947200003 PM 10501801 ER PT J AU Kaneko, O Soubes, SC Miller, LH AF Kaneko, O Soubes, SC Miller, LH TI Plasmodium falciparum: Invasion of Aotus monkey red blood cells and adaptation to Aotus monkeys SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Aotus monkey; invasion; malaria; Plasmodium falciparum ID ERYTHROCYTES; ANTIGEN; POLYMORPHISMS; EXPRESSION; SURFACE; STRAIN; DNA C1 NIAID, Parasit Dis Lab, Malaria Cell Biol Sect, NIH, Bethesda, MD 20892 USA. RP Miller, LH (reprint author), NIAID, Parasit Dis Lab, Malaria Cell Biol Sect, NIH, 9000 Rockville Pike,Room B1-37,4 Ctr Dr, Bethesda, MD 20892 USA. NR 16 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD OCT PY 1999 VL 93 IS 2 BP 116 EP 119 DI 10.1006/expr.1999.4441 PG 4 WC Parasitology SC Parasitology GA 241KC UT WOS:000082881300010 PM 10502476 ER PT J AU Dikalov, SI Mason, RP AF Dikalov, SI Mason, RP TI Reassignment of organic peroxyl radical adducts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE peroxyl radical; alkoxyl radical; spin trap; radical adduct; peroxidase; oxygen-17; DMPO; TMIO; free radicals ID TERT-BUTYL HYDROPEROXIDE; ELECTRON-SPIN-RESONANCE; CUMENE HYDROPEROXIDE; LIVER-MITOCHONDRIA; ALKOXYL; HYDROXYL; HEMATIN; DMPO; SPECTROSCOPY; SPECTRA AB The study of the important role of peroxyl radicals in biological systems is limited by their difficult detection with direct electron spin resonance (ESR). Many ESR spectra were assigned to 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/peroxyl radical adducts based only on the close similarity of their ESR spectra to that of DMPO/superoxide radical adduct in conjunction with their insensitivity to superoxide dismutase, which distinguishes the radical adduct from DMPO/superoxide radical adduct. Later, the spin-trapping literature reported that DMPO/peroxyl radical adducts have virtually the same hyperfine coupling constants as synthesized alkoxyl radical adducts, raising the issue of the correct assignment of peroxyl radical adducts. However, using O-17-isotope labelling, the methylperoxyl and methoxyl radical adducts should be distinguishable. We have reinvestigated the spin trapping of the methylperoxyl radical. The methylperoxyl radical was generated in aerobic solution with O-17-molecular oxygen either in a Fenton system with dimethylsulfoxide or in a chloroperoxidase system with tert-butyl hydroperoxide. Two different spin traps, DMPO and 2,2,4-trimethyl-2H-imidazole-1-oxide (TMIO), were used to trap methylperoxyl radical. O-17-labelled methanal was used to synthesize methoxyl radical adducts by nucleophylic addition. It was shown that the O-17 hyperfine coupling constants of radical adducts formed in methylperoxyl radical-generating systems are identical to that of the methoxyl radical adduct. Therefore, methylperoxyl radical-producing systems form detectable methoxyl radical adduct, but not detectable methylperoxyl radical adducts at room temperature. One of the possible mechanisms is the decomposition of peroxyl radical adduct with the formation of secondary alkoxyl radical adduct. These results allow us to reinterpret previously published data reporting detection of peroxyl radical adducts. We suggest that detection of O-17-alkoxyl radical adduct from O-17-labelled molecular oxygen can be used as indirect evidence for peroxyl radical generation. (C) 1999 Elsevier Science Inc. C1 NIEHS, Pharmacol & Chem Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Dikalov, SI (reprint author), NIEHS, Pharmacol & Chem Lab, NIH, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 33 TC 83 Z9 83 U1 2 U2 20 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 PY 1999 VL 27 IS 7-8 BP 864 EP 872 DI 10.1016/S0891-5849(99)00134-3 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 240ZM UT WOS:000082856700016 PM 10515591 ER PT J AU Rota, C Chignell, CF Mason, RP AF Rota, C Chignell, CF Mason, RP TI Evidence for free radical formation during the oxidation of 2 '-7 '-dichlorofluorescin to the fluorescent dye 2 '-7 '-dichlorofluorescein by horseradish peroxidase: Possible implications for oxidative stress measurements SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE 2 '-7 '-dichlorofluorescin; 2 '-7 '-dichlorofluorescein; oxidation; free radical; superoxide; hydrogen per; oxide; spin trapping ID RESPIRATORY BURST ACTIVITY; REACTIVE OXYGEN; HYDROGEN-PEROXIDE; NITRIC-OXIDE; IN-VITRO; PROBE 2',7'-DICHLOROFLUORESCIN; RECEPTOR ACTIVATION; ENDOTHELIAL-CELLS; DIHYDRORHODAMINE-123; PEROXYNITRITE AB The oxidation of 2'-7'-dichlorofluorescin (DCFH) to the fluorescent 2'-7'-dichlorofluorescein (DCF) by horseradish peroxidase (HRP) was investigated by fluorescence, absorption, and electron spin resonance spectroscopy (ESR). As has been previously reported, HRP/H2O2 oxidized DCFH to the highly fluorescent DCF. However, DCF fluorescence was still observed when H2O2 was omitted, although its intensity was reduced by 50%. Surprisingly, the fluorescence increase, in the absence of exogenous H2O2, was still strongly inhibited by catalase, demonstrating that H2O2 was present and necessary for DCF formation. H2O2 was apparently formed during either chemical or enzymatic deacetylation of 2'-7'-dichlorofluorescin diacetate (DCFH-DA), probably by auto-oxidation. Spectrophotometric measurements clearly showed that DCFH could be oxidized either by HRP-compound I or HRP-compound II with the obligate generation of the DCF semiquinone free radical (DCF.-). Oxidation of DCF.- to DCF by oxygen would yield superoxide (O-2(.-)). ESR spectroscopy in conjunction with the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) revealed the presence of both superoxide and hydroxyl radicals in the DCFH/H2O2/HRP system. Both radicals were also detected in the absence of added H2O2, although the intensities of the resultant adducts were decreased. This work demonstrates that DCF fluorescence cannot be used reliably to measure O-2(.-) in cells because O-2(.-) itself is formed during the conversion of DCFH to DCF by peroxidases. The disproportionation of superoxide forms H2O2 which, in the presence of peroxidase activity, will oxidize more DCFH to DCF with self-amplification of the fluorescence. Because the deacetylation of DCFH-DA, even by esterases, can produce H2O2, the use of this probe to measure H2O2 production in cells is problematic. (C) 1999 Elsevier Science Inc. C1 NIEHS, Pharmacol & Chem Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Mason, RP (reprint author), NIEHS, Pharmacol & Chem Lab, NIH, F0-01,POB 12233, Res Triangle Pk, NC 27709 USA. NR 45 TC 256 Z9 260 U1 1 U2 35 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 PY 1999 VL 27 IS 7-8 BP 873 EP 881 DI 10.1016/S0891-5849(99)00137-9 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 240ZM UT WOS:000082856700017 PM 10515592 ER PT J AU Heitman, J Allen, B Alspaugh, JA Kwon-Chung, KJ AF Heitman, J Allen, B Alspaugh, JA Kwon-Chung, KJ TI On the origins of congenic MAT alpha and MATa strains of the pathogenic yeast Cryptococcus neoformans SO FUNGAL GENETICS AND BIOLOGY LA English DT Review DE C-neoformans; basidiomycete; mating; sexual cycle; fungal pathogen; mycology ID KARYOTYPES; GENE AB The basidiomycetous yeast Cryptococcus neoformans infects humans and causes a meningoencephalitis that is uniformly fatal if untreated. The organism has a defined sexual cycle involving mating of haploid MATa and MAT alpha strains, gene disruption by transformation and homologous recombination is now readily accomplished, and robust animal models for infection have been well established. In addition, a pair of congenic MAT alpha and MATa haploid strains have been constructed that permit detailed studies on physiology and virulence by classical genetic approaches. These strains represent a valuable resource for further studies in this organism, and the genomic sequence of one of these strains, JEC21 (=B-4500), was recently chosen to be sequenced by an international consortium. Because of the importance of these strains for genetic studies in C, neoformans and the fact that the genomic sequence of one of these strains is in progress, we review here how these congenic strains were originally constructed, (C) 1999 academic Press. C1 Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Genet, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Pharmacol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Canc Biol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Microbiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Med, Durham, NC 27710 USA. NIAID, Bethesda, MD 20892 USA. RP Heitman, J (reprint author), Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Genet, 322 Carl Bldg, Durham, NC 27710 USA. FU NIAID NIH HHS [R01 AI39115, R01 AI41937, R01 AI42159] NR 14 TC 62 Z9 62 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1087-1845 J9 FUNGAL GENET BIOL JI Fungal Genet. Biol. PD OCT PY 1999 VL 28 IS 1 BP 1 EP 5 DI 10.1006/fgbi.1999.1155 PG 5 WC Genetics & Heredity; Mycology SC Genetics & Heredity; Mycology GA 252UL UT WOS:000083520600001 PM 10512666 ER PT J AU Ebert, AD Wechselberger, C Brandt, R Martinez-Lacaci, I Bianco, C Salomon, DS AF Ebert, AD Wechselberger, C Brandt, R Martinez-Lacaci, I Bianco, C Salomon, DS TI Importance of EGF-related peptides and their receptors in breast cancer SO GEBURTSHILFE UND FRAUENHEILKUNDE LA German DT Review ID EPIDERMAL-GROWTH-FACTOR; HER2/NEU-OVEREXPRESSING METASTATIC BREAST; TYROSINE KINASE INHIBITOR; MESSENGER-RNA EXPRESSION; FACTOR-ALPHA; PROGNOSTIC-SIGNIFICANCE; MONOCLONAL-ANTIBODY; ESTROGEN-RECEPTOR; GENE-EXPRESSION; ERBB RECEPTORS AB Worldwide, breast cancer is the second leading type of cancer in women. In Germany, nearly 40000 new cases of breast cancer and 15000 deaths are reported each year. Determining the etiological and pathogenetic factors that contribute to breast cancer will provide important insights into the design of novel preventive, diagnostic and therapeutic approaches. One extremely productive avenue is the study of growth factors and their receptors in breast cancer. Different families of growth factors are involved in the regulation of growth, differentiation, transformation and apoptosis as well as angiogenesis, migration and metastasis. The EGF-superfamily is one of the largest known family of growth factors. Members of this family include epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), amphiregulin, betacellulin, epiregulin, and heparin-binding EGF, as well as the Cripto- and heregulin-subfamilies. Activation of specific intracellular signaling pathways by EGF-related growth factors occurs by activation of the type I EGF receptor-related erb B-tyrosine kinase family. The EGF-receptor family consists of erb B (EGF-receptor, EGF-R), erb B-2 (HER1/neu), erb B-3 (HER3/neu) and erb B-4 (HER4/neu). It is well established that the overexpression of the EGF-R or erb B-2 is correlated with a more aggressive tumor behavior and is one of the more unfavorable prognostic markers in breast cancer. The erb B-receptors are important targets for novel therapeutic approaches as evidenced by the fact that Herceptin(TM), a humanized monoclonal antibody generated against erb B-2, has been shown to be therapeutically effective in advanced human breast cancer. In the forseeable future, the modern arsenal of breast cancer treatment will be supplemented by effective, biological-oriented therapeutic modalities. C1 Free Univ Berlin, Klinikum Benjamin Franklin, Frauenklin, D-12200 Berlin, Germany. Free Univ Berlin Poliklin, Klinikum Benjamin Franklin, D-12200 Berlin, Germany. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Novartis Pharma Inc, Oncol Pharmacol, Basel, Switzerland. RP Ebert, AD (reprint author), Free Univ Berlin, Klinikum Benjamin Franklin, Frauenklin, Hindenburgdamm 30, D-12200 Berlin, Germany. NR 133 TC 0 Z9 0 U1 3 U2 5 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0016-5751 J9 GEBURTSH FRAUENHEILK JI Geburtshilfe Frauenheilkd. PD OCT PY 1999 VL 59 IS 10 BP 495 EP 506 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 245LP UT WOS:000083110400003 ER PT J AU Auerbach, JD AF Auerbach, JD TI From the SWS president - Gender as proxy SO GENDER & SOCIETY LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Auerbach, JD (reprint author), NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-2432 J9 GENDER SOC JI Gend. Soc. PD OCT PY 1999 VL 13 IS 5 BP 581 EP 583 DI 10.1177/089124399013005001 PG 3 WC Sociology; Women's Studies SC Sociology; Women's Studies GA 239WX UT WOS:000082793900001 ER PT J AU Kuschak, TI Taylor, C McMillan-Ward, E Israels, S Henderson, DW Mushinski, JF Wright, JA Mai, S AF Kuschak, TI Taylor, C McMillan-Ward, E Israels, S Henderson, DW Mushinski, JF Wright, JA Mai, S TI The ribonucleotide reductase R2 gene is a non-transcribed target of c-Myc-induced genomic instability SO GENE LA English DT Article DE extrachromosomal elements; gene amplification; oncogenes; ribonucleotide reductase; tumorigenesis ID ORNITHINE DECARBOXYLASE; DIHYDROFOLATE-REDUCTASE; MALIGNANT TRANSFORMATION; AMPLIFICATION; CELLS; MOUSE; OVEREXPRESSION; EXPRESSION; ONCOGENES; DNA AB The c-Myc oncoprotein is highly expressed in malignant cells of many cell types, but the mechanism by which it contributes to the transformation process is not fully understood. Here, we show for the first time that constitutive or activated overexpression of the c-myc gene in cultured mouse B lymphocytes is followed by chromosomal and extrachromosomal amplification as well as rearrangement of the ribonucleotide reductase R2 gene locus. Electron micrographs and fluorescent in situ hybridization (FISH) demonstrate the c-Myc-dependent generation of extrachromosomal elements, some of which contain R2 sequences. However, unlike other genes that have been shown to be targets of c-Myc-dependent genomic instability, amplification of the R2 gene is not associated with alterations in R2 mRNA or protein expression. These data suggest that c-Myc-dependent genomic instability involves a greater number of genes than previously anticipated, but not all of the genes that are amplified in this system are transcriptionally upregulated. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. Manitoba Canc Treatment & Res Fdn, Winnipeg, MB R3E 0V9, Canada. Univ Manitoba, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada. Univ Manitoba, Dept Pediat, Winnipeg, MB R3E 0V9, Canada. NCI, Mol Genet Sect, Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Dept Human Genet, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Biochem & Mol Biol, Winnipeg, MB R3E 0V9, Canada. Univ Manitoba, Dept Physiol, Winnipeg, MB R3E 0V9, Canada. Sunnybrook Hlth Sci Ctr, GeneSense Technol Inc, Toronto, ON M4N 3M5, Canada. RP Mai, S (reprint author), Manitoba Inst Cell Biol, 100 Olivia St, Winnipeg, MB R3E 0V9, Canada. RI Mai, Sabine/E-5667-2017; OI Mai, Sabine/0000-0002-5797-2201; Israels, Sara/0000-0002-1849-4825 NR 39 TC 23 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 1 PY 1999 VL 238 IS 2 BP 351 EP 365 DI 10.1016/S0378-1119(99)00341-8 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 244XL UT WOS:000083076000008 PM 10570963 ER PT J AU Lin, Y Devin, A Rodriguez, Y Liu, ZG AF Lin, Y Devin, A Rodriguez, Y Liu, ZG TI Cleavage of the death domain kinase RIP by Caspase-8 prompts TNF-induced apoptosis SO GENES & DEVELOPMENT LA English DT Article DE TNF; apoptosis; NF-kappa B; RIP; caspase ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; INDUCED CELL-DEATH; FACTOR-ALPHA; SIGNALING COMPLEX; ACTIVATION; RECEPTOR; PROTEIN; FAS; TRAF2 AB Although the molecular mechanisms of TNF signaling have been largely elucidated, the principle that regulates the balance of life and death is still unknown. We report here that the death domain kinase RIP, a key component of the TNF signaling complex, was cleaved by Caspase-8 in TNF-induced apoptosis. The cleavage site was mapped to the aspartic acid at position 324 of RIP. We demonstrated that the cleavage of RIP resulted in the blockage of TNF-induced NF-kappa B activation. RIPc, one of the cleavage products, enhanced interaction between TRADD and FADD/MORT1 and increased cells' sensitivity to TNF. Most importantly, the Caspase-8 resistant RIP mutants protected cells against TNF-induced apopotosis. These results suggest that cleavage of RIP is an important process in TNF-induced apoptosis. Further more, RIP cleavage was also detected in other death receptor-mediated apoptosis. Therefore, our study provides a potential mechanism to convert cells from life to death in death receptor-mediated apoptosis. C1 NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NR 61 TC 430 Z9 440 U1 2 U2 10 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 1999 VL 13 IS 19 BP 2514 EP 2526 DI 10.1101/gad.13.19.2514 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 250GY UT WOS:000083381700006 PM 10521396 ER PT J AU Galperin, MY Koonin, EV AF Galperin, MY Koonin, EV TI Functional genomics and enzyme evolution - Homologous and analogous enzymes encoded in microbial genomes SO GENETICA LA English DT Article ID ESCHERICHIA-COLI; HYPERTHERMOPHILIC ARCHAEON; MYCOPLASMA-GENITALIUM; HELICOBACTER-PYLORI; PYROCOCCUS-FURIOSUS; BACTERIAL GENOMES; PROTEIN SEQUENCES; GENE; CLONING; OXIDOREDUCTASES AB Computational analysis of complete genomes, followed by experimental testing of emerging hypotheses - the area of research often referred to as 'functional genomics' - aims at deciphering the wealth of information contained in genome sequences and at using it to improve our understanding of the mechanisms of cell function. This review centers on the recent progress in the genome analysis with special emphasis on the new insights in enzyme evolution. Standard methods of predicting functions for new proteins are listed and the common errors in their application are discussed. A new method of improving the functional predictions is introduced, based on a phylogenetic approach to functional prediction, as implemented in the recently constructed Clusters of Orthologous Groups (COG) database (available at http://www.ncbi.nlm.nih.gov/COG). This approach provides a convenient way to characterize the protein families (and metabolic pathways) that are present or absent in any given organism. Comparative analysis of microbial genomes based on this approach shows that metabolic diversity generally correlates with the genome size-parasitic bacteria code for fewer enzymes and lesser number of metabolic pathways than their free-living relatives. Comparison of different genomes reveals another evolutionary trend, the non-orthologous gene displacement of some enzymes by unrelated proteins with the same cellular function. An examination of the phylogenetic distribution of such cases provides new clues to the problems of biochemical evolution, including evolution of glycolysis and the TCA cycle. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 54 TC 47 Z9 48 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0016-6707 J9 GENETICA JI Genetica PD OCT PY 1999 VL 106 IS 1-2 BP 159 EP 170 DI 10.1023/A:1003705601428 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 248LE UT WOS:000083275400018 PM 10710722 ER PT J AU Kleymenova, EV DeClue, JE Walker, CL AF Kleymenova, EV DeClue, JE Walker, CL TI Genetic variants of the tuberous sclerosis 2 tumour suppressor gene in mouse t haplotypes SO GENETICAL RESEARCH LA English DT Article ID T/T COMPLEX; CHROMOSOME-17; REGION; IDENTIFICATION; EVOLUTION; CLONING; PRODUCT AB The murine t complex on chromosome 17 contains a number of homozygous lethal and semi-lethal mutations that disrupt development of the mouse embryo. We recently characterized an embryonic lethality in the rat that results from a germ-line mutation in the tuberous sclerosis 2 (Tsc-2) tumour suppressor gene (the Eker mutation). Remarkably, mouse embryos homozygous for t(w8) mutation display cranial defects reminiscent of those observed in rat embryos homozygous for the Eker mutation. To determine whether the Tsc-2 gene, which is in the t complex, is mutated in t(w8) or other t haplotypes, we characterized this gene in a series of t haplotype mice. Four Tsc-2 polymorphisms were identified: three in the coding region and one intronic that appeared to be common to all t haplotypes analysed. No evidence was found to argue that the Tsc-2 gene is altered in t(w8) haplotype mice. However, in the t(w5) haplotype we found a G to T mutation in Tsc-2 that was present only in this t haplotype. In contrast to other polymorphisms within the Tsc-2 coding region which did not result in amino acid changes in Tsc-2 gene product tuberin, this mutation substituted a phenylalanine for a conserved cysteine in t(w5) tuberin. Within the t complex, the Tsc-2 gene and the putative t(w5) locus appeared to map to different positions, complicating identification of Tsc-2 as a candidate for the t(w5) locus and suggesting that the G to T mutation in the Tsc-2 gene may have arisen independently of the t(w5) functional mutation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, Smithville, TX 78957 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Kleymenova, EV (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, Pk Rd 1 C, Smithville, TX 78957 USA. FU NCI NIH HHS [CA 63613] NR 25 TC 1 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0016-6723 J9 GENET RES JI Genet. Res. PD OCT PY 1999 VL 74 IS 2 BP 139 EP 144 DI 10.1017/S0016672399003985 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 255HB UT WOS:000083662500004 PM 10584558 ER PT J AU Edskes, HK Hanover, JA Wickner, RB AF Edskes, HK Hanover, JA Wickner, RB TI Mks1p is a regulator of nitrogen catabolism upstream of Ure2p in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; GATA FACTORS; NEGATIVE REGULATOR; FILAMENTOUS GROWTH; SHUTTLE VECTORS; GENE-EXPRESSION; CYCLIC-AMP; YEAST; PROTEIN; SYSTEM AB The supply of nitrogen regulates yeast genes affecting nitrogen catabolism, pseudohyphal growth, and meiotic sporulation. Ure2p of Saccharomyces cerevisiae is a negative regulator of nitrogen catabolism that inhibits Gln3p, a positive regulator of DAL5, and other genes of nitrogen assimilation. Dal5p, the allantoate permease, allows ureidosuccinate uptake (Usa(+)) when cells grow on a poor nitrogen source such as proline. We find that overproduction of Mks1p allows uptake of ureidosuccinate on ammonia and lack of Mks1p prevents uptake of ureidosuccinate or Dal5p expression on proline. Overexpression of Mks1p does not affect cellular levels of Ure2p. An mks1 ure2 double mutant can take up ureidosuccinate on either ammonia or proline. Moreover, overexpression of Ure2p suppresses the ability of Mks1p overexpression to allow ureidosuccinate uptake on ammonia. These results suggest that Mks1p is involved in nitrogen control upstream of Ure2p as follows: NH3(sic) Mks1p(sic) Ure2p(sic) Gln3p --> DAL5. Either overproduction of Mks1p or deletion of MKS1 interferes with pseudohyphal growth. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Rm 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. NR 45 TC 44 Z9 44 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 1999 VL 153 IS 2 BP 585 EP 594 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 244KZ UT WOS:000083051400006 PM 10511541 ER PT J AU Grushcow, JM Holzen, TM Park, KJ Weinert, T Lichten, M Bishop, DK AF Grushcow, JM Holzen, TM Park, KJ Weinert, T Lichten, M Bishop, DK TI Saccharomyces cerevisiae checkpoint genes MEC1, RAD17 and RAD24 are required for normal meiotic recombination partner choice SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; B-TYPE CYCLINS; SYNAPTONEMAL COMPLEX; DNA-DAMAGE; DROSOPHILA-MELANOGASTER; BUDDING YEAST; ATAXIA-TELANGIECTASIA; CHROMOSOME SYNAPSIS; MEIOSIS; REPAIR AB Checkpoint gene function prevents meiotic progression when recombination is blocked by mutations in the recA homologue DMC1. Bypass of dmc1 arrest by mutation of the DNA damage checkpoint genes MEC1, RAD17 or RAD24 results in a dramatic loss of spore viability, suggesting that these genes play an important role in monitoring the progression of recombination. We show here that the role of mitotic checkpoint genes in meiosis is not limited to maintaining arrest in abnormal meioses; mec1-1, rad24, and rad17 single mutants have additional meiotic defects. All three mutants display Zip1 polycomplexes in two- to threefold more nuclei than observed in wild-type controls, suggesting that synapsis may be aberrant. Additionally, all three mutants exhibit elevated levels of ectopic recombination in a novel physical assay. rad17 mutants also alter the fraction of recombination events that are accompanied by an exchange of flanking markers. Crossovers are associated with up to 90% of recombination events for one pair of alleles in rad17, as compared with 65% in wild type. Meiotic progression is not required to allow ectopic recombination in rad17 mutants, as it still occurs at elevated levels in ndt80 mutants that arrest in prophase regardless of checkpoint signaling. These observations support the suggestion that MEC1, RAD17, and RAD24, in addition to their proposed monitoring function, act to promote normal meiotic recombination. C1 Univ Chicago, Med Ctr, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. NCI, Biochem Lab, Div Canc Biol Diag & Ctr, Bethesda, MD 20892 USA. RP Bishop, DK (reprint author), Univ Chicago, Med Ctr, Dept Radiat & Cellular Oncol, 5841 S Maryland Ave,MC1105, Chicago, IL 60637 USA. RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 FU NIGMS NIH HHS [GM50936] NR 60 TC 100 Z9 104 U1 0 U2 4 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 1999 VL 153 IS 2 BP 607 EP 620 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 244KZ UT WOS:000083051400008 PM 10511543 ER PT J AU Cheung, VG Dalrymple, HL Narasimhan, S Watts, J Schuler, G Raap, AK Morley, M Bruzel, A AF Cheung, VG Dalrymple, HL Narasimhan, S Watts, J Schuler, G Raap, AK Morley, M Bruzel, A TI A resource of mapped human bacterial artificial chromosome clones SO GENOME RESEARCH LA English DT Article ID HUMAN-GENOME; RESOLUTION AB To date, despite the increasing number of genomic tools, there is no repository of ordered human BAC clones that covers entire chromosomes. This project presents a resource of mapped large DNA fragments that span eight human chromosomes at similar to 1-Mb resolution. These DNA fragments are bacterial artificial chromosome (BAC) clones anchored to sequence tagged site (STS) markers. This clone collection, which currently contains 759 mapped clones, is useful in a wide range of applications from microarray-based gene mapping to identification of chromosomal mutations. In addition to the clones themselves, we describe a database, GenMapDB (http://genomics.med.upenn.edu/genmapdb), that contains information about each clone in our collection. C1 Univ Penn, Childrens Hosp, Dept Pediat, Philadelphia, PA 19104 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands. RP Cheung, VG (reprint author), Univ Penn, Childrens Hosp, Dept Pediat, Philadelphia, PA 19104 USA. FU NHGRI NIH HHS [HG01880, R01 HG001880]; NIDCD NIH HHS [DC00154] NR 10 TC 11 Z9 12 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 1999 VL 9 IS 10 BP 989 EP 993 DI 10.1101/gr.9.10.989 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 246JR UT WOS:000083161100009 PM 10523527 ER PT J AU Feingold, EA Penny, LA Nienhuis, AW Forget, BG AF Feingold, EA Penny, LA Nienhuis, AW Forget, BG TI An olfactory receptor gene is located in the extended human beta-globin gene cluster and is expressed in erythroid cells SO GENOMICS LA English DT Article ID LOCUS ACTIVATION REGION; HEREDITARY PERSISTENCE; FETAL HEMOGLOBIN; ODORANT RECEPTOR; CHROMATIN STRUCTURE; MESSENGER-RNA; HUMAN GENOME; FAMILY; DELETION; IDENTIFICATION AB An olfactory receptor gene was identified near the 3' breakpoint of a naturally occurring deletion (HPFH-1) in the human beta-globin gene cluster on chromosome 11p15.5. The gene encodes an amino acid sequence that is 40 to 51% identical to that of a set of olfactory receptors that have only recently been identified as a distinct family of receptors. There are two orthologous genes in the mouse that encode amino acid sequences that are 73 and 71% identical, respectively, to that encoded by the human gene. This olfactory receptor gene is expressed at the RNA level in human and murine erythroid cells at all stages of development. This aberrant expression is probably due to the location of the gene in the transcriptionally active chromatin domain of the extended beta-globin gene cluster in erythroid cells. (C) 1999 Academic Press. C1 Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. NHLBI, Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Forget, BG (reprint author), Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. NR 58 TC 47 Z9 50 U1 0 U2 0 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 1999 VL 61 IS 1 BP 15 EP 23 DI 10.1006/geno.1999.5935 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 247JQ UT WOS:000083218000003 PM 10512676 ER PT J AU McCallion, P Toseland, RW Lacey, D Banks, S AF McCallion, P Toseland, RW Lacey, D Banks, S TI Educating nursing assistants to communicate more effectively with nursing home residents with dementia SO GERONTOLOGIST LA English DT Article DE nursing home; nursing assistant; dementia; intervention ID GLOBAL DETERIORATION SCALE; ALZHEIMERS-DISEASE; CARE; PROGRAM; FACILITIES; VALIDATION; THERAPY; STAFF AB This article describes the development and evaluation of a Nursing Assistant Communication Skills Program (NACSP). NACSP was designed to help nursing assistants (NAs) interact more effectively with nursing home residents with moderate and severe dementia. In two skilled-care nursing homes, NAs in four units were randomly assigned by unit to NACSP or to a wait-list control condition (UC) and were assessed at baseline, 3 months, and 6 months. NACSP resulted in improvement in the well-being of nursing home residents being cared for by NAs who had received the NACSP training. It was also found that NACSP resulted in greater knowledge of caregiving responses and reduced turnover rates among NAs, but the program had no impact on their knowledge of dementia. To disseminate the NACSP program, a leader manual, an accompanying training videotape, and a workbook for participants were developed. C1 SUNY Albany, Sch Social Welf, Ringel Inst Gerontol, Albany, NY 12222 USA. NIH, New York State Off Mental Hlth, Bethesda, MD 20892 USA. NIH, Crit Care Med Div, Bethesda, MD 20892 USA. RP McCallion, P (reprint author), SUNY Albany, Sch Social Welf, Ringel Inst Gerontol, Albany, NY 12222 USA. NR 46 TC 94 Z9 96 U1 0 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 1999 VL 39 IS 5 BP 546 EP 558 PG 13 WC Gerontology SC Geriatrics & Gerontology GA 331UU UT WOS:000088037700004 PM 10568079 ER PT J AU Proia, RL AF Proia, RL TI Functions of glycosphingolipids as revealed by gene targeting SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1999 VL 9 IS 10 MA 41 BP 1110 EP 1110 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240DF UT WOS:000082810000056 ER PT J AU Stone, AL Longas, MO AF Stone, AL Longas, MO TI Structure-function relations of heparin-mimetic sulfated glucuronoxylyl-oligosaccharides isolated by a combinatorial-type approach vs antiviral and anti-thrombin target functions: Proton NMR studies SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Purdue Univ, Dept Chem & Phys, Calumet Hammond, IN 46323 USA. NICHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1999 VL 9 IS 10 MA 73 BP 1119 EP 1119 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240DF UT WOS:000082810000088 ER PT J AU Ramakrishnan, B Qasba, PK AF Ramakrishnan, B Qasba, PK TI Conversion f Gal-T1 to Galt4: Alpha-lactalbumin dependent galactosyltransferase activity of phe mutants of bovine Gal-T1 SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Glycobiol Sect, LECB,DBS, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1999 VL 9 IS 10 MA 103 BP 1127 EP 1127 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240DF UT WOS:000082810000118 ER PT J AU Boeggeman, EE Qasba, PK AF Boeggeman, EE Qasba, PK TI Effects of metal ions on beta 4Gal-T1 activity SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. SAIC, Frederick, MD 21702 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1999 VL 9 IS 10 MA 110 BP 1129 EP 1129 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240DF UT WOS:000082810000125 ER PT J AU Qasba, PK Ramakrishnan, B Shah, PS AF Qasba, PK Ramakrishnan, B Shah, PS TI Alpha-lactalbumin stimulates milk beta-1,4-galactosyltransferase (Gal-T1) to transfer glucose from UDP-Glucose to N-acetylglucosamine: Involvement of trp 198 of Gal-T1 in the interactions with alpha-lactalbumin SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Bethesda, MD 20892 USA. NCI, DBS, LECB, Struct Glycobiol Sect, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1999 VL 9 IS 10 MA 109 BP 1129 EP 1129 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240DF UT WOS:000082810000124 ER PT J AU Suzuki, N Johnson, JR Chen, HC Lee, YC AF Suzuki, N Johnson, JR Chen, HC Lee, YC TI Major glycoproteins derived from pigeon egg white are inhibitors of uropathogenic E-coli expressing P Fimbriae binding to Gal alpha 1-4Gal SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Johns Hopkins Univ, McCollum Pratt Inst, Baltimore, MD 21218 USA. Univ Minnesota, Dept Med Infect Dis, Vet Adm Med Ctr, Minneapolis, MN 55417 USA. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1999 VL 9 IS 10 MA 143 BP 1138 EP 1139 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240DF UT WOS:000082810000158 ER PT J AU Hepbildikler, ST Proia, RL Sandhoff, K AF Hepbildikler, ST Proia, RL Sandhoff, K TI Enzymatic characterization of human lysosomal beta-hexosaminidase S SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. NIDDK, Sect Biochem Genet, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1999 VL 9 IS 10 MA 194 BP 1153 EP 1154 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240DF UT WOS:000082810000209 ER PT J AU Zapka, J Estabrook, B Gilliland, J Leviton, L Meischke, H Melville, S Taylor, J Daya, M Laing, B Meshack, A Reyna, R Robbins, M Hand, M Finnegan, J AF Zapka, J Estabrook, B Gilliland, J Leviton, L Meischke, H Melville, S Taylor, J Daya, M Laing, B Meshack, A Reyna, R Robbins, M Hand, M Finnegan, J TI Health care providers' perspectives on patient delay for seeking care for symptoms of acute myocardial infarction SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID PREVENTIVE SERVICES; CARDIOVASCULAR-DISEASE; THROMBOLYTIC THERAPY; CONTROLLED TRIAL; HEART-ATTACK; INTERVENTION; PHYSICIANS; EDUCATION; OUTCOMES; PROGRAM AB To inform intervention development in a multisite randomized community trial, the Rapid Early Action for Coronary Treatment (REACT) project formative research was undertaken for the purpose of investigating the knowledge, beliefs, perceptions, and usual practice of health care professionals. A total of 24 key informant interviews of cardiologists and emergency physicians and 15 focus groups (91 participants) were conducted in five major geographic regions: Northeast, Northwest, Southeast, Southwest, and Midwest, Transcript analyses revealed that clinicians are somewhat unaware of the empirical evidence related to the problem of patient delay, are concerned about the practice constraints they face, and would benefit from concrete suggestions about how to improve patient education and encourage fast action. Findings provide guidance for selection of educational strategies and messages for health providers as well as patients and the public. C1 Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. Univ Alabama, Sch Med, Birmingham, AL 35233 USA. Texas Dept Hlth, Bur HIV & STD, Austin, TX 78756 USA. Univ Alabama, Tuscaloosa, AL 35401 USA. Oregon Hlth Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77225 USA. Univ Texas, Ctr Hlth Promot, Austin, TX 78712 USA. Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. NHLBI, Off Prevent Educ & Control, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. RP Zapka, J (reprint author), Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. FU NHLBI NIH HHS [U01-HL-53141, U01-HL-53149, U01-HL-53412] NR 48 TC 13 Z9 13 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 1999 VL 26 IS 5 BP 714 EP 733 DI 10.1177/109019819902600511 PG 20 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 236UD UT WOS:000082616800010 PM 10533175 ER PT J AU Conner, EA Lemmer, ER Sanderson, ND Factor, VM Omori, M Wirth, PJ Thorgeirsson, SS AF Conner, EA Lemmer, ER Sanderson, ND Factor, VM Omori, M Wirth, PJ Thorgeirsson, SS TI Overexpression of transcription factor E2F-1 in the liver causes hepatocellular carcinoma in mice. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 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 1999 VL 30 IS 4 SU S MA 588 BP 307A EP 307A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700586 ER PT J AU Kawai, HF Furuke, K Gagneten, S Kaneko, S Harris, C Feinstone, SM AF Kawai, HF Furuke, K Gagneten, S Kaneko, S Harris, C Feinstone, SM TI Hepatitis C virus core protein confers growth advantage and specific protection from TNF-alpha mediated cell death on immortalizednormal human hepatocyte cell line but does not change cell cycle profile nor NF-kappa B activation status. SO HEPATOLOGY LA English DT Meeting Abstract C1 Kanazawa Univ, Sch Med, Kanazawa, Ishikawa 920, Japan. US FDA, Bethesda, MD 20014 USA. NCI, Bethesda, MD 20892 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 1999 VL 30 IS 4 SU S MA 619 BP 315A EP 315A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700616 ER PT J AU Monga, PS Weinstein, M Rashid, A Tang, Y Iqbal, S Deng, CX Mishra, L AF Monga, PS Weinstein, M Rashid, A Tang, Y Iqbal, S Deng, CX Mishra, L TI 3147 essential cooperative function of TGF beta signalling molecules SMAD2/3 for liver formation can be rescued by HGF. SO HEPATOLOGY LA English DT Meeting Abstract C1 VAMC, Fels Canc Inst, Philadelphia, PA USA. NIDDK, NIH, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, 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 1999 VL 30 IS 4 SU S MA 629 BP 318A EP 318A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700631 ER PT J AU Chiang, JY Kimmel, R Weinberger, C Stroup, D AF Chiang, JY Kimmel, R Weinberger, C Stroup, D TI Farnesoid X receptor (FXR) is a bile acid receptor that mediates transcriptional regulation of the cholesterol 7 alpha-hydroxylase gene (CYP7A1) by bile acids SO HEPATOLOGY LA English DT Meeting Abstract C1 NE Ohio Univ, Coll Med, Rootstown, OH 44272 USA. NIEHS, Res Triangle Pk, NC 27709 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 1999 VL 30 IS 4 SU S MA 633 BP 319A EP 319A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700635 ER PT J AU Kono, H Rusyn, I Bladford, BU Segel, B Holland, SM Thurman, RG AF Kono, H Rusyn, I Bladford, BU Segel, B Holland, SM Thurman, RG TI Kupffer cell nadph oxidase plays an important role in early alcohol-induced liver injury in mice SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. NIH, Bethesda, MD 20892 USA. RI Rusyn, Ivan/S-2426-2016 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 1999 VL 30 IS 4 SU S MA 702 BP 336A EP 336A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700701 ER PT J AU Forns, X Payette, PJ Ma, XY Emerson, SU Davis, H Mushahwar, I Purcell, RH Bukh, J AF Forns, X Payette, PJ Ma, XY Emerson, SU Davis, H Mushahwar, I Purcell, RH Bukh, J TI DNA immunization of macaques and chimpanzees with plasmids encoding hepatitis C virus (HCV) envelope E2 protein. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID, Hepatitis Viruses Sect, LID, NIH, Bethesda, MD 20892 USA. Ottawa Civic Hosp, Loeb Res Inst, Ottawa, ON K1Y 4E9, Canada. Abbott Labs, Virus Discovery Grp, Chicago, IL 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 1999 VL 30 IS 4 SU S MA 769 BP 353A EP 353A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700768 ER PT J AU Lin, HJ Seeff, LB Barbosa, L Hollinger, FB AF Lin, HJ Seeff, LB Barbosa, L Hollinger, FB TI Hypervariable region 1 of the hepatitis C virus (HCV) genome in infected transfusion recipients and their respective donors. SO HEPATOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. NHLBI, 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 1999 VL 30 IS 4 SU S MA 793 BP 359A EP 359A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700792 ER PT J AU Manickan, E Satoi, J Thomson, M Liang, JT AF Manickan, E Satoi, J Thomson, M Liang, JT TI Regulated liver-specific expression of transgene in mice using the tetracycline-inducible system. SO HEPATOLOGY LA English DT Meeting Abstract C1 Natl Inst Hlth, 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 1999 VL 30 IS 4 SU S MA 925 BP 392A EP 392A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700924 ER PT J AU Liu, JJ Park, RT Liu, YP Klaassen, CD Waalkes, MP Park, RT Anderson, S Corton, C AF Liu, JJ Park, RT Liu, YP Klaassen, CD Waalkes, MP Park, RT Anderson, S Corton, C TI Gene expression pattern in mice and rats produced by the hepatoprotectant oleanolic acid. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIEHS, NCI, Res Triangle Pk, NC USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. CIIT, Res Triangle Pk, NC 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 1999 VL 30 IS 4 SU S MA 948 BP 397A EP 397A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700947 ER PT J AU Mishra, L Monga, PP Rashid, A Danovitch, S Fleury, T Iqbal, SA Tang, Y Deng, CX Mishra, B AF Mishra, L Monga, PP Rashid, A Danovitch, S Fleury, T Iqbal, SA Tang, Y Deng, CX Mishra, B TI 3147 disruption of TGF beta signaling by SMAD2, SMAD3 and ELF spectrins in primary biliary cirrhosis. SO HEPATOLOGY LA English DT Meeting Abstract C1 Temple Univ, VAMC, Fels Inst, Philadelphia, PA 19122 USA. JHU, Baltimore, MD USA. GWU, Washington, DC USA. Sibley Hosp, Washington, DC USA. Temple Univ, DVAMC, Fels Inst, Philadelphia, PA 19122 USA. NIDDK, NIH, Bethesda, MD USA. NHGRI, CGTB, 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 1999 VL 30 IS 4 SU S MA 964 BP 401A EP 401A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700963 ER PT J AU Arichi, T Saito, T Major, ME Shirai, M Engelhard, VH Feinstone, SM Berzofsky, JA AF Arichi, T Saito, T Major, ME Shirai, M Engelhard, VH Feinstone, SM Berzofsky, JA TI A DNA vaccine as a prophylaxis for hepatitis C virus (HCV) infection. HCV specific CTL induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. Univ Virginia, Charlottesville, VA 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 1999 VL 30 IS 4 SU S MA 994 BP 409A EP 409A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700994 ER PT J AU Chang, KM Thimme, R Melpolder, J Pemberton, J Moorhead-Loudis, J McHutchison, JG Alter, HJ Chisari, FV AF Chang, KM Thimme, R Melpolder, J Pemberton, J Moorhead-Loudis, J McHutchison, JG Alter, HJ Chisari, FV TI Differential CD4 and CD8 T cell responses to HCV in chronically infected patients and in spontaneously recovered patients. SO HEPATOLOGY LA English DT Meeting Abstract C1 Scripps Res Inst, La Jolla, CA USA. Natl Inst Hlth, Bethesda, MD USA. Natl Inst Hlth, Bethesda, MD 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 1999 VL 30 IS 4 SU S MA 997 BP 410A EP 410A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700996 ER PT J AU Thimme, R Guidotti, LG Bukh, J Koch, R Pemberton, J Purcell, RH Chisari, FV AF Thimme, R Guidotti, LG Bukh, J Koch, R Pemberton, J Purcell, RH Chisari, FV TI Different intrahepatic cytoknie priles during acure HBV and HCV infection in the same chimpanzees. SO HEPATOLOGY LA English DT Meeting Abstract C1 Scripps Res Inst, La Jolla, CA USA. Natl Inst Hlth, Bethesda, MD 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 1999 VL 30 IS 4 SU S MA 1000 BP 410A EP 410A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700999 ER PT J AU Wedemeyer, H He, XS Davis, AR Ghany, M Lau, D Davis, MM Greenberg, H Alter, H Liang, TJ Hoofnagle, J Rehermann, B AF Wedemeyer, H He, XS Davis, AR Ghany, M Lau, D Davis, MM Greenberg, H Alter, H Liang, TJ Hoofnagle, J Rehermann, B TI A strong TCl recall response is mediated by a small number of circulating CTL after recovery from hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract C1 Stanford Univ, Palo Alto, CA 94304 USA. NIDDK, LDS, NIH, Bethesda, MD USA. NIH, Dept Blood Trasnfus, 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 1999 VL 30 IS 4 SU S MA 998 BP 410A EP 410A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700998 ER PT J AU Forns, X Emerson, SU Purcell, RH Bukh, J AF Forns, X Emerson, SU Purcell, RH Bukh, J TI Deletion mutant of hepatitis C virus (HCV) molecular infectious clone lacking the hypervariable region 1 (HVR1) is viable but attenuated in vivo. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID, Hepatitis Viruses Sect, LID, NIH, Bethesda, MD USA. NIAID, Mol Hepatitis Sect, LID, NIH, Bethesda, MD USA. NR 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1046 BP 422A EP 422A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701046 ER PT J AU Lopez-Labrador, FX He, XS Berenguer, M Lu, Y Boisvert, J Cheung, R Rehermann, BR Davis, MM Wright, T Greenberg, H AF Lopez-Labrador, FX He, XS Berenguer, M Lu, Y Boisvert, J Cheung, R Rehermann, BR Davis, MM Wright, T Greenberg, H TI Direct visualisation of hepatitis C virus-specific cytotoxic T cells using peptide-MHC tetramers and analysis of aminoacid variations within the viral epitope. SO HEPATOLOGY LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Vet Adm Med Ctr, Stanford, CA 94305 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIDDKD, 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 1999 VL 30 IS 4 SU S MA 1047 BP 422A EP 422A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701045 ER PT J AU Thimme, R Bukh, J Chang, KM Pemberton, J Purcell, RH Chisari, FV AF Thimme, R Bukh, J Chang, KM Pemberton, J Purcell, RH Chisari, FV TI HCV persists despite a multispecific peripheral and intrahepatic T cell response in acutely infected chimpanzees. 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 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 1999 VL 30 IS 4 SU S MA 1048 BP 422A EP 422A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701047 ER PT J AU Ros, JE Geuken, M Larusso, NF Thorgeirsson, SS Jansen, PL Muller, M AF Ros, JE Geuken, M Larusso, NF Thorgeirsson, SS Jansen, PL Muller, M TI ABC-transporter gene expression in cholangiocytes and hepatic oval cells reveals a multidrug resistance phenotype. SO HEPATOLOGY LA English DT Meeting Abstract C1 GUIDE, Div Gastroenterol & Hepatol, Groningen, Netherlands. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. NCI, Expt Carcinogenesis Lab, 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 1999 VL 30 IS 4 SU S MA 1087 BP 432A EP 432A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701084 ER PT J AU Torii, N Zhang, ZS Hu, ZY Liang, J AF Torii, N Zhang, ZS Hu, ZY Liang, J TI Structural and functional studies of hepadnavirus X gene in vivo. SO HEPATOLOGY LA English DT Meeting Abstract C1 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 1999 VL 30 IS 4 SU S MA 1114 BP 439A EP 439A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701113 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 Acute resolving monoclonal hepatitis C virus (HCV) infection in a chimpanzee modifies subsequent infections with the homologous monoclonal virus 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 3 Z9 3 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 1999 VL 30 IS 4 SU S MA 1167 BP 452A EP 452A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701164 ER PT J AU Arichi, T Major, M Wedemeyer, H Nascimbeni, M Gagneten, S Kolykhalov, AA Berzofsky, JA Rice, CM Feinstone, SM Rehermann, B AF Arichi, T Major, M Wedemeyer, H Nascimbeni, M Gagneten, S Kolykhalov, AA Berzofsky, JA Rice, CM Feinstone, SM Rehermann, B TI A vigorous HCV-helicase specific T helper response dominates in the liver of a chimpanzee during acute, self-limited hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIDDK, LDS, NIH, Bethesda, MD USA. Washington Univ, St Louis, MO 63130 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 1999 VL 30 IS 4 SU S MA 1171 BP 453A EP 453A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701168 ER PT J AU Lechmann, MT Vergalla, J Satoi, J Thomas, BF Liang, J AF Lechmann, MT Vergalla, J Satoi, J Thomas, BF Liang, J TI Induction of humoral and cellular immune responses in mice by immunization with insect-cell derived HCV-like particles. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1170 BP 453A EP 453A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701169 ER PT J AU Ghany, MG Alter, HJ Melpolder, JC Kleiner, DE Doo, E Conry-Cantilena, C Liang, TJ Hoofnagle, JH AF Ghany, MG Alter, HJ Melpolder, JC Kleiner, DE Doo, E Conry-Cantilena, C Liang, TJ Hoofnagle, JH TI Five-year follow-up of blood donors with antibody to hepatitis C virus: Clinical, biochemical, virological and histological features. 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 1999 VL 30 IS 4 SU S MA 1355 BP 499A EP 499A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701352 ER PT J AU Lau, DT Maertens, G Hoofnagle, JH AF Lau, DT Maertens, G Hoofnagle, JH TI Humoral immune response in hepatitis C infection: Fall in anti-HCV levels among long-term sustained responders to interferon therapy. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. Innogenet, Ghant, Belgium. NIH, Bethesda, MD 20892 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 1999 VL 30 IS 4 SU S MA 1357 BP 500A EP 500A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701355 ER PT J AU Brouwer, KL Amos, PL Booth, CL Lecluyse, EL Stieger, B Meier, PJ AF Brouwer, KL Amos, PL Booth, CL Lecluyse, EL Stieger, B Meier, PJ TI Time-course of bile acid, organic anion and organic cation transporter expression in rat hepatocytes cultured for 5 days in a collagen-sandwich configuration. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Zurich Hosp, Dept Med, CH-8091 Zurich, Switzerland. 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 1999 VL 30 IS 4 SU S MA 1484 BP 531A EP 531A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701481 ER PT J AU El-Serag, HB Everhart, JE AF El-Serag, HB Everhart, JE TI Improved survival following esophageal variceal hemorrhage over an 11-year period in the department of veterans affairs (VA). SO HEPATOLOGY LA English DT Meeting Abstract C1 VAMC, Albuquerque, NM USA. Univ New Mexico, Albuquerque, NM 87131 USA. NIDDK, 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 1999 VL 30 IS 4 SU S MA 1670 BP 578A EP 578A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701667 ER PT J AU Herion, DW Arioglu, E Doo, E Kleiner, D Taylor, S Liang, TJ Hoofnagle, J AF Herion, DW Arioglu, E Doo, E Kleiner, D Taylor, S Liang, TJ Hoofnagle, J TI Severe insulin resistance syndromes and NASH. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1713 BP 589A EP 589A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701708 ER PT J AU Park, YM Tabor, E Kim, BS AF Park, YM Tabor, E Kim, BS TI Mutations of precore and proximal core regions of hepatitis B virus genome in serum of hepatocellular carcinoma patients SO HEPATOLOGY RESEARCH LA English DT Article DE HBV; mutant HBV; precore gene mutation; core gene mutation; HCC ID NUCLEOTIDE-SEQUENCE ANALYSIS; CHRONIC ACTIVE HEPATITIS; FULMINANT-HEPATITIS; E-ANTIGEN; LIVER-TRANSPLANTATION; ACUTE EXACERBATION; RECURRENT DISEASE; CHRONIC INFECTION; HBV VARIANTS; MUTANT AB In the present study, genetic alterations of the precore and proximal core regions (codons 1-50) were determined in HBV isolated from the serum of 58 patients with HCC and hepatitis B surface antigen (HBsAg) in their serum to identify any role of such genetic changes in HBV genome for hepatocarcinogenesis. DNA extracted from the serum of 16 patients with chronic hepatitis B but no HCC were used as controls. In HCC patients, mutations of T-1846, C-1858, A(1896), and A(1899) were identified in 48, 5, 86 and 36%, respectively. A(1896) mutation is associated with T-1846 and A(1899) mutations more frequently in HCC patients than in chronic hepatitis B patients. Fourteen mutations of the proximal core region in HBV genomes from HCC patients were observed in codons 5, 13, 21, 22, 26, 27, 31, 35 and 41. The median number of mutations in the proximal core gene was 7 from HBeAg-negative HCCs, 5 in HBeAg-positive HCCs, and 4 in patients with chronic hepatitis B without HCC. These results suggest that mutations of the precore and proximal core gene sequences may preferentially occur in specific nucleotides and the continuous replication of such mutant HBV might play a role in HBV-related hepatocarcinogenesis. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, Bethesda, MD USA. Kangnam St Marys Hosp, Dept Internal Med, Seoul 137040, South Korea. Catholic Univ Korea, Coll Med, WHO,Seocho Ku, Collaborating Ctr Reference & Res Viral Hepatitis, Seoul 137040, South Korea. RP Park, YM (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 38 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD OCT PY 1999 VL 16 IS 1 BP 49 EP 58 DI 10.1016/S1386-6346(99)00038-8 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247BF UT WOS:000083200200006 ER PT J AU Yu, H Wang, LJ Flippen-Anderson, JL Tian, XR Coop, A Rice, KC AF Yu, H Wang, LJ Flippen-Anderson, JL Tian, XR Coop, A Rice, KC TI Synthesis of a novel 7,14 beta-ethano-bridged opiate SO HETEROCYCLES LA English DT Article AB A novel 7,14 beta-ethano-bridged opiate (1) was prepared from the known 14-alkenylcodeinone (3) in two steps. Selective reduction of the enone double bond of 3 followed by ozonolysis led to an aldehyde intermediate, which was cyclized in situ through an intramolecular aldol condensation to give the rigid hexacyclic derivative (1). C1 NIDDKD, Med Chem Lab, Bethesda, MD 20892 USA. USN, Res Lab, Washington, DC 20375 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, Bldg 8,Room B1-23, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD OCT 1 PY 1999 VL 51 IS 10 BP 2343 EP 2347 PG 5 WC Chemistry, Organic SC Chemistry GA 248AP UT WOS:000083253400006 ER PT J AU Ezer, S Bayes, M Elomaa, O Schlessinger, D Kere, J AF Ezer, S Bayes, M Elomaa, O Schlessinger, D Kere, J TI Ectodysplasin is a collagenous trimeric type II membrane protein with a tumor necrosis factor-like domain and co-localizes with cytoskeletal structures at lateral and apical surfaces of cells SO HUMAN MOLECULAR GENETICS LA English DT Review ID HYPOHIDROTIC ECTODERMAL DYSPLASIA; MACROPHAGE SCAVENGER RECEPTORS; XIII-COLLAGEN; FAS-LIGAND; EDA GENE; FAMILY; BINDING; CLONING; SUPERFAMILY; MUTATIONS AB Anhidrotic ectodermal dysplasia (EDA) is a human genetic disorder of impaired ectodermal appendage development. The EDA gene encodes isoforms of a novel transmembrane protein, ectodysplasin. The sequence of the longest isoform includes an interrupted collagenous domain of 19 Gly-X-Y repeats and a motif conserved in the tumor necrosis factor (TNF)-related ligand family, In order to understand better the function of the ectodysplasin protein molecule and its domains, we have studied the processing and localization of wildtype and mutated isoforms in transfected human fetal kidney 293 and monkey kidney COS-1 cells. Similar to other members of collagenous membrane proteins and members of TNF-related ligands, ectodysplasin is a type II membrane protein and it forms trimers. The membrane localization of ectodysplasin is asymmetrical: it is found on the apical and lateral surfaces of the cells where it colocalizes with cytoskeletal structures. The TNF-like motif and cysteines found near the C-terminus are necessary for correct transport to the cell membrane, but the intracellular and collagenous domains are not required for the localization pattern. Our results suggest that ectodysplasin is a new member in the TNF-related ligand family involved in the early epithelial-mesenchymal interaction that regulates ectodermal appendage formation. C1 Univ Helsinki, Finnish Genome Ctr, FIN-00014 Helsinki, Finland. Univ Helsinki, Haartman Inst, Dept Med Genet, FIN-00014 Helsinki, Finland. NIA, Genet Lab, Baltimore, MD 21224 USA. RP Ezer, S (reprint author), Univ Helsinki, Finnish Genome Ctr, POB 21 Tukholmankatu 2, FIN-00014 Helsinki, Finland. RI Kere, Juha/A-9179-2008 OI Kere, Juha/0000-0003-1974-0271 NR 36 TC 96 Z9 104 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1999 VL 8 IS 11 BP 2079 EP 2086 DI 10.1093/hmg/8.11.2079 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 242QM UT WOS:000082952700015 PM 10484778 ER PT J AU Roche, PA AF Roche, PA TI Intracellular protein traffic in lymphocytes: "How do I get THERE from HERE?" SO IMMUNITY LA English DT Review ID TRANS-GOLGI NETWORK; ENDOPLASMIC-RETICULUM; CELL-SURFACE; ANTIGEN PRESENTATION; MEMBRANE-PROTEIN; DENDRITIC CELLS; MOLECULES; COMPLEXES; INTERNALIZATION; ASSOCIATION C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 41 TC 15 Z9 15 U1 1 U2 2 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 1999 VL 11 IS 4 BP 391 EP 398 DI 10.1016/S1074-7613(00)80114-4 PG 8 WC Immunology SC Immunology GA 249QE UT WOS:000083343100001 PM 10549621 ER PT J AU Baas, A Gao, XJ Chelvanayagam, G AF Baas, A Gao, XJ Chelvanayagam, G TI Peptide binding motifs and specificities for HLA-DQ molecules SO IMMUNOGENETICS LA English DT Article DE HLA-DQ; peptide binding; peptide motifs; autoimmune disease ID MAJOR HISTOCOMPATIBILITY COMPLEX; DEPENDENT DIABETES-MELLITUS; MHC PROTEIN HLA-DR1; CLASS-II MOLECULES; CRYSTAL-STRUCTURE; ANTIGEN; IDENTIFICATION; RESIDUES; BETA-1-ASTERISK-0201); SUSCEPTIBILITY AB HLA-DQ molecules have been associated with susceptibility to a number of autoimmune and other diseases, possibly through the peptide repertoire that can be presented by different allelic products. It is thus of importance to understand which peptides can be bound by different HLA-DQ allelic products. Recently, a model for HLA-DQ has been described and used to derive peptide positional environments for HLA-DQ allelic products. By combining the peptide positional environments with known HLA-DQ peptide binding motifs, a set of predictions of likely anchor motifs for many of the products of HLA-De allelic variants are made and presented in a table referred to as a roadmap for HLA-DQ peptide binding specificities. C1 Australian Natl Univ, John Curtin Sch Med Res, Human Genet Grp, Canberra, ACT 0200, Australia. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Chelvanayagam, G (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Human Genet Grp, Mills Rd, Canberra, ACT 0200, Australia. NR 50 TC 22 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD OCT PY 1999 VL 50 IS 1-2 BP 8 EP 15 DI 10.1007/s002510050680 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 249GP UT WOS:000083325200002 PM 10541801 ER PT J AU Sehgal, D Johnson, G Wu, TT Mage, RG AF Sehgal, D Johnson, G Wu, TT Mage, RG TI Generation of the primary antibody repertoire in rabbits: expression of a diverse set of Igk-V genes may compensate for limited combinatorial diversity at the heavy chain locus SO IMMUNOGENETICS LA English DT Article DE rabbit; germline Igk-V genes; expressed Igk-V genes; IGVK families; combinatorial diversity ID KAPPA-LIGHT-CHAINS; J-C LOCUS; REGION GENE; SOMATIC DIVERSIFICATION; VARIABLE REGIONS; HYPERMUTATION MECHANISMS; CONVERSION EVENTS; LYMPHOID-TISSUES; BASILEA RABBITS; ADULT-RABBITS AB In mouse and human, generation of combinatorial diversity through use of different heavy and light chain variable region genes in immunoglobulin rearrangements can be a major contributor to the primary antibody repertoire. In rabbits, the contribution of the combinatorial mechanism to heavy chain diversity is minimal, as only a few Igh-V genes are rearranged and expressed. To investigate the contribution of combinatorial diversity toward generation of the rabbit V-kappa repertoire, we constructed five genomic libraries from rabbit kidney DNA and 1 cDNA library from the bone marrow of a 1-day-old rabbit using a series of polymerase chain reaction-based strategies. Our analyses indicate that most of the sequences that we recovered from our libraries belong to a single family and some are extremely similar. The actual number of germline Igk-V genes is potentially greater than our conservative estimate of at least 39, 28 of which we found expressed as mRNA. The germline Igk-V genes display different lengths of the coding region 3' of Cys 88 ranging from 7 to 12 amino acids, resulting in CDR3 length heterogeneity among functional V(kappa)J(kappa) sequences ranging from 8 to 15 amino acids. Some of the V(kappa)J(kappa) junctions had N and P nucleotide additions. Thus, in contrast to limited combinatorial diversity of its heavy chain, the rabbit can draw upon a diverse set of germline Igk-V genes. The kappa light chain has the potential to be a major contributor toward generation of the antibody specificities of the rabbit pre-immune repertoire. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Wu, Tai/B-7638-2009 FU NIAID NIH HHS [5 R24 AI25616-10] NR 63 TC 30 Z9 31 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD OCT PY 1999 VL 50 IS 1-2 BP 31 EP 42 DI 10.1007/s002510050683 PG 12 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 249GP UT WOS:000083325200005 PM 10541804 ER PT J AU Qian, YM Haino, M Kelly, K Song, WC AF Qian, YM Haino, M Kelly, K Song, WC TI Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55) SO IMMUNOLOGY LA English DT Article ID TRANSMEMBRANE RECEPTOR CD97; COMPLEMENT; ACTIVATION; ANTIGEN; PROTEIN; FAMILY; CARCINOMAS; CLONING; CALCIUM; SURFACE AB CD97 is a newly identified, activation-associated human leucocyte antigen with seven putative transmembrane domains. It has an extended extracellular segment containing several adhesion molecule structure motifs, and has been shown to interact with the human complement regulator, decay-accelerating factor (DAF, CD55). To understand further the interaction between CD97 and DAF, as well as the structure and function of CD97 in general, we have cloned the mouse CD97 cDNA and studied the encoded protein for its membrane association property and ability to interact specifically with the murine decay-accelerating factor. The full-length mouse CD97 cDNA that we have cloned and characterized encodes a protein that is 60% identical to the three epidermal growth factor (EGF) domain-containing form of human CD97 but does not contain the Arg-Gly-Asp (RGD) motif which is present in human CD97. Two other alternatively spliced forms of mouse CD97 were also identified. These forms differ by the number of EGF-like sequence repeats present in the N-terminal region. Northern blot analysis revealed that CD97 is expressed widely in mouse tissues and in resting as well as activated cultured mouse splenocytes. Transient transfection of human embryonic kidney (HEK) 293 cells with the mouse CD97 cDNA in a green-fluorescence protein vector (pEGFP-N1) showed plasma membrane targeting of the expressed protein. Western blot analysis confirmed its membrane association and identified the existence of a processed C-terminal fragment, supporting the notion that CD97 on the cell membrane is composed of post-translationally generated subunits. Adhesion studies demonstrated that normal, but not DAF knockout mouse erythrocytes and splenocytes adhered to mouse CD97-transfected HEK cells. The interaction of CD97 and DAF was found to be species-restrictive in that human erythrocytes were unable to bind to mouse CD97-transfected HEK cells. These results indicate that the general structure, membrane association property and DAF-binding ability of CD97 are conserved and that the adhesive interaction between CD97 and DAF is independent of the RGD motif. The finding that CD97 is distributed widely among various mouse tissues suggests that CD97 may have other roles beyond lymphocyte activation. C1 Univ Penn, Sch Med, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Song, WC (reprint author), Univ Penn, Sch Med, Ctr Expt Therapeut, 1351 BRBII-III,421 Curie Blvd, Philadelphia, PA 19104 USA. NR 26 TC 55 Z9 56 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD OCT PY 1999 VL 98 IS 2 BP 303 EP 311 PG 9 WC Immunology SC Immunology GA 245RT UT WOS:000083122500019 PM 10540231 ER PT J AU Hook, S Camberis, M Prout, M Konig, M Zimmer, A Van Heeke, G Le Gros, G AF Hook, S Camberis, M Prout, M Konig, M Zimmer, A Van Heeke, G Le Gros, G TI Preproenkephalin, is a Th2 cytokine but is not required for Th2 differentiation in vitro SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE IL-4; preproenkephalin; Th2 immune responses ID PROENKEPHALIN-A; MONONUCLEAR-CELLS; MESSENGER-RNA; MET-ENKEPHALIN; T-CELLS; PEPTIDES; EXPRESSION; PROLIFERATION; LYMPHOCYTES AB Preproenkephalin (PPNK) mRNA expression has been detected in many cells of the immune system, including monocytes and lymphocytes. In the present paper. the expression of PPNK mRNA in purified CD4(+) Th1 and Th2 lymphocyte subpopulations is investigated and correlated with the presence of the opioid neuropeptides leu- and met-enkephalin. We found that PPNK mRNA and met-enkephalin were present at higher levels in the Th2 cultures compared with the Th1 cultures. Lymphocytes from PPNK-deficient mice were then used to look at the role of PPNK in Th2 lymphocyte differentiation. Lymphocytes from these mice could be driven into a Th2 phenotype, suggesting that cultures containing IL-4 do not require PPNK for Th2 differentiation. C1 Wellington Sch Med, Malaghan Inst Med Res, Wellington, New Zealand. NIMH, Genet Lab, Unit Mouse Genet, Bethesda, MD 20892 USA. Novartis Horsham Res Ctr, Horsham, W Sussex, England. RP Hook, S (reprint author), Wellington Sch Med, Malaghan Inst Med Res, POB 7060, Wellington, New Zealand. RI Le Gros, Graham/C-6725-2011; Zimmer, Andreas/B-8357-2009 FU Wellcome Trust NR 19 TC 19 Z9 19 U1 0 U2 2 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD OCT PY 1999 VL 77 IS 5 BP 385 EP 390 DI 10.1046/j.1440-1711.1999.00842.x PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 240UW UT WOS:000082845900002 PM 10540203 ER PT J AU Wu, TH Gu, XX AF Wu, TH Gu, XX TI Outer membrane proteins as a carrier for detoxified lipooligosaccharide conjugate vaccines for nontypeable Haemophilus influenzae SO INFECTION AND IMMUNITY LA English DT Article ID NONTYPABLE HEMOPHILUS-INFLUENZAE; OTITIS-MEDIA; IMMUNOLOGICAL PROPERTIES; MOLECULAR-WEIGHT; IMMUNE-RESPONSES; CHAIN-LENGTH; POLYSACCHARIDE; IMMUNOGENICITY; CHINCHILLAS; SERUM AB Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media and respiratory tract infections. Outer membrane proteins (OMP) and lipooligosaccharide (LOS) are major surface antigens of NTHi and potential vaccine candidates. De-O-acylated LOS (dLOS) or oligosaccharide (OS) was coupled to total OMP to form dLOS-OMP and OS-OMP conjugates, while a dLOS-tetanus toroid Fl was synthesized for comparison. These conjugates mere evaluated in mice and rabbits for immunogenicity. dLOS-OMP elicited a better boostable antibody response against LOS than did dLOS-TT, while OS-OMP was not immunogenic. Formulation of the conjugates with Ribi adjuvant significantly enhanced the immunogenicity of dLOS-OMP and dLOS-TT but not that of OS-OMP. In addition, rabbit antisera elicited by dLOS OMP but not dLOS-TT (or OMP alone) demonstrated bactericidal activity against 40% of the NTHi strains tested. These results indicate that dLOS is a better derivative of LOS than OS and that OMP is a good carrier for NTHi LOS-based conjugate vaccines. C1 NIDCD, Immunol Lab, NIH, Rockville, MD 20850 USA. RP Gu, XX (reprint author), NIDCD, Immunol Lab, NIH, 5 Res Court,5A31, Rockville, MD 20850 USA. NR 36 TC 11 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1999 VL 67 IS 10 BP 5508 EP 5513 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 240ET UT WOS:000082813500074 PM 10496940 ER PT J AU Pavliakova, D Chu, CY Bystricky, S Tolson, NW Shiloach, J Kaufman, JB Bryla, DA Robbins, JB Schneerson, R AF Pavliakova, D Chu, CY Bystricky, S Tolson, NW Shiloach, J Kaufman, JB Bryla, DA Robbins, JB Schneerson, R TI Treatment with succinic anhydride improves the immunogenicity of Shigella flexneri type 2a O-specific polysaccharide-protein conjugates in mice SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; SERUM ANTIBODIES; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; DYSENTERIAE TYPE-1; DIARRHEA; ADULTS; TOXIN; LIPOPOLYSACCHARIDE; VACCINES AB Seroepidemiological data and a clinical trial with a Shigella sonnei O-specific polysaccharide (O-SP)Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conjugate provide evidence that a critical level of immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies in serum confers protection against shigellosis. We evaluated the immunogenicity of conjugates whose carrier proteins and O-SPs were treated,vith succinic anhydride (SA), which reacts with amino groups at neutral pH to form amide-linked carboxyls (succinylation). Conjugates were synthesized with either of two genetically inactivated medically useful toxins, the diphtheria protein CRM9 or rEPA, bound to the O-SP of Shigella flexneri type 2a. Conjugates composed of the succinylated protein, succinylated O-SP, or both succinylated components were administered to mice by a clinically relevant scheme, and their levels of serum IgG anti-LPS and anti-proteins were assayed 7 days after the second and third injections. CRM9 served as a more immunogenic carrier than rEPA. Conjugates composed of succinylated components were more immunogenic than the conjugates composed of the native components. SA treatment of both the carrier protein and the O-SP did not confer an advantage over the succinylated protein alone. Conjugates prepared with native proteins, in general, elicited slightly higher levels of IgG protein antibodies than conjugates composed of the SA-treated proteins. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schneerson, R (reprint author), NICHHD, NIH, Bldg 6,Room 424, Bethesda, MD 20892 USA. NR 47 TC 14 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1999 VL 67 IS 10 BP 5526 EP 5529 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 240ET UT WOS:000082813500078 PM 10496944 ER PT J AU Levine, SJ AF Levine, SJ TI Diagnosing pulmonary infections in HIV-positive patients - Part 1: Epidemiology, etiology, and evaluation SO INFECTIONS IN MEDICINE LA English DT Article DE pneumonia; infection, respiratory; immunosuppression; HIV; infection, opportunistic ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; BACTERIAL PNEUMONIA; DISSEMINATED HISTOPLASMOSIS; KAPOSIS-SARCOMA; CT FINDINGS; AIDS; TUBERCULOSIS; COMPLICATIONS; PNEUMOTHORAX AB Despite advances in managing patients infected with HIV, opportunistic and nonopportunistic pulmonary infections continue to be an important cause of morbidity and mortality. The risk of developing severe lower respiratory tract infections is directly related to the degree of underlying immunosuppression, as predicted by a CD4+ T-lymphocyte count of less than 200 to 250/mu L. In this issue, I discuss risk factors and methods of evaluation for HIV-infected patients with pulmonary disease. In a subsequent issue, I will present a general approach to the diagnosis of pulmonary disease in HIV-positive patients. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 41 TC 1 Z9 1 U1 0 U2 0 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD OCT PY 1999 VL 16 IS 10 BP 637 EP + PG 8 WC Infectious Diseases SC Infectious Diseases GA 252CG UT WOS:000083482700005 ER PT J AU Linnekin, D AF Linnekin, D TI Early signaling pathways activated by c-Kit in hematopoietic cells SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE stem cell factor; signal transduction; hematopoiesis; growth factors; cytokines ID RECEPTOR TYROSINE KINASE; COLONY-STIMULATING FACTOR; LIGAND-INDEPENDENT ACTIVATION; CHRONIC MYELOGENOUS LEUKEMIA; GROWTH-FACTOR RECEPTORS; STEM-CELL; PROTEIN-KINASE; MAST-CELL; PHOSPHATIDYLINOSITOL 3-KINASE; MULTIPLE CYTOKINES AB c-Kit is a receptor tyrosine kinase that binds stem cell factor (SCF). Structurally, c-Kit contains five immunoglobulin-like domains extracellularly and a catalytic domain divided into two regions by a 77 amino acid insert intracellularly. Studies in white spotting and steel mice have shown that functional SCF and c-Kit are critical in the survival and development of stem cells involved in hematopoiesis, pigmentation and reproduction. Mutations in c-Kit are associated with a variety of human diseases. Interaction of SCF with c-Kit rapidly induces receptor dimerization and increases in autophosphorylation activity. Downstream of c-Kit, multiple signal transduction components are activated, including phosphatidylinositol-3-kinase, Src family members, the JAK/STAT pathway and the Ras-Raf-MAP kinase cascade. Structure-function studies have begun to address the role of these signaling components in SCF-mediated responses. This review will focus on the biochemical mechanism of action of SCF in hematopoietic cells. Published by Elsevier Science Ltd. C1 NCI, Basic Res Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Linnekin, D (reprint author), NCI, Basic Res Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 171 TC 262 Z9 276 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD OCT PY 1999 VL 31 IS 10 BP 1053 EP 1074 DI 10.1016/S1357-2725(99)00078-3 PG 22 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249GN UT WOS:000083325100010 PM 10582339 ER PT J AU Ruscetti, SK AF Ruscetti, SK TI Deregulation of erythropoiesis by the Friend spleen focus-forming virus SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE Friend spleen focus-forming virus; viral envelope glycoprotein; erythroleukemia; Epo receptor; Epo signal transduction pathways ID TYROSINE-PHOSPHORYLATED PROTEIN; CYTOKINE RECEPTOR SUPERFAMILY; COMPLETE NUCLEOTIDE-SEQUENCE; ERYTHROID PROGENITOR CELLS; MEMBRANE GLYCOPROTEIN GP55; ANEMIA-INDUCING STRAINS; CELLULAR P53 GENE; ENV-GENE; HEMATOPOIETIC-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE AB The proliferation and differentiation of erythroid cells is a highly regulated process that is controlled primarily at the level of interaction of erythropoietin (Epo) with its specific cell surface receptor (EpoR). However, this process is deregulated in mice infected with the Friend spleen focus-forming virus (SFFV). Unlike normal erythroid cells, erythroid cells from SFFV-infected mice are able to proliferate and differentiate in the absence of Epo, resulting in erythroid hyperplasia and leukemia. Over the past 20 years, studies have been carried out to identify the viral genes responsible for the pathogenicity of SFFV and to understand how expression of these genes leads to the deregulation of erythropoiesis in infected animals. The studies have revealed that SFFV encodes a unique envelope glycoprotein which interacts specifically with the EpoR at the cell surface, resulting in activation of the receptor and subsequent activation of erythroid signal transduction pathways. This leads to the proliferation and differentiation of erythroid precursor cells in the absence of Epo. Although the precise mechanism by which the viral protein activates the EpoR is not yet known, it has been proposed that it causes dimerization of the receptor, resulting in constitutive activation of Epo signal transduction pathways. While interaction of the SFFV envelope glycoprotein with the EpoR leads to Epo-independent erythroid hyperplasia, this is not sufficient to transform these cells. Transformation requires the viral activation of the cellular gene Sfpi-1, whose product is thought to block erythroid cell differentiation. By understanding how SFFV can deregulate erythropoiesis, we may gain insights into the causes and treatment of related diseases in man. Published by Elsevier Science Ltd. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Ruscetti, SK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 160 TC 39 Z9 41 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD OCT PY 1999 VL 31 IS 10 BP 1089 EP 1109 DI 10.1016/S1357-2725(99)00074-6 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249GN UT WOS:000083325100012 PM 10582341 ER PT J AU Fucich, LF Freeman, SF Boh, EE McBurney, E Marrogi, AJ AF Fucich, LF Freeman, SF Boh, EE McBurney, E Marrogi, AJ TI Atypical cutaneous lymphocytic infiltrate and a role for quantitative immunohistochemistry and gene rearrangement studies SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; T-CELL LYMPHOMAS; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; DIAGNOSIS; EXPRESSION; INTERRATER; CRITERIA; LESIONS AB Aim To help clarify the significance of the T-cell receptor (TCR) gene rearrangement and its relationship to the immunophenotyping of histologically atypical cutaneous T-cell lymphoid infiltrates (ACLIs). Materials and methods One hundred and twenty-four patients presented with lesions clinically suspicious for cutaneous T-cell lymphoma (CTCL). The average age was 55.8 years with a mean follow-up duration of 26.2 months. Cases were classified as malignant (64 cases), inflammatory dermatosis (28 cases), and indeterminate (32 cases), based on follow-up data and histopathology. Quantitative immunophenotyping with computer-assisted imaging was performed using immunohistochemical stains of anti-CDS, CD4, CD5, CD7, CD8, CD20, CD30, CD56, CD68, Bcl-2, p53, and proliferating cell nuclear antigen (PCNA). Results Abnormal immunophenotypic expression in 87.5% of the malignant cases, including CD4 or CD8 predominance (67%), deletion of pan-T-cell antigens (16.1%), and activation of antigen/oncogene expression (47%), was observed. In addition, 36 clinically malignant cases displayed rearranged bands by polymerase chain reaction (PCR) with TCR beta and gamma. Two benign cases displayed abnormal immunophenotype and two others showed rearranged bands. All of these patients responded to topical steroid therapy with complete resolution. Nineteen indeterminate cases displayed either rearranged bands or immunophenotypic abnormalities, 15 of which were reclassified as malignant. All but three patients improved after CTCL treatment. Conclusion Quantitative immunophenotyping and gene rearrangement analysis can provide detailed information for classifying ACLIs with 91% diagnostic sensitivity and 87% specificity. C1 Mobile Infirm, Dept Pathol, Mobile, AL USA. Tulane Univ, Sch Med, Dept Pathol, New Orleans, LA 70118 USA. Tulane Univ, Sch Med, Dept Lab Med, New Orleans, LA 70118 USA. Tulane Univ, Sch Med, Dept Dermatol, New Orleans, LA 70118 USA. Louisiana State Univ, Sch Med, Dept Surg, New Orleans, LA 70112 USA. RP Marrogi, AJ (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Rm 2C25, Bethesda, MD 20692 USA. NR 31 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD OCT PY 1999 VL 38 IS 10 BP 749 EP 756 DI 10.1046/j.1365-4362.1999.00809.x PG 8 WC Dermatology SC Dermatology GA 253RK UT WOS:000083569400006 PM 10561046 ER PT J AU Weiss, HA Brinton, LA Potischman, NA Brogan, D Coates, RJ Gammon, MD Malone, KE Schoenberg, JB AF Weiss, HA Brinton, LA Potischman, NA Brogan, D Coates, RJ Gammon, MD Malone, KE Schoenberg, JB TI Breast cancer risk in young women and history of selected medical conditions SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast cancer; medical history; diabetes; ovarian cysts ID SERUM-CHOLESTEROL; HODGKINS-DISEASE; THYROID-DISEASE; NORWEGIAN WOMEN; INSULIN; HORMONES; EPIDEMIOLOGY; CHOLELITHIASIS; ENDOMETRIOSIS; TRIGLYCERIDES AB Background Several common medical conditions are associated with altered hormone levels, and may thus plausibly influence breast cancer risk. Few studies have examined such relationships, and we utilized a population-based case-control study of young women in the US to examine breast cancer risk following a history of various medical conditions. Relationships between breast cancer and each medical condition examined are biologically plausible, and relevant in terms of public health. Methods The study included 2173 breast cancer cases and 1990 population-based controls from three areas of the US, under 55 years, who were administered a questionnaire including details of physician-diagnosed medical conditions. Results No significantly increased or decreased breast cancer risk was associated with a history of thyroid disease, gallbladder disease, colorectal polyps, diabetes, high blood pressure, high cholesterol or surgery for endometriosis. There was some evidence of an increased breast cancer risk associated with ovarian cysts among women who did not receive an oophorectomy (relative risk [RR] = 1.94, 95% CI: 1.0-3.9). Non-significant increases in breast cancer risk were observed following diagnoses of several other cancers, including thyroid cancer, basal cell carcinoma, Hodgkin's disease and malignant melanoma. Conclusions To conclude, our generally null results from this large, population-based study support results from previous studies in providing reassurance that women with a history of several common medical conditions do not appear to be at an increased risk of breast cancer at a young age. C1 Natl Canc Inst, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. ESB, DCPC, NCCDPHP, Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY 10032 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. New Jersey State Dept Hlth, Special Epidemiol Program, Trenton, NJ 08625 USA. RP Brinton, LA (reprint author), Natl Canc Inst, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S Rm 7068,6120 Exec Blvd,MSC 7234, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 55 TC 73 Z9 76 U1 0 U2 2 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 1999 VL 28 IS 5 BP 816 EP 823 DI 10.1093/ije/28.5.816 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 258FG UT WOS:000083827000002 PM 10597976 ER PT J AU Krebs, PA Albuquerque, A Quezado, M Bryant, B Sobel, ME Merino, MJ Otis, CN AF Krebs, PA Albuquerque, A Quezado, M Bryant, B Sobel, ME Merino, MJ Otis, CN TI The use of microsatellite instability in the distinction between synchronous endometrial and colonic adenocarcinomas SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE microsatellite instability; microdissection; synchronous carcinoma ID HUMAN SOLID TUMORS; GENOMIC INSTABILITY; HUMAN CANCER; CARCINOMAS; OVARIAN AB The association of endometrial carcinoma with other gynecologic neoplasms, especially ovarian and fallopian tube carcinoma. has been well documented and is usually interpreted as a result of a field defect. Sporadic synchronous primary carcinomas occurring in the endometrium and colon are extremely rare, especially in the absence of the familial genetic abnormalities seen in hereditary nonpolyposis colorectal carcinoma (HNPCC) syndrome, and may present a diagnostic dilemma. Two cases of synchronous adenocarcinomas of the endometrium and colon were studied for genetic abnormalities and differences to test for the presence of two primary tumors. Primary tumors, metastases, and normal tissues were microdissected from formalin-fixed, paraffin-embedded tissues. PCR amplification was performed for microsatellite DNA markers on chromosome 17q and 11q13. The colonic tumors were moderately and poorly differentiated, invasive, nonmucinous adenocarcinomas, whereas one uterine tumor was endometrioid adenocarcinoma and the other was papillary serous carcinoma. Although microsatellite instability, as evidenced by changes in the lengths of the amplified PCR products, was detected at 17q and 11q13 loci in the uterine and colonic neoplasms, the patterns of instability differed between the two primary tumor sites. Moreover, the lymph node metastasis in one colonic tumor had genetic alterations that differed from that of the primary tumor. In both patients, the molecular studies suggested the presence of two synchronous primary tumors. Molecular techniques may assist in distinguishing two separate primaries by determining the contraction and expansion of microsatellite regions in DNA obtained by microdissection from the primary tumors and associated metastases. C1 Tufts Univ, Sch Med, Baystate Med Ctr, Dept Pathol, Springfield, MA 01199 USA. NCI, Surg Pathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Mol Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Otis, CN (reprint author), Tufts Univ, Sch Med, Baystate Med Ctr, Dept Pathol, Springfield, MA 01199 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1999 VL 18 IS 4 BP 320 EP 324 DI 10.1097/00004347-199910000-00005 PG 5 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 245RW UT WOS:000083122800005 PM 10542939 ER PT J AU Yang, XQ Tahin, Q Hu, YF Russo, IH Balsara, BR Mihaila, D Slater, C Barrett, JC Russo, J AF Yang, XQ Tahin, Q Hu, YF Russo, IH Balsara, BR Mihaila, D Slater, C Barrett, JC Russo, J TI Functional roles of chromosomes 11 and 17 in the transformation of human breast epithelial cells in vitro SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE human breast epithelial cells; cell transformation; microcell-mediated chromosome transfer; chromosome 11; chromosome 17 ID TUMOR SUPPRESSOR GENE; CHEMICAL-CARCINOGENS; CANCER CELLS; NEOPLASTIC TRANSFORMATION; LINE; P53; HETEROZYGOSITY; INSTABILITY; TELOMERASE; FRAGMENTS AB Genomic alterations in primary breast cancer play a role in the initiation and progression of the disease. We have analyzed the molecular events involved in the initiation and progression of the neoplastic process in an in vitro experimental system. Immortalization of human breast epithelial cells (HBEC) is associated with 3:9 translocation, p53 mutation and microsatellite instability (MSI) of chromosomes 11p13, and 17p. BP1-E cells, derived from the immortalized MCF-10F cells transformed by the carcinogen benzo(a)pyrene (BP), express in vitro growth advantage, anchorage independence, enhanced chemoinvasiveness, loss of ductulogenic capabilities and tumorigenesis in a heterologous host. This neoplastic progression is also associated with mutations and/or amplification of c-H-I-ns, int-2, c-neu, c-myc and MDM2, MSI at 11q25 and 13q12-q13 and loss of heterozygosity at 17p. In order to test whether chromosomes 11 or 17 play a functional role in the phenotypic expression of transformation of BP1E cells, we utilized microcell-mediated chromosome transfer (MMCT) technique for inserting the corresponding normal chromosomes to these transformed cells. BP1E cells were transfected with PsV2neo plasmid and fused with microcells obtained from the mouse cell line A9, containing a normal chromosome II or 17 (A9-11neo and A9-17neo cells, selected in G418 and cloned. Sixteen primary microcell hybrids from each chromosome transfer, designated BP1E-11neo and BP1E-17neo survived selection in G-418 containing medium. A single clone from each group, BP1E-11neo #145 and BP1E-17neo D100, survived subcloning and were utilized for a detailed panel of analyses. The presence of a donor chromosome was confirmed by dual color fluorescence in. situ hybridization (FISH), Southern blot analysis of the marker vector pSV2neo, and microsatellite polymorphism analysis. The transfer of the normal chromosomes II and 17 resulted in a 50% and 90% inhibition of cell growth respectively, and reduced both colony efficiency and colony size. Telomerase activity was significantly reduced only by chromosome 17 insertion, providing a possible explanation for the more significant senescence observed in BP1E-17neo D100 cells. Microsatellite polymorphism analysis revealed that three loci, 11q13-23, 11q23.1, and 11q23.3 (markers D11S911, DRD2, and D11S29) were retained in BP1E-11neo #145 cells, and two, 17q24.2-25.2, 17q25.2 (markers D17S515 and D17S785 were retained in BP1E-17neo D100 cells. We conclude that the specific regions of normal chromosomes 11 and 17 transferred play a functional role in the expression of immortal and transformed phenotypes of HBEC in vitro. C1 Fox Chase Canc Ctr, Breast Canc Res Lab, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Lab Mol Cytogenet, Philadelphia, PA 19111 USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. RP Russo, J (reprint author), Fox Chase Canc Ctr, Breast Canc Res Lab, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [R01 CA67238] NR 39 TC 22 Z9 22 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 1999 VL 15 IS 4 BP 629 EP 638 PG 10 WC Oncology SC Oncology GA 239UC UT WOS:000082787200004 PM 10493942 ER PT J AU Westergaard, GC Wagner, JL Suomi, SJ AF Westergaard, GC Wagner, JL Suomi, SJ TI Manipulative tendencies of captive Cebus albifrons SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE capuchin; Cebus albifrons; hand preference; tool use; reaching posture ID CHIMPANZEES; APELLA; TOOL AB We conducted two experiments to examine the manipulative tendencies of captive Cebus albifrons. In Experiment I we examined hand preference for reaching by providing subjects with food either on the cage floor (to facilitate quadrupedal reaching) or at the height of an upright subject's shoulder (to facilitate bipedal reaching). In Experiment 2 we examined combinatorial manipulation by providing subjects with nesting containers and other portable manipulanda. Results indicate that C. albifrons exhibits greater use of the right hand for bipedal versus quadrupedal reaching (exhibiting a group-level lack of bias for bipedal reaching and a left-hand bias for quadrupedal reaching), combines objects using a simple pairing strategy, and uses and produces simple tools. Aspects of these findings parallel those for Cebus apella. C1 NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. Mannheimer Fdn Inc, Homestead, FL 33034 USA. RP Westergaard, GC (reprint author), Labs Virginia Inc, POB 557, Yemassee, SC 29945 USA. NR 15 TC 7 Z9 7 U1 2 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD OCT PY 1999 VL 20 IS 5 BP 751 EP 759 DI 10.1023/A:1020756803437 PG 9 WC Zoology SC Zoology GA 258ZH UT WOS:000083869200008 ER PT J AU Ciernik, IF Romero, P Berzofsky, JA Carbone, DP AF Ciernik, IF Romero, P Berzofsky, JA Carbone, DP TI Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE mutant p53; T-cell epitopes; tumor vaccine; cellular immunity; radiation; tumor immunogenicity ID MUTANT P53; DENDRITIC CELLS; LUNG-CANCER; ANTIGEN PRESENTATION; APOPTOTIC CELLS; BREAST-CANCER; WILD-TYPE; GENE; LYSOZYME; FREQUENT AB Background: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. Methods: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. Results: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. Conclusions: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines. (C) 1999 Elsevier Science Inc. C1 CHU Vaudois, Lausanne Branch, Ludwig Inst Canc Res, Div Clin Oncoimmunol, CH-1011 Lausanne, Switzerland. NCI, Metab Branch, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Vanderbilt Canc Ctr, Nashville, TN USA. RP Ciernik, IF (reprint author), CHU Vaudois, Lausanne Branch, Ludwig Inst Canc Res, Div Clin Oncoimmunol, Rue Bugnon 46, CH-1011 Lausanne, Switzerland. FU NCI NIH HHS [R01-CA61242] NR 29 TC 16 Z9 17 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 1999 VL 45 IS 3 BP 735 EP 741 DI 10.1016/S0360-3016(99)00226-6 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 243EA UT WOS:000082983000031 PM 10524430 ER PT J AU Tamm, ER Russell, P Epstein, DL Johnson, DH Piatigorsky, J AF Tamm, ER Russell, P Epstein, DL Johnson, DH Piatigorsky, J TI Modulation of myocilin/TIGR expression in human trabecular meshwork SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 10-15, 1998 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID OPEN-ANGLE GLAUCOMA; ALPHA-B-CRYSTALLIN; TIGR GENE; MECHANICAL STRETCH; CLINICAL-FEATURES; CULTURED HUMAN; CELLS; MUTATION; PROTEIN; IDENTIFICATION AB PURPOSE. TO study factors that modulate myocilin/trabecular meshwork inducible glucocorticoid response protein (TIGR) mRNA expression in human trabecular meshwork (TM). METHODS. mRNA from fresh TM of four human donors, from perfused anterior segment organ cultured TM of three donors, and from four primary TM cell lines of different donors was isolated. The full length cDNA of myocilin/TIGR was cloned from TM mRNA using a polymerase chain reaction approach and used as probe for northern blot analysis hybridization. Trabecular meshwork cell cultures were treated with transforming growth factor (TGF)-beta 1 (1 ng/ml), dexamethasone (10(-7) M), and mechanical stretch (10%). RESULTS. mRNA for myocilin/TIGR could be readily detected by northern blot analysis hybridization in 2 to 3 mu g of total RNA from all fresh and all organ-cultured TM samples. In contrast, no mRNA for myocilin/TIGR could be detected in 20 mu g of rotal RNA isolated from three different primary TM cell lines. Only one TM cell line had a baseline expression of myocilin/TIGR, which was 35- to 55-fold lower than that of fresh or organ-cultured TM samples. Treatment of TM cell cultures with dexamethasone for 1 day markedly increased expression of myocilin/TIGR mRNA, an effect that was even more pronounced after 3 days of treatment. Treatment with TGF-beta 1 for 24 hours had no effect; however, after 3 and 12 days of treatment a 3.8- and 4-fold increase in myocilin/TIGR mRNA expression was observed. Expression of myocilin/TIGR mRNA was also increased after 10% mechanical stretch; however, in contrast to the effects of TGF-beta 1, this effect was observed much earlier (8-24 hours) after treatment. CONCLUSIONS. Dynamic mechanical stimuli maintain myocilin/TIGR expression in TM in situ and lack of these stimuli in monolayer cell cultures might be involved in downregulation of myocilin/ TIGR expression. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. Duke Univ, Ctr Eye, Durham, NC USA. Mayo Clin, Rochester, MN USA. RP Tamm, ER (reprint author), Univ Erlangen Nurnberg, Dept Anat 2, Univ Str 19, D-91054 Erlangen, Germany. FU NEI NIH HHS [EY01894] NR 35 TC 121 Z9 127 U1 0 U2 4 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 1999 VL 40 IS 11 BP 2577 EP 2582 PG 6 WC Ophthalmology SC Ophthalmology GA 240WR UT WOS:000082850500016 PM 10509652 ER PT J AU Lai, JC Lobanoff, MC Fukushima, A Wawrousek, EF Chan, CC Whitcup, SM Gery, I AF Lai, JC Lobanoff, MC Fukushima, A Wawrousek, EF Chan, CC Whitcup, SM Gery, I TI Uveitis induced by lymphocytes sensitized against a transgenically expressed lens protein SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ADOPTIVE TRANSFER; RATS AB PURPOSE. Previously established experimental models for lens-associated uveitis (LAU) are all mediated by antibodies. The present study analyzed the features of a novel experimental intraocular inflammatory eye disease that is mediated by lymphocytes targeted at a lens antigen. METHODS. Conventional technologies were used to generate three lines of transgenic (Tg) mice, expressing hen egg lysozyme (HEL) under the control of the alpha A-crystallin prometer. To induce intraocular inflammation, these Tg mice were injected with lymphocytes from syngeneic wild-type donors sensitized against HEL. Before their injection, the cells were stimulated in culture with HEL. To release lenticular material, some eyes were capsulotomized. Ocular his topathologic changes were examined by routine methods. Levels of HEL antibody were measured by enzyme-linked immunosorbent assay, whereas cellular immunity was determined by the lymphocyte proliferation assay. RESULTS. Intraocular inflammation developed in HEL-Tg mice injected with syngeneic lymphocytes sensitized against HEL. The severity of inflammation was directly related to the number of injected cells, as well as to the accessibility of HEL. The most intense inflammation was seen in Tg mice in which the lens was disintegrated due to high production of I-ILL. In mice with no apparent lenticular changes the inflammation was enhanced by capsulotomy. The inflammation affected all segments of the eye and persisted for at least 39 days after adoptive transfer of cells. Four days after cell injection, the inflammation consisted of subacute infiltration, with both mononuclear and polymorphonuclear leukocytes, whereas more chronic in filtration was seen at later times. Vigorous cellular immunity but no antibody to HEL was found in recipient mice, thus demonstrating the exclusive participation of cellular immunity in the pathogenesis of this experimental disease. CONCLUSIONS. Transgenic mice expressing FILL in their lenses develop intraocular inflammation after injection of syngeneic lymphocytes sensitized against HEL. This experimental disease is a novel cell-mediated model for LAU. C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Gery, I (reprint author), NEI, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. RI Wawrousek, Eric/A-4547-2008 NR 10 TC 13 Z9 13 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 1999 VL 40 IS 11 BP 2735 EP 2739 PG 5 WC Ophthalmology SC Ophthalmology GA 240WR UT WOS:000082850500036 PM 10509672 ER PT J AU Delle Fave, G Frati, L Jensen, RT AF Delle Fave, G Frati, L Jensen, RT TI Advances in digestive endocrine tumours - Foreword SO ITALIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material C1 Univ Rome La Sapienza, Rome, Italy. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Delle Fave, G (reprint author), Univ Rome La Sapienza, Piazzale Aldo Moro 5, Rome, Italy. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PACINI EDITORE PI OSPEDALETTO PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE, 56014 OSPEDALETTO PISA, ITALY SN 1125-8055 J9 ITAL J GASTROENTEROL JI Ital. J. Gastroenterol. Hepatol. PD OCT PY 1999 VL 31 SU 2 BP S93 EP S93 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 254VA UT WOS:000083631800001 ER PT J AU Doppman, JL Jensen, RT AF Doppman, JL Jensen, RT TI Localization of gastroenteropancreatic tumours by angiography SO ITALIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT Symposium on Advances in Digestive Endocrine Tumours CY SEP 29-30, 1997 CL ROME, ITALY DE neuroendocrine tumours; selective arterial stimulation; selective arteriography ID ZOLLINGER-ELLISON SYNDROME; DUODENAL GASTRINOMAS; INJECTION; CT AB Neuroendocrine tumours are seen on arteriography as diffusely enhancing masses without tumour vessels and without arteriovenous shunting. In 70 patients with surgically proven tumours, the sensitivity of angiography was 68% for extrapancreatic and 86% for hepatic lesions. Hepatic metastases have always been easier to demonstrate arteriographically than the primary tumour because of the absence of overlying bowel. Portal venous sampling is a sensitive technique for detecting functioning gastroenteropancreatic tumours. Sampling the small veins about the pancreatic head yielded a sensitivity of 62% but this is an invasive procedure in which considerable experience is required. Intra-arterial secretagogue, secretin for gastrinomas and calcium for insulinomas, selectively injected into the pancreatic and the hepatic arteries produce a diagnostic gastrin or insulin gradient respectively. The localization sensitivity of arterial stimulation with venous sampling is 77-89% for gastrinoma and 92% for pancreatic insulinoma. Recently, spiral CT in conjunction with selective intra-arterial rather than intravenous injection of contrast may increase the detection sensitivity of duodenal and pancreatic gastrinomas. C1 Natl Inst Digest & Kidney Dis, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. Natl Inst Digest & Kidney Dis, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Doppman, JL (reprint author), Natl Inst Digest & Kidney Dis, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, NIH, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU PACINI EDITORE PI OSPEDALETTO PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE, 56014 OSPEDALETTO PISA, ITALY SN 1125-8055 J9 ITAL J GASTROENTEROL JI Ital. J. Gastroenterol. Hepatol. PD OCT PY 1999 VL 31 SU 2 BP S163 EP S166 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 254VA UT WOS:000083631800015 PM 10604123 ER PT J AU Jensen, RT Gibril, F AF Jensen, RT Gibril, F TI Somatostatin receptor scintigraphy in gastrinomas SO ITALIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT Symposium on Advances in Digestive Endocrine Tumours CY SEP 29-30, 1997 CL ROME, ITALY DE gastrinomas; imaging; pancreatic endocrine tumour; Zollinger-Ellison syndrome ID ZOLLINGER-ELLISON-SYNDROME; PANCREATIC ENDOCRINE TUMORS; ENDOSCOPIC ULTRASONOGRAPHY; GASTROENTEROPANCREATIC TUMORS; LOCALIZATION; MANAGEMENT; SENSITIVITY; METASTASES; IMPACT; SRS AB Recent studies report that the radiolabelled synthetic somatostatin analogue, [In-111-DTPA-DPhe(1)]octreotide, is useful for imaging carcinoid tumours and pancreatic endocrine tumours. At present, if is unclear whether this method is superior to conventional imaging studies (computed tomography, magnetic resonance imaging, ultrasound, angiography) and what its role should be, if any, in the management of these patients. The aim of this paper is to review Jive recent studies performed at the National Institutes of Health in patients with Zollinger-Ellison syndrome to define the role of somatostatin receptor scintigraphy. Patients were from a tertiary referral centre, all had Zollinger-Ellison syndrome. In Study n. 1: the sensitivity of somatostatin receptor scintigraphy was assessed compared to conventional studies in 80 patients. Study n. 2: the effect of somatostatin receptor scintigraphy on management was determined in 122 patients. Study n. 3: ability of somatostatin receptor scintigraphy and other conventional methods to distinguish small hepatic metastases (<2 cm) from hepatic haemangiomas was assessed in 29 patients. Study n. 4: somatostatin receptor scintigraphy, magnetic resonance imaging and bane scanning were compared in 115 consecutive patients to detect bone metastases. Study n. 5. ability of somatostatin receptor scintigraphy to detect gastrinomas found at surgery in 35 patients and its effect on cure rate and determinants of detection of gastrinomas by somatostatin receptor scintigraphy were analysed. Briefly, results showed: Study n. 1: somatostatin receptor scintigraphy is the most sensitive modality for detection of primary or metastatic gastrinomas; Study n. 2: somatostatin receptor scintigraphy changes management in 47% of cases; Study n. 3: somatostatin receptor scintigraphy is the only method to distinguish small liver metastases from small haemangiomas; Study n. 4: somatostatin receptor scintigraphy and magnetic resonance imaging have higher sensitivity and predictive values for bone metastases than bone scanning; Study n. 5: somatostatin receptor scintigraphy misses 33% of gastrinomas found at surgery, primarily small duodenal tumours. Size is the important factor. The use of somatostatin receptor scintigraphy does not increase cure rate, ln conclusion, Somatostatin receptor scintigraphy is now the imaging method of choice in patients with Zollinger-Ellison syndrome for preoperative primary tumour localization, detection of bone or liver metastases, and to distinguish small liver metastases from small hepatic haemangiomas. Its specificity appears to be high but has been poorly studied as has the use of it in combination with endoscopic ultrasound. Studies by others suggest these recommendations will apply to carcinoid tumours and other pancreatic endocrine tumours except insulinomas. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 27 TC 10 Z9 10 U1 0 U2 0 PU PACINI EDITORE PI OSPEDALETTO PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE, 56014 OSPEDALETTO PISA, ITALY SN 1125-8055 J9 ITAL J GASTROENTEROL JI Ital. J. Gastroenterol. Hepatol. PD OCT PY 1999 VL 31 SU 2 BP S179 EP S185 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 254VA UT WOS:000083631800018 PM 10604126 ER PT J AU Tio, TL AF Tio, TL TI Endoscopic ultrasonography in patients with gastrinomas SO ITALIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT Symposium on Advances in Digestive Endocrine Tumours CY SEP 29-30, 1997 CL ROME, ITALY DE endoscopic ultrasonography; pancreatic endocrine tumours ID PREOPERATIVE TNM CLASSIFICATION; CARCINOMA; ENDOSONOGRAPHY; TOMOGRAPHY; TUMORS; VATER; DUCT AB Placing the endoscopic ultrasound transducer in the descending duodenum, the duodenal bulb and the stomach, all the pancreas can be imaged. Endoscopic ultrasonography is a sophisticated imaging technique able to accurately diagnose and localize primary endocrine tumours of the pancreas (mostly insulinoma and gastrinoma) which may not be detectable with other imaging modalities. Furthermore, endoscopic ultrasonography-guided fine needle aspiration allows cytology and/or biopsy specimens to be obtained that are crucial for clinicians in decision making. In the case of extrapancreatic endocrine tumours, which are often localized in the second and third part of the duodenum, endoscopic ultrasonography may have difficulty in localizing small and flat lesions. In this case, the initial step would be identification of duodenal nodules by duodenoscopy and thereafter a catheter echoprobe can be inserted to identify the extent of submucosal lesion. Then gastroduodenal nodules found by endoscopy and confirmed by endoscopic ultrasonography can be removed endoscopically using the technique of mucosectomy. In the case of large pancreatic lesions, endoscopic tattoo with dye-India ink or methylene blue may become helpful for the surgeon to perform local resection via duodenostomy. C1 Georgetown Univ, Med Ctr, Dept Gastroenterol, Washington, DC 20007 USA. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. RP Tio, TL (reprint author), Georgetown Univ, Med Ctr, Dept Gastroenterol, 3800 Reservoir Rd, Washington, DC 20007 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU PACINI EDITORE PI OSPEDALETTO PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE, 56014 OSPEDALETTO PISA, ITALY SN 1125-8055 J9 ITAL J GASTROENTEROL JI Ital. J. Gastroenterol. Hepatol. PD OCT PY 1999 VL 31 SU 2 BP S172 EP S178 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 254VA UT WOS:000083631800017 PM 10604125 ER PT J AU Sun, MK AF Sun, MK TI Hypoxia, ischemic stroke, and memory deficits: Prospects for therapy SO IUBMB LIFE LA English DT Review DE cardiorespiratory regulation; hippocampus; hypoxia; ischemia; learning and memory; stroke; neuronal survival ID CYTOCHROME-C; CHEMOREFLEX EXCITATION; VASOMOTOR NEURONS; CARDIAC-ARREST; MICE LACKING; APOPTOSIS; DEATH; BCL-2; RAT; MITOCHONDRIA AB Oxygenation of cells and tissues in mammals according to metabolic needs is always: a life-or-death necessity. Over the last decade, life scientists have gained an impressive understanding of cellular and molecular mechanisms in hypoxic-ischemic injury and memory deficits, survival, and death. Functional recovery from hypoxia-ischemia depends on holy the individual responds to the insult, and whether appropriate responses are initiated and maintained. Unraveling the biochemical and molecular mechanisms and responses of hypoxia-ischemia is likely to dramatically shape and improve medical practice in the treatments of hypoxia-ischemia and memory deficits. C1 NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Sun, MK (reprint author), NINDS, Lab Adapt Syst, NIH, Bldg 36,Room 4A24,36 Convent Dr, Bethesda, MD 20892 USA. NR 47 TC 8 Z9 8 U1 0 U2 1 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 PY 1999 VL 48 IS 4 BP 373 EP 378 DI 10.1080/713803535 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 263ML UT WOS:000084128400003 PM 10632564 ER PT J AU Devouassoux, G Foster, B Scott, LM Metcalfe, DD Prussin, C AF Devouassoux, G Foster, B Scott, LM Metcalfe, DD Prussin, C TI Frequency and characterization of antigen-specific IL-4-and IL-13-producing basophils and T cells in peripheral blood of healthy and asthmatic subjects SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE basophils; T cell; cytokines; flow cytometry; human; allergy; asthma ID HUMAN B-CELLS; MIXED LEUKOCYTE-CULTURES; FLOW CYTOMETRIC ANALYSIS; LATE-PHASE RESPONSE; HUMAN IGE SYNTHESIS; HUMAN MAST-CELLS; FC-EPSILON-RI; INTRACELLULAR INTERLEUKIN-4; CYTOKINE PRODUCTION; HISTAMINE-RELEASE AB Background: Both basophils and T cells are known to secrete IL-4 and IL-13 after activation with either nonspecific stimuli or specific antigen, but the relative contribution of these 2 cell types to overall cytokine production is unclear. Objectives: To further characterize basophil cytokine production and compare it with that of T cells, we examined the frequency of IL-4- and IL-13-producing basophils and T cells in human PBMCs by means of flow cytometry after activation in allergic asthmatic and normal subjects. Methods: PBMCs obtained from whole blood after Percoll gradient were activated with specific antigen or ionomycin and fixed. PBMCs were made permeable; stained with antibodies to IgE, CD3, and either IL-4 or IL-13; and analyzed by means of flow cytometry, Results: Preformed cytokines were not detected in unactivated basophils, After ionomycin activation, 60% to 90% of basophils from both control and allergic asthmatic subjects expressed IL-4 and IL-13, Specific antigen induced cytokine expression by 10% to 20% of basophils from the asthmatic group only. After specific antigen activation, basophils accounted for 4 times more IL-4-producing cells than did T cells, IL-4 and IL-13 production at 2 hours was exclusively from basophils, After allergen activation, CD40 ligand was upregulated on a subset of peripheral blood basophils, Conclusions: These data demonstrate that basophils are the predominant peripheral blood cells that express IL-4 and IL-13 in the first 6 hours after antigen activation and strengthen the putative role of basophils both in IgE production and in the generation of allergic inflammation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Devouassoux, G (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C209,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. OI Prussin, Calman/0000-0002-3917-3326 FU NIAID NIH HHS [201-AI-00709-05] NR 46 TC 81 Z9 82 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 1999 VL 104 IS 4 BP 811 EP 819 PN 1 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 248NG UT WOS:000083281200013 PM 10518826 ER PT J AU Joseph, RE Hold, KM Wilkins, DG Rollins, DE Cone, EJ AF Joseph, RE Hold, KM Wilkins, DG Rollins, DE Cone, EJ TI Drug testing with alternative matrices - II. Mechanisms of cocaine and codeine deposition in hair SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID STRATUM-CORNEUM; METABOLITES; EXCRETION; PLASMA; ABUSE; TIME; BENZOYLECGONINE; OPIATES; LIPIDS; FIBERS C1 NIDA, Addict Res Ctr, Baltimore, MD 21224 USA. Univ Utah, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. RP Joseph, RE (reprint author), NIDA, Addict Res Ctr, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 34 TC 18 Z9 19 U1 0 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 1999 VL 23 IS 6 BP 396 EP 408 PG 13 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 242TL UT WOS:000082957700003 PM 10517543 ER PT J AU Wilkins, DG Rollins, DE Valdez, AS Mizuno, A Krueger, GG Cone, EJ AF Wilkins, DG Rollins, DE Valdez, AS Mizuno, A Krueger, GG Cone, EJ TI A retrospective study of buprenorphine and norbuprenorphine in human hair after multiple doses SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID HUMAN SCALP HAIR; THERAPEUTIC COMPLIANCE; DOSAGE HISTORY; TIME MARKER; ABUSE; DRUGS; METHAMPHETAMINE; PLASMA; DISPOSITION; AMPHETAMINE C1 Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. Univ Utah, Sch Med, Div Dermatol, Salt Lake City, UT 84112 USA. NIDA, Intramural Res Program, Baltimore, MD 21146 USA. RP Wilkins, DG (reprint author), Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, 20 South 2030 East,Room 490, Salt Lake City, UT 84112 USA. FU NIDA NIH HHS [DA09096] NR 37 TC 13 Z9 14 U1 0 U2 1 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 1999 VL 23 IS 6 BP 409 EP 415 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 242TL UT WOS:000082957700004 PM 10517544 ER PT J AU Hold, KM Borges, CR Wilkins, DG Rollins, DE Joseph, RE AF Hold, KM Borges, CR Wilkins, DG Rollins, DE Joseph, RE TI Detection of nandrolone, testosterone, and their esters in rat and human hair samples SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID MASS-SPECTROMETRY C1 Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. NIDA, Addict Res Ctr, Baltimore, MD 21224 USA. RP Rollins, DE (reprint author), Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, 20 S 2030 E RM 490, Salt Lake City, UT 84112 USA. FU NIDA NIH HHS [DA07280, DA09096] NR 12 TC 18 Z9 18 U1 0 U2 1 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 1999 VL 23 IS 6 BP 416 EP 423 PG 8 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 242TL UT WOS:000082957700005 PM 10517545 ER PT J AU ElSohly, MA Stanford, DF Murphy, TP Lester, BM Wright, LL Smeriglio, VL Verter, J Bauer, CR Shankaran, S Bada, HS Walls, HC AF ElSohly, MA Stanford, DF Murphy, TP Lester, BM Wright, LL Smeriglio, VL Verter, J Bauer, CR Shankaran, S Bada, HS Walls, HC TI Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID DEPENDENT MOTHERS; COCAINE EXPOSURE; INFANTS; URINE; BENZOYLECGONINE; NEWBORNS C1 ElSohly Labs Inc, Oxford, MS 38655 USA. NIDA, NICHD Neonatal Res Network, ACYF, CSAT, Bethesda, MD USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL USA. RP ElSohly, MA (reprint author), ElSohly Labs Inc, 5 Ind Pk Dr, Oxford, MS 38655 USA. FU NICHD NIH HHS [5-U10-HD27904-02] NR 22 TC 37 Z9 38 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 1999 VL 23 IS 6 BP 436 EP 445 PG 10 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 242TL UT WOS:000082957700008 PM 10517548 ER PT J AU Nath, N Eldefrawi, M Wright, J Darwin, D Huestis, M AF Nath, N Eldefrawi, M Wright, J Darwin, D Huestis, M TI A rapid reusable fiber optic biosensor for detecting cocaine metabolites in urine SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; SIGNAL ACQUISITION; IMMUNOSENSOR; DRUGS; FLUOROSENSOR; ABUSE; SITE C1 Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Eldefrawi, M (reprint author), Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, 655 W Baltimore St, Baltimore, MD 21201 USA. OI NATH, NIDHI/0000-0002-2738-9461 FU NIDA NIH HHS [DA-10459] NR 28 TC 19 Z9 19 U1 0 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 1999 VL 23 IS 6 BP 460 EP 467 PG 8 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 242TL UT WOS:000082957700011 PM 10517551 ER PT J AU Roberts, KP Blades, M AF Roberts, KP Blades, M TI Children's memory and source monitoring of real-life and televised events SO JOURNAL OF APPLIED DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID SOURCE MISATTRIBUTIONS; RETENTION INTERVAL; IMAGINED ACTIONS; SOURCE ERRORS; PRESCHOOLERS; AGE; SUGGESTIBILITY; DISCRIMINATION; REPETITION; TESTIMONY AB It is theoretically and practically important to know whether children confuse memories of different events to which they have been exposed. In two studies, children aged 4 and 10 years watched two related events; one event was live and the other was a video recording. Half of the children watched a video that was similar to the live event, and the remaining children watched a video that was dissimilar. One week later, children in the similar condition confused the two events more than those in the different condition when freely recalling (Experiments 1 and 2) and in response to focused questions (Experiment 1). The 10-year olds reported more information than the 4-year olds and were more accurate overall, confusing the events less than the 4-year olds. When the events were presented 1 day after each other (Experiment 2), the reports were more inaccurate than when the events were separated by a 2-day interval, but this did not affect the number of rimes the events were confused. The results suggest that mere exposure to similar events in different media can contaminate memories, and the findings are discussed in relation to children's sourer monitoring and eyewitness memory. C1 Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. RP Roberts, KP (reprint author), NICHHD, Sect Social & Emot Dev, 9190 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 27 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0193-3973 J9 J APPL DEV PSYCHOL JI J. Appl. Dev. Psychol. PD OCT-DEC PY 1999 VL 20 IS 4 BP 575 EP 596 DI 10.1016/S0193-3973(99)00030-1 PG 22 WC Psychology, Developmental SC Psychology GA 275RJ UT WOS:000084833700005 ER PT J AU Visser, M Fuerst, T Lang, T Salamone, L Harris, TB AF Visser, M Fuerst, T Lang, T Salamone, L Harris, TB CA Hlth Aging Body Composition Study TI Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE computed tomography; elderly; multicompartment models ID TOTAL-BODY WATER; ADIPOSE-TISSUE; DEXA; TOMOGRAPHY; HYDRATION; ADULTS; WOMEN AB The aim of the study was to examine the accuracy of fan-beam dual-energy X-ray absorptiometry (DEXA) for measuring total body fat-free mass (FFM) and leg muscle mass (MM) in elderly persons. Participants were 60 men and women aged 70-79 yr and with a body mass index of 17.5-39.8 kg/m(2). FFM and MM at four leg regions were measured by using DEXA (Hologic 4500A, v8.21). A four-compartment body composition model (4C) and multislice computed tomography (CT) of the legs were used as the criterion methods for FFM and MM, respectively. FFM by DEXA was positively associated with FFM by 4C (R(2) = 0.98, SE of estimate = 1.6 kg). FFM. by DEXA. was higher [53.5 +/- 12.0 (SD) kg] than FFM by 4C (51.6 +/- 11.9 kg; P < 0.001). No association was observed between the difference and the mean of the two methods. MM. by DEXA was positively associated with CT at all four leg regions (R(2) = 0.86-0.96). MM by DEXA was higher than by CT in three regions. The results of this study suggest that fan-beam DEXA offers considerable promise for the measurement of total body FFM and leg MM in elderly persons. C1 Vrije Univ Amsterdam, Inst Res Extramural Med, Fac Med, NL-1081 BT Amsterdam, Netherlands. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94105 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Visser, M (reprint author), Vrije Univ Amsterdam, Inst Res Extramural Med, Fac Med, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM m.visser.emgo@med.vu.nl RI Lang, Thomas/B-2685-2012 OI Lang, Thomas/0000-0002-3720-8038 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2106, N01-AG-62103] NR 18 TC 229 Z9 233 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 1999 VL 87 IS 4 BP 1513 EP 1520 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 244NP UT WOS:000083057900039 PM 10517786 ER PT J AU Tsai, HF Wheeler, MH Chang, YC Kwon-Chung, KJ AF Tsai, HF Wheeler, MH Chang, YC Kwon-Chung, KJ TI A developmentally regulated gene cluster involved in conidial pigment biosynthesis in Aspergillus fumigatus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CRNA-NIIA-NIAD; MELANIN BIOSYNTHESIS; CRYPTOCOCCUS-NEOFORMANS; COLLETOTRICHUM-LAGENARIUM; WANGIELLA-DERMATITIDIS; NITRATE ASSIMILATION; VERTICILLIUM-DAHLIAE; STRUCTURAL-ANALYSIS; NIDULANS; VIRULENCE AB Aspergillus fumigatus, a filamentous fungus producing bluish-green conidia, is an important opportunistic pathogen that primarily affects immunocompromised patients. Conidial pigmentation of A. fumigatus significantly influences its virulence in a murine model. In the present study, six genes, forming a gene cluster spanning 19 kb, were identified as involved in conidial pigment biosynthesis in A. fumigatus. Northern blot analyses showed the six genes to be developmentally regulated and expressed during conidiation. The gene products of alb1 (for "albino 1"), arp1 (for "aspergillus reddish-pink 1"), and arp2 have high similarity to polyketide synthases, scytalone dehydratases, and hydroxynaphthalene reductases, respectively, found in the dihydroxynaphthalene (DHN)-melanin pathway of brown and black fungi. The abr1 gene (for "aspergillus brown 1") encodes a putative protein possessing two signatures of multicopper oxidases. The abr2 gene product has homology to the laccase encoded by the yA gene of Aspergillus nidulans. The function of ayg1 (for "aspergillus yellowish-green 1") remains unknown. Involvement of the six genes in conidial pigmentation was confirmed by the altered conidial color phenotypes that resulted from disruption of each gene in A. fumigatus. The presence of a DHN-melanin pathway in A. fumigatus was supported by the accumulation of scytalone and flaviolin in the arp1 deletant, whereas only flaviolin was accumulated in the arp2 deletants. Scytalone and flaviolin are well-known signature metabolites of the DHN-melanin pathway. Based on DNA sequence similarity, gene disruption results, and biochemical analyses, we conclude that the 19-kb DNA fragment contains a six-gene cluster which is required for conidial pigment biosynthesis in A. fumigatus. However, the presence of abr1, abr2, and ayg1 in addition to alb1, arp1, and arp2 suggests that conidial pigment biosynthesis in A. fumigatus is more complex than the known DHN-melanin pathway. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. ARS, Cotton Pathol Res Unit, So Crops Res Lab, USDA, College Stn, TX 77845 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11C304,10 Ctr Dr,MSC 1882, Bethesda, MD 20892 USA. NR 44 TC 195 Z9 219 U1 2 U2 32 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1999 VL 181 IS 20 BP 6469 EP 6477 PG 9 WC Microbiology SC Microbiology GA 243PM UT WOS:000083006500032 PM 10515939 ER PT J AU Rota, C Fann, YC Mason, RP AF Rota, C Fann, YC Mason, RP TI Phenoxyl free radical formation during the oxidation of the fluorescent dye 2 ',7 '-dichlorofluorescein by horseradish peroxidase - Possible consequences for oxidative stress measurements SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-SPIN RESONANCE; REACTIVE OXYGEN; HYDROGEN-PEROXIDE; NITRIC-OXIDE; PROBE 2',7'-DICHLOROFLUORESCIN; RECEPTOR ACTIVATION; CELL-LINE; IN-VITRO; STIMULATION; SUPEROXIDE AB The oxidation of the fluorescent dye 2',7' dichlorofluorescein (DCF) by horseradish peroxidase was investigated by optical absorption, electron spin resonance (ESR), and oxygen consumption measurements. Spectrophotometric measurements showed that DCF could be oxidized either by horseradish peroxidase-compound I or -compound II with the obligate generation of the DCF phenoxyl radical (DCF'), This one-electron oxidation was confirmed by ESR spin-trapping experiments. DCF' oxidizes GSH, generating the glutathione thiyl radical (GS'), which was detected by the ESR spin-trapping technique. In this case, oxygen was consumed by a sequence of reactions initiated by the GS' radical. Similarly, DCF' oxidized NADH, generating the NAD' radical that reduced oxygen to superoxide (O-2(radical anion)), which was also detected by the ESR spin-trapping technique. Superoxide dismutated to generate H2O2, which reacted with horseradish peroxidase, setting up an enzymatic chain reaction leading to H2O2 production and oxygen consumption. In contrast, when ascorbic acid reduced the DCF phenoxyl radical back to its parent molecule, it formed the unreactive ascorbate anion radical. Clearly, DCF catalytically stimulates the formation of reactive oxygen species in a manner that is dependent on and affected by various biochemical reducing agents, This study, together with our earlier studies, demonstrates that DCFH cannot be used conclusively to measure superoxide or hydrogen peroxide formation in cells undergoing oxidative stress. C1 NIEHS, Informat Technol Support Serv, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, Free Radical Metabolite Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Mason, RP (reprint author), NIEHS, Informat Technol Support Serv, NIH, MD F0-01,POB 12233, Res Triangle Pk, NC 27709 USA. NR 45 TC 168 Z9 173 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 1999 VL 274 IS 40 BP 28161 EP 28168 DI 10.1074/jbc.274.40.28161 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700017 PM 10497168 ER PT J AU Strumberg, D Nitiss, JL Dong, JW Kohn, KW Pommier, Y AF Strumberg, D Nitiss, JL Dong, JW Kohn, KW Pommier, Y TI Molecular analysis of yeast and human type II topoisomerases - Enzyme-DNA and drug interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EUKARYOTIC TOPOISOMERASE; SEQUENCE SPECIFICITY; CLEAVAGE; COMPLEX; BINDING; MECHANISM; POISONS; GYRASE; DETERMINANTS; CYTOTOXICITY AB The DNA sequence selectivity of topoisomerase LI (top2)-DNA cleavage complexes was examined for the human (top2 alpha), yeast, and Escherichia coli (i.e, gyrase) enzymes in the absence or presence of anticancer or antibacterial drugs. Species-specific differences were observed for calcium-promoted DNA cleavage. Similarities and differences in DNA cleavage patterns and nucleic acid sequence preferences were also observed between the human, yeast, and E. coli top2 enzymes in the presence of the non-intercalators fluoroquinolone CP-115,953, etoposide, and azatoxin and the intercalators amsacrine and mitoxantrone. Additional base preferences were generally observed for the yeast when compared with the human top2 alpha enzyme. Preferences in the immediate flanks of the top2-mediated DNA cleavage sites are, however, consistent with the drug stacking model for both enzymes. We also analyzed and compared homologous mutations in yeast and human top2, i.e. Ser(740) --> Trp and Ser(763) --> Trp, respectively. Both mutations decreased the reversibility of the etoposide-stabilized cleavage sites and produced consistent base sequence preference changes. These data demonstrate similarities and differences between human and yeast top2 enzymes. They also indicate that the structure of the enzyme/DNA interface plays a key role in determining the specificity of top2 poisons and cleavage sites for both the intercalating and non-intercalating drugs. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Rm 5D02, Bethesda, MD 20892 USA. RI Nitiss, John/E-9974-2010; OI Nitiss, John/0000-0002-1013-4972 FU NCI NIH HHS [CA21765, CA52814] NR 53 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 1999 VL 274 IS 40 BP 28246 EP 28255 DI 10.1074/jbc.274.40.28246 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700029 PM 10497180 ER PT J AU Kramer, PR Fragoso, G Pennie, W Htun, H Hager, GL Sinden, RR AF Kramer, PR Fragoso, G Pennie, W Htun, H Hager, GL Sinden, RR TI Transcriptional state of line mouse mammary tumor virus promoter can affect topological domain size in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI-CELLS; LONG TERMINAL REPEAT; DNA TOPOISOMERASE-I; SHOCK GENE LOCUS; TORSIONAL TENSION; CHROMATIN STRUCTURE; MMTV PROMOTER; INVIVO; ACTIVATION; NUCLEOSOME AB Unrestrained DNA supercoiling and the number of topological domains were measured within a 1.8 megabase pair chromosomal region consisting of about 200 tandem repeats of a mouse mammary tumor virus promoter-driven ha-v-ras gene. When uninduced, unrestrained negative supercoiling was organized into 32-kilobase pair (kb) topological domains. Upon induction, DNA supercoiling throughout the region was completely relaxed. Supercoiling was detected, however, when elongation was blocked before or following induction. The formation of transcription initiation complexes upon addition of dexamethasone decreased the domain size to 16 kb. During transcription the domain size was 9 kb, the length of one repeat. These results suggest that topological domain boundaries can be "functional" in nature, being established by the formation of activated and elongating transcription complexes. C1 Texas A&M Univ Syst, Hlth Sci Ctr, Inst Biosci & Technol, Ctr Genome Res, Houston, TX 77030 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20896 USA. RP Sinden, RR (reprint author), Texas A&M Univ Syst, Hlth Sci Ctr, Inst Biosci & Technol, Ctr Genome Res, 2121 W Holcombe Blvd, Houston, TX 77030 USA. OI Kramer, Phillip/0000-0003-0117-542X FU NIEHS NIH HHS [P01 ES05652] NR 52 TC 38 Z9 40 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 1999 VL 274 IS 40 BP 28590 EP 28597 DI 10.1074/jbc.274.40.28590 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700074 PM 10497225 ER PT J AU Paz, K Liu, YF Shorer, H Hemi, R LeRoith, D Quan, M Kanety, H Seger, R Zick, Y AF Paz, K Liu, YF Shorer, H Hemi, R LeRoith, D Quan, M Kanety, H Seger, R Zick, Y TI Phosphorylation of insulin receptor substrate-1 (IRS-1) by protein kinase B positively regulates IRS-1 function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; TYROSINE PHOSPHORYLATION; GLUCOSE-TRANSPORTER-4 TRANSLOCATION; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOTYROSINE PROTEIN; JUXTAMEMBRANE REGION; SIGNAL-TRANSDUCTION; GLUCOSE-TRANSPORT; POTENTIAL ROLE; ADIPOSE-CELLS AB Incubation of cells with insulin leads to a transient rise in Tyr phosphorylation of insulin receptor substrate (IRS) proteins, accompanied by elevation in their Ser(P)/Thr(P) content and their dissociation from the insulin receptor (IR), Wortmannin, a phosphatidylinositol 3-kinase inhibitor, selectively prevented the increase in Ser(P)/Thr(P) content of IRS-1, its dissociation from IR, and the decrease in its Tyr(P) content following 60 min of insulin treatment. Four conserved phosphorylation sites within the phosphotyrosine binding/SAIN domains of IRS-1 and IRS-S served as in vitro substrates for protein kinase B (PKB), a Ser/Thr kinase downstream of phosphatidylinositol 3-kinase, Furthermore, PKB and IRS-1 formed stable complexes in vivo, and overexpression of PKB enhanced Ser phosphorylation of IRS-l. Overexpression of PKB did not affect the acute Tyr phosphorylation of IRS-l; however, it significantly attenuated its rate of Tyr dephosphorylation following 60 min of treatment with insulin. Accordingly, overexpression of IRS-1(4A), lacking the four potential PKB phosphorylation sites, markedly enhanced the rate of Tyr dephosphorylation of IRS-I, while inclusion of vanadate reversed this effect. These results implicate a wortmannin-sensitive Ser/Thr kinase, different from PKB, as the kinase that phosphorylates IRS-I and acts as the feedback control regulator that turns off insulin signals by inducting the dissociation of IRS proteins from IR, In contrast, insulin-stimulated PKB-mediated phosphorylation of Ser residues within the phosphotyrosine binding/SAIN domain of IRS-1 protects IRS-1 from the rapid action of protein-tyrosine phosphatases and enables it to maintain its Tyr-phosphorylated active conformation. These findings implicate PHB as a positive regulator of IRS-l functions. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. Chaim Sheba Med Ctr, Inst Endocrinol, IL-52621 Tel Hashomer, Israel. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol & Cellular Endocrinol Branch, Bethesda, MD 20892 USA. RP Zick, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NR 56 TC 150 Z9 159 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 1999 VL 274 IS 40 BP 28816 EP 28822 DI 10.1074/jbc.274.40.28816 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700104 PM 10497255 ER PT J AU Robey, PG Biano, P AF Robey, PG Biano, P TI The role of osteogenic cells in the pathophysiology of Paget's disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 3rd International Symposium on Pagets Disease CY NOV 29-30, 1998 CL NAPA, CALIFORNIA ID OSTEOCLASTOGENESIS-INHIBITORY FACTOR; POLYMERASE CHAIN-REACTION; CHROMOSOME 18Q; BONE TISSUE; FIBROUS DYSPLASIA; GENETIC-LINKAGE; IN-VITRO; OSTEOPROTEGERIN; HYBRIDIZATION; EXPRESSION C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. Univ La Sapienza, Dipartimento Med Sperimentale & Patol, Div Pathol Anat & Histopathol, Rome, Italy. RP Robey, PG (reprint author), Bldg 30,Room 228,30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 64 TC 14 Z9 14 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1999 VL 14 SU 2 BP 9 EP 16 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240AZ UT WOS:000082804600003 PM 10510207 ER PT J AU Cooper, GS AF Cooper, GS TI Genetic studies of osteoporosis: What have we learned? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material ID BONE-MINERAL DENSITY; D-RECEPTOR GENOTYPE; ALLELES; WOMEN; POLYMORPHISMS; POSTMENOPAUSAL; POPULATION; FRACTURE; VIEW C1 NIEHS, Epidemiol Branch A305, Durham, NC 27709 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch A305, POB 12233, Durham, NC 27709 USA. NR 23 TC 11 Z9 13 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1999 VL 14 IS 10 BP 1646 EP 1648 DI 10.1359/jbmr.1999.14.10.1646 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 238VA UT WOS:000082732700002 PM 10491210 ER PT J AU Ho, N Punturieri, A Wilkin, D Szabo, J Johnson, M Whaley, J Davis, J Clark, A Weiss, S Francomano, C AF Ho, N Punturieri, A Wilkin, D Szabo, J Johnson, M Whaley, J Davis, J Clark, A Weiss, S Francomano, C TI Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID MOLECULAR-CLONING; GENE; OSTEOCLASTOMAS AB Pycnodyostosis, an autosomal recessive osteosclerosing skeletal disorder, has recently been shown to result from mutations in the cathepsin K gene. Cathepsin K, a lysosomal cysteine protease with an abundant expression in osteoclasts, has been implicated in osteoclast-mediated bone resorption and remodeling. DNA sequence analysis of the cathepsin K gene in a nonconsanguineous family demonstrated compound heterozygozity for mutations in two affected siblings. We have identified a missense mutation with a single base G-->A transition at cDNA nucleotide 236, resulting in conversion of a conserved glycine to a glutamine residue (G79E), The other mutation is an A-->T transition at nucleotide 154, leading to the substitution of a lysine residue by a STOP codon (K52X) predicting premature termination of the precursor cathepsin K polypeptide. Sequencing of genomic and cDNAs from the parents demonstrated that the missense mutation was inherited from the father and the nonsense mutation from the mother. Protein expression in both affected children was virtually absent, while in the parents was reduced by 50-80% compared with controls. The protein studies demonstrate that even significantly reduced cathepsin K levels do not have any phenotypic effect, whereas absent cathepsin K results in pycnodysostosis. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ctr Comprehens Canc, Div Hematol Oncol, Ann Arbor, MI 48109 USA. NCI, NIH, Bethesda, MD 20892 USA. Proteomix Inc, San Diego, CA USA. RP Francomano, C (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10C101, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R37-AI21301] NR 17 TC 34 Z9 38 U1 1 U2 3 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1999 VL 14 IS 10 BP 1649 EP 1653 DI 10.1359/jbmr.1999.14.10.1649 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 238VA UT WOS:000082732700003 PM 10491211 ER PT J AU Buzard, GS Enomoto, T Hongyo, T Perantoni, AO Diwan, BA Devor, DE Reed, CD Dove, LF Rice, JM AF Buzard, GS Enomoto, T Hongyo, T Perantoni, AO Diwan, BA Devor, DE Reed, CD Dove, LF Rice, JM TI neu mutation in schwannomas induced transplacentally in Syrian golden hamsters by N-nitrosoethylurea: high incidence but low allelic representation SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE neu; transplacental; schwannoma; peripheral nerve tumor; hamster ID EPIDERMAL GROWTH-FACTOR; DIFFERENTIATION FACTOR; NERVOUS-SYSTEM; CELL LINEAGE; ERBB-2 GENE; TRANSMEMBRANE DOMAIN; SIGNAL-TRANSDUCTION; FACTOR-RECEPTOR; POINT MUTATION; ONCOGENE AB Peripheral nerve tumors (PNT) and melanomas induced transplacentally on day 14 of gestation in Syrian golden hamsters by N-nitrosoethylurea were analyzed for activated oncogenes by the NIH 3T3 transfection assay, and for mutations in the neu oncogene by direct sequencing, allele-specific oligonucleotide hybridization, MnlI restriction-fragment-length polymorphism, single-strand conformation polymorphism, and mismatch amplification mutation assays. All (67/67) of the PNT, but none of the melanomas, contained a somatic missense T --> A transversion within the neu oncogene transmembrane domain at a site corresponding to that which also occurs in rat schwannomas transplacentally induced by N-nitrosoethylurea. In only 2 of the 67 individual hamster PNT did the majority of tumor cells appear to carry the mutant neu allele, in contrast to comparable rat schwannomas in which it overwhelmingly predominates. The low fraction of hamster tumor cells carrying the mutation was stable through multiple transplantation passages. In the hamster, as in the rat, specific point-mutational activation of the neu oncogene thus constitutes the major pathway for induction of PNT by transplacental exposure to am alkylating agent, but the low allelic representation of mutant neu in hamster PNT suggests a significant difference in mechanism by which the mutant oncogene acts in this species. C1 NCI, Carcinogenesis Study Sect, Intramural Res Support Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, FCRDC, Frederick, MD 21702 USA. RP Buzard, GS (reprint author), NCI, Carcinogenesis Study Sect, Intramural Res Support Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Bldg 538, Frederick, MD 21702 USA. NR 48 TC 6 Z9 6 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD OCT PY 1999 VL 125 IS 10 BP 529 EP 540 DI 10.1007/s004320050313 PG 12 WC Oncology SC Oncology GA 235XW UT WOS:000082570000001 PM 10473865 ER PT J AU Masiero, L Lapidos, KA Ambudkar, I Kohn, EC AF Masiero, L Lapidos, KA Ambudkar, I Kohn, EC TI Regulation of the RhoA pathway in human endothelial cell spreading on type IV collagen: role of calcium influx SO JOURNAL OF CELL SCIENCE LA English DT Article DE calcium; RhoA; angiogenesis; actin stress fiber ID FOCAL ADHESION KINASE; ACTIN STRESS FIBERS; GTP-GAMMA-S; GROWTH-FACTOR; FAMILY GTPASES; SMOOTH-MUSCLE; CYTOSKELETON; STIMULATION; RECEPTOR; PROTEIN AB We have shown that nonvoltage-operated Ca2+ entry regulates human umbilical vein endothelial cell adhesion, migration, and proliferation on type IV collagen, We now demonstrate a requirement for Ca2+ influx for activation of the RhoA pathway during endothelial cell spreading on type IV collagen. Reorganization of actin into stress fibers was complete when the cells where fully spread at 90 minutes. No actin organization into stress fibers was seen in endothelial cells plated on type I collagen, indicating a permissive effect of type TV collagen, CAI, a blocker of nonvoltage-operated Ca2+ channels, prevented development of stress fiber formation in endothelial cells on type IV collagen, This permissive effect was augmented by Ca2+ influx, as stimulated by 0.5 mu M thapsigargin or 0.1 mu M ionomycin, yielding faster development of actin stress fibers, Ca2+ influx and actin rearrangement in response to thapsigargin and ionomycin were abrogated by CAI, Activated, membrane-bound RhoA is a substrate for C3 exoenzyme which ADP-ribosylates and inactivates RhoA, preventing actin stress fiber formation. Pretreatment of endothelial cells with C3 exoenzyme prevented basal and thapsigargin-augmented stress fiber formation, While regulation of Ca2+ influx did not alter RhoA translocation, it reduced in vitro ADP-ribosylation of RhoA (P-2<0.05), suggesting Ca2+ influx is needed for RhoA activation during spreading on type IV collagen; no Ca2+ regulated change in RhoA was seen in HUVECs spreading on type I collagen matrix, Blockade of Ca2+ influx of HUVEC spread on type IV collagen also reduced tyrosine phosphorylation of p190Rho-GAP and blocked thapsigargin-enhanced binding of p190Rho-GAP to focal adhesion kinase, Thus, Ca2+ influx is necessary for RhoA activation and for linkage of the RhoA/stress fiber cascade to the focal adhesion/focal adhesion kinase pathway during human umbilical vein endothelial cell spreading on type IV collagen. C1 NCI, Mol Signaling Sect, Pathol Lab, Bethesda, MD 20892 USA. NIDR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Mol Signaling Sect, Pathol Lab, Bethesda, MD 20892 USA. NR 34 TC 52 Z9 52 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT PY 1999 VL 112 IS 19 BP 3205 EP 3213 PG 9 WC Cell Biology SC Cell Biology GA 250JK UT WOS:000083385100004 PM 10504326 ER PT J AU Everett, RD Earnshaw, WC Pluta, AF Sternsdorf, T Ainsztein, AM Carmena, M Ruchaud, S Hsu, WL Orr, A AF Everett, RD Earnshaw, WC Pluta, AF Sternsdorf, T Ainsztein, AM Carmena, M Ruchaud, S Hsu, WL Orr, A TI A dynamic connection between centromeres and ND10 proteins SO JOURNAL OF CELL SCIENCE LA English DT Article DE ND10; PML nuclear domain; centromere; proteasome inhibitor ID ACUTE PROMYELOCYTIC LEUKEMIA; DOT-ASSOCIATED PROTEINS; POSITION-EFFECT VARIEGATION; NUCLEAR-BODIES; COVALENT MODIFICATION; CHROMOSOMAL PROTEIN; BINDING PROTEIN; CENP-C; PML; HETEROCHROMATIN AB ND10, otherwise known as nuclear dots, PML nuclear bodies or PODs, are punctate foci in interphase nuclei that contain several cellular proteins. The functions of ND10 have not been well defined, but they are sensitive to external stimuli such as stress and virus infection, and they are disrupted in malignant promyelocytic leukaemia cells, Herpes simplex virus type 1 regulatory protein Vmw110 induces the proteasome-dependent degradation of ND10 component proteins PML and Sp100, particularly the species of these proteins which are covalently conjugated to the ubiquitin-like protein SUMO-1. We have recently reported that Vmw110 also induces the degradation of centromere protein CENP-C with consequent disruption of centromere structure, These observations led us to examine whether there were hitherto undetected connections between ND10 and centromeres. In this paper we report that hDaxx and HP1 (which have been shown to interact with CENP-C and Sp100, respectively) are present in a proportion of both ND10 and interphase centromeres, Furthermore, the proteasome inhibitor MG132 induced an association between centromeres and ND10 proteins PML and Sp100 in a significant number of cells in the G(2) phase of the cell cycle, These results imply that there is a dynamic, cell cycle regulated connection between centromeres and ND10 proteins which can be stabilised by inhibition of proteasome-mediated proteolysis. C1 MRC, Virol Unit, Glasgow G11 5JR, Lanark, Scotland. Univ Edinburgh, Inst Cell & Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland. Univ Maryland, Inst Biotechnol, Dept Mol Biol & Biophys, Baltimore, MD 21201 USA. Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Everett, RD (reprint author), MRC, Virol Unit, Church St, Glasgow G11 5JR, Lanark, Scotland. FU Wellcome Trust [, 073915] NR 44 TC 88 Z9 92 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT PY 1999 VL 112 IS 20 BP 3443 EP 3454 PG 12 WC Cell Biology SC Cell Biology GA 257NC UT WOS:000083787200005 PM 10504293 ER PT J AU Sasaki, CY Lin, HC Passaniti, A AF Sasaki, CY Lin, HC Passaniti, A TI Regulation of urokinase plasminogen activator (uPA) activity by E-cadherin and hormones in mammary epithelial cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX; CARCINOMA-CELLS; BREAST-CARCINOMA; IN-VITRO; INVASION; METASTASIS; RECEPTOR; SURVIVAL; PATHWAYS; BIOLOGY AB Urokinase plasminogen activator (uPA) is involved in proteolysis of extracellular matrix during development and tumor cell invasion. In the present study, we examined the regulation of uPA in hormone-responsive, noninvasive mammary epithelial cells by using fibrinolytic and caseinolytic enzyme activity assays. Urokinase PA expression was activated after contact with fibrin and initiation of cell-cell interactions that were mediated by E-cadherin. Fibrinolysis occurred in zones surrounding cellular aggregates. Stromal matrix proteins that disrupted aggregation or anti-E-cadherin antibodies that inhibited cellular compaction inhibited fibrinolysis perhaps by increasing cell-matrix adhesion or preventing E-cadherin signaling, respectively. Aggregation required the presence of divalent cations and was inhibited by serum and ethylene diaminetetraacetic acid, whereas serine protease inhibitors reduced uPA activity without affecting aggregation. inhibitors of PA (type 2; PAI-2) and a specific antisense uPA oligonucleotide also reduced enzymatic activity, suggesting that fibrinolysis depends on translational regulation of uPA. In addition, the activation of plasmin from plasminogen was inhibited by anti-E-cadherin antibodies and PAI-2, consistent with a role for uPA. The data also support a role for transcriptional regulation of uPA activity because treatment of cells with progesterone, hydrocortisone, or dexamethasone inhibited uPA activation on fibrin without affecting cellular aggregation. Estradiol and insulin did not alter, whereas human chorionic gonadotropin and prolactin increased uPA activity. The expression of the 55-kDa uPA activity was consistent with specific hormone action and correlated with protein expression by immunoblotting. Therefore, the alteration of downstream signaling events by hormones may affect uPA production. These results indicate that uPA is an enzyme that may be important in the degradation of extracellular matrix during development and that specific E-cadherin interactions and hormones can regulate its activity, investigation of the regulation of uPA in these cells may be useful in understanding and manipulating mammary gland remodeling. J. Cell. Physiol. 181:7-13, 1999. Published 1999 Wiley-Liss, Inc. C1 NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Passaniti, A (reprint author), Univ Maryland, Greenebaum Canc Ctr, Dept Pathol, 655 W Baltimore St, Baltimore, MD 21201 USA. NR 29 TC 8 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 1999 VL 181 IS 1 BP 1 EP 13 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 229DW UT WOS:000082179100001 PM 10457348 ER PT J AU Berezhkovskii, AM Bezrukov, SM Bicout, DJ Weiss, GH AF Berezhkovskii, AM Bezrukov, SM Bicout, DJ Weiss, GH TI The influence of polymer on the diffusion of a spherical tracer SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PROBING ALAMETHICIN CHANNELS; WATER-SOLUBLE POLYMERS; ION-CHANNEL; FIXED AXES; PORE; CHAINS; SPANS AB We analyze how the addition of a small number of polymer molecules influences the diffusion constant of a spherical tracer, whose radius is small compared to the size of the polymer. We show that the polymer chain can be regarded as a two-dimensional object which is an impenetrable obstacle for the tracer. It is also shown that the diffusion constant of the tracer, in contrast to the solution viscosity, is independent of chain length, depending only on the monomer concentration. (C) 1999 American Institute of Physics. [S0021-9606(99)52437-9]. C1 NICHHD, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. RP Berezhkovskii, AM (reprint author), NICHHD, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. NR 24 TC 8 Z9 8 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 1 PY 1999 VL 111 IS 13 BP 5641 EP 5644 DI 10.1063/1.479865 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 238UW UT WOS:000082732100003 ER PT J AU Spinella, GM AF Spinella, GM TI Research directions: Follow-up of the Joubert Syndrome Workshop, October 21, 1998 SO JOURNAL OF CHILD NEUROLOGY LA English DT Article C1 NINDS, Div Fundamental Neurosci & Dev Disorders, NIH, Bethesda, MD 20892 USA. RP Spinella, GM (reprint author), NINDS, Div Fundamental Neurosci & Dev Disorders, NIH, 6001 Execut Blvd,Room 2132, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD OCT PY 1999 VL 14 IS 10 BP 667 EP 668 DI 10.1177/088307389901401008 PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 240DE UT WOS:000082809900008 PM 10511340 ER PT J AU Ozata, M Ozdemir, IC Licinio, J AF Ozata, M Ozdemir, IC Licinio, J TI Human leptin deficiency caused by a missense mutation: Multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EARLY-ONSET OBESITY; FRAMESHIFT MUTATION; CIRCULATING LEPTIN; MORBID-OBESITY; THYROID STATUS; HORMONE; WOMEN; RECEPTOR; PUBERTY; SIGNAL AB We have previously demonstrated that genetically based leptin deficiency due to a missense leptin gene mutation in a highly consanguineous extended Turkish pedigree is associated with morbid obesity and hypogonadism. We have now performed detailed assessments of endocrine, sympathetic, and immune function. We have also identified a new adult female homozygous patient in this extended family who is severely obese and amenorrheic. In this family all wild-type and heterozygous individuals have normal body weight. Seven obese members of this family, whom we presume to have been leptin deficient, died during childhood. There are several findings that indicate potentially novel targets for leptin action in humans. Four homozygous patients (1 adult male, 2 adult females, and 1 child) have sympathetic system dysfunction, whereas all heterozygous subjects have normal sympathetic system function. Despite sympathetic system dysfunction and postural hypotension, 1 of 3 homozygous adult patients has impaired renin-aldosterone function. The patients also exhibit alterations in GH and PTH-calcium function, and 1 of them has decreased bone mineral density. Despite their obesity, these patients do not have risk factors for cardiovascular disease, such as hypertension, impairments in lipid metabolism, or hyperglycemia. These data support the hypothesis that the obese may have central, but not peripheral, resistance to the effects of leptin and that hyperglycemia may mediate the cardiovascular morbidity of the obese who are not leptin deficient. Furthermore, these data indicate that there may be several new targets for leptin action in human physiology. Such new targets may lead to novel pharmacological strategies for the use of leptin agonists and antagonists in the treatment of human disease. All 19 normal weight individuals in this family are alive, whereas 7 of 11 obese individuals died in childhood after infections. The odds ratio for mortality in the context of this obesity phenotype is 25.4, indicating that this mutation severely impairs key biological functions during childhood, negatively impacting on survival. We found that only the obese child in this family had thyroid function abnormalities. The oldest homozygous female patient started to menstruate, albeit with a luteal phase defect, 7 months ago, after a delay of over 20 yr, whereas the younger adult subjects are still hypogonadic. Thus, we conclude that due to their long life span, humans who survive the negative effects of leptin deficiency during childhood can, in contrast to ob/ob mice, over decades compensate some of the effects of leptin deficiency on immunity and endocrine function through mechanisms that remain to be elucidated. C1 Gulhane Mil Med Acad, Dept Endocrinol & Metab, TR-06018 Ankara, Turkey. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Licinio, J (reprint author), Univ Calif Los Angeles, Dept Psychol, Gonda Ctr 3554, 695 Charles Young Dr S, Los Angeles, CA 90095 USA. EM Licinio@ucla.edu NR 46 TC 415 Z9 438 U1 0 U2 4 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 1999 VL 84 IS 10 BP 3686 EP 3695 DI 10.1210/jc.84.10.3686 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 243TL UT WOS:000083013300045 PM 10523015 ER PT J AU Gladwin, MT Schechter, AN Shelhamer, JH Pannell, LK Conway, DA Hrinczenko, BW Nichols, JS Pease-Fye, ME Noguchi, CT Rodgers, GP Ognibene, FP AF Gladwin, MT Schechter, AN Shelhamer, JH Pannell, LK Conway, DA Hrinczenko, BW Nichols, JS Pease-Fye, ME Noguchi, CT Rodgers, GP Ognibene, FP TI Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID S-NITROSOHEMOGLOBIN; BLOOD-FLOW; INHIBITION; DISEASE; NITROSOTHIOLS; MECHANISMS; ANEMIA; NO AB Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of P-chain cysteine 93, raise the possibilty of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P-50, did not respond to inhaled NO, either in controls or in individuals with sickle cell disease. At baseline, the arterial and venous levels of nitrosylated hemoglobin were not significantly different, but NO inhalation led to a dose-dependent increase in mean nitrosylated hemoglobin, and at the highest dosage, a significant arterial-venous difference emerged. The levels of nitrosylated hemoglobin are tao low to affect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular perfusion. C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, NIDDK, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. NIH, NIDDK, Biol Chem Lab, Bethesda, MD 20892 USA. NIH, NIDDK, Structural Mass Spectrometry Grp, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 26 TC 76 Z9 77 U1 0 U2 1 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 1999 VL 104 IS 7 BP 937 EP 945 DI 10.1172/JCI7637 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WH UT WOS:000083469000016 PM 10510334 ER PT J AU Schnermann, J Briggs, JP AF Schnermann, J Briggs, JP TI The macula densa is worth its salt SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID GLOMERULAR-FILTRATION RATE; ACUTE VOLUME EXPANSION; NITRIC-OXIDE SYNTHASE; TUBULOGLOMERULAR FEEDBACK; BARTTERS-SYNDROME; HYPOKALEMIC ALKALOSIS; MUTATIONS; COTRANSPORTER; CELLS C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10,Room 4D51,10 Ctr Dr MSC 1370, Bethesda, MD 20892 USA. RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 NR 20 TC 18 Z9 18 U1 0 U2 0 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 1999 VL 104 IS 8 BP 1007 EP 1009 DI 10.1172/JCI8539 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WJ UT WOS:000083469100004 PM 10525035 ER PT J AU Thomson, SC Bachmann, S Bostanjoglo, M Ecelbarger, CA Peterson, OW Schwartz, D Bao, DJ Blantz, RC AF Thomson, SC Bachmann, S Bostanjoglo, M Ecelbarger, CA Peterson, OW Schwartz, D Bao, DJ Blantz, RC TI Temporal adjustment of the juxtaglomerular apparatus during sustained inhibition of proximal reabsorption SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE; TUBULOGLOMERULAR FEEDBACK; DIETARY SALT; RAT-KIDNEY AB Tubuloglomerular feedback (TGF) stabilizes nephron function by causing changes in single-nephron GFR (SNGFR) to compensate for changes in late proximal flow (VLP). TGF responds within seconds and reacts over a narrow range of VLP that surrounds normal VLP. To accommodate sustained increases in VLP, TGF must reset around the new flow. We studied TGF resetting by inhibiting proximal reabsorption with benzolamide (BNZ; administered repeatedly over a 24-hour period) in Wistar-Froemter rats. BNZ acutely activates TGF, thereby reducing SNGFR. Micropuncture was performed 6-10 hours after the fourth BNZ dose, when diuresis had subsided. BNZ caused glomerular hyperfiltration, which was prevented with inhibitors of macula densa nitric oxide synthase (NOS). Because of hyperfiltration, BNZ increased VLP and distal flow but did not affect the basal TGF stimulus (early distal salt concentration). BNZ slightly blunted normalized maximum TGF response and the basal state of TGF activation. BNZ sensitized SNGFR to reduction by S-methyl-thiocitrulline (SMTC) and caused the maximum TGF response to be strengthened by SMTC. Sensitization to type I NOS (NOS-I) blockers correlated with increased macula densa NOS-I immunoreactivity. Tubular transport measurements confirmed that BNZ affected TGF within the juxtaglomerular apparatus. During reduced proximal reabsorption, TGF resets to accommodate increased flow and SNGFR through a mechanism involving macula densa NOS. C1 Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, San Diego, CA 92161 USA. San Diego Vet Affairs Med Ctr, San Diego, CA 92161 USA. Vet Affairs Med Ctr, San Diego, CA 92161 USA. Vet Med Res Fdn, San Diego, CA 92161 USA. Humboldt Univ, Inst Anat, D-14050 Berlin, Germany. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Thomson, SC (reprint author), Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. FU NIDDK NIH HHS [DK-28602, R01 DK028602] NR 20 TC 42 Z9 42 U1 0 U2 0 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 1999 VL 104 IS 8 BP 1149 EP 1158 DI 10.1172/JCI5156 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WJ UT WOS:000083469100023 PM 10525054 ER PT J AU Masilamani, S Kim, GH Mitchell, C Wade, JB Knepper, MA AF Masilamani, S Kim, GH Mitchell, C Wade, JB Knepper, MA TI Aldosterone-mediated regulation of ENaC alpha,beta, and gamma subunit proteins in rat kidney SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID EPITHELIAL SODIUM-CHANNEL; NA+ CHANNEL; BETA-SUBUNITS; EXPRESSION; LOCALIZATION AB Aldosterone stimulates sodium transport in the renal collecting duct by activating the epithelial sodium channel (ENaC). To investigate the basis of this effect, we have developed a novel set of rabbit polyclonal antibodies to the 3 subunits of ENaC and have determined the abundance and distribution of ENaC subunits in the principal cells of the rat renal collecting duct. Elevated circulating aldosterone (due to either dietary NaCl restriction or aldosterone infusion) markedly increased the abundance of alpha ENaC protein without increasing the abundance of the beta and gamma subunits. Thus, alpha ENaC is selectively induced by aldosterone. In addition, immunofluorescence immunolocalization showed a striking redistribution in ENaC labeling to the apical region of the collecting duct principal cells. Finally, aldosterone induced a shift in molecular weight of gamma ENaC from 85 kDa to 70 kDa, consistent with physiological proteolytic clipping of the extracellular loop as postulated previously. Thus, at the protein level, the response of ENaC to aldosterone stimulation is heterogenous, with both quantitative and qualitative changes that can explain observed increases in ENaC-mediated sodium transport. C1 NIH, NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Knepper, MA (reprint author), NIH, NHLBI, Kidney & Electrolyte Metab Lab, Bldg 10,Room 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 22 TC 367 Z9 368 U1 0 U2 7 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 1999 VL 104 IS 7 BP R19 EP R23 DI 10.1172/JCI7840 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WH UT WOS:000083469000021 PM 10510339 ER PT J AU Muller, FMC Kasai, M Francesconi, A Brillante, B Roden, M Peter, J Chanock, SJ Walsh, TJ AF Muller, FMC Kasai, M Francesconi, A Brillante, B Roden, M Peter, J Chanock, SJ Walsh, TJ TI Transmission of an azole-resistant isogenic strain of Candida albicans among human immunodeficiency virus-infected family members with oropharyngeal candidiasis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ANTIFUNGAL DRUG-RESISTANCE; HIV-POSITIVE PATIENTS; NEUTROPENIC PATIENTS; ORAL CANDIDIASIS; FLUCONAZOLE; EPIDEMIOLOGY AB We report transmission of an azole-resistant, isogenic strain of Candida albicans in a human immunodeficiency virus (HIV)-infected family of two children with symptomatic oropharyngeal candidiasis and a mother with asymptomatic colonization over a 5-year period. These findings were confirmed by three different molecular epidemiology methods: interrepeat PCR, Southern hybridization with a C, albicans repetitive element 2 probe, and electrophoretic karyotyping. This study contributes to an evolving understanding of the mode of transmission of C, albicans, particularly in children, and underscores the importance of monitoring specimens from family members of HIV-infected patients. C1 Univ Wurzburg, Inst Mol Infektionsbiol, D-97070 Wurzburg, Germany. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Muller, FMC (reprint author), Univ Wurzburg, Inst Mol Infektionsbiol, Rontgenring 11, D-97070 Wurzburg, Germany. NR 23 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1999 VL 37 IS 10 BP 3405 EP 3408 PG 4 WC Microbiology SC Microbiology GA 237FN UT WOS:000082644800063 PM 10488220 ER PT J AU Rowlings, PA Curtis, RE Passweg, JR Deeg, HJ Socie, G Travis, LB Kingma, DW Jaffe, ES Sobocinski, KA Horowitz, MM AF Rowlings, PA Curtis, RE Passweg, JR Deeg, HJ Socie, G Travis, LB Kingma, DW Jaffe, ES Sobocinski, KA Horowitz, MM TI Increased incidence of Hodgkin's disease after allogeneic bone marrow transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; DISORDERS; LEUKEMIA; AIDS AB Purpose: Immune dysregulation associated with allogeneic bone marrow transplantation (BMT) is linked to an increased risk of posttransplant lymphoproliferative disorders (PTLD); however, reports of Hodgkin's disease (HD) after transplantation are rare. Patients and Methods: We evaluated the risk of HD among 18,531 persons receiving allogeneic BMT between 1964 and 1992 at 235 centers. The number of HD cases was compared with that expected in the general population. Risk factors were identified using Poisson regression and a nested case-control study. Results: Risk of HD was increased in the postBMT population compared with the general population with an observed-to-expected incidence ratio (O/E) of 6.2 (observed cases, n = 8; 95% confidence interval [CI], 2.7 to 12). A significantly increased risk of HD remained after excluding two human immunodeficiency virus-positive patients (observed cases, n = 6; O/E = 4.7, 95% CI, 1.7 to 10.3). Mixed cellularity subtype predominated (five of eight cares, 63%). Five of six assessable cases contained Epstein-Barr virus (EBV) genome, Posttransplant HD differed from PTLD by letter onset (> 2.5 years) and lack of association with established risk factors (such as T-cell depletion and HLA disparity). Patients with HD were more likely than matched controls to have had grade 2 to 4 acute graft-versus-host disease (GVHD), required therapy for chronic GVHD, or both (P = .002), although analysis included small numbers of patients. Conclusion: The increased incidence of HD among BMT recipients adds support to current theories which link overstimulation of cell-mediated immunity and exposure to EBV with various subtypes of HD. The long latency of HD after transplant and lack of association with risk factors for PTLD is noteworthy and should be explored further for possible insights into pathogenesis. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Biol & Diag, Pathol Lab, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Prince Wales Hosp, Dept Haematol, Randwick, NSW 2031, Australia. Kantonsspital, Dept Innere Med, CH-4031 Basel, Switzerland. Hop St Louis, Paris, France. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Curtis, RE (reprint author), NCI, Div Canc Epidemiol & Genet, Executive Plaza S,Suite 7042, Bethesda, MD 20892 USA. FU NCI NIH HHS [CP-51028, CP-51027, P01-CA-18029] NR 21 TC 50 Z9 51 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1999 VL 17 IS 10 BP 3122 EP 3127 PG 6 WC Oncology SC Oncology GA 241YQ UT WOS:000082911800016 PM 10506608 ER PT J AU Kefford, RF Bishop, JAN Bergman, W Tucker, MA AF Kefford, RF Bishop, JAN Bergman, W Tucker, MA CA Melanoma Genetics Consortium TI Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the melanoma genetics consortium SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; ATYPICAL-MOLE SYNDROME; FAMILIAL MELANOMA; DYSPLASTIC NEVI; CDKN2A MUTATIONS; PRONE FAMILIES; HEREDITARY MELANOMA; GERMLINE MUTATIONS; PANCREATIC-CANCER; INVASIVE MELANOMA C1 Univ Sydney, Westmead Inst Canc Res, Westmead Hosp, Sydney, NSW 2130, Australia. St James Univ Hosp, Imperial Canc Res Fund, Canc Med Res Unit, Leeds LS9 7TF, W Yorkshire, England. Leiden Univ, Med Ctr, Leiden, Netherlands. NCI, Rockville, MD USA. RP Kefford, RF (reprint author), Univ Sydney, Westmead Inst Canc Res, Westmead Hosp, Sydney, NSW 2130, Australia. RI Bianchi Scarra, Giovanna/G-8933-2014; Tucker, Margaret/B-4297-2015; OI Bianchi Scarra, Giovanna/0000-0002-6127-1192; Newton Bishop, Julia/0000-0001-9147-6802 NR 52 TC 143 Z9 145 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1999 VL 17 IS 10 BP 3245 EP 3251 PG 7 WC Oncology SC Oncology GA 241YQ UT WOS:000082911800034 PM 10506626 ER PT J AU Jacobsen, FM Comas-Diaz, L AF Jacobsen, FM Comas-Diaz, L TI Donepezil for psychotropic-induced memory loss SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ALZHEIMERS-DISEASE; DOUBLE-BLIND; SCOPOLAMINE; COGNITION; MOOD; DISORDERS; BEHAVIOR; DEMENTIA; AGENTS AB Background: Donepezil is an acetylcholinesterase inhibitor marketed for treatment of memory loss and behavioral deterioration associated with the acetylcholine deficit of Alzheimer's disease. We investigated the utility and tolerability of donepezil in nongeriatric affective illness for treatment of psychotropic-induced memory loss, dry mouth, and constipation. Method: Nondemented outpatients with stabilized DSM-IV affective illness took 5 mg/day of donepezil for 3 weeks and then increased to 10 mg/day in open trials. Self-rating scales of target symptoms were completed by patients before and 3 to 4 weeks after starting each dose condition. Patients who chose to continue donepezil therapy returned for clinical monitoring every 4 to 8 weeks. Results: Eleven women and 11 men (mean +/- SD age = 45.4 +/- 8.5 years) completed donepezil trials. Nineteen patients with memory loss rat-ed improvement while taking 5 mg/day of donepezil (p < .001); subsequently, 6 rated further improvement with 10 mg/day (p = .057). Donepezil, 5 mg/day, also reduced ratings of dry mouth (N = 16; p < .001) and constipation(N = 11; p < .05). Side effects included insomnia, nausea, vomiting, and diarrhea; surprisingly, 2 bipolar patients became manic within hours of starting donepezil. Sixteen patients (72%) continued donepezil for an average of 7 months. Consideration of family histories suggested that donepezil response in affective illness may be an early indicator of vulnerability to dementia of the Alzheimer's type. Conclusion: (1) Donepezil can reduce memory loss, dry mouth, and constipation in nongeriatric affective patients, but may trigger mania; and (2) long-term follow-up will reveal the predictive value for dementia of donepezil's memory restoration in nongeriatric subjects. C1 George Washington Univ, Sch Med, Transcultural Mental Hlth Inst, Washington, DC 20036 USA. George Washington Univ, Sch Med, Dept Psychiat & Behav Serv, Washington, DC 20036 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Jacobsen, FM (reprint author), George Washington Univ, Sch Med, Transcultural Mental Hlth Inst, 1301 20th ST NW,Suite 711, Washington, DC 20036 USA. NR 37 TC 20 Z9 20 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 1999 VL 60 IS 10 BP 698 EP 704 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 250LF UT WOS:000083389300009 PM 10549687 ER PT J AU Alcalay, R Alvarado, M Balcazar, H Newman, E Huerta, E AF Alcalay, R Alvarado, M Balcazar, H Newman, E Huerta, E TI Salud para su Corazon: A community-based Latino cardiovascular disease prevention and outreach model SO JOURNAL OF COMMUNITY HEALTH LA English DT Article ID HEALTH PROMOTION; NATIONAL-HEALTH; HEART-DISEASE; RISK-FACTORS; EDUCATION; AMERICAN; KNOWLEDGE; MORTALITY; HISPANICS; BEHAVIOR AB Cardiovascular disease (CVD) is the leading cause of death for Latinos living in the United States. This population is generally unaware of important lifestyle or behavioral changes that can prevent CVD. The National Heart, Lung, and Blood Institute (NHLBI) designed and implemented Salud para su Corazon (Health for Your Heart), a culturally appropriate, community-based, theory-driven intervention model. NHLBI's goals were: (1) to design an intervention model appropriate to Latino populations; (2) to pilot test the model in a specific community with the objectives of increasing awareness about heart disease, raising knowledge about CVD prevention, and promoting heart-healthy lifestyles; and (3) to disseminate the model and the materials developed to other communities with similar needs. An agency-community partnership, under the leadership of the Community Alliance for Heart Health, guided all stages of the community intervention project. The multimedia bilingual community intervention included television telenovela format public service announcements (PSAs), radio programs, brochures, recipe booklets, charlas, a promotores training manual, and motivational videos. An evaluation survey assessed the impact of the intervention. A pre-post intervention survey was conducted with more than 300 participants, and results showed that the respondents were substantially more aware of risk factors for CVD, and had greatly increased their knowledge of ways to prevent heart disease. Dissemination efforts have resulted in numerous requests by health organizations, universities, and health maintenance organizations (HMOs) for educational materials and communication strategies produced by Salud para su Corazon. In addition, Univision, the largest Spanish-language broadcast television network, is airing the initiative's PSAs. Also, training seminars for promotores are being conducted in different regions of the United States, and several locations are planning to replicate this study. C1 Univ Calif Davis, Dept Commun, Davis, CA 95616 USA. NHLBI, Minor Hlth Educ Program, Bethesda, MD 20892 USA. NHLBI, Outreach Program, Bethesda, MD 20892 USA. Arizona State Univ, Tempe, AZ 85287 USA. Washington Hosp Ctr, Washington, DC 20010 USA. RP Alcalay, R (reprint author), Univ Calif Davis, Dept Commun, Davis, CA 95616 USA. NR 38 TC 58 Z9 58 U1 0 U2 12 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD OCT PY 1999 VL 24 IS 5 BP 359 EP 379 DI 10.1023/A:1018734303968 PG 21 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 250LE UT WOS:000083389200004 PM 10555925 ER PT J AU Stein, MT Zentall, S Shaywitz, S Shaywitz, B AF Stein, MT Zentall, S Shaywitz, S Shaywitz, B TI A school-aged child with delayed reading skills SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE dyslexia; phonetic code; learning disabilities AB CASE. During a health supervision visit, the father of a 7.5-year-old African American second-grader asked about his son's progress in reading. He was concerned when, at a recent teacher-parent conference to review Darren's progress, the teacher remarked that Darren was not keeping up with reading skills compared with others in his class. She said that he had difficulty sounding out some words correctly. In addition, he could not recall words he had read the day before. The teacher commented that Darren was a gregarious, friendly child with better-than-average verbal communication skills. His achievement at math was age-appropriate; spelling, however, was difficult for Darren, with many deleted letters and reversals of written letters. A focused history did not reveal any risk factors for a learning problem in the prenatal or perinatal periods. Early motor, language, and social milestones were achieved on time. Darren had not experienced any head injury, loss of consciousness, or chronic medical illness. He had several friends, and his father denied any behavioral problems at home or at school. His teacher completed a DSM-IV-specific behavioral survey for attention-deficit/hyperactivity disorder (ADHD). It did not show any evidence of ADHD. Darren's father completed 1 year of college and is currently the manager of a neighborhood convenience store. His mother had a high school education; she recalled that she found it difficult to complete assignments that required reading or writing. She is employed as a waitress. Darren does not have any siblings. The pediatrician performed a complete physical examination, the results of which were normal, including visual acuity, audiometry, and a neurological examination. It was noted that Darren seemed to pause several times in response to questions or commands. On two occasions, during finger-nose testing and a request to assess tandem gait, directions required repetition. Overall, he was pleasant and seemed to enjoy the visit. His pediatrician concluded that he had a learning problem but she was uncertain about the next step. She asked herself, "Is there anything else I can do in the office to evaluate Darren's problem with learning? Should I quickly refer him for educational testing or encourage a reading tutor? What questions can I ask his teacher that would be helpful? Am I missing a medical disorder?". C1 Univ Calif San Diego, San Diego, CA 92103 USA. Purdue Univ, W Lafayette, IN 47907 USA. NICHD, Yale Ctr Study Learning & Attent, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. RP Stein, MT (reprint author), Univ Calif San Diego, San Diego, CA 92103 USA. NR 9 TC 4 Z9 4 U1 1 U2 3 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 1999 VL 20 IS 5 BP 381 EP 385 PG 5 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 245PP UT WOS:000083117600015 PM 10533999 ER PT J AU Brown, LM Zahm, SH Hoover, RN Fraumeni, JF AF Brown, LM Zahm, SH Hoover, RN Fraumeni, JF TI Bracken fern consumption and human bladder cancer SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 NR 6 TC 1 Z9 1 U1 1 U2 2 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 1999 VL 53 IS 10 BP 653 EP 653 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 239RK UT WOS:000082783300019 PM 10616681 ER PT J AU Wang, GH Garvey, TL Cohen, JI AF Wang, GH Garvey, TL Cohen, JI TI The murine gammaherpesvirus-68 M11 protein inhibits Fas- and TNF-induced apoptosis SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID DEATH EFFECTOR; B-CELLS; HUMAN HERPESVIRUS-8; EPITHELIAL-CELLS; BCL-2 HOMOLOG; VIRUS; INFECTION; ENCODES; BHRF1; ALPHA AB The murine gammaherpesvirus-68 (MHV-68) M11 gene encodes a protein predicted to have limited homology to the bcl-2 family of proteins, Unlike most of the other viral bcl-2 homologues, which have both BH1 and BH2 domains conserved with respect to bcl-2, the M11 protein has a BH1 domain, but apparently lacks a BH2 domain. Transfection of HeLa cells with an epitope-tagged MHV-68 M11 construct showed that the protein is predominantly located in the cytoplasm of cells. In HeLa cells, M11 inhibited apoptosis induced by anti-Fas antibody and by TNF-alpha. Thus, despite its limited conservation with respect to other bcl-2 family members, the MHV-68 M11 protein is a potent inhibitor of apoptosis. C1 NIAID, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 60 Z9 64 U1 1 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 1999 VL 80 BP 2737 EP 2740 PN 10 PG 4 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 241BZ UT WOS:000082863400024 PM 10573168 ER PT J AU Wilson, KE Li, ZQ Kara, M Gardner, KL Roberts, DD AF Wilson, KE Li, ZQ Kara, M Gardner, KL Roberts, DD TI beta(1) integrin- and proteoglycan-mediated stimulation of T lymphoma cell adhesion and mitogen-activated protein kinase signaling by thrombospondin-1 and thrombospondin-1 peptides SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; BINDING PEPTIDES; TERMINAL DOMAIN; HEPARIN-BINDING; SEQUENCE MOTIF; MELANOMA-CELLS; RECEPTOR; GROWTH; PROLIFERATION; CD36 AB Cell-cell and cell-matrix interactions play important regulatory roles in lymphocyte homeostasis, Thrombospondin-1 (TSP1) is a matricellular protein that differentially promotes the adhesion of resting and activated T cells. In this work, we show that adhesion of Jurkat T cells on substrates coated with TSP1 or TSP1-derived peptides is mediated by beta(1) integrins, CD47, and heparan sulfate proteoglycans. Interactions with TSP1 or TSP1 peptides stimulated CD3-induced Pas activation and tyrosine phosphorylation of several T cell proteins, The signals from TSP1 and its derived peptides differentially synergized with activation of the TCR to induce phosphorylation of tinker for activation of T Cells (LAT) and extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase, and p38 kinases, The phosphorylation of ERK in the presence of full-length TSP1 was transient and dependent on a beta(1) integrin receptor. Interestingly, peptides derived from the type 1 repeats of TSP1 and a CD47-binding peptide from the carboxyl-terminal domain of TSP1 also stimulated mitogen-activated protein (MAP) kinase phosphorylation, Moreover, the TSP1 heparin-binding peptide synergized with Ab-ligated TCR to transduce signals to the nucleus, detected by activation of AP-1- and Elk-dependent transcription. This TSP1 peptide-dependent activation of AP-1 was inhibited by both heparin and the MAP/ERK kinase inhibitor PD98059, providing a functional link between adhesion molecule interaction and nuclear transactivation events via the MAP kinase pathways. These findings have implications for the role of extracellular TSP1 and TSP1 fragments in the regulation of T cell function during hemostasis, wound repair, and other inflammatory responses. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 56 TC 48 Z9 48 U1 1 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 1999 VL 163 IS 7 BP 3621 EP 3628 PG 8 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900009 PM 10490955 ER PT J AU Zeller, JC Panoskaltsis-Mortari, A Murphy, WJ Ruscetti, FW Narula, S Roncarolo, MG Blazar, BR AF Zeller, JC Panoskaltsis-Mortari, A Murphy, WJ Ruscetti, FW Narula, S Roncarolo, MG Blazar, BR TI Induction of CD4(+) T cell alloantigen-specific hyporesponsiveness by IL-10 and TGF-beta(1) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; MYELIN BASIC-PROTEIN; VERSUS-HOST DISEASE; IN-VIVO; TRANSFORMING GROWTH-FACTOR-BETA-1; INFLAMMATORY DISEASE; CYTOKINE PRODUCTION; CHRONIC REJECTION; TRANSGENIC MICE; BONE-MARROW AB Induction and maintenance of Ag-specific tolerance are pivotal for immune homeostasis, prevention of autoimmune disorders, and the goal of transplantation. Recent studies suggest that certain cytokines, notably IL-10 and TGF-beta, may play a role in downregulating immune functions. To further examine the role of cytokines in Ag-specific hyporesponsiveness, murine CD4(+) T cells were exposed ex vivo to alloantigen-bearing stimulators in the presence of exogenous IL-10 and/or TGF-beta. Primary but not secondary alloantigen proliferative responses were inhibited by IL-10 alone. However, the combined addition of TL-10+ TGF-beta markedly induced alloantigen hyporesponsiveness in both primary and secondary MLR cultures. Alloantigen-specific hyporesponsiveness was observed also under conditions in which nominal Ag responses were intact, In adoptive transfer experiments, IL-10 + TGF-beta-treated CD4(+) T cells, but not T cells treated with either cytokine alone, mere markedly impaired in inducing graft-vs-host disease alloresponses to MHC class II disparate recipients. These data provide the first formal evidence that IL-10 and TGF-beta have at least an additive effect in inducing alloantigen-specific tolerance, and that in vitro cytokines can be exploited to suppress CD4(+) T cell-mediated Ag-specific responses in vivo. C1 Univ Minnesota, Ctr Canc, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. SAIC Frederick, Frederick, MD 21702 USA. NCI, Lab Leukocyte Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. Telethon Inst Gene Therapy H San Raffaele, Milan, Italy. RP Blazar, BR (reprint author), Univ Minnesota Hosp & Clin, Box 109 Mayo Bldg,420 SE Delaware St, Minneapolis, MN 55455 USA. FU NHLBI NIH HHS [R37 HL-56067]; NIAID NIH HHS [P01 AI-35296, R01 AI-34495]; Telethon [TGT00A03, TGT06S01] NR 41 TC 158 Z9 165 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1999 VL 163 IS 7 BP 3684 EP 3691 PG 8 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900017 PM 10490963 ER PT J AU Chung, DH Dorfman, J Plaksin, D Natarajan, K Belyakov, IM Hunziker, R Berzofsky, JA Yokoyama, WM Mage, MG Margulies, DH AF Chung, DH Dorfman, J Plaksin, D Natarajan, K Belyakov, IM Hunziker, R Berzofsky, JA Yokoyama, WM Mage, MG Margulies, DH TI NK and CTL recognition of a single chain H-2D(d) molecule: Distinct sites of H-2D(d) interact with NK and TCR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; NATURAL-KILLER-CELLS; HISTOCOMPATIBILITY COMPLEX MOLECULE; RECEPTOR LY-49A RECOGNIZES; CD8+ T-CELLS; ANTIGEN PRESENTATION; BONE-MARROW; INHIBITORY RECEPTORS; PEPTIDE REPERTOIRE; ANTIBODY FRAGMENTS AB We generated transgenic mice expressing a single-chain beta(2)-microglobulin (beta(2)m)-H-2D(d), The cell-surface beta(2)m-H-2D(d) molecule was expressed on a beta(2)m-deficient background and reacted with appropriate mAbs, It was of the expected m.w, and directed the normal development of CD8(+) T cells in the thymus of a broad TCR repertoire, It also presented both exogenously provided and endogenous peptide Ags to effector CD8(+) T cells, In tests of NK cell education and function, it failed to reveal any interaction with NK cells, suggesting that the site of the interaction of NK receptors with H-2D(d) was disrupted, Thus, the sites of TCR and NK receptor interaction with H-2D(d) are distinct, an observation consistent with independent modes of TCR and NK receptor evolution and function. C1 NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. EM dhm@nih.gov RI Chung, Doo Hyun/J-2791-2012; Margulies, David/H-7089-2013; Dorfman, Jeffrey/B-4854-2011; OI Dorfman, Jeffrey/0000-0001-9938-8911; Margulies, David/0000-0001-8530-7375 NR 75 TC 23 Z9 23 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 1999 VL 163 IS 7 BP 3699 EP 3708 PG 10 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900019 PM 10490965 ER PT J AU Pahlevan, AA Wright, DJM Andrews, C George, KM Small, PLC Foxwell, BM AF Pahlevan, AA Wright, DJM Andrews, C George, KM Small, PLC Foxwell, BM TI The inhibitory action of Mycobacterium ulcerans soluble factor on monocyte/T cell cytokine production and NF-kappa B function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; SIGNAL-TRANSDUCTION; KINASE PATHWAYS; FACTOR-ALPHA; IFN-GAMMA; ACTIVATION; TNF; INTERLEUKIN-1; RECEPTOR; PHOSPHORYLATION AB Buruli ulcer is a chronic and progressive necrotizing ulcer for which there is no medical treatment. Historically, a soluble toxin (factor) derived from the causative Mycobacterium ulcerans was found to induce the massive necrosis of skin and s.c. tissue seen in this condition. However, the persistence of the disease is thought to be caused by a lack of any immune response. We therefore investigated whether the factor was related to immunosuppression. A protocol to partially purify the factor was developed, and its effects on immune competent cells were tested. The factor produced >95% inhibition of LPS-induced release of TNF and IL-10 from human monocytes and caused a loss of adherence of these cells without cell death. The factor also blocked the production of IL-2 from activated T lymphocytes, The factor had no effect on TNF-induced cytotoxicity, but abrogated TNF-induced NF-kappa B activation. Surprisingly, a synergy was observed between the factor and phorbol ester directed NF-kappa B activation. The factor had no effect on IL-1- or LPS-induced NF-kappa B activity, indicating selective activity of the factor. The factor did not inhibit the degradation of I kappa B alpha induced by TNF, indicating that the target for its activity lies within an undefined part of the TNF signaling mechanism. The data indicate that the localized immunosuppression associated with Buruli ulcer relates to the activity of the released factor, and this may provide a target for future therapeutic strategies for this intractable disease. C1 Univ London Imperial Coll Sci Technol & Med, Med Microbiol Sect, London W6 8RF, England. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Kennedy Inst Rheumatol, Cytokine Biol & Signal Transduct Lab, London, England. RP Wright, DJM (reprint author), Univ London Imperial Coll Sci Technol & Med, Med Microbiol Sect, Charing Cross Campus,Fulham Palace Rd, London W6 8RF, England. FU Wellcome Trust NR 60 TC 92 Z9 92 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 1999 VL 163 IS 7 BP 3928 EP 3935 PG 8 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900048 PM 10490994 ER PT J AU Kobayashi, S Yoshida, K Ward, JM Letterio, JJ Longenecker, G Yaswen, L Mittleman, B Mozes, E Roberts, AB Karlsson, S Kulkarni, AB AF Kobayashi, S Yoshida, K Ward, JM Letterio, JJ Longenecker, G Yaswen, L Mittleman, B Mozes, E Roberts, AB Karlsson, S Kulkarni, AB TI beta(2)-microglobulin-deficient background ameliorates lethal phenotype of the TGF-beta 1 null mouse SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; SYSTEMIC LUPUS-ERYTHEMATOSUS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GROWTH-FACTOR-BETA-1 KNOCKOUT MICE; I-DEFICIENT MICE; MHC CLASS-II; T-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; TGF-BETA; FACTOR-BETA-1-DEFICIENT MICE AB TGF-beta 1 null (TGF-beta 1(-/-)) mice die at 3-4 wk of age and show an autoimmune inflammatory phenotype associated with enhanced expression of both class I and II MHC molecules, To determine the role of MHC class I Ags in the autoimmune manifestations and the inflammation observed in TGF-beta 1(-/-) mice, we generated TGF-beta 1(-/-) mice in the genetic background of beta(2)-microglobulin deficiency (beta(2)M(-/-)). TGF-beta 1(-/-);beta(2)M(-/-) mice had improved survival compared with TGF-beta 1(-/-) mice. Histopathological examination showed less severe inflammation, especially in the heart, where Mac-2 reactive macrophages were significantly decreased as compared with TGF-beta 1(-/-) mice. In vivo depletion of CD8(+) T cells in TGF-beta 1(-/-) mice confirmed suppression of inflammation and reduction in the severity of the wasting syndrome. MHC class IT mRNA expression in TGF-beta 1(-/-);beta(2)M(-/-) mice was also lower than that in TGF-beta 1(-/-) mice, suggesting reduced systemic inflammation. Autoimmune response as judged by serum Ab titers to ssDNA and 16/6 Id and by immune complex deposits in kidney was reduced in TGF-beta 1(-/-);beta(2)M(-/-) mice, when compared with that in TGF-beta 1(-/-) mice. Our data thus indicate that MHC class I molecules influence the development of the autoimmunity and the inflammation seen in TGF-beta 1(-/-) mice and CD8(+) T cells may have a contribution to the inflammation in TGF-beta 1(-/-) mice. C1 Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Sci, NIH, Frederick, MD 21702 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, Gene Targeting Facil,Bldg 30,Room 529,30 Convent, Bethesda, MD 20892 USA. NR 57 TC 45 Z9 46 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 1999 VL 163 IS 7 BP 4013 EP 4019 PG 7 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900058 PM 10491004 ER PT J AU Song, XY Zeng, L Pilo, CM Zagorski, J Wahl, SM AF Song, XY Zeng, L Pilo, CM Zagorski, J Wahl, SM TI Inhibition of bacterial cell wall-induced leukocyte recruitment and hepatic granuloma formation by TGF-beta gene transfer SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSGENIC MICE; CYTOKINE REGULATION; LIVER-DISEASE; TISSUE-REPAIR; FIBROSIS; EXPRESSION; CHEMOKINE AB Intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats results in dissemination of SCW to the liver, spleen, bone marrow, and peripheral joints. The uptake of SCW by Kupffer cells in the liver initiates a chain of events largely mediated by T lymphocytes and macrophages. Local synthesis and secretion of cytokines and growth factors in response to the persistent SCW lead to the evolution and maintenance of a chronic T cell-dependent granulomatous response and result in granuloma formation and irreversible hepatic fibrosis, In an attempt to impede the development of the chronic granulomatous lesions in the liver, we injected a plasmid DNA encoding TGF-beta 1 i.m. to the SCW animals to determine the effect of TGF-beta 1 gene transfer on the course of liver inflammation and fibrosis, A single injection of plasmid DNA encoding TGF-beta 1 resulted in virtual abolition of the development of the SCW-induced hepatic granuloma formation and matrix expansion. TGF-beta 1 DNA not only reduced key proinflammatory cytokines including TNF-alpha, IL-1 beta, IFN-gamma, and IL-18, but also inhibited both CXC and CC chemokine production, thereby blocking inflammatory cell recruitment and accumulation in the liver. Moreover, TGF-beta 1 gene delivery inhibited its own expression in the liver tissue, which is otherwise up-regulated in SCW-injected animals. Our study suggests that TGF-beta 1 gene transfer suppresses hepatic granuloma formation by blocking the recruitment of inflammatory cells to the liver, and thus mag provide a new approach to the control of hepatic granulomatous and fibrotic diseases. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Room 332,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 44 TC 12 Z9 12 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 1999 VL 163 IS 7 BP 4020 EP 4026 PG 7 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900059 PM 10491005 ER PT J AU Azimi, N Jacobson, S Leist, T Waldmann, TA AF Azimi, N Jacobson, S Leist, T Waldmann, TA TI Involvement of IL-15 in the pathogenesis of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis: Implications for therapy with a monoclonal antibody directed to the IL-2/15R beta receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KILLER-CELL CYTOTOXICITY; NF-KAPPA-B; CEREBROSPINAL-FLUID; LYMPHOCYTES-T; BETA-CHAIN; NEUROLOGICAL DISEASE; INTERFERON-GAMMA; DENDRITIC CELLS; GENE-EXPRESSION; INTERLEUKIN-15 AB Human T lymphotropic virus type I (HTLV-I) is the causative agent of an inflammatory neurological disease termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), An ongoing lymphocyte activation exists in patients with HAM/ TSP, which was demonstrated by the spontaneous proliferation of their PBMC ex vivo. It was shown that spontaneous proliferation present in HAM/TSP is due, in part, to an IC-2/IL-2R autocrine loop. However, addition of Abs against IL-2 or IL-2R alpha only partially inhibited the spontaneous proliferation. Since IL-15 is a cytokine with similar functional characteristics to those of IL-2, we reasoned that IL-15 might be an additional growth factor that contributes to the spontaneous proliferation observed in HAM/TSP. In this study, we demonstrated that IL-15 mRNA expression was elevated in PBMC obtained from HAM/TSP patients when compared with those of the normal donors. Furthermore, we showed that the addition of blocking Abs against IL-15 or its receptor inhibited the spontaneous proliferation of HAM/TSP PBMC. Addition of Abs directed toward both IL-15 and IL-2, or their receptors, inhibited the proliferation almost completely. These data suggest the existence of two autocrine loops involving IL-15/IL-15R and IL-2/IL-2R, both contributing to the spontaneous proliferation of HAM/TSP PBMC. C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Azimi, N (reprint author), NCI, Metab Branch, Div Clin Sci, NIH, Bldg 10,Room 4N-102,10 Ctr Dr,MSC 1374, Bethesda, MD 20892 USA. NR 55 TC 60 Z9 62 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 1999 VL 163 IS 7 BP 4064 EP 4072 PG 9 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900065 PM 10491011 ER PT J AU Auwaerter, PG Rota, PA Elkins, WR Adams, RJ DeLozier, T Shi, YQ Bellini, WJ Murphy, BR Griffin, DE AF Auwaerter, PG Rota, PA Elkins, WR Adams, RJ DeLozier, T Shi, YQ Bellini, WJ Murphy, BR Griffin, DE TI Measles virus infection in rhesus macaques: Altered immune responses and comparison of the virulence of six different virus strains SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; EOSINOPHILIA; IMMUNODEFICIENCY; RNA; INTERLEUKIN-5; ANTIBODY; CELLS; GENES; HOST AB Measles remains a major cause of childhood mortality, with questions about virus virulence and pathogenesis still requiring answers. Rhesus macaques were infected with 5 different culture-adapted strains of measles virus, including 2 from patients with progressive vaccine-induced disease, and a sixth nonculture-adapted strain, Bilthoven. All caused infection detectable by reverse transcriptase-polymerase chain reaction and induction of antibody. Chicago-1 and Bilthoven induced viremias detectable by leukocyte cocultivation. Bilthoven induced Koplik's spots, conjunctivitis, and rash. Lymphopenia and depressed interleukin (IL)-2 production were followed by monocytosis and eosinophilia, All monkeys, including 41 involved in a primate facility outbreak, showed suppressed responses to phytohemagglutinin. As the rash resolved production of IL-2, IL-1 beta, tumor necrosis factor-alpha, IL-6, and IL-5 mRNA increased. Monkeys are useful for studies of measles immunopathogenesis, but virus strains must be carefully chosen. Increased virulence of vaccine strains isolated from immunocompromised infants with fatal infections was not evident. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21205 USA. Ctr Dis Control & Prevent, Publ Hlth Serv, US Dept HHS, Atlanta, GA USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Griffin, DE (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St,Rm E5132, Baltimore, MD 21205 USA. FU NIAID NIH HHS [AI35149] NR 52 TC 95 Z9 97 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 1999 VL 180 IS 4 BP 950 EP 958 DI 10.1086/314993 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500003 PM 10479117 ER PT J AU O'Brien, TR Kedes, D Ganem, D Macrae, DR Rosenberg, PS Molden, J Goedert, JJ AF O'Brien, TR Kedes, D Ganem, D Macrae, DR Rosenberg, PS Molden, J Goedert, JJ TI Evidence for concurrent epidemics of human herpesvirus 8 and human immunodeficiency virus type 1 in US homosexual men: Rates, risk factors, and relationship to Kaposi's sarcoma 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 DNA-SEQUENCES; SEXUAL TRANSMISSION; INFECTION; AIDS; ANTIBODIES; COHORT; ANTIGENS; CONTACT; FORMS AB We examined human herpesvirus 8 (HHV-8) seroprevalence and seroincidence among 245 homosexual men from New York City (NYC) and Washington, DC (DC) who have been followed since 1982. An immunofluorescence assay measured antibodies to a latent HHV-8 nuclear antigen. Seroprevalence was 20.4% in 1982; seroincidence was similar to 15%/year during 1982-1983 but fell sharply thereafter, NYC men had a higher seroprevalence (odds ratio, 3.43; P < .001) and seroincidence (rate ratio, 2.13; P = .01) than DC men. Risk of Kaposi's sarcoma (KS) was increased in seropositive men (adjusted relative hazard, 3.58; P = .02), Among men who were seropositive for both human immunodeficiency virus type 1 and HHV-8, the 10-year cumulative risk of KS was 39%; time from coinfection to KS diagnosis ranged from 15 to 154 months (median, 63.5 months). This study shows an epidemic of HHV-8 among US homosexual men in the early 1980s that was associated with a high risk of developing KS. C1 NCI, Viral Epidemiol Branch, US PHS, US Dept HHS, Rockville, MD 20852 USA. NCI, Biostat Branch, Rockville, MD USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP O'Brien, TR (reprint author), NCI, Viral Epidemiol Branch, US PHS, US Dept HHS, 6120 Execut Blvd,EPS 8016, Rockville, MD 20852 USA. NR 36 TC 102 Z9 106 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 1999 VL 180 IS 4 BP 1010 EP 1017 DI 10.1086/315039 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500011 PM 10479125 ER PT J AU Wright, PF Lambert, JS Gorse, GJ Hsieh, RH McElrath, MJ Weinhold, K Wara, DW Anderson, EL Keefer, MC Jackson, S Wagner, LJ Francis, DP Fast, PE McNamara, J AF Wright, PF Lambert, JS Gorse, GJ Hsieh, RH McElrath, MJ Weinhold, K Wara, DW Anderson, EL Keefer, MC Jackson, S Wagner, LJ Francis, DP Fast, PE McNamara, J CA AIDS Vaccine Evaluation Grp TI Immunization with envelope MN rgp120 vaccine in human immunodeficiency virus-infected pregnant women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MOTHER-TO-CHILD; MATERNAL IMMUNIZATION; RECOMBINANT GP160; HIV-1 INFECTION; TRANSMISSION; TYPE-1; SAFETY; IMMUNOGENICITY; NEWBORNS; INFANTS AB Twenty-six human immunodeficiency virus (HIV)-infected pregnant women participated in a placebo-controlled study of immunogenicity and safety of multiple doses of MN rgp120 vaccine over the last half of pregnancy. The women had CD4 lymphocyte counts >400/mm(3), no AIDS-defining illness and normal pregnancies. Vaccination was well tolerated, with no significant local or systemic reactions in the women and no adverse outcomes in the infants attributable to the vaccine. Vaccination did not alter plasma RNA reverse transcriptase-polymerase chain reaction copy number; moreover, immunization was not associated with changes in CD4 counts or HIV binding and neutralization antibody titers, Infants were followed up until 18 months of age. Five of 26 infants (19%) were HIV infected, with infection occurring in children of both vaccinated and placebo women. Analysis of factors that influence transmission did not disclose associations with immunization status, viral load, CD4 count, or maternal viral neutralization titers. C1 Vanderbilt Univ, Med Ctr, Div Pediat Infect Dis, Sch Med, Nashville, TN 37232 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. EMMES Corp, Potomac, MD USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Sch Med, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VaxGen, Brisbane, CA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Alabama, Birmingham, AL USA. St Louis Univ, St Louis, MO 63103 USA. Vet Affairs Med Ctr, St Louis, MO USA. RP Wright, PF (reprint author), Vanderbilt Univ, Med Ctr, Div Pediat Infect Dis, Sch Med, D-7219 MCN, Nashville, TN 37232 USA. FU NIAID NIH HHS [N01 AI-45207, N01 AI-45208, N01 AI-45211] NR 24 TC 26 Z9 27 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 1999 VL 180 IS 4 BP 1080 EP 1088 DI 10.1086/314985 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500020 PM 10479134 ER PT J AU Dezzutti, CS Swords, WE Guenthner, PC Sasso, DR Wahl, LM Drummond, AH Newman, GW King, CH Quinn, FD Lal, RB AF Dezzutti, CS Swords, WE Guenthner, PC Sasso, DR Wahl, LM Drummond, AH Newman, GW King, CH Quinn, FD Lal, RB TI Involvement of matrix metalloproteinases in human immunodeficiency virus type I-induced replication by clinical Mycobacterium avium isolates 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 NECROSIS-FACTOR-ALPHA; HUMAN MACROPHAGES; T-CELLS; COMPLEX BACTEREMIA; IMMUNE ACTIVATION; MONONUCLEAR-CELLS; CHRONIC INFECTION; MONOCYTOID CELLS; TISSUE INHIBITOR; PERIPHERAL-BLOOD AB The role of Mycobacterium avium isolates in modulating human immunodeficiency virus type 1 (HIV-1) replication was examined by use of an in vitro, resting T cell system. Two human clinical isolates (serotypes 1 and 4) but not an environmental M. avium isolate (serotype 2) enhanced HIV-1 replication. The M. avium-induced HIV-1 replication was not associated with cell activation or differential cytokine production or utilization. Addition of matrix metalloproteinase (MMP) inhibitors and their in vivo regulators, tissue inhibitors of metalloproteinases-1 and -2, abrogated M. avium-induced HIV-1 replication 80%-95%. The MMP inhibitors did not have any effect on the HIV-1 protease activity, suggesting that they may affect cellular processes. Furthermore, MMP-9 protein was differentially expressed after infection with clinical M. avium isolates and paralleled HIV-1 p24 production. Collectively, these data suggest that M. avium-induced HIV-1 replication is mediated, in part, through the induction of MMP-9. C1 Ctr Dis Control & Prevent, HIV & Retrovirus Dis Branch, Div AIDS STD & TB Lab Res, Atlanta, GA USA. Ctr Dis Control & Prevent, TB Mycobacteriol Branch, Div AIDS STD & TB Lab Res, Atlanta, GA USA. Ctr Dis Control & Prevent, HIV Immunol & Diagnost Branch, Div AIDS STD & TB Lab Res, Atlanta, GA USA. Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD USA. British Biotech Pharmaceut Ltd, Oxford, England. RP Dezzutti, CS (reprint author), CDC, DASTLR, HARB, Mailstop G-19,1600 Clifton Rd NE, Atlanta, GA 30333 USA. NR 53 TC 12 Z9 12 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 1999 VL 180 IS 4 BP 1142 EP 1152 DI 10.1086/314992 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500027 PM 10479141 ER PT J AU Yaganehdoost, A Graviss, EA Ross, MW Adams, GJ Ramaswamy, S Wanger, A Frothingham, R Soini, H Musser, JM AF Yaganehdoost, A Graviss, EA Ross, MW Adams, GJ Ramaswamy, S Wanger, A Frothingham, R Soini, H Musser, JM TI Complex transmission dynamics of clonally related virulent Mycobacterium tuberculosis associated with barhopping by predominantly human immunodeficiency virus-positive gay men SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 124th Annual Meeting of the American-Public-Health-Association CY NOV 17-21, 1996 CL NEW YORK, NEW YORK SP Amer Public Hlth Assoc ID FRAGMENT-LENGTH-POLYMORPHISM; DRUG-RESISTANT TUBERCULOSIS; NEW-YORK-CITY; STRAIN DIFFERENTIATION; CONTROL STRATEGIES; SAN-FRANCISCO; EPIDEMIOLOGY; OUTBREAK; IS6110; DISSEMINATION AB Limited data suggest that measures to reduce tuberculosis transmission should be based on locations rather than on personal contacts. Molecular epidemiologic methods (analysis of IS6110 patterns, spoligotypes, variable numbers of tandem DNA repeats, and automated DNA sequence data) identified a cohort of 48 persons who were infected with progeny of the same Mycobacterium tuberculosis strain. Epidemiologic investigation documented that a large proportion of the patients were gay white human immunodeficiency virus-positive men, Most practiced barhopping, an activity that involved patronizing many bars in the same neighborhood each night, Few subjects were directly linked to more than 1 or 2 other persons by conventional investigation methods, which shows that the transmission dynamics were unusually complex compared with most previously described episodes of strain spread. The data support the concept that identification of locations where pathogen dissemination likely occurs may provide additional strategies for targeted tuberculosis control. C1 Baylor Coll Med, Inst Study Human Bacterial Pathogenesis, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Duke Univ, Med Ctr, Durham, NC USA. Vet Adm Med Ctr, Durham, NC USA. RP Musser, JM (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. FU NIDA NIH HHS [DA-09238] NR 37 TC 52 Z9 52 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 1999 VL 180 IS 4 BP 1245 EP 1251 DI 10.1086/314991 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500040 PM 10479154 ER PT J AU Su, H Morrison, R Messer, R Whitmire, W Hughes, S Caldwell, HD AF Su, H Morrison, R Messer, R Whitmire, W Hughes, S Caldwell, HD TI The effect of doxycycline treatment an the development of protective immunity in a murine model of chlamydial genital infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GENE KNOCKOUT MICE; TRACT INFECTION; GAMMA-INTERFERON; TRACHOMATIS INFECTION; MOUSE PNEUMONITIS; ECTOPIC PREGNANCY; IFN-GAMMA; CELLS; INFERTILITY; SALPINGITIS AB Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) worldwide. Antibiotics are effective in treating infection; however, reinfection is common, This observation has led to the conclusion that infection fails to elicit a protective antichlamydial immune response. It was postulated that high reinfection rates might be due to early eradication of organisms from genital tissue after antibiotic intervention, which could negatively influence the development of naturally acquired protective immunity. This hypothesis was tested by use of a murine model of female genital infection. The findings show that doxycycline intervention of infection, although very effective in eradicating chlamydiae from genital tissue and preventing upper genital tract disease, significantly inhibits the development of protective immunity. If antibiotic intervention of human chlamydial genital infection has a similar effect on protective immunity, it could have important implications in the understanding of immunity to infection and future public health efforts to control chlamydial STD. C1 NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Lab, Hamilton, MT 59840 USA. Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. RP Caldwell, HD (reprint author), NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Lab, 903 S 4th St, Hamilton, MT 59840 USA. FU NIAID NIH HHS [AI38991] NR 31 TC 67 Z9 67 U1 0 U2 3 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 1999 VL 180 IS 4 BP 1252 EP 1258 DI 10.1086/315046 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500041 PM 10479155 ER PT J AU Lau, DTY Miller, KD Detmer, J Kolberg, J Herpin, B Metcalf, JA Davey, RT Hoofnagle, JH AF Lau, DTY Miller, KD Detmer, J Kolberg, J Herpin, B Metcalf, JA Davey, RT Hoofnagle, JH TI Hepatitis G virus and human immunodeficiency virus coinfection: Response to interferon-alpha therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-12, 1997 CL CHICAGO, ILLINOIS SP Amer Assoc Study Liver Dis ID C VIRUS; INFECTION; RNA; PREVALENCE; GENOTYPES; SEQUENCES; DISEASE; CLONING; LIVER AB The prevalence and consequences of hepatitis G virus (HGV) infection were determined in 180 patients with human immunodeficiency virus (HIV) infection (predominantly male homosexuals) who participated in a trial that compared treatment with zidovudine versus interferon (IFN)-alpha versus the combination. HGV RNA levels were measured by branched DNA signal amplification assay. Initially, 66 (37%) had HGV RNA. Sexual transmission was the sole risk factor for infection in all but 4 subjects. Pretreatment clinical features were similar between HGV RNA-positive and -negative patients. After 6 months, only 5% treated with zidovudine became HGV RNA negative, compared with 95% who received IFN-alpha alone and 66% on combination therapy with low-dose IFN-alpha. After therapy, HGV RNA levels returned to baseline in most subjects. Thus, HGV infection is common among HIV-infected homosexual males but does not appear to influence clinical features in early HIV infection. HGV RNA levels are suppressed by IFN but not by zidovudine. C1 NIDDK, Div Digest Dis & Nutr, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Clin & Mol Retroviral Sect, NIH, Bethesda, MD 20892 USA. Chiron Diagnost, Emeryville, CA USA. RP Hoofnagle, JH (reprint author), NIDDK, Div Digest Dis & Nutr, Liver Dis Sect, NIH, Bldg 31,Rm 9A23, Bethesda, MD 20892 USA. NR 14 TC 24 Z9 25 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 1999 VL 180 IS 4 BP 1334 EP 1337 DI 10.1086/315031 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500053 PM 10479167 ER PT J AU Bhakuni, V Kulkarni, S Ali, V Singh, UK Levy, HB Maheshwari, RK AF Bhakuni, V Kulkarni, S Ali, V Singh, UK Levy, HB Maheshwari, RK TI Immunochemotherapy for Leishmania donovani infection in golden hamsters: Combinatorial action of poly ICLC plus L-arginine and sodium stibogluconate (Stibanate (R)) SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID VISCERAL LEISHMANIASIS; PENTAVALENT ANTIMONY; INTERFERON-GAMMA; DRUGS; CHEMOTHERAPY AB We demonstrate that golden hamsters infected with Leishmania donovani amastigotes develop the capacity to eliminate intracellular pathogens on treatment with low-dose standard antileishmanial sodium stibogluconate (Stibanate) in combination with polyinosinic-polycytidilic acid stabilized with polylysine and carboxymethy-cellulose (poly ICLC), a potent inducer of interferon (IFN) and immune enhancer, plus L-arginine. Data suggest that low doses of both Stibanate and poly ICLC plus L-arginine provide marginal inhibition against L. donovani infection in golden hamsters, When given in combination, however, a significant inhibition was achieved without toxicity, as all the animals survived up to 45 or 60 days. These results suggest that combination therapy using Stibanate and poly ICLC plus L-arginine map be very effective in reducing the dose of Stibanate and, hence, its dose-dependent toxicity in clinical situations. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Ctr Combat Casualty & Life Sustainment Res, Bethesda, MD 20814 USA. Cent Drug Res Inst, Div Membrane Biol, Lucknow 226001, Uttar Pradesh, India. NIAID, NIH, Bethesda, MD 20892 USA. RP Maheshwari, RK (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, Ctr Combat Casualty & Life Sustainment Res, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD OCT PY 1999 VL 19 IS 10 BP 1103 EP 1106 DI 10.1089/107999099313037 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 246KP UT WOS:000083163200003 PM 10547149 ER PT J AU Tezuka, T Cui, CY Aragane, Y Maeda, A Piao, YU Kim, LH Takahashi, M AF Tezuka, T Cui, CY Aragane, Y Maeda, A Piao, YU Kim, LH Takahashi, M TI Bikunin, a serine protease inhibitor, is present on the cell boundary of epidermis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Kinki Univ, Sch Med, Dept Dermatol, Osaka 589, Japan. NIA, IRP, Genet Lab, NIH, Baltimore, MD 21224 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1999 VL 113 IS 4 MA 16 BP 699 EP 699 PG 1 WC Dermatology SC Dermatology GA 243AJ UT WOS:000082974700044 ER PT J AU Sullivan, SK McGrath, DA Liao, F Boehme, SA Farber, JM Bacon, KB AF Sullivan, SK McGrath, DA Liao, F Boehme, SA Farber, JM Bacon, KB TI MIP-3 alpha induces human eosinophil migration and activation of the mitogen-activated protein kinases (p42/p44 MAPK) SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemokines; signaling ID DENDRITIC CELLS; CHEMOTACTIC ACTIVITY; CHEMOKINE RECEPTORS; SIGNAL-TRANSDUCTION; T-LYMPHOCYTES; CLONING; RAC; IDENTIFICATION; ORGANIZATION; PATHWAYS AB The CC chemokine macrophage inflammatory protein-3 alpha (MIP-3 alpha) is the product of recent electronic cloning efforts, however, little characterization of its spectrum of biological effects has been undertaken, Human eosinophils exhibited pertussis-toxin-sensitive migration in response to human recombinant (hr)MIP-3 alpha. Messenger RNA for the MIP-3 alpha receptor, CCR-6, and low levels of surface expression were demonstrated by reverse transcriptase-polymerase chain reaction and FACS analysis, Analyses of cell signaling revealed dose-dependent increases in intracellular calcium mobilization, calciurn transients that were, however, greatly reduced when compared with MCP-3-induced responses, Further investigations of MIP-3 alpha-induced signal transduction revealed time- and dose-dependent, partially pertussis toxin-dependent, increases in phosphorylation of the p42/P44 mitogen-activated protein kinases (MAPK) that occurred at 10- to 100-fold lower concentrations, and that were linked to a phosphoinositide 3-kinase pathway. These results suggest that MIP-3 alpha can regulate multiple, parallel signal transduction pathways in eosinophils, and suggest that MAPK activation by MIP-3 alpha in eosinophils is a significant signaling pathway for migration induction. C1 Neurocrine Biosci Inc, Dept Immunol, San Diego, CA 92121 USA. Neurocrine Biosci Inc, Dept Mol Biol, San Diego, CA 92121 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Bacon, KB (reprint author), Neurocrine Biosci Inc, Dept Immunol, 10555 Sci Ctr Dr, San Diego, CA 92121 USA. NR 25 TC 41 Z9 42 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 1999 VL 66 IS 4 BP 674 EP 682 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 245ZM UT WOS:000083138700021 PM 10534125 ER PT J AU Baltus, B Buitenhuis, M van Dijk, TB Vinson, C Raaijmakers, JAM Lammers, JWJ Koenderman, L de Groot, RP AF Baltus, B Buitenhuis, M van Dijk, TB Vinson, C Raaijmakers, JAM Lammers, JWJ Koenderman, L de Groot, RP TI C/EBP regulates the promoter of the eosinophil-derived neurotoxin/RNS2 gene in human eosinophilic cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE granulocytes; transcription regulation ID BINDING-PROTEIN-ALPHA; FACTOR-RECEPTOR PROMOTER; PULMONARY IMMUNE CELLS; TRANSCRIPTION FACTOR; CATIONIC PROTEIN; MOLECULAR-CLONING; LINEAGE COMMITMENT; INTRONIC ENHANCER; FAMILY MEMBERS; DEFICIENT MICE AB The eosinophil-derived neurotoxin (EDN), a member of the mammalian ribonuclease family, is found in the large specific granules of human eosinophilic leukocytes. We have investigated the role of the C/EBP transcription factor family in the regulation of EDN promoter activity. Here we show that the C/EBP family is involved in intrinsic regulation of EDN promoter activity. We have identified a C/EBP binding site located at -124 in the proximal promoter of the EDN gene. Mutation of this C/EBP site results in a decrease of promoter activity in HL-60-eos cells as well as in eosinophils differentiated in vitro from CD34(+) cells. Different C/EBP proteins are able to bind to the C/EBP site as shown by gel shift assay. Our results indicate the importance of the C/EBP family in the regulation of the EDN gene in eosinophils. C1 Univ Utrecht Hosp, Dept Pulm Dis, NL-3584 CX Utrecht, Netherlands. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP de Groot, RP (reprint author), Univ Utrecht Hosp, Dept Pulm Dis, G03-550,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. OI Koenderman, Leo/0000-0002-5636-6453 NR 52 TC 14 Z9 15 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 1999 VL 66 IS 4 BP 683 EP 688 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 245ZM UT WOS:000083138700022 PM 10534126 ER PT J AU Couture, P Otvos, JD Cupples, LA Wilson, PWF Schaefer, EJ Ordovas, JM AF Couture, P Otvos, JD Cupples, LA Wilson, PWF Schaefer, EJ Ordovas, JM TI Association of the A-204C polymorphism in the cholesterol 7 alpha-hydroxylase gene with variations in plasma low density lipoprotein cholesterol levels in the Framingham Offspring Study SO JOURNAL OF LIPID RESEARCH LA English DT Article DE LDL-cholesterol; cholesterol 7 alpha-hydroxylase; genetic polymorphism ID CORONARY HEART-DISEASE; APOLIPOPROTEIN-E POLYMORPHISM; BILE-ACID SYNTHESIS; RECEPTOR GENE; APO-B; FAMILIES; LIPIDS; HYPERCHOLESTEROLEMIA; IDENTIFICATION; TRIGLYCERIDES AB The first reaction of the catabolic pathway of cholesterol is catalyzed by CYP7 and serves as the rate-limiting step and major site of regulation of bile acid synthesis in the liver, A common A to C substitution at position -204 of the promoter of CYP7 gene has been associated with variations in plasma LDL-cholesterol concentrations but the effect of this polymorphism is unknown in the general population, The aim of the present study was therefore to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1139 male and 1191 female Framingham Offspring participants, In men, the C variant was associated with higher plasma concentrations of LDL- cholesterol and this association remained significant after adjustment for familial relationship, age, BMI, smoking, alcohol intake, the use of beta-blockers, and apoE genotype, The C variant was also associated with an increased TC/ HDL ratio in men, Variance components analysis indicated that allelic variability at nucleotide -204 of the CYP7 gem and polymorphism of the apoE gene accounted for 1 and 5% of the variation of plasma LDL-cholesterol concentrations, respectively, In women, however, there was no relationship between LDL-cholesterol and the A-204C polymorphism but subjects homozygous for the CC genotype had significantly lower triglyceride levels than heterozygotes, Moreover, no significant relationship was found between the A-204C variants and lipoprotein particle diameter or the prevalence of coronary heart disease in both genders.jlr Thus, our results show that the A-204C polymorphism in the CYP7 gem is associated with statistically significant variations in LDL-C and triglyceride concentrations in men and women, respectively, but the cumulative effects of these variations on atherosclerotic risk remain uncertain. C1 Tufts Univ, Lipid Metab Lab, USDA, Jean Mayer Human Nutr Ctr, Boston, MA 02111 USA. N Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. RP Ordovas, JM (reprint author), Tufts Univ, Lipid Metab Lab, USDA, Jean Mayer Human Nutr Ctr, Boston, MA 02111 USA. FU NHLBI NIH HHS [HL35243, HL54776]; PHS HHS [N01-38038] NR 47 TC 78 Z9 85 U1 0 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 1999 VL 40 IS 10 BP 1883 EP 1889 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244BL UT WOS:000083031900016 PM 10508208 ER PT J AU Salustri, C Yang, Y Glover, GH AF Salustri, C Yang, Y Glover, GH TI Simple but reliable solutions for spiral MRI gradient design SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE spiral MRI; fast imaging; magnetic resonance imaging ID ACQUISITION; BRAIN; FMRI; FLOW AB The efficiency of gradient design in MRI is limited by the simple fact that the gradient coil current and slew rate cannot exceed hardware threshold values. In spiral MRI, which requires gradients to be very rapidly switched between positive and negative values, minimization of the acquisition time is achieved by maintaining the current and slew rate as high as possible during the entire measurement. Since the current and slew rate compete against each other, an efficient gradient design consists of two parts in which current and slew rate are pushed alternatively to their limits. Values for these types of gradients can be obtained by solving numerically the equation of motion for the spiral trajectory, This paper shows that simple but reasonable mathematical approximations deliver reliable analytical solutions, Images obtained using these analytical solutions do not show evident distortions when compared with images obtained with numerical solutions. (C) 1999 Academic Press. C1 CNR, Inst Solid State Elect, I-00156 Rome, Italy. NIH, OD, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Lucas MRI Ctr, Dept Diagnost Radiol, Stanford, CA 94305 USA. RP Salustri, C (reprint author), CNR, Inst Solid State Elect, I-00156 Rome, Italy. NR 20 TC 6 Z9 6 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 1999 VL 140 IS 2 BP 347 EP 350 DI 10.1006/jmre.1999.1831 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 243WL UT WOS:000083020400006 PM 10497042 ER PT J AU Gruschus, JM Ferretti, JA AF Gruschus, JM Ferretti, JA TI Signal enhancement using 45 degrees water flipback for 3D N-15-edited ROESY and NOESY HMQC and HSQC SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE PFG (pulsed field gradients); protein-water cross-relaxation rates; radiation damping suppression; high molecular weight; water suppression ID HIGH-FIELD NMR; HIV-1 PROTEASE; SPECTROSCOPY; RELAXATION; PROTEINS; DNA; SENSITIVITY; HYDRATION; DYNAMICS; BACK AB A novel implementation of the water flipback technique employing a 45 degrees flip-angle water-selective pulse is presented. The use of this water flipback technique is shown to significantly enhance signal in 3D N-15-edited ROESY in a 20 kDa complex of the vnd/NK-2 homeodomain bound to DNA, The enhancement is seen relative to the same experiment using weak water presaturation during the recovery delay. This enhancement is observed for the signals from both labile and nonlabile protons. ROESY and NOESY pulse sequences with 45 degrees water flipback are presented using both HMQC and HSQC for the N-15 dimension. The 45 degrees flipback pulse is followed by a gradient, a water selective 180 degrees pulse, and another gradient to remove quadrature images and crosspeak phase distortion near the water frequency. Radiation damping of the water magnetization during the t(1) and t(2) evolution periods is suppressed using gradients, Water resonance planes from NOESY-HMQC and NOESY-HSQC spectra show that the HMQC version of the pulse sequences can provide stronger signal for very fast exchanging protons, The HSQC versions of the ROESY and NOESY pulse sequences are designed for the quantitative determination of protein-water crossrelaxation rates, with no water-selective pulses during the mixing time and with phase cycling and other measures for reducing axial artifacts in the water signal. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gruschus, JM (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 27 TC 10 Z9 10 U1 2 U2 6 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 1999 VL 140 IS 2 BP 451 EP 459 DI 10.1006/jmre.1999.1852 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 243WL UT WOS:000083020400014 PM 10497050 ER PT J AU Cordier, F Rogowski, M Grzesiek, S Bax, A AF Cordier, F Rogowski, M Grzesiek, S Bax, A TI Observation of through-hydrogen-bond (2h)J(HC ') in a perdeuterated protein SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID PYROCOCCUS-FURIOSUS; COUPLINGS; RUBREDOXIN; NMR AB It is demonstrated that J connectivity between amide protons and hydrogen-bond-accepting carbonyl carbons can be observed in perdeuterated human ubiquitin. A selective pulse scheme is used to detect these small (2h)J(HC') interactions in the presence of the much larger through-covalent-bond (2)J(HC') and (3)J(HC') couplings. The ratio of the observed through-H-bond correlation intensity and the (2)J(HC') connectivity observed in a reference spectrum indicates (2h)J(HC') values of ca. 0.4-0.6 Hz, which are only slightly smaller than the corresponding (3h)J(NC') values. However, for technical reasons, (2h)J(HC') couplings are more difficult to measure than (3h)J(NC'). (C) 1999 Academic Press. C1 Forschungszentrum Julich, Inst Biol Struct, D-52425 Julich, Germany. Univ Dusseldorf, Inst Phys Biol, D-40225 Dusseldorf, Germany. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Cordier, F (reprint author), Forschungszentrum Julich, Inst Biol Struct, Postfach 1913, D-52425 Julich, Germany. NR 15 TC 75 Z9 77 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD OCT PY 1999 VL 140 IS 2 BP 510 EP 512 DI 10.1006/jmre.1999.1899 PG 3 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 243WL UT WOS:000083020400024 PM 10497060 ER PT J AU Hacia, JG Collins, FS AF Hacia, JG Collins, FS TI Mutational analysis using oligonucleotide microarrays SO JOURNAL OF MEDICAL GENETICS LA English DT Review DE mutational analysis; oligonucleotide microarrays; DNA chips ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENETIC BIT ANALYSIS; DNA ARRAYS; HYBRIDIZATION; MICROCHIPS; IDENTIFICATION; DIAGNOSTICS; GENOMICS C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bldg 49-3A14, Bethesda, MD 20892 USA. NR 54 TC 109 Z9 116 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD OCT PY 1999 VL 36 IS 10 BP 730 EP 736 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 244EG UT WOS:000083038400002 PM 10528850 ER PT J AU Ruchkin, DS Berndt, RS Johnson, R Grafman, J Ritter, W Canoune, HL AF Ruchkin, DS Berndt, RS Johnson, R Grafman, J Ritter, W Canoune, HL TI Lexical contributions to retention of verbal information in working memory: Event-related brain potential evidence SO JOURNAL OF MEMORY AND LANGUAGE LA English DT Article DE working memory; verbal; lexical; semantic; phonological; retention; serial recall task; event-related potentials ID SHORT-TERM-MEMORY; POSITRON EMISSION TOMOGRAPHY; NEUROPSYCHOLOGICAL EVIDENCE; WORD-FREQUENCY; SERIAL-RECALL; LANGUAGE; REHEARSAL; STORAGE; SPAN; REDINTEGRATION AB The present study investigated whether lexical codes contribute to retention of verbal information in working memory. We used event-related brain potentials (ERPs) recorded while participants were performing a serial recall task to show differences in brain activity during retention of words or pseudowords. The effects of lexical status and memory load (task difficulty) upon ERP activity during retention also differed, with memory load affecting ERP indices of phonological processing. The timing of the ERPs suggested that the influence of lexical status upon retention began during encoding. The contrast between ERPs in the serial recall task and in a control task with negligible memory demand indicated that the effect of lexical status in the retention interval of the memory task was specific to consciously controlled memory operations. These results support the View that lexical codes actively contribute to retention of words in working memory, (C) 1999 Academic Press. C1 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. Queens Coll, Flushing, NY 11367 USA. NINDS, Cognit Neurosci Sect, Med Neurol Branch, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. RP Ruchkin, DS (reprint author), Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. EM druchkin@umaryland.edu OI Grafman, Jordan H./0000-0001-8645-4457 NR 58 TC 21 Z9 22 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0749-596X J9 J MEM LANG JI J. Mem. Lang. PD OCT PY 1999 VL 41 IS 3 BP 345 EP 364 DI 10.1006/jmla.1999.2644 PG 20 WC Linguistics; Psychology; Psychology, Experimental SC Linguistics; Psychology GA 241GT UT WOS:000082874800003 ER PT J AU Ponting, CP AF Ponting, CP TI Raf-like Ras/Rap-binding domains in RGS12-and still-life-like signalling proteins SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE regulator of G protein signalling; LGN motifs; G(i)alpha GTPase; Tiam-1; signalling pathway ID GTPASE-ACTIVATING PROTEINS; ALPHA-SUBUNITS; FAMILY; IDENTIFICATION; EXCHANGERS; CLONING; GAIP AB Ras proteins play critical roles in regulating cell growth and differentiation, and mutated Ras genes are expressed in a variety of human cancers. Consequently, much interest has centered on the binding partners of Ras, including the Ras-binding domain (RBD) of Raf kinase. Here evidence is presented that domains homologous to the Raf RED are present in tandem in RGS12, RGS14 and LOGO, and singly in molecules similar to mouse Tiam-1. In addition; RGS12, RGS14 and LOCO are shown to contain single "LGN motifs" that are guanine nucleotide exchange factors specific for the cc-subunit of G proteins. These findings indicate "cross-talk" interactions between signalling pathways involving Ras and Rap and pathways involving Rho, Rac and Ga GTPases. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20814 USA. RP Ponting, CP (reprint author), Univ Oxford, Dept Human Anat & Genet, MRC, Funct Genet Unit, S Pk Rd, Oxford OX1 3QX, England. NR 29 TC 46 Z9 47 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD OCT PY 1999 VL 77 IS 10 BP 695 EP 698 DI 10.1007/s001099900054 PG 4 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 258UH UT WOS:000083857200002 PM 10606204 ER PT J AU Kennelly, EJ Flynn, TJ Mazzola, EP Roach, JA McCloud, TG Danford, DE Betz, JM AF Kennelly, EJ Flynn, TJ Mazzola, EP Roach, JA McCloud, TG Danford, DE Betz, JM TI Detecting potential teratogenic alkaloids from blue cohosh rhizomes using an in vitro rat embryo culture SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID QUINOLIZIDINE ALKALOIDS; CAULOPHYLLUM THALICTROIDES; C-13-NMR; SYSTEM AB The novel alkaloid thalictroidine (1), as well as the known alkaloids taspine (2), magnoflorine (3), anagyrine (4), baptifoline (5), 5,6-dehydro-alpha-isolupanine (6), alpha-isolupanine (7), lupanine (8), N-methylcytisine (9), and sparteine (10), were identified from an extract of Caulophyllum thalictroides rhizomes. N-Methylcytisine exhibited teratogenic activity in the rat embryo culture (REC), an in vitro method to detect potential teratogens. The structure of 1 was elucidated using various spectroscopic methods, primarily by NMR techniques. Thalictroidine, anagyrine, and a-isolupanine were not teratogenic in the REC at tested concentrations. Taspine (2) showed high embryotoxicity, but no teratogenic activity, in the REC. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Kennelly, EJ (reprint author), CUNY Herbert H Lehman Coll, Dept Biol Sci, 250 Bedford Pk Blvd W, Bronx, NY 10468 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 24 TC 36 Z9 39 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 1999 VL 62 IS 10 BP 1385 EP 1389 DI 10.1021/np9901581 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 250CL UT WOS:000083371400008 PM 10543898 ER PT J AU Dai, JR Hallock, YF Cardellina, JH Boyd, MR AF Dai, JR Hallock, YF Cardellina, JH Boyd, MR TI 20-O-beta-glucopyranosyl camptothecin from Mostuea brunonis: A potential camptothecin pro-drug with improved solubility SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID OPHIORRHIZA-PUMILA; GLYCOCAMPTOTHECIN; STRICTOSIDINE; CHABOSIDE; SCREEN AB Bioassay-guided fractionation of the organic extracts of whole plants of Mostuea brunonis (Loganiaceae), using the National Cancer Institute's (NCI) human tumor-based in vitro antitumor screen, led to the isolation and identification of camptothecin 20-O-beta-D-glucoside (1) and three moderately cytotoxic alkaloids, the known deoxypumiloside (2) and strictosamide (3), and the new 2'-O-acetylstrictosamide (4), from the cytotoxic alkaloid fractions. While the previously unknown 20-O-beta-D-glucopyranosyl camptothecin exhibited greater solubility in alcohol, DMSO-H(2)O and H(2)O than camptothecin, it was essentially inactive in the NCI's in vitro 60-cell line primary antitumor screen. However, it could be vulnerable to de-glucosidation in vivo, and may, therefore, merit additional evaluation as a potential prodrug of camptothecin that could be more readily formulated than the parent agent. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Bldg 1052,Room 121, Frederick, MD 21702 USA. EM boyd@dtpax2.ncifcrf.gov NR 23 TC 23 Z9 29 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 1999 VL 62 IS 10 BP 1427 EP 1429 DI 10.1021/np990100m PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 250CL UT WOS:000083371400018 PM 10543908 ER PT J AU Zahn-Waxler, C Hastings, PD AF Zahn-Waxler, C Hastings, PD TI Unto others: The evolution and psychology of unselfish behavior. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIMH, Intramural Res Programs, Bethesda, MD 20892 USA. RP Zahn-Waxler, C (reprint author), NIMH, Intramural Res Programs, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 1999 VL 187 IS 10 BP 645 EP 647 DI 10.1097/00005053-199910000-00011 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 246FQ UT WOS:000083154100011 ER PT J AU Feldman, DE Nicoll, RA Malenka, RC AF Feldman, DE Nicoll, RA Malenka, RC TI Synaptic plasticity at thalamocortical synapses in developing rat somatosensory cortex: LTP, LTD, and silent synapses SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE long-term potentiation; long-term depression; barrel cortex; silent synapses; thalamocortical synapses ID LONG-TERM POTENTIATION; MOUSE BARREL CORTEX; EXPERIENCE-DEPENDENT PLASTICITY; VIBRISSA-RELATED PATTERNS; VISUAL-CORTEX; LAYER-IV; GLUTAMATERGIC SYNAPSES; POSTNATAL BLOCKADE; CORTICAL ACTIVITY; RECEPTOR BLOCKADE AB Thalamocortical synaptic transmission in the rat's primary somatosensory (S1) cortex is modified by sensory experience during a critical period early in life. Despite the importance of such plasticity for the maturation of thalamocortical circuits, the synaptic basis of this plasticity is unknown. Here, we review evidence suggesting that long-term potentiation and depression (LTP and LTD) of thalamocortical synaptic transmission may be involved in this plasticity. In an in vitro slice preparation, thalamocortical synaptic responses exhibit N-methyl-D-aspartate (NMDA) receptor-dependent LTP and LTD during a developmental period similar to the critical period in vivo. The inability to induce LTP and LTD after the critical period may result in part from a developmental reduction in the duration of NMDA receptor currents. In addition, during the critical period many thalamocortical synapses exhibit NMDA receptor currents but no detectable AMPA receptor currents, and thus may be functionally silent at resting membrane potentials, LTP converts silent synapses to functional ones by causing the rapid appearance of AMPA currents. These observations suggest that thalamocortical synapses may be formed as silent synapses which are subsequently made functional by LTP. LTP and LTD may then regulate the efficacy of these functional synapses and thereby contribute to experience dependent changes in S1 thalamocortical circuits. (C) 1999 John Wiley & Sons. Inc. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. RP Feldman, DE (reprint author), NINDS, Neural Dev Sect, NIH, Bldg 36,Rm 2C02,36 Convent Dr, Bethesda, MD 20892 USA. RI yu, yan/C-2322-2012 NR 80 TC 138 Z9 144 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD OCT PY 1999 VL 41 IS 1 BP 92 EP 101 DI 10.1002/(SICI)1097-4695(199910)41:1<92::AID-NEU12>3.0.CO;2-U PG 10 WC Neurosciences SC Neurosciences & Neurology GA 242QF UT WOS:000082951700012 PM 10504196 ER PT J AU Burke, Z Wells, T Carter, D Klein, D Baler, R AF Burke, Z Wells, T Carter, D Klein, D Baler, R TI Genetic targeting: The serotonin N-acetyltransferase promoter imparts circadian expression selectively in the pineal gland and retina of transgenic rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE pineal gland; rat arylalkylamine N-acetyltransferase promoter; circadian rhythm; retina ID MESSENGER-RNA; ADRENERGIC REGULATION; PHOTORECEPTOR CELLS; BINDING-PROTEIN; CYCLIC-AMP; REPRESSOR; CREM; TRANSCRIPTION; ACTIVATION; DIRECTS AB The arylalkylamine N-acetyltransferase (AA-NAT) gene is strongly expressed in the rat primarily in the pineal gland; low levels of expression are also found in the retina. AA-NAT catalyzes the key regulatory step controlling rhythmic melatonin output: the acetylation of serotonin, In the rat, the AA-NAT gene is expressed at night, This is controlled partly by cyclic AMP (cAMP) acting through a composite cAMP-responsive element-CCAAT site located upstream of the transcription start point. In the present study, we have extended our previous in vitro findings and found that additional elements in the 5' flanking region and first intron play an important role in the regulation of the AA-NAT gene. This led us to test the influence of an AA-NAT 5' flanking segment on the expression of the bacterial chloramphenicol acetyltransferase gene in a rat transgenic model. The results of this study clearly demonstrate that the segment of the AA-NAT gene that encompasses the minimal promoter and the first intron is able to confer the highly specific pineal/retinal and time-of-day patterns of AA-NAT gene expression. This advance also provides a tool that selectively targets genetic expression to pinealocytes and retinal photoreceptors, providing new experimental opportunities to probe gene expression in these tissues. C1 NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. Univ Wales, Sch Biosci, Cardiff CF1 3NS, S Glam, Wales. NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Baler, R (reprint author), NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bldg 36,Rm 2A-09, Bethesda, MD 20892 USA. RI Wells, Timothy/A-6484-2010; Carter, David/A-4479-2010; OI Carter, David/0000-0002-8419-3975; Wells, Timothy/0000-0003-3618-0595 NR 28 TC 36 Z9 37 U1 0 U2 1 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 1999 VL 73 IS 4 BP 1343 EP 1349 DI 10.1046/j.1471-4159.1999.0731343.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 236TZ UT WOS:000082616200002 PM 10501177 ER PT J AU Lee, HW Hahm, SH Hsu, CM Eiden, LE AF Lee, HW Hahm, SH Hsu, CM Eiden, LE TI Pituitary adenylate cyclase-activating polypeptide regulation of vasoactive intestinal polypeptide transcription requires Ca2+ influx and activation of the serine/threonine phosphatase calcineurin SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE vasoactive intestinal polypeptide; primary chromaffin cells; pituitary adenylate cyclase-activating polypeptide; calcium influx; calcineurin activation ID ADRENAL CHROMAFFIN CELLS; CYCLIC-AMP; CYCLOSPORINE-A; MEMBRANE DEPOLARIZATION; CATECHOLAMINE SECRETION; TYROSINE-HYDROXYLASE; SIGNAL-TRANSDUCTION; GENE-TRANSCRIPTION; PACAP; EXPRESSION AB A >15-fold increase in vasoactive intestinal polypeptide (VIP) mRNA and VIP peptide levels occurred in primary chromaffin cells following exposure to the neurotrophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)-27 with an EC50 of similar to 2 nM. PACAP induction of VIP expression was blocked by methoxyverapamil or by a combination of nimodipine and omega-conotoxin MVIIC, indicating a requirement for PACAP-initiated calcium entry through voltage-dependent calcium channels for regulation of VIP biosynthesis. Ascomycin, which inhibits calcineurin through formation of an ascomycin/FKBP12/calcineurin ternary complex, abolished the PACAP-evoked increase in VIP expression, whereas rapamycin, which also binds to FKBP12 but does not cause inhibition of calcineurin, did not. Cyclosporin A, which inhibits calcineurin through formation of a cyclosporin A/cyclophilin/calcineurin complex, also abolished PACAP-evoked VIP biosynthesis, These data indicate that PACAP regulates the expression of VIP via a signaling pathway that requires calcium influx and activation of calcineurin. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Lee, HW (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 33 TC 19 Z9 19 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 1999 VL 73 IS 4 BP 1769 EP 1772 DI 10.1046/j.1471-4159.1999.731769.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 236TZ UT WOS:000082616200052 PM 10501227 ER PT J AU Recanzone, GH Wurtz, RH AF Recanzone, GH Wurtz, RH TI Shift in smooth pursuit initiation and MT and MST neuronal activity under different stimulus conditions SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TEMPORAL VISUAL AREA; MONKEY SUPERIOR COLLICULUS; SACCADE-RELATED ACTIVITY; EYE-MOVEMENTS; MACAQUE MONKEY; EXPANSION CONTRACTION; FUNCTIONAL-PROPERTIES; VECTOR SUMMATION; RECEPTIVE-FIELD; ROTATION CELLS AB The activity of neurons in extrastriate middle temporal (MT) and medial superior temporal (MST) areas were studied during the initiation of pursuit eye movements in macaque monkeys. The intersecting motion of two stimuli was used to test hypotheses about how these direction- and speed-sensitive neurons contribute to the generation of pursuit. The amplitude and direction of the initial saccade to the target and the initial speed and direction of pursuit were best predicted by a vector-average model of the underlying neuronal activity with relatively short time and spatial separation before a visual pursuit target and a distracter stimulus crossed in the visual field. The resulting eye movements were best described by a winner-take-all model when the time and spatial separation between the two stimuli was increased before the stimuli crossed. Neurons in MT and MST also shifted their activity from that best described by a vector average to a winner-take-all model under the same stimulus conditions. The changes in activity of neurons in both areas were generally similar to each other during these changes in pursuit initiation. Thus a slight alteration in the target motion produced a concurrent shift in both the neuronal processing and the movement execution. We propose that the differences in the oculomotor behavior can be accounted for by shifts in the overlap of active neuronal populations within MT and MST. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. Univ Calif Davis, Sec Neurobiol Physiol & Behav, Davis, CA 95616 USA. RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [DC-02371] NR 55 TC 50 Z9 50 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 1999 VL 82 IS 4 BP 1710 EP 1727 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 264CH UT WOS:000084162100006 PM 10515961 ER PT J AU Coghill, RC Sang, CN Maisog, JH Iadarola, MJ AF Coghill, RC Sang, CN Maisog, JH Iadarola, MJ TI Pain intensity processing within the human brain: A bilateral, distributed mechanism SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CINGULATE CORTEX; NOCICEPTIVE NEURONS; AUTOMATED ALGORITHM; WORKING-MEMORY; RHESUS-MONKEY; AREA; PET; PERCEPTION; SPACE AB Functional imaging studies of human subjects have identified a diverse assortment of brain areas that are engaged in the processing of pain. Although many of these brain areas are highly interconnected and are engaged in multiple processing roles, each area has been typically considered in isolation. Accordingly, little attention has been given to the global functional organization of brain mechanisms mediating pain processing. In the present investigation, we have combined positron emission tomography with psychophysical assessment of graded painful stimuli to better characterize the multiregional organization of supraspinal pain processing mechanisms and to identify a brain mechanism subserving the processing of pain intensity. Multiple regression analysis revealed statistically reliable relationships between perceived pain intensity and activation of a functionally diverse group of brain regions, including those important in sensation, motor control, affect, and attention. Pain intensity-related activation occurred bilaterally in the cerebellum, putamen, thalamus, insula, anterior cingulate cortex, and secondary somatosensory cortex, contralaterally in the primary somatosensory cortex and supplementary motor area, and ipsilaterally in the ventral premotor area. These results confirm the existence of a highly distributed, bilateral supraspinal mechanism engaged in the processing of pain intensity. The conservation of pain intensity information across multiple, functionally distinct brain areas contrasts sharply with traditional views that sensory-discriminative processing of pain is confined within the somatosensory cortex and can account for the preservation of conscious awareness of pain intensity after extensive cerebral cortical lesions. C1 NIDR, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Coghill, RC (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Neurobiol & Anat, Winston Salem, NC 27157 USA. NR 59 TC 593 Z9 608 U1 8 U2 32 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 1999 VL 82 IS 4 BP 1934 EP 1943 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 264CH UT WOS:000084162100028 PM 10515983 ER PT J AU Moore, LE Chub, N Tabak, J O'Donovan, M AF Moore, LE Chub, N Tabak, J O'Donovan, M TI NMDA-induced dendritic oscillations during a soma voltage clamp of chick spinal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dendritic oscillations; chick spinal neurons; NMDA; electrotonic structure; frequency domain; impedance ID METHYL-D-ASPARTATE; ARBITRARILY BRANCHING CABLES; PASSIVE MEMBRANE-PROPERTIES; NEOCORTICAL PYRAMIDAL NEURONS; SPONTANEOUS RHYTHMIC ACTIVITY; CELL PATCH CLAMP; ELECTRICAL-PROPERTIES; HIPPOCAMPAL-NEURONS; SYNAPTIC POTENTIALS; LAMPREY AB An investigation of dendritic membrane properties was performed by whole-cell patch measurements of the biophysical properties of intact chick spinal neurons that are involved in rhythmogenesis. A whole-cell voltage clamp of the somatic membrane was used to block NMDA-induced voltage oscillations from the cell body, thus partially isolating the intrinsic oscillatory properties of dendritic membranes from those of the soma. An experimental approach was developed that takes into account the complexity of the dendritic tree in an environment as normal as possible, without the need for cell isolation or slice preparations. A computational study of the experimentally determined model showed that excitatory amino acid receptors on dendrites can dynamically control the electrotonic length of the dendrites through the activation of negative slope conductances. These experiments demonstrate the presence of NMDA receptors on the dendrites and that they induce intrinsic oscillations when the synaptic input from other cells is significantly reduced. C1 CNRS, Lab Neurobiol Reseaux Sensorimoteurs, UPRES 7060, F-75270 Paris 06, France. NIH, Neural Control Lab, Bethesda, MD 20892 USA. RP Moore, LE (reprint author), CNRS, Lab Neurobiol Reseaux Sensorimoteurs, UPRES 7060, 45 Rue St-Peres, F-75270 Paris 06, France. RI tabak, joel/K-1549-2013 NR 59 TC 15 Z9 16 U1 0 U2 0 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 1999 VL 19 IS 19 BP 8271 EP 8280 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 240BG UT WOS:000082805400015 PM 10493728 ER PT J AU Cui, CH Mayer, ML AF Cui, CH Mayer, ML TI Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE kainate receptors; polyamines; glutamate receptors; ATPA; iodowillardiine; coassembly; heteromeric glutamate receptors ID HIGH-AFFINITY KAINATE; CULTURED HIPPOCAMPAL-NEURONS; GLUTAMATE RECEPTORS; SYNAPTIC TRANSMISSION; RAT HIPPOCAMPUS; SUBUNITS GLUR5; ACID RECEPTORS; GRANULE CELLS; ION CHANNELS; DRG-NEURONS AB In the CNS kainate subtype glutamate receptors (GluRs) are likely to be heteromeric assemblies containing multiple gene products. However, although recombinant kainate receptors from the GluR5-GluR7 gene family have been studied extensively in their homomeric forms, there have been no tests to determine whether these subunits can coassemble with each other. We used the GluR5 selective agonists (RS)-2-amino-3(3-hydroxy-5-tertbutylisoxazol-4-yl) propanoic acid (ATPA) and (S)-5-iodowillardiine (I-will) to test for the coassembly of GluR5 with GluR6 and GluR7 by measuring changes in rectification that occur for heteromeric receptors containing both edited and unedited Q/R site subunits. Birectifying ATPA and I-will responses resulting from polyamine block for homomeric GluR5(Q) became outwardly rectifying when GluR6(R) was coexpressed with GluR5(Q), although GluR6 was not activated by ATPA or I-will, indicating the formation of heteromeric receptors. Similar approaches showed the coassembly of GluR7 with GluR6 and GluR5. Heteromeric kainate receptors containing both GluR5 and GluR6 subunits exhibited novel functional properties, including reduced desensitization and faster recovery from desensitization than those recorded for homomeric GluR5. Coexpression of GluR6 with GluR5 also enhanced the magnitude of responses to GluR5 selective agonists. In contrast, the coassembly of GluR7 with GluR6 markedly decreased the amplitude of agonist responses. Our results indicate that, similar to AMPA receptors, the kainate receptor subunits GluR5-GluR7 exhibit promiscuous coassembly. The formation of heteromeric kainate receptors may help to explain why the functional properties of native kainate receptors differ from those that have been reported for recombinant kainate receptors. C1 NICHHD, Cellular & Mol Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Mayer, ML (reprint author), NICHHD, Cellular & Mol Neurophysiol Lab, NIH, Bldg 49,Room SA78,49 Convent Dr, Bethesda, MD 20892 USA. RI Mayer, Mark/H-5500-2013 NR 53 TC 100 Z9 102 U1 0 U2 2 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 1999 VL 19 IS 19 BP 8281 EP 8291 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 240BG UT WOS:000082805400016 PM 10493729 ER PT J AU Alkon, DL AF Alkon, DL TI Ionic conductance determinants of synaptic memory nets and their implications for Alzheimer's disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE ionic conductance determinants; memory; synaptic memory nets; Alzheimer's disease ID HIPPOCAMPAL-NEURONS; POTASSIUM CHANNELS; MOLLUSCAN PHOTORECEPTOR; ASSOCIATIVE MEMORY; CURRENTS; CALCIUM; DIVERSITY; ANTISENSE; RAT AB Electrical and chemical signals representing macroscopic "perturbations" in brain networks engage large numbers of transient "microscopic" ionic channel fluctuations in producing long-lasting changes of conductance land thus potential). Repeated electrical and chemical signals that occur during associative training of living organisms (from mollusc to mammal) can cause ionic conductance changes lasting from days to many weeks. If a stimulus pattern reoccurs with sufficient frequency, voltage-dependent K+ conductances-responsible for both synaptic and intrinsic membrane currents-become progressively less probabilistic and more deterministic. In effect, more deterministic ion channel functions record in associative memory more deterministic (i.e., higher probability) events in the environment. This memory has been found to be stored within brain networks as ensembles of local dendritic ionic conductance changes distributed throughout brain regions such as the hippocampus and cerebellar cortex. Numerous other studies taken together support the hypothesis that distributed dendritic loci store associative memory, do not involve long-term potentiation, are also loci for Alzheimer's disease (AD) pathophysiology, and can contribute to, if not be responsible for, early memory loss in clinically manifest AD. Published 1999 Wiley-Liss, Inc.(dagger) C1 NINDS, Lab Adapt Syst, Basci Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Alkon, DL (reprint author), NINDS, Lab Adapt Syst, Basci Neurosci Program, NIH, Bethesda, MD 20892 USA. NR 24 TC 14 Z9 16 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 1 PY 1999 VL 58 IS 1 BP 24 EP 32 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 239AP UT WOS:000082746900004 PM 10491569 ER PT J AU Lu, B Chow, A AF Lu, B Chow, A TI Neurotrophins and hippocampal synaptic transmission and plasticity SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Review DE neurotrophins; brain-derived neurotrophic factor (BDNF); synaptic transmission; long-term potentiation (LTP); hippocampus; vesice docking; CAI synapse ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; AMYLOID-PRECURSOR PROTEIN; NECROSIS-FACTOR-ALPHA; RAT VISUAL-CORTEX; DEVELOPING NEUROMUSCULAR SYNAPSES; PAIRED-PULSE FACILITATION; CORTICAL DENDRITIC GROWTH; MESSENGER-RNA EXPRESSION; CEREBELLAR GRANULE CELLS AB Neurotrophins are traditionally thought to be secretory proteins that regulate long-term survival and differentiation of neurons. Recent studies have revealed a previously unexpected role for neurotrophins in synaptic development and plasticity in diverse neuronal populations. In this review, we focus on the synaptic function of brain-derived neurotrophic factor (BDNF) in the hippocampus, Although a variety of in vitro experiments have shown the ability of BDNF to acutely modulate synaptic transmission, whether BDNF truly potentiates basal synaptic transmission in hippocampal neurons remains controversial. More consistent evidence has been obtained for the role of BDNF in long-term potentiation (LTP), a cellular model for learning and memory, BDNF also potentiates high frequency transmission by modulating the number of docked vesicles and the levels of the vesicle protein synaptobrevin and synaptophysin at the CA1 synapses. Both pre- and postsynaptic effects of BDNF have been demonstrated. Recent studies have begun to address the role of BDNF in late-phase LTP and in the development of hippocampal circuit. BDNF and other neurotrophins may represent a new class of neuromodulators that regulate neuronal connectivity and synaptic efficacy. Published 1999 Wiley-Liss, Inc.(dagger) C1 NICHD, Unit Synapse Dev & Plast, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHD, Unit Synapse Dev & Plast, Dev Neurobiol Lab, NIH, Bldg 49,Rm 5A38,49 Convent Dr,MSC4480, Bethesda, MD 20892 USA. NR 130 TC 183 Z9 190 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 1 PY 1999 VL 58 IS 1 BP 76 EP 87 DI 10.1002/(SICI)1097-4547(19991001)58:1<76::AID-JNR8>3.0.CO;2-0 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 239AP UT WOS:000082746900008 PM 10491573 ER PT J AU Heiss, JD Patronas, N DeVroom, HL Shawker, T Ennis, R Kammerer, W Eidsath, A Talbot, T Morris, J Eskioglu, E Oldfield, EH AF Heiss, JD Patronas, N DeVroom, HL Shawker, T Ennis, R Kammerer, W Eidsath, A Talbot, T Morris, J Eskioglu, E Oldfield, EH TI Elucidating the pathophysiology of syringomyelia SO JOURNAL OF NEUROSURGERY LA English DT Article DE syringomyelia; radiography; neurophysiology; Arnold-Chiari malformation ID POSTERIOR CRANIAL FOSSA; CHIARI-I MALFORMATION; NATURAL-HISTORY; PATHOGENESIS AB Object. Syringomyelia causes progressive myelopathy. Most patients with syringomyelia have a Chiari I mal formation of the cerebellar tonsils. Determination of the pathophysiological mechanisms underlying the progression of syringomyelia associated with the Chiari I malformation should improve strategies to halt progression of myelopathy. Methods. The authors prospectively studied 20 adult patients with both Chiari I malformation and symptomatic syringomyelia. Testing before surgery included the following: clinical examination; evaluation of anatomy by using T-1-weighted magnetic resonance (MR) imaging; evaluation of the syrinx and cerebrospinal fluid (CSF) velocity and flow by using phase-contrast cine MR imaging; and evaluation of lumbar and cervical subarachnoid pressure at rest, during the Valsalva maneuver, during jugular compression, and following removal of CSF (CSF compliance measurement). During surgery, cardiac-gated ultrasonography and pressure measurements were obtained from the intracranial, cervical subarachnoid, and lumbar intrathecal spaces and syrinx. Six months after surgery, clinical examinations, MR imaging studies, and CSF pressure recordings were repeated. Clinical examinations and MR imaging studies were repeated annually. For comparison, 18 healthy volunteers underwent T-1-weighted MR imaging, cine MR imaging, and cervical and lumbar subarachnoid pressure testing. Compared with healthy volunteers, before surgery, the patients had decreased anteroposterior diameters of the ventral and dorsal CSF spaces at the foramen magnum. In patients, CSF velocity at the foramen magnum was increased, but CSF flow was reduced. Transmission of intracranial pressure across the foramen magnum to the spinal subarachnoid space in response to jugular compression was partially obstructed. Spinal CSF compliance was reduced, whereas cervical subarachnoid pressure and pulse pressure were increased. Syrinx fluid flowed inferiorly during systole and superiorly during diastole on cine MR imaging. At surgery, the cerebellar tonsils abruptly descended during systole and ascended during diastole, and the upper pole of the syrinx contracted in a manner synchronous with tonsillar descent and with the peak systolic cervical subarachnoid pressure wave. Following surgery, the diameter of the CSF pas sages at the foramen magnum increased compared with preoperative values, and the maximum flow rate of CSF across the foramen magnum during systole increased. Transmission of pressure across the foramen magnum to the spinal subarachnoid space in response to jugular compression was normal and cervical subarachnoid mean pressure and pulse pressure decreased to normal. The maximum syrinx diameter decreased on MR imaging in all patients. Cine MR imaging documented reduced velocity and flow of the syrinx fluid. Clinical symptoms and signs improved or remained stable in all patients, and the tonsils resumed a normal shape. Conclusions. The progression of syringomyelia associated with Chiari I malformation is produced by the action of the cerebellar tonsils, which partially occlude the subarachnoid space at the foramen magnum and act as a piston on the partially enclosed spinal subarachnoid space. This creates enlarged cervical subarachnoid pressure waves that compress the spinal cord from without, not from within, and propagate syrinx fluid caudally with each heartbeat, which leads to syrinx progression. The disappearance of the abnormal shape and position of the tonsils after simple decompressive extraarachnoidal surgery suggests that the Chiari I malformation of the cerebellar tonsils is acquired, not congenital. Surgery limited to suboccipital craniectomy, C-l laminectomy, and duraplasty eliminates this mechanism and eliminates syringomyelia and its progression without the risk of more invasive procedures. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Heiss, JD (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,10-5D37,MSC-1414, Bethesda, MD 20892 USA. NR 21 TC 254 Z9 262 U1 0 U2 7 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1999 VL 91 IS 4 BP 553 EP 562 DI 10.3171/jns.1999.91.4.0553 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 239HV UT WOS:000082763400004 PM 10507374 ER PT J AU Davies, M Paterson, IC Stone, A Huntley, S Patel, V Curtis, R Matthews, JB Pring, M Eveson, JW Prime, SS AF Davies, M Paterson, IC Stone, A Huntley, S Patel, V Curtis, R Matthews, JB Pring, M Eveson, JW Prime, SS TI Loss of differentiation of 4NQO-induced rat malignant oral keratinocytes correlates with metastatic dissemination and is associated with a reduced cellular response to TGF-beta 1 and an altered receptor profile SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE differentiation; keratinocytes; metastases; TGF-beta ID GROWTH-FACTOR-BETA; BENIGN SKIN TUMORS; MOUSE SKIN; TRANSFORMING GROWTH-FACTOR-BETA-1; IN-VITRO; SPINDLE CARCINOMAS; EPITHELIAL-CELLS; HIGH-RISK; EXPRESSION; PROGRESSION AB This study examined the metastatic capacity of clonal populations of 4NQO-induced rat malignant oral keratinocytes following orthotopic transplantation to athymic mice. Polygonal and spindle cells formed well-differentiated squamous cell carcinomas (keratin positive and vimentin negative) and undifferentiated spindle cell tumours (keratin negative and vimentin positive), respectively, in almost 100% of animals at the site of inoculation (floor of mouth). Transplantation of 5x10(6) cells of either cell type at high cell density resulted in approximately 50% of animals forming pulmonary metastases. By contrast, inoculation of 2x10(6) differentiated polygonal cells resulted in the formation of significantly fewer pulmonary metastases than the undifferentiated spindle cells. A single well-differentiated clone of polygonal cells and 3 of 4 of the undifferentiated spindle cell lines produced comparable levels of TGF-beta 1. One undifferentiated spindle cell line expressed significantly more TGF-beta 1 and, following transplantation orthotopically, fewer animals formed pulmonary metastases despite the formation of primary tumours in almost all grafted animals, suggesting that TGF-beta 1 can act as a tumour suppressor in this cell type. All cell lines produced comparable amounts of TGF-beta 2. The clones of polygonal cells were markedly inhibited and the spindle cells were only partially inhibited by exogenous TGF-beta 1. Both cell types expressed high-affinity TGF-beta cell surface receptors; the ratio of type I to type II TGF-beta receptors was 1.0:<3.0 in the spindle cells and 1.0:17.9 in the polygonal clone. The results suggest that differentiated rat malignant oral keratinocytes are less aggressive and have a decreased potential to metastasise than their undifferentiated spindle cell counterparts. This may be attributable, in part, to a change in TGF-beta receptor profile leading to the partial loss of response to exogenous TGF-beta 1. C1 Univ Bristol, Dept Oral & Dent Sci, Div Oral Med Pathol & Microbiol, Bristol, Avon, England. NIH, Cellular Dev & Oncol Lab, Bethesda, MD 20892 USA. Millennium Pharmaceut, Cambridge, MA USA. Univ Birmingham, Dept Oral Pathol, Birmingham, W Midlands, England. RP Prime, SS (reprint author), Univ Bristol, Bristol Dent Hosp & Sch, Div Oral Med Pathol & Microbiol, Lower Maudlin St, Bristol BS1 2LY, Avon, England. RI Paterson, Ian/G-8688-2011 NR 46 TC 7 Z9 7 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD OCT PY 1999 VL 28 IS 9 BP 397 EP 405 PG 9 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA 247JC UT WOS:000083216800003 PM 10535362 ER PT J AU Wilk, A Grajkowski, A Phillips, LR Beaucage, SL AF Wilk, A Grajkowski, A Phillips, LR Beaucage, SL TI The 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group as an alternative to the 2-cyanoethyl group for phosphate protection in the synthesis of oligodeoxyribonucleotides SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SULFUR-TRANSFER REAGENT; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; OLIGONUCLEOTIDE SYNTHESIS; PHOSPHORAMIDITE; DEPROTECTION; DERIVATIVES; ACTIVATION; SUPPORTS; CLEAVAGE; MONOMERS AB The 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group for phosphate protection in the synthesis of oligodeoxyribonucleotides has been developed to completely prevent nucleobase alkylation by acrylonitrile that could potentially occur upon deprotection of the traditional 2-cyanoethyl phosphate protecting group. The properties of this new phosphate protecting group were evaluated using the model phosphotriester 9. The mechanism of phosphate deprotection was studied by treating 9 with concentrated NH4OH. NMR analysis,of the deprotection reaction demonstrated that cleavage of the N-trifluoroacetyl group is rate-limiting. The resulting phosphotriester intermediate 13 was also shown to undergo rapid cyclodeesterification to produce O,O-diethyl phosphate 15 and N-methylpyrrolidine -16 (Scheme 2). Given the facile removal of the 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting group under mild basic conditions, its utilization in oligonucleotide synthesis began with the preparation of the deoxyribonucleoside phosphoramidites 4a-d (Scheme 3). The coupling efficiency of 4a-d and conventional a-cyanoethyl deoxyribonucleoside phosphoramidites 24a-d was then compared in the solid-phase synthesis of the 20-mer d(ATCCGTAGCTAAGGTCATGC). As previously observed in the deprotection of 9, the 4-[N-methyl,N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting groups were easily and completely removed from the oligonucleotide by using either concentrated NH4OH or pressurized ammonia gas. Analysis of the deprotected oligomer by polyacrylamide gel electrophoresis (Figure 3) indicated that the phosphoramidites 4a-d are as efficient as the 2-cyanoethyl phosphoramidites 24a-d in the synthesis of the 20-mer. Furthermore, following digestion of the crude 20-mer by snake venom phosphodiesterase and bacterial alkaline phosphatase, HPLC analysis showed complete hydrolysis to individual nucleosides and no detectable nucleobase modification. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 34 Z9 34 U1 3 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD OCT 1 PY 1999 VL 64 IS 20 BP 7515 EP 7522 DI 10.1021/jo990835w PG 8 WC Chemistry, Organic SC Chemistry GA 244DP UT WOS:000083036800033 ER PT J AU Prusiewicz, CB Sangaiah, B Tomer, KB Gold, A AF Prusiewicz, CB Sangaiah, B Tomer, KB Gold, A TI A robust synthetic route to 2 '-deoxy-3 '-nucleotide derivatives of modified nucleobases SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ADDUCTS; CYCLOPENTAPYRENE; EPOXIDE; CYCLOPENTA(CD)PYRENE; CARCINOGEN; CIS C1 Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Gold, A (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. RI Tomer, Kenneth/E-8018-2013 NR 24 TC 3 Z9 3 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD OCT 1 PY 1999 VL 64 IS 20 BP 7628 EP 7632 DI 10.1021/jo982473i PG 5 WC Chemistry, Organic SC Chemistry GA 244DP UT WOS:000083036800049 ER PT J AU Costantini, M Toscani, F Gallucci, M Brunelli, C Miccinesi, G Tamburini, M Paci, E Di Giulio, P Peruselli, C Higginson, I Addington-Hall, J AF Costantini, M Toscani, F Gallucci, M Brunelli, C Miccinesi, G Tamburini, M Paci, E Di Giulio, P Peruselli, C Higginson, I Addington-Hall, J CA Italian Cooperative Res Grp Palliative Med TI Terminal cancer patients and timing of referral to palliative care: A multicenter prospective cohort study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE palliative care; cancer; survival ID SURVIVAL; HOSPICE; INDEXES; SERVICE; LENGTH; HOME AB This study describes the characteristics of a representative sample of terminally ill cancer patients at admission to Italian palliative care programs, the rate and reasons for discontinuation of care, and survival after enrollment. All Italian palliative care units (PCUs) specifically committed to palliative care were asked to consecutively register all new patients (n = 3901) between January and June, 1995. Fifty-eight of the 62 PCUs contacted by the Steering Committee completed the study. A random sample of 589 evaluable patients was prospectively selected from the 2667 eligible patients. Patients were mostly referred by a general practitioner (31.2 %) or a specialist (42.1 %). Most patients (84.7 %) were followed until death. Seventy-seven discontinued care because of hospital admission (6.6 %), change of residence (3.9 %), refusal (1.7 %), or improvement (0.8 %). Median survival was 37.9 days; 14.3 % of the patients died within 7 days, and 15.3 % lived longer than 180 days. A statistically significant association between survival and gender cancer type setting of the first visit, and type of unit was observed. In Italy, as in other countries with different health systems, referral of cancer patients to palliative care tends to occur late in the course of the disease. This study suggests that the process of enrollment and the duration of patients' survival in palliative care, when studied in large unselected populations, can provide important information relevant to the care of terminally ill patients. J. Pain Symptom Manage 1999;18:243-252. (C) U.S. Cancer Pain Relief Committee, 1999. C1 Natl Canc Inst, Clin Epidemiol & Trials Unit, I-16132 Genoa, Italy. Crehoma Hosp, Palliat Care Unit, Cremona, Italy. Desio Hosp, Palliat Care Unit, Milan, Italy. Natl Canc Inst, Div Psychol, Milan, Italy. CSPO, Dept Epidemiol, Florence, Italy. Mario Negri Inst Pharmacol Res, Nursing Res Unit, Milan, Italy. Merate Hosp, Palliat Care Unit, Milan, Italy. Univ London Kings Coll, Sch Med & Dent, Dept Palliat Care & Policy, London, England. RP Costantini, M (reprint author), Natl Canc Inst, Clin Epidemiol & Trials Unit, LR Benzi 10, I-16132 Genoa, Italy. RI Higginson, Irene/C-7309-2012; costantini, massimo/G-1443-2012; Brunelli , Cinzia/B-9361-2017; OI Brunelli , Cinzia/0000-0003-3905-1289; costantini, massimo/0000-0002-5293-7079 NR 25 TC 55 Z9 56 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 1999 VL 18 IS 4 BP 243 EP 252 DI 10.1016/S0885-3924(99)00084-6 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 244XU UT WOS:000083076700002 PM 10534964 ER PT J AU Cobo, F Hernandez, S Hernandez, L Pinyol, M Bosch, F Esteve, J Lopez-Guillermo, A Palacin, A Raffeld, M Montserrat, E Jaffe, ES Campo, E AF Cobo, F Hernandez, S Hernandez, L Pinyol, M Bosch, F Esteve, J Lopez-Guillermo, A Palacin, A Raffeld, M Montserrat, E Jaffe, ES Campo, E TI Expression of potentially oncogenic HHV-8 genes in an EBV-negative primary effusion lymphoma occurring in an HIV-seronegative patient SO JOURNAL OF PATHOLOGY LA English DT Article DE primary effusion lymphoma; human herpesvirus 8; Epstein-Barr virus; human immunodeficiency virus; HHV-8 gene expression ID SARCOMA-ASSOCIATED HERPESVIRUS; PROTEIN-COUPLED RECEPTOR; KAPOSIS-SARCOMA; DNA-SEQUENCES; MALIGNANT-LYMPHOMA; VIRUS; KSHV; HUMAN-HERPESVIRUS-8; HOMOLOG; PATHWAY AB Primary effusion lymphoma (PEL) is a novel lymphoproliferative disorder associated with human herpesvirus 8 (HHV-8) infection. Most PELs develop in HIV-seropositive individuals and are nearly always positive for Epstein-Barr virus (EBV), a finding which obscures the role of HHV-8 in lymphomagenesis. However, rare EBV-negative PEL cases occurring in HIV-seronegative patients have been reported, suggesting that HHV-8 may be pathogenetic by itself, To investigate whether HHV-8 may contribute to PEL development in the absence of EBV, the expression of seven potentially oncogenic HHV-8 open reading frames (ORF-s) (ORF72/viral cyclin D, ORF16/viral bcl-2, ORF74/viral G-protein coupled receptor, ORFK2/viral IL-6, ORF13/viral FLICE inhibitory protein, ORFK9/viral interferon regulatory factor, and ORFK1, equivalent to the gene encoding herpesvirus saimiri transforming protein) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in an EBV-negative PEL presenting in an HIV-negative patient. RNA transcripts were demonstrated for the seven HHV-8 genes, and this was confirmed by hybridization to specific oligonucleotide probes. The expression of potentially oncogenic HHV-8 genes in this HIV-, EBV-negative PEL case suggests that HHV-8 may induce malignant transformation of B-lymphocytes through different molecular pathways in the absence of EBV infection. Copyright (C) 1999 John Whey & Sons, Ltd. C1 IDIBAPS, Hosp Clin Barcelona, Dept Pathol, Hematopathol Sect, Barcelona 08036, Spain. IDIBAPS, Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Campo, E (reprint author), IDIBAPS, Hosp Clin Barcelona, Dept Pathol, Hematopathol Sect, Villarroel 170, Barcelona 08036, Spain. RI Hernandez-Llodra, S/H-6863-2014; OI Hernandez-Llodra, S/0000-0003-3963-3756; Bosch, Francesc/0000-0001-9241-2886; Campo, elias/0000-0001-9850-9793 NR 28 TC 31 Z9 31 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 1999 VL 189 IS 2 BP 288 EP 293 DI 10.1002/(SICI)1096-9896(199910)189:2<288::AID-PATH419>3.0.CO;2-F PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 239RL UT WOS:000082783400023 PM 10547588 ER PT J AU Morrison, JA Sprecher, DL Barton, BA Waclawiw, MA Daniels, SR AF Morrison, JA Sprecher, DL Barton, BA Waclawiw, MA Daniels, SR TI Overweight, fat patterning, and cardiovascular disease risk factors in black and white girls: The National Heart, Lung, and Blood Institute Growth and Health Study SO JOURNAL OF PEDIATRICS LA English DT Article ID METABOLIC COMPLICATIONS; CHILDREN; OBESITY; PREVALENCE AB Objective: To determine the association of overweight and central adiposity with cardiovascular disease risk factors in black and white 9- and 10-year-old girls. Design: Gross-sectional analysis of baseline data collected From participants in the National Heart, Lung, and Blood Institute Growth and Health Study. Girls were classified as overweight or not with the use of the age- and sex-specific 85th percentiles of the body mass index (kilograms per square meter) distributions from the combined NHANES (I and II) data set. Mean indexes of central adiposity, blood pressure levels, and lipid concentrations and the clustering of risk factors based on published cut points were compared between weight groups by race and by central adiposity group within weight and race groups. Results: Overweight was associated with increased risk factor levels and with increased clustering in both black and white girls. Among overweight girls greater central adiposity was associated with higher risk factor levels and increased clustering. Conclusions: Given the associations between cardiovascular disease risk factors and both overweight and central adiposity, the secular trends toward increased obesity in American youth portend a worsening of cardiovascular disease risk profiles. C1 Maryland Med Res Inst, Baltimore, MD 21210 USA. Univ Cincinnati, Coll Med, Dept Pediat, Div Cardiol, Cincinnati, OH USA. Cleveland Clin Fdn, Dept Cardiol, Prevent Sect, Cleveland, OH 44195 USA. NHLBI, Off Biostat Res, Bethesda, MD USA. RP Barton, BA (reprint author), Maryland Med Res Inst, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [HC 55025, HC 55026, HL 48941] NR 21 TC 105 Z9 108 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 1999 VL 135 IS 4 BP 458 EP 464 DI 10.1016/S0022-3476(99)70168-X PG 7 WC Pediatrics SC Pediatrics GA 246DU UT WOS:000083149800013 PM 10518079 ER PT J AU Schumann, BC Striegel-Moore, RH McMahon, RP Waclawiw, MA Morrison, JA Schreiber, GB AF Schumann, BC Striegel-Moore, RH McMahon, RP Waclawiw, MA Morrison, JA Schreiber, GB TI Psychometric properties of the self-perception profile for children in a biracial cohort of adolescent girls: The NHLBI growth and health study SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article AB The National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) is an epidemiologic study of 1,213 Black and 1,166 White girls (ages 9-10) of risk factors for obesity. NGHS used Harter's Self-Perception Profile for Children (SPPC) to measure domain-specific competence and overall self-worth. This report reviews the psychometric properties of the SPPC in this biracial cohort at baseline and Year 3 visits (ages 11-12). Simple structure yielding unique components for each of the SPPC domains was obtained for White but not Black girls, whether analyzed overall or by parental education level. Internal consistency was higher for White girls in both years. The lack of simple structure was reflected in the higher correlations among the subscales for Black girls. The structure and internal consistency improved in Year 3 for Black girls, indicating that the physical appearance and athletic competence domains were not yet fully differentiated at baseline. Readers should be cautious, however, when interpreting the SPPC in young Black girls. C1 Maryland Med Res Inst, Coordinating Ctr, Natl Heart Lung & Blood Inst Growth & Hlth Study, Baltimore, MD 21210 USA. Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Div Cardiol, Cincinnati, OH 45229 USA. Westat Inc, Ctr Clin, Natl Heart Lung & Blood Inst Growth & Hlth Study, Rockville, MD 20850 USA. RP Schumann, BC (reprint author), Maryland Med Res Inst, Coordinating Ctr, Natl Heart Lung & Blood Inst Growth & Hlth Study, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. RI McMahon, Robert/C-5462-2009 FU NHLBI NIH HHS [N01-HC-55023]; PHS HHS [N01-55026] NR 15 TC 27 Z9 27 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD OCT PY 1999 VL 73 IS 2 BP 260 EP 275 DI 10.1207/S15327752JPA7302_5 PG 16 WC Psychology, Clinical; Psychology, Social SC Psychology GA 258YV UT WOS:000083868000005 PM 10624004 ER PT J AU Munzar, P Laufert, MD Kutkat, SW Novakova, J Goldberg, SR AF Munzar, P Laufert, MD Kutkat, SW Novakova, J Goldberg, SR TI Effects of various serotonin agonists, antagonists, and uptake inhibitors on the discriminative stimulus effects of methamphetamine in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VENTRAL TEGMENTAL AREA; 5-HT3 RECEPTOR ANTAGONISTS; L-DEPRENYL SELEGILINE; DOPAMINE RELEASE; DRUG DISCRIMINATION; NUCLEUS-ACCUMBENS; PHARMACOLOGICAL CHARACTERIZATION; SQUIRREL-MONKEYS; D-AMPHETAMINE; COCAINE AB Neurochemical studies indicate that methamphetamine increases central serotonin (5-HT) levels more markedly than other psychomotor stimulants such as amphetamine or cocaine. In the present study, we investigated 5-HT involvement in the discriminative stimulus effects of methamphetamine. In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine i.p. from saline under a fixed-ratio schedule of food presentation, the effects of selected 5-HT agonists, antagonists, and uptake inhibitors were tested. Fluoxetine (1.8-18.0 mg/kg) and clomipramine (3.0-18.0 mg/kg), selective serotonin uptake inhibitors, did not produce any methamphetamine-like discriminative stimulus effects when administered alone, but fluoxetine (5.6 mg/kg), unlike clomipramine (5.6 mg/kg), significantly shifted the methamphetamine dose-response curve to the left. Both 8-hydroxy-2-dipropylaminotetralin (0.03-0.56 mg/kg), a full agonist, and buspirone (1.0-10.0 mg/kg), a partial agonist at 5-HT1A receptors, partially generalized to the training dose of methamphetamine but only at high doses that decreased response rate. This generalization was antagonized by the coadministration of the 5-HT1A antagonist WAY-100635 (1.0 mg/kg). WAY-100635 (1.0 mg/kg) also partially reversed the leftward shift of the methamphetamine dose-response curve produced by fluoxetine. (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (0.3 mg/kg), a 5-HT2A/2C agonist, shifted the methamphetamine dose-response curve to the left, and this leftward shift was antagonized by the coadministration of ketanserin (3.0 mg/kg), a 5-HT2A/2C antagonist. Ketanserin (3.0 mg/kg) also produced a shift to the right in the methamphetamine dose-response curve and completely reversed the leftward shift in the methamphetamine dose-response curve produced by fluoxetine. In contrast, tropisetron (1.0 mg/kg), a 5-HT3 antagonist, produced a shift to the left of the methamphetamine dose-response curve, and this effect of tropisetron was antagonized by the coadministration of m-chlorophenyl-biguanide (1.8 mg/kg), a 5-HT3 agonist. The present data suggest that the 5-HT system plays a modulatory role in the discriminative stimulus effects of methamphetamine. These effects appear to be mediated through 5-HT release and blockade of reuptake and subsequent activation of 5-HT2A/2C receptors, with limited involvement of other 5-HT receptor subtypes. C1 NIDA, Preclin Pharmacol Lab, NIH, Baltimore, MD 21224 USA. Masaryk Univ, Fac Med, Dept Pharmacol, Brno, Czech Republic. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Lab, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 53 TC 45 Z9 45 U1 1 U2 1 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 1999 VL 291 IS 1 BP 239 EP 250 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 238QK UT WOS:000082721100032 PM 10490910 ER PT J AU Katz, JL Kopajtic, TA Myers, KA Mitkus, RJ Chider, M AF Katz, JL Kopajtic, TA Myers, KA Mitkus, RJ Chider, M TI Behavioral effects of cocaine: Interactions with D1 dopaminergic antagonists and agonists in mice and squirrel monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DISCRIMINATIVE STIMULUS PROPERTIES; SCHEDULE-CONTROLLED BEHAVIOR; RECEPTOR AGONISTS; D-1 RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; D1-AGONIST SKF-38393; FEEDING-BEHAVIOR; RHESUS-MONKEYS; RAT; SCH-23390 AB The present study compared interactions among dopamine D1-like agonists and partial agonists with cocaine on the locomotor stimulant effects of cocaine, as well as the discriminative-stimulus effects of cocaine, and effects of cocaine on rates of responding. Cocaine alone produced a dose-related stimulation of locomotor activity in Swiss-Webster mice and a dose-related increase in the proportion of responses on the cocaine-appropriate response key in squirrel monkeys (Saimiri sciureus) trained to discriminate cocaine (0.3 mg/kg i.m.) from saline. None of the D1 dopaminergic agents fully reproduced these effects, with SKF 77434 producing marginal stimulation of locomotor activity and SCH 23390, SCH 39166, and SKF 77434 producing some, although incomplete substitution for cocaine in monkeys discriminating cocaine. The D1 dopamine antagonists SCH 23390, SCH 39166, and A-69024 dose-dependently shifted the cocaine dose-effect curve for locomotor activity to the right and decreased the efficacy of cocaine. The same compounds shifted the discriminative-stimulus effects of cocaine to the right without altering efficacy of cocaine. In contrast to the effects on locomotor activity, the maximal shift to the right in the discriminative-stimulus effects of cocaine was similar to 3-fold, with higher doses of the antagonists producing no greater shifts in the cocaine dose-effect curve than with intermediate doses. The partial D1 agonists (+/-)-SKF 38393, (1) SKF 38393, and SKF 77434 also dose-dependently shifted the dose-effect curve for locomotor stimulant effects to the right and decreased the maximal effect of cocaine. These compounds only shifted the discriminative-stimulus effects of cocaine to a 2-fold maximum. In general, cocaine effects on rates of responding in the subjects discriminating cocaine from saline were only minimally antagonized by coadministration of the D1 dopaminergic agents. Both potency for producing behavioral effects alone and in antagonizing the effects of cocaine were related to binding affinities assessed by displacement of [H-3] SCH 23390 from rat striatum. These results suggest that actions mediated by D1-like receptors contribute to the behavioral effects of cocaine. However, the various limitations to the degree of antagonism accomplished indicate that D1-like dopaminergic actions appear to be more involved in the effects of cocaine on locomotor activity, relatively less involved in the discriminative-stimulus effects of cocaine, and least involved in the effects of cocaine on operant response rates. This differential involvement of D1 dopamine receptors in these various behavioral effects of cocaine suggests problems in predicting clinical efficacy of at least D1 receptor antagonists as potential treatments for cocaine abuse. Additional studies are necessary to determine whether the antagonism of cocaine can predict therapeutic efficacy at all, and, if so, which effects when antagonized are the best predictors. C1 NIDA, Psychobiol Sect, Addict Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Addict Res Ctr, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 55 TC 43 Z9 43 U1 0 U2 1 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 1999 VL 291 IS 1 BP 265 EP 279 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 238QK UT WOS:000082721100035 PM 10490913 ER PT J AU Inoue, M Shimohira, I Yoshida, A Zimmer, A Takeshima, H Sakurada, T Ueda, H AF Inoue, M Shimohira, I Yoshida, A Zimmer, A Takeshima, H Sakurada, T Ueda, H TI Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DELTA-OPIOID RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; ORPHANIN-FQ; MICE; CLONING; RAT; LOCALIZATION; ANTAGONIST; CAPSAICIN AB We previously reported that the intraplantar (i.pl.) application of nociceptin/orphanin FQ (N/OFQ) at extremely low doses elicited a nociception through a substance P (SP) release from nociceptor endings. In the present study, the nociception induced by SP (and N/OFQ) was abolished by intrathecal (i.t.) injection of neurokinin(1) (SP receptor) antagonist, suggesting the involvement of the stimulation of nociceptive primary SP neuron and SP release into spinal synapses. On the other hand, similar low doses of N/OFQ (i.t.) exerted nociceptive responses, characterized by scratching, biting, and licking, and these responses were blocked by an neurokinin(1) antagonist (i.t.) or capsaicin pretreatment or in tachykinin 1 gene knockout mice (tac1(-/-) mice), suggesting that N/OFQ receptor (NOR) also exists on the spinal terminals of SP neurons. When wide ranges of N/OFQ doses were used, a typical bell-shaped dose-response relationship was observed in both peripheral and central nociception tests. Furthermore, N/OFQ (1 nmol) administered i.pl. blocked SP (i.pl.)-induced flexor responses, which were abolished by pertussis toxin pretreatment or in NOR gene knockout (NOR-/-) mice. On the other hand, N/OFQ administered i.t. blocked SP (i.t.)-induced scratching, biting, and licking in capsaicin-pretreated and tac1(-/-) mice, and this antinociception was abolished in NOR-/- mice. All these findings suggest that N/OFQ has biphasic actions depending on doses in the nociceptors and spinal synapses and has postsynaptic antinociceptive actions in spinal cord by modulating SP signaling. C1 Nagasaki Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol & Neurosci, Nagasaki 8528521, Japan. NIMH, Genet Sect, Bethesda, MD 20892 USA. Univ Tokyo, Fac Med, Dept Pharmacol, Tokyo 113, Japan. Daiichi Coll Pharmaceut Sci, Dept Biochem, Fukuoka 815, Japan. RP Ueda, H (reprint author), Nagasaki Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol & Neurosci, 1-14 Bunkyo Machi, Nagasaki 8528521, Japan. RI Zimmer, Andreas/B-8357-2009 NR 32 TC 74 Z9 74 U1 0 U2 2 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 1999 VL 291 IS 1 BP 308 EP 313 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 238QK UT WOS:000082721100040 PM 10490918 ER PT J AU Tortella, FC Britton, P Williams, A Lu, XCM Newman, AH AF Tortella, FC Britton, P Williams, A Lu, XCM Newman, AH TI Neuroprotection (focal ischemia) and neurotoxicity (electroencephalographic) studies in rats with AHN649, a 3-amino analog of dextromethorphan and low-affinity N-methyl-D-aspartate antagonist SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CEREBRAL-ARTERY OCCLUSION; BLOOD-BRAIN-BARRIER; RECEPTOR ANTAGONIST; NMDA RECEPTOR; MEDIATED NEUROPROTECTION; GLYCINE SITE; REPERFUSION; INJURY; MK-801; DRUGS AB AHN649, an analog of dextromethorphan (DM) and a relatively selective low-affinity N-methyl-D-aspartate antagonist, was evaluated for neuroprotective effects using the rat intraluminal filament model of temporary middle cerebral artery occlusion. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. In vehicle-treated rats, middle cerebral artery occlusion resulted in neurological deficits and severe infarction measuring 232 +/- 25 mm(3), representing approximately 25% contralateral hemispheric infarction. Post-treatment with AHN649 (0.156-20 mg/kg i.v.) or DM (0.156-10 mg/kg i.v.) significantly reduced cortical infarct volume by 40 to 60% compared with vehicle-control treatments. AHN649 neuroprotection was linear and dose dependent (ED50 = 0.80 mg/kg), whereas DM neuroprotection (ED50 = 1.25 mg/kg) was nonlinear and less effective at the higher doses (2.5-10 mg/kg). Although impaired neurological function scores improved in all groups by 24 to 72 h, the most dramatic improvement was associated with AHN649 treatments. In a rat electroencephalographic model of brain function, separate neurotoxicity experiments revealed that acute i.v. doses of DM caused seizures (ED50 = 19 mg/kg) and death (LD50 = 27 mg/kg). In contrast, AHN649 failed to induce seizure activity at doses up to 100 mg/kg (LD50 = 79 mg/kg). Collectively, AHN649 is described as a potent, efficacious neuroprotective agent devoid of serious central nervous system neurotoxicity and possessing potential therapeutic value as antistroke treatment. Furthermore, the feasibility of targeting low-affinity N-methyl-D-aspartate-site ligands as postinjury therapy for ischemic brain injury has been confirmed. C1 Walter Reed Army Inst Res, Dept Neuropharmacol & Mol Biol, Div Neurosci, Washington, DC 20307 USA. NIDA, Addict Res Ctr, Drug Dev Grp, Baltimore, MD 21224 USA. RP Tortella, FC (reprint author), Walter Reed Army Inst Res, Dept Neuropharmacol & Mol Biol, Div Neurosci, Washington, DC 20307 USA. NR 42 TC 44 Z9 44 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 1999 VL 291 IS 1 BP 399 EP 408 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 238QK UT WOS:000082721100052 PM 10490930 ER PT J AU Zimmerberg, J Coorssen, JR Vogel, SS Blank, PS AF Zimmerberg, J Coorssen, JR Vogel, SS Blank, PS TI Sea urchin egg preparations as systems for the study of calcium-triggered exocytosis SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Journal-of-Physiology Symposium on Secretion - Mechanisms and Regulation of Exocytosis CY APR 17, 1999 CL WASHINGTON, D.C. SP Journal Physiol ID INTRACELLULAR PROTEIN-TRANSPORT; INDIVIDUAL SECRETORY VESICLES; CORTICAL GRANULE EXOCYTOSIS; BOVINE CHROMAFFIN CELLS; MEMBRANE-FUSION; PLASMA-MEMBRANE; IN-VITRO; INVITRO; COMPLEX; MICROSCOPY AB This paper reviews recent work in our laboratory on the mechanism of calcium-triggered exocytosis. Upon echinoderm egg fertilization, cortical secretory vesicle exocytosis is massive and synchronous. By combining physiological and molecular analyses with a variety of purified membrane isolates containing secretory vesicles that fuse to the plasma membrane or each other, we have characterized the final steps of this calcium-triggered exocytosis. Our kinetic analysis led to a functional definition of the fusion complex whose activation by calcium follows Poisson statistics. The properties of this complex are compared with the properties of the heterotrimeric SNARE protein complex that is present in the cortical vesicle system. Our data do not support the hypothesis that this particular heterotrimeric complex is by itself the biological fusogen. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 48 TC 21 Z9 21 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 1 PY 1999 VL 520 IS 1 BP 15 EP 21 DI 10.1111/j.1469-7793.1999.00015.x PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 246ER UT WOS:000083151900005 PM 10517796 ER PT J AU Sheikh, A Horowitz, AM AF Sheikh, A Horowitz, AM TI Benefits of fluoride toothpaste SO JOURNAL OF SCHOOL HEALTH LA English DT Letter C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Sheikh, A (reprint author), Natl Inst Dent & Craniofacial Res, Bldg 45,Room 3-AN-44, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD OCT PY 1999 VL 69 IS 8 BP 299 EP 299 PG 1 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 245RU UT WOS:000083122600001 PM 10544360 ER PT J AU Schulz, GM Dingwall, WO Ludlow, CL AF Schulz, GM Dingwall, WO Ludlow, CL TI Speech and oral motor learning in individuals with cerebellar atrophy SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; NICTITATING-MEMBRANE RESPONSE; FUNCTIONAL-ANATOMY; ARM MOVEMENTS; DYSARTHRIA; CHILDREN; LESIONS; HUMANS; ADULTS; PET AB The purpose of this study was to determine whether cerebellar pathology interferes with motor learning for either speech or novel tasks. Practice effects were contrasted between persons with cerebellar cortical atrophy (CCA) and control participants on previously learned real speech, nonsense speech, and novel nonspeech oral-movement tasks. Studies of limb motor learning suggested that control participants would evidence reduced variability increased speed of movement, and reduced movement amplitude with practice as compared with the CCA group. No significant differences were found between the real- and nonsense-speech tasks. For both speech tasks, although neither group reduced their movement variability with practice, both groups significantly reduced law closing displacement and velocity with practice. For the novel nonspeech oral-movement task, no change with practice was observed in either group in terms of variability amplitude, or peak velocity. No effects of cerebellar pathology were seen in either the speech- or oral-movement tasks. These results demonstrated that with practice of speech tasks, a previously learned motor skill, movement speed and displacement decreased in both groups. Therefore, the effects of practice differed between previously learned speech tasks and the novel oral-movement task regardless of cerebellar pathology. C1 Univ Maryland, Dept Speech & Hearing Sci, College Pk, MD 20742 USA. Natl Inst Deafness & Other Commun Disorders, Voice & Speech Sect, NIH, Bethesda, MD USA. RP Schulz, GM (reprint author), Univ Florida, Dept Commun Sci & Disorders, POB 117420, Gainesville, FL 32611 USA. OI Schulz, Geralyn/0000-0003-3831-8105; Ludlow, Christy/0000-0002-2015-6171 FU NIDCD NIH HHS [Z01 DC 00005-07 VSS] NR 89 TC 13 Z9 13 U1 0 U2 2 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT PY 1999 VL 42 IS 5 BP 1157 EP 1175 PG 19 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 241JL UT WOS:000082879300011 PM 10515513 ER PT J AU Tager-Flusberg, H Cooper, J AF Tager-Flusberg, H Cooper, J TI Present and future possibilities for defining a phenotype for specific language impairment SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE specific language impairment; language phenotype; sensitive diagnostic measures ID CHILDREN; SLI AB This brief report summarizes a workshop that was held at the National institutes of Health in April 1998. The goal of the workshop was to further the development of a definition for the phenotype of specific language impairment (SLI). The report includes a discussion of research recommendations that will refine our current views of the definition of the SLI phenotype and sets out priority areas that are in need of Further study to help advance understanding of this complex language-based disorder. C1 Eunice Kennedy Shriver Ctr Mental Retardat Inc, Ctr Res Dev Disorders, Waltham, MA 02452 USA. Univ Massachusetts, Boston, MA 02125 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Tager-Flusberg, H (reprint author), Eunice Kennedy Shriver Ctr Mental Retardat Inc, Ctr Res Dev Disorders, 200 Trapelo Rd, Waltham, MA 02452 USA. RI Tager-Flusberg, Helen/D-5265-2009 FU NIDCD NIH HHS [P01 DC 03610]; PHS HHS [R01 38668] NR 9 TC 105 Z9 107 U1 1 U2 3 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT PY 1999 VL 42 IS 5 BP 1275 EP 1278 PG 4 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 241JL UT WOS:000082879300019 PM 10515521 ER PT J AU Dimitriadis, EK Chadwick, RS AF Dimitriadis, EK Chadwick, RS TI Solution of the inverse problem for a linear cochlear model: A tonotopic cochlear amplifier SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID OUTER HAIR-CELLS; BASILAR-MEMBRANE VIBRATION; GUINEA-PIG; 3-DIMENSIONAL MODEL; TECTORIAL MEMBRANE; TRAVELING-WAVE; ACTIVE PROCESS; ORGAN; CORTI; MECHANICS AB The extraordinary fine-tuning characteristic of normal mammalian hearing is attributed to physiological mechanisms collectively known as the cochlear amplifier (CA), which amplifies and sharpens the basilar membrane (BM) vibration response to incoming acoustic pressure oscillations. Electromechanical properties of outer hair cells (OHCs) are believed to be the critical component of the CA, but its "circuitry" as yet remains unknown. Here, the required frequency-space response characteristics of the CA are computationally determined when typical in vivo tuning data are introduced as input to a linear hydroelastic cochlear model whose cross-sectional dynamics are represented by two coupled vibrational degrees of freedom. It is assumed that the CA senses motion at the tectorial membrane (TM) reticular lamina (RL) and applies proportional, equal, and opposite forces to the BM and the RL. The results show the CA to be tonotopically tuned, meaning it conforms to a space-frequency similarity principle like other cochlear dynamical responses. This requires that the active mechanism use information distributed along the cochlear partition. The physiological mechanism responsible for such behavior remains unknown, but here the computed CA characteristics can be qualitatively reproduced by a circuit spanning the length of the cochlea. This does not preclude other mechanisms, but is intended to motivate closer experimental investigation of extracellular and intercellular ionic flow pathways. [S0001-4966(99)00109-5]. C1 NIH, Bioengn & Phys Sci Program, ORS, OD, Bethesda, MD 20892 USA. NIDCD, Lab Cellular Biol, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA. RP Dimitriadis, EK (reprint author), NIH, Bioengn & Phys Sci Program, ORS, OD, Bethesda, MD 20892 USA. NR 54 TC 7 Z9 8 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 1999 VL 106 IS 4 BP 1880 EP 1892 DI 10.1121/1.427937 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 244VK UT WOS:000083071300027 PM 10530013 ER PT J AU Murphy, DGM Mentis, MJ Pietrini, P Grady, CL Moore, CJ Horwitz, B Hinton, V Dobkin, CS Schapiro, MB Rapoport, SI AF Murphy, DGM Mentis, MJ Pietrini, P Grady, CL Moore, CJ Horwitz, B Hinton, V Dobkin, CS Schapiro, MB Rapoport, SI TI Premutation female carriers of fragile X syndrome: A pilot study on brain anatomy and metabolism SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE fragile X syndrome; positron emission tomography; magnetic resonance imaging; brain ID CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; TURNERS-SYNDROME; CHROMOSOME; SCHIZOPHRENIA; NEUROANATOMY; INVOLVEMENT; DIAGNOSIS; PHENOTYPE; DISORDER AB Objective: It was thought that premutation carriers of fragile X syndrome (FraX) have no neurobiological abnormalities, but there have been no quantitative studies of brain morphometry and metabolism. Thus the authors investigated brain structure and metabolism in premutation carriers of FraX. Method: Eight normal IQ, healthy female premutation FraX carriers aged 39 +/- 9 years (mean +/- SD) and 32 age-sex-handedness-matched controls (39 +/- 10 years) were studied; in vivo brain morphometry was measured using volumetric magnetic resonance imaging, and regional cerebral metabolic rates for glucose were measured using positron emission tomography and (18F)-2-fluoro-2-deoxy-D-glucose. Results: Compared with controls, FraX premutation carriers had a significant (1) decrease in volume of whole brain, and caudate and thalamic nuclei bilaterally; (2) increase in volume of hippocampus and peripheral CSF bilaterally, and third ventricle; (3) relative hypometabolism of right parietal, temporal, and occipital association areas; (4) bilateral relative hypermetabolism of hippocampus; (5) relative hypermetabolism of left cerebellum; and (6) difference in right-left asymmetry of the Wernicke and Broca language areas. Conclusions: Premutation carriers of FraX, as defined by analysis of peripheral lymphocytes, have abnormalities in brain anatomy and metabolism. The biological basis for this is unknown, but most likely it includes tissue heterogeneity for mutation status. The findings may be of relevance to people counseling families with FraX and to understanding other neuropsychiatric disorders which are associated with expansion of triplet repeats and genetic anticipation. C1 Inst Psychiat, Dept Psychol Med, London SE5 8AF, England. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. Inst Basic Res Dev Disabil, Staten Isl, NY USA. RP Murphy, DGM (reprint author), Inst Psychiat, Dept Psychol Med, DeCrespigny Pk, London SE5 8AF, England. FU Wellcome Trust NR 43 TC 27 Z9 27 U1 2 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 1999 VL 38 IS 10 BP 1294 EP 1301 DI 10.1097/00004583-199910000-00019 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 240ZU UT WOS:000082857300019 PM 10517063 ER PT J AU Domanski, MJ Sakseena, S Epstein, AE Hallstrom, AP Brodsky, MA Kim, S Lancaster, S Schron, E AF Domanski, MJ Sakseena, S Epstein, AE Hallstrom, AP Brodsky, MA Kim, S Lancaster, S Schron, E CA AVID Investigators TI Relative effectiveness of the implantable cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular dysfunction who have survived malignant ventricular arrhythmias SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HOSPITAL CARDIAC-ARREST; MYOCARDIAL-INFARCTION; RANDOMIZED TRIAL; THERAPY; DEATH; TACHYARRHYTHMIAS; DISEASE; FAILURE AB OBJECTIVES We sought to assess the effect of baseline ejection fraction on survival difference between patients with life-threatening ventricular arrhythmias who were treated with an antiarrhythmic drug (AAD) or implantable cardioverter-defibrillator (ICD). BACKGROUND The Antiarrhythmics Versus Implantable Defibrillators (AVID) study demonstrated improved survival in patients with ventricular fibrillation or ventricular tachycardia with a left ventricular ejection fraction (LVEF) less than or equal to 0.40 or hemodynamic compromise, METHODS Survival differences between AAD-treated and ICD-treated patients entered into the AVID study (patients presenting with sustained ventricular arrhythmia associated with an LVEF less than or equal to 0.40 or hemodynamic compromise) were compared at different levels of ejection fraction. RESULTS In patients with an LVEF greater than or equal to 0.35, there was no difference in survival between AAD-treated and ICD-treated patients. A test for interaction was not significant, but had low power to detect an interaction. For patients with an LVEF 0.20 to 0.34, there was a significantly improved survival with ICD as compared with AAD therapy. In the smaller subgroup with an LVEF <0.20, the same magnitude of survival difference was seen as that in the 0.20 to 0.34 LVEF subgroup, but the difference did not reach statistical significance. CONCLUSIONS These data suggest that patients with relatively well-preserved LVEF (greater than or equal to 0.35) may not have better survival when treated with the ICD as compared with AADs. At a lower LVEF, the ICD appears to offer improved survival as compared with AADs, Prospective studies with larger patient numbers are needed to assess the effect of relatively well-preserved ejection fraction (greater than or equal to 0.35) on the relative treatment effect of AADs and the ICDs. (J Am Coll Cardiol 1999;34:1090-5) (C) 1999 by the American College of Cardiology. C1 NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. Robert Wood Johnson Med Sch, Eastern Heart Inst, Atlantic Hlth Syst, Newark, NJ USA. Univ Alabama, Birmingham, AL USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif, Orange, CA USA. Montefiore Med Ctr, Bronx, NY 10467 USA. RP Domanski, MJ (reprint author), NHLBI, Clin Trials Grp, 6701 Rockledge Dr,Room 8146, Bethesda, MD 20892 USA. NR 17 TC 144 Z9 150 U1 0 U2 1 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 1999 VL 34 IS 4 BP 1090 EP 1095 DI 10.1016/S0735-1097(99)00327-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242JN UT WOS:000082936900021 PM 10520795 ER PT J AU Epstein, AE Powell, J Yao, Q Ocampo, C Lancaster, S Rosenberg, Y Cannom, DS Herre, JM Greene, HL AF Epstein, AE Powell, J Yao, Q Ocampo, C Lancaster, S Rosenberg, Y Cannom, DS Herre, JM Greene, HL CA AVID Investigaros TI In-hospital versus out-of-hospital presentation of life-threatening ventricular arrhythmias predicts survival - Results from the AVID Registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LONG-TERM SURVIVAL; AMERICAN-HEART-ASSOCIATION; CARDIAC-CARE-COMMITTEE; CARDIOPULMONARY RESUSCITATION; ARREST; FIBRILLATION; DEFIBRILLATION; PROFESSIONALS; STATEMENT; SUPPORT AB OBJECTIVES This study describes the outcomes of patients from the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study Registry to determine how the location of ventricular arrhythmia presentation influences survival. BACKGROUND Most studies of cardiac arrest report outcome following out-of-hospital resuscitation. In contrast, there are minimal data on long-term outcome following in-hospital cardiac arrest. METHODS The AVID Study was a multicenter, randomized comparison of drug and defibrillator strategies to treat life-threatening ventricular arrhythmias. A Registry was maintained of all patients with sustained ventricular arrhythmias at each study site. The present study includes patients who had AVID-eligible arrhythmias, both randomized and not randomized. Patients with in-hospital and out-of-hospital presentations are compared. Data on long-term mortality were obtained through the National Death Index. RESULTS The unadjusted mortality rates at one- and two-year follow-ups were 23% and 31.1% for patients with in-hospital presentations, and 10.5% and 16.8% for those with out-of-hospital presentations (p < 0.001), respectively. The adjusted mortality rates at one- and two-year follow-ups were 14.8% and 20.9% for patients with in-hospital presentations, and 8.4% and 14.1% for those with out-of-hospital presentations (p < 0.001), respectively. The adjusted long-term relative risk for in-hospital versus out-of-hospital presentation was 1.6 (95% confidence interval [CI] 1.3-1.9). CONCLUSIONS Compared with patients with out-of-hospital presentations of life-threatening ventricular arrhythmias not due to a reversible cause, patients with in-hospital presentations have a worse long-term prognosis. Because location of ventricular arrhythmia presentation is an independent predictor of long-term outcome, it should be considered as an element of risk stratification and when planning clinical trials. (J Am Coll Cardiol 1999;34:1111-6) (C) 1999 by the American College of Cardiology. C1 Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Rochester, Sch Med & Dent, Dept Cardiol, Rochester, NY USA. NHLBI, NIH, Bethesda, MD 20892 USA. Los Angeles Cardiol Associates, Los Angeles, CA USA. Cardiol Consultants, Norfolk, VA USA. RP Epstein, AE (reprint author), AVID CTC, 1107 NE 45th St,Room 505, Seattle, WA 98105 USA. FU NHLBI NIH HHS [N01-HC-25117] NR 29 TC 19 Z9 19 U1 0 U2 2 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 1999 VL 34 IS 4 BP 1111 EP 1116 DI 10.1016/S0735-1097(99)00305-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242JN UT WOS:000082936900025 PM 10520799 ER PT J AU Levy, D Merz, CNB Cody, RJ Fouad-Tarazi, FM Francis, CK Pfeffer, MA Scott, NA Swan, HJC Taylor, MP Weinberger, MH AF Levy, D Merz, CNB Cody, RJ Fouad-Tarazi, FM Francis, CK Pfeffer, MA Scott, NA Swan, HJC Taylor, MP Weinberger, MH TI Hypertension detection, treatment and control - A call to action for cardiovascular specialists SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ISOLATED SYSTOLIC HYPERTENSION; CONGESTIVE-HEART-FAILURE; BLOOD-PRESSURE; DISEASE; TRIALS; PROGRESSION; PREVALENCE; POPULATION; HEALTH; STROKE C1 Univ Michigan Hlth Syst, Ann Arbor, MI USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. NR 17 TC 12 Z9 12 U1 0 U2 0 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 1999 VL 34 IS 4 BP 1360 EP 1362 DI 10.1016/S0735-1097(99)00385-X PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242JN UT WOS:000082936900049 PM 10520821 ER PT J AU Slavin, HC AF Slavin, HC TI Toward 'molecular gastronomy,' or what's in a taste? SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 9 TC 2 Z9 2 U1 1 U2 5 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1999 VL 130 IS 10 BP 1497 EP 1500 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 244NM UT WOS:000083057700020 PM 10570598 ER PT J AU Thompson, B Demark-Wahnefried, W Taylor, G McClelland, JW Stables, G Havas, S Feng, ZD Topor, M Heimendinger, J Reynolds, KD Cohen, N AF Thompson, B Demark-Wahnefried, W Taylor, G McClelland, JW Stables, G Havas, S Feng, ZD Topor, M Heimendinger, J Reynolds, KD Cohen, N TI Baseline fruit and vegetable intake among adults in seven 5 A Day study centers located in diverse geographic areas SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID CANCER PREVENTION; UNITED-STATES; QUESTIONNAIRE; DIET; HEALTH AB Objective To examine baseline rates of fruit and vegetable consumption among adults in the 5 A Day research trials in order to identify any regional and sociodemographic differences associated with daily servings. Design The main outcome measure was the frequency of fruits and vegetables consumed within 1 month of the baseline survey as assessed by a 7-item food frequency questionnaire (FFQ). Subjects/setting Participants (N=15,060) were from 7 study centers. Study centers included schools (N=48), worksites (N=60), churches (N=50), or the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinics (N=15) in interventions to increase fruit and vegetable consumption. Statistical analyses Means and standard errors, adjusting for clusters, were calculated. A mixed linear model analyzed relationships between fruit and vegetable consumption and regional center, gender, age, race, education, income, marital status, food-shopping responsibility, and whether one lives with children. Results Results indicate an overall mean intake of 3.6 daily servings of fruits and vegetables. Significant differences in mean daily servings were found among the regional study centers (low of 3.0 to high of 4.1). There were significant differences in mean daily consumption by age (<30 years= 3.7 servings per day; 30 to 49 years=3.4; greater than or equal to 50 years=3.7), education (>high school=3.4 servings per day; high school graduate=3.4; some college=3.5; college graduate=3.9), race (black=3.7 servings per day; Hispanic=3.0; white=3.6; other=3.7), marital status (married=3.6 servings per day; single=3.5), and food-shopping responsibilities (little=3.2 servings per day; about half=3.6; most=3.8). Only 17% of respondents ate 5 or more servings of fruits and vegetables per day. Conclusions The 7 regions showed significant variability in daily fruit and vegetable consumption, suggesting that a single national message to increase fruit and vegetable consumption may not reach the population segments most in need of changing. It is advisable to spend more time understanding the food consumption habits of the population under investigation to develop messages to foster behavior change. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Duke Univ, Med Ctr, Durham, NC USA. Minnesota Dept Hlth, Minneapolis, MN USA. N Carolina State Univ, Raleigh, NC 27695 USA. NCI, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Epidermiol & Preventive Med, Baltimore, MD 21201 USA. Informat Management Serv Inc, Silver Spring, MD USA. AMC, Canc Res Ctr, Denver, CO USA. Univ Alabama, Dept Hlth Behav, Sch Publ Hlth, Birmingham, AL USA. Univ Massachusetts, Dept Nutr, Amherst, MA 01003 USA. NIH, Bethesda, MD 20892 USA. RP Thompson, B (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MP-702,Box 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [R01 CA059805] NR 30 TC 102 Z9 104 U1 2 U2 8 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 1999 VL 99 IS 10 BP 1241 EP 1248 DI 10.1016/S0002-8223(99)00306-5 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 243UB UT WOS:000083014700023 PM 10524389 ER PT J AU Yaffe, K Browner, W Cauley, J Launer, L Harris, T AF Yaffe, K Browner, W Cauley, J Launer, L Harris, T TI Association between bone mineral density and cognitive decline in older women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT American-Geriatric-Society Meeting CY MAY, 1998 CL SEATTLE, WASHINGTON SP Amer Geriatr Soc DE bone mineral density; cognition; older women; dementia; estrogen ID ESTROGEN REPLACEMENT THERAPY; ALZHEIMERS-DISEASE; OSTEOPOROTIC FRACTURES; POSTMENOPAUSAL WOMEN; VERTEBRAL DEFORMITIES; COMMUNITY WOMEN; MOVIES PROJECT; ELDERLY WOMEN; HIP FRACTURE; RISK-FACTORS AB OBJECTIVE: To test the hypothesis that bone mineral density (BMD), a marker of cumulative estrogen exposure, is associated with cognitive function in nondemented older women. DESIGN: A prospective cohort study. SETTING: Clinical centers in Baltimore, Maryland, Minneapolis, Minnesota, the Monongahela Valley near Pittsburgh, Pennsylvania, and Portland, Oregon. PARTICIPANTS: We evaluated 8333 older community-dwelling women enrolled in the Study of Osteoporotic Fractures who mere not taking estrogen replacement. MEASUREMENTS: Calcaneal and hip BMD were measured at baseline and at follow-up (4-6 years later);vertebral fractures were ascertained radiologically at year 6. Women were administered a modified Mini-Mental State Exam, Trails B, and Digit Symbol at baseline and at follow-up. RESULTS: Compared with women with higher bone mineral density, women with low baseline BMD had up to 8% worse baseline cognitive scores (P = .001) and up to 6% worse repeat cognitive scores (P = .001), even after multivariate adjustments. For 1 SD decrease in baseline hip BMD or calcaneal BMD, women had a 32% (95% CI, 19-47%) or a 33% (95% CI, 20-48%) greater odds of cognitive deterioration (worst 10th percentile of change). Women with vertebral fractures had lower cognitive test scores and a greater odds of cognitive deterioration than those without fractures (OR = 1.29; 95%CI, 1.03-1.60). CONCLUSIONS: Women with osteoporosis, whether measured by baseline BMD, reductions in BMD, or vertebral fractures, have poorer cognitive function and greater risk of cognitive deterioration. Our findings suggest a link between two of the most common conditions affecting older women. Further understanding of this association may be important for new treatment and prevention directions. C1 Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Vet Affairs Med Ctr, Box 111G,4150 Clement St, San Francisco, CA 94121 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [AG05394, AG05407]; NIAMS NIH HHS [AR35582] NR 56 TC 49 Z9 49 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1999 VL 47 IS 10 BP 1176 EP 1182 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 244BH UT WOS:000083031600002 PM 10522949 ER PT J AU Taaffe, DR Duret, C Wheeler, S Marcus, R AF Taaffe, DR Duret, C Wheeler, S Marcus, R TI Once-weekly resistance exercise improves muscle strength and neuromuscular performance in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE muscle strength; exercise; training frequencies; older people ID LUMBAR EXTENSION STRENGTH; HIGH-INTENSITY; SKELETAL-MUSCLE; TRAINING FREQUENCY; SERUM-ALBUMIN; ELDERLY WOMEN; RISK-FACTORS; MEN; HYPERTROPHY; PRESCRIPTION AB OBJECTIVE: To determine the effect of frequency of resistive training on gain in muscle strength and neuromuscular performance in healthy older adults. DESIGN: A randomized controlled trial with subjects assigned either to high-intensity resistance training 1 (EX1), 2 (EX2), or 3 (EX3) days per week for 24 weeks or to a control group (CO). SETTING: An exercise facility at an academic medical center. SUBJECTS: Forty-six community-dwelling healthy men (n = 29) and women (n = 17) aged 65 to 79 years. INTERVENTION: Progressive resistance training consisting of three sets of eight exercises targeting major muscle groups of the upper and lower body, at 80% of one-repetition maximum (1-RM) for eight repetitions, either 1, 2, or 3 days per week. MEASURES: Dynamic muscle strength (1-RM) using isotonic equipment every 4 weeks, bone mineral density and body composition by dual energy X-ray absorptiometry (DXA), and neuromuscular performance by timed chair rise and B-meter backward tandem walk. RESULTS: For each of the eight exercises, muscle strength increased in the exercise groups relative to CO (P < .01), with no difference among EX1, EX2 and EX3 groups at any measurement interval. Percent change averaged 3.9 +/-: 2.4 (CO), 37.0 +/- 15.2 (EX1), 41.9 +/- 18.2 (EX2), and 39.7 +/- 9.8 (EX3). The time to rise successfully from the chair 5 times decreased significantly (P < .01) at 24 weeks, whereas improvement in the 6-meter backward tandem walk approached significance (P = .10) in the three exercise groups compared with CO. Changes in chair rise ability were correlated to percent changes in quadriceps strength (r = -0.40, P < .01) and lean mass (r = -0.40, P < .01). CONCLUSIONS: A program of once or twice weekly resistance exercise achieves muscle strength gains similar to 3 days per week training in older adults and is associated with improved neuromuscular performance. Such improvement could potentially reduce the risk of falls and fracture in older adults. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Palo Alto, CA 94304 USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. RP Taaffe, DR (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,7201 Wisconsin Ave,Suite 3C-309, Bethesda, MD 20892 USA. NR 47 TC 193 Z9 203 U1 5 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1999 VL 47 IS 10 BP 1208 EP 1214 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 244BH UT WOS:000083031600007 PM 10522954 ER PT J AU Murase, T Ecelbarger, CA Baker, EA Tian, Y Knepper, MA Verbalis, JG AF Murase, T Ecelbarger, CA Baker, EA Tian, Y Knepper, MA Verbalis, JG TI Kidney aquaporin-2 expression during escape from antidiuresis is not related to plasma or tissue osmolality SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID REGULATED WATER CHANNEL; COLLECTING DUCT; RAT-KIDNEY; VASOPRESSIN; GENE; PERMEABILITY; MECHANISMS; PRESSURE; STRETCH; SODIUM AB Recent results indicate that renal escape from vasopressin-induced antidiuresis is accompanied by a marked downregulation of whole kidney aquaporin-2 (AQP-2) protein and mRNA expression. However, in those studies, the escaped animals were also markedly hypo-osmolar compared to controls as a result of water loading during antidiuresis. The present studies evaluated whether systemic or local osmolality contributes to the downregulation of AQP-2 expression in this model. In the first study, two groups of 1-deamino-[8-D-arginine]-vasopressin (dDAVP)-infused rats were water-loaded; after establishment of escape, one group was then water-restricted for 4 d to reverse the escape, whereas the other group continued daily water loading. Whole kidney AQP-2 protein was measured by Western blotting, and inner medulla AQP-2 mRNA was determined by Northern blotting. Results were compared to dDAVP-mfused rats fed solid chow. After 4 d of water restriction, urine volume decreased to the same level as in the rats on solid chow; however, plasma sodium concentrations and plasma osmolality remained low. Despite maintenance of significant hypo-osmolality, rats in which escape was subsequently reversed by water restriction reestablished high dDAVP-stimulated kidney levels of AQP-2 after 4 d of water restriction. In the second study, AQP-2, expression was evaluated in different regions of kidneys from water-loaded rats undergoing escape from antidiuresis. Despite markedly different interstitial osmolalities, significant downregulation of AQP-2 expression compared to dDAVP-infused control rats was seen in the inner medulla, outer medulla, and cortex. Thus, neither systemic nor interstitial osmolality appears to appreciably be correlated with downregulation of kidney AQP-2 expression during escape from antidiuresis. These results therefore suggest that additional vasopressin- and osmolality-independent factors, likely related to the effects of extracellular fluid volume expansion, also regulate kidney AQP-2 expression in rats. C1 Georgetown Univ, Dept Med, Div Endocrinol, Washington, DC 20007 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Murase, T (reprint author), Georgetown Univ, Div Endocrinol & Metab, Bldg D,Room 350,4000 Reservoir Rd NW, Washington, DC 20007 USA. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NIDDK NIH HHS [DK38094, K01 DK002672] NR 34 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1999 VL 10 IS 10 BP 2067 EP 2075 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 239BA UT WOS:000082747900001 PM 10505682 ER PT J AU Zambrano, NR Lubensky, IA Merino, MJ Lineman, WM Walther, MM AF Zambrano, NR Lubensky, IA Merino, MJ Lineman, WM Walther, MM TI Histopathology and molecular genetics of renal tumors: Toward unification of classification system. SO JOURNAL OF UROLOGY LA English DT Review DE carcinoma, renal cell; pathology; histology; classification; genes ID COLLECTING DUCT CARCINOMA; VON-HIPPEL-LINDAU; GROWTH-FACTOR RECEPTOR; COMPARATIVE GENOMIC HYBRIDIZATION; CHROMOPHOBE CELL-CARCINOMA; POLYMERASE CHAIN-REACTION; SUPPRESSOR GENE; METANEPHRIC ADENOMA; MEDULLARY CARCINOMA; MET PROTOONCOGENE AB Purpose: We characterize the genetic abnormalities associated with pathological subtypes of renal tumors, which may help diagnosis or prognostication. Materials and Methods: A comprehensive literature review of genetic abnormalities associated with different renal tumor subtypes was performed. Results: Studies of sporadic and hereditary forms suggest that abnormalities in the von Hippel-Lindau and met genes are the earliest changes in conventional (clear cell) and papillary basophilic renal cancers, respectively. Renal oncocytoma and chromophobe carcinoma have common genetic abnormalities, suggesting a relationship. A similar finding has been observed between papillary adenoma and papillary basophilic renal cancer. Conclusions: These findings suggest that molecular diagnostic testing will help determine histopathological diagnosis, identify tumor types with similar genetic abnormalities suggesting a common origin and indicate potential prognostic markers for future study. C1 NCI, Pathol Lab, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Pathol Lab, Urol Oncol Branch, NIH, Bldg 10,Room 2B-43,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. NR 199 TC 107 Z9 109 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 1999 VL 162 IS 4 BP 1246 EP 1258 DI 10.1016/S0022-5347(05)68259-6 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 234XY UT WOS:000082510700002 PM 10492174 ER PT J AU Gilliland, FD Hoffman, RM Hamilton, A Albertsen, P Eley, JW Harlan, L Stanford, JL Hunt, WC Potosky, A AF Gilliland, FD Hoffman, RM Hamilton, A Albertsen, P Eley, JW Harlan, L Stanford, JL Hunt, WC Potosky, A TI Predicting extracapsular extension of prostate cancer in men treated with radical prostatectomy: Results from the population based prostate cancer outcomes study SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; prostatectomy; neoplasms by histologic type; epidemiology ID TERM FOLLOW-UP; PATHOLOGICAL STAGE; CLINICAL STAGE; GLEASON SCORE; NEW-MEXICO; ANTIGEN; TRENDS; RECURRENCE; SURVIVAL; RISE AB Purpose: We investigated whether clinical information routinely available in community practice could predict extracapsular extension of clinically localized prostate cancer in men undergoing radical prostatectomy. Materials and Methods: We examined prostate cancer outcomes in a population based sample of 3,826 patients with primary prostate cancer in 6 regions of the United States covered by the Surveillance, Epidemiology, and End Results program. Stratified and weighted logistic regression was used to identify predictors of and probabilities for extracapsular extension of clinically localized tumors treated with radical prostatectomy. Results: Nearly 47% of men undergoing radical prostatectomy had extraprostatic extension. The strongest predictors were elevated prostate specific antigen (PSA) greater than 20 versus less than 4 ng./ml. (odds ratio 5.88, 95% confidence interval 2.90 to 11.15), Gleason score greater than 8 versus less than 6 (1.73, 1.04 to 2.87) and age greater than 70 versus less than 50 years (1.91, 0.98 to 3.70). Ethnicity and region were not associated with increased risk of extraprostatic extension. A nomogram developed from our model predicts extracapsular extension ranging from 24% in men younger than 50 years with PSA less than 4 ng./ml. and a Gleason score of less than 7 to 85% in those 70 years old or older with PSA greater than 20 ng./ml. and a Gleason score of 8 or more. If prostatectomy were limited to patients with less than 60% probability of extraprostatic extension based on the nomogram, 95% of those with organ confined cancers would undergo definitive surgery and 18% of those with extracapsular extension would be spared the morbidity of surgery. Conclusions: In a population based analysis of prostate cancer practice patterns PSA, Gleason score and age are clinically useful predictors of extracapsular extension. Although extracapsular extension may be an imperfect predictor of cancer outcomes, our nomogram provides more realistic probabilities for extracapsular extension than those based on institutional series. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ New Mexico, Hlth Sci Ctr, Dept Gen Med, Vet Adm Med Ctr,New Mexico Tumor Registry, Albuquerque, NM USA. Univ Connecticut, Hlth Sci Ctr, Div Urol, Farmington, CT USA. Emory Univ, Rollins Sch Publ Hlth, Georgia Ctr Canc Stat, Atlanta, GA 30322 USA. Univ Utah, Sch Med, Utah Canc Registry, Salt Lake City, UT USA. Univ Utah, Sch Med, Div Urol, Salt Lake City, UT USA. NCI, Div Canc Control & Prevent, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Gilliland, FD (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. NR 24 TC 48 Z9 51 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 1999 VL 162 IS 4 BP 1341 EP 1345 DI 10.1016/S0022-5347(05)68281-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 234XY UT WOS:000082510700024 PM 10492193 ER PT J AU Moir, S Lapointe, R Malaspina, A Ostrowski, M Cole, CE Chun, TW Adelsberger, J Baseler, M Hwu, P Fauci, AS AF Moir, S Lapointe, R Malaspina, A Ostrowski, M Cole, CE Chun, TW Adelsberger, J Baseler, M Hwu, P Fauci, AS TI CD40-mediated induction of CD4 and CXCR4 on B lymphocytes correlates with restricted susceptibility to human immunodeficiency virus type 1 infection: Potential role of B lymphocytes as a viral reservoir SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; IN-VITRO; PRODUCTIVE INFECTION; CELL ACTIVATION; HIV-1 INFECTION; T-LYMPHOCYTES; KAPPA-B; EXPRESSION; REPLICATION; MACROPHAGES AB Human immunodeficiency virus type I (HIV-I) replicates primarily in lymphoid tissues where it has ready access to activated immune competent cells. We used one of the major pathways of immune activation, namely, CD40-CD40L interactions, to study the infectability of B lymphocytes isolated from peripheral blood mononuclear cells. Highly enriched populations of B lymphocytes generated in the presence of interleukin-4 and oligomeric soluble CD40L upregulated costimulatory and activation markers, as well as HIV-1 receptors CD4 and CXCR4, but not CCR5, By using single-round competent luciferase viruses complemented,vith either amphotropic or HIV-derived envelopes, me found a direct correlation between upregulation of HIV-1 receptors and the susceptibility of the B lymphocytes to infection with dual-tropic and T-tropic strains of HIV-1; in contrast, cells were resistant to M-tropic strains of HIV-1. HIV-1 envelope-mediated infection was completely abolished with either an anti-CD4 monoclonal antibody or a peptide known to directly block CXCR4 usage and partially blocked with stromal cell-derived factor 1, all of which had no effect on the entry of virus pseudotyped with amphotropic envelope. Full virus replication kinetics confirmed that infection depends on CXCR4 usage. Furthermore, productive cycles of virus replication occurred rapidly yet under most conditions, without the appearance of syncytia. Thus, an activated immunological environment may induce the expression of HIV-1 receptors on B lymphocytes, priming them for infection with selective strains of HIV-I and allowing them to serve as a potential viral reservoir. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,MSC-1576,Bldg 10,Rm 6A02, Bethesda, MD 20892 USA. FU PHS HHS [N01-56000] NR 41 TC 50 Z9 53 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 7972 EP 7980 PG 9 WC Virology SC Virology GA 235QP UT WOS:000082554300006 PM 10482544 ER PT J AU LeBlanc, RA Pesnicak, L Cabral, ES Godleski, M Straus, SE AF LeBlanc, RA Pesnicak, L Cabral, ES Godleski, M Straus, SE TI Lack of interleukin-6 (IL-6) enhances susceptibility to infection but does not alter latency or reactivation of herpes simplex virus type 1 in IL-6 knockout mice SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSDUCING RECEPTOR COMPONENT; CELL-MEDIATED-IMMUNITY; SIGNAL-TRANSDUCTION; GENITAL HERPES; CYTOKINE; NEURONS; GP130; NUMBER; RESPONSES; MEDICINE AB The ability of the pleotropic, proinflammatory cytokine interleukin-6 (IL-6) to affect the replication, latency, and reactivation of herpes simplex virus type 1 (HSV-1) in cell culture and in IL-6 knockout (KO) mice was studied. In initial studies, we found no effect of exogenous IL-6, monoclonal antibodies to IL-6, or monoclonal antibody to the IL-6 coreceptor, gp130, on HSV-1 replication in vitro by plaque assay or reactivation ex vivo by explant cocultivation of latently infected murine trigeminal ganglia (TG). Compared with the wild-type (WT) mice, the IL-6 KO mice were less able to survive an ocular challenge with 10(5) PFU of HSV-1 (McKrae) (40% survival of WT and 7% survival KO mice; P = 0.01). There was a sixfold higher 50% lethal dose of HSV-1 in WT than IL-6 KO mice (1.7 x 10(4) and 2.7 x 10(3) PFU, respectively). No differences were observed in titers of virus recovered from the eyes, TG, or brains or in the rates of virus reactivation by explant cocultivation of TG from latently infected WT or KO mice. Exposure of latently infected mice to UV light resulted in comparable rates of reactivation and in the proportions of WT and KO animals experiencing reactivation. Moreover, quantitative PCR assays showed nearly identical numbers of HSV-1 genomes in latently infected WT and IL-6 KO mice. These studies indicate that while IL-6 plays a role in the protection of mice from lethal HSV infection, it does not substantively influence HSV replication, spread to the nervous system, establishment of latency, or reactivation. C1 NIH, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), Rm 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 38 TC 43 Z9 43 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8145 EP 8151 PG 7 WC Virology SC Virology GA 235QP UT WOS:000082554300026 PM 10482564 ER PT J AU Gorelick, RJ Fu, W Gagliardi, TD Bosche, WJ Rein, A Henderson, LE Arthur, LO AF Gorelick, RJ Fu, W Gagliardi, TD Bosche, WJ Rein, A Henderson, LE Arthur, LO TI Characterization of the block in replication of nucleocapsid protein zinc finger mutants from Moloney murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMER-BINDING-SITE; REVERSE TRANSCRIPTION; VIRAL REPLICATION; RETROVIRAL DNA; POL GENE; IN-VITRO; TYPE-1; RNA; SEQUENCE; INTEGRATION AB Mutagenesis studies have shown that retroviral nucleocapsid (NC) protein Zn2+ fingers (-Cys-X-2-Cys-X-4-His-X-4-Cys- [CCHC]) perform multiple functions in the virus life cycle. Moloney murine leukemia virus mutants His 34-->Cys (CCCC) and Cys 39-->His (CCHH) were able to package their genomes normally but were replication defective. Thermal dissociation experiments showed that the CCHH mutant was not defective in genomic RNA dimer structure. Primer tRNA placement on the viral genome and the ability of the tRNA to function in reverse transcription initiation in vitro also appear normal. Some "full-length" DNA copies of the viral genome were synthesized in mutant virus-infected cells. The CCCC and CCHH mutants produced these DNA copies at greatly reduced levels. Circle junction fragments, amplified from two-long-terminal-repeat viral DNA (vDNA) by PCR were cloned and characterized. Remarkably, it was discovered that vDNA isolated from cells infected with mutant virions had a wide variety of abnormalities at the site at which the two ends of the linear precursor had been ligated to form the circle (i.e., the junction between the 5' end of U3 and the 3' end of U5). In some molecules, bases were missing from regions corresponding to the U3 and U5 linear vDNA termini; in others, the viral sequences extended either beyond the U5 sequences into the primer-binding site and 5' leader or beyond the U3 sequences into the polypurine tract into the env coding region. Still other molecules contained nonviral sequences between the linear vDNA termini. Such defective genomes would certainly be unsuitable substrates for integration. Thus, strict conservation of the CCHC structure in NC is required for infection events prior to and possibly including integration. C1 NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Virol & Carcinogenesis Lab, Frederick, MD 21702 USA. RP Gorelick, RJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Bldg 535,Room 410,POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-46000, N01-CO-56000] NR 36 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8185 EP 8195 PG 11 WC Virology SC Virology GA 235QP UT WOS:000082554300031 PM 10482569 ER PT J AU Polacino, PS Stallard, V Klaniecki, JE Pennathur, S Montefiori, DC Langlois, AJ Richardson, BA Morton, WR Benveniste, RE Hu, SL AF Polacino, PS Stallard, V Klaniecki, JE Pennathur, S Montefiori, DC Langlois, AJ Richardson, BA Morton, WR Benveniste, RE Hu, SL TI Role of immune responses against the envelope and the core antigens of simian immunodeficiency virus SIVmne in protection against homologous cloned and uncloned virus challenge in macaques SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; HUMAN MONOCLONAL-ANTIBODIES; 2 IMMUNODOMINANT DOMAINS; LONG-TERM PROTECTION; T-LYMPHOCYTE CLONES; GAG-ENV PARTICLES; NEUTRALIZING ANTIBODIES; HIV-1 INFECTION; TRANSMEMBRANE PROTEIN; CELLULAR-IMMUNITY AB We previously showed that envelope (gp160)-based vaccines, used in a live recombinant virus priming and subunit protein boosting regimen, protected macaques against intravenous and intrarectal challenges with the homologous simian immunodeficiency virus SIVmne clone E11S. However, the breadth of protection appears to be limited, since the vaccines were only partially effective against intravenous challenge by the uncloned SIVmne. To examine factors that could affect the breadth and the efficacy of this immunization approach, we studied (i) the effect of priming by recombinant vaccinia virus; (ii) the role of surface antigen gp130; and (iii) the role of core antigens (Gag and Pol) in eliciting protective immunity. Results indicate that (i) priming with recombinant vaccinia virus was more effective than subunit antigen in eliciting protective responses; (ii) while both gp130 and gp160 elicited similar levels of SN-specific antibodies, gp130 was not as effective as gp160 in protection, indicating a possible role for the transmembrane protein in presenting functionally important epitopes; and (iii) although animals immunized with core antigens failed to generate any neutralizing antibody and were infected upon challenge, their virus load was 50- to 100-fold lower than that of the controls, suggesting the importance of cellular immunity or other core-specific immune responses in controlling acute infection. Complete protection against intravenous infection by the pathogenic uncloned SIVmne was achieved by immunization with both the envelope and the core antigens. These results indicate that immune responses to both antigens may contribute to protection and thus argue for the inclusion of multiple antigens in recombinant vaccine designs. C1 Univ Washington, Reg Primate Res Ctr, Seattle, WA 98121 USA. Univ Washington, Dept Biostat, Seattle, WA 98121 USA. Bristol Myers Squibb Pharmaceut Res Inst, Seattle, WA 98121 USA. Duke Univ, Med Ctr, Durham, NC USA. NCI, Frederick, MD 21701 USA. RP Hu, SL (reprint author), Univ Washington, Reg Primate Res Ctr, 3000 Western Ave, Seattle, WA 98121 USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCRR NIH HHS [P51 RR000166, RR00166]; NIAID NIH HHS [AI26503, AI85343] NR 80 TC 63 Z9 63 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8201 EP 8215 PG 15 WC Virology SC Virology GA 235QP UT WOS:000082554300033 PM 10482571 ER PT J AU Wu, JW Davis, MD Owens, RA AF Wu, JW Davis, MD Owens, RA TI Factors affecting the terminal resolution site endonuclease, helicase, and ATPase activities of adeno-associated virus type 2 Rep proteins SO JOURNAL OF VIROLOGY LA English DT Article ID INHIBITS CELLULAR-TRANSFORMATION; DOMINANT-NEGATIVE MUTANT; ADENOASSOCIATED VIRUS; DNA-REPLICATION; WILD-TYPE; GENE-PRODUCT; SEQUENCE REQUIREMENTS; MUTATIONAL ANALYSIS; INVITRO RESOLUTION; VIRAL REPLICATION AB The Rep68 and Rep78 proteins (Rep68/78) of adeno-associated virus type 2 (AAV) are critical for AAV replication and site-specific integration. They bind specifically to the AAV inverted terminal repeats (ITRs) and possess ATPase, helicase, and strand-specific/site-specific endonuclease activities. In the present study, we further characterized the AAV Rep68/78 helicase, ATPase, and endonuclease activities by using a maltose binding protein-Rep68 fusion (MBP-Rep68 Delta) produced in Escherichia coli cells and Rep78 produced in vitro in a rabbit reticulocyte lysate system. We found that the minimal length of single-stranded DNA capable of stimulating the ATPase activity of MBP-Rep68 Delta is 100 to 200 bases. The degree of stimulation correlated positively with the length of single-stranded DNA added to the reaction mixture. We then determined the ATP concentration needed for optimal MBP-Rep68 Delta helicase activity and showed that the helicase is active over a wide range of ATP concentrations. We determined the directionality of MBP-Rep68 Delta helicase activity and found that it appears to move in a 3' to 5' direction, which is consistent with a model in which AAV Rep68/78 participates in AAV DNA replication by unwinding DNA ahead of a cellular DNA polymerase. In this report, we also demonstrate that single-stranded DNA is capable of inhibiting the MBP-Rep68 Delta or Rep78 endonuclease activity greater than Id-fold. In addition, we show that removal of the secondary Rep68/78 binding site, which is found only in the hairpin form of the AAV ITR, causes a three- to eightfold reduction in the ability of the ITR to be used as a substrate for the Rep78 or MBP-Rep68 Delta endonuclease activity. This suggests that contact between Rep68/78 and this secondary element may play an important role in the Rep-mediated endonuclease activity. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Owens, RA (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Bldg 8,Rm 309,8 Ctr Dr,MSC 0840, Bethesda, MD 20892 USA. NR 73 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8235 EP 8244 PG 10 WC Virology SC Virology GA 235QP UT WOS:000082554300036 PM 10482574 ER PT J AU Wyand, MS Manson, K Montefiori, DC Lifson, JD Johnson, RP Desrosiers, RC AF Wyand, MS Manson, K Montefiori, DC Lifson, JD Johnson, RP Desrosiers, RC TI Protection by live, attenuated simian immunodeficiency virus against heterologous challenge SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS-MONKEYS; IN-VIVO; LYMPHOCYTE DEPLETION; VACCINE PROTECTION; IMMUNE-RESPONSES; SIV REPLICATION; T-LYMPHOCYTES; HIV TYPE-1; NEF GENE; MACAQUES AB We examined the ability of a live, attenuated deletion mutant of simian immunodeficiency virus (SIV), SIVmac239 Delta 3, which is missing nef and vpr genes, to protect against challenge by heterologous strains SHIV89.6p and SIVsmE660. SHIVS9.6p is a pathogenic, recombinant SIV in which the envelope gene has been replaced by a human immunodeficiency virus type 1 envelope gene; other structural genes of SHIV89.6p are derived from SIVmac239. SIVsmE660 is an uncloned, pathogenic, independent isolate from the same primate lentivirus subgrouping as SIVmac but with natural sequence variation in all structural genes. The challenge with SHIV89.6p was performed by the intravenous route 37 months after the time of vaccination. By the criteria of CD4(+) cell counts and disease, strong protection against the SHIV89.6p challenge was observed in four of four vaccinated monkeys despite the complete mismatch of env sequences. However, SHIV89.6p infection was established in all four previously vaccinated monkeys and three of the four developed fluctuating viral loads between 300 and 10,000 RNA copy equivalents per mi of plasma 30 to 72 weeks postchallenge. When other vaccinated monkeys were challenged with SIVsmE660 at 28 months after the time of vaccination, SIV loads were lower than those observed in unvaccinated controls but the level of protection was less than what was observed against SHIV89.6p in these experiments and considerably less than the level of protection against SIVmac251 observed in previous experiments. These results demonstrate a variable level of vaccine protection by Live, attenuated SIVmac239 Delta 3 against heterologous virus challenge and suggest that even live, attenuated vaccine approaches for AIDS will Face significant hurdles in providing protection against the natural variation present in field strains of virus. The results further suggest that factors other than anti-Env immune responses can be principally responsible for the vaccine protection by live, attenuated SIV. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Primedica, Worcester, MA 01608 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. RP Desrosiers, RC (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, 1 Pine Hill Dr,Box 9102, Southborough, MA 01772 USA. FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168]; NIAID NIH HHS [U01 AI035365, AI35365, N01-AI-65303, P01 AI035365, R01 AI065303] NR 36 TC 189 Z9 191 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8356 EP 8363 PG 8 WC Virology SC Virology GA 235QP UT WOS:000082554300048 PM 10482586 ER PT J AU Shimizu, YK Hijikata, M Kiyohara, T Kitamura, Y Yoshikura, H AF Shimizu, YK Hijikata, M Kiyohara, T Kitamura, Y Yoshikura, H TI Replication of GB virus C (hepatitis G virus) in interferon-resistant Daudi cells SO JOURNAL OF VIROLOGY LA English DT Article ID CIRCULATING IMMUNE-COMPLEXES; INFECTION; CULTURES AB We previously reported that Daudi cells, a Burkitt's lymphoma cell line, were capable of supporting productive infection of hepatitis C virus (HCV), During continual cultivation after HCV infection, the culture became resistant to interferons (IFNs), This resistant cell line, coded as H-903, was used as host cells for replication of GB virus C (GBV-C), also known as hepatitis G virus. GBV-C RNA was detected in the culture by reverse transcription-PCR for more than 130 days after inoculation, while it was detected for 44 days but not later in the parental IFN-sensitive Daudi cells. Productive infection of GBV-C in the H-903 system was confirmed by serially inoculating supernatants from infected cultures into uninfected cells. The viral E2 antigen was detected by immunofluorescence in the cells inoculated with the fifth passage of GBV-C, The presumed capsid-coding region of the viral genome in the inoculum, in the serially passaged virus, or in the virus produced by a long-term culture was only 16 amino acids long, suggesting that the GBV-C with a short core sequence was replication competent. C1 Natl Inst Infect Dis, Dept Infect Dis & Vaccine Control, Tokyo 2080011, Japan. Natl Inst Infect Dis, Div Mol Genet, Tokyo 2080011, Japan. Toshiba Gen Hosp, Tokyo 1408522, Japan. RP Shimizu, YK (reprint author), NIAID, Hepatitis Viruses Sect, LID, NIH, Bldg 7,Room 200, Bethesda, MD 20892 USA. NR 15 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8411 EP 8414 PG 4 WC Virology SC Virology GA 235QP UT WOS:000082554300054 PM 10482592 ER PT J AU Dittmer, U Race, B Hasenkrug, KJ AF Dittmer, U Race, B Hasenkrug, KJ TI Kinetics of the development of protective immunity in mice vaccinated with a live attenuated retrovirus SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA VIRUSES; SIMIAN IMMUNODEFICIENCY VIRUS; HOST GENETIC-CONTROL; T-CELL SUBSETS; MONOCLONAL-ANTIBODIES; ENVELOPE PROTEIN; FRIEND-LEUKEMIA; ERYTHROLEUKEMIA; INFECTION; IMMUNIZATION AB Vaccination of mice with a live attenuated vaccine virus induces potent protection against subsequent challenge with pathogenic Friend retroviral complex. The kinetic studies presented here demonstrate protection from acute splenomegaly as early as 1 week postvaccination. At this time point virus-specific cytotoxic T lymphocytes (CTL) were demonstrable in direct chromium release assays. However, during the first 2 weeks after vaccination protection was incomplete since the mice were not protected against establishment of low-level persistent infections in the spleen. By 3 weeks postvaccination the animals were protected against the establishment of persistent virus as well as acute splenomegaly. The timing of this complete protection correlated with the presence of both virus-neutralizing antibodies and primed CTL in the immunized mice. Within 3 days of virus challenge, vaccinated mice showed high levels of activated B cells and CD4(+) and CD8(+) T cells, indicating an efficient priming of all lymphocyte subsets. Despite very limited replication of the vaccine virus, the protective effect was long lived and was still present 6 months after immunization. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 37 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8435 EP 8440 PG 6 WC Virology SC Virology GA 235QP UT WOS:000082554300057 PM 10482595 ER PT J AU Masuda, M Kakushima, N Wilt, SG Ruscetti, SK Hoffman, PM Iwamoto, A Masuda, M AF Masuda, M Kakushima, N Wilt, SG Ruscetti, SK Hoffman, PM Iwamoto, A Masuda, M TI Analysis of receptor usage by ecotropic murine retroviruses, using green fluorescent protein-tagged cationic amino acid transporters SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOTHELIAL-CELL TROPISM; LEUKEMIA-VIRUS PVC-211; BINDING DOMAIN; NERVOUS-SYSTEM; IN-VITRO; BRAIN; FAMILY; IDENTIFICATION; GLYCOPROTEIN; EXPRESSION AB Entry of ecotropic murine leukemia virus (MuLV) into host cells is initiated by interaction between the receptor-binding domain of the viral SU protein and the third extracellular domain (TED) of the receptor, cationic amino acid transporter 1 (CAT1). To study the molecular basis for the retrovirus-receptor interaction, mouse CAT1 (mCAT1) was expressed in human 293 cells as a fusion protein with jellyfish green fluorescent protein (GFP). Easily detected by fluorescence microscopy and immunoblot analysis with anti-GFP antibodies, the mCAT1-GFP fusion protein was expressed in an N-glycosylated form on the cell surface and in the Golgi apparatus, retaining the ecotropic receptor function. The system was applied to compare Friend MuLV (F-MuLV) and its neuropathogenic variant, PVC-211 MuLV, which exhibits a unique cellular tropism and host range, for the ability to use various CAT family members as a receptor. The results indicated that F-MuLV and PVC-211 MuLV could infect the cells expressing wild-type mCAT1 at comparable efficiencies and that rat CAT3, but not mCAT2, conferred a low but detectable level of susceptibility to F-MuLV and PVC-211 MuLV. The data also suggested that CAT proteins might be expressed in an oligomeric form. Further application of the system developed in this study may provide useful insights into the entry mechanism of ecotropic MuLV. C1 Univ Tokyo, Dept Microbiol, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan. Univ Tokyo, Inst Med Sci, Dept Infect Dis, Tokyo 1088639, Japan. Dept Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Frederick, MD 21702 USA. RP Masuda, M (reprint author), Univ Tokyo, Dept Microbiol, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM mmasuda@m.u-tokyo.ac.jp NR 40 TC 31 Z9 31 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8623 EP 8629 PG 7 WC Virology SC Virology GA 235QP UT WOS:000082554300077 PM 10482615 ER PT J AU Stegalkina, SS Guerrero, A Walton, KD Liu, XW Robinson, GW Hennighausen, L AF Stegalkina, SS Guerrero, A Walton, KD Liu, XW Robinson, GW Hennighausen, L TI Transcription originating in the long terminal repeats of the endogenous mouse mammary tumor virus MTV-3 is activated in Stat5a-null mice and picks up hitchhiking exons SO JOURNAL OF VIROLOGY LA English DT Article ID GENE-EXPRESSION; NUCLEAR FACTOR; TISSUE; STAT5B; TUMORIGENESIS; PREGNANCY; PROMOTER; ELEMENTS; SEQUENCE; CLONING AB The enhancer within the long terminal repeats (LTRs) of acquired somatic mouse mammary tumor viruses (MMTV) can activate juxtaposed genes and induce mammary tumors. In contrast, germ line proviral MMTV genomes are integrated in the host genome and considered to be genetically confined transcription units. Here we demonstrate that transcription initiated in an MMTV provirus proceeds into banking host sequences. We discovered multiple polyadenylated transcripts which are induced in Stat5a null mice. These range from 1.5 kb to more than 8 kb and are specifically expressed in mammary tissue from pregnant and lactating mice from the 129 but not C57BL/6 strain. The RNAs emanate from both LTRs of the endogenous MTV-3 provirus on chromosome 11 and proceed at least 10 kb into the juxtaposed genomic territory. Transcripts originating in the 5' LTR splice from the native splice site within the MMTV envelope gene into at least six exons, three of which contain functional internal splice sites. The combination of alternative splicing and the use of several polyadenylation sites ensure the generation of multiple transcripts. To date no significant open reading frame has been discovered. Furthermore, we demonstrate that transcription from the MMTV 5' LTR is highly active in the absence of Stat5a, a transcription factor that had been shown previously to be required for transcription from the MMTV LTR. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Rm 101, Bethesda, MD 20892 USA. EM mammary@nih.gov RI Robinson, Gertraud/I-2136-2012; OI Walton, Katherine/0000-0001-9108-5617 NR 27 TC 5 Z9 5 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 1999 VL 73 IS 10 BP 8669 EP 8676 PG 8 WC Virology SC Virology GA 235QP UT WOS:000082554300082 PM 10482620 ER PT J AU Fox, JM Stevenson, MAM Bloom, ME AF Fox, JM Stevenson, MAM Bloom, ME TI Replication of Aleutian mink disease parvovirus in vivo is influenced by residues in the VP2 protein SO JOURNAL OF VIROLOGY LA English DT Article ID ACUTE INTERSTITIAL PNEUMONIA; CANINE PARVOVIRUS; HOST-RANGE; REYES-SYNDROME; ADULT MINK; 5'-TERMINAL PALINDROME; MOLECULAR CLONES; APLASTIC-ANEMIA; B19 INFECTION; CELL-CULTURE AB Aleutian mink disease parvovirus (ADV) is the etiological agent of Aleutian disease of mink Several ADV isolates have been identified which vary in the severity of the disease they elicit. The isolate ADV-Utah replicates to high levels in mink, causing severe Aleutian disease that results in death within 6 to 8 weeks, but does not replicate in Crandell feline kidney (CrFK) cells. In contrast, ADV-G replicates in CrFK cells but does not replicate in mink The ability of the virus to replicate in vivo is determined by virally encoded determinants contained within a defined region of the VP2 gene (M. E. Bloom, J. M. Fox, B. D. Berry, K. L. Oie, and J. B. Wolfin-barger. Virology 251:288-296, 1998). Within this region, ADV-G and ADV-Utah differ at only five amino acid residues. To determine which of these five amino acid residues comprise the in vivo replication determinant, site-directed mutagenesis was performed to individually convert the amino acid residues of ADV-G to those of ADV-Utah. A virus in which the ADV-G VP2 residue at 534, histidine (H), was converted to an aspartic acid (D) of ADV-Utah replicated in CrFK cells as efficiently as ADV-G. H534D also replicated in mink, causing transient viremia at 30 days postinfection and a strong antibody response. Animals infected with this virus developed diffuse hepatocellular microvesicular steatosis, an abnormal accumulation of intracellular fat, but did not develop classical Aleutian disease. Thus, the substitution of an aspartic acid at residue 534 for a histidine allowed replication of ADV-G in mink, but the ability to replicate was not sufficient to cause classical Aleutian disease. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Fox, JM (reprint author), 903 S 4th St, Hamilton, MT 59840 USA. NR 48 TC 18 Z9 20 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8713 EP 8719 PG 7 WC Virology SC Virology GA 235QP UT WOS:000082554300087 PM 10482625 ER PT J AU Kabrane-Lazizi, Y Meng, XJ Purcell, RH Emerson, SU AF Kabrane-Lazizi, Y Meng, XJ Purcell, RH Emerson, SU TI Evidence that the genomic RNA of hepatitis E virus is capped SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNAS; CELLS AB Hepatitis E virus (HEV) is an unclassified virus with a positive-sense RNA genome and an undefined replication strategy. In order to determine whether the HEV genome is capped or not, we developed a reverse transcription-PCR assay that is based on the ability of a monoclonal antibody to recognize 7-methylguanosine (m(7)G), Antibody to m7G bound RNA extracted from virions of two different HEV genotypes, The cap analog competitively inhibited the binding of virion RNAs, demonstrating that HEV has a capped RNA genome. C1 NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, Mol Hepatitis Sect, NIH, Bethesda, MD 20892 USA. RP Kabrane-Lazizi, Y (reprint author), NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 18 TC 70 Z9 74 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1999 VL 73 IS 10 BP 8848 EP 8850 PG 3 WC Virology SC Virology GA 235QP UT WOS:000082554300104 PM 10482642 ER PT J AU Long, JM Mouton, PR Jucker, M Ingram, DK AF Long, JM Mouton, PR Jucker, M Ingram, DK TI What counts in brain aging? Design-based stereological analysis of cell number SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID HUMAN CEREBRAL-CORTEX; DENTATE GYRUS; ALZHEIMERS-DISEASE; ARBITRARY PARTICLES; HIPPOCAMPAL-NEURONS; UNBIASED ESTIMATION; MOUSE HIPPOCAMPUS; COGNITIVE DECLINE; LOCUS-COERULEUS; AGED RATS AB The advent and implementation of new design-based stereological techniques allows the quantification of cell number without the assumptions required when obtaining areal densities. These new techniques are rapidly becoming the standard for quantifying cell number, particularly in aging studies. Recently, studies using stereological techniques have failed to confirm earlier findings regarding age-associated neural loss. This newly emerging view of retained cell number during aging is having a major impact on biogerontology, prompting revaluation of long-standing hypotheses of age-related cell loss as causal for age-related impairments ill brain functioning. Rather than focus on neuronal loss as the end-result of a negative cascade of neuronal injury, research has begun to consider that age-related behavioral declines may reflect neuronal dysfunction (e.g., synaptic or receptor loss, signal transduction deficits) instead of neuronal death. Here we discuss design-based stereology in the context of age-related change in brain cell number and its impact on consideration of structural change in brain aging. Emergence of this method of morphometrics, however, can have relevance to many areas of gerontological research. C1 NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Neuropathol Lab, Baltimore, MD 21205 USA. Univ Basel, Inst Pathol, Dept Neuropathol, Basel, Switzerland. RP Long, JM (reprint author), NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 82 TC 77 Z9 78 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 1999 VL 54 IS 10 BP B407 EP B417 DI 10.1093/gerona/54.10.B407 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XK UT WOS:000088043800001 PM 10568523 ER PT J AU Leveille, SG Guralnik, JM Hochberg, M Hirsch, R Ferrucci, L Langlois, J Rantanen, T Ling, S AF Leveille, SG Guralnik, JM Hochberg, M Hirsch, R Ferrucci, L Langlois, J Rantanen, T Ling, S TI Low back pain and disability in older women: Independent association with difficulty but not inability to perform daily activities SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MINI-MENTAL-STATE; FUNCTIONAL LIMITATIONS; JOINT IMPAIRMENT; PREDICTORS; REHABILITATION; PREVALENCE; STRENGTH; DISEASE; HEALTH; RISK AB Background. Low back pain is a highly prevalent chronic condition, yet little is known about the disabling effects of this common problem in older adults. This study examines the relationship between the presence and severity of low back pain and disability in older women. Methods. The study population was 1,002 disabled older women participating in a population-based prospective study of disablement. Key outcome measures of disability included level of difficulty and inability to perform the following daily activities: light housework, shopping, walking one-quarter mile, climbing stairs, lifting, and activities of daily living (ADLs). Results. Forty-two percent of participants reported they had low back pain for at least one month in the year before baseline. The prevalence of severe back pain decreased markedly with age (10% of those greater than or equal to 85 yr versus 23% in each of the two younger 10 yr age groups). After multivariate adjustments, women with severe back pain were 3 to 4 times more likely than other women to have a lot of difficulty with light housework or shopping. There was also an increased likelihood of difficulty with mobility tasks and basic ADLs among those with severe back pain. No associations were found between back pain and being unable to perform any of the daily activities studied, indicating possible differences in disablement processes leading to functional difficulties versus functional incapacity. Conclusions. There was a strong association between back pain and functional difficulties in older women, pointing to the need for further research using longitudinal methods. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Maryland, Dept Med, Baltimore, MD 21201 USA. Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. I Fraticini Natl Res Inst, INRCA, Dept Geriatr, Florence, Italy. Ctr Dis Control & Prevent, Atlanta, GA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Leveille, SG (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 35 TC 62 Z9 63 U1 2 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 1999 VL 54 IS 10 BP M487 EP M493 DI 10.1093/gerona/54.10.M487 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XK UT WOS:000088043800008 PM 10568530 ER PT J AU Linehan, WM AF Linehan, WM TI Inherited cancers of the kidney: Family studies, genes, and biochemistry SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract ID PAPILLARY RENAL CARCINOMAS; TUMOR-SUPPRESSOR GENE; PRODUCT C1 NCI, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1999 VL 56 IS 4 BP 1191 EP 1192 DI 10.1046/j.1523-1755.1999.0560041191.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 237GV UT WOS:000082648200012 ER PT J AU Poncelet, AC de Caestecker, MP Schnaper, HW AF Poncelet, AC de Caestecker, MP Schnaper, HW TI The transforming growth factor-beta/SMAD signaling pathway is present and functional in human mesangial cells SO KIDNEY INTERNATIONAL LA English DT Article DE type I collagen; serine phosphoacceptor sites; luciferase; glomerulosclerosis; extracellular matrix ID MAD-RELATED PROTEIN; TGF-BETA RECEPTOR; EXTRACELLULAR-MATRIX; TUMOR-SUPPRESSOR; MESSENGER-RNA; ALPHA-2(I) COLLAGEN; TRANSCRIPTIONAL ACTIVATION; FIBRONECTIN SYNTHESIS; ENDOTHELIAL-CELLS; GENE-EXPRESSION AB Background. Transforming growth factor-beta (TGF-beta) signals through a unique set of intracellular proteins, called SMADs, that have been characterized mainly in transient overexpression systems. Because several models of glomerulosclerosis suggest a role for TGF-beta in the extracellular matrix accumulation, we sought to characterize the role of SMAD proteins in mediating TGF-beta 1 responses in a more physiological system using nontransformed human mesangial cells. Methods. Endogenous SMAD expression and its modulation by TGF-beta 1 were evaluated by Western and Northern blot analyses. Phosphorylation of Smad2 and Smad3 was determined by both phospholabeling and immunoblot. SMAD function and its role in type I collagen transcription were investigated in cotransfection experiments using promoter-luciferase reporter gene constructs. Results. Cultured human mesangial cells express Smad2, SmadS, and Smad4 proteins. TGF-beta 1 down-regulated Smad3 mRNA and protein expression, respectively, after 4 and 24 hours of treatment, whereas Smad2 and Smad4 were less affected. Both Smad2 and Smad3 were phosphorylated in response to TGF-beta 1 beginning at 5 minutes, with maximal phosphorylation at 15 minutes, and decreasing phosphorylation by 2 hours. Smad2/3 and Smad4 coimmunoprecipitate only after TGF-beta 1 treatment. The activity of a transiently transfected, TGF-beta-responsive construct, p3TP-Lux, was stimulated 3.6-fold by TGF-beta 1. Overexpressed wild-type Smad3 increased basal luciferase activity, which was further stimulated by TGF-beta 1. A dominant negative mutant form of Smad3 lacking the C-terminal serine phosphoacceptor sites (Smad3A) inhibited TGF-beta 1-induced luciferase activity. TGF-beta 1 also increased the activation of an alpha 2(I) collagen promoter-luciferase reporter construct transfected into mesangial cells. This activation was inhibited by cotransfection with the Smad3A mutant. Conclusions. Smad2, Smad3, and Smad4 are present and activated by TGF-beta 1 in human mesangial cells. The SMAD pathway is functional in these cells and appears to be involved in TGF-beta 1-induced type I collagen gene transcription. These findings raise the possibility that SMAD signaling plays a role in glomerular matrix accumulation. C1 Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Childrens Mem Inst Educ & Res, Chicago, IL 60611 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Poncelet, AC (reprint author), Pediat W-140,Ward 12-110,303 E Chicago Ave, Chicago, IL 60611 USA. FU NHLBI NIH HHS [HL53918]; NIDDK NIH HHS [DK49362, DK53576, R01 DK049362] NR 56 TC 117 Z9 141 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1999 VL 56 IS 4 BP 1354 EP 1365 DI 10.1046/j.1523-1755.1999.00680.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 237GV UT WOS:000082648200044 PM 10504488 ER PT J AU Franklin, CL Riley, LK Livingston, RS Beckwith, CS Hook, RR Besch-Williford, CL Hunziker, R Gorelick, PL AF Franklin, CL Riley, LK Livingston, RS Beckwith, CS Hook, RR Besch-Williford, CL Hunziker, R Gorelick, PL TI Enteric lesions in SCID mice infected with "Helicobacter typhlonicus," a novel urease-negative Helicobacter species SO LABORATORY ANIMAL SCIENCE LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; CHRONIC ACTIVE HEPATITIS; 16S RIBOSOMAL-RNA; SP-NOV; CAMPYLOBACTER-CINAEDI; BACTERIAL-INFECTION; LABORATORY MICE; IDENTIFICATION; BILIS; SEQUENCE AB Background and Purpose: Several rodent helicobacters have been associated with chronic active hepatitis or inflammatory bowel disease. Severe combined immunodeficient (SCID) mice appear to be inherently susceptible to disease attributable to these emerging pathogens. With the advent of polymerase chain reaction (PCR) analysis, it has become clear that several as yet unidentified Helicobacter species may also colonize rodents, but their capacity to cause disease is unknown. Methods: A Helicobacter species isolated from feces of a BALB/c mouse and provisionally named "H, typhlonicus" was used to inoculate helicobacter-free 4-week-old SCID mice (n = 11 males and 11 females). At various weeks after inoculation, mice were sacrificed and liver and intestinal specimens were collected for histologic examination and PCR analyses. Results: The C.B-17 scid/scid mice inoculated with "H, typhlonicus" developed moderate to severe proliferative typhlocolitis, similar to that seen in SCID mice infected with H, hepaticus or H, bills, However, in contrast to mice infected with H, hepaticus or H, bills, lesions of chronic active hepatitis were not detected in mice inoculated with "H, typhlonicus." A similar disease syndrome developed in SCID mice cohabitated with B6D2F1 mice naturally infected with a novel Helicobacter species that was genetically identical to "H. typhlonicus," Conclusion: "Helicobacter typhlonicus" joins a growing list of helicobacters that are capable of inducing enteric disease in immunodeficient mice. C1 Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65201 USA. NIAID, Transgen Lab, Frederick, MD 21701 USA. NCI, Anim Hlth Diagnost Lab, Lab Sci Program, Frederick Canc Res & Dev Ctr,SAIC Frederick, Frederick, MD 21701 USA. RP Franklin, CL (reprint author), Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65201 USA. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 61 Z9 62 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD OCT PY 1999 VL 49 IS 5 BP 496 EP 505 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 250NE UT WOS:000083393800006 PM 10551450 ER PT J AU Thigpen, JE Setchell, KDR Ahlmark, KB Locklear, J Spahr, T Caviness, GF Goelz, MF Haseman, JK Newbold, RR Forsythe, DB AF Thigpen, JE Setchell, KDR Ahlmark, KB Locklear, J Spahr, T Caviness, GF Goelz, MF Haseman, JK Newbold, RR Forsythe, DB TI Phytoestrogen content of purified, open- and closed-formula laboratory animal diets SO LABORATORY ANIMAL SCIENCE LA English DT Article ID SOY PROTEIN; ESTROGENIC ACTIVITY; BONE LOSS; ENVIRONMENTAL ESTROGENS; SOYBEAN ISOFLAVONES; PREMENOPAUSAL WOMEN; MAMMARY-CANCER; MOUSE BIOASSAY; RODENT DIETS; RATS AB Background and Purpose: Phytoestrogens exert estrogenic effects on the central nervous system, induce estrus, and stimulate growth of the genital tract of female animals. Over 300 plants and plant products, including some used in laboratory animal diets, contain phytoestrogens. Therefore, the source and concentration of phytoestrogens in rodent diets were determined. Methods: Twelve rodent diets and six major dietary ingredients were assayed for phytoestrogens (daidzein, genistein, formononetin, biochanin A, and coumestrol), using high-performance liquid chromatography, Three rodent diets recently formulated to reduce phytoestrogen content also were assayed. Results: Formononetin, biochanin A, and coumestrol were not detected. Soybean meal was the major source of daidzein and genistein; their concentrations were directly correlated to the percentage of soybean meal in each diet. Conclusions: High, variable concentrations of daidzein and genistein are present in some rodent diets, and dietary phytoestrogens have the potential to alter results of studies of estrogenicity, Careful attention should be given to diet phytoestrogen content, and their concentration should be reported. A standardized, open-formula diet in which estrogenic substances have been reduced to levels that do not alter results of studies that are influenced by exogenous estrogens is recommended. C1 Natl Inst Environm Hlth Sci, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Toxicol Lab, Res Triangle Pk, NC USA. Childrens Hosp, Med Ctr, Dept Pediat Gastroenterol, Cincinnati, OH 45229 USA. RP Thigpen, JE (reprint author), Natl Inst Environm Hlth Sci, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. NR 70 TC 179 Z9 181 U1 0 U2 6 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD OCT PY 1999 VL 49 IS 5 BP 530 EP 536 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 250NE UT WOS:000083393800011 PM 10551455 ER PT J AU Mertts, M Garfield, S Tanemato, K Tomarev, SI AF Mertts, M Garfield, S Tanemato, K Tomarev, SI TI Identification of the region in the N-terminal domain responsible for the cytoplasmic localization of Myoc/Tigr and its association with microtubules SO LABORATORY INVESTIGATION LA English DT Article ID OPEN-ANGLE GLAUCOMA; PRIMARY CONGENITAL GLAUCOMA; TRABECULAR MESHWORK CELLS; CYTOCHROME P4501B1; MOLECULAR-CLONING; GENE; OLFACTOMEDIN; PROTEIN; MUTATIONS; TIGR AB Mutations in the MYOC/TIGR gene are associated with juvenile open-angle glaucoma and in some cases may be involved in the formation of sporadic primary open-angle glaucoma in humans. To better understand the functions of the MYOC/TIGR protein, its intracellular distribution was investigated using green fluorescent protein (GFP) as a marker. The results indicated that the recombinant mouse and human Myoc/Tigr-GFP proteins are located in the cytoplasm of the transfected cells in which they colocalize with microtubules. Deletion analysis demonstrated that the N-terminal region (positions 1-124 and 15-138 in the mouse and human proteins, respectively) encoded by exon 1 is critical for the cytoplasmic localization of Myoc/Tigr. Most of the known mutations in the human MYOC/TIGR gene implicated in juvenile and sporadic primary open-angle glaucoma formation are located outside the region responsible for the cytoplasmic localization of the protein. However, some of these mutations may alter the tertiary structure of the protein and subsequently modify its interaction with microtubules. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Tomarev, SI (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Room 2A04,6 Ctr Dr MSC 2730, Bethesda, MD 20892 USA. NR 31 TC 44 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 1999 VL 79 IS 10 BP 1237 EP 1245 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 246GT UT WOS:000083156600007 PM 10532587 ER PT J AU Coleman, AE Forest, ST McNeil, N Kovalchuk, AL Ried, T Janz, S AF Coleman, AE Forest, ST McNeil, N Kovalchuk, AL Ried, T Janz, S TI Cytogenetic analysis of the bipotential murine pre-B cell lymphoma, P388, and its derivative macrophage-like tumor, P388D1, using SKY and CGH SO LEUKEMIA LA English DT Article DE molecular cytogenetics; bilineage differentiation potential; phorbol ester-induced cytogenetic changes; karyotypic instability ID COMPARATIVE GENOMIC HYBRIDIZATION; DIFFERENTIATION; AMPLIFICATION; CHROMOSOMES; RESISTANCE; RECEPTOR; LINE; MICE AB Spectral karyotyping (SKY) and comparative genomic hybridization (CGH) were used to elucidate the divergent cytogenetic make-up of the prototypical bilineage lymphoblastic pre-B lymphoma, P388, and its progenitor macrophage-like tumor, P388D1. P388 was found to be diploid and genomically stable. P388D1 was triploid, highly unstable and characterized by numerous marker chromosomes (Chrs) and composite rearrangements. The karyotype of P388D1 was so complex that its clonal relatedness to P388 would have remained questionable without confirmation by molecular analysis of the clonotypic immunoglobulin heavy-chain and light-chain gene recombinations that coexisted in both tumors. The intrinsic instability of the P388D1 genome was indicated by the observation that only four out of 42 aberrations uncovered by SKY (in a total of 27 metaphases) occurred consistently (100% incidence), whereas 27 changes occurred non-randomly (27 to 96% incidence) and 11 alterations randomly (4 to 11% incidence). Persistent cytogenetic instability was also observed in P388 'macrophages' after phorbol ester- and ionomycin-induced conversion in vitro of P388 lymphoma cells. The 'cytogenetic noise' in these cells was manifested by a multiplicity of sporadic chromosomal aberrations; ie 25 distinct changes were identified by SKY in 40 metaphases. The results in P388D1 and P388 'macrophages' were interpreted to indicate that the myeloid differention program in the bipotential pre-B cell lymphoma P388 is invariably characterized by karyotypic instability. The study presented here demonstrates the power of the combined SKY and CGH approach to resolve complicated karyotypes of important and widely used mouse tumors. C1 Natl Human Genome Res Inst, Genet Lab, Div Basic Sci, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. RP Janz, S (reprint author), NCI, LG, DBS, Bldg 37,Rm 2B10, Bethesda, MD 20892 USA. NR 36 TC 10 Z9 10 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1999 VL 13 IS 10 BP 1592 EP 1600 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 242XB UT WOS:000082966000017 PM 10516761 ER PT J AU Virta, A Barnett, AL Pierpaoli, C AF Virta, A Barnett, AL Pierpaoli, C TI Visualizing and characterizing white matter fiber structure and architecture in the human pyramidal tract using diffusion tensor MRI SO MAGNETIC RESONANCE IMAGING LA English DT Article DE diffusion MRI; white matter; anisotropy; aging; human ID HUMAN BRAIN; IN-VIVO; ARTIFACTS; SPECTROSCOPY; ANISOTROPY; MOTION; IMAGES; STROKE AB We used diffusion tensor imaging to assess diffusion anisotropy in the pyramidal tract in ten young, and ten elderly subjects (five males and five females in each group). The purpose of this study was to define normative values for anisotropy at different anatomic levels of the brainstem as well as to assess differences due to age, gender, and laterality. In all subjects, anisotropy was highest in the cerebral peduncle, lowest in the caudal pens, and intermediate in the medulla, In the pens and medulla the regional variability was high, with significant differences in anisotropy even between contiguous slices. Multifactorial ANOVA (performed using the average value of anisotropy within each region of interest) revealed that elderly subjects had significantly lower values than young subjects in the cerebral peduncle, with no differences in the pens and medulla, No significant differences in anisotropy due to gender and side were found. The differences in anisotropy at different levels of the brainstem reflect differences in the local architecture of white matter fibers. Anisotropy is high in the cerebral peduncle because fibers have a highly ordered arrangement, while in the pens and medulla, anisotropy is lower because the local fiber architecture is less coherent due to the presence of other fibers and nuclei. The biologic meaning of the intergroup differences in anisotropy is discussed in light of the structure and architecture of the tissue under investigation. We also consider potential sources of,artifacts, such as noise and motion, partial volume contamination, anatomic mismatching, and the use of inappropriate statistical tests. We conclude that the age-related decrease in anisotropy in the cerebral peduncle is not artifactual but rather reflects subtle structural changes of the aging white matter, Our study however shows that caution must be exercised in interpreting diffusion anisotropy data, (C) 1999 Elsevier Science Inc. C1 NICHD, NIH, Neuroimaging Branch, Bethesda, MD 20892 USA. RP Pierpaoli, C (reprint author), NICHD, NIH, Neuroimaging Branch, Bldg 13,Room 3N17,13 S Dr, Bethesda, MD 20892 USA. RI Pierpaoli, Carlo/E-1672-2011 NR 32 TC 145 Z9 153 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD OCT PY 1999 VL 17 IS 8 BP 1121 EP 1133 DI 10.1016/S0730-725X(99)00048-X PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 237BU UT WOS:000082634400004 PM 10499674 ER PT J AU Liddell, RA Hirano, MC Mock, BA AF Liddell, RA Hirano, MC Mock, BA TI Mouse Chromosome 4 SO MAMMALIAN GENOME LA English DT Article C1 NCI, Genet Lab, DBS, NIH, Bethesda, MD 20892 USA. RP Mock, BA (reprint author), NCI, Genet Lab, DBS, NIH, Bldg 37,Room 2B-08,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 1999 VL 10 IS 10 BP 943 EP 943 DI 10.1007/s003359901123 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800005 PM 10501946 ER PT J AU Kozak, CA Stephenson, DA AF Kozak, CA Stephenson, DA TI Mouse Chromosome 5 SO MAMMALIAN GENOME LA English DT Article C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. UCL, Dept Genet & Biometry, London NX1 2HE, England. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, 4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 1999 VL 10 IS 10 BP 944 EP 944 DI 10.1007/s003359901124 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800006 PM 10501947 ER PT J AU Burmeister, M Bryda, EC Bureau, JF Noben-Trauth, K AF Burmeister, M Bryda, EC Bureau, JF Noben-Trauth, K TI Mouse Chromosome 10 SO MAMMALIAN GENOME LA English DT Article C1 Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA. Marshall Univ, Sch Med, Dept Microbiol Mol Genet & Immunol, Huntington, WV 25704 USA. Inst Pasteur, Unite Virus Lents, F-75724 Paris, France. Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. RP Burmeister, M (reprint author), Univ Michigan, Mental Hlth Res Inst, 205 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. RI Burmeister, Margit/A-3157-2013 OI Burmeister, Margit/0000-0002-1914-2434 FU NIDCD NIH HHS [DC02982, DC03771]; NINDS NIH HHS [NS32130] NR 0 TC 1 Z9 1 U1 0 U2 0 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 1999 VL 10 IS 10 BP 950 EP 951 DI 10.1007/s003359901129 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800011 PM 10501952 ER PT J AU Stephenson, DA Lueders, KK AF Stephenson, DA Lueders, KK TI Mouse Chromosome 13 SO MAMMALIAN GENOME LA English DT Article C1 McLaughlin Res Inst Biomed Sci, Great Falls, MT 59405 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stephenson, DA (reprint author), McLaughlin Res Inst Biomed Sci, 1520 23rd St S, Great Falls, MT 59405 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 1999 VL 10 IS 10 BP 954 EP 954 DI 10.1007/s003359901132 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800014 PM 10501955 ER PT J AU Huppi, K Siwarski, D Kim, J Letts, V AF Huppi, K Siwarski, D Kim, J Letts, V TI Mouse Chromosome 15 SO MAMMALIAN GENOME LA English DT Article C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Huppi, K (reprint author), NCI, Genet Lab, NIH, Bldg 37,Rm 2B-21, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 1999 VL 10 IS 10 BP 956 EP 956 DI 10.1007/s003359901134 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800016 PM 10501957 ER PT J AU Reeves, RH Cabin, DE AF Reeves, RH Cabin, DE TI Mouse Chromosome 16 SO MAMMALIAN GENOME LA English DT Article C1 Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. Natl Human Genome Res Inst, Lab Genet Dis Res, Bethesda, MD 20892 USA. RP Reeves, RH (reprint author), Johns Hopkins Univ, Sch Med, Dept Physiol, P203,725 N Wolfe St, Baltimore, MD 21205 USA. FU NHGRI NIH HHS [HG00405, HG24605] NR 0 TC 5 Z9 5 U1 0 U2 0 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 1999 VL 10 IS 10 BP 957 EP 957 DI 10.1007/s003359901135 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800017 PM 10501958 ER PT J AU Vajo, Z King, LM Jonassen, T Wilkin, DJ Ho, N Munnich, A Clarke, CF Francomano, CA AF Vajo, Z King, LM Jonassen, T Wilkin, DJ Ho, N Munnich, A Clarke, CF Francomano, CA TI Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging SO MAMMALIAN GENOME LA English DT Article ID PROTEIN SECONDARY STRUCTURE; SACCHAROMYCES-CEREVISIAE; LIFE-SPAN; DROSOPHILA-MELANOGASTER; SUPEROXIDE-DISMUTASE; CALORIC RESTRICTION; OXIDATIVE DAMAGE; COQ7 GENE; STRESS; OVEREXPRESSION AB Mutations in the Caenorhabditis elegans gene clk-1 have a major effect on slowing development and increasing life span. The Saccharomyces cerevisiae homolog COQ7 encodes a mitochondrial protein involved in ubiquinone biosynthesis and, hence, is required for respiration and gluconeogenesis. In this study, RT-PCR and 5' RACE were used to isolate both human and mouse clk-1/COQ7 homologs. Human CLK-1 was mapped to Chr 16(p12-13.1) by Radiation Hybrid (RH) and fluorescence in situ hybridization (FISH) methods. The number and location of human CLK1 introns were determined, and the location of introns TI and TV are the same as in C. elegans. Northern blot analysis showed that three different isoforms of CLK-1 mRNA are present in several tissues and that the isoforms differ in the amount of expression. The functional equivalence of human CLK-1 to the yeast COQ7 homolog was tested by introducing either a single or multicopy plasmid containing human CLK-1 cDNA into yeast coq7 deletion strains and assaying for growth on a nonfermentable carbon source. The human CLK-1 gene was able to functionally complement yeast coq7 deletion mutants. The protein similarities and the conservation of function of the CLK-1/clk-I/COQ7 gene products suggest a potential link between the production of ubiquinone and aging. C1 NIH, Natl Human Genome Res Inst, Med Genet Branch, 10 Ctr Dr MSC 1852,Bldg 10,Room 10C101, Bethesda, MD 20892 USA. Hop Necker Enfants Malad, Med Genet Serv, INSERM, U393, F-75743 Paris, France. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. RP Francomano, CA (reprint author), Vet Affairs Med Ctr, Dept Endocrinol & Med, 650 E Indian Sch Rd, Phoenix, AZ 85012 USA. FU NIGMS NIH HHS [GM45952, GM0785] NR 39 TC 51 Z9 55 U1 3 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 1999 VL 10 IS 10 BP 1000 EP 1004 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800029 PM 10501970 ER PT J AU Newton, G Weremowicz, S Morton, CC Jenkins, NA Gilbert, DJ Copeland, NG Lawler, J AF Newton, G Weremowicz, S Morton, CC Jenkins, NA Gilbert, DJ Copeland, NG Lawler, J TI The thrombospondin-4 gene SO MAMMALIAN GENOME LA English DT Article ID OLIGOMERIC MATRIX PROTEIN; EXTRACELLULAR-MATRIX; NEURITE OUTGROWTH; CHROMOSOMAL LOCALIZATION; INSITU HYBRIDIZATION; MURINE DEVELOPMENT; NERVOUS-SYSTEM; AVIAN EMBRYO; MOUSE; EXPRESSION AB Thrombospondins are a family of extracellular, adhesive proteins that are widely expressed in vertebrates. Five distinct gene products, designated thrombospondin-1 through -4 and cartilage oligomeric matrix protein (COMP), have been identified. With the exception of thrombospondin-4, the structure and location of thrombospondin genes have been determined in the human and/or mouse genomes. In this study, the structure and location of the murine thrombospondin-4 gene and the location of the human thrombospondin-4, gene are reported. The murine thrombospondin-4 gene is approximately 4.5 kb in length and includes 22 exons, Interspecific backcross analysis of progeny derived from matings of (C57BL/6J x Mus spretus)F-1 x C57BL/6J mice indicates that the thrombospondin-4 gene is tightly linked to the Dhfr locus on murine Chromosome (Chr) 13. The human gene maps to Chr 5 in band q13 by in situ hybridization to human metaphase chromosomes. The thrombospondin-4, promoter is similar to promoters of some housekeeping, growth control, and other thrombospondin genes in that it contains multiple GC box sequences and lacks a CAAT box. The presence of multiple E-box sequence motifs is consistent with thrombospondin-4 expression in muscle and bone tissue. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Lawler, J (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Res N RN-270C,99 Brookline Ave, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL 49081] NR 65 TC 12 Z9 13 U1 0 U2 1 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 1999 VL 10 IS 10 BP 1010 EP 1016 DI 10.1007/s003359901149 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800031 PM 10501972 ER PT J AU Lyu, MS Rhee, SG Chae, HZ Lee, TH Adamson, MC Kang, SW Jin, DY Jeang, KT Kozak, CA AF Lyu, MS Rhee, SG Chae, HZ Lee, TH Adamson, MC Kang, SW Jin, DY Jeang, KT Kozak, CA TI Genetic mapping of six mouse peroxiredoxin genes and fourteen peroxiredoxin related sequences SO MAMMALIAN GENOME LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; ALKYL HYDROPEROXIDE REDUCTASE; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; CLONING; PROTEIN; PEROXIDASE; MUTATION; DEFENSE; FAMILY C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 21 TC 29 Z9 29 U1 0 U2 1 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 1999 VL 10 IS 10 BP 1017 EP 1019 DI 10.1007/s003359901150 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800032 PM 10501973 ER PT J AU Gilbert, DJ Engel, H Wang, XL Grzeschik, KH Copeland, NG Jenkins, NA Kilimann, MW AF Gilbert, DJ Engel, H Wang, XL Grzeschik, KH Copeland, NG Jenkins, NA Kilimann, MW TI The neurobeachin gene (Nbea) identifies a new region of homology between mouse central Chromosome 3 and human Chromosome 13q13 SO MAMMALIAN GENOME LA English DT Article ID HUMAN GENOME; MAP C1 Ruhr Univ Bochum, Inst Physiol Chem, D-44780 Bochum, Germany. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Marburg, Fachbereich Med, Abt Allgeneine Humangenet, D-35037 Marburg, Germany. Ruhr Univ Bochum, Inst Physiol Chem, D-44780 Bochum, Germany. RP Kilimann, MW (reprint author), Ruhr Univ Bochum, Inst Physiol Chem, D-44780 Bochum, Germany. NR 8 TC 6 Z9 6 U1 0 U2 0 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 1999 VL 10 IS 10 BP 1030 EP 1031 DI 10.1007/s003359901154 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 238LB UT WOS:000082710800036 PM 10501977 ER PT J AU Hospenthal, PDD Chung, KJK Bennett, JE AF Hospenthal, PDD Chung, KJK Bennett, JE TI Comments on airborne Aspergillus and incidence of invasive aspergillosis - Response SO MEDICAL MYCOLOGY LA English DT Letter C1 NIH, Dept Hlth & Social Serv, Bethesda, MD 20892 USA. RP Hospenthal, PDD (reprint author), NIH, Dept Hlth & Social Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD OCT PY 1999 VL 37 IS 5 BP 374 EP 374 PG 1 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 245NW UT WOS:000083115900011 ER PT J AU Taaffe, DR Duret, C Cooper, CS Marcus, R AF Taaffe, DR Duret, C Cooper, CS Marcus, R TI Comparison of calcaneal ultrasound and DXA in young women SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE high-impact loading; weight-bearing activity; ultrasound; densitometry ID BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; QUANTITATIVE ULTRASOUND; OS CALCIS; HIP FRACTURE; DENSITOMETRIC MEASUREMENTS; POSTMENOPAUSAL WOMEN; SKELETAL SITES; ATTENUATION; MASS AB Purpose: The purpose of the study was to assess quantitative ultrasound (QUS) parameters in collegiate female gymnasts, a population whose training incorporates high-impact loading, which is particularly osteogenic, and to determine the discriminative capacity of this relatively new radiation-free technique compared with bone densitometry in a young healthy population. Methods: We studied 19 collegiate gymnasts and 23 healthy controls undergoing regular weight-bearing activity, matched for age (gymnasts 19.2 +/- 1.2, controls 19.9 +/- 1.6 yr) and body weight (gymnasts 56.7 +/- 3.7, controls 57.7 +/- 7.8 kg). QUS parameters of the calcaneus (broadband ultrasound attenuation (BUA), bone velocity (BV), and speed of sound (SOS)) were measured by a Walker Sonix UBA 575+. Bone mineral density (BMD; g.cm(-2)) of the lumbar spine, hip (Femoral neck, trochanter. Ward's triangle) and whole body was assessed by dual energy x-ray absorptiometry (DXA, Hologic QDR 1000/W). Data analysis included unpaired two-tailed Student's t-tests, analysis of variance, Pearson product-moment, and Spearman rank-order correlations. Results: Regional and whole body BMD of gymnasts was greater than controls (P < 0.001), with the difference being 7-28%. Average QUS parameters of the right and left calcaneus were also higher (P < 0.001) in the gymnasts. BUA, BV, and SOS were significantly (P < 0.001) correlated to each bone site with r = 0.54-0.79. Analysis of receiver operating characteristic (ROC) curves indicated no significant difference in sensitivity and specificity for QUS and DXA measures. Conclusions: These results indicate that QUS parameters of the calcaneus are higher in young women gymnasts compared to individuals who undergo regular weight-bearing activity and that QUS parameters are able to discriminate between these two groups in a similar manner as does regional and whole body BMD. C1 VAMC, Musculoskeletal Res Lab, Aging Study Unit, Ctr Geriatr Res Educ & Clin, Palo Alto, CA USA. Charles Sturt Univ, Human Movement Studies Unit, Bathurst, NSW 2795, Australia. RP Taaffe, DR (reprint author), NIA, EDB Program, Gateway Bldg,7201 Wisconsin Ave,Suite 3C-309, Bethesda, MD 20892 USA. NR 36 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD OCT PY 1999 VL 31 IS 10 BP 1484 EP 1489 DI 10.1097/00005768-199910000-00020 PG 6 WC Sport Sciences SC Sport Sciences GA 244MM UT WOS:000083055400020 PM 10527324 ER PT J AU Rivas, G Stafford, W Minton, AP AF Rivas, G Stafford, W Minton, AP TI Characterization of heterologous protein-protein interactions using analytical ultracentrifugation SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID LAMBDA CI-REPRESSOR; SEDIMENTATION EQUILIBRIUM; LAMM EQUATION; QUANTITATIVE CHARACTERIZATION; ANALYTICAL CENTRIFUGATION; MACROMOLECULAR SOLUTIONS; ARBITRARY CONCENTRATION; ASSOCIATION CONSTANTS; RAPID-DETERMINATION; SELF-ASSOCIATION AB Methods for quantitative characterization of heterologous protein-protein interactions by means of analytical ultracentrifugation (AUC) include sedimentation equilibrium, tracer sedimentation equilibrium, sedimentation velocity, and analytical band sedimentation. Fundamental principles governing the behavior of macromolecules in a centrifugal field are summarized, and the application of these principles to the interpretation of data obtained from each type of experiment is reviewed. Instrumentation and software for the acquisition and analysis of data obtained from different types of AUC experiments are described. (C) 1999 Academic Press. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. CSIC, Ctr Invest Biol, E-28006 Madrid, Spain. Boston Biomed Res Inst, Boston, MA 02114 USA. RP Minton, AP (reprint author), NIDDKD, NIH, Bldg 8,Room 226, Bethesda, MD 20892 USA. OI Rivas, German/0000-0003-3450-7478 NR 79 TC 73 Z9 73 U1 0 U2 6 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 1999 VL 19 IS 2 BP 194 EP 212 DI 10.1006/meth.1999.0851 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 247ZJ UT WOS:000083250600003 PM 10527726 ER PT J AU Wang, AP Wada, A Yahiro, K Nomura, T Fujii, Y Okamoto, K Mizuta, Y Kohno, S Moss, J Hirayama, T AF Wang, AP Wada, A Yahiro, K Nomura, T Fujii, Y Okamoto, K Mizuta, Y Kohno, S Moss, J Hirayama, T TI Identification and characterization of the Aeromonas sobria hemolysin glycoprotein receptor on Intestine 407 cells SO MICROBIAL PATHOGENESIS LA English DT Article DE Aeromonas sobria; hemolysin; toxin receptor; glycoprotein receptor; toxin action ID FORMING TOXIN AEROLYSIN; ANCHORED PROTEIN; HYDROPHILA; ERYTHROCYTES; MODEL AB Aeromonas sobria hemolysin is important in the pathogenesis of diarrhoea caused by this enteropathogenic bacterium. By immunoprecipitation analysis using hemolysin and anti-hemolysin antibody, a 66 kDa protein (p66) was identified as a receptor for A. sobria hemolysin on Intestine 407 cells. Treatment of p66 with N-glycosidase F reduced the apparent sized of p66 to 60 kDa on SDS-polyacrylamide gels, p66, released from Intestine 407 cells following incubation with phosphatidylinositol-specific phospholipase C (PI-PLC) treatment, bound A. sobria hemolysin. Thus treatment of Intestine 407 cells with PI-PLC resulted in the remarkable decrease of the sensitivity to A. sobria hemolysin. These results are consistent with the hypothesis that p66, the binding protein for A. sobria hemolysin, is a glycosylphosphatidylinositol-anchored glycoprotein expressed on the surface of Intestine 407 cells and probably plays a role as a receptor for A. sobria hemolysin on the intestinal cells. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 8528523, Japan. Tokushima Bunri Univ, Fac Pharmaceut Sci, Dept Biochem, Tokushima 7708514, Japan. Tokushima Bunri Univ, Fac Pharmaceut Sci, Inst Pharmacognosy, Tokushima 7708514, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. RI OKAMOTO, Keinosuke/B-2257-2011 NR 22 TC 9 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD OCT PY 1999 VL 27 IS 4 BP 215 EP 221 DI 10.1006/mpat.1999.0299 PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA 245EK UT WOS:000083093100004 PM 10502462 ER PT J AU van Leeuwen, JEM Paik, PK Samelson, LE AF van Leeuwen, JEM Paik, PK Samelson, LE TI The oncogenic 70Z Cbl mutation blocks the phosphotyrosine binding domain-dependent negative regulation of ZAP-70 by c-Cbl in Jurkat T cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; PROTEIN-TYROSINE KINASE; OF-FUNCTION MUTATION; ANTIGEN-RECEPTOR; SIGNAL-TRANSDUCTION; EGF RECEPTOR; PHOSPHORYLATION SITES; DISTINCT PATHWAYS; ERBB RECEPTORS; DOMINANT ROLE AB T-cell receptor (TCR) engagement results in the activation of Src family (Lck and Fyn) and ZAP-70 protein tyrosine kinases, leading to tyrosine phosphorylation of multiple cellular substrates including the complex adapter protein c-Cbl. Moreover, Cbl is tyrosine phosphorylated upon engagement of growth factor receptors, cytokine receptors, and immunoreceptors and functions as a negative regulator of tyrosine kinase signalling pathways. Cbl associates via its phosphotyrosine binding (PTB) domain to the ZAP-70 pY292 negative regulatory phosphotyrosine. me recently demonstrated that the oncogenic Cbl mutant, 70Z Cbl, requires its PTB domain to upregulate NFAT in unstimulated Jurkat T cells, Here, we demonstrate that kinase-dead but not wild-type forms of Fyn, Lck, and ZAP-70 block 70Z Cbl-mediated NFAT activation. Moreover, 70Z Cbl does not upregulate NFAT in the ZAP-70-deficient P116 Jurkat T-cell line. The requirement for Fyn, Lck, and ZAP-70 is not due to tyrosine phosphorylation of 70Z Cbl, as mutation of all tyrosines in, or deletion of, the C-terminal region of 70Z Cbl (amino acids 655 to 906) blocks 70Z Cbl tyrosine phosphorylation but enhances 70Z Cbl-mediated NFAT activation. Further, 70Z Cbl does not cooperate with ZAP-70 Y292F to upregulate NFAT, indicating that 70Z Cbl and ZAP-70 do not activate parallel signalling pathways, Finally, the upregulation of NFAT observed upon ZAP-70 overexpression is blocked by Cbl in a PTB domain-dependent manner. We conclude that oncogenic 70Z Cbl acts as a dominant negative to block the PTB domain-dependent negative regulatory role of endogenous Cbl on ZAP-70, leading to constitutive ZAP-70 signalling and activation of transcription factors. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP van Leeuwen, JEM (reprint author), NCI, Cellular & Mol Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI van Leeuwen, Jeroen/G-3555-2010 NR 72 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1999 VL 19 IS 10 BP 6652 EP 6664 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200018 PM 10490604 ER PT J AU Chin, AID Shu, JY Shi, CS Yao, ZB Kehrl, JH Cheng, GH AF Chin, AID Shu, JY Shi, CS Yao, ZB Kehrl, JH Cheng, GH TI TANK potentiates tumor necrosis factor receptor-associated factor-mediated c-Jun N-terminal kinase/stress-activated protein kinase activation through the germinal center kinase pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KAPPA-B ACTIVATION; TRAF-INTERACTING PROTEIN; TNF RECEPTOR; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAIN; INDUCED APOPTOSIS; GROWTH-FACTOR; RING FINGER; FAMILY; STRESS AB Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are mediators of many members of the TNF receptor superfamily and can activate both the nuclear factor kappa B (NF-kappa B) and stress-activated protein kinase (SAPK; also known as c-jun N-terminal kinase) signal transduction pathways. We previously described the involvement of a TRAF-interacting molecule, TRAF-associated NF-kappa B activator (TANK), in TRAF2-mediated NF-kappa B activation. Here we show that TANK synergized with TRAF2, TRAF5, and TRAF6 but not with TRAF3 in SAPK activation. TRAF2 and TANK individually formed weak interactions with germinal center kinase (GCK)-related kinase (GCKR). However, when coexpressed, they formed a strong complex with GCKR, thereby providing a potential mechanism for TRAF and TANK synergy in GCKR-mediated SAPK activation, which is important in TNF family receptor signaling. Our results also suggest that TANK can form potential intermolecular as well as intramolecular interactions between its amino terminus and carboxyl terminus. This study suggests that TANK is a regulatory molecule controlling the threshold of NF-kappa B and SAPK activities in response to activation of TNF receptors. In addition, CD40 activated endogenous GCKR in primary B cells, implicating GCK family proteins in CD40-mediated B-cell functions. C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Inst Mol Biol, Los Angeles, CA 90095 USA. NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Hoechst Marion Roussel, CNS Dept, Bridgewater, NJ 08807 USA. RP Cheng, GH (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA. OI Kehrl, John/0000-0002-6526-159X FU NIGMS NIH HHS [R01 GM057559, T32 GM008042, GM 08042, GM57559] NR 60 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1999 VL 19 IS 10 BP 6665 EP 6672 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200019 PM 10490605 ER PT J AU Sakaguchi, K Lorenzi, MV Bottaro, DP Miki, T AF Sakaguchi, K Lorenzi, MV Bottaro, DP Miki, T TI The acidic domain and first immunoglobulin-like loop of fibroblast growth factor receptor 2 modulate downstream signaling through glycosaminoglycan modification SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEPARAN-SULFATE; PROTEOLYTIC DEGRADATION; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; FACTOR FAMILY; FGF; BINDING; ACTIVATION; SPECIFICITY; EXPRESSION AB Fibroblast growth factor receptors (FGFRs) are membrane-spanning tyrosine kinases that have been implicated in a variety of biological processes including mitogenesis, cell migration, development, and differentiation. We identified a unique isoform of FGFR2 expressed as a diffuse band with an unusually large molecular mass. This receptor is modified by glycosaminoglycan at a Ser residue located immediately N terminal to the acidic box, a stretch of acidic amino acids. The acidic box and the glycosaminoglycan modification site are encoded by an alternative exon of the FGFR2 gene. The acidic box appears to play an important role in glycosaminoglycan modification, and the presence of this domain is required for modification by heparan sulfate glycosaminoglycan. Moreover, the presence of the first immunoglobulin-like domain encoded by another alternative exon abrogated the modification. The high-affinity receptor with heparan sulfate modification enhanced receptor autophosphorylation, substrate phosphorylation, and ternary complex factor-independent gene expression. It also sustained mitogen-activated protein kinase activity and increased eventual DNA synthesis, a long-term response to fibroblast growth factor stimulation, at physiological ligand concentrations. We propose a novel regulation mechanism of FGFR2 signal transduction through glycosaminoglycan modification. C1 Wakayama Med Coll, Dept Mol Med, Wakayama 6418509, Japan. NIDR, Glycobiol Program, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wakayama Med Coll, Dept Mol Med, 811-1 Kimiidera, Wakayama 6418509, Japan. EM ksaka@wakayama-med.ac.jp RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 52 TC 12 Z9 12 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 1999 VL 19 IS 10 BP 6754 EP 6764 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200028 PM 10490614 ER PT J AU Kim, MK Nikodem, VM AF Kim, MK Nikodem, VM TI hnRNP U inhibits carboxy-terminal domain phosphorylation by TFIIH and represses RNA polymerase II elongation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR RIBONUCLEOPROTEIN-K; CDK-ACTIVATING KINASE; TRANSCRIPTION FACTOR; IN-VITRO; P-TEFB; SUBSTRATE-SPECIFICITY; MATRIX PROTEIN; REPEAT DOMAIN; SAF-A; BINDING AB This study describes a potential new function of hnRNP U as an RNA polymerase (Pol II) elongation inhibitor. We demonstrated that a subfraction of human hnRNP U is associated with the Pol II holoenzyme in vivo and as such recruited to the promoter as part of the preinitiation complex. hnRNP U, however, appears to dissociate from the Pol II complex at the early stage of transcription and is therefore absent from the elongating Pol II complex. When tested in the human immunodeficiency virus type I transcription system, hnRNP U inhibits elongation rather than initiation of transcription by Pol II. This inhibition requires the carboxy-terminal domain (CTD) of Pol II. We showed that hnRNP U can bind TFIIH in vivo under certain conditions and inhibit TFIIH-mediated CTD phosphorylation in vitro. We find that the middle domain of hnRNP U is sufficient to mediate its Pol II association and its inhibition of TFIIH-mediated phosphorylation and Pol II elongation. The abilities of hnRNP U to inhibit TFIIH-mediated CTD phosphorylation and its Pol II association are necessary for hnRNP U to mediate the repression of Pol II elongation. Based on these observations, we suggest that a subfraction of hnRNP U, as a component of the Pol II holoenzyme, may downregulate TFIIH-mediated CTD phosphorylation in the basal transcription machinery and repress Pol II elongation. With such functions, hnRNP U might provide one of the mechanisms by which the CTD is maintained in an unphosphorylated state in the Pol II holoenzyme. C1 NHLBI, Lab Mol Hematol, NIH, Bethesda, MD 20892 USA. NIDDKD, Mechanisms Gene Regulat Sect, Genet Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Kim, MK (reprint author), NHLBI, Lab Mol Hematol, NIH, Bldg 10,Room 7D11,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 57 TC 50 Z9 50 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1999 VL 19 IS 10 BP 6833 EP 6844 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200036 PM 10490622 ER PT J AU Basrai, MA Velculescu, VE Kinzler, KW Hieter, P AF Basrai, MA Velculescu, VE Kinzler, KW Hieter, P TI NORF5/HUG1 is a component of the MEC1-mediated checkpoint response to DNA damage and replication arrest in Saccharomyces cerevisiae SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID S-PHASE CHECKPOINT; CELL-CYCLE; RIBONUCLEOTIDE REDUCTASE; ATAXIA-TELANGIECTASIA; RAD9 CHECKPOINT; PROTEIN-KINASE; BUDDING YEAST; HUMAN GENE; TRANSCRIPTION; EXPRESSION AB Analysis of global gene expression in Saccharomyces cerevisiae by the serial analysis of gene expression technique has permitted the identification of at least 302 previously unidentified transcripts from nonannotated open reading frames (NORFs). Transcription of one of these, NORF5/HUG1 (hydroxyurea and UV and gamma radiation induced), is induced by DNA damage, and this induction requires MEC1, a homolog of the ataxia telangiectasia mutated (ATM) gene. DNA damage-specific induction of HUG1, which is independent of the cell cycle stage, is due to the alleviation of repression by the Crt1p-Ssn6p-Tup1p complex. Overexpression of HUG1 is lethal in combination with a mec1 mutation in the presence of DNA damage or replication arrest, whereas a deletion of HUG1 rescues the lethality due to a mec1 null allele. HUG1 is the first example of a NORF with important biological functional properties and defines a novel component of the MEC1 checkpoint pathway. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21231 USA. Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada. RP Basrai, MA (reprint author), NCI, Dept Genet, Div Clin Sci, Med Branch, Bethesda, MD 20889 USA. FU NCI NIH HHS [P01 CA016519, CA16519]; NICHD NIH HHS [HD24605, P01 HD024605] NR 49 TC 72 Z9 77 U1 2 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1999 VL 19 IS 10 BP 7041 EP 7049 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200055 PM 10490641 ER PT J AU Adler, HT Chinery, R Wu, DY Kussick, SJ Payne, JM Fornace, AJ Tkachuk, DC AF Adler, HT Chinery, R Wu, DY Kussick, SJ Payne, JM Fornace, AJ Tkachuk, DC TI Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HERPES-SIMPLEX VIRUS; YEAST SWI/SNF COMPLEX; DAMAGE-INDUCIBLE GENE; SWI-SNF COMPLEX; 11Q23 REARRANGEMENTS; MLL GENE; CHROMOSOMAL TRANSLOCATIONS; DROSOPHILA-TRITHORAX; TUMOR PROGRESSION AB One of the most common chromosomal abnormalities in acute leukemia is a reciprocal translocation involving the HRX gene (also called MLL, ALL-1, or HTRX) at chromosomal locus 11q23, resulting in the formation of HRX fusion proteins. Using the yeast two-hybrid system and human cell culture coimmunoprecipitation experiments, we show here that HRX proteins interact directly with the GADD34 protein. We have found that transfected cells overexpressing GADD34 display a significant increase in apoptosis after treatment with ionizing radiation, indicating that GADD34 expression not only correlates with apoptosis but also can enhance apoptosis. The amino-terminal third of the GADD34 protein was necessary for this observed increase in apoptosis. Furthermore, coexpression of three different HRX fusion proteins (HRX-ENL, HRX-AF9, and HRX-ELL) had an anti-apoptotic effect, abrogating GADD34-induced apoptosis. In contrast, expression of wild-type HRX gave rise to an increase in apoptosis. The difference observed here between wild-type HRX and the leukemic HRX fusion proteins suggests that inhibition of GADD34-mediated apoptosis may be important to leukemogenesis, We also show here that GADD34 binds the human SNF5/INI1 protein, a member of the SNF/SWI complex: that can remodel chromatin and activate transcription. These studies demonstrate, for the first time, a gain of function for leukemic HRX fusion proteins compared to wild-type protein. We propose that the role of HRX fusion proteins as negative regulators of post-DNA-damage-induced apoptosis is important to leukemia progression. C1 VA Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN 37232 USA. NCI, Div Basic Sci, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Tkachuk, DC (reprint author), VA Puget Sound Hlth Care Syst, Dept Pathol, 1660 S Columbian Way,Mail Stop 113, Seattle, WA 98108 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [CA73969, CA 68485, P30 CA068485] NR 60 TC 112 Z9 119 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1999 VL 19 IS 10 BP 7050 EP 7060 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200056 PM 10490642 ER PT J AU Zhu, SY Oh, HS Shim, M Sterneck, E Johnson, PF Smart, RC AF Zhu, SY Oh, HS Shim, M Sterneck, E Johnson, PF Smart, RC TI C/EBP beta modulates the early events of keratinocyte differentiation involving growth arrest and keratin 1 and keratin 10 expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EXTRACELLULAR CALCIUM CONCENTRATIONS; TERMINAL ADIPOCYTE DIFFERENTIATION; MOUSE SKIN CARCINOGENESIS; EPIDERMAL DIFFERENTIATION; TRANSCRIPTION FACTORS; GENE-EXPRESSION; NUCLEAR FACTOR; MESSENGER-RNA; IN-VITRO; FAMILY AB The epidermis is a stratified squamous epithelium composed primarily of keratinocytes that become postmitotic and undergo sequential changes in gene expression during terminal differentiation. The expression of the transcription factor CCAAT/enhancer binding protein beta (C/EBP beta) within mouse epidermis and primary keratinocytes has recently been described; however, the function of C/EBP beta within the epidermal keratinocyte is unknown. We report here that transient transfection of mouse primary keratinocytes with a C/EBP-responsive promoter-reporter construct resulted in a sevenfold increase in luciferase activity when keratinocytes were switched to culture conditions that induce growth arrest and differentiation. Forced expression of C/EBP beta in BALB/MK2 keratinocytes inhibited growth, induced morphological changes consistent with a more differentiated phenotype, and upregulated two early markers of differentiation, keratin 1 (K1) and keratin 10 (K10) but had a minimal effect on the expression of late-stage markers, loricrin and involucrin. Analysis of the epidermis of C/EBP beta-deficient mice revealed a mild epidermal hyperplasia and decreased expression of K1 and K10 but not of involucrin and loricrin. C/EBP beta-deficient primary keratinocytes were partially resistant to calcium-induced growth arrest. Analysis of terminally differentiated spontaneously detached keratinocytes or those induced to differentiate by suspension culture revealed that C/EBP beta-deficient keratinocytes displayed striking decreases in K1 and K10, while expression of later-stage markers was only minimally altered. Our results demonstrate that C/EBP beta plays an important role in the early events of stratified squamous differentiation in keratinocytes involving growth arrest and K1 and K10 expression. C1 N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. NCI, Eukaryot Transcript Regulat Grp, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Smart, RC (reprint author), N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 60 TC 102 Z9 107 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1999 VL 19 IS 10 BP 7181 EP 7190 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200067 PM 10490653 ER PT J AU Mullins, C Hartnell, LM Wassarman, DA Bonifacino, JS AF Mullins, C Hartnell, LM Wassarman, DA Bonifacino, JS TI Defective expression of the mu 3 subunit of the AP-3 adaptor complex in the Drosophila pigmentation mutant carmine SO MOLECULAR AND GENERAL GENETICS LA English DT Article DE clathrin; sorting; tyrosine-based signal; pigment; Hermansky-Pudlak syndrome ID CLATHRIN-ASSOCIATED PROTEINS; SORTING SIGNALS; ALPHA-ADAPTIN; MOLECULAR CHARACTERIZATION; VESICLE FORMATION; COATED VESICLES; YEAST VACUOLE; MEDIUM CHAINS; BINDING SITE; TRANSPORT AB The adaptor protein (AP) complexes AP-1, AP-2, and AP-3 mediate coated vesicle formation and sorting of integral membrane proteins in the endocytic and late exocytic pathways in mammalian cells. A search of the Drosophila melanogaster expressed sequence tag (EST) database identified orthologs of family members mammalian medium (II) chain families mu 1, mu 2, and mu 3, of the corresponding AP complexes, and delta-COP, the analogous component of the coatomer (COPI) complex. The Drosophila orthologs exhibit a high degree of sequence identity to mammalian medium chain and delta-COP proteins. Northern analysis demonstrated that medium chain and delta-COP mRNAs are expressed uniformly throughout fly development. Medium chain and delta-COP genes were cytologically mapped and the mu 3 gene was found to localize to a region containing the pigmentation locus carmine (cm). Analysis of genomic DNA of the cml mutant allele indicated the presence of a large insertion in the coding region of the mu 3 gene and Northern analysis revealed no detectable mu 3 mRNA. Light microscopy of the cm(1) mutant showed a reduction in primary, secondary, and tertiary pigment granules in the adult eye. These findings provide evidence of a role for mu 3 in the sorting processes required for pigment granule biogenesis in Drosophila. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. NR 65 TC 45 Z9 46 U1 2 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD OCT PY 1999 VL 262 IS 3 BP 401 EP 412 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 258KU UT WOS:000083839000001 PM 10589826 ER PT J AU Klymkowsky, MW Williams, BO Barish, GD Varmus, HE Vourgourakis, YE AF Klymkowsky, MW Williams, BO Barish, GD Varmus, HE Vourgourakis, YE TI Membrane-anchored plakoglobins have multiple mechanisms of action in Wnt signaling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ADENOMATOUS POLYPOSIS-COLI; BETA-CATENIN GENE; GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR LEF-1; TUMOR-SUPPRESSOR PROTEIN; EARLY XENOPUS-EMBRYOS; AXIS FORMATION; HEPATOCELLULAR CARCINOMAS; FUNCTIONAL INTERACTION; NUCLEAR-LOCALIZATION AB In Wnt signaling, beta-catenin and plakoglobin transduce signals to the nucleus through interactions with TCF-type transcription factors. However, when plakoglobin is artificially engineered to restrict it to the cytoplasm by fusion with the transmembrane domain of connexin (cnxPg), it efficiently induces a Wnt-like axis duplication phenotype in Xenopus. Ln Xenopus embryos, maternal XTCF3 normally represses ventral expression of the dorsalizing gene Siamois. Two models have been proposed to explain the Wnt-like activity of cnxPg: 1) that cnxPg inhibits the machinery involved in the turnover of cytosolic beta-catenin, which then accumulates and inhibits maternal XTCF3, and 2) that cnxPg directly acts to inhibit XTCF3 activity. To distinguish between these models, we created a series of N-terminal deletion mutations of cnxPg and examined their ability to induce an ectopic axis in Xenopus, activate a TCF-responsive reporter (OT), stabilize beta-catenin, and colocalize with components of the Wnt signaling pathway. cnxPg does not colocalize with the Wnt pathway component Dishevelled, but it does lead to the redistribution of APC and Axin, two proteins involved in the regulation of beta-catenin turnover. Expression of cnxPg increases levels of cytosolic beta-catenin; however, this effect does not completely explain its signaling activity. Although cnxPg and Wnt-1 stabilize beta-catenin to similar extents, cnxPg activates OT to 10- to 20-fold higher levels than Wnt-1. Moreover, although LEF1 and TCF4 synergize with beta-catenin and plakoglobin to activate OT, both suppress the signaling activity of cnxPg. In contrast, XTCF3 suppresses the signaling activity of both beta-catenin and cnxPg. Both exogenous XLEF1 and XTCF3 are sequestered in the cytoplasm of Xenopus cells by cnxPg. Based an these data, we conclude that, in addition to its effects on beta-catenin, cnxPg interacts with other components of the Wnt pathway, perhaps TCFs, and that these interactions contribute to its signaling activity. C1 Univ Colorado, Boulder, CO 80309 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Klymkowsky, MW (reprint author), Univ Colorado, Boulder, CO 80309 USA. RI Williams, Bart/A-3539-2013; OI Williams, Bart/0000-0002-5261-5301; Klymkowsky, Mike/0000-0001-5816-9771 FU NIGMS NIH HHS [GM54001, R01 GM054001] NR 96 TC 38 Z9 38 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 1999 VL 10 IS 10 BP 3151 EP 3169 PG 19 WC Cell Biology SC Cell Biology GA 245PE UT WOS:000083116700008 PM 10512857 ER PT J AU Jayanthi, S Ordonez, S McCoy, MT Cadet, JL AF Jayanthi, S Ordonez, S McCoy, MT Cadet, JL TI Dual mechanism of Fas-induced cell death in neuroglioma cells: a role for reactive oxygen species SO MOLECULAR BRAIN RESEARCH LA English DT Article DE reactive oxygen species; superoxide dismutase; catalase; neuroglioma; anti-Fas antibody ID TUMOR-NECROSIS-FACTOR; FREE-RADICALS; SUPEROXIDE-DISMUTASE; SURFACE ANTIGEN; POLY(ADP-RIBOSE) SYNTHETASE; MONOCLONAL-ANTIBODY; MEDIATED APOPTOSIS; CYTOCHROME-C; IN-VITRO; T-CELLS AB ApoI/Fas belongs to the tumor necrosis factor receptor (TNFR) superfamily and mediates cell death in various cell types. A dual mode of Fas-triggered cell death has been reported depending on cell types used in the experiments. The present study was carried out to test the possible role of reactive oxygen species in this dual mechanism in neuroglioma cells. Anti-Fas antibody caused dose-dependent and time-dependent increase in cell death measured by lactate dehydrogenase (LDH) release in control neuroglioma cells and in cells that were transfected with catalase cDNA. However, cells transfected with copper/zinc superoxide dismutase (Cu/ZnSOD) cDNA showed marked attenuation of Fas-induced LDH release. Moreover, flow cytometry and confocal microscopy revealed that Fas-induced cell death in control cells occur mostly through an apoptotic process. This process was also completely abrogated in cells overexpressing catalase or copper/zinc superoxide dismutase (Cu/ZnSOD). Further experiments revealed that Fas-induced cell death was associated with increased formation of superoxide anions in control neuroglioma cells and in cells overexpressing catalase. These increases were significantly suppressed by Cu/ZnSOD overexpression. These data indicate that Fas-mediated cell death in neuroglioma cells occur, in part, through the production of reactive oxygen species (ROS). These observations also suggest that Fas-induced cell death in these cells occur through apoptosis and necrosis. Thus overexpression of Cu/ZnSOD caused the suppression of both types of Fas-induced cell death whereas catalase prevented apoptotic but not necrotic cell death. These observations are discussed in terms of their support for a role for both peroxides and superoxide radicals in Fas-induced cell death. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NIDA, Mol Neuropsychiat Sect, NIH, Div Intramural Res Programs, Baltimore, MD 21224 USA. RP NIDA, Mol Neuropsychiat Sect, NIH, Div Intramural Res Programs, POB 5180, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov NR 47 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 1 PY 1999 VL 72 IS 2 BP 158 EP 165 DI 10.1016/S0169-328X(99)00216-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 245MZ UT WOS:000083113900006 ER PT J AU Zhang, PS Johnson, PS Zollner, C Wang, WF Wang, ZJ Montes, AE Seidleck, BK Blaschak, CJ Surratt, CK AF Zhang, PS Johnson, PS Zollner, C Wang, WF Wang, ZJ Montes, AE Seidleck, BK Blaschak, CJ Surratt, CK TI Mutation of human mu opioid receptor extracellular "disulfide cysteine'' residues alters ligand binding but does not prevent receptor targeting to the cell plasma membrane SO MOLECULAR BRAIN RESEARCH LA English DT Article DE morphine; G protein; agonist; substance abuse ID SITE-DIRECTED MUTAGENESIS; HORMONE RECEPTOR; N-ETHYLMALEIMIDE; SELECTIVITY; SULFHYDRYL; AFFINITY; AGONIST; DISTINGUISHES; INACTIVATION; RHODOPSIN AB The FL opioid receptor, a primary site of action in the brain for opioid neuropeptides and opiate drugs of abuse, is a member of the seven transmembrane, G protein-coupled receptor (GPCR) superfamily. Two cysteine residues, one in each of the first two of three extracellular loops (ECLs), are highly conserved among GPCRs, and there is direct or circumstantial evidence that the residues form a disulfide bond in many of these receptors. Such a bond would dramatically govern the topology of the ECLs, and possibly affect the position of the membrane-spanning domains. Recent findings from several laboratories indicate the importance of the ECLs for opioid ligand selectivity. These conserved cysteine residues in the mu opioid receptor were studied using site-directed mutagenesis. Little or no specific binding of radiolabled opiate alkaloid or opioid peptide agonists or antagonists was observed for receptors mutated at either "disulfide cysteine" residue. Each mutant mu opioid receptor was expressed in both transiently- and stably-transfected cells, in some cases at levels comparable to the wild type receptor. The two point mutants possessing serine-for-cysteine substitutions were also observed to successfully reach the cell plasma membrane, as evidenced by electron microscopy. Consistent with related work with other GPCRs, the mu opioid receptor apparently also employs the extracellular disulfide bond. This information now permits accurate molecular modeling of extracellular aspects of the receptor, including plausible scenarios of mu receptor docking of opioid Ligands known to require specific extracellular loop features for high affinity binding. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Surratt, CK (reprint author), Albert Einstein Coll Med, Dept Neurosci, 1410 Pelham Pkwy S, Bronx, NY 10461 USA. NR 30 TC 27 Z9 31 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 1 PY 1999 VL 72 IS 2 BP 195 EP 204 DI 10.1016/S0169-328X(99)00241-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 245MZ UT WOS:000083113900010 ER PT J AU Pascale, A Bhagavan, S Nelson, TJ Neve, RL McPhie, DL Etcheberrigaray, R AF Pascale, A Bhagavan, S Nelson, TJ Neve, RL McPhie, DL Etcheberrigaray, R TI Enhanced BK-induced calcium responsiveness in PC12 cells expressing the C100 fragment of the amyloid precursor protein SO MOLECULAR BRAIN RESEARCH LA English DT Article DE PC12; C100; bradykinin; calcium ID FAMILIAL ALZHEIMERS-DISEASE; CARBOXYL-TERMINAL FRAGMENT; BETA-PROTEIN; INOSITOL 1,4,5-TRISPHOSPHATE; APP670/671 MUTATION; NEUROTOXICITY; PEPTIDE; ACCUMULATION; FIBROBLASTS; RELEASE AB Several lines of evidence have implicated the amyloid precursor protein (APP) and its metabolic products as key players in Alzheimer's disease (AD) pathophysiology. The approximately 100 amino acid C-terminal fragment (C100) of APP has been shown to accumulate intracellularly in neurons expressing familial AD (FAD) mutants of APP and to cause neurodegeneration when expressed in transfected neuronal cells. Transgenic animals expressing this fragment in the brain also exhibit some neuropathological and behavioral AD-like deficits. Here, we present evidence that PC12 cells expressing the C100 fragment either via stable transfections or herpes simplex virus-mediated infections show alterations in calcium handling that are similar to those previously shown in fibroblasts from AD patients. This alteration in calcium homeostasis may contribute to the deleterious effects of C100 in PC12 cells. Our data also lend support for a pathophysiological role for C100 since it induces an alteration thought to play an important role in AD pathology. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Georgetown Univ, Med Ctr, Lab Appl Neurosci, Inst Cognit & Computat Sci, Washington, DC 20007 USA. NINDS, Lab Adapt Syst, Bethesda, MD 20892 USA. Harvard Univ, McLean Hosp, Sch Med, Dept Genet, Belmont, MA 02178 USA. RP Etcheberrigaray, R (reprint author), NeuroLog, 9700 Great Seneca Highway,Suite 220, Rockville, MD 20850 USA. NR 55 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 1 PY 1999 VL 72 IS 2 BP 205 EP 213 DI 10.1016/S0169-328X(99)00223-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 245MZ UT WOS:000083113900011 ER PT J AU Lim, IK Park, SC Song, KY Park, TJ Lee, MS Kim, SJ Hyun, BH AF Lim, IK Park, SC Song, KY Park, TJ Lee, MS Kim, SJ Hyun, BH TI Regulation of selection of liver nodules initiated with N-nitrosodiethylamine and promoted with nodularin injections in Fischer 344 male rats by reciprocal expression of transforming growth factor-beta 1 and its receptors SO MOLECULAR CARCINOGENESIS LA English DT Article DE glutathione-s-transferase placental form; transforming growth factor-beta receptors; hepatocarcinogenesis; liver regeneration ID TGF-BETA RECEPTOR; HUMAN HEPATOCELLULAR-CARCINOMA; II RECEPTOR; KARYOTYPIC CHANGES; TUMOR PROMOTION; MESSENGER-RNA; CELLS; HEPATOCYTES; APOPTOSIS; GENES AB To investigate how glutathione-s-transferase placental form (GST-P)+ hyperplastic nodules (HNs) are selected and to determine the driving force for progression or regression of HNs, changes in transforming growth factor-beta 1 (TGF-beta) and its receptors were examined during hepatocarcinogenesis initiated by N-nitrosodiethylamine (DEN) and promoted by nodularin. The induction of TGF-beta 1 expression in the GST-P+ HNs was dependent on nodularin injections for 10 wk, which started the third week after DEN initiation. The kinetics of TGF-beta 1 induction during carcinogenesis were quite different from that of simple regeneration after partial hepatectomy (PH): hepatocytes initiated with DEN alone induced TGF-beta 1 expression for 24 d, and subsequent stimulation by PH on the fourteenth day after DEN initiation super-induced TGF-beta 1 mRNA (50 times that of the control level), as opposed to a transient expression for less than 5 d by PH alone. GST-P+ HNs did not express TGF-beta receptors I (RI) and II (RII) during the early stage of carcinogenesis, whereas the surrounding hepatocytes strongly expressed both of these receptors. On cessation of nodularin injection, however, the expression of RI and RII in the HNs changed significantly: RII+ nodules appeared, and the number and area of RII+/- nodules were significantly increased at 10 wk after the cessation. These findings indicate that induction of TGF-beta expression in GST-P+ HNs might be a strong selection pressure that allows outgrowth of RII- nodules during liver carcinogenesis. (C) 1999 Wiley-Liss, Inc. C1 Ajou Univ, Sch Med, Dept Biochem & Mol Biol, Suwon 442749, South Korea. Seoul Natl Univ, Coll Med, Dept Biochem, Seoul, South Korea. Chung Ang Univ, Coll Med, Dept Pathol, Seoul 156756, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Res Inst Biosci & Biotechnol, Yusong, South Korea. RP Lim, IK (reprint author), Ajou Univ, Sch Med, Dept Biochem & Mol Biol, Suwon 442749, South Korea. NR 41 TC 12 Z9 14 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 1999 VL 26 IS 2 BP 83 EP 92 DI 10.1002/(SICI)1098-2744(199910)26:2<83::AID-MC3>3.0.CO;2-4 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 243CB UT WOS:000082978600003 PM 10506752 ER PT J AU Ondrey, FG Dong, G Sunwoo, J Chen, Z Wolf, JS Crowl-Bancroft, CV Mukaida, N Van Waes, C AF Ondrey, FG Dong, G Sunwoo, J Chen, Z Wolf, JS Crowl-Bancroft, CV Mukaida, N Van Waes, C TI Constitutive activation of transcription factors NF-kappa B, AP-1, and NF-IL6 in human head and neck squamous cell carcinoma cell lines that express pro-inflammatory and pro-angiogenic cytokines SO MOLECULAR CARCINOGENESIS LA English DT Article DE transcription factors; NF-kappa B; AP-1; NF-IL6; cytokine; interleukin-1 alpha; interleukin-6; interleukin-8; granulocyte-macrophage colony-stimulating factor ID NEOPLASTIC TRANSFORMATION; INTERLEUKIN-8 GENE; DNA-BINDING; I TAX; ALPHA; PROLIFERATION; PROMOTER; CANCER; TUMOR; DIFFERENTIATION AB We previously reported that human head and neck squamous cell carcinomas (HNSCCs) express the proinflammatory and pro-angiogenic cytokines interleukin (IL)-1 alpha, IL-6, IL-8, and granulocyte-macrophage colony stimulating factor in vitro and in vive. The promoter region of the genes encoding these cytokines include binding sites for the transcription factors nuclear factor (NF) KB/Rel A, activator protein-1 (AP-1), and CCAAT enhancer-binding protein beta (C/EBPP, or NF-IL6), which have been reported to contribute to activation of these cytokine genes. In the study presented here, we examined the activation, composition, and function of these transcription factors in HNSCC cell lines that express pro-inflammatory cytokines, by using electrophoretic mobility shift and reporter-gene assays. Constitutive activation of NF-kappa B, AP-1, and NF-IL6 DNA-binding proteins was detected. Supershift analysis with antibodies specific for NF-kappa B, AP-1, and NF-IL6 binding proteins showed that the NF-kappa B-binding protein included p65/Rel A and p50; AP-1 activity included c-jun, junB, junD, and Fra-1; and NF-IL6 included C/EBPP. Mutational analysis of the NF-kappa B, AP-1, and NF-IL6 sites in the IL-8 promoter region showed that NF-kappa B and AP-1 sites contributed to constitutive IL-8 reporter activity in HNSCC. HNSCC lines that exhibited increased IL-8 secretion relative to simian virus 40-immortalized and primary keratinocyte cell lines also demonstrated a concordant increase in NF-kappa B reporter activity relative to nonmalignant keratinocytes. We concluded that the early transcription factors NF-kappa B, AP-1, and NF-IL6 are constitutively activated in human HNSCC cell lines and that NF-kappa B and AP-1 promote expression of the proinflammatory and pro-angiogenic cytokine IL-8 in HNSCC. The demonstration of the activation of these transcription factors will be helpful in defining the identity and role of these and other early gene products that contribute to pathogenesis of the malignant phenotype in HNSCC and in defining potential targets for pharmacologic and molecular therapy of HNSCC. Published 1999 Wiley-Liss, Inc.(dagger). C1 NIDCD, HNSB, Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. Kanazawa Univ, Canc Res Inst, Div Mol Pharmacol, Kanazawa, Ishikawa 920, Japan. RP Van Waes, C (reprint author), NIDCD, HNSB, Tumor Biol Sect, NIH, Bldg 10,Rm 5D55,10 Ctr Dr, Bethesda, MD 20892 USA. RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 FU NIDCD NIH HHS [DC-00016] NR 44 TC 190 Z9 193 U1 0 U2 5 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 1999 VL 26 IS 2 BP 119 EP 129 DI 10.1002/(SICI)1098-2744(199910)26:2<119::AID-MC6>3.0.CO;2-N PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 243CB UT WOS:000082978600006 PM 10506755 ER PT J AU Recio, JA Zambrano, N de la Pena, L Powers, C Siwarski, D Huppi, K Notario, V AF Recio, JA Zambrano, N de la Pena, L Powers, C Siwarski, D Huppi, K Notario, V TI cDNA isolation, expression, and chromosomal localization of the mouse Pcph proto-oncogene SO MOLECULAR CARCINOGENESIS LA English DT Article DE carcinogenesis; molecular cloning; sequencing; linkage analysis ID MICE; CPH; FIBROBLASTS; PROTEINS; CELLS; GENE; RAS AB We report here the isolation and characterization of a cDNA from mouse thymus encoding the murine homolog of the protein product of the Syrian hamster Pcph proto-oncogene. The single open reading frame identified in the cDNA sequence encoded a protein predicted to have 428 amino acids, which shared 93.7% amino acid identity with the Syrian hamster Pcph within the first 412 residues but had a shorter, highly dissimilar C-terminus. Northern and western analyses revealed that Pcph mRNA and protein were widely distributed in mouse embryo and adult tissues, with the highest expression in adults detected in kidney and liver. The mouse Pcph proto-oncogene was mapped by linkage analysis to within 3.3 +/- 2.3 cM of Pkch-rs1 I on chromosome 12. These data should prove valuable in designing studies to define the cellular function of the Pcph proto-oncogene. (C) 1999 Wiley-Liss, Inc. C1 Georgetown Univ, Med Ctr, Dept Radiat Med, Expt Carcinogenesis Lab, Washington, DC 20007 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Notario, V (reprint author), Georgetown Univ, Med Ctr, Dept Radiat Med, Expt Carcinogenesis Lab, Res Bldg,Room E215A,3970 Reservoir Rd NW, Washington, DC 20007 USA. RI Powers, Ciaran/E-3890-2011 FU NCI NIH HHS [P30 CA 51008, CA 64472] NR 23 TC 12 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 1999 VL 26 IS 2 BP 130 EP 136 DI 10.1002/(SICI)1098-2744(199910)26:2<130::AID-MC7>3.0.CO;2-N PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 243CB UT WOS:000082978600007 PM 10506756 ER PT J AU Zorn, AM Barish, GD Williams, BO Lavender, P Klymkowsky, MW Varmus, HE AF Zorn, AM Barish, GD Williams, BO Lavender, P Klymkowsky, MW Varmus, HE TI Regulation of Wnt signaling by sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin SO MOLECULAR CELL LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR LEF-1; XENOPUS EMBRYOS; AXIS SPECIFICATION; SPEMANN ORGANIZER; BINDING-SITES; DNA-BINDING; GENE; DROSOPHILA; DOMAIN AB Using a functional screen in Xenopus embryos, we identified a novel function for the HMG box protein XSox17 beta. Ectopic expression of XSox17 beta ventralizes embryos by inhibiting the Wnt pathway downstream of beta-catenin but upstream of the Wnt-responsive gene Siamois. XSox17 beta also represses transactivation of a TCF/LEF-dependent reporter construct by Wnt and beta-catenin. In animal cap experiments, it both activates transcription of endodermal genes and represses beta-catenin-stimulated expression of dorsal genes. The inhibition activity of XSox17 beta maps to a region C-terminal to the HMG box; this region of XSox17 beta physically interacts with the Armadillo repeats of beta-catenin. Two additional Sox proteins, XSox17 alpha and XSox3, likewise bind to beta-catenin and inhibit its TCF-mediated signaling activity. These results reveal an unexpected mechanism by which Sox proteins can modulate Wnt signaling pathways. C1 Wellcome Trust, Canc Res Campaign, Inst Canc & Dev Biol, Cambridge CB2 1QR, England. Univ London Kings Coll, Dept Resp Med & Allergy, London SE1 9RT, England. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Colorado, Boulder, CO 80309 USA. RP Zorn, AM (reprint author), Wellcome Trust, Canc Res Campaign, Inst Canc & Dev Biol, Tennis Court Rd, Cambridge CB2 1QR, England. RI Williams, Bart/A-3539-2013 OI Williams, Bart/0000-0002-5261-5301 FU NIGMS NIH HHS [GM54001]; Wellcome Trust NR 60 TC 252 Z9 262 U1 1 U2 7 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 1999 VL 4 IS 4 BP 487 EP 498 DI 10.1016/S1097-2765(00)80200-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249WR UT WOS:000083356700004 PM 10549281 ER PT J AU Natarajan, K Jackson, BM Zhou, H Winston, F Hinnebusch, AG AF Natarajan, K Jackson, BM Zhou, H Winston, F Hinnebusch, AG TI Transcriptional activation by Gcn4p involves independent interactions with the SWI/SNF complex and the SRB/mediator SO MOLECULAR CELL LA English DT Article ID RNA-POLYMERASE-II; TATA-BINDING PROTEIN; SACCHAROMYCES-CEREVISIAE; HISTONE ACETYLATION; COACTIVATOR COMPLEX; YEAST GCN5P; IN-VITRO; EXPRESSION; HOLOENZYME; SAGA AB Mutations in three subunits of the SWI/SNF complex and in the Med2p subunit of the SRB/mediator of pol II holoenzyme impaired Gcn4p-activated transcription of HIS3 without reducing Gcn4p-independent transcription of this gene. Recombinant Gcn4p interacted with SWI/SNF and SRB/mediator subunits in cell extracts in a manner dependent on the same hydrophobic clusters in the Gcn4p activation domain; however, higher concentrations of Gcn4p were required for binding to SWI/SNF versus SRB/mediator subunits. In addition, SRB/mediator and SWI/SNF subunits did not coimmunopreciptate from the extracts. These findings, together with the fact that Gcn4p specifically interacted with purified SWI/SNF, strongly suggest that Gcn4p independently recruits SWI/SNF and holoenzyme to its target promoters in the course of activating transcription. C1 NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM32967] NR 47 TC 125 Z9 125 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 1999 VL 4 IS 4 BP 657 EP 664 DI 10.1016/S1097-2765(00)80217-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249WR UT WOS:000083356700021 PM 10549298 ER PT J AU Bandyopadhyay, G Standaert, ML Sajan, MP Karnitz, LM Cong, L Quon, MJ Farese, RV AF Bandyopadhyay, G Standaert, ML Sajan, MP Karnitz, LM Cong, L Quon, MJ Farese, RV TI Dependence of insulin-stimulated glucose transporter 4 translocation on 3-phosphoinositide-dependent protein kinase-1 and its target threonine-410 in the activation loop of protein kinase C-zeta SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GLUCOSE-TRANSPORTER-4 TRANSLOCATION; PHOSPHATIDYLINOSITOL 3-KINASE; 3T3-L1 ADIPOCYTES; POTENTIAL ROLE; AKT; REQUIREMENT AB Previous studies have suggested that 1) atypical protein kinase C (PKC) isoforms are required for insulin stimulation of glucose transport; and 2) 3-phosphoinositide-dependent protein kinase-1 (PDK-1) is required for activation of atypical PKCa. presently, we evaluated the role of PDK-1, both in the activation of PKC-zeta, and the translocation of epitope-tagged glucose transporter 4 (GLUT4) to the plasma membrane, during insulin action in transiently transfected rat adipocytes. Overexpression of wild-type PDK-1 provoked increases in the activity of cotransfected hemagglutinin (HA)-tagged PKC-zeta and concomitantly enhanced HA-tagged GLUT4 translocation. Expression of both kinase-inactive PDK-1 and an activation-resistant form of PKC-zeta that is mutated at Thr-410, the immediate target of PDK-1 in the activation loop of PKC-zeta, inhibited insulin-induced increases in both HA-PKC-zeta activity and HA-GLUT4 translocation to the same extent as kinase-inactive PKC-zeta. Moreover, the inhibitory effects of kinase-inactive PDK-1 were fully reversed by cotransfection of wild-type PDK-1 and partly reversed by wild-type PKC-zeta but not by wild-type PKB. In contrast to the T410A PKC-zeta mutant, an analogous double mutant of PKB (T308A/S473A) that is resistant to PDK-1 activation had only a small effect on insulin-stimulated HA-GLUT4 translocation and did not inhibit HA-GLUT4 translocation induced by overexpression of wild-type PDK-1. Our findings suggest that both PDK-1 and its downstream target, Thr-410 in the activation loop of PKC-zeta, are required for insulin-stimulated glucose transport. C1 James A Haley Vet Hosp, Res Serv VAR 151, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA. Mayo Clin & Mayo Fdn, Dept Radiat Oncol, Rochester, MN 55905 USA. NHLBI, Hypertens Endocrine Branch, Bethesda, MD 20892 USA. RP Farese, RV (reprint author), James A Haley Vet Hosp, Res Serv VAR 151, 13000 Bruce B Downs Blvd, Tampa, FL 33612 USA. RI Quon, Michael/B-1970-2008; Farese, Robert/B-3605-2015 FU NIDDK NIH HHS [2R01DK-38079-09A1, R01 DK065969] NR 18 TC 66 Z9 70 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1999 VL 13 IS 10 BP 1766 EP 1772 DI 10.1210/me.13.10.1766 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 242AF UT WOS:000082915500012 PM 10517677 ER PT J AU Wallis, DE Muenke, M AF Wallis, DE Muenke, M TI Molecular mechanisms of holoprosencephaly SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE holoprosencephaly; forebrain development; sonic hedgehog; ZICS; SIX3; nodal; one-eyed pinhead; TGIF ID LEMLI-OPITZ-SYNDROME; BONE MORPHOGENETIC PROTEINS; POLARITY GENE HEDGEHOG; MURINE HOMEOBOX GENE; TGF-BETA SUPERFAMILY; SONIC-HEDGEHOG; SIGNALING PATHWAY; EYE DEVELOPMENT; RETINOIC ACID; FLOOR PLATE AB Holoprosencephaly (HPE) is the most common developmental defect of the forebrain in humans. Several distinct human genes for holoprosencephaly have now been identified. They include Sonic hedgehog (SBR), ZIC2, and SIX3. Many additional genes involved in forebrain development are rapidly being cloned and characterized in model vertebrate organisms. These include Patched (Pfc), Smoothened (Smo), cubitus interuptus (ci)/Gli wingless (wg/Wnt, decapentaplegic (dpp)/BMP, Hedgehog interacting protein (Hip), nodal, Smads, One-eyed pinhead (Oep), and TO-Interacting Factor (TGIF). However, further analysis is needed before their roles in HPE can be established. Here we present an overview of the presently known genes causing human holoprosencephaly and describe candidate genes involved in forebrain development identified in other systems. A model is discussed for how these genes may interact within and between several different signaling pathways to direct the formation of the forebrain. (C) 1999 Academic Press. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Wallis, DE (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. NR 132 TC 90 Z9 91 U1 0 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD OCT PY 1999 VL 68 IS 2 BP 126 EP 138 DI 10.1006/mgme.1999.2895 PG 13 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 251DD UT WOS:000083428600003 PM 10527664 ER PT J AU Hehr, U Muenke, M AF Hehr, U Muenke, M TI Craniosynostosis syndromes: From genes to premature fusion of skull bones SO MOLECULAR GENETICS AND METABOLISM LA English DT Review ID GROWTH-FACTOR RECEPTOR-2; SAETHRE-CHOTZEN-SYNDROME; BEARE-STEVENSON-SYNDROME; JACKSON-WEISS-SYNDROME; AUTOSOMAL-DOMINANT CRANIOSYNOSTOSIS; APPARENTLY BALANCED TRANSLOCATIONS; IMMUNOGLOBULIN-LIKE DOMAIN; CUTIS-GYRATA SYNDROME; CROUZON-SYNDROME; PFEIFFER-SYNDROME C1 Univ Halle Wittenberg, Dept Human Genet & Med Biol, Halle, Germany. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Hehr, U (reprint author), Univ Halle Wittenberg, Dept Human Genet & Med Biol, Halle, Germany. FU NICHD NIH HHS [HD29862, HD28732] NR 112 TC 58 Z9 59 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD OCT PY 1999 VL 68 IS 2 BP 139 EP 151 DI 10.1006/mgme.1999.2915 PG 13 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 251DD UT WOS:000083428600004 PM 10527665 ER PT J AU Tayebi, N Stone, DL Sidransky, E AF Tayebi, N Stone, DL Sidransky, E TI Type 2 Gaucher disease: An expanding phenotype SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE glucocerebrosidase deficiency; hydrops fetalis; congenital ichthyosis; genotype; lethal ID HUMAN GLUCOCEREBROSIDASE GENE; NONIMMUNE HYDROPS-FETALIS; PERMEABILITY BARRIER; CONGENITAL ICHTHYOSIS; TARGETED DISRUPTION; MOUSE MODEL; MUTATIONS; IDENTIFICATION; DEFICIENCY; PSEUDOGENE C1 NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, NIH, Bldg 49,Room B1EE16,49 Convent Dr,MSC4405, Bethesda, MD 20892 USA. EM sidranse@irp.nimh.nih.gov NR 80 TC 25 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD OCT PY 1999 VL 68 IS 2 BP 209 EP 219 DI 10.1006/mgme.1999.2918 PG 11 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 251DD UT WOS:000083428600010 PM 10527671 ER PT J AU Introne, W Boissy, RE Gahl, WA AF Introne, W Boissy, RE Gahl, WA TI Clinical, molecular, and cell biological aspects of Chediak-Higashi syndrome SO MOLECULAR GENETICS AND METABOLISM LA English DT Review ID HERMANSKY-PUDLAK-SYNDROME; STORAGE POOL DEFICIENCY; BONE-MARROW TRANSPLANTATION; MOUSE CHROMOSOME-13; GRISCELLI-SYNDROME; ACCELERATED PHASE; PROTEIN COMPLEX; SORTING SIGNALS; SYNDROME GENE; MYOSIN-V AB Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by variable degrees of oculocutaneous albinism, easy bruisability, and bleeding as a result of deficient platelet dense bodies, and recurrent infections, with neutropenia, impaired chemotaxis and bactericidal activity, and abnormal NK cell function. Neurologic involvement is variable, but often includes peripheral neuropathy. Most patients also undergo an "accelerated phase," which is a nonmalignant lymphohistiocytic infiltration of multiple organs resembling lymphoma. Death often occurs in the first decade from infection, bleeding, or development of the accelerated phase. The hallmark of CHS is the presence of huge cytoplasmic granules in circulating granulocytes and many other cell types. These granules are peroxidase-positive and contain lysosomal enzymes, suggesting that they are giant lysosomes or, in the case of melanocytes, giant melanosomes, The underlying defect in CHS remains elusive, but the disorder can be considered a model for defects in vesicle formation, fusion, or trafficking. Because the beige mouse demonstrates many characteristics similar to those of human CHS patients, including dilution of coat color, recurrent infections, and the presence of giant granules, it is considered the animal homologue of CHS. The beige gene, Lyst, was mapped and sequenced in 1996, prompting identification of the human LYST gene on chromosome 1q42. Lyst and LYST show 86.5% sequence homology. LYST encodes a 429 kDa protein with a function that remains unknown, but the source of extensive speculation among students of cell biology. (C) 1999 Academic Press. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH USA. RP Introne, W (reprint author), NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 144 TC 147 Z9 159 U1 1 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD OCT PY 1999 VL 68 IS 2 BP 283 EP 303 DI 10.1006/mgme.1999.2927 PG 21 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 251DD UT WOS:000083428600019 PM 10527680 ER EF