FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Philibert, RA St Jean, PL Schork, NJ Anderson, MC Dalwadi, H Damschroder-Williams, PJ Doherty, AE Dymarskaia, I Ehlert, M Murray, M Galdzicka, M Ingraham, LJ Lau, E Long, RT Patel, A Paul, SP Remortel, BG Stubblefield, BK Martin, BM Allen, CR Pauls, DL Elston, RC Egeland, JA Paul, SM Ginns, EI AF Philibert, RA St Jean, PL Schork, NJ Anderson, MC Dalwadi, H Damschroder-Williams, PJ Doherty, AE Dymarskaia, I Ehlert, M Murray, M Galdzicka, M Ingraham, LJ Lau, E Long, RT Patel, A Paul, SP Remortel, BG Stubblefield, BK Martin, BM Allen, CR Pauls, DL Elston, RC Egeland, JA Paul, SM Ginns, EI TI Update on candidate susceptibility loci identified from a genome-wide search for chromosome regions linked to bipolar affective disorder in the old order amish. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Univ Miami, Sch Med, Dept Psychiat, Hershey, PA USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1612 BP A277 EP A277 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001614 ER PT J AU Pilz, DT Macha, ME Precht, KS Dobyns, WB Smith, ACM Ledbetter, DH AF Pilz, DT Macha, ME Precht, KS Dobyns, WB Smith, ACM Ledbetter, DH TI FISH analysis in 100 patients with Isolated Lissencephaly Sequence (ILS): LIS1 probes significantly increase deletion detection rate. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Chicago, Ctr Med Genet, Chicago, IL 60637 USA. Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 162 BP A32 EP A32 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000165 ER PT J AU Platte, P Pugh, EW Wilson, AF Bailey-Wilson, JE Stunkard, AJ AF Platte, P Pugh, EW Wilson, AF Bailey-Wilson, JE Stunkard, AJ TI Segregation analysis of body size in the Old Order Amish SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Natl Human Genome Res Inst, Baltimore, MD USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1206 BP A208 EP A208 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001208 ER PT J AU Plotz, P Becker, J Lee, L Hermans, M Reuser, A Huie, M Hirschhorn, R Raben, N AF Plotz, P Becker, J Lee, L Hermans, M Reuser, A Huie, M Hirschhorn, R Raben, N TI Glycogen storage disease type II in Africans and African-Americans. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, ARB, NIH, Bethesda, MD USA. Erasmus Univ, NL-3000 DR Rotterdam, Netherlands. NYU, New York, NY 10003 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1507 BP A259 EP A259 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001508 ER PT J AU Pras, E Aksentijevich, I Balow, JE Pras, M Kastner, DL AF Pras, E Aksentijevich, I Balow, JE Pras, M Kastner, DL TI Genotype analysis of unaffected sibs in families with familial Mediterranean fever does not reveal evidence for heterozygote advantage. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Chaim Sheba Med Ctr, Inst Human Genet, Tel Hashomer, Israel. Chaim Sheba Med Ctr, Inst Human Genet, Tel Hashomer, Israel. Chaim Sheba Med Ctr, Dept Med F, Tel Hashomer, Israel. Chaim Sheba Med Ctr, Heller Inst Med Res, Tel Hashomer, Israel. NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2264 BP A387 EP A387 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002265 ER PT J AU Probst, FJ Wang, A Friedman, TB Camper, SA AF Probst, FJ Wang, A Friedman, TB Camper, SA TI Genetic and physical map of the shaker-2 critical region, a mouse model for nonsyndromic deafness. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. NIDCD, NIH, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1404 BP A242 EP A242 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001406 ER PT J AU Raben, N Lee, L Nagaraju, K LaMarca, ME King, CM Sauer, B Plotz, P AF Raben, N Lee, L Nagaraju, K LaMarca, ME King, CM Sauer, B Plotz, P TI Targeted disruption of the mouse acid maltase gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, ARB, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1510 BP A259 EP A259 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001512 ER PT J AU Reddy, PH Williams, M Miller, G Glass, M Paylor, R Garrett, L Herkenham, M Crawley, J Tagle, DA AF Reddy, PH Williams, M Miller, G Glass, M Paylor, R Garrett, L Herkenham, M Crawley, J Tagle, DA TI Transgenic mouse models for Huntington's disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Ctr Res Resources, Bethesda, MD USA. NIMH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 274 BP A52 EP A52 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000277 ER PT J AU Reissner, K Tayebi, N Almashana, S Blitzer, M Cowan, TM Hassan, M Maddalena, A Spence, C Sidransky, E Karson, E AF Reissner, K Tayebi, N Almashana, S Blitzer, M Cowan, TM Hassan, M Maddalena, A Spence, C Sidransky, E Karson, E TI Heteroallelism for a novel recombinant allele and a rare splice junction mutation in the glucocerebrosidase locus presenting with hydrops fetalis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Div Human Genet, Baltimore, MD 21201 USA. Holy Cross Hosp, Silver Spring, MD USA. Genet & IVF Inst, Fairfax, VA 22039 USA. Columbia Hosp Women, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 923 BP A161 EP A161 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000926 ER PT J AU Richard, G Andreoli, JM Smith, LE Compton, JG AF Richard, G Andreoli, JM Smith, LE Compton, JG TI Characterization and mapping of two novel human connexins to the candidate region for erythrokeratodermia variabilis (EKV) on chromosome 1p. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1043 BP A181 EP A181 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001046 ER PT J AU Robertson, NG Skvorak, AB Heller, S Yin, Y Nguyen, T Weremowicz, S Kovatch, KA Battey, JF Bieber, FR Hudspeth, AJ Morton, CC AF Robertson, NG Skvorak, AB Heller, S Yin, Y Nguyen, T Weremowicz, S Kovatch, KA Battey, JF Bieber, FR Hudspeth, AJ Morton, CC TI Characterization of a novel cochlear gene in human, mouse and chicken: a positional candidate gene for the human deafness disorder, DFNA9. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. NIDCD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1044 BP A181 EP A181 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001044 ER PT J AU Robin, NH Polinkovsky, A Gunay-Aygun, M Thomas, JT Irons, M Lynn, A Goodman, FR Reardon, W Kant, SG Brunner, HG van der Burgt, I Chitayat, D Morrison, S Luyten, FP Warman, ML AF Robin, NH Polinkovsky, A Gunay-Aygun, M Thomas, JT Irons, M Lynn, A Goodman, FR Reardon, W Kant, SG Brunner, HG van der Burgt, I Chitayat, D Morrison, S Luyten, FP Warman, ML TI Brachydactyly type C is caused by mutations in the morphogen CDMP-1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Genet, Sch Med, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Pediat, Sch Med, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Radiol, Sch Med, Univ Hosp Cleveland, Cleveland, OH 44106 USA. NIH, Bethesda, MD 20892 USA. NEMC, Floating Hosp Children, Div Genet, Boston, MA USA. Inst Child Hlth, Mol Med Unit, London, England. Inst Child Hlth, Mothercare Unit Clin Genet, London, England. Leiden Univ Hosp, Dept Clin Genet, Leiden, Netherlands. Univ Nijmegen Hosp, Dept Clin Genet, NL-6500 HB Nijmegen, Netherlands. Hosp Sick Children, Div Clin Genet, Toronto, ON M5G 1X8, Canada. RI Brunner, Han/C-9928-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 251 BP A48 EP A48 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000251 ER PT J AU Rogan, PK Schneider, TD Faux, B Wijnen, J Radice, P Baba, S Scott, R Viel, A Genuardi, M Khan, PM Fodde, R AF Rogan, PK Schneider, TD Faux, B Wijnen, J Radice, P Baba, S Scott, R Viel, A Genuardi, M Khan, PM Fodde, R CA ICG-HNPCC TI Information theory-based analysis of splice junction mutations in hereditary non-polyposis colon cancer (HNPCC). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Allegheny Univ Hlth Sci, Pittsburgh, PA 21701 USA. NCI, Frederick Canc Res & Dev Ctr, NL-2300 RA Frederick, MD USA. Leiden Univ, I-20133 Leiden, Netherlands. Ist Nazl Tumori, Milan, Italy. Hamamatsu Univ Sch Med, CH-4031 Hamamatsu, Shizuoka, Japan. Kantonsspital, I-33081 Basel, Switzerland. Ctr Riferimento Oncol, Aviano, Italy. Univ Cattolica Sacro Cuore, Rome, Italy. 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 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 438 BP A80 EP A80 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000439 ER PT J AU Roig, C Ho, N Francomano, CA AF Roig, C Ho, N Francomano, CA TI Epidermal Nevus Syndrome with localized cranial defects. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 624 BP A111 EP A111 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000625 ER PT J AU Roschke, AV Thraves, PJ Kuettel, MR Dritschild, A Ried, T AF Roschke, AV Thraves, PJ Kuettel, MR Dritschild, A Ried, T TI SKY and CGH analysis of genetic changes involved in radiation-induced neoplastic transformation of human prostate epithelial cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 439 BP A80 EP A80 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000442 ER PT J AU Saito, M Matsumine, H Tanaka, H Ishikawa, A Shimoda-Matsubayashi, S Schaffer, AA Mizuno, Y Tsuji, S AF Saito, M Matsumine, H Tanaka, H Ishikawa, A Shimoda-Matsubayashi, S Schaffer, AA Mizuno, Y Tsuji, S TI Refinement of the gene locus for autosomal recessive juvenile parkinsonism (AR-JP) on chromosome 6q25.2-27 and identification of markers exhibiting linkage disequilibrium. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Niigata Univ, Brain Res Inst, Dept Neurol, Niigata 951, Japan. Nishiojiya Natl Hosp, Niigata 947, Japan. Juntendo Univ, Sch Med, Tokyo 113, Japan. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1708 BP A293 EP A293 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001710 ER PT J AU Samango-Sprouse, C Vezina, LG Brasseux, C Tillman, S Tifft, CJ AF Samango-Sprouse, C Vezina, LG Brasseux, C Tillman, S Tifft, CJ TI Cranial magnetic resonance findings and the neurodevelopmental performance in the young child with neurofibromatosis type 1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Radiol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Biostat, Washington, DC 20010 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 178 BP A35 EP A35 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000181 ER PT J AU Schaffer, AA Becker, A Geiger, D AF Schaffer, AA Becker, A Geiger, D TI Automatic selection of loop breakers for genetic linkage analysis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Baltimore, MD USA. Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1710 BP A293 EP A293 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001711 ER PT J AU Schilling, G Borchelt, DR Ratovitski, T Sharp, AH Cooper, JK Coleman, JW Duan, K Copeland, N Jenkins, NA Trottier, Y Mandel, JL Becher, M Price, DL Ross, CA AF Schilling, G Borchelt, DR Ratovitski, T Sharp, AH Cooper, JK Coleman, JW Duan, K Copeland, N Jenkins, NA Trottier, Y Mandel, JL Becher, M Price, DL Ross, CA TI Phenotype of transgenic mice expressing truncated protein with an expanded glutamine repeat of the Huntington's disease cDNA SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Sch Med, Baltimore, MD USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, Frederick, MD 21702 USA. CNRS, IGBMC, Strasbourg, France. RI Trottier, Yvon/H-8852-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1870 BP A320 EP A320 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001874 ER PT J AU Schleutker, J Matikainen, M Smith, JR Wyszynski, DF Pukkala, E Sankila, R Gillanders, E Freas-Lutz, D Pugh, EW Tilli, E Visakorpi, T Tammela, TLJ Brownstein, MJ Collins, FC Bailey-Wilson, JE Trent, JM Kallioniemi, OP AF Schleutker, J Matikainen, M Smith, JR Wyszynski, DF Pukkala, E Sankila, R Gillanders, E Freas-Lutz, D Pugh, EW Tilli, E Visakorpi, T Tammela, TLJ Brownstein, MJ Collins, FC Bailey-Wilson, JE Trent, JM Kallioniemi, OP TI Search for founder effects: A genetic and epidemiologic study of hereditary prostate cancer in Finland. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Tampere Univ Hosp, Canc Genet Lab, Tampere, Finland. Tampere Univ Hosp, Dept Urol, Tampere, Finland. Finnish Canc Registry, FIN-00170 Helsinki, Finland. NHGRI, 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 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1711 BP A293 EP A293 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001714 ER PT J AU Schmitt, ES Proud, VK Boyd, EF Spinner, RJ Carey, ML Schwartz, CF Friedman, TB AF Schmitt, ES Proud, VK Boyd, EF Spinner, RJ Carey, ML Schwartz, CF Friedman, TB TI Clinical and molecular studies of PAX3 and TWIST mutations in a unique five-generation family with craniofacial malformations, heterochromia, and white hair patches. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Eastern Virginia Med Sch, Childrens Hosp Kings Daughters, Dept Pediat, Div Gen Med, Norfolk, VA 23501 USA. Mission Gen Ctr, Asheville, NC USA. Mayo Clin, Rochester, MN USA. Human Genome Sci Inc, Rockville, MD USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 628 BP A112 EP A112 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000630 ER PT J AU Schriml, LM Dean, M AF Schriml, LM Dean, M TI Characterizing the ABC superfamily via backcross panel mapping in Mus musculus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 195 BP A38 EP A38 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000198 ER PT J AU Schrock, E Veldman, T Padilla-Nash, H Ning, Y Spurbeck, J Jalal, S Shaffer, LG Papenhausen, P Kozma, C Phelan, MC Kjeldsen, E Schonberg, SA O'Brien, P Biesecker, L du Manoir, S Ried, T AF Schrock, E Veldman, T Padilla-Nash, H Ning, Y Spurbeck, J Jalal, S Shaffer, LG Papenhausen, P Kozma, C Phelan, MC Kjeldsen, E Schonberg, SA O'Brien, P Biesecker, L du Manoir, S Ried, T TI Spectral karyotyping refines cytogenetic diagnostics of constitutional chromosomal abnormalities. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIHGR, NHGRI, NIH, Bethesda, MD USA. Baylor Coll Med, Dept Mol & Human Genet, Rochester, MN USA. Labcorp, Res Triangle Pk, NC USA. Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 796 BP A140 EP A140 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000800 ER PT J AU Seldin, MF Schuler, GD AF Seldin, MF Schuler, GD TI Definition of human/mouse homology relationships using ESTs. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Davis, Rowe Program Genet, Davis, CA USA. Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1412 BP A243 EP A243 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001413 ER PT J AU Seppala, R Lehto, VP Gahl, WA AF Seppala, R Lehto, VP Gahl, WA TI Molecular cloning of the rate-limiting enzyme in sialic acid synthesis, uridinediphosphate-N-acetylglucosamine-2-epimerase (UDP-GlcNAc-2-epimerase): Implications for sialuria. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD USA. Univ Oulu, Dept Pathol, Oulu, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1519 BP A261 EP A261 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001520 ER PT J AU Shroyer, NF Singh, N Allikmets, R Hutchinson, A Peiffer, A Li, YX Lupski, JR Leppert, M Lewis, RA AF Shroyer, NF Singh, N Allikmets, R Hutchinson, A Peiffer, A Li, YX Lupski, JR Leppert, M Lewis, RA TI Genotype/phenotype analysis of a retinal specific ABC transporter gene, ABCR, in Stargardt disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Baylor Coll Med, Cell & Mol Biol Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Utah, Dept Human Genet, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2028 BP A346 EP A346 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002031 ER PT J AU Sidjanin, DJ Parker-Wilson, DM Neuhauser-Klaus, A Pretsch, W Favor, J Ohtaka-Maruyama, C Liu, Y Skach, W Chepelinsky, A Stambolian, D AF Sidjanin, DJ Parker-Wilson, DM Neuhauser-Klaus, A Pretsch, W Favor, J Ohtaka-Maruyama, C Liu, Y Skach, W Chepelinsky, A Stambolian, D TI Characterization of the mutation in the Mip gene which results in autosomal dominant cataract in mice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NEI, Bethesda, MD 20892 USA. GSF, Inst Mammalian Genet, Natl Res Ctr Environm & Hlth, Neuherberg, Germany. RI Ohtaka-Maruyama, chiaki/G-6943-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 38 BP A9 EP A9 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000037 ER PT J AU Sidransky, E Lau, EK Winfield, S Stubblefield, BK Zimran, A Tayebi, N Ginns, EI AF Sidransky, E Lau, EK Winfield, S Stubblefield, BK Zimran, A Tayebi, N Ginns, EI TI Identification of two novel polymorphisms in the glucocerebrosidase gene region. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. Shaare Zedek Med Ctr, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2318 BP A396 EP A396 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002321 ER PT J AU Skoultchi, AI Puech, A Saint-Jore, B Funke, B Copeland, N Jenkins, N Pandita, R Carlson, C Sirotkin, H Kucherlapati, R Morrow, BE AF Skoultchi, AI Puech, A Saint-Jore, B Funke, B Copeland, N Jenkins, N Pandita, R Carlson, C Sirotkin, H Kucherlapati, R Morrow, BE TI Comparative mapping of the human and mouse VCFS/DGS syntenic region discloses the presence of a large internal rearrangement. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. Frederick Canc Res & Dev Ctr, Frederick, MD USA. RI PUECH, Anne/A-7470-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 296 BP A55 EP A55 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000297 ER PT J AU Smith, ACM Dykens, E Greenberg, F AF Smith, ACM Dykens, E Greenberg, F TI Sleep disturbance among 39 patients with Smith-Magenis syndrome (del 17p11.2). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Med Genet Branch, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 639 BP A113 EP A113 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000641 ER PT J AU Smith, MW Dean, M Carrington, M Winkler, C Huttley, GA Lomb, DA Goedert, JJ O'Brien, TR Jacobson, LP Kaslow, R Buchbinder, S Vittinghoff, E Vlahov, D Hoots, K Hilgartner, MW O'Brien, SJ AF Smith, MW Dean, M Carrington, M Winkler, C Huttley, GA Lomb, DA Goedert, JJ O'Brien, TR Jacobson, LP Kaslow, R Buchbinder, S Vittinghoff, E Vlahov, D Hoots, K Hilgartner, MW O'Brien, SJ CA Hemophilia Growth Dev Study Multicenter AIDS Cohort Multicenter Hemophilia Cohort Study San Francisco City Cohort ALIVE Study TI Influence of CCR2 and CCR5 receptor genetic variants on HIV-1 infection and disease progression. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC Frederick, Frederick, MD USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL USA. San Francisco City Clin, Dept Publ Hlth, San Francisco, CA USA. Univ Texas, Sch Med, Dept Pediat, Houston, TX USA. Univ Texas, Sch Med, Dept Internal Med, Houston, TX USA. Cornell Univ, Med Ctr, New York Hosp, Div Pediat Hematol & Oncol, New York, NY 10021 USA. RI Smith, Michael/B-5341-2012; Dean, Michael/G-8172-2012; Huttley, Gavin/G-5169-2015 OI Dean, Michael/0000-0003-2234-0631; Huttley, Gavin/0000-0001-7224-2074 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 232 BP A45 EP A45 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000233 ER PT J AU Sonies, BC Solomon, B Ondrey, F McCullagh, L Greenberg, F Smith, ACM AF Sonies, BC Solomon, B Ondrey, F McCullagh, L Greenberg, F Smith, ACM TI Oral-motor & otolaryngologic findings in 14 patients with Smith-Magenis syndrome (17p11.2): Results of an interdisciplinary study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. NHGRI, NIH, Bethesda, MD USA. NIDCD, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 13 BP A5 EP A5 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000016 ER PT J AU St Jean, PL Schork, NJ Thiel, B Philibert, RA Egeland, JA Paul, SM Ginns, EI AF St Jean, PL Schork, NJ Thiel, B Philibert, RA Egeland, JA Paul, SM Ginns, EI TI Segment sharing analysis of bipolar affective disorder in the Old Order Amish. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Biostat & Epidemiol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. Univ Miami, Dept Psychiat, Miami, FL 33152 USA. Lilly Res Labs, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1726 BP A296 EP A296 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001728 ER PT J AU Stephan, DA Gu, JZ Malechek, L Bittner, M Jiang, Y Carstea, ED Morris, JA Tagle, DA Meltzer, PS Rosenfeld, MA Trent, JM AF Stephan, DA Gu, JZ Malechek, L Bittner, M Jiang, Y Carstea, ED Morris, JA Tagle, DA Meltzer, PS Rosenfeld, MA Trent, JM TI Application of DNA microarray technology to identify loss-of-function disease genes: Niemann-Pick Type C (NPC) disease as a model system. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 188 BP A37 EP A37 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000189 ER PT J AU Sutherland, HF Kim, UJ Kimber, WL Wynshaw-Boris, A Scambler, PJ AF Sutherland, HF Kim, UJ Kimber, WL Wynshaw-Boris, A Scambler, PJ TI Comparative mapping of Hu22q11 and the conserved syntenic region of MMU16 reveals disruption to linkage conservation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Inst Child Hlth, London, England. CALTECH, Pasadena, CA 91125 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RI Scambler, Peter/C-4998-2008 OI Scambler, Peter/0000-0002-1487-4628 NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1422 BP A245 EP A245 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001424 ER PT J AU Szabo, JK Wilkin, DJ Cameron, R Henderson, S Bellus, G Kaitila, I Loughlin, J Munnich, A Sykes, B Bonaventure, J Francomano, CA AF Szabo, JK Wilkin, DJ Cameron, R Henderson, S Bellus, G Kaitila, I Loughlin, J Munnich, A Sykes, B Bonaventure, J Francomano, CA TI The achondroplasia mutation occurs exclusively on the paternally derived fibroblast growth factor receptor 3 (FGFR3) allele. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. Hop Necker Enfants Malad, INSERM U393, Paris, France. Univ Oxford, John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England. Univ Helsinki Hosp, Dept Clin Genet, Helsinki, Finland. NR 0 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2040 BP A348 EP A348 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002043 ER PT J AU Tagle, DA Brown, K Carstea, ED Morris, JA Coleman, KG Loftus, SK Zhang, D Cummings, C Gu, J Mosbrook, D Rosenfeld, MA Pavan, WJ Pentchev, PG AF Tagle, DA Brown, K Carstea, ED Morris, JA Coleman, KG Loftus, SK Zhang, D Cummings, C Gu, J Mosbrook, D Rosenfeld, MA Pavan, WJ Pentchev, PG TI Identification and characterization of the Niemann-Pick type C gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 283 BP A53 EP A53 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000282 ER PT J AU Tayebi, N Reissner, K Orvisky, E Ehlert, M Martin, BM Sidransky, E Ginns, EI Krasnewich, D AF Tayebi, N Reissner, K Orvisky, E Ehlert, M Martin, BM Sidransky, E Ginns, EI Krasnewich, D TI Analysis of a phosphomannomutase 2 gene in American patients with type 1 carbohydrate-deficient glycoprotein syndrome (CDGS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2041 BP A348 EP A348 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002041 ER PT J AU Taymans, S Macrae, CA Casey, M Merliss, A Lin, JP Rocchi, M Kirschner, LS Basson, CT Stratakis, CA AF Taymans, S Macrae, CA Casey, M Merliss, A Lin, JP Rocchi, M Kirschner, LS Basson, CT Stratakis, CA TI A refined genetic, radiation hybrid and physical map of the Carney complex (CNC) locus on chromosome 2p16; evidence for genetic heterogeneity in the syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Cornell Univ Med Coll, New York Hosp, Dept Med, New York, NY USA. NICHD, Unit Genet & Endocrinol, SPE, DEB,NIH, Bethesda, MD USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 461 BP A84 EP A84 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000465 ER PT J AU Tenhunen, K Jalanko, A McKinney, CE Lamarca, ME Autti, T Rapola, J Ginns, EI Peltonen, L AF Tenhunen, K Jalanko, A McKinney, CE Lamarca, ME Autti, T Rapola, J Ginns, EI Peltonen, L TI Knock-out mouse model for human aspartylglucosaminuria closely resembles the human disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Dept Radiol, FIN-00014 Helsinki, Finland. Univ Helsinki, Childrens Hosp, Helsinki, Finland. NR 3 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1528 BP A262 EP A262 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001530 ER PT J AU Thibodeau, SN Wang, Z Tester, DJ French, AJ Schroeder, JJ Bissonet, AS Roberts, SG Blut, ML Schaid, DJ Smith, JR Trent, JM AF Thibodeau, SN Wang, Z Tester, DJ French, AJ Schroeder, JJ Bissonet, AS Roberts, SG Blut, ML Schaid, DJ Smith, JR Trent, JM TI Linkage analysis at the HPC1 locus in hereditary prostate cancer families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Natl Human Genome Res Inst, Bethesda, MD USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1733 BP A297 EP A297 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001737 ER PT J AU Tsao, H Benoit, E Huebner, K Thiele, C Haluska, FG AF Tsao, H Benoit, E Huebner, K Thiele, C Haluska, FG TI Identification of novel mutations in the exon of CDK4 containing the p16-binding region. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Thomas Jefferson Med Ctr, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 467 BP A85 EP A85 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000471 ER PT J AU Tsipouras, P Kilpatrick, MW Lembessis, P Thomas, JT Luyten, FP Costa, T AF Tsipouras, P Kilpatrick, MW Lembessis, P Thomas, JT Luyten, FP Costa, T TI Abnormal limb development in Grebe syndrome caused by mutations in cartilage-derived morphogenetic protein-1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UCONN, Ctr Hlth, Dept Pediat, Farmington, CT USA. NIDR, Bone Res Branch, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 227 BP A44 EP A44 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000228 ER PT J AU Usdin, K De-levi, S Grabczyk, E Lavedan, C Nussbaum, RL Weitzmann, MN Woodford, KJ AF Usdin, K De-levi, S Grabczyk, E Lavedan, C Nussbaum, RL Weitzmann, MN Woodford, KJ TI Unusual nucleic acid structures, DNA instability and the triplet expansion diseases. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1885 BP A322 EP A322 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001885 ER PT J AU Vahava, O Morell, R Ploplis, B Friedman, TB Avraham, KB AF Vahava, O Morell, R Ploplis, B Friedman, TB Avraham, KB TI Non-syndromic autosomal dominant progressive hearing loss in an Israeli family. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1740 BP A298 EP A298 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001741 ER PT J AU Vajo, Z Francomano, CA Wilkin, DJ AF Vajo, Z Francomano, CA Wilkin, DJ TI Characterization of the human CLK-1 cDNA; association between aging and coenzyme Q biosynthesis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1530 BP A263 EP A263 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001534 ER PT J AU Van Laer, L Van Camp, G van Zuijlen, D Green, ED Verstreken, M Schatteman, I Van de Heyning, P Balemans, W Coucke, P Greinwald, JH Smith, RJH Huizing, E Willems, P AF Van Laer, L Van Camp, G van Zuijlen, D Green, ED Verstreken, M Schatteman, I Van de Heyning, P Balemans, W Coucke, P Greinwald, JH Smith, RJH Huizing, E Willems, P TI Refinement of the DFNA5 candidate region, construction of a YAC contig, and exclusion of a fetal-cochlear expressed candidate gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. Univ Utrecht Hosp, Dept Otorhinolaryngol, Utrecht, Netherlands. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Univ Antwerp Hosp, Dept Otorhinolaryngol, Antwerp, Belgium. Univ Iowa Hosp & Clin, Dept Otorhinolaryngol, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1743 BP A298 EP A298 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001745 ER PT J AU Vandenbergh, DJ Thompson, M Cook, E Schaeffer, J George, S Bendahhou, E You, JT Hazama, M Comings, D O'Dowd, B Uhl, GR AF Vandenbergh, DJ Thompson, M Cook, E Schaeffer, J George, S Bendahhou, E You, JT Hazama, M Comings, D O'Dowd, B Uhl, GR TI High conservation of dopamine transporter sequences among human individuals. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDA, Mol Neurob Branch, IRP, NIH, Lexington, KY 40583 USA. Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. Calif State Univ Northridge, Dept Chem, Northridge, CA 91330 USA. City Hope Natl Med Ctr, Dept Med Genet, Duarte, CA USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21224 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2238 BP A382 EP A382 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002240 ER PT J AU Vikkula, M Boon, LM Zhuang, Z Warman, ML Liotta, L Mulliken, JB Olsen, BR AF Vikkula, M Boon, LM Zhuang, Z Warman, ML Liotta, L Mulliken, JB Olsen, BR TI Molecular background of congenital venous malformations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Catholic Univ Louvain, Ctr Vasc Anomalies, Brussels, Belgium. Catholic Univ Louvain, ICP, Human Mol Genet Grp, Brussels, Belgium. NCI, Pathol Lab, Bethesda, MD 20892 USA. CWRU, Dept Genet, Cleveland, OH USA. Childrens Hosp, Div Plast Surg, Boston, MA 02115 USA. HMS, Dept Cell Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 51 BP A12 EP A12 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000052 ER PT J AU Wang, YF Gillanders, E Wang, S Freas-Lutz, D Sun, C Zebrak, J Pawlik, J Rutkiewicz, E Witt, M Diehl, SR AF Wang, YF Gillanders, E Wang, S Freas-Lutz, D Sun, C Zebrak, J Pawlik, J Rutkiewicz, E Witt, M Diehl, SR TI Genome Scan for susceptibility loci for Kartagener syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD USA. Inst TB & Lung Dis, Rabka, Poland. Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1750 BP A300 EP A300 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001752 ER PT J AU Watanabe, A Takeda, K Ploplis, B Tachibana, M AF Watanabe, A Takeda, K Ploplis, B Tachibana, M TI Epistatic relationship of genes for Waardenburg syndrome type 1 and type 2: MITF is regulated by PAX3. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1888 BP A323 EP A323 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001892 ER PT J AU Watanabe, RM Hauser, ER Valle, T Eriksson, J Bergman, RN Ghosh, S Boehnke, M AF Watanabe, RM Hauser, ER Valle, T Eriksson, J Bergman, RN Ghosh, S Boehnke, M TI Familiality of minimal model-derived quantitative metabolic traits in a Finnish cohort. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Natl Publ Hlth Inst, Helsinki, Finland. Univ So Calif, Sch Med, Los Angeles, CA 90089 USA. Natl Human Genome Res Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1751 BP A300 EP A300 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001755 ER PT J AU Weaver, ZA McCormack, SJ Liyanage, MS DuManoir, S Dickson, RB Wynshaw-Boris, A Brody, L Ried, T AF Weaver, ZA McCormack, SJ Liyanage, MS DuManoir, S Dickson, RB Wynshaw-Boris, A Brody, L Ried, T TI Chromosomal aberrations in the mammary tumors of transgenic mice detected by multicolor spectral karyotyping (SKY). 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 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 483 BP A87 EP A87 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000485 ER PT J AU Wilkin, DJ Liberfarb, R Mortier, GR Warman, M Cohn, DH Francomano, CA AF Wilkin, DJ Liberfarb, R Mortier, GR Warman, M Cohn, DH Francomano, CA TI Genetic heterogeneity in Stickler syndrome: phenotypic exploration. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. State Univ Ghent Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. Case Western Reserve Univ, Cleveland, OH 44106 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RI Mortier, Geert/D-2542-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2055 BP A351 EP A351 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002057 ER PT J AU Wilson, AF Bailey-Wilson, JE AF Wilson, AF Bailey-Wilson, JE TI Effect of misspecification of trait genotypic means on the power of lod-score linkage analysis using computer simulation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Ctr Human Genome Res, Baltimore, MD 21224 USA. Louisiana State Univ, Med Ctr, Dept Biometry & Genet, New Orleans, LA 70112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1184 BP A205 EP A205 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001188 ER PT J AU Winfield, SL Tayebi, N Martin, BM Ginns, EI Sidransky, E AF Winfield, SL Tayebi, N Martin, BM Ginns, EI Sidransky, E TI The identification of three additional genes contiguous to the glucocerebrosidase locus: implications for Gaucher disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurosci Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2302 BP A393 EP A393 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002304 ER PT J AU Wolf, NG Abdul-Karim, FW Farver, C Ried, T Schrock, E du Manoir, S Schwartz, S AF Wolf, NG Abdul-Karim, FW Farver, C Ried, T Schrock, E du Manoir, S Schwartz, S TI Analysis of ovarian borderline tumors using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 489 BP A88 EP A88 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446000491 ER PT J AU Woods, KS Wright, M Ide, S Ho, N Krizman, D Coleman, K Szabo, J Polymeropoulos, M Francomano, C Goodship, J AF Woods, KS Wright, M Ide, S Ho, N Krizman, D Coleman, K Szabo, J Polymeropoulos, M Francomano, C Goodship, J TI Towards positional cloning of the gene involved in Ellis Van Crevald syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. LGDR, Bethesda, MD USA. MGB, Bethesda, MD USA. NCI, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NINDS, DMNB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1433 BP A246 EP A246 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001435 ER PT J AU Wu, SM Stratakis, CA Bourdony, CJ Rennert, OM Chen, WY AF Wu, SM Stratakis, CA Bourdony, CJ Rennert, OM Chen, WY TI Molecular genetics of syndromes of adrenocorticotropin (ACTH) resistance: Novel mutation of the ACTH receptor gene in hereditary glucocorticoid resistance patient and refinement of the Allgrove syndrome locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC 20057 USA. NICHD, DEB, NIH, Bethesda, MD USA. San Juan Hosp, San Juan, PR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2058 BP A351 EP A351 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002061 ER PT J AU Wyszynski, DF Zeiger, J Tilli, E Bailey-Wilson, JE Beaty, TH AF Wyszynski, DF Zeiger, J Tilli, E Bailey-Wilson, JE Beaty, TH TI Survey of genetic counselors and clinical geneticists on recurrence risks for non-syndromic oral clefts. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Western Maryland Coll, Westminster, MD 21157 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1114 BP A193 EP A193 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001117 ER PT J AU Young, T Ronan, S Drahozal, L Wildenberg, S Oetting, W Atwood, L Wilkin, D King, R AF Young, T Ronan, S Drahozal, L Wildenberg, S Oetting, W Atwood, L Wilkin, D King, R TI Exclusion of loci for Marfan and Stickler Syndromes, and congenital juvenile glaucoma in pedigrees of familial pathologic myopia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN 55455 USA. NIH, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2365 BP A404 EP A404 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002366 ER PT J AU Zabarovsky, ER Kashuba, VI Gizatullin, R Protopopov, A Kiss, C Li, J Fedorova, L Zabarovska, V Domninsky, D Muravenko, O Allikmets, RL Zakharyev, V Lerman, M Dean, M Grafodatsky, AS Zelenin, AV Drabkin, H Sheer, D Sumegi, J Winberg, G Kisselev, LL Klein, G AF Zabarovsky, ER Kashuba, VI Gizatullin, R Protopopov, A Kiss, C Li, J Fedorova, L Zabarovska, V Domninsky, D Muravenko, O Allikmets, RL Zakharyev, V Lerman, M Dean, M Grafodatsky, AS Zelenin, AV Drabkin, H Sheer, D Sumegi, J Winberg, G Kisselev, LL Klein, G TI Analysis of 1.000 human chromosome 3 specific Notl linking clones. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Karolinska Inst, Microbiol & Tumor Biol Ctr, Stockholm, Sweden. VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. FCRDC, NCI, Lab Viral Carcinogenesis & Immunobiol, Frederick, MD USA. Inst Cytol & Genet, Novosibirsk, Russia. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Imperial Canc Res Fund, London WC2A 3PX, England. Univ Nebraska, Med Ctr, Dept Pathol Microbiol, Omaha, NE USA. RI Zabarovsky, Eugene/A-6645-2010; Winberg, Gosta/I-5686-2013; Graphodatsky, Alexander/B-4922-2010 OI Graphodatsky, Alexander/0000-0002-8282-1085 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1437 BP A247 EP A247 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001440 ER PT J AU Zhang, J Kumar, A Ferrans, VJ Fricker, FJ Wallace, MR AF Zhang, J Kumar, A Ferrans, VJ Fricker, FJ Wallace, MR TI Familiar restrictive cardiomyopathy: Molecular genetic studies in a large kindred. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL 32611 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 2366 BP A404 EP A404 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446002369 ER PT J AU Zheng, CJ Guo, SW Byers, B AF Zheng, CJ Guo, SW Byers, B TI Biased oocyte maturation rates may increase genetic fitness but may contribute to age-dependent reproductive failure. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCD, NIH, Epidemiol Branch, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1997 VL 61 IS 4 SU S MA 1252 BP A216 EP A216 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YQ995 UT WOS:000071446001255 ER PT J AU Berghella, V Tolosa, JE Kuhlman, K Weiner, S Bolognese, RJ Wapner, RJ AF Berghella, V Tolosa, JE Kuhlman, K Weiner, S Bolognese, RJ Wapner, RJ TI Cervical ultrasonography compared with manual examination as a predictor of preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Society-of-Perinatal-Obstetricians CY JAN 20-25, 1997 CL ANAHEIM, CA SP Soc Perinatal Obstetricians DE cervix uteri; preterm delivery; risk prediction; ultrasonography ID FETAL FIBRONECTIN; UTERINE CERVIX; DIGITAL EXAMINATION; PREMATURE DELIVERY; CONTROLLED TRIAL; RISK; PREGNANCY; LENGTH; LABOR; CERCLAGE AB OBJECTIVE: Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery. STUDY DESIGN: One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospectively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix. The primary outcome studied was preterm (<35 weeks) delivery. RESULTS: Excluding six induced preterm deliveries, 96 pregnancies were analyzed. The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm (n = 17) and 31.3 mm in pregnancies delivered at term (n = 79) (p = 0.003); the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies, respectively (not significant). The sixteenth-and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately Go < 0.0005). The 25th percentiles of ultrasonographic (25 mm) and manual (16 mm) cervical lengths showed relative risks for preterm delivery of 4.8 (95% confidence interval 2.1 to 11.1, p = 0.0004) and 2.0 (95% confidence interval 0.5 to 4.7, p = 0.1), respectively; sensitivity, specificity, and positive and negative predictive values were 59%, 85%, 45%, 91%, and 41%, 77%, 28%, and 86%, respectively. CONCLUSION: Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination. Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks' gestation. C1 PENN HOSP,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19107. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. RP Berghella, V (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,PHILADELPHIA,PA 19107, USA. OI Berghella, Vincenzo/0000-0003-2854-0239 NR 32 TC 140 Z9 147 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1997 VL 177 IS 4 BP 723 EP 730 DI 10.1016/S0002-9378(97)70259-X PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YF245 UT WOS:A1997YF24500001 PM 9369810 ER PT J AU Csaky, KG Caruso, RC AF Csaky, KG Caruso, RC TI Gallium nitrate optic neuropathy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID TRANSFERRIN AB PURPOSE: To report a patient with visual loss after systemic administration of gallium nitrate. METHOD: Case report, RESULTS: After receiving intravenous gallium nitrate, a 77-year-old man developed bilateral visual loss and optic neuropathy with central scotomas on visual field testing and diminished P-2-wave amplitude on visual evoked potential examination. The condition worsened after oral corticosteroid therapy. Partial recovery of optic nerve function in both eyes was present after 12 months of oral ferrous sulfate administration. CONCLUSIONS: Partially reversible bilateral optic neuropathy may occur after administration of gallium nitrate in the absence of other chemotherapeutic agents, Ophthalmic examinations are indicated in patients who receive gallium nitrate. RP Csaky, KG (reprint author), NEI,IMMUNOL LAB,NIH,BLDG 10,10N 119,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 5 TC 5 Z9 6 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 1997 VL 124 IS 4 BP 567 EP 568 PG 2 WC Ophthalmology SC Ophthalmology GA XZ001 UT WOS:A1997XZ00100022 PM 9323956 ER PT J AU Sipowicz, MA Chomarat, P Diwan, BA Anver, MA Awasthi, YC Ward, JM Rice, JM Kasprzak, KS Wild, CP Anderson, LM AF Sipowicz, MA Chomarat, P Diwan, BA Anver, MA Awasthi, YC Ward, JM Rice, JM Kasprzak, KS Wild, CP Anderson, LM TI Increased oxidative DNA damage and hepatocyte overexpression of specific cytochrome P450 isoforms in hepatitis of mice infected with Helicobacter hepaticus SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; CHRONIC ACTIVE HEPATITIS; RAT-LIVER; LIPID-PEROXIDATION; TRANSGENIC MICE; PRIMARY CULTURE; EXPRESSION; MOUSE; INDUCTION; ENZYMES AB A recently discovered bacterium, Helicobacter hepaticus, infects the intrahepatic bile canaliculi of mice, causing a severe chronic hepatitis culminating in liver cancer, Thus, it affords an animal model for study of bacteria-associated tumorigenesis including H. pylori-related gastric cancer, Reactive oxygen species are often postulated to contribute to this process, We now report that hepatitis of male mice infected with H. hepaticus show significant increases in the oxidatively damaged DNA deoxynucleoside 8-hydroxydeoxyguanosine, with the degree of damage increasing with progression of the disease. Perfusion of infected livers with nitro blue tetrazolium revealed that superoxide was produced in the cytoplasm of hepatocytes, especially in association with plasmacytic infiltrates near portal triads, Contrary to expectations, Kupffer cells, macrophages, and neutrophils were rarely involved. However, levels of cytochrome P450 (CYP) isoforms 1A2 and 2A5 in hepatocytes appeared to be greatly increased, as indicated by the number of cells positive in immunohistochemistry and the intensity of staining in many cells, concomitant with severe hepatitis, The CYP2A5 immunohistochemical staining co-localized with formazan deposits resulting from nitro blue tetrazolium reduction and occurred in nuclei as well as cytoplasm, These findings suggest that CYP2A5 contributes to the superoxide production and 8-hydroxydeoxyguanosine formation, although reactive oxygen species from an unknown source in the hepatocytes leading to CYP2A5 induction or coincidental occurrence of these events are also possibilities, Three glutathione S-transferase isoforms, mGSTP1-1 (pi), mGSTA1-1 (YaYa), and mGSTA4-4, also showed striking increases evidencing major oxidative stress in these livers. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,VET & TUMOR PATHOL SECT,ANIM SCI BRANCH,FREDERICK,MD 21702. NCI,DIV BASIC SCI,FREDERICK,MD 21702. INT AGCY RES CANC,UNIT ENVIRONM CARCINOGENESIS,F-69372 LYON,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. FU NIEHS NIH HHS [ES06052] NR 45 TC 51 Z9 53 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1997 VL 151 IS 4 BP 933 EP 941 PG 9 WC Pathology SC Pathology GA XZ753 UT WOS:A1997XZ75300007 PM 9327726 ER PT J AU Vortmeyer, AO Lubensky, IA Fogt, F Linehan, WM Khettry, U Zhuang, ZP AF Vortmeyer, AO Lubensky, IA Fogt, F Linehan, WM Khettry, U Zhuang, ZP TI Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SOMATIC MUTATIONS; RENAL-CARCINOMA; DISEASE; HEMANGIOBLASTOMAS; HETEROZYGOSITY; CYSTADENOMAS; CHROMOSOME-3; MEMBERS AB An association between pancreatic microcystic (serous) adenomas (MCAs) and von Hippel-Lindau (VHL) disease has been suggested. However, genetic alterations of the VHL gene in MCAs of the pancreas have never been reported. In this study, we performed genetic analysis of 12 pancreatic MCAs. In 2 cases, VHL disease was documented clinically, and 10 cases were sporadic, For LOH analysis, tumor and normal pancreatic cells were procured from formalin-fixed, paraffin-embedded material using tissue microdissection, After DNA extraction, the samples were amplified by polymerase chain reaction using the polymorphic markers D3S2452, D3S1110, D3S192, and D3S656. In addition, the sporadic tumors were analyzed for VHL gene mutations using probes 3b/10b and K55/K56. Both MCAs associated with VHL disease showed LOH with at least one of the microsatellite markers tested, Among the 10 sporadic cases, 7 tumors showed LOH at the VHL gene locus, A somatic VHL gene mutation on exon 2 was documented in one sporadic case, The study provides the first direct genetic evidence for the role of the VHL gene in MCA tumorigenesis. Furthermore, VHL gene alterations may be detected in both VHL-associated and sporadic pancreatic MCAs. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,UROL ONCOL BRANCH,BETHESDA,MD 20892. DEACONESS HOSP,BOSTON,MA. NR 29 TC 53 Z9 59 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1997 VL 151 IS 4 BP 951 EP 956 PG 6 WC Pathology SC Pathology GA XZ753 UT WOS:A1997XZ75300009 PM 9327728 ER PT J AU Guinee, D Brambilla, E Fleming, M Hayashi, T Rahn, M Koss, M Ferrans, V Travis, W AF Guinee, D Brambilla, E Fleming, M Hayashi, T Rahn, M Koss, M Ferrans, V Travis, W TI The potential role of BAX and BCL-2 expression in diffuse alveolar damage SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; TUMOR-SUPPRESSOR P53; CELL-DEATH; IN-VIVO; INTERSTITIAL PNEUMONIA; OXYGEN PNEUMONITIS; ANTIGEN RETRIEVAL; INDUCED APOPTOSIS; FREE-RADICALS AB Apoptosis of type II pneumocytes has been identified in diffuse alveolar damage (DAD), is associated with p53 and WAF1 expression, and may be of pathogenetic importance, BAX, a homologue of BCL-2, is induced by p53 and is a promoter of apoptosis. The proapoptotic effect of BAX is negatively regulated by its binding with BCL-2, In this study, we sought to investigate the role of BAX and BCL-2 in DAD, We hypothesized that alterations in BAX and BCL-2 expression may be important in determining the susceptibility of type II pneumocytes and interstitial cells to apoptosis, Twenty-eight cases of DAD and 16 control cases (ie, lung tissues adjacent to resected tumors) were retrieved from the files of the University of Utah and the Armed Forces Institute of Pathology. Immunohistochemical stains were performed with antigen retrieval by microwave using antibodies recognizing BAX and BCL-2, The percentage of positively staining pneumocytes and interstitial cells was estimated in each case to the nearest 10%, BAX expression was markedly increased in pneumocytes and interstitial cells in DAD compared with control lung tissues, In DAD, BAX was identified on an average of 80% of alveolar pneumocytes (range 30 to 100%) and 70% of interstitial cells (range 20 to 90%), In control lungs, BAX was identified on an average of 10% of pneumocytes (range 0 to 20%) but not in interstitial cells. Focal BCL-2 staining was identified in interstitial myofibroblasts in 7 of 25 cases of DAD but was only identified in bronchiolar epithelium of control lungs, These results suggest that the induction of BAX in DAD may enhance the susceptibility of alveolar epithelial cells to apoptosis, whereas BCL-2 expression may contribute to the absence of apoptosis in interstitial myofibroblasts, Expression of BCL-2 in interstitial myofibroblasts may contribute to the development of pulmonary fibrosis in some patients. C1 CHRU,PATHOL CELLULAIRE LAB,GRENOBLE,FRANCE. ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC 20306. NIH,BETHESDA,MD 20892. RP Guinee, D (reprint author), UNIV UTAH,MED CTR,DEPT PATHOL,A513,50 N MED DR,SALT LAKE CITY,UT 84132, USA. RI Brambilla, Elisabeth/L-8796-2013 NR 72 TC 76 Z9 79 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1997 VL 151 IS 4 BP 999 EP 1007 PG 9 WC Pathology SC Pathology GA XZ753 UT WOS:A1997XZ75300014 PM 9327733 ER PT J AU Verdery, RB Ingram, DK Roth, GS Lane, MA AF Verdery, RB Ingram, DK Roth, GS Lane, MA TI Caloric restriction increases HDL2 levels in rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE aging; nutrition; primates; atherosclerosis; high-density lipoprotein ID AGE-RELATED-CHANGES; HIGH-DENSITY-LIPOPROTEIN; DIETARY RESTRICTION; FOOD RESTRICTION; MYOCARDIAL-INFARCTION; SERUM-LIPIDS; A-I; CHOLESTEROL; METABOLISM; SUBFRACTIONS AB Caloric restriction (CR) prolongs the life of rodents and other small animals, but the benefits of CR for primates and people are as yet unknown, and mechanisms by which CR may slow aging remain unidentified. A study of rhesus monkeys, Macaca mulatta, is underway to determine if CR might prolong life span in primates and to evaluate potential mechanisms for Life prolongation. Thirty rhesus monkeys in three age cohorts, restricted to 70% of ad libitum calorie intake for 6-7 yr, were compared with 30 controls. Plasma lipid, lipoprotein, and high-density lipoprotein (HDL) apolipoproteins and subfractions were measured and compared with weight, percent fat; glucose, and insulin level. CR caused decreased triglyceride levels in adult-monkeys and increased levels of HDL2b, the HDL subfraction associated with protection from atherosclerosis. Multivariate statistical analyses showed that differences in lipid and lipoprotein levels occurring with CR could be accounted for, at least in part; by decreased body mass and improved glucose regulation. These studies have used a novel dietary modification paradigm in nonhuman primates focused on calorie reduction. Results suggest that CR, as mediated by its beneficial effect on body composition and glucose metabolism, could prolong human life by decreasing the incidence of atherosclerosis. C1 NIA, MOL PHYSIOL & GENET SECT,NATHAN W SHOCK LABS, GERONTOL RES CTR,HOPKINS BAYVIEW MED CTR, BALTIMORE, MD 21224 USA. RP Verdery, RB (reprint author), ARIZONA CTR AGING, 1821 E ELM ST, TUCSON, AZ 85719 USA. FU NIA NIH HHS [K01-AG-00414] NR 29 TC 53 Z9 54 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 1997 VL 273 IS 4 BP E714 EP E719 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA YA435 UT WOS:A1997YA43500009 PM 9357800 ER PT J AU Morita, T Hanaoka, K Morales, MM MontroseRafizadeh, C Guggino, WB AF Morita, T Hanaoka, K Morales, MM MontroseRafizadeh, C Guggino, WB TI Cloning and characterization of maxi K+ channel alpha-subunit in rabbit kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE potassium channels; cloning; calcium; potassium transport ID THICK ASCENDING LIMB; ACTIVATED POTASSIUM CHANNELS; PROXIMAL TUBULE CELLS; APICAL MEMBRANE; PRIMARY CULTURE; VOLUME REGULATION; XENOPUS-OOCYTES; PROTEIN-KINASE; SMOOTH-MUSCLE; BETA-SUBUNIT AB We have identified in rabbit renal cells two alternatively spliced transcripts Of the alpha-subunit rbslo1 and rbslo2. Rbslo1 has a novel ''in-frame'' 174-bp insertion immediately after the predicted S8 transmembrane segment, whereas rbslo2 has a 104-bp deletion between S9 and S10, creating a frameshift and a premature termination codon. Amino acid identity between mouse maxi K+ channel alpha-subunit (mslo) and rbslo1 was 99%. Two transcript sizes of 4.2 and 7.5 kb were detected in brain, kidney, stomach, testis, and lung. Rbslo is expressed in glomeruli, thin limbs Of Henle's loop, medullary and cortical thick ascending limbs of Henle's loop, and cortical, outer, and inner medullary collecting ducts; however, it was rarely detected in proximal convoluted tubules. Rbslo1 is most abundant in inner medulla. Expressed in Xenopus oocytes, rbslo1 generates depolarization-activated, outwardly rectifying K+ currents. Rbslo1 expressed in Chinese hamster ovary cells could be activated by depolarization and Ca2+, These data suggest that rbslo transcripts are expressed in multiple nephron segments and that the magnitude of mRNA expression varies among different nephron segments. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT PHYSIOL, BALTIMORE, MD 21205 USA. NIA, BALTIMORE, MD 21205 USA. FU NIDDK NIH HHS [DK-32753] NR 34 TC 53 Z9 54 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 1997 VL 273 IS 4 BP F615 EP F624 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA YA441 UT WOS:A1997YA44100014 PM 9362339 ER PT J AU Greenfield, SF Reizes, JM Magruder, KM Muenz, LR Kopans, B Jacobs, DG AF Greenfield, SF Reizes, JM Magruder, KM Muenz, LR Kopans, B Jacobs, DG TI Effectiveness of community-based screening for depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 149th Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NY SP Amer Psychiat Assoc ID UNITED-STATES; DISORDERS; PREVALENCE AB Objective: The effectiveness of a voluntary depression screening program was assessed by determining 1) whether participants in the 1994 National Depression Screening Day went for recommended follow-up examinations and 2) the characteristics that differentiated those who did and did not return. Method: Randomly selected participants (N=1,169) from 99 facilities completed a follow-up telephone survey. Results: Of 805 people for whom follow-up was recommended, 56.5% (N=455) went for an appointment. The severity of depressive symptoms Irt these subjects ranged from severe (33.4%, N=152) and marked (41.3%, N=188) to minimal (17.1%, N=78) and nor mal (8.1%, N=37). Subjects with marked or severe depression were move likely to respond to the screening recommendation that were those with minimal depressive symptoms. However, at each level of symptom severity, subjects who had received previous treatment were more likely to adhere to the screening recommendation that? were those with no previous treatment. Of those who returned for a recommended follow-up, 72.1% were diagnosed with depression. Of those who did not return, 29.5% cited lack of insurance, underinsurance, or inadequate finances, and 38.0% felt they could ''handle'' depression on their own. Conclusions: Voluntary screening for depression is an effective way to bring cel tain untreated depressed individuals to treatment. Inadequate insurance and the belief that individuals can manage depression on their own continue to be barriers to seeking treatment among some depressed individuals who attend a depression screening program. C1 UNIV PENN,PHILADELPHIA,PA 19104. NIMH,ROCKVILLE,MD 20857. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. FU NIAAA NIH HHS [AA-09881]; NIDA NIH HHS [DA-07252, DA-09400] NR 24 TC 46 Z9 49 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 1997 VL 154 IS 10 BP 1391 EP 1397 PG 7 WC Psychiatry SC Psychiatry GA XY997 UT WOS:A1997XY99700010 PM 9326821 ER PT J AU OSullivan, RL Keuthen, NJ Christenson, GA Mansueto, CS Stein, DJ Swedo, SE AF OSullivan, RL Keuthen, NJ Christenson, GA Mansueto, CS Stein, DJ Swedo, SE TI Trichotillomania: Behavioral symptom or clinical syndrome? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID OBSESSIVE-COMPULSIVE DISORDER; MGH HAIRPULLING SCALE; DOUBLE-BLIND; HAIR PULLERS; FLUOXETINE; CLOMIPRAMINE; CROSSOVER C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. UNIV MINNESOTA,BOYNTON HLTH CTR,DEPT PSYCHIAT,MINNEAPOLIS,MN. BOWIE STATE UNIV,BOWIE,MD. UNIV STELLENBOSCH,DEPT PSYCHIAT,ZA-7600 STELLENBOSCH,SOUTH AFRICA. NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RI Citations, TLC SAB/C-4006-2011; OI Stein, Dan/0000-0001-7218-7810 NR 52 TC 24 Z9 24 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 1997 VL 154 IS 10 BP 1442 EP 1449 PG 8 WC Psychiatry SC Psychiatry GA XY997 UT WOS:A1997XY99700018 PM 9326829 ER PT J AU Mann, JJ Malone, KM Nielsen, DA Goldman, D Erdos, J Gelernter, J AF Mann, JJ Malone, KM Nielsen, DA Goldman, D Erdos, J Gelernter, J TI Possible association of a polymorphism of the tryptophan hydroxylase gene with suicidal behavior in depressed patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; METABOLITES; INPATIENTS; DISORDERS AB Objective: This study was designed to test the hypothesis that serotonin-system-related genes may be correlated with suicide risk. Method: Fifty-one unrelated Caucasian inpatients with major depression, with or without a history of suicidal acts, were genotyped for a biallelic polymorphism at the tryptophan hydroxylase locus. Results: The less common tryptophan hydroxylase U allele occurred with greater frequency in the patients who had attempted suicide. A logistic regression analysis confirmed an association between tryptophan hydroxylase gene type and lifetime history of suicide attempts. Conclusions: Serotonergic-system-related genes may influence the risk of suicide in persons with major depression. C1 YALE UNIV,SCH MED,VA MED CTR,DEPT PSYCHIAT,DIV MOL PSYCHIAT,W HAVEN,CT 06516. NEW YORK STATE PSYCHIAT INST & HOSP,MENTAL HLTH CLIN RES CTR STUDY SUICIDAL BEHAV,NEW YORK,NY 10032. COLUMBIA UNIV,NEW YORK,NY 10027. NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIMH NIH HHS [MH-30929, MH-46745, MH-48514] NR 18 TC 148 Z9 154 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 1997 VL 154 IS 10 BP 1451 EP 1453 PG 3 WC Psychiatry SC Psychiatry GA XY997 UT WOS:A1997XY99700020 PM 9326831 ER PT J AU Denicoff, KD SmithJackson, EE Bryan, AL Ali, SO Post, RM AF Denicoff, KD SmithJackson, EE Bryan, AL Ali, SO Post, RM TI Valproate prophylaxis in a prospective clinical trial of refractory bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FOLLOW-UP; MANIA; DIVALPROEX; EFFICACY; PLACEBO AB Objective: The authors studied the efficacy of valproate plus lithium and of triple therapy with lithium, carbamazepine, and valproate in refractory bipolar illness. Method: The subjects were 24 bipolar outpatients who had completed on intended 3-year crossover study comparing lithium, carbamazepine, and their combination. Patients entered a 1-year phase of valproate plus lithium because of inadequate response or major side effects, and patients with inadequate responses were offered an additional year of treatment with all three mood-stabilizing drugs. Results: Six (33%) of the 18 evaluable patients had moderate to marked responses to valproate plus lithium; four of these six had not responded to any previous treatment condition. Three of seven patients responded to triple therapy, although only one response was marked. Conclusions: Some outpatients with bipolar disorder refractory to lithium and carbamazepine received clinically relevant prophylactic benefit from valproate when used with lithium or in triple therapy. RP Denicoff, KD (reprint author), NIMH,SECT PSYCHOBIOL,BIOL PSYCHIAT BRANCH,RM 3N212,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Ali, Syed/0000-0003-3131-3299 NR 13 TC 57 Z9 58 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 1997 VL 154 IS 10 BP 1456 EP 1458 PG 3 WC Psychiatry SC Psychiatry GA XY997 UT WOS:A1997XY99700022 PM 9326833 ER PT J AU Svinarich, DM Gomez, R Romero, R AF Svinarich, DM Gomez, R Romero, R TI Detection of human defensins in the placenta SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 19-22, 1997 CL SAN DIEGO, CA SP Soc Gynecol Invest DE antimicrobial peptides; human neutrophil proteins; infection; sequence analysis; transcription; 3'-RACE-PCR ID ANTIMICROBIAL PEPTIDE; SMALL-INTESTINE; GENE; CELLS AB PROBLEM: The placenta is a highly selective barrier against the hematogenous dissemination of infectious agents. Despite the presence of seemingly intact physical and immunologic barriers, infections nonetheless occur. These observations prompted the examination of placental tissue, amnion, and chorion for previously unrecognized protective mechanisms. METHOD OF STUDY: Messenger RNA from term placenta, amnion, and chorion were reverse transcribed using a 3' RACE adapter. 3' rapid amplification of cDNA ends (RACE)-polymerase chain reaction (PCR) was conducted on cDNA from these tissues to detect the presence of human defensins. Southern analysis and partial sequence analysis were subsequently performed to confirm identity. RESULTS: PCR amplification of placental, amnion, and chorion cDNA yielded a 468-bp product and a weakly detectable band of 300 bp. Southern analysis demonstrated two corresponding hybridizing bands in the placenta, amnion, and chorion but not from a negative cDNA control. Partial sequence analysis of the 468-bp product from placenta confirmed the presence of either defensin 1 or 3 in human placenta, CONCLUSIONS: The human placenta, amnion, and chorion express defensins at the level of transcription. These findings suggest that a novel and previously unrecognized mechanism of protecting the fetus against infection may be present within these tissues. C1 WAYNE STATE UNIV,SCH MED,DEPT PEDIAT,DETROIT,MI 48201. WAYNE STATE UNIV,SCH MED,DEPT IMMUNOL,DETROIT,MI 48201. WAYNE STATE UNIV,SCH MED,DEPT MICROBIOL,DETROIT,MI 48201. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD. RP Svinarich, DM (reprint author), WAYNE STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,CS MOTT CTR,275 E HANCOCK AVE,DETROIT,MI 48201, USA. NR 10 TC 36 Z9 36 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD OCT PY 1997 VL 38 IS 4 BP 252 EP 255 PG 4 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA YA037 UT WOS:A1997YA03700003 PM 9352011 ER PT J AU Fish, JE Peters, SP Chambers, CV McGeady, SJ Epstein, KR Boushey, HA Cherniack, RM Chinchilli, VM Drazen, JM Fahy, JV Hurd, SS Israel, E Lazarus, SC Lemanske, RF Martin, RJ Mauger, EA Sorkness, C Szefler, SJ AF Fish, JE Peters, SP Chambers, CV McGeady, SJ Epstein, KR Boushey, HA Cherniack, RM Chinchilli, VM Drazen, JM Fahy, JV Hurd, SS Israel, E Lazarus, SC Lemanske, RF Martin, RJ Mauger, EA Sorkness, C Szefler, SJ TI An evaluation of colchicine as an alternative to inhaled corticosteroids in moderate asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID HUMAN LEUKOCYTES; PEAK FLOW; MILD; LEUKOTRIENE-B4; MICROTUBULES; MECHANISM; RELEASE AB Colchicine demonstrates an array of anti-inflammatory properties of potential relevance to asthma. However, the efficacy of colchicine as an alternative to inhaled corticosteroid therapy for asthma is unknown. Five centers participated in a controlled trial testing the hypothesis that in patients with moderate asthma needing inhaled corticosteroids for control, colchicine provides therapeutic benefit as measured by maintenance of control when inhaled steroids are discontinued. Subjects were stabilized on triamcinolane acetonide (800 mu g daily) and then enrolled in a 2-wk run-in during which all subjects took both colchicine (0.6 mg/twice a day) and triamcinolone. At the end of the run-in, all subjects discontinued triamcinolone and were randomised to continued colchicine (n = 35) or placebo (n = 36) for a 6-wk double-blind treatment period. The treatment groups were similar in terms of disease severity. After corticosteroid withdrawal, 60% of colchicine-treated and 56% of placebo-treated subjects were considered treatment failures as defined by preset criteria. No significant difference in survival curves was found between treatment groups (log rank = 0.38). Other measures, including changes in FEV1, peak expiratory flow, symptoms, rescue albuterol use, and quality of life scores, also did not differ between groups. Of note, subjects failing treatment had significantly greater methacholine responsiveness at baseline than did survivors (PC20, 0.81 +/- 1.38 versus 2.11 +/- 2.74 mg/ml; p = 0.01). An analysis of treatment failures suggested that the criteria selected for failure reflected a clinically meaningful but safe level of deterioration. We conclude that colchicine is no better than placebo as an alternative to inhaled corticosteroids in patients with moderate asthma. Additionally, we conclude that the use of treatment failure as the primary outcome variable in an asthma clinical trial where treatment is withdrawn is feasible and safe under carefully monitored conditions. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. MILTON S HERSHEY MED CTR,HERSHEY,PA. UNIV WISCONSIN,MADISON,WI 53706. NATL JEWISH MED & RES CTR,DENVER,CO. NHLBI,BETHESDA,MD 20892. RP Fish, JE (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PULM MED,ROOM 805 COLL,1025 WALNUT ST,PHILADELPHIA,PA 19107, USA. RI Drazen, Jeffrey/E-5841-2012 FU NHLBI NIH HHS [U10 HL-51810, U10 HL-51834, U10 HL-51831] NR 28 TC 28 Z9 28 U1 0 U2 3 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 1997 VL 156 IS 4 BP 1165 EP 1171 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA YA438 UT WOS:A1997YA43800019 PM 9351617 ER PT J AU BallardBarbash, R Taplin, SH Yankaskas, BC Ernster, VL Rosenberg, RD Carney, PA Barlow, WE Geller, BM Kerlikowske, K Edwards, BK Lynch, CF Urban, N Key, CR Poplack, SP Worden, JK Kessler, LG AF BallardBarbash, R Taplin, SH Yankaskas, BC Ernster, VL Rosenberg, RD Carney, PA Barlow, WE Geller, BM Kerlikowske, K Edwards, BK Lynch, CF Urban, N Key, CR Poplack, SP Worden, JK Kessler, LG TI Breast cancer surveillance consortium: A national mammography screening and outcomes database SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID FOLLOW-UP; SENSITIVITY; REGISTRY; BENEFIT C1 GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,SEATTLE,WA 98101. UNIV N CAROLINA,DEPT RADIOL,CHAPEL HILL,NC 27599. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131. DARTMOUTH HITCHCOCK MED CTR,NEW HAMPSHIRE MAMMOG NETWORK,NORRIS COTTON CANC CTR,LEBANON,NH 03756. UNIV VERMONT,VERMONT CANC CTR,BURLINGTON,VT 05401. UNIV IOWA,COLL MED,IOWA CITY,IA 52242. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. US FDA,ROCKVILLE,MD 20850. COLORADO DEPT HLTH & ENVIRONM,DENVER,CO. RP BallardBarbash, R (reprint author), NCI,APPL RES BRANCH,DCPC,NIH,EXECUT PLAZA N,RM 313,6130 EXECUT BLVD,MSC 7344,BETHESDA,MD 20892, USA. NR 25 TC 248 Z9 248 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1997 VL 169 IS 4 BP 1001 EP 1008 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XW981 UT WOS:A1997XW98100014 PM 9308451 ER PT J AU Avila, JL Avila, A Polegre, MA Marquez, VE AF Avila, JL Avila, A Polegre, MA Marquez, VE TI Specific inhibitory effect of 3-deazaneplanocin A against several Leishmania mexicana and L-braziliensis strains SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID S-ADENOSYLHOMOCYSTEINE HYDROLASE; AMERICAN LEISHMANIA; CARBOCYCLIC NUCLEOSIDES; ANTIVIRAL ACTIVITIES; TRYPANOSOMA-CRUZI; POTENT INHIBITOR; NEPLANOCIN-A; MULTIPLICATION; SINEFUNGIN; DONOVANI AB The growth inhibitory effect of 3-deazaneplanocin A (c(3)NpcA) was tested against some pathogenic members of the family of American Trypanosomatidae. Under our culture conditions, c(3)NpcA displayed a strongly and uniformly leishmanistatic effect on all 23 American Leishmania (L. mexicana and L. brasiliensis) strains in the study (mean dose producing 50% inhibition compared with control parasite growth [ID50] = 96 ng/ml, 0.32 mu M), but showed no inhibition against the several T. cruzi and T. rangeli strains tested with concentrations up to 10,000 ng/ml. This compound also induced a substantial expansion of the intracellular pools of both S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet), as well as a significant diminution of the AdoMet:AdoHcy ratio. Strong AdoHcy hydrolase activity was detected in American Leishmania promastigotes. At at a dose of 200 ng/ml, c(3)NpcA inhibited S-adenosyl-L-H-3-methylmethionine and (3)-thymidine incorporation by promastigotes after four days incubation in the presence of the drug. At a dose of 100 ng/ml, c(3)NpcA eliminated approximately 56% of the L. mexicana and L. brasiliensis from infected human macrophages, compared with simultaneously cultivated controls. Two schedules of 10 consecutive intraperitoneal injections of c(3)NpcA, with doses ranging from 0.5 to 1.5 mg/kg/day, significantly reduced development of cutaneous leishmanial infection produced in inbred BALB/c mice by L. b. guyanensis inoculation, although a few parasites remained at the inoculation site. C1 NCI,NIH,BETHESDA,MD 20892. RP Avila, JL (reprint author), INST BIOMED,APARTADO 4043,CARACAS 1010A,VENEZUELA. NR 24 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 1997 VL 57 IS 4 BP 407 EP 412 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA YC073 UT WOS:A1997YC07300005 PM 9347954 ER PT J AU Lee, G Pollard, HB AF Lee, G Pollard, HB TI Highly sensitive and stable phosphatidylserine liposome aggregation assay for annexins SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID PLACENTAL ANTICOAGULANT PROTEIN; CA-2+-DEPENDENT PHOSPHOLIPID-BINDING; ROUS-SARCOMA VIRUS; VESICLE AGGREGATION; LIPOCORTIN FAMILY; CHANNEL ACTIVITY; MEMBRANE-FUSION; A-431 CELLS; SUBSTRATE; PHOSPHORYLATION AB Annexins are a gene family of Ca2+-dependent membrane binding proteins which interact specifically with acidic phospholipids. We describe here details of highly sensitive and precise assays for annexins I and V, utilizing turbidometric analysis of phosphatidylserine Liposome aggregation. In the case of annexin I, the new assay is 7-fold more sensitive than the conventional chromaffin granule aggregation assay in terms of threshold for detection and the rate of increase of initial absorbance is 15-fold greater. Annexin V, which binds but does not aggregate liposomes, can be assayed on the basis of inhibition of Ca2+-dependent liposome aggregation. Further comparative advantages of the assay include lower expense and increased shelf life of the liposome reagent. C1 UNIFORMED SERV UNIV HLTH SCI,SCH MED,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. NIDDKD,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892. NR 30 TC 23 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT 1 PY 1997 VL 252 IS 1 BP 160 EP 164 DI 10.1006/abio.1997.2311 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XZ290 UT WOS:A1997XZ29000022 PM 9324954 ER PT J AU Pearson, TA Stone, EJ AF Pearson, TA Stone, EJ TI Community trials for cardiopulmonary health: Directions for public health practice, policy, and research SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material C1 NHLBI,BETHESDA,MD 20892. RP Pearson, TA (reprint author), UNIV ROCHESTER,SCH MED,ROCHESTER,NY 14627, USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 1997 VL 7 IS 7 SU S BP S1 EP S3 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YD395 UT WOS:A1997YD39500001 ER PT J AU Stone, EJ Pearson, TA Fortmann, SP McKinlay, JB AF Stone, EJ Pearson, TA Fortmann, SP McKinlay, JB TI Community-based prevention trials: Challenges and directions for public health practice, policy, and research SO ANNALS OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Conference on Community Trials for Cardiopulmonary Health - Directions for Public Health Practice, Policy and Research CY SEP 25-26, 1996 CL BETHESDA, MD SP NHLBI DE evidence-based public health practice; cardiovascular prevention trials ID STANFORD 5-CITY PROJECT; DISEASE PREVENTION; RISK-FACTORS; INTERVENTION; DESIGN; EDUCATION; PROGRAM; CATCH; NIH AB For over 20 years the National Heart, Lung, and Blood Institute (NHLBI) has supported community-based prevention research focused on cardiopulmonary risk-reduction. These prevention trials have involved intact groups in various major community settings as well as total communities. The mixed findings from these trials have advanced research and analytical methods, measurement approaches, and intervention strategies for community-based prevention studies and evidence-based public health practice. In addition, they have raised cross-cutting issues for the multidisciplinary research teams working in this field. The purpose of this article is to summarize findings from a NHLBI conference including: 1) a description of where prevention trials in varying community settings fit in the NHLBI research continuum; 2) a summary of findings from prevention trials in major community settings including schools, worksites, health care practices, religious groups, and entire communities; 3) a summary of the issues for research design, analysis, for practice, future research, and policy. (C) 1997 Elsevier Science Inc. C1 UNIV ROCHESTER,SCH MED,ROCHESTER,NY. STANFORD UNIV,SCH MED,PALO ALTO,CA 94304. NEW ENGLAND RES INST,WATERTOWN,MA 02172. RP Stone, EJ (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,6107 ROCKLEDGE DR,MSC 7936,ROOM 8134,BETHESDA,MD 20892, USA. NR 46 TC 23 Z9 23 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 1997 VL 7 IS 7 SU S BP S113 EP S120 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YD395 UT WOS:A1997YD39500013 ER PT J AU Schiffmann, R Heyes, MP Aerts, JM Dambrosia, JM Patterson, MC DeGraba, T Parker, CC Zirzow, GC Oliver, K Tedeschi, G Brady, RO Barton, NW Nagineni, C Kaneski, CR Murray, GJ Higgins, JJ Tournay, A Banerjee, TK Kreps, C Scott, LJC McKee, MA Crutchfield, K Frei, K AF Schiffmann, R Heyes, MP Aerts, JM Dambrosia, JM Patterson, MC DeGraba, T Parker, CC Zirzow, GC Oliver, K Tedeschi, G Brady, RO Barton, NW Nagineni, C Kaneski, CR Murray, GJ Higgins, JJ Tournay, A Banerjee, TK Kreps, C Scott, LJC McKee, MA Crutchfield, K Frei, K TI Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Academy-of-Neurology CY MAR, 1996 CL SAN FRANCISCO, CA SP Amer Acad Neurol ID INHERITED ENZYME DEFICIENCY; PERFORMANCE LIQUID-CHROMATOGRAPHY; KYNURENINE PATHWAY METABOLISM; BLOOD-BRAIN-BARRIER; QUINOLINIC ACID; CEREBROSPINAL-FLUID; REPLACEMENT THERAPY; PURIFIED GLUCOCEREBROSIDASE; SYSTEM; CHITOTRIOSIDASE AB We prospectively evaluated the clinical and biochemical responses to enzyme-replacement therapy (ERT) with macrophage-targeted glucocerebrosidase (Ceredase) infusions in 5 patients (age, 3.5-8.5 years) with type 3 Gaucher's disease. The patients were followed for up to 5 years. Enzyme dosage ranged from 120 to 480 U/kg of body weight/month. Systemic manifestations of the disease regressed in all patients. Neurological deficits remained stable in 3 patients and slightly improved in 1. One patient developed myoclonic encephalopathy. Cognitive deterioration occurred in 1 patient and electroencephalographic deterioration in 2. Sequential cerebrospinal fluid (CSF) samples were obtained during the first 3 years of treatment in 3 patients and were analyzed for biochemical markers of disease burden. Glucocerebroside and psychosine levels were not elevated in these specimens, whereas chitotriosidase and quinolinic acid were elevated in 2 patients. Progressive decrease in the CSF levels of these latter macrophage markers during 3 years of treatment implies a decreased number of Gaucher sells in the cerebral perivascular space. Similar changes were not observed in the patient who had a poor neurological outcome. In conclusion, ERT reverses systemic manifestations of type 3 Gaucher's disease and appears to reduce the burden of Gaucher cells in the brain-CSF compartment in some patients. C1 NINCDS,NEUROIMAGING BRANCH,NIH,BETHESDA,MD 20892. NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,NIH,BETHESDA,MD 20892. UNIV AMSTERDAM,EC SLATER INST BIOCHEM RES,DEPT BIOCHEM,NL-1012 WX AMSTERDAM,NETHERLANDS. NEI,IMMUNOL LAB,BETHESDA,MD 20892. RP Schiffmann, R (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,NIH,BLDG 10,ROOM 3D03,10 CTR DR,MSC 1260,BETHESDA,MD 20892, USA. RI Aerts, Johannes/A-1028-2009; OI Kaneski, Christine/0000-0003-1453-2502; Patterson, Marc/0000-0002-1116-126X NR 45 TC 81 Z9 84 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 1997 VL 42 IS 4 BP 613 EP 621 DI 10.1002/ana.410420412 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YA463 UT WOS:A1997YA46300011 PM 9382473 ER PT J AU Gutierrez, MI Bhatia, K Cherney, B Capello, D Gaidano, G Magrath, I AF Gutierrez, MI Bhatia, K Cherney, B Capello, D Gaidano, G Magrath, I TI Intraclonal molecular heterogeneity suggests a hierarchy of pathogenetic events in Burkitt's lymphoma SO ANNALS OF ONCOLOGY LA English DT Article DE bcl-6; c-myc; EBV; p53; pathogenesis ID EPSTEIN-BARR-VIRUS; P53 MUTATIONS; FOLLICULAR LYMPHOMA; CLONAL EXPANSION; TRANSGENIC MICE; MYC; SUBSEQUENT; INFECTION; DOMAIN; CELLS AB Background. Burkitt's lymphoma is a B-cell neoplasm characterized by a chromosomal translocation involving the c-myc gene. BL may carry, besides the c-myc translocation, several other lesions including a) mutations in c-myc, b) mutations in bcl-6, c) mutations in p53 and d) EBV genomes. In this report we describe a unique study of the timing of these genetic lesions during the evolution and progression of Burkitt's lymphoma. Materials and methods. From each of two patients with Burkitt's lymphoma, we established three different cell lines - from different sites or at different times in the clinical course of the disease (diagnosis and relapse). Chromosomal aberrations were analyzed by karyotyping and the presence of molecular lesions determined by Southern blot, PCR, SSCP and sequence analyses. Results. In each patient all the clones carry identical c-myc translocations, identical bcl-6 status (wild type or mutant) and the same productive VDJ rearrangement. However, within each individual patient, we could demonstrate the presence of intraclonal variation with respect to EBV, p53 mutations and c-myc mutations. Conclusions: c-myc translocation and bcl-6 mutations appear to be early events, mutations in the coding region of c-myc occur early but are an ongoing event, while mutations in the p53 gene seem to occur later. Discrete clonal bands reflecting independent EBV infection were observed in the cell lines from one HIV-associated Burkitt's lymphoma, suggesting the possibility that EBV infection may occur as a late event, at least in some HIV associated lymphomas. C1 NCI,LYMPHOMA BIOL SECT,PEDIAT BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD. UNIV TURIN,DIV INTERNAL MED,NOVARA,ITALY. RI Capello, Daniela/J-4110-2012 OI Capello, Daniela/0000-0001-9157-8753 NR 22 TC 20 Z9 20 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 1997 VL 8 IS 10 BP 987 EP 994 DI 10.1023/A:1008265304712 PG 8 WC Oncology SC Oncology GA YG830 UT WOS:A1997YG83000018 PM 9402172 ER PT J AU Santi, P Leone, MS Passarelli, B Cicchetti, S Imperiale, A Young, VL Knapp, TR AF Santi, P Leone, MS Passarelli, B Cicchetti, S Imperiale, A Young, VL Knapp, TR TI Mammographic visualization of a nonpalpable breast mass through a radiolucent breast implant SO ANNALS OF PLASTIC SURGERY LA English DT Article ID AUGMENTATION MAMMAPLASTY; FILLER MATERIALS; CANCER AB We report a woman who underwent augmentation mammaplasty as part of a clinical trial of the Trilucent (soybean oil-filled) breast implant in Genoa, Italy. Five months after surgery a mammography was performed in response to the patient's complaints of pressure and tightness in the area of her left breast. The mammogram clearly demonstrated a 5-mm fibroadenoma of the left breast. This is the first documented case of a nonpalpable breast lesion that was detected by mammography through the new radiolucent, triglyceride-filled implant. C1 IST SCI STUDIO & CURA TUMORI,IST,RADIODIAGNOST DIV,GENOA,ITALY. WASHINGTON UNIV,SCH MED,DIV PLAST & RECONSTRUCT SURG,ST LOUIS,MO 63130. LIPOMATRIX INC,NEUCHATEL,SWITZERLAND. RP Santi, P (reprint author), NATL CANC INST,DEPT PLAST & RECONSTRUCT SURG,LGO ROSANNA BENZI 10,I-16132 GENOA,ITALY. NR 14 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD OCT PY 1997 VL 39 IS 4 BP 333 EP 336 DI 10.1097/00000637-199710000-00001 PG 4 WC Surgery SC Surgery GA YA598 UT WOS:A1997YA59800001 PM 9339273 ER PT J AU Monks, A Scudiero, DA Johnson, GS Paull, KD Sausville, EA AF Monks, A Scudiero, DA Johnson, GS Paull, KD Sausville, EA TI The NCI anti-cancer drug screen: a smart screen to identify effectors of novel targets SO ANTI-CANCER DRUG DESIGN LA English DT Review ID TUMOR-CELL-LINES; CYTOTOXICITY; SENSITIVITY; INHIBITION; DISCOVERY; MECHANISM; LEUKEMIA; PATTERNS; PANEL C1 NCI,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,NIH,BETHESDA,MD 20892. RP Monks, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21702, USA. NR 26 TC 161 Z9 163 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD OCT PY 1997 VL 12 IS 7 BP 533 EP 541 PG 9 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA YG047 UT WOS:A1997YG04700002 PM 9365500 ER PT J AU Lee, CGL Jeang, KT Martin, MA Pastan, I Gottesman, MM AF Lee, CGL Jeang, KT Martin, MA Pastan, I Gottesman, MM TI Efficient long-term coexpression of a hammerhead ribozyme targeted to the U5 region of HIV-1 LTR by linkage to the multidrug-resistance gene SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RIBOSOME ENTRY SITE; APE LEUKEMIA-VIRUS; BONE-MARROW CELLS; HUMAN MDR1 GENE; P-GLYCOPROTEIN; IN-VITRO; INTERNAL INITIATION; PROGENITOR CELLS; HAIRPIN RIBOZYME AB Ribozymes as anti-HIV-l agents hold promise for the treatment of AIDS, They can be delivered into cells either exogenously or through an expression system, For effective protection against HIV-1, sufficient and sustained amounts of the antiviral ribozymes must be delivered into target cells, The coexpression of a dominant selectable marker with ribozymes would serve to enrich for cells containing the molecular antiviral and facilitate prolonged expression of these ribozymes, The multidrug resistance gene (MDR1) is a potential clinically relevant selectable marker and offers many advantages over other known dominant selectable markers, including the use of diverse pharmacologically characterized drug or drug combinations for selection, Harvey sarcoma-based retroviral vectors encoding the MDR1 multidrug transporter with a hammerhead ribozyme targeted to highly conserved sequences within the HIV-1 U5 LTR segment have been constructed in a bicistronic format, The internal ribosome entry site (IRES) from encephalomyocarditis virus was used to initiate translation of the MDR1 mRNA, The ribozyme remained functional despite being tethered to MDR1, Longterm, high-level expression of both the ribozyme and MDR1, as evident by RT-PCR and FAGS analysis, was observed in a human T cell line containing the construct selected with vincristine, a cytotoxic substrate for the multidrug transporter. C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20895. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20895. RP Lee, CGL (reprint author), NCI,CELL BIOL LAB,NIH,BLDG 37,ROOM 1B22,37 CONVENT DR MSC 4255,BETHESDA,MD 20895, USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 62 TC 11 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD OCT PY 1997 VL 7 IS 5 BP 511 EP 522 DI 10.1089/oli.1.1997.7.511 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA YE279 UT WOS:A1997YE27900008 PM 9361910 ER PT J AU Delporte, C Panyutin, IG Sedelnikova, OA Lillibridge, CD OConnell, BC Baum, BJ AF Delporte, C Panyutin, IG Sedelnikova, OA Lillibridge, CD OConnell, BC Baum, BJ TI Triplex-forming oligonucleotides can modulate aquaporin-5 gene expression in epithelial cells SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID BINDING REPRESSES TRANSCRIPTION; POLYLYSINE DNA COMPLEXES; HELIX FORMATION; WATER CHANNELS; IN-VITRO; ADENOVIRUS; INHIBITION; PROMOTER; DELIVERY; OLIGO(DG) AB Tripler-forming oligonucleotides (TFOs) may provide a useful approach to decrease gene transcription in vivo. We have identified two sequences in the rat aquaporin 5 (rAQP5) cDNA that are capable of forming a DNA triple helix. We designed four TFOs based on these sequences (a purine and a pyrimidine TFO per sequence). All four TFOs were able to bind to the rAQP5 cDNA at varying efficiencies in vitro as measured by using gel mobility shift assays. The TFOs were delivered to intact MDCK epithelial cells via adenovirus-polylysine complexes. Experiments with fluorescein-isothiocyanate-labeled oligonucleotides delivered in this way showed primarily a nuclear localization. Three of the four TFOs internalized by adenovirus-polylysine complexes were capable of decreasing rAQP5 expression in intact MDCK cells infected with a recombinant adenovirus encoding rAQP5. These data show that adenovirus-polylysine-TFO complexes can result in TFO delivery to the nucleus in intact epithelial cells and that TFOs may provide a useful way to selectively modulate rAQP5 gene expression. C1 NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. RP Delporte, C (reprint author), NIDR,GTTB,NIH,BLDG 10,ROOM 1N-113,MSC 1190,BETHESDA,MD 20892, USA. OI O'Connell, Brian/0000-0003-4529-7664 NR 44 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD OCT PY 1997 VL 7 IS 5 BP 523 EP 529 DI 10.1089/oli.1.1997.7.523 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA YE279 UT WOS:A1997YE27900009 PM 9361911 ER PT J AU Niebylski, ML Peacock, MG Fischer, ER Porcella, SF Schwan, TG AF Niebylski, ML Peacock, MG Fischer, ER Porcella, SF Schwan, TG TI Characterization of an endosymbiont infecting wood ticks, Dermacentor andersoni, as a member of the genus Francisella SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; SPOTTED-FEVER GROUP; RICKETTSIAE; TULARENSIS; IDENTIFICATION; SEQUENCES; STRAINS; TISSUES AB A microorganism (Dermacantor andersoni symbiont [DAS]) infecting Rocky Mountain wood ticks (D. andersoni) collected in the Bitterroot Mountains of western Montana was characterized as an endosymbiont belonging to the genus Francisella. Previously described as Wolbachia like, the organism's DNA was amplified from both naturally infected tick ovarial tissues and Vero cell cultures by PCR assay with primer sets derived from eubacterial 16S ribosomal DNA (rDNA) and Francisella membrane protein genes. The 16S rDNA gene sequence of the DAS was most similar (95.4%) to that of Francisella tularensis subsp. tularensis. Through a combination of Gimenez staining, PCR assay, and restriction fragment length polymorphism analysis, 102 of 108 female ticks collected from 1992 to 1996 were infected. Transovarial transmission to female progeny was 95.6%, but we found no evidence of horizontal transmission. C1 NIAID, ROCKY MT LABS, ROCKY MT MICROSCOPY BRANCH, NIH, HAMILTON, MT 59840 USA. RP Niebylski, ML (reprint author), NIAID, ROCKY MT LABS, MICROBIAL STRUCT & FUNCT LAB, NIH, 903 S 4TH ST, HAMILTON, MT 59840 USA. NR 45 TC 73 Z9 75 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 1997 VL 63 IS 10 BP 3933 EP 3940 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA XY723 UT WOS:A1997XY72300029 PM 9327558 ER PT J AU Carreno, RA Kissinger, JC McCutchan, TF Barta, JR AF Carreno, RA Kissinger, JC McCutchan, TF Barta, JR TI Phylogenetic analysis of haemosporinid parasites (Apicomplexa: Haemosporina) and their coevolution with vectors and intermediate hosts SO ARCHIV FUR PROTISTENKUNDE LA English DT Article; Proceedings Paper CT 11th Biennial Meeting of the International-Society-for-Evolutionary-Protistology CY AUG 08-13, 1996 CL UNIV KOLN, COLOGNE, GERMANY SP Int Soc Evolutionary Protistol, Deut Forschungsgemeinsch, Bonn, Minist Wissensch & Forsch Landes Nordrhein Westfalen, Univ Koln, Int Sci Fdn, New York HO UNIV KOLN DE definitive hosts; Diptera; evolution; Haemoproteus; Leucocytozoon; Plasmodium; ultrastructure ID AEGYPTI NOV-SP; HAEMOPROTEUS-MELEAGRIDIS HAEMOSPORINA; FINE-STRUCTURE; LEUCOCYTOZOON-SMITHI; EVOLUTIONARY RELATIONSHIPS; SPOROGONIC DEVELOPMENT; ELECTRON-MICROSCOPE; ERYTHROCYTIC STAGES; RIBOSOMAL-RNA; PLASMODIUM AB The phylogeny of representative species of the apicomplexan order Haemosporina DANILEWSKY, 1885 was reconstructed by cladistic analysis. Life cycle and ultrastructural characters for members of the genera Plasmodium, Haemoproteus, Leucocytozoon, Hepatocystis, and Polychromophilus were assessed using Eimeria tenella as an outgroup. Each of these genera was monophyletic and a clade containing Haemoproteus, Hepatocystis, and Polychromophilus was the sister group to Plasmodium. There was no obvious correlation between the parasite phylogeny and that of the vertebrate hosts. There was however, a general agreement between the parasite phylogeny and that of the dipteran hosts. There was no pattern of strict cospeciation between parasites and these overall host groups, but there appears to be more evidence of coevolution of parasites with their vectors than with their vertebrate hosts. This correspondence is indicative of a more ancient parasite-vector association. C1 UNIV GUELPH,ONTARIO VET COLL,DEPT PATHOBIOL,GUELPH,ON N1G 2W1,CANADA. NIAID,GROWTH & DEV SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RI Kissinger, Jessica/E-9610-2010; OI Kissinger, Jessica/0000-0002-6413-1101; Barta, John/0000-0001-6896-2271 NR 85 TC 8 Z9 8 U1 1 U2 6 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0003-9365 J9 ARCH PROTISTENKD JI Arch. Protistenkd. PD OCT PY 1997 VL 148 IS 3 BP 245 EP 252 PG 8 WC Microbiology SC Microbiology GA YG288 UT WOS:A1997YG28800003 ER PT J AU Tsilou, E Hamel, CP Yu, S Redmond, TM AF Tsilou, E Hamel, CP Yu, S Redmond, TM TI RPE65, the major retinal pigment epithelium microsomal membrane protein, associates with phospholipid liposomes SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE phospholipids; liposomes; retinal pigment epithelium; Ca2+-independent; microsomal membranes ID BOVINE SEMINAL PLASMA; BINDING-PROTEIN; MONOCLONAL-ANTIBODIES; AGGREGATION; RECEPTOR; VESICLES; IDENTIFICATION; CALPACTIN; EXCHANGE; CLONING AB The retinal pigment epithelium (RPE)-specific protein RPE65 is the major protein of the RPE microsomal membrane fraction, Though RPE65 lacks transmembrane domains or signal peptide, detergents are required for its maximally effective solubilization in isotonic buffers, However, in 0.75-1.0 M KCl, RPE65 is as soluble without detergent, indicating a peripheral membrane association, We wished to understand why this non-membrane-inserted protein was so closely associated with RPE microsomal membranes, To explore the possible involvement of interactions with phospholipids, an isotonic salt-soluble extract of RPE was incubated with phosphatidylcholine (PC)/phosphatidylserine (PS)/phosphatidylinositol liposomes and centrifuged to sediment the liposomes. RPE65 cosedimented with the liposome pellet, RPE65 also cosedimented with synthetic dipalmitoyl-, 1-palmitoyl, 2-docosahexaenoyl-PC or dipalmitoyl-PS liposomes. Incubation with 1 mM Ca2+ or 1 mM EGTA had no effect, indicating a Ca2+-independent association. A spectrophotometric assay showed that this interaction of RPE65 with phospholipid vesicles resulted in increased light scattering, consistent with phospholipid vesicle aggregation, Resonance energy transfer experiments showed that any putative aggregation occurred without subsequent vesicle fusion, This PC affinity was further confirmed by incubation of RPE extract with dimyristoyl-PC-immobilized artificial membrane (IAM.PC) matrix, The RPE65 selectively bound and was elutable with 2% detergent. This RPE65-phospholipid liposome association may explain the solubilization characteristics of RPE65 and may be related to the function of RPE65 and to its physical association with the RPE smooth endoplasmic reticulum. (C) 1997 Academic Press. C1 NEI,RETINAL CELL & MOL BIOL LAB,NIH,BETHESDA,MD 20892. OI Redmond, T. Michael/0000-0002-1813-5291 NR 34 TC 37 Z9 38 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 1 PY 1997 VL 346 IS 1 BP 21 EP 27 DI 10.1006/abbi.1997.0276 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YA566 UT WOS:A1997YA56600004 PM 9328280 ER PT J AU Rapoport, JL Giedd, J Kumra, S Jacobsen, L Smith, A Lee, P Nelson, J Hamburger, S AF Rapoport, JL Giedd, J Kumra, S Jacobsen, L Smith, A Lee, P Nelson, J Hamburger, S TI Childhood-onset schizophrenia - Progressive ventricular change during adolescence SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CAUDATE NUCLEI VOLUMES; BRAIN MORPHOLOGY; ENLARGEMENT; CLOZAPINE; DISORDER; MRI AB Background: There is controversy about progression in brain abnormalities in later-onset schizophrenia. This study looked for more striking progression in brain abnormalities during adolescence in a chronically ill, treatment-refractory sample of patients with childhood-onset schizophrenia who had had more prepsychotic developmental disturbance, but clinical and neurobiological characteristics similar to those of patients with treatment-refractory adult-onset schizophrenia who have poor outcome. Methods: Anatomic brain magnetic resonance images were obtained for 16 children and adolescents with onset of schizophrenia by 12 years of age and 24 temporally yoked, age-and sex-matched healthy controls. Subjects were scanned on initial admission and rescanned after 2 years with the identical equipment and measurement methods. Results: Childhood schizophrenics showed a significantly greater increase in ventricular volume than did controls, for whom ventricles did not increase significantly (analysis of variance, diagnosis x time, F = 16.1, P < .001). A significant decrease in midsagittal thalamic area was also seen for the schizophrenics (P = .03), which was unchanged at rescan for controls. These differential brain changes correlated significantly with each other and tended to be predicted by both prepsychotic developmental abnormality (Premorbid Assessment Scale, P = .06) and Brief Psychiatric Rating Scale at follow-up (P = .07). Conclusions: More consistent progressive ventricular enlargement was seen during adolescence for this childhood-onset sample than has been reported for adult-onset populations. The brain imaging results support other clinical data showing both early and late deviations in brain development for at least this rare subgroup of treatment-refractory, very-early-onset schizophrenic patients. RP Rapoport, JL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 50 TC 192 Z9 192 U1 7 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1997 VL 54 IS 10 BP 897 EP 903 PG 7 WC Psychiatry SC Psychiatry GA YA733 UT WOS:A1997YA73300001 PM 9337768 ER PT J AU Zahn, TP Jacobsen, LK Gordon, CT McKenna, K Frazier, JA Rapoport, JL AF Zahn, TP Jacobsen, LK Gordon, CT McKenna, K Frazier, JA Rapoport, JL TI Autonomic nervous system markers of psychopathology in childhood-onset schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CONDUCTANCE ORIENTING RESPONSE; SKIN-CONDUCTANCE; ELECTRODERMAL ACTIVITY; SPONTANEOUS FLUCTUATIONS; CLINICAL STATE; CHILDREN; CLOZAPINE; SYMPTOMATOLOGY; DEPRESSION; FLUPHENAZINE AB Background: Consistent abnormalities in peripheral indicators of autonomic activity, ie, skin conductance (SC) and heart rate (HR), have been reported in adult-onset schizophrenia. Herein, we use these markers to test the hypothesis of continuity between childhood-onset schizophrenia and adult-onset schizophrenia. Methods: Skin conductance and HR were recorded from 21 severely ill children and adolescents (mean age, 14.1 years) with childhood-onset (less than or equal to 12 years) schizophrenia (patient group) and from 54 age-matched controls (control group) during a rest period, a series of innocuous tones, reaction time insructions, and a simple warned reaction time task. Results: During rest, patients had higher rates of spontaneous SC responses (SCRs) and HRs than controls, but their SC level was marginally lower and declined more slowly over time. Half of the patients, compared with 4% of the controls, failed to give SC-orienting responses to the first 2 tones. Patients who responded had impaired SCR magnitudes, and their habituation was more erratic than that of controls. The increase in SC level and SCR frequency at the onset of the task period was greatly attenuated in the patients, so that both variables were higher in controls. Patients bad smaller SCRs and anticipatory HR responses to the reaction time stimuli. Skin conductance nonresponding was associated with negative and total symptoms, and spontaneous SCR frequency was associated with positive symptoms. Conclusions: The findings show similar abnormalities in autonomic nervous system activity in childhood-onset schizophrenia to those found in adult chronic schizophrenia, thus supporting the hypothesis of continuity of the childhood and adult forms of the illness. Comparisons with data from other childhood disorders suggest that the combination of low-elicited SC activity with high levels of spontaneous SC activity may be specific to schizophrenia. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Zahn, TP (reprint author), NIMH,LAB BRAIN & COGNIT,FED BLDG,ROOM B1A14,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 76 TC 46 Z9 46 U1 5 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1997 VL 54 IS 10 BP 904 EP 912 PG 9 WC Psychiatry SC Psychiatry GA YA733 UT WOS:A1997YA73300002 PM 9337769 ER PT J AU Su, TP Malhotra, AK Hadd, K Breier, A Pickar, D AF Su, TP Malhotra, AK Hadd, K Breier, A Pickar, D TI D-2 dopamine receptor occupancy: A crossover comparison of risperidone with clozapine therapy in schizophrenic patients SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NR 5 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1997 VL 54 IS 10 BP 972 EP 973 PG 2 WC Psychiatry SC Psychiatry GA YA733 UT WOS:A1997YA73300016 PM 9337781 ER PT J AU Niemela, JE Cecco, SA Rehak, NN Elin, RJ AF Niemela, JE Cecco, SA Rehak, NN Elin, RJ TI The effect of smoking on the serum ionized magnesium concentration is method-dependent SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NICOTINE; CALCIUM; INVIVO; BLOOD AB Objective.-To investigate the effect of smoking on serum ionized magnesium concentration ([Mg2+]) determined by the NOVA and AVL Mg ion-selective electrodes (Mg ISEs). Methods.-Subjects were apparently healthy smokers (n = 30) and nonsmokers (n = 30). We determined NOVA and AVL [Mg2+] in their serum and in test solutions containing compounds increased by smoking. We also determined subjects' white blood cell and differential counts. Results.-For smokers, the mean values for NOVA and AVL [Mg2+] differed significantly (0.41 vs 0.52 mmol/L, respectively). We found a significant intramethod difference in NOVA [Mg2+] (0.11 mmol/L, P<.0001) between smokers and nonsmokers. A dose-dependent decrease in NOVA [Mg2+] was observed with an increase in cigarettes/day. NOVA [Mg2+] inversely correlated with white blood cell counts. There was no interference by the test compounds with either Mg ISE. Conclusion.-Smoking may induce a serum factor, possibly related to white blood cells, that negatively interferes with the response of the NOVA Mg ISE. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. OI Niemela, Julie/0000-0003-4197-3792 NR 17 TC 7 Z9 7 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 1997 VL 121 IS 10 BP 1087 EP 1092 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA YB125 UT WOS:A1997YB12500011 PM 9341589 ER PT J AU Vreugdenhil, H Brouwers, P Wolters, P Bakker, D Moss, H AF Vreugdenhil, H Brouwers, P Wolters, P Bakker, D Moss, H TI Spontaneous eye blinking, a measure of dopaminergic function, in children with acquired immunodeficiency syndrome SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article; Proceedings Paper CT 19th Annual Mid-Year Meeting of the International-Neuropsychological-Society CY JUN 20, 1996 CL VELDHOVEN, NETHERLANDS SP Int Neuropsychol Soc ID SYMPTOMATIC HIV DISEASE; DEFICIT-HYPERACTIVITY DISORDER; NERVOUS-SYSTEM; VIRUS-INFECTION; PEDIATRIC AIDS; BRAIN-SCAN; CT; ABNORMALITIES; RATES; THERAPY AB Objective: To investigate possible alterations in dopaminergic function in children with acquired immunodeficiency syndrome by evaluating spontaneous eye blink rate, a putative measure of central dopaminergic function. Design: Evaluation of previously videotaped test sessions of a consecutive case series of 50 children (mean age, 5.2 years; range, 2-12 years) with acquired immunodeficiency syndrome. Setting: Government medical research center. Results: Intrarater reliability was high, expected covariation of blink rate with age and concurrent mental activity were confirmed, and obtained rates were similar to published data. Higher blink rates, suggestive of increased dopaminergic function, were associated with more severe cortical atrophy (P < .05) and white matter abnormality (P < .05) on computed tomographic brain scans. The presence or severity of basal ganglia calcifications did not seem to influence blink rate. In addition, higher blink rates were associated with higher ratings of depressed affect (P < .05) and lower ratings of hyperactive behaviors (P < .05) during other test activities. Conclusions: The higher blink rates in human immunodeficiency virus-infected children with more severe cortical abnormalities suggest increased central dopamine activity compared with that in children without cortical computed tomographic brain scan abnormalities. Thus, as a result of structural brain abnormalities, neurotransmitter levels in children with acquired immunodeficiency syndrome may vary and this may be reflected in their socioemotional functioning. C1 NCI,PEDIAT NEUROPSYCHOL GRP,NIH,HIV & AIDS MALIGNANCY BRANCH,BETHESDA,MD 20892. MED ILLNESS COUNSELING CTR,CHEVY CHASE,MD. FREE UNIV AMSTERDAM,DEPT PEDIAT NEUROPSYCHOL,AMSTERDAM,NETHERLANDS. NR 54 TC 6 Z9 6 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD OCT PY 1997 VL 151 IS 10 BP 1025 EP 1032 PG 8 WC Pediatrics SC Pediatrics GA YA946 UT WOS:A1997YA94600011 PM 9343014 ER PT J AU Kim, SS Owens, IS Sheen, YY AF Kim, SS Owens, IS Sheen, YY TI Comparison of glucuronidating activity of two human cDNAs, UDPGTh1 and UDPGTh2 SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Article DE UDP-glucuronosyltransferase cDNA; UDPCTh1; UDPGTh2; HLUG25; chimeric cDNA ID UDP-GLUCURONOSYLTRANSFERASE; MESSENGER-RNA; CLONING AB Two human liver UDP-glucuronosyltransferase cDNA clones, HLUG25 and UDPGTh2 were previously shown to encode isozymes active in the glucuronidation of hyodeoxycholic acid (HDCA) and certain estrogen derivatives (e.g., estriol and 3,4-catechol estrogens), respectively. In this study we have found that the UDPGTh2-encoded isoform (UDPGTh2) and HLUG25-encoded isoform (UDPGTh1) have parallel aglycone specificities. When expressed in COS 1 cells, each isoform metabolized three types of dihydroxy- or trihydroxy-substituted ring structures, including the 3,4-catechol estrogen (4-hydroxyestrone), estriol, 17-epiestriol, and HDCA, but the UDPGTh2 isozyme was 100-fold more efficient than UDPGTh1. UDPGTh1 and UDPGTh2 were 86% identical overall (76 differences out of 528 amino acids), including 55 differences in the first 300 amino acids of the amino terminus, a domain which conferred the. substrate specificity. The data indicated that a high level of conservation in the amino terminus was not required for the preservation of substrate selectivity. Analysis of glucuronidation activity encoded by UDPGTh1/UDPGTh2 chimeric cDNA constructed at their common restriction sites, Sac I (codon 297), Nco I (codon 385), and Hha I (codon 469), showed that nine amino acids between residues 385 and 469 were important for catalytic efficiency, suggesting that this region represented a domain which was critical for the catalysis but distinct from that responsible for aglycone selection. These data indicate that UDPGTh2 is a primary isoform responsible for the detoxification of the bile salt intermediate as well as the active estrogen intermediates. C1 EWHA WOMANS UNIV,COLL PHARM,SEOUL 120750,SOUTH KOREA. NICHHD,SECT DRUG METAB,HERITABLE DIS BRANCH,NIH,BETHESDA,MD. NR 11 TC 1 Z9 1 U1 0 U2 0 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD OCT PY 1997 VL 20 IS 5 BP 454 EP 458 DI 10.1007/BF02973939 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YD399 UT WOS:A1997YD39900012 PM 18982489 ER PT J AU Dong, M Owens, IS Sheen, YY AF Dong, M Owens, IS Sheen, YY TI Cloning and expression of human liver UDP-glucuronosyltransferase cDNA, UDPCTh2 SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Article DE UDP-glucuronosyltransferase cDNA; UDPGTh2; tunicamycin ID FUNCTIONAL-HETEROGENEITY; ACID; GLUCURONYLTRANSFERASE; GLUCURONIDATION; ENZYME; FORM AB The human liver cDNA clone UDPGTh2, encoding a liver UDP-glucuronosyltransferase (UDPGT) was isolated from a lambda gt 11 cDNA library by hybridization to mouse transferase cDNA clone, UDPGTm1. UDPGTh2 encoded a 529 amino acid protein with an amino terminus membrane-insertion signal peptide and a carboxyl terminus membrane-spanning region. There were three potential asparagine-linked glycosylation sites at residues 67, 68, and 315. In order to obtain UDPGTh2 protein encoded from cloned human liver UDP-glucuronosyltransferase cDNA, the clone was inserted into the pSVL vector (pUDPGTh2) and expressed in COS 1 cells. The presence of a transferase with Mr similar to 52,000 in transfected cells cultured in the presence of [S-35]methionine was shown by immunocomplexed products with goat antimouse transferase IgG and protein A-Sepharose and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The expressed UDPGT was a glycoprotein as indicated by electrophoretic mobility shift in Mr similar to 3,000-4,000 when expressed in the presence of tunicamycin. The extent of glycosylation was difficult to assess, although one could assume that glycosyl structures incorporated at the level of endoplasmic reticulum were always the core oligosaccharides. Thus, it is likely that at least two moieties inserted can account for the shift of Mr similar to 3,000-4,000. This study demonstrates the cDNA and deduced amino acid sequence of human liver UDP-glucuronosyltransferase cDNA, UDPGTh2. C1 EWHA WOMANS UNIV,COLL PHARM,SEOUL 120750,SOUTH KOREA. NICHHD,SECT DRUG METAB,HERITABLE DIS BRANCH,NIH,BETHESDA,MD. NR 15 TC 3 Z9 3 U1 0 U2 0 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD OCT PY 1997 VL 20 IS 5 BP 459 EP 464 DI 10.1007/BF02973940 PG 6 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YD399 UT WOS:A1997YD39900013 PM 18982490 ER PT J AU Ahn, MR Owens, IS Sheen, YY AF Ahn, MR Owens, IS Sheen, YY TI Expression of human liver 3,4-catechol estrogens UDP-glucuronosyltransferase cDNA in COS 1 cells SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Article DE UDP-glucuronosyltransferase cDNA; UDPGTh2; 4-hydroxyestrone; estriol ID HUMAN-BREAST-CANCER; ANTIESTROGEN-BINDING-SITES; FUNCTIONAL-HETEROGENEITY; RECEPTOR; ACID; FORM; GLUCURONIDATION; SEQUENCE; CLONING; PROTEIN AB The human cDNA clone UDPGTh2, encoding a liver UDP-glucuronosyltransferase (UDPGT), was isolated from a lambda gt 11 cDNA library by hybridization to mouse transferase cDNA clone, UDPGTm1. The two clones had 74% nucleotide sequence identities in the coding region UDPGTh2 encoded a 529 amino acid protein with an amino terminus membrane-insertion signal peptide and a carboxyl terminus membrane-spanning region. In order to establish substrate specificity, the clone was inserted into the pSVL vector (pUDPGTh2) and expressed in COS 1 cells. Sixty potential substrates were tested using cells transfected with pUDPGTh2. The order of relative substrate activity was as follows. 4-hydroxyestrone > estriol >2-hydroxyestriol > 4-hydroxyestradiol > alpha-hydroxyestradiol > 5 alpha-androstane-3 alpha, 11 beta, 17 beta-triol=5 beta-androstane-3 alpha, 11 beta, 17 beta-triol. There were only trace amounts of gulcuronidation of 2-hydroxyestradiol and 2-hydroxyestrone, and in contrast to other cloned transferase, no gulcuronidation of either the primary estrogens and androgens (estrone, 17 beta-estradiol/testosterone, androsterone) or any of the exogenous substrates tested was detected. A lineweaver-Burk plot of the effect of 4-hydroxyestrone concentration on the velocity of glucuronidation showed an apparent Km of 13 mu M. The unique specificity of this transferase might play an important role in regulating the level and activity of these potent and active estrogen metabolites. C1 EWHA WOMANS UNIV,COLL PHARM,SEOUL 120750,SOUTH KOREA. NICHHD,SECT DRUG METB,HERITABLE DIS BRANCH,NIH,BETHESDA,MD. NR 28 TC 1 Z9 1 U1 0 U2 1 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD OCT PY 1997 VL 20 IS 5 BP 465 EP 470 DI 10.1007/BF02973941 PG 6 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YD399 UT WOS:A1997YD39900014 PM 18982491 ER PT J AU Evans, RW Shaten, BJ Hempel, JD Cutler, JA Kuller, LH AF Evans, RW Shaten, BJ Hempel, JD Cutler, JA Kuller, LH TI Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE homocyst(e)ine; cardiovascular disease; MRFIT; prospective ID CORONARY HEART-DISEASE; SERUM TOTAL HOMOCYSTEINE; PLASMA HOMOCYST(E)INE; MYOCARDIAL-INFARCTION; VASCULAR-DISEASE; METHYLENETETRAHYDROFOLATE REDUCTASE; ISCHEMIC STROKE; ARTERY DISEASE; FOLATE; HYPERHOMOCYSTEINEMIA AB A nested case-control study was undertaken involving men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Serum samples from 712 men, stored for up to 20 years, were analyzed for homocyst(e)ine. Cases involved nonfatal myocardial infarctions (MIs), identified through the active phase of the study, which ended on February 28, 1982, and deaths due to coronary heart disease (CHD), monitored through 1990. The nonfatal MIs occurred within 7 years of sample collection, whereas the majority of CHD deaths occurred more than 11 years after sample collection. Mean homocyst(e)ine concentrations were in the expected range and did not differ significantly between case patients and control subjects: MI cases, 12.6 mu mol/L; MI controls, 13.1 mu mol/L; CHD death cases, 12.8 mu mol/L; and CHD controls, 12.7 mu mol/L. Odds ratios versus quartile 1 for CHD deaths and MIs combined were as follows: quartile 2, 1.03; quartile 3, 0.84; and quartile 4, 0.92. Thus, in this prospective study, no association of homocyst(e)ine concentration with heart disease was detected. Homocyst(e)ine levels were weakly associated with the acute-phase protein (C-reactive protein). These results are discussed with respect to the suggestion that homocyst(e)ine is an independent risk factor for heart disease. C1 UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15261. UNIV MINNESOTA,MRFIT COORDINATING CTR,DIV BIOSTAT,MINNEAPOLIS,MN. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP Evans, RW (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,503 PARRAN HALL,130 DESOTO ST,PITTSBURGH,PA 15261, USA. FU NHLBI NIH HHS [R01-HL-43232] NR 50 TC 268 Z9 277 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 1997 VL 17 IS 10 BP 1947 EP 1953 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YE282 UT WOS:A1997YE28200015 PM 9351358 ER PT J AU Hong, MK Vossoughi, J Mintz, GS Kauffman, RD Hoyt, RF Cornhill, JF Herderick, EE Leon, MB Hoeg, JM AF Hong, MK Vossoughi, J Mintz, GS Kauffman, RD Hoyt, RF Cornhill, JF Herderick, EE Leon, MB Hoeg, JM TI Altered compliance and residual strain precede angiographically detectable early atherosclerosis in low-density lipoprotein receptor deficiency SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cholesterol; compliance; intravascular ultrasound; residual strain; atherosclerosis ID CORONARY-ARTERY DISEASE; LEFT-VENTRICULAR HYPERTROPHY; ZERO-STRESS STATE; INTRAVASCULAR ULTRASOUND; WHHL-RABBIT; HUMAN AORTA; HYPERLIPIDEMIC ATHEROGENESIS; CHOLESTEROL ACYLTRANSFERASE; MYOCARDIAL-INFARCTION; TRANSGENIC RABBITS AB Background This study was performed to detect changes in vascular biomechanical properties early in atherogenesis. Methods and Results Age- and weight-matched LDL-receptor deficient Watanabe hypercholesterolemic male rabbits (Group I: n=11) and normal rabbits (Group II: n=11) were studied. Easting plasma lipoprotein concentrations, aortic angiography and intravascular ultrasound, in vivo aortic compliance evaluation, ex vivo aortic residual strain measurements, aortic lipid content and histopathology were determined. Plasma cholesterol was increased 9.8 fold and aortic cholesterol content was increased from 20 to 43 fold in Group I compared to Group II, respectively (P<.00005). Angiography revealed no stenoses in either group, whereas intravascular ultrasound and histological studies of Group I showed small circumferential plaques with <10% cross-sectional area involvement. The residual strain in Group I was significantly increased in the ascending thoracic aorta (22.1+/-6.9% versus 10.4+/-3.2% in Group II, P<.0001), descending thoracic aorta (15.7+/-7.2% versus 4.8+/-1.3% in Group II, P<.0001), and abdominal aorta (18.0+/-4.8% versus 8.3+/-6.3% in Group II, P<.005). Changes in residual strain were inversely correlated with the aortic cholesterol content in the ascending thoracic aorta (r=-.72; P=-.001), descending thoracic aorta (r=-.95; P<.001), and abdominal aorta (r=-.51; P=.019). Conclusions Early atherosclerosis in LDL-receptor deficient rabbits, undetectable by angiography yet observed by intravascular ultrasound imaging and histology, is associated with marked changes in ex vivo residual strain. Alterations in vascular biomechanical properties, associated with changes in cholesterol content, may have physiologic consequences and may be useful in detecting and quantitating early atherosclerosis. C1 NHLBI,CELL BIOL SECT,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NHLBI,LAB ANIM MED & SURG,NIH,BETHESDA,MD 20892. WASHINGTON HOSP CTR,DEPT INTERNAL MED,DIV CARDIOL,WASHINGTON,DC 20010. UNIV DIST COLUMBIA,ENGN RES CTR,WASHINGTON,DC. CLEVELAND CLIN,CLEVELAND,OH 44106. OHIO STATE UNIV,CTR BIOMED ENGN,COLUMBUS,OH 43210. FU NHLBI NIH HHS [HL-54246-01] NR 76 TC 23 Z9 23 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 1997 VL 17 IS 10 BP 2209 EP 2217 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YE282 UT WOS:A1997YE28200048 PM 9351391 ER PT J AU Rubin, FA Rothman, SW AF Rubin, FA Rothman, SW TI Extinction or revitalization: Clinical microbiologists look to the future SO ASM NEWS LA English DT Editorial Material C1 NIAID,DIV MICROBIOL & INFECT DIS,NIH,ROCKVILLE,MD. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,OFF RES MANAGEMENT,WASHINGTON,DC 20307. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0044-7897 J9 ASM NEWS JI ASM News PD OCT PY 1997 VL 63 IS 10 BP 530 EP 531 PG 2 WC Microbiology SC Microbiology GA XZ520 UT WOS:A1997XZ52000004 ER PT J AU Brewer, HB AF Brewer, HB TI Gene targets for treatment of cardiovascular disease SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 2 EP 2 DI 10.1016/S0021-9150(97)88130-0 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10600007 ER PT J AU SantamarinaFojo, S AF SantamarinaFojo, S TI Use of transgenic animal models to study enzymes involved in lipoprotein metabolism and atherosclerosis SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 5 EP 5 DI 10.1016/S0021-9150(97)88135-X PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10600013 ER PT J AU Brousseau, ME Wang, J Demosky, SJ Vaisman, BL SantamarinaFojo, S Brewer, HB Hoeg, JM AF Brousseau, ME Wang, J Demosky, SJ Vaisman, BL SantamarinaFojo, S Brewer, HB Hoeg, JM TI Correction of hypoalphalipoproteinemia in LDL receptor deficiency by lecithin:cholesterol acyltransferase (LCAT) SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 32 EP 33 DI 10.1016/S0021-9150(97)88256-1 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10600134 ER PT J AU Tornwall, ME Virtamo, J Haukka, J Aro, A Albanes, D Edwards, BK Huttunen, J AF Tornwall, ME Virtamo, J Haukka, J Aro, A Albanes, D Edwards, BK Huttunen, J TI Alpha-tocopherol and beta-carotene supplementation and incidence of intermittent claudication SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NATL PUBL HLTH INST,ATBC STUDY,HELSINKI,FINLAND. NCI,BETHESDA,MD 20892. RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 NR 0 TC 1 Z9 1 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 51 EP 51 DI 10.1016/S0021-9150(97)88344-X PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10600221 ER PT J AU Cannon, RO AF Cannon, RO TI Effects of estrogen on the endothelium in postmenopausal women: Implications for atherosclerosis SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 113 EP 113 DI 10.1016/S0021-9150(97)88623-6 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10600502 ER PT J AU Brook, JG Gordon, D Rifkind, B AF Brook, JG Gordon, D Rifkind, B TI Prevention of stroke by cholesterol-lowering: A meta-analysis SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 TECHNION ISRAEL INST TECHNOL,RAMBAM MED CTR,DEPT MED D,HAIFA,ISRAEL. NHLBI,DIV CARDIOVASC DIS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 122 EP 122 DI 10.1016/S0021-9150(97)88666-2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10600540 ER PT J AU Bader, G Edelstein, C Shamburek, RD Nishiwaki, M Scanu, AM Fellin, R Brewer, HB AF Bader, G Edelstein, C Shamburek, RD Nishiwaki, M Scanu, AM Fellin, R Brewer, HB TI The in vivo of metabolism of free-Apo(a) in normals and subjects with abetalipoproteinemia SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NHLBI,MDB,NIH,BETHESDA,MD 20892. UNIV CHICAGO,CHICAGO,IL 60637. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 137 EP 137 DI 10.1016/S0021-9150(97)88737-0 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10600615 ER PT J AU Rapola, JM Virtamo, J Ripatti, S Heinonen, OP Taylor, PR Albanes, D Huttunen, JK AF Rapola, JM Virtamo, J Ripatti, S Heinonen, OP Taylor, PR Albanes, D Huttunen, JK TI Alpha-tocopherol and beta-carotene supplementation in primary prevention of major coronary events SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NATL PUBL HLTH INST,HELSINKI,FINLAND. UNIV HELSINKI,DEPT PUBL HLTH,FIN-00014 HELSINKI,FINLAND. NCI,BETHESDA,MD 20892. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 2 Z9 2 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 207 EP 207 DI 10.1016/S0021-9150(97)89071-5 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10600946 ER PT J AU Kruth, HS Zhang, WY Gaynor, PM AF Kruth, HS Zhang, WY Gaynor, PM TI Aggregated LDL induces and enters surface-connected compartments of human monocyte-macrophages: A process independent of the LDL receptor SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NHLBI,SECT EXPT ATHEROSCLEROSIS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 233 EP 233 DI 10.1016/S0021-9150(97)89239-8 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10601074 ER PT J AU Hu, YH Cheng, L Hochleitner, BW Xu, QB AF Hu, YH Cheng, L Hochleitner, BW Xu, QB TI Activation of mitogen-activated protein kinases and activator protein-1 in rat arteries after balloon injury SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 AUSTRIAN ACAD SCI,INST BIOMED AGING RES,INNSBRUCK,AUSTRIA. UNIV INNSBRUCK HOSP,DEPT SURG,A-6020 INNSBRUCK,AUSTRIA. NIA,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 242 EP 242 DI 10.1016/S0021-9150(97)89283-0 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10601117 ER PT J AU Hoeg, JM Hong, MK Vossoughi, J Mintz, GS Summers, RM Hoyt, RF Wolff, S Leon, MB Ellehham, S AF Hoeg, JM Hong, MK Vossoughi, J Mintz, GS Summers, RM Hoyt, RF Wolff, S Leon, MB Ellehham, S TI Characterizing and quantitating early atherogenesis in rabbits and man in vivo SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 WASHINGTON HOSP CTR,BETHESDA,MD. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 295 EP 295 DI 10.1016/S0021-9150(97)89525-1 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10601356 ER PT J AU Li, ZH Lakatta, EG AF Li, ZH Lakatta, EG TI Localized apoptosis and enhanced expression of p53 and interleukin-1 beta converting enzyme (ICE) proteins in human aortic atherosclerotic lesions SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 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 1997 VL 134 IS 1-2 SI SI BP 299 EP 299 DI 10.1016/S0021-9150(97)89542-1 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10601371 ER PT J AU Nishiwaki, M Ishikawa, T Nazih, H Bader, G Remaley, A Tally, G Shemburek, R Hannuskela, M Brewer, HB AF Nishiwaki, M Ishikawa, T Nazih, H Bader, G Remaley, A Tally, G Shemburek, R Hannuskela, M Brewer, HB TI Human lecithin:cholesterol acyltransferase deficiency: In vivo LpX kinetics and its cell association with various cells SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NATL DEF MED COLL,TOKOROZAWA,SAITAMA 359,JAPAN. NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 352 EP 352 DI 10.1016/S0021-9150(97)89793-6 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10601623 ER PT J AU Sakai, N Vaisman, BL Koch, CA Hoyt, RF Meyn, SM Paiz, JA Brewer, HB SantamarinaFojo, S AF Sakai, N Vaisman, BL Koch, CA Hoyt, RF Meyn, SM Paiz, JA Brewer, HB SantamarinaFojo, S TI Lecithin:Cholesterol acyltransferase (LCAT) knockout mice: A new animal model for human LCAT-deficiency SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NHLBI,LAMS,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 372 EP 373 DI 10.1016/S0021-9150(97)89890-5 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10601718 ER PT J AU Sakai, N Arai, T Maruyama, T Yamashita, S SantamarinaFojo, S Brewer, HB Matsuzawa, Y AF Sakai, N Arai, T Maruyama, T Yamashita, S SantamarinaFojo, S Brewer, HB Matsuzawa, Y TI Two novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic patients SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 OSAKA UNIV,SCH MED,DEPT INTERNAL MED 2,SUITA,OSAKA 565,JAPAN. NHLBI,MDB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 373 EP 373 DI 10.1016/S0021-9150(97)89891-7 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10601719 ER PT J AU Nazih, H Remaley, A Hannuksela, M Meyn, SM Kindt, MR Alaupovic, P Brewer, HB AF Nazih, H Remaley, A Hannuksela, M Meyn, SM Kindt, MR Alaupovic, P Brewer, HB TI Relative importance of apoE in cholesterol efflux SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. LIPOPROT LAB,OKLAHOMA CITY,OK. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1997 VL 134 IS 1-2 SI SI BP 378 EP 378 DI 10.1016/S0021-9150(97)89914-5 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY106 UT WOS:A1997XY10601744 ER PT J AU Dhib-Jalbut, S McFarland, HF AF Dhib-Jalbut, S McFarland, HF TI Treatment of multiple sclerosis with interferon beta(1b) SO BAILLIERES CLINICAL NEUROLOGY LA English DT Article DE interferon beta(1b); Betaseron; multiple sclerosis ID SUPPRESSOR-CELL-FUNCTION; GAMMA-INDUCED EXPRESSION; IN-VITRO; REDUCES EXACERBATIONS; MAGNETIC-RESONANCE; ALPHA-INTERFERON; DOWN-REGULATION; RECOMBINANT; BETA-1B; ANTIGEN AB Interferon beta(1b) is now an established therapeutic option for relapsing remitting multiple sclerosis. More recently, it has also been shown to slow down disease progression in secondary progressive multiple sclerosis. Interferon beta(1b)'s clinical effect is reflected in MRI studies demonstrating a dramatic effect in reducing disease activity. The drug is generally well tolerated, but its efficacy can be compromised in some patients by the emergence of neutralizing antibodies. This chapter will focus on interferon beta(1b) (Betaseron) treatment for multiple sclerosis, its clinical and MRI effects, and its putative mechanism of action. C1 Univ Maryland Hosp, Dept Neurol, Baltimore, MD 21201 USA. NINCDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Dhib-Jalbut, S (reprint author), Univ Maryland Hosp, Dept Neurol, 22 S Greene St,Rm N4W46, Baltimore, MD 21201 USA. NR 73 TC 0 Z9 0 U1 1 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0961-0421 J9 BAILLIERE CLIN NEUR JI Baillieres Clin. Neurol. PD OCT PY 1997 VL 6 IS 3 BP 467 EP 480 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 168UQ UT WOS:000078711900006 PM 10101584 ER PT J AU Forlino, A DAmato, E Valli, M Camera, G Hopkins, E Marini, JC Cetta, G Coviello, DA AF Forlino, A DAmato, E Valli, M Camera, G Hopkins, E Marini, JC Cetta, G Coviello, DA TI Phenotypic comparison of an osteogenesis imperfecta type IV proband with a de novo alpha 2(I) Gly922->Ser substitution in type I collagen and an unrelated patient with an identical mutation SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Article ID TRIPLE-HELICAL DOMAIN; GLYCINE SUBSTITUTIONS; PRENATAL-DIAGNOSIS; PATERNAL MOSAICISM; CHAIN; GENE; PROCOLLAGEN; FIBROBLASTS; CONFORMATION; DEPOSITION AB We examined the type I collagen synthesized by cultured dermal fibroblasts from a patient affected with osteogenesis imperfecta (OI) type IV. Both normal and abnormal trimers were produced, The mutant collagen molecules were excessively modified intracellularly, had a melting temperature 4 degrees C lower than the control, were secreted at a reduced rate, and underwent delayed processing to mature alpha chains. Molecular investigations identified a G --> A transition in one COL1A2 allele, resulting in a Gly922 --> Ser substitution in the alpha 2(I) chain. The proband's mutation was demonstrated to arise ''de novo'' by the absence of the mutant allele restriction enzyme pattern from parental genomic DNA. We analyzed the insoluble extracellular matrix deposited by long-term cultured fibroblasts from our patient and from a previously described unrelated individual who carries an identical substitution, In both cases, the mutant chain constituted 10-15% of the total alpha chains deposited. We also present here the first detailed comparison of phenotype between unrelated OI patients with an identical collagen mutation, These two patients are both Caucasian females, ages 8 and 9 years, each diagnosed as type IV OI by the Sillence classification, They have a similar phenotype including moderate skeletal fragility with several femur fractures, dentinogenesis imperfecta, wormian bone, and reduced height and weight, We conclude that this phenotype is related both to the location of this mutation and to the similar extent of matrix incorporation by the mutant chains, Molecular and biochemical studies of unrelated individuals with identical amino acid substitutions in type I collagen resulting in either similar or dissimilar clinical outcomes will make a significant contribution to identifying the factors involved in the modulation of the OI phenotype. (C) 1997 Academic Press. C1 UNIV GENOA, INST BIOL & GENET, I-16132 GENOA, ITALY. UNIV PAVIA, DEPT BIOCHEM A CASTELLANI, I-27100 PAVIA, ITALY. NICHHD, SECT CONNECT TISSUE DISORDERS, HERITABLE DISORDERS BRANCH, NIH, BETHESDA, MD USA. GALLIERA HOSP, CTR HUMAN GENET, GENOA, ITALY. RI Forlino, Antonella/H-5385-2015; Coviello, Domenico/J-9477-2016 OI Forlino, Antonella/0000-0002-6385-1182; Coviello, Domenico/0000-0001-8440-865X NR 30 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD OCT PY 1997 VL 62 IS 1 BP 26 EP 35 DI 10.1006/bmme.1997.2620 PG 10 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA YG929 UT WOS:A1997YG92900005 PM 9367795 ER PT J AU DeBerry, C Mou, S Linnekin, D AF DeBerry, C Mou, S Linnekin, D TI Stat1 associates with c-kit and is activated in response to stem cell factor SO BIOCHEMICAL JOURNAL LA English DT Article ID COLONY-STIMULATING FACTOR; EPIDERMAL GROWTH-FACTOR; CYTOKINE RECEPTOR SUPERFAMILY; DNA-BINDING PROTEINS; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; INTERFERON-GAMMA; PROTOONCOGENE PRODUCT; TARGETED DISRUPTION AB Interaction of stem cell factor (SCF), a haematopoietic growth factor, with the receptor tyrosine kinase c-kit leads to autophosphorylation of c-kit as well as tyrosine phosphorylation of various substrates. Little is known about the role of the JAK/STAT pathway in signal transduction via receptor tyrosine kinases, although this pathway has been well characterized in cytokine receptor signal transduction. We recently found that the Janus kinase Jak2 associates with c-kit and that SCF induces rapid and transient phosphorylation of Jak2. Here we present evidence that SCF activates the transcription factor Stat1. Phosphorylated c-kit co-immunoprecipitates with Stat1 within 1 min of SCF stimulation of the human cell line MO7e. Coprecipitation experiments using glutathione S-transferase fusion proteins indicate that association with c-kit is mediated by the Stat1 SH2 domain. Stat1 is rapidly tyrosine-phosphorylated in response to SCF in MO7e cells, the murine cell line FDCP-1 and normal progenitor cells. SCF-induced phosphorylation of Jak2 and Stat1 was also observed in murine 3T3 fibroblasts stably transfected with full-length human c-kit receptor. Furthermore c-kit directly phosphorylates Stat1 fusion proteins in in vitro kinase assays. Electrophoretic mobility-shift assays with nuclear extracts from SCF-stimulated cell lines and normal progenitor cells indicate that activated Stat1 binds the m67 oligonucleotide, a high-affinity SIE promoter sequence. These results demonstrate that Stat1 is activated in response to SCF, and suggest that Stat1 is a component of the SCF signal-transduction pathway. C1 NCI,LAB LEUKOCYTE BIOL,DIV BASIC SCI,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,IRSP,FREDERICK,MD 21702. NR 55 TC 74 Z9 74 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 1997 VL 327 BP 73 EP 80 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XZ162 UT WOS:A1997XZ16200011 PM 9355737 ER PT J AU Sharief, FS Tsoi, SCM Li, SSL AF Sharief, FS Tsoi, SCM Li, SSL TI cDNA cloning and genomic organization of enhancer of split groucho gene from nematode Caenorhabditis elegans SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID LOOP-HELIX PROTEINS; DROSOPHILA-ENHANCER; BETA-SUBUNIT; SACCHAROMYCES-CEREVISIAE; EARLY NEUROGENESIS; MOLECULAR-CLONING; MELANOGASTER; COMPLEX; LOCUS; MOUSE AB This first genomic Enhancer of split groucho (ESG) gene and its full length complementary DNA (cDNA) from nematode C. elegans were cloned and sequenced via homology with the corresponding Drosophila groucho cDNA. The cDNA of 2.1-Kb encodes a protein of 612 amino acids, and the nematode ESG protein is the smallest and most different in structure compared to all ESG related proteins. The gene isolated is 4,246-bp in size, including 1,219-bp promoter region. A putative TATA-box at position -1166, two consensus sequence of ACTGG, characteristic of leader binding protein-1 (LBP-1) binding motifs at position -563 and -211 and nine CAAT boxes were found in the promoter region of ESG gene. The protein-coding sequence is interrupted by five introns. The length of introns 1 to 5 is 52, 252, 87, 53 and 518 bp, respectively. The overall structural relationships of the ESG-related proteins among human, mouse, rat, Xenopus, Drosophila and nematode were also analyzed. C1 Natl Sun Yat Sen Univ, Dept Life Sci, Kaohsiung 80424, Taiwan. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Li, SSL (reprint author), Natl Sun Yat Sen Univ, Dept Life Sci, Kaohsiung 80424, Taiwan. NR 22 TC 6 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE, NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD OCT PY 1997 VL 43 IS 2 BP 327 EP 337 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ214 UT WOS:000073190900011 PM 9350340 ER PT J AU Candeias, SM Durum, SK Muegge, K AF Candeias, SM Durum, SK Muegge, K TI p53-dependent apoptosis and transcription of p21(waflcip1/sdi1) in SCID mice following gamma-irradiation SO BIOCHIMIE LA English DT Article DE p53; DNA-dependent protein kinase; ionizing radiation; apoptosis; radiosensitivity ID DEPENDENT PROTEIN-KINASE; V(D)J RECOMBINATION; MOUSE THYMOCYTES; DNA-DAMAGE; HUMAN P53; REPAIR; DIFFERENTIATION; WAF1/CIP1; MUTATION; PATHWAY AB The recruitment and activation of DNA-repair mechanisms at the sites of DNA-damage after exposure of cells to genotoxic stress are poorly understood. The DNA-dependent kinase (DNA-PK) was considered to be a likely candidate for initiating these events because of the conditions required for its activation, its phosphorylation of p53 in vitro and the extreme radiosensitivity induced by its inactivation in vivo. We analyzed irradiation-induced p53-activation in SCID mice, which lack DNA-PK activity, and found that p53-dependent apoptosis and p21(waf/cipl/sdil) transcription in these animals are at least as efficient as in wild-type mice. Thus, our results show that DNA-PK is not the main sensor for genotoxic stress and is not required for p53 activation. In fact, they rather suggest that DNA-PK may play a role in p53 down-regulation. C1 NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Candeias, SM (reprint author), CEA Grenoble, DBMS, ICH, INSERM U238, 17 Rue Martyrs, F-38054 Grenoble 9, France. NR 24 TC 13 Z9 14 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD OCT PY 1997 VL 79 IS 9-10 BP 607 EP 612 DI 10.1016/S0300-9084(97)82010-X PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZD116 UT WOS:000072653000011 PM 9466699 ER PT J AU Wu, C Kobayashi, H Sun, B Yoo, TM Paik, CH Gansow, OA Carrasquillo, JA Pastan, I Brechbiel, MW AF Wu, C Kobayashi, H Sun, B Yoo, TM Paik, CH Gansow, OA Carrasquillo, JA Pastan, I Brechbiel, MW TI Stereochemical influence on the stability of radio-metal complexes in vivo. Synthesis and evaluation of the four stereoisomers of 2-(p-nitrobenzyl)-trans-CyDTPA SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID PARTICLE-MEDIATED RADIOIMMUNOTHERAPY; LABELING MONOCLONAL-ANTIBODIES; CHELATING AGENT; CARCINOMA XENOGRAFTS; IN-VIVO; BIODISTRIBUTION; LIGANDS; DTPA; MICE; B3 AB Distinct differences in in vivo stability of the two diastereomeric C-Functionalized CyDTPA chelating agents, (CHX-A DTPA and CHX-B DTPA, both racemates), as recently reported prompted further investigation as to why differences in configuration produced striking effects on the in vivo stability of their yttrium complexes. To this end, the four individual component stereoisomers of CHX-A and CHX-B were synthesized and ability to bind yttrium was investigated both in vitro and in vivo. Published by Elsevier Science Ltd. C1 NCI,RADIAT ONCOL BRANCH,RADIOIMMUNE & INORGAN CHEM SECT,NIH,BETHESDA,MD 20892. NCI,DEPT NUCL MED,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 27 TC 98 Z9 98 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 1997 VL 5 IS 10 BP 1925 EP 1934 DI 10.1016/S0968-0896(97)00130-2 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA YE023 UT WOS:A1997YE02300005 PM 9370037 ER PT J AU Jones, LN Simon, M Watts, NR Booy, FP Steven, AC Parry, DAD AF Jones, LN Simon, M Watts, NR Booy, FP Steven, AC Parry, DAD TI Intermediate filament structure: hard alpha-keratin SO BIOPHYSICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 12th International Biophysics Congress CY AUG 12-16, 1996 CL AMSTERDAM, NETHERLANDS DE intermediate filament; wool; alpha-keratin; disulfide bonds; mass measurements; X-ray diffraction ID TRANSMISSION ELECTRON-MICROSCOPY; EPIDERMAL KERATIN; ASSEMBLED INVITRO; MASS ANALYSIS; COILED-COILS; MOLECULES; VIMENTIN; STEM; MICROFIBRIL; MECHANISM AB Structurally there are four classes of intermediate filaments (IF) with distinct but closely related axial organisations. One of these, hard alpha-keratin IF, has been studied to clarify several apparently exceptional features which include the number of molecules in the IF cross-section and the mode by which the axial organisation of its constituent molecules is stabilised. Using the dark-field mode of the STEM at the Brookhaven National Laboratory (USA) mass measurements were obtained from unstained IF isolated from hair keratin. The data thus obtained show that the number of chains in cross-section is about 30 (+/-3: standard deviation) and is very similar to the numbers determined in previous STEM experiments for the dominant filament type in other classes of IF (about 32). Furthermore, re-analysis of the low-angle equatorial X-ray diffraction pattern reveals, in contrast to earlier work, solutions that are compatible with the number of chains in cross-section indicated by the STEM data. The absence of the head-to-tail overlap between parallel molecules characteristic of most IF may be compensated in hard alpha-keratin by a network of intermolecular disulfide bonds. It is concluded that native IF of hard alpha-keratin and desmin/vimentin - and probably many other kinds of IF as well - contain about 32 chains in cross-section, and that the axial structures of these various kinds of IF differ in small but significant ways, while generally observing the same basic modes of aggregation. (C) 1997 Elsevier Science B.V. C1 CSIRO, Div Wool Technol, Belmont, Vic 3216, Australia. Brookhaven Natl Lab, Upton, NY 11973 USA. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. Massey Univ, Dept Phys, Palmerston North, New Zealand. RP Jones, LN (reprint author), CSIRO, Div Wool Technol, POB 21, Belmont, Vic 3216, Australia. NR 39 TC 36 Z9 36 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD OCT PY 1997 VL 68 IS 1-3 BP 83 EP 93 DI 10.1016/S0301-4622(97)00013-6 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA YU299 UT WOS:000071702700009 PM 9468612 ER PT J AU Perera, L Li, LP Darden, T Monroe, DM Pedersen, LG AF Perera, L Li, LP Darden, T Monroe, DM Pedersen, LG TI Prediction of solution structures of the Ca2+-bound gamma-carboxyglutamic acid domains of protein S and homolog growth arrest specific protein 6: Use of the particle mesh Ewald method SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; HUMAN FACTOR-IX; BLOOD-COAGULATION; PROTHROMBIN FRAGMENT-1; MEMBRANE-BINDING; NUCLEIC-ACIDS; FORCE-FIELD; GAS6; RECEPTOR; RESIDUES AB The solution structures of the N-terminal domains of protein S, a plasma vitamin K-dependent glycoprotein, and its homolog growth arrest specific protein 6 (Gas6) were predicted by molecular dynamics computer simulations. The initial structures were based on the x-ray crystallographic structure of the corresponding region of bovine prothrombin fragment 1. The subsequent molecular dynamics trajectories were calculated using the second-generation AMBER force field. The long-range electrostatic forces were evaluated by the particle mesh Ewald method. The structures that stabilized over a 400-ps time interval were compared with the corresponding region of the simulated solution structure of bovine prothrombin fragment 1. Structural properties of the gamma-carboxyglutamic acid (Cia) domains obtained from simulations and calcium binding were found to be conserved for all three proteins. Analysis of the predicted solution structure of the Cia domain of Gas6 suggests that this domain should bind with negatively charged phospholipid surfaces analogous to bovine prothrombin fragment 1 and protein S. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-06350] NR 43 TC 11 Z9 11 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1997 VL 73 IS 4 BP 1847 EP 1856 PG 10 WC Biophysics SC Biophysics GA XY955 UT WOS:A1997XY95500014 PM 9336180 ER PT J AU Koenig, BW Strey, HH Gawrisch, K AF Koenig, BW Strey, HH Gawrisch, K TI Membrane lateral compressibility determined by NMR and X-ray diffraction: Effect of acyl chain polyunsaturation SO BIOPHYSICAL JOURNAL LA English DT Article ID DEUTERIUM MAGNETIC-RESONANCE; ROD OUTER SEGMENT; PHOSPHOLIPID-BILAYERS; LECITHIN BILAYERS; PHASE-TRANSITION; HYDRATION FORCES; LIPID BILAYERS; THERMAL FLUCTUATIONS; ORIENTATIONAL ORDER; BENDING ELASTICITY AB The elastic area compressibility modulus, K-a, of lamellar liquid crystalline bilayers was determined by a new experimental approach using H-2-NMR order parameters of lipid hydrocarbon chains together with lamellar repeat spacings measured by x-ray diffraction. The combination of NMR and x-ray techniques yields accurate determination of lateral area per lipid molecule. Samples of saturated, monounsaturated, and polyunsaturated phospholipids were equilibrated with polyethylene glycol (PEG) 20,000 solutions in water at concentrations from 0 to 55 wt % PEG at 30 degrees C. This procedure is equivalent to applying 0 to 8 dyn/cm lateral pressure to the bilayers. The resulting reductions in area per lipid were measured with a resolution of +/-0.2 Angstrom(2) and the fractional area decrease was proportional to applied lateral pressure, For 1,2-dimyristoyl(d54)-sn-glycero-3-phosphocholine, 1-stearoyl(d35)-2-oleoyl-sn-glycero-3-phosphocholine (SOPC-d(35)), and 1-stearoyl(d35)-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC-d(35)) cross-sectional areas per molecule in excess water of 59.5, 61.4, and 69.2 Angstrom(2) and bilayer elastic area compressibility moduli of 141, 221, and 121 dyn/cm were determined, respectively. Combining NMR and x-ray results enables the determination of compressibility differences between saturated and unsaturated hydrocarbon chains. In mixed-chain SOPC-d(35) both chains have similar compressibility moduli; however, in mixed-chain polyunsaturated SDPC-d(35), the saturated stearic acid chain appears to be far less compressible than the polyunsaturated docosahexaenoic acid chain. C1 NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,NIH,ROCKVILLE,MD 20852. NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,ROCKVILLE,MD 20852. RI Koenig, Bernd/B-4315-2008; Strey, Helmut/B-5456-2009 OI Koenig, Bernd/0000-0002-5300-6276; NR 70 TC 203 Z9 204 U1 3 U2 36 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1997 VL 73 IS 4 BP 1954 EP 1966 PG 13 WC Biophysics SC Biophysics GA XY955 UT WOS:A1997XY95500025 PM 9336191 ER PT J AU Xavier, KA Shick, KA SmithGill, SJ Willson, RC AF Xavier, KA Shick, KA SmithGill, SJ Willson, RC TI Involvement of water molecules in the association of monoclonal antibody HyHEL-5 with bobwhite quail lysozyme SO BIOPHYSICAL JOURNAL LA English DT Article ID ENTHALPY-ENTROPY COMPENSATION; ANTIGEN-BINDING; CYTOCHROME-C; BOUND WATER; ANTILYSOZYME ANTIBODIES; 3-DIMENSIONAL STRUCTURE; PROTEIN SOLVATION; LIGAND-BINDING; OSMOTIC-STRESS; AVIAN LYSOZYME AB Fluorescence polarization spectroscopy and isothermal titration calorimetry were used to study the influence of osmolytes on the association of the anti-hen egg lysozyme (HEL) monoclonal antibody HyHEL-5 with bobwhite quail lysozyme (BWQL). BWQL is an avian species variant with an Arg-->Lys mutation in the HyHEL-5 epitope, as well as three other mutations outside the HyHEL-5 structural epitope, This mutation decreases the equilibrium association constant of HyHEL-5 for BWQL by over 1000-fold as compared to HEL. The three-dimensional structure of this complex has been obtained recently. Fluorescein-labeled BWQL, obtained by labeling at pH 7.5 and purified by hydrophobic interaction chromatograpy, bound HyHEL-5 with an equilibrium association constant close to that determined for unlabeled BWQL by isothermal titration calorimetry. Fluorescence titration, stopped-flow kinetics, and isothermal titration calorimetry experiments using various concentrations of the osmolytes glycerol, ethylene glycol, and betaine to perturb binding gave a lower limit of the uptake of similar to 6-12 water molecules upon formation of the HyHEL-5/BWQL complex. C1 UNIV HOUSTON,DEPT CHEM ENGN,HOUSTON,TX 77204. UNIV HOUSTON,DEPT BIOCHEM & BIOPHYS SCI,HOUSTON,TX 77204. NCI,GENET LAB,NIH,BETHESDA,MD 20982. FU NIGMS NIH HHS [GM44344] NR 69 TC 41 Z9 41 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1997 VL 73 IS 4 BP 2116 EP 2125 PG 10 WC Biophysics SC Biophysics GA XY955 UT WOS:A1997XY95500041 PM 9336207 ER PT J AU Fisher, CL Pei, GK AF Fisher, CL Pei, GK TI Modification of a PCR-based site-directed mutagenesis method SO BIOTECHNIQUES LA English DT Article ID POLYMERASE CHAIN-REACTION; EFFICIENT; DELETION C1 NCI,FREDERICK,MD 21701. NR 12 TC 232 Z9 233 U1 3 U2 10 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1997 VL 23 IS 4 BP 570 EP & PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA070 UT WOS:A1997YA07000001 PM 9343663 ER PT J AU Jorgensen, ST Tangney, M Starnes, RL Amemiya, K Jorgensen, PL AF Jorgensen, ST Tangney, M Starnes, RL Amemiya, K Jorgensen, PL TI Cloning and nucleotide sequence of a thermostable cyclodextrin glycosyltransferase gene from Thermoanaerobacter sp. ATCC 53627 and its expression in Escherichia coli SO BIOTECHNOLOGY LETTERS LA English DT Article ID ALPHA-AMYLASE; RECLASSIFICATION; ENZYME; EM1 AB A gene, cgtA, encoding an extremely thermostable cyclodextrin glycosyltransferase (CGTase) was cloned from a thermophilic anaerobe, Thermoanaerobacter sp. ATCC 53627, and expressed in Escherichia coli. DNA and protein sequencing revealed that the mature enzyme of 683 amino acid residues (MW 75 kDa) was preceded by a signal peptide of 27 amino acid residues. The sequence of the Thermoanaerobacter CGTase was similar to sequences of Bacillus CGTases, with more than 58% identity, and very similar (89% identity) to a CGTase enzyme from Thermoanaerobacterium thermosulfurogenes. C1 HERIOT WATT UNIV,DEPT BIOL SCI,EDINBURGH EH14 4AS,MIDLOTHIAN,SCOTLAND. NN ENTOTECH INC,DAVIS,CA. NIH,BETHESDA,MD 20892. RP Jorgensen, ST (reprint author), NOVO NORDISK AS,DEPT BACTERIAL GENE TECHNOL,DK-2880 BAGSVAERD,DENMARK. NR 10 TC 14 Z9 14 U1 2 U2 4 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0141-5492 J9 BIOTECHNOL LETT JI Biotechnol. Lett. PD OCT PY 1997 VL 19 IS 10 BP 1027 EP 1031 DI 10.1023/A:1018459703742 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA YC503 UT WOS:A1997YC50300020 ER PT J AU Molldrem, JJ Clave, E Jiang, YZ Mavroudis, D Raptis, A Hensel, N Agarwala, V Barrett, AJ AF Molldrem, JJ Clave, E Jiang, YZ Mavroudis, D Raptis, A Hensel, N Agarwala, V Barrett, AJ TI Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; MARROW TRANSPLANTATION; PERIPHERAL-BLOOD; CELLS; RELAPSE; GENE AB We previously showed that a peptide (PR1) derived from the primary granule enzyme proteinase 3 induced peptide specific cytotoxic T lymphocytes (CTL) in a normal HLA-A2.1(+) individual. These CTL showed HLA-restricted cytotoxicity to myeloid leukemias (which overexpress proteinase 3). To further investigate their antileukemic potential, we studied the ability of PR1-specific CTL, derived from two HLA-A2.1(+) normal individuals, to inhibit colony-forming unit granulocyte-macrophage (CFU-GM) from normal and leukemic individuals. CTL from 20 day PR1 peptide-pulsed lymphocyte cultures showed 89% to 98% HLA-A2.1-restricted colony inhibition of chronic myeloid leukemia targets. Colony formation in normal HLA-A2.1(+) bone marrow or HLA-A2.1(-) CML cells was not inhibited. Sequencing of the exon encoding PR1 showed that colony inhibition was not caused by polymorphic differences in proteinase 3 between effecters and targets. Analysis by flow cytometry showed that proteinase 3 was overexpressed in the leukemia targets compared with normal marrow targets (median channel fluorescence 1,399 v 298, P = .009). These results show that PR1-specific allogeneic T cells preferentially inhibit leukemic CFU-GM based on overexpression of proteinase 3, and that proteinase 3-specific CTL could be used for leukemia-specific adoptive immunotherapy. C1 NHLBI,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 17 TC 183 Z9 185 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1997 VL 90 IS 7 BP 2529 EP 2534 PG 6 WC Hematology SC Hematology GA XY703 UT WOS:A1997XY70300003 PM 9326217 ER PT J AU Zhu, QL Watanabe, C Liu, T Hollenbaugh, D Blaese, RM Kanner, SB Aruffo, A Ochs, HD AF Zhu, QL Watanabe, C Liu, T Hollenbaugh, D Blaese, RM Kanner, SB Aruffo, A Ochs, HD TI Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype SO BLOOD LA English DT Article ID SRC HOMOLOGY-3 DOMAINS; T-CELLS; ACTIN POLYMERIZATION; TYROSINE KINASES; GTPASE CDC42; B-CELLS; IDENTIFICATION; LYMPHOCYTES; PLATELETS; BINDING AB Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT), caused by mutations of the WAS protein (WASP) gene, represent different phenotypes of the same disease. To demonstrate a phenotype/genotype correlation, we determined WASP gene mutations in 48 unrelated WAS families. Mutations included missense (20 families) and nonsense (eight) mutations located mostly in exons 1 to 4, and splice-site mutations (seven) and deletions and insertions (13) located preferentially in exons 7 to 11. Both genomic DNA and cDNA were sequenced and WASP expression was measured in cell lysates using peptide-specific rabbit anti-WASP antibodies. WASP was expressed in hematopoietic cell lines including bone marrow-derived CD34(+) cells. Missense mutations located in exons 1 to 3 caused mild disease in all but one family and permitted WASP expression, although frequently at decreased concentration. Missense mutations affecting exon 4 were associated with classic WAS and, with one exception, barely detectable WASP. Nonsense mutations caused classic WAS and lack of protein. Insertions, deletions, and splice-site mutations resulted in classic WAS and absent, unstable, truncated, or multiply spliced protein. Using affinity precipitation, WASP was found to bind to Src SH3-containing proteins Fyn, Lck, PLC-gamma,and Grb2, and mutated WASP, if expressed, was able to bind to Fyn-glutathione S-transferase (GST) fusion protein. We conclude that missense mutations affecting the PH domain (exons 1 to 3) of WASP inhibit less important functions of the protein and result in a mild phenotype, and that missense mutations affecting exon 4 and complex mutations affecting the 3' portion of WASP interfere with crucial functions of the protein and cause classic WAS. (C) 1997 by The American Society of Hematology. C1 UNIV WASHINGTON,SCH MED,DEPT PEDIAT,DIV INFECT DIS IMMUNOL & RHEUMATOL,SEATTLE,WA 98195. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. FU NICHD NIH HHS [HD17427] NR 46 TC 174 Z9 184 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1997 VL 90 IS 7 BP 2680 EP 2689 PG 10 WC Hematology SC Hematology GA XY703 UT WOS:A1997XY70300021 PM 9326235 ER PT J AU vanRhee, F Szydlo, RM Hermans, J Devergie, A Frassoni, F Arcese, W deWitte, T Kolb, HJ Niederwiser, D Jacobsen, N Gahrton, G Bandini, G Carreras, E Bacigalupo, A Michallet, M Ruutu, T Reiffers, J Goldman, JM Apperley, J Gratwohl, A AF vanRhee, F Szydlo, RM Hermans, J Devergie, A Frassoni, F Arcese, W deWitte, T Kolb, HJ Niederwiser, D Jacobsen, N Gahrton, G Bandini, G Carreras, E Bacigalupo, A Michallet, M Ruutu, T Reiffers, J Goldman, JM Apperley, J Gratwohl, A TI Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE CML; BMT; long-term outcome ID CHRONIC MYELOID-LEUKEMIA; MINIMAL RESIDUAL DISEASE; VERSUS-HOST DISEASE; 1ST CHRONIC PHASE; INTERFERON-ALPHA; CHRONIC GRAFT; RELAPSE; DONOR AB The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor. RP vanRhee, F (reprint author), NHLBI,HEMATOL BRANCH,NIH,RM 7C-103,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI apperley, jane/B-4367-2009; Szydlo, Richard/C-6678-2012; Witte, T.J.M./L-4762-2015 OI Szydlo, Richard/0000-0003-1102-8298; NR 25 TC 105 Z9 108 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1997 VL 20 IS 7 BP 553 EP 560 DI 10.1038/sj.bmt.1700933 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA YA274 UT WOS:A1997YA27400004 PM 9337056 ER PT J AU Goel, V Grafman, J Tajik, J Gana, S Danto, D AF Goel, V Grafman, J Tajik, J Gana, S Danto, D TI A study of the performance of patients with frontal lobe lesions in a financial planning task SO BRAIN LA English DT Article DE planning; problem solving; prefrontal cortex; information processing theory ID TEMPORAL LOBECTOMY; PREFRONTAL CORTEX; PROBLEM SPACES; DAMAGE; IMPAIRMENTS; DESIGN AB It has long been argued that patients with lesions in the prefrontal cortex have difficulties in decision making and problem solving in real-world, ill-structured situations, particularly problem types involving planning and lookahead components. Recently, several researchers have questioned our ability to capture and characterize these deficits adequately using just the standard neuropsychological test batteries, and have called for tests that reflect real-world task requirements more accurately. We present data from 10 patients with focal lesions to the prefrontal cortex and 10 normal control subjects engaged in a real-world financial planning task. We also introduce a theoretical framework and methodology developed in the cognitive science literature for quantifying and analysing the complex data generated by problem-solving tasks. Our findings indicate that patient performance is impoverished at a global level but not at the local level. Patients have difficulty in organizing and structuring their problem space. Once they begin problem solving, they have difficulty in allocating adequate effort to each problem-solving phase. Patients also have difficulty dealing with the fact that there are no right or wrong answers nor official termination points in real-world planning problems. They also find it problematic to generate their own feedback. They invariably terminate the session before the details are fleshed out and all the goals satisfied Finally, patients do not take full advantage of the fact that constraints on real-world problems are negotiable. However it is not necessary to postulate a 'planning' deficit It is possible to understand the patients' difficulties in real world planning tasks in terms of the following four accepted deficits: inadequate access to 'structured event complexes', difficulty in generalizing from particulars, failure to shift between 'mental sets', and poor judgment regarding adequacy and completeness of a plan. C1 NINCDS,COGNIT NEUROSCI SECT,NIH,BETHESDA,MD 20892. RP Goel, V (reprint author), YORK UNIV,DEPT PSYCHOL,4700 KEELE ST,N YORK,ON M3J 1P3,CANADA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 50 TC 114 Z9 117 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 1997 VL 120 BP 1805 EP 1822 DI 10.1093/brain/120.10.1805 PN 10 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YC954 UT WOS:A1997YC95400009 PM 9365372 ER PT J AU Blaxton, TA Theodore, WH AF Blaxton, TA Theodore, WH TI The role of the temporal lobes in recognizing visuospatial materials: Remembering versus knowing SO BRAIN AND COGNITION LA English DT Article ID RECOLLECTIVE EXPERIENCE; RECOGNITION MEMORY; EPILEPSY; IMPAIRMENT; LOBECTOMY; AWARENESS; DESIGNS; WORD AB Recognition memory for abstract visuospatial designs was assessed In unilateral temporal lobe epilepsy (TLE) patients and normal controls using a remember/know recognition paradigm. Subjects assigned ''remember'' judgments to recognized items for which they could recall the study presentation, and ''know'' judgments to items recognized on the basis of familiarity without conscious recollection of the study episode. In Experiment 1 normal controls and left TLE patients gave more ''know'' than ''remember'' recognition judgments for visuospatial materials. Right TLE subjects, however, showed the opposite response pattern. Experiment la demonstrated that this dissociation between left and right temporal patients occurred in both presurgery and postsurgery patients. In Experiment 2 recognition was assessed following encoding conditions in which subjects answered questions about either the number of lines in the designs or the appropriateness of verbal labels for presented stimuli. The previous pattern of ''know'' and ''remember'' responses was replicated for all groups in the line count condition, but was reversed for normal controls in the label condition. These results are interpreted within a theoretical framework in which ''remember'' responses are based on the contribution of distinctiveness of individual items to recognition whereas ''know'' judgements reflect perceptual fluency. (C) 1997 Academic Press. C1 NINCDS, NIH, BETHESDA, MD USA. NR 43 TC 44 Z9 45 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD OCT PY 1997 VL 35 IS 1 BP 5 EP 25 DI 10.1006/brcg.1997.0902 PG 21 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA YB983 UT WOS:A1997YB98300002 PM 9339299 ER PT J AU Jordan, NJ Watson, ML Williams, RJ Roach, AG Yoshimura, T Westwick, J AF Jordan, NJ Watson, ML Williams, RJ Roach, AG Yoshimura, T Westwick, J TI Chemokine production by human vascular smooth muscle cells: modulation by IL-13 SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE chemokine; interleukin (IL)-1 alpha; IL-8; IL-10; IL-13; TNF alpha; RANTES; MCP-1; smooth muscle ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HUMAN T-LYMPHOCYTES; BLOOD MONONUCLEAR LEUKOCYTES; HUMAN ENDOTHELIAL-CELLS; LOW-DENSITY-LIPOPROTEIN; ADHESION MOLECULE-1; HUMAN KERATINOCYTES; RANTES CHEMOKINE; GENE-EXPRESSION; CYTOKINE RANTES AB 1 The production of chemokines by vascular smooth muscle cells (SMC) is implicated in the pathogenesis of atherosclerosis, although the factors regulating chemokine production by these cells are incompletely characterized. 2 We describe the differential stimulation of interleukin-(IL)-8, monocyte chemoattractant protein (MCP)-1 and regulated on activation normal T-cell expressed and secreted (RANTES) synthesis following treatment of human vascular SMC with IL-1 alpha or tumour necrosis factor alpha (TNF alpha). Under basal conditions, cultured SMC release very low amounts of IL-8, MCP-1 and RANTES as assessed by specific ELISA. Concentration-response studies with IL-1 alpha or TNF alpha revealed that each stimulus induced a similar amount of MCP-1. In contrast approximately three fold more IL-8 was induced by IL-1 alpha than by TNF alpha whereas significant RANTES production was induced only by TNF alpha. These findings point to a divergence in the regulation of synthesis of the different chemokines in response to IL-1 alpha or TNF alpha stimulation. 3 The T-cell derived cytokines IL-10 and IL-13 were also found to have differential effects on chemokine production by SMC. IL-13, but not IL-IO, significantly enhanced IL-8 and MCP-1 release in response to IL-1 alpha or TNF alpha. This increase in chemokine release appeared to be accounted for by increased mRNA expression. 4 These findings provide support for the concept that smooth muscle cells can have an active role in a local immune response via the production of chemokines which can be selectively modulated by T-cell derived cytokines. C1 RHONE POULENC RORER,DAGENHAM RES CTR,DAGENHAM RM10 7XS,ESSEX,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Jordan, NJ (reprint author), UNIV BATH,SCH PHARM & PHARMACOL,DEPT PHARMACOL,CLAVERTON DOWN,BATH BA2 7AY,AVON,ENGLAND. RI Jordan, Nicola/B-3341-2013 FU Wellcome Trust NR 61 TC 54 Z9 55 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD OCT PY 1997 VL 122 IS 4 BP 749 EP 757 DI 10.1038/sj.bjp.0701433 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YB247 UT WOS:A1997YB24700021 PM 9375973 ER PT J AU Naficy, AB Clemens, JD Rao, MR AF Naficy, AB Clemens, JD Rao, MR TI Randomized controlled clinical trials of experimental vaccines SO BULLETIN DE L INSTITUT PASTEUR LA English DT Review DE controlled clinical trial, random allocation, experimental vaccine; efficacy, effectiveness, methodology, public health; review ID REQUIRING PROLONGED OBSERVATION; CREDULOUS IDOLATRY; SAMPLE-SIZE; EFFICACY; DESIGN; ALLOCATION; BIOSTATISTICS; BANGLADESH; CHOLERA; PATIENT AB Randomized controlled clinical trials to evaluate the clinical protection conferred by experimental vaccines and to provide further evidence of their safety are invariably demanded by regulatory agencies before these candidate vaccines can be licensed and introduced into routine public health practice. This review addresses the design of such trials. C1 NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. RP Naficy, AB (reprint author), NICHHD, Epidemiol Branch, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD OCT-DEC PY 1997 VL 95 IS 4 BP 187 EP 196 DI 10.1016/S0020-2452(97)83527-1 PG 10 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA ZK012 UT WOS:000073276100001 ER PT J AU Wood, FB Wallingford, KT Siegel, ER AF Wood, FB Wallingford, KT Siegel, ER TI Transitioning to the Internet: Results of a National Library of Medicine user survey SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB In late 1995, several months prior to the introduction of Internet Grateful Med, the National Library of Medicine (NLM) conducted a customer survey as part of its efforts to make a transition from Grateful Med to new forms of electronic information access and retrieval. A questionnaire survey was mailed to a sample of 2,500 online users randomly selected from domestic users (excluding fixed-fee users) who searched NLM databases during the second quarter of 1995. The final response rate was nearly 83% of eligible respondents. About 70% of NLM customers responding already had access to the Internet, and of those, more than 90% had access to the World Wide Web. However, only 26% of customers with Internet access were using the Internet to access NLM databases. Health care providers account for about 46% of NLM customers but, as a group, search NLM databases relatively infrequently even though they have higher-end equipment. Librarians and information professionals represent about one-fifth of NLM customers and are by far the most intensive users, but tend to have lower-end equipment. Overall, the survey results provide a strong basis for the transition to Internet-based delivery of NLM online database services, including Internet Grateful Med and the NLM family of World Wide Web sites. However, Internet access is uneven, especially in rural areas and at hospitals. This reinforces the need for continuing special outreach efforts directed at improving access for rural and hospital based users and rural libraries, upgrading computer equipment for medical librarians, and training health care providers in more effective use of Internet-based biomedical information resources. C1 Natl Lib Med, Off Hlth Informat Programs Dev, Bethesda, MD 20894 USA. RP Wood, FB (reprint author), Natl Lib Med, Off Hlth Informat Programs Dev, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 8 TC 10 Z9 11 U1 0 U2 2 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1997 VL 85 IS 4 BP 331 EP 340 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA YM280 UT WOS:000071047800002 PM 9431421 ER PT J AU Greenberg, SJ AF Greenberg, SJ TI The "dreadful visitation": Public health and public awareness in seventeenth century London SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB The decision was made in Britain three centuries ago that an educated populace was best able to deal with a public health crisis of staggering proportions-outbreaks of bubonic and pneumonic plague. As early as 1603, the printing press was enlisted to educate the public about urgent health issues. This education took several forms. The City of London, with the tacit permission of the Crown, printed bills of mortality that reported who was dying of what in London, detailed by parish, for the years in the seventeenth century when plague deaths were reported. New books about plague prevention and cures were published; older works were reprinted. The resulting wealth of data gave impetus to the evolution of the new field of epidemiological demographics, founded by John Graunt and Sir William Petty. Publishing in the plague years also established a model for informing the general populace that is not without parallel in today's "information society." C1 Natl Lib Med, Div Med, Bethesda, MD 20894 USA. RP Greenberg, SJ (reprint author), Natl Lib Med, Div Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 15 TC 2 Z9 4 U1 0 U2 2 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1997 VL 85 IS 4 BP 391 EP 401 PG 11 WC Information Science & Library Science SC Information Science & Library Science GA YM280 UT WOS:000071047800010 PM 9431429 ER PT J AU Dahlem, RW AF Dahlem, RW TI A history of medical informatics in the United States: 1950 to 1990. SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Book Review C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Dahlem, RW (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1997 VL 85 IS 4 BP 443 EP 443 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA YM280 UT WOS:000071047800020 ER PT J AU Yancik, R AF Yancik, R TI Cancer burden in the aged - An epidemiologic and demographic overview SO CANCER LA English DT Article; Proceedings Paper CT Oncology Geriatric Education Retreat - Integrating Geriatrics into Oncology Training CY FEB 21-26, 1997 CL SAN JUAN, PR DE cancer; elderly; incidence; mortality; aging; aging population; comorbid conditions ID OLDER PATIENTS AB Sixty percent of all cancer occurs in persons aged greater than or equal to 65 years. This article provides an overview of aspects of the burden of cancer in the elderly, highlighting certain demographic and epidemiologic data. It served as a frame of reference for participants in the Oncology Geriatric Education Retreat, San Juan, Puerto Rico, February 21-26, 1997. Information comes from several major sources: U. S. Bureau of the Census; National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program; National Center for Health Statistics; National Institute on Aging (NIA)/NCI SEER Study on Comorbidity and Cancer in the Elderly; and NCI cancer prevalence estimates. Data on the aging population demonstrate an unprecedented expansion of the segment of the population aged greater than or equal to 65 years. By 2030, 1 in 5 Americans will be aged greater than or equal to 65 years. Because cancer incidence and mortality rates are highest in persons aged greater than or equal to 65 years, expansion of this age group takes on great importance for medical professionals who provide treatment to older aged cancer patients. In addition, older aged cancer patients are likely to have preexisting conditions at diagnosis, creating a special clinical challenge. There is an urgent need to better understand the influence of aging on the early detection, diagnosis, and treatment of cancer. Clinicians who treat older persons (geriatricians, oncologists, and other health professionals) can benefit from the integration of the knowledge and approaches of each others' fields. The foundation for this multidisciplinary effort is linked with the education and training of future clinicians. (C) 1997 American Cancer Society. RP Yancik, R (reprint author), NIA,GERIATR PROGRAM,NIH,GATEWAY BLDG,SUITE 3E327,7201 WISCONSIN AVE MSC 9,BETHESDA,MD 20892, USA. NR 26 TC 345 Z9 365 U1 2 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1997 VL 80 IS 7 BP 1273 EP 1283 DI 10.1002/(SICI)1097-0142(19971001)80:7<1273::AID-CNCR13>3.0.CO;2-4 PG 11 WC Oncology SC Oncology GA XX211 UT WOS:A1997XX21100013 PM 9317180 ER PT J AU Ershler, WB Longo, DL AF Ershler, WB Longo, DL TI The biology of aging - The current research agenda SO CANCER LA English DT Article; Proceedings Paper CT Oncology Geriatric Education Retreat - Integrating Geriatrics into Oncology Training CY FEB 21-26, 1997 CL SAN JUAN, PR DE aging; theories of aging; cancer and aging; immune senescence; free radicals; telomeres; immunosurveillance ID MALE RHESUS-MONKEYS; LONGITUDINAL GOMPERTZIAN ANALYSIS; MITOCHONDRIAL-DNA DELETIONS; LIFE-SPAN; SUPEROXIDE-DISMUTASE; DIETARY RESTRICTION; SKELETAL-MUSCLE; ANIMAL-MODEL; REPLICATIVE CAPACITY; ALZHEIMERS-DISEASE AB There has been and will continue to be a dramatic shift in the composition of our population with regard to age. Over the next several decades, the percentage of the population that is older than 65 years will nearly double. This has obvious and striking implications, particularly for health care. In anticipation of this change, there has been increased research activity in an attempt to understand the basic biology of aging and the mechanisms whereby older individuals become susceptible to disease. The authors reviewed MEDLINE data from the past 2 decades and key articles from the literature to develop a comprehensive overview of the background and current status of research in biomedical gerontology. They found that research in the mechanisms of aging has expanded strikingly during the past 20 years, and that there is now a more precise understanding of age-associated changes in cellular and molecular functions. Scientific overlap of these age-associated changes with the biology of cancer is now recognized. An appraisal of our current understanding of aging (or lack thereof) is made in this article. Selected key research questions are also presented, some of which are particularly germane to cancer biology and clinical oncology. (C) 1997 American Cancer Society. C1 EASTERN VIRGINIA MED SCH, GLENNAN CTR GERIATR & GERONTOL, NORFOLK, VA 23501 USA. RP Ershler, WB (reprint author), NIA, GERONTOL RES CTR, NIH, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 103 TC 33 Z9 35 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1997 VL 80 IS 7 BP 1284 EP 1293 DI 10.1002/(SICI)1097-0142(19971001)80:7<1284::AID-CNCR14>3.0.CO;2-3 PG 10 WC Oncology SC Oncology GA XX211 UT WOS:A1997XX21100014 PM 9317181 ER PT J AU SlavinChiorini, DC Kashmiri, SVS Lee, HS Milenic, DE Poole, DJ Bernon, E Schlom, J Hand, PH AF SlavinChiorini, DC Kashmiri, SVS Lee, HS Milenic, DE Poole, DJ Bernon, E Schlom, J Hand, PH TI A CDR-grafted (humanized) domain-deleted antitumor antibody SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article ID SINGLE-CHAIN-FV; MONOCLONAL-ANTIBODY; RADIOIMMUNOGUIDED SURGERY; COLORECTAL-CANCER; CH2 DOMAIN; IMMUNOGLOBULIN; ANTIGEN; B72.3; SERUM; LOCALIZATION AB While several murine monoclonal antibodies (MAbs) directed against carcinoma associated antigens have shown excellent tumor targeting properties in clinical trials, the use of radiolabelled MAbs for both diagnostic and therapeutic applications has been hindered by two factors: (a) the induction of host anti-immunoglobulin (Ig) responses and (b) slow plasma clearance of unbound radiolabelled MAb, resulting in bone marrow toxicity for therapeutic application, and long intervals between MAb administration and tumor detection for diagnostic applications. This report describes the development of the first recombinant Ig with properties designed to reduce or eliminate both of the above problems: a complementarity determining region (CDR)-grafted humanized (Hu) MAb with a CH2 domain deletion (Delta CH2). The MAb chosen for engineering was CC49, which is directed against a pancarcinoma antigen designated TAG-72 that is expressed on the majority of colorectal, gastric, breast ovarian, prostate, pancreatic and lung carcinomas. When characterized for antigen binding in solid phase competition radioimmunoassays, the HuCC49 Delta CH2 MAb completely inhibited the binding of murine (mu) CC49 and HuCC49 for TAG-72. The relative affinity constants (K-a) of MAbs HuCC49 Delta CH2, HuCC49 and muCC49 were 5.1 x 10(-9), 2.1 x 10(-9) and 2.3 x 1O(-9) respectively. The plasma clearance of I-131-HuCC49 Delta CH2 was significantly faster than that of intact I-125-HuCC49 after either i.v. or i.p. administration in athymic mice (p(2)0.05). Biodistribution studies in athymic mice bearing human colon carcinoma xenografts after i.v. or ip. administration of I-131-HuCC49 Delta CH2 and I-125-HuCC49 demonstrated the efficient tumor localization and substantially lower percent of the injected dose (%ID/g) of the HuCC49 Delta CH2 in normal tissues. This is reflected in the significantly higher radiolocalization indices (%ID/g in tumor divided by %ID/g in normal tissue) observed with the HuCC49 Delta CH2 for most normal tissues tested (p(2)0.05). The differential between the rate of plasma clearance of HuCC49 Delta CH2 and HuCC49 was even more pronounced in SCID mice, which have been shown to be an appropriate model to study the metabolism of human IgG. These studies thus describe the development of a recombinant Ig molecule which, for the first time, combines 1) the properties of more rapid blood clearance than an intact humanized Ig molecule-without loss of antigen binding affinity-and 2) reduced potential for eliciting a human anti-murine antibody (HAMA) response in patients. These studies also demonstrate the potential utility of HuCC49 Delta CH2 for i.p. as well as i.v. radioimmunodiagnosis and radioimmunotherapy in patients with TAG-72 positive tumors. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 32 TC 47 Z9 47 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD OCT PY 1997 VL 12 IS 5 BP 305 EP 316 DI 10.1089/cbr.1997.12.305 PG 12 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA YL430 UT WOS:A1997YL43000003 PM 10851481 ER PT J AU Merrill, RM Weed, DL Feuer, EJ AF Merrill, RM Weed, DL Feuer, EJ TI The lifetime risk of developing prostate cancer in white and black men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DEVELOPING BREAST-CANCER; RATES AB Two factors help explain increases in the lifetime risk of developing cancer: (a) decreasing overall mortality rates such that people are now living to older ages when cancer rates rise rapidly; and (b) increasing numbers of cancer cases discovered by new medical procedures, screening tests, and changes in the population risk factors, Prostate cancer lifetime risk estimates are particularly influenced by improved mortality rates and increased detection of asymptomatic disease, In this study, we report trends in lifetime risk estimates of developing prostate cancer in white and black men in the United States, from 1975 to 1993, and focus on the effects of changing mortality and screening, For the study period 1975-1977 to 1991-1993, the lifetime risk of developing invasive prostate cancer increased from 7.3 to 19.6% for whites and from 8.5 to 18.6% for blacks, When we recalculated these estimates using age-specific incidence trends from 1975 through 1989 (thereby controlling for the effect of prostate-specific antigen serum testing on prostate cancer incidence rates), the lifetime risk estimates in 1991-1993 fell to 13.8% for whites and 12.5% for blacks, When we made an additional assumption, basing lifetime risk estimates on higher 1975-1977 mortality rates, the lifetime risk estimates in 1991-1993 became 11.3% for whites and 11.8% for blacks, It is also shown that although mortality rates have improved for white and black men over the study period, they are much larger for blacks than whites in younger age groups, when the prevalence of prostate cancer is relatively low, As a result, fewer blacks survive to older ages when age-specific prostate cancer rates are large, It is of note that blacks have higher incidence rates for prostate cancer than do whites at every age-specific interval, Hence, increasing trends in lifetime risk of prostate cancer suggest, in large part, longer life expectancy and better detection methods. RP Merrill, RM (reprint author), NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,EPN 313,6130 EXECUT BLVD,MSC 7344,BETHESDA,MD 20892, USA. NR 23 TC 34 Z9 36 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 1997 VL 6 IS 10 BP 763 EP 768 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YA561 UT WOS:A1997YA56100002 PM 9332756 ER PT J AU Hildesheim, A Schiffman, MH Tsukui, T Swanson, CA Lucci, J Scott, DR Glass, AG Rush, BB Lorincz, AT Corrigan, A Burk, RD Helgesen, K Houghten, RA Sherman, ME Kurman, RJ Berzofsky, JA Kramer, TR AF Hildesheim, A Schiffman, MH Tsukui, T Swanson, CA Lucci, J Scott, DR Glass, AG Rush, BB Lorincz, AT Corrigan, A Burk, RD Helgesen, K Houghten, RA Sherman, ME Kurman, RJ Berzofsky, JA Kramer, TR TI Immune activation in cervical neoplasia: Cross-sectional association between plasma soluble interleukin 2 receptor levels and disease SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; T-CELL; RHEUMATOID-ARTHRITIS; SERUM; RESPONSES; DIFFERENTIATION; IMMUNIZATION; LYMPHOCYTES; REGRESSION AB In a previous study (Tsukui et al., Cancer Res., 56: 3967-3974, 1996), we observed an inverse association between degree of cervical neoplasia and interleukin (IL) 2 production by peripheral blood mononuclear cells in response to human papillomavirus (HPV) 16 E6 and E7 peptides in vitro. This suggested that a Th1-mediated cellular immune response might be important in host immunological control of HPV infection and that a lack of such a response might predispose to progression of cervical disease. To follow up on these findings, we have conducted a cross-sectional study of women with various degrees of cervical neoplasia to investigate the association between overall immune activation and cervical disease. A total of 235 women were recruited into our study; 120 of these women were participants in our previous study in which IL-2 production in response to HPV-16-specific peptides was measured. The study population included 34 women with invasive cancer, 62 women with high-grade squamous intraepithelial lesions (HSILs), and 105 women with low-grade squamous intraepithelial lesions (LSILs). In addition, 34 cytologically normal women with no past history of squamous intraepithelial lesions despite confirmed HPV-16 infection in the 5 years preceding the study were selected as controls. As our measure of overall immune activation, serum samples obtained from study participants were tested for soluble IL-2 receptor (sIL-2R) level using an ELISA method. The mean sIL-2R levels were found to increase with increasing disease severity (P-trend = 0.0002). Among cytologically normal, HPV-exposed women, the mean receptor level in serum was 465.8 units/ml compared to 467.6 units/ml among LSIL subjects, 514.9 units/ml among HSIL subjects, and 695.5 units/ml among women with invasive cervical cancer. Similarly, the proportion of women with elevated slL-2R levels (defined as greater than or equal to 450 units/ml) increased with increasing disease severity from 35.2% among normal study subjects to 70.6% among cancer patients (P-trend = 0.003). Among the subgroup of subjects for whom in vitro IL-2 production in response to HPV-16-specific peptides was measured, we examined the association between in vitro IL-2 production and serum levels of sIL-2R. sIL-2R levels were higher, on average, among those women who were positive in our IL-2 production assay compared to those who were negative, but the differences did not reach statistical significance (P > 0.05). We also observed a trend of increasing slL-2R level with increasing disease severity both in women who were positive and in women who were negative for our IL-2 production assay, but the trend was only significant among those who were negative for IL-2 production (P-trend = 0.01). Results from our studies suggest that although the immune system of women with cervical neoplasia is nonspecifically activated as disease severity increases, the ability of those women with HSILs or cancer to mount a Th1-mediated immune response to HPV peptides appears to decrease compared to women with LSILs or normal women infected with HPV. Increased overall activation along with decreased Th1 immune response among women with increasing cervical disease severity might be explained by an increased Th2-mediated immune response, a response that we hypothesize is ineffective in controlling the viral infection and its early cytological manifestations. Future studies should directly assess Th2-mediated responses to confirm this hypothesis. Also, future efforts should be aimed at determining whether the associations observed are causally related to disease progression or an effect of the disease. C1 NCI,MOL IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SW MED SCH,DALLAS,TX 75235. KAISER PERMANENTE,PORTLAND,OR 97227. DIGENE CORP,SILVER SPRING,MD 20904. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. TORREY PINES INST MOL STUDIES,LA JOLLA,CA 92121. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. JOHNS HOPKINS UNIV HOSP,DEPT PATHOL,BALTIMORE,MD 21205. USDA,BELTSVILLE HUMAN NUTR RES CTR,CAROTENOIDS RES UNIT,BELTSVILLE,MD 20705. RP Hildesheim, A (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EPN ROOM 443,BETHESDA,MD 20892, USA. NR 45 TC 30 Z9 32 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 1997 VL 6 IS 10 BP 807 EP 813 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YA561 UT WOS:A1997YA56100009 PM 9332763 ER PT J AU Boiko, IV Mitchell, MF Pandey, DK White, RA Hu, W Malpica, A Nishioka, K Boone, CW Atkinson, EN Hittelman, WN AF Boiko, IV Mitchell, MF Pandey, DK White, RA Hu, W Malpica, A Nishioka, K Boone, CW Atkinson, EN Hittelman, WN TI DNA image cytometric measurement as a surrogate end point biomarker in a phase I trial of alpha-difluoromethylornithine for cervical intraepithelial neoplasia SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CELL-GROWTH; POLYAMINES; CHEMOTHERAPY; MALIGNANCY; CANCER AB Cervical intraepithelial neoplasia grade 3 (GIN 3) is considered a high-risk precursor of invasive cervical cancer. cu-Difluoromethylornithine (DFMO) is a promising antiproliferative chemopreventive agent, The purpose of this study was to evaluate image cytometric measurement of nuclear DNA (ICM-DNA) as a surrogate end point biomarker (SEE) in a Phase I trial of DFMO for GIN. Thirty patients with CIN 3 were treated with DFMO at five doses, ranging from 0.0625 to 1.0 g/m(2)/day, for 1 month, Half of the patients had histological responses. Twenty-five pre-and posttreatment cervical biopsy specimens (from 11 responders and 14 nonresponders) were available for this analysis, ICM-DNA was performed on 4-mu m sections cut from formalin-fixed tissue blocks and stained with a thionin-SO2 Feulgen reaction, ICM-DNAs for each case were expressed as normalized measurements (against the nuclear modal absorbance of lymphocytes) of the absorbance of each cell of interest and were presented in bar histograms, The mean normalized summed absorbance (Sigma ODn) was obtained as a mean histogram of the cell population of interest, Nineteen (76%) of 25 patients had a significant decrease in Sigma ODn after DFMO treatment, Posttreatment values were significantly lower than pretreatment values in a paired analysis, and responders had significantly lower values than nonresponders, Analyses of different ICM-DNA references, including percentile values of Sigma ODn distribution, DNA malignancy grade, and 5c exceeding rate, showed a decrease of mean Sigma ODn during DFMO treatment, In addition, the summed posttreatment Sigma ODn histograms also showed progressively shorter right shoulders compared with pretreatment histograms in both responders and nonresponders, We concluded that the modulation of Sigma ODn reflected the chemoprevention effect of DFMO even before morphological changes appeared, and thus, ICM-DNA may be useful as a SEE in chemoprevention trials of DFMO. Additional reasons for using ICM-DNA as a SEE are the relative simplicity of its use, the high accuracy of the results, the low cost of the reagents, the ability to use small tissue samples, and the objectivity and reproducibility of the procedure. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT GYNECOL ONCOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CLIN INVEST,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT BIOMATH,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT PATHOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT SURG ONCOL,HOUSTON,TX 77030. NCI,CHEMOPREVENT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. FU NCI NIH HHS [CN-25433-02] NR 35 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 1997 VL 6 IS 10 BP 849 EP 855 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YA561 UT WOS:A1997YA56100015 PM 9332769 ER PT J AU Peters, J Dimond, E Jenkins, J AF Peters, J Dimond, E Jenkins, J TI Clinical applications of genetic technologies to cancer care SO CANCER NURSING LA English DT Article ID BREAST-CANCER; CHEMOPREVENTION; DEBRISOQUINE; PREVENTION; PHENOTYPE; RISK C1 NCI,NATL NAVAL MED CTR,NIH,BETHESDA,MD 20892. RP Peters, J (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT HUMAN GENET,130 DESOTO,A-300 CRABTREE,PITTSBURGH,PA 15261, USA. NR 47 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD OCT PY 1997 VL 20 IS 5 BP 359 EP 376 DI 10.1097/00002820-199710000-00007 PG 18 WC Oncology; Nursing SC Oncology; Nursing GA YF891 UT WOS:A1997YF89100007 PM 9394058 ER PT J AU Kim, CY Tsai, MH Osmanian, C Graeber, TG Lee, JE Giffard, RG DiPaolo, JA Peehl, DM Giaccia, AJ AF Kim, CY Tsai, MH Osmanian, C Graeber, TG Lee, JE Giffard, RG DiPaolo, JA Peehl, DM Giaccia, AJ TI Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions SO CANCER RESEARCH LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; UTERINE CERVIX; P53 STATUS; CARCINOMA; EXPRESSION; PROTEIN; HYPOXIA; TRANSFORMATION; CARCINOGENESIS; ASSOCIATION AB Since human papillomavirus (HPS') infection is strongly associated with cervical neoplasia and tumor hypoxia has prognostic significance in human cervical carcinomas, we examined the relationship between hypoxia and apoptosis in human cervical epithelial cells expressing high-risk HPV type 16 oncoproteins. In vitro, hypoxia stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV ES and E7 genes hut not in cervical fibroblasts infected with E6 and E7. Furthermore, cell lines derived from HPV-associated human cervical squamous cell carcinomas were substantially less sensitive to apoptosis induced by hypoxia, indicating that these cell lines have acquired additional genetic alterations that reduced their apoptotic sensitivity. Although the process of long-term cell culturing resulted in selection for subpopulations of HPV oncoprotein-expressing cervical epithelial cells with diminished apoptotic potential, the exposure of cells to hypoxia greatly accelerated the selection process. These results provide evidence for the role of hypoxia-mediated selection of cells with diminished apoptotic potential in the progression of human tumors and can in part explain why cervical tumors that possess low pO(2) values are more aggressive. C1 STANFORD UNIV, SCH MED, MAYER CANC BIOL RES LABS, STANFORD, CA 94305 USA. STANFORD UNIV, SCH MED, DEPT RADIAT ONCOL, STANFORD, CA 94305 USA. STANFORD UNIV, SCH MED, DEPT UROL, STANFORD, CA 94305 USA. STANFORD UNIV, SCH MED, DEPT ANESTHESIA, STANFORD, CA 94305 USA. NCI, BIOL LAB, BETHESDA, MD 20892 USA. OI Lee, Jong Eun/0000-0001-6203-7413; Graeber, Thomas/0000-0001-8574-9181 FU NCI NIH HHS [R01CA50995, R01CA64489] NR 25 TC 125 Z9 127 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1997 VL 57 IS 19 BP 4200 EP 4204 PG 5 WC Oncology SC Oncology GA XZ011 UT WOS:A1997XZ01100013 PM 9331075 ER PT J AU OConnor, PM Jackman, J Bae, I Myers, TG Fan, SJ Mutoh, M Scudiero, DA Monks, A Sausville, EA Weinstein, JN Friend, S Fornace, AJ Kohn, KW AF OConnor, PM Jackman, J Bae, I Myers, TG Fan, SJ Mutoh, M Scudiero, DA Monks, A Sausville, EA Weinstein, JN Friend, S Fornace, AJ Kohn, KW TI Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGING AGENTS; CHEMOTHERAPEUTIC-AGENTS; DIVERSE PANEL; MUTATIONS; GENE; SENSITIVITY; PROTEIN; RADIOSENSITIVITY; IDENTIFICATION; CYTOTOXICITY AB In the present study, we report the characterization of the p53 tumor suppressor pathway in the 60 cell lines of the National Cancer Institute (NCI) anticancer drug screen, as well as correlations between the integrity of this pathway and the growth-inhibitory potency of 123 anticancer agents in this screen. Assessment of p53 status in these lines was achieved through complete p53 cDNA sequencing, measurement of basal p53 protein levels and functional assessment of (a) transcriptional activity of p53 cDNA from each line in a yeast assay, (b) gamma-ray-induced G(1) phase cell cycle arrest, and (c) gamma-ray-induced expression of CIP1/WAF1, GADD45, and MDM2 mRNA. Our investigations revealed that p53 gene mutations were common in the NCI cell screen lines: 39 of 58 cell lines analyzed contained a mutant p53 sequence. cDNA derived from almost all of the mutant p53 cell lines failed to transcriptionally activate a reporter gene in yeast, and the majority of mutant p53 lines studied expressed elevated basal levels of the mutant p53 protein. In contrast to most of the wild-type p53-containing lines, cells containing mutant p53 sequence were also deficient in gamma-ray induction of CIP1/WAF1, GADD45, and MDM2 mRNA and the ability to arrest in G(1) following gamma-irradiation. Taken together, these assessments provided indications of the integrity of the p53 pathway in the 60 cell lines of the NCI cell screen. These individual p53 assessments were subsequently used to probe a database of growth-inhibitory potency for 123 ''standard agents,'' which included the majority of clinically approved anticancer drugs. These 123 agents have been tested against these lines on multiple occasions, and a proposed mechanism of drug action had previously been assigned to each agent. Our analysis revealed that cells with mutant p53 sequence tended to exhibit less growth inhibition in this screen than the wild-type p53 cell lines when treated with the majority of clinically used anticancer agents: including DNA cross-linking agents, antimetabolites, and topoisomerase I and II inhibitors. Similar correlations were uncovered when we probed this database using most of the other indices of p53 status we assessed in the lines. Interestingly, a class of agents that differed in this respect was the antimitotic agents. Growth-inhibitory activity of these agents tended, in this assay, to be independent of p53 status. Our characterization of the p53 pathway in the NCI cell screen lines should prove useful to researchers investigating fundamental aspects of p53 biology and pharmacology, This information also allows for the large-scale analysis of the more than 60,000 compounds tested against these lines for novel agents that might exploit defective p53 function as a means of preferential toxicity. C1 NCI,FREDERICK CANC RES & DEV CTR,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. FRED HUTCHINSON CANC RES CTR,MOL PHARMACOL LAB,SEATTLE,WA 98104. RP OConnor, PM (reprint author), NCI,DIV BASIC SCI,MOL PHARMACOL LAB,NIH,BLDG 37,ROOM 5C25,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 44 TC 744 Z9 754 U1 3 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1997 VL 57 IS 19 BP 4285 EP 4300 PG 16 WC Oncology SC Oncology GA XZ011 UT WOS:A1997XZ01100028 PM 9331090 ER PT J AU SalazarOnfray, F Nakazawa, T Chhajlani, V Petersson, M Karre, K Masucci, G Celis, E Sette, A Southwood, S Appella, E Kiessling, R AF SalazarOnfray, F Nakazawa, T Chhajlani, V Petersson, M Karre, K Masucci, G Celis, E Sette, A Southwood, S Appella, E Kiessling, R TI Synthetic peptides derived from the melanocyte-stimulating hormone receptor MC1R can stimulate HLA-A2-restricted cytotoxic T lymphocytes that recognize naturally processed peptides on human melanoma cells SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; MELANOCORTIN RECEPTOR; MOLECULAR-CLONING; HLA-A; IMMUNODOMINANT PEPTIDE; B16 MELANOMA; IDENTIFICATION; MUTANT; DIFFERENTIATION; TYROSINASE AB Human melanoma-specific HLA-A2 restricted CTLs have recently been shown to recognize antigens expressed by melanoma lines and normal melanocytes, including Melan-A/Mart-1, gp100, gp75, and tyrosinase. Herein, we define HLA-A2-restricted CTL epitopes from a recently cloned melanocortin 1 receptor (MC1R), which belongs to a new subfamily of the G-protein-coupled receptors expressed on melanomas and melanocytes. Thirty-one MC1R-derived peptides were selected on the basis of HLA-A2-specific motifs and tested for their HLA-A2 binding capacity. Of a group of 12 high or intermediate HLA-AZ binding peptides, three nonamers, MC1R244 (TILLGIFFL), MC1R283 (FLALIICNA), and MC1R291 (AIIDPLIYA), were found to induce peptide-specific CTLs from peripheral blood mononuclear cells of healthy HLA-A2+ donors after repeated in vitro stimulation with peptide-pulsed antigen-presenting cells, The CTLs raised against these three HLA-A2+-restricted peptides could recognize naturally processed peptides from HLA-A2+ melanomas and from Cos7 cells cotransfected with MC1R and HLA-A2. CTLs induced by the MC1R291 peptide (but not induced or induced only to a very low extent bg the other two MCR1 peptide epitopes) shored cross-reactions with two other members of the melanocortin receptor family, which are more broadly expressed on other tissues, Taken together, our findings have implications in relation both to autoimmunity and immunotherapy of malignant melanomas. C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. BIOMED CTR,DEPT PHARMACEUT BIOSCI,S-75124 UPPSALA,SWEDEN. AB HASSLE,DEPT CELL BIOL,S-43183 MOLNDAL,SWEDEN. KAROLINSKA HOSP,RADIUM HEMMET,DEPT EXPT ONCOL,S-17176 STOCKHOLM,SWEDEN. CYTEL CORP,DEPT CELL IMMUNOL,SAN DIEGO,CA 92121. NCI,DEPT HLTH & HUMAN SERV,NIH,BETHESDA,MD 20892. NR 44 TC 42 Z9 42 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1997 VL 57 IS 19 BP 4348 EP 4355 PG 8 WC Oncology SC Oncology GA XZ011 UT WOS:A1997XZ01100035 PM 9331097 ER PT J AU Li, SF Washburn, KA Moore, R Uno, T Teng, C Newbold, RR McLachlan, JA Negishi, M AF Li, SF Washburn, KA Moore, R Uno, T Teng, C Newbold, RR McLachlan, JA Negishi, M TI Developmental exposure to diethylstilbestrol elicits demethylation of estrogen-responsive lactoferrin gene in mouse uterus SO CANCER RESEARCH LA English DT Article ID DNA METHYLATION; NEOPLASTIC TRANSFORMATION; REPRODUCTIVE-TRACT; BREAST-CANCER; PROTEIN; ADENOCARCINOMA; EXPRESSION; PROMOTER; VAGINA; PERIOD AB Alteration of DNA demethylation in five CpG sites (-547, -533, -475, -464, and -454) immediately upstream from the estrogen response element of lactoferrin promoter was determined in the uteri of immature (17-day-old) and mature (21- and 30-day-old) mice treated neonatally with DES, Only the CpG/-464 was found to be abnormally demethylated by diethylstilbestrol (DES) treatment in the mature uteri. This abnormal demethylation occurred in specific response to DES in neonatal mice, because DES injected into the 30-day-old mature mice did not demethylate CpG/-464. This site, however, remained methylated in the neonatally DES-treated/ovariectomized mice, indicating that this DES-elicited demethylation is under hormonal control. Thus, neonatal DES treatment appeared to imprint an abnormal, site-specific demethylation of CpG/-464, which requires ovarian hormones to occur in adult mice, Moreover, the demethylation was maintained in uterine tumors of the neonatally DES-treated mice, This mode of demethylation is reminiscent of uterine tumor formation, which also depends on both neonatal DES exposure and ovarian hormone stimulation in adulthood, Thus, neonatal DES treatment may induce tumor formation as well as demethylation through a common cellular process. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,NIH,RES TRIANGLE PK,NC 27709. NIEHS,TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. TULANE UNIV,TULANE XAVIER CTR BIOENVIRONM RES,NEW ORLEANS,LA 70112. TULANE UNIV,DEPT PHARMACOL,NEW ORLEANS,LA 70112. NR 28 TC 177 Z9 183 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1997 VL 57 IS 19 BP 4356 EP 4359 PG 4 WC Oncology SC Oncology GA XZ011 UT WOS:A1997XZ01100036 PM 9331098 ER PT J AU Lista, F Bertness, V Guidos, CJ Danska, JS Kirsch, IR AF Lista, F Bertness, V Guidos, CJ Danska, JS Kirsch, IR TI The absolute number of trans-rearrangements between the TCRG and TCRB loci is predictive of lymphoma risk: A severe combined immune deficiency (SCID) murine model SO CANCER RESEARCH LA English DT Article ID T-CELL RECEPTOR; COMBINED IMMUNODEFICIENCY MUTATION; ATAXIA-TELANGIECTASIA GENE; BROKEN DNA-MOLECULES; GAMMA-DELTA-GENES; V(D)J RECOMBINATION; ANTIGEN RECEPTOR; MOUSE THYMOCYTES; PROTEIN-KINASE; CHROMOSOMAL TRANSLOCATIONS AB Pilot studies in human populations have demonstrated a correlation between the level of antigen receptor trans-rearrangements and risk (at the population level) of lymphoid malignancy, Irradiation of newborn severe combined immune deficiency mice results in an increased risk of subsequent development of thymic lymphoma (100% of mice so irradiated are dead of thymic lymphoma by 20 weeks of age), We, therefore, assayed the occurrence of trans-rearrangements in this well-controlled mouse mutant system and found a 50-100-fold increase in the absolute number of TCRGV-TCRBJ trans-rearrangements compared to unirradiated litter-mates (and a comparable fold increase over age-matched BALB/c mice) at 2 weeks following irradiation, We also found a marked disproportion in generating trans-rearrangements versus intralocus rearrangements in the severe combined immune deficiency system compared to BALB/c, independent of irradiation. The trans-rearrangements noted were polyclonal in nature, These data, again, suggest that the absolute level of antigen receptor trans-rearrangements may serve as a biomarker of lymphoma risk. C1 NCI,MED BRANCH,DEPT GENET,BETHESDA,MD 20899. CTR STUDI & RIC SANITA ESERCITO,I-00184 ROME,ITALY. UNIV TORONTO,HOSP SICK CHILDREN,RES INST,TORONTO,ON M5G 1X8,CANADA. UNIV TORONTO,DEPT IMMUNOL,TORONTO,ON M5G 1X8,CANADA. NR 50 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1997 VL 57 IS 19 BP 4408 EP 4413 PG 6 WC Oncology SC Oncology GA XZ011 UT WOS:A1997XZ01100042 PM 9331104 ER PT J AU Diwan, BA Anderson, LM Ward, JM AF Diwan, BA Anderson, LM Ward, JM TI Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER; DNA-ADDUCTS; RATS AB Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age, However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring, Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks, Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks, Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Diwan, BA (reprint author), NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,BLDG 538,FREDERICK,MD 21702, USA. NR 24 TC 29 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1997 VL 18 IS 10 BP 2009 EP 2014 DI 10.1093/carcin/18.10.2009 PG 6 WC Oncology SC Oncology GA YB225 UT WOS:A1997YB22500023 PM 9364013 ER PT J AU Lazarous, DF Shou, M Stiber, JA Dadhania, DM Thirumurti, V Hodge, E Unger, EF AF Lazarous, DF Shou, M Stiber, JA Dadhania, DM Thirumurti, V Hodge, E Unger, EF TI Pharmacodynamics of basic fibroblast growth factor: route of administration determines myocardial and systemic distribution SO CARDIOVASCULAR RESEARCH LA English DT Article DE angiogenesis; bFGF; pharmacodynamics; myocardium; growth factors; dog ID COLLATERAL DEVELOPMENT; EXTRACELLULAR-MATRIX; HEPARIN-BINDING; RABBIT MODEL; ANGIOGENESIS; ISCHEMIA; RATS; IMMUNOLOCALIZATION; CIRCULATION; INJECTION AB Objective: We have shown that basic fibroblast growth factor (bFGF/FGF-2) enhances myocardial collateral development in a canine model of progressive coronary occlusion when delivered via the left atrial or intracoronary routes; however, we have found intravenous bFGF ineffective in the same model. Data on the fate and efficacy of intravenous bFGF are limited. We hypothesized that first pass lung uptake might limit myocardial bFGF availability after intravenous injection. We postulated that delivery of bFGF through the distal port of a wedged Swan Ganz catheter might circumvent this problem by restricting exposure of bFGF to a limited number of pulmonary binding sites. This study evaluated differential regional uptake of I-125 labeled bFGF following bolus intravenous, Swan Ganz, left atrial, intracoronary, and pericardial delivery. Methods: Mongrel dogs were used. Human recombinant bFGF, monoiodinated with I-125, was mixed with cold bFGF to a specific activity of 0.03 mu Ci/mu g. Approximately 100 mu g/kg was injected per animal by the intravenous, left atrial, Swan Ganz, intracoronary, or pericardial route. Dogs were killed 15 min or 150 min later. The heart, lungs, Liver, spleen, and kidneys were harvested and I-125 activity was assessed. Immunohistochemical and pharmacokinetic studies were also performed. Results: Serum half life of bFGF was comparable after intracoronary, intravenous and left atrial delivery (50 min); however, there were significant differences with regard to pharmacodynamics. After intracoronary administration, 3-5% of the total bFGF dose was recovered from the heart, with the peptide immunolocalized to the extracellular matrix and vascular endothelium. In contrast, only 1.3% of the injected bFGF was localized to the he;ut after left atrial administration, and 0.5% was recovered after intravenous or Swan Ganz delivery, Pericardial administration resulted in substantial cardiac bFGF delivery 19% was present at 150 min, Myocardial uptake was similar with Swan Ganz and intravenous delivery, suggesting that the administered dose did not saturate available pulmonary binding sites, Conclusions: These data predict efficacy of intracoronary, left atrial, and pericardial bFGF for myocardial angiogenesis, and a lack of efficacy after bolus intravenous and Swan Ganz administration. (C) 1997 Elsevier Science B.V. RP Lazarous, DF (reprint author), NHLBI,CARDIOL BRANCH,EXPT PHYSIOL & PHARMACOL SECT,NIH,BLDG 10,ROOM 7B15,10 CTR DR MSC 1650,BETHESDA,MD 20892, USA. NR 31 TC 118 Z9 121 U1 0 U2 2 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 1997 VL 36 IS 1 BP 78 EP 85 DI 10.1016/S0008-6363(97)00142-9 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YE631 UT WOS:A1997YE63100011 PM 9415275 ER PT J AU Kaufmann, WK Schwartz, JL Hurt, JC Byrd, LL Galloway, DA Levedakou, E Paules, RS AF Kaufmann, WK Schwartz, JL Hurt, JC Byrd, LL Galloway, DA Levedakou, E Paules, RS TI Inactivation of G(2) checkpoint function and chromosomal destabilization are linked in human fibroblasts expressing human papillomavirus type 16 E6 SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID CELL-CYCLE CONTROL; LI-FRAUMENI SYNDROME; DNA-DAMAGE; TYROSINE PHOSPHORYLATION; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; EPITHELIAL-CELLS; EXCISION-REPAIR; GROWTH ARREST; G1 ARREST AB Chromosomal stability was linked to G(2) checkpoint function in human fibroblasts expressing the human papillomavirus type 16 E6 oncoprotein. Soon after expression of E6, cells displayed an undamaged, diploid karyotype and normal mitotic delay after gamma-irradiation, As the EG-expressing cells aged through their in vitro life span, G(2) checkpoint function diminished progressively, After 30-70 population doublings, 60-86% of the E6 cells displayed defective G(2) checkpoint response. This attenuation of G(2) checkpoint function was also associated with radiation-resistant cyclin B1/CDK1 protein kinase activity, Numerical and structural abnormalities of chromosomes developed in unirradiated E6 cells with kinetics that mirrored the loss of G(2) checkpoint function. A significant correlation between inactivation of the G(2) checkpoint and acquisition of chromosomal abnormalities was found, suggesting that the G(2) checkpoint represents a barrier to genetic instability in cells lacking G(1) checkpoint function. C1 UNIV N CAROLINA,DEPT PATHOL & LAB MED,CHAPEL HILL,NC 27599. UNIV WASHINGTON,DEPT RADIAT ONCOL,SEATTLE,WA 98195. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NIEHS,GROWTH CONTROL & CANC GRP,RES TRIANGLE PK,NC 27709. RP Kaufmann, WK (reprint author), UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CB 7295,ROOM 351,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [CA64795, CA42765, P01 CA042765]; NIGMS NIH HHS [GM51827] NR 45 TC 57 Z9 58 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1997 VL 8 IS 10 BP 1105 EP 1114 PG 10 WC Cell Biology SC Cell Biology GA YC358 UT WOS:A1997YC35800008 PM 9342189 ER PT J AU Ray, PE Saavedra, JM AF Ray, PE Saavedra, JM TI Selective chronic sodium or chloride depletion specifically modulates subfornical organ atrial natriuretic peptide receptor number in young rats SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE electrolyte metabolism; water deprivation; circumventricular organs; paraventricular nucleus; atrial natriuretic factor; extracellular fluid volume ID ANGIOTENSIN-II RECEPTORS; BLOOD-PRESSURE; RENIN RELEASE; BINDING-SITES; BRAIN PASTE; VASOPRESSIN; PLASMA; AUTORADIOGRAPHY; LOCALIZATION; STIMULATION AB 1. We studied the effects of selective chronic sodium depletion of chloride depletion on atrial natriuretic peptide receptor number in the subfornical organ and paraventricular nucleus of young rats. 2. Sodium or chloride depletion decreased plasma levels of atrial natriuretic peptide, increased plasma renin activity, and induced extracellular fluid volume contraction, Chloride depletion induced more significant changes in extracellular fluid volume contraction than sodium depletion. 3. In the subfornical organ, atrial natriuretic peptide receptor number significantly decreased (30%) after sodium depletion, while chloride depletion induced a smaller, not statistically significant decrease. Conversely, atrial natriuretic peptide receptors located in the paraventricular nucleus of young rats were not significantly affected by sodium or chloride depletion. 4. Water deprivation reversed the decrease in atrial natriuretic peptide receptors produced by sodium depletion, Water-deprived sodium-depleted rats actually had higher numbers of atrial natriuretic peptide receptors in the subfornical organ than control rats. These changes were associated with severe extracellular fluid volume contraction and up regulation of brain vasopressin mRNA steady-state levels. Thus, the direction of change in the number of subfornical organ atrial natriuretic peptide receptors was dependent on the degree of extracellular fluid volume contraction. 5. Our results suggest that atrial natriuretic peptide receptors located in the subfornical organ, and not in the paraventricular nucleus, are selectively regulated by sodium depletion and extracellular fluid volume contraction. C1 CHILDRENS NATL MED CTR,CHILDRENS RES INST,CTR 4,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,WASHINGTON,DC. NIMH,PHARMACOL SECT,CLIN SCI LAB,BETHESDA,MD 20892. RP Ray, PE (reprint author), CHILDRENS NATL MED CTR,CHILDRENS RES INST,DEPT NEPHROL,ROOM R-211,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. FU NHLBI NIH HHS [R0-1 HL 55605]; NIDDK NIH HHS [R0-1 DK 4919] NR 37 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD OCT PY 1997 VL 17 IS 5 BP 455 EP 470 DI 10.1023/A:1026302703894 PG 16 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA YC661 UT WOS:A1997YC66100002 PM 9353588 ER PT J AU Kadiiska, MB Mason, RP Dreher, KL Costa, DL Ghio, AJ AF Kadiiska, MB Mason, RP Dreher, KL Costa, DL Ghio, AJ TI In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID IN-VIVO; OXIDANT GENERATION; DNA-DAMAGE; ADDUCTS; METALS; ACID; ALPHA-(4-PYRIDYL-1-OXIDE)-N-TERT-BUTYLNITRONE; HYDROPEROXIDES; IDENTIFICATION; INHALATION AB Exposure to air pollution particles can be associated with increased human morbidity and mortality. The mechanism(s) of lung injury remains unknown. We tested the hypothesis that lung exposure to oil fly ash (an emission source air; pollution particle) causes in vivo free radical production. Electron spin resonance (ESR) in conjunction with the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) was used to detect radical adducts. Rats were instilled with 500 mu g of either oil fly ash or saline, Twenty-four hours later, ESR spectroscopy of the chloroform extract from lungs of animals exposed to the oil fly ash gave a spectrum consistent with a carbon-centered radical adduct (hyperfine coupling constants a(N) = 15.0 G and a(beta)(H) = 2.5 G), while those spectra from lungs instilled with saline revealed a much weaker signal. This signal was reproduced by instilling animals with the soluble fraction of the ail fly ash, which contains soluble metal compounds. The same signal was observed after instillation of either a mixture of vanadium, nickel, and iron sulfates or VOSO4 alone, We conclude that, after instillation of an air pollution par-tide in the rat, ESR analysis of lung tissue demonstrates in vivo free radical production, This generation of free radicals appears to be associated with soluble metals in the oil fly ash. C1 US EPA,NHEERL,HSD,CRB,RES TRIANGLE PK,NC 27711. NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709. NR 40 TC 125 Z9 130 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 1997 VL 10 IS 10 BP 1104 EP 1108 DI 10.1021/tx970049r PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA YB089 UT WOS:A1997YB08900007 PM 9348432 ER PT J AU Rose, ML Germolec, D Arteel, GE Schoonhoven, R Thurman, RG AF Rose, ML Germolec, D Arteel, GE Schoonhoven, R Thurman, RG TI Dietary glycine prevents increases in hepatocyte proliferation caused by the peroxisome proliferator WY-14,643 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID RAT KUPFFER CELLS; NECROSIS-FACTOR-ALPHA; HYPOLIPIDEMIC DRUGS; DNA-SYNTHESIS; LIVER; CALCIUM; CARCINOGENESIS; SUSCEPTIBILITY; MACROPHAGES; NAFENOPIN AB Peroxisome proliferators are a group of nongenotoxic carcinogens which include a number of hypolipidemic drugs, solvents, and industrial plasticizers. Although the mechanism by which they cause cancer remains unknown, one likely possibility is that they act as tumor promoters by increasing cell proliferation. Hepatic Kupffer cells represent a rich source of mitogenic cytokines (e,g., tumor necrosis factor alpha, TNF alpha) and are stimulated by peroxisome proliferators. Since glycine prevents activation of Kupffer cells, these experiments were designed to test the hypothesis that a diet containing glycine could block the mitogenic effect of the peroxisome proliferator [[4-chloro-6-(2,3-xylidino)pyrimidinyl]thio]acetate acid(WY-14,643). The effects of a glycine-enriched diet on WY-14,643-induced increases in cell proliferation after a single dose or after feeding WY-14,643 in the diet for 3 weeks were assessed. As expected, 24 h after a single dose of WY-14,643, rates of cell proliferation increased from basal values of 0.7 +/- 0.3% to 5.1 +/- 0.5%, Glycine largely prevented the increase caused by WY-14,643 with proliferation only reaching 1.9 +/ 0.4% (p < 0,05), Acyl CoA oxidase increased from 1.4 +/- 0.1 to 3.5 +/- 0.6 nmol of H2O2 min(-1) (mg of protein)(-1) (P < 0,05) indicating that peroxisome-specific enzyme activity was induced about 2-fold in livers of WY-14,643-treated rats after 24 h. Unlike cell proliferation, however, acyl CoA oxidase was not affected by dietary glycine, consistent with the hypothesis that cell proliferation and peroxisome proliferation occur via different mechanisms, After 3 weeks, dietary glycine reduced basal rates of cell proliferatian by about 50% and completely prevented the sustained 5-fold increase in cell proliferation caused by feeding WY-14,643. Moreover, the 3-fold increase in TNF alpha mRNA caused by WY-14,643 was blocked completely by the glycine-enriched diet. Similarly, immunohistochemical staining for TNF alpha was increased B-fold by WY-14,643, an increase which was prevented by dietary glycine. However, the g-fold increase in acyl. CoA oxidase activity was unaffected by glycine under similar conditions demonstrating that, a diet containing 5% glycine prevents increased hepatocyte proliferation caused by a potent peroxisome proliferator without affecting induction of peroxisomes. These data demonstrate that a glycine-enriched diet prevents stimulated cell proliferation most likely by inhibiting TNF alpha. production and raise the possibility that dietary glycine will be effective in preventing cancer caused by nongenotoxic carcinogens such as WY-14,643. C1 UNIV N CAROLINA,DEPT PHARMACOL,LAB HEPATOBIOL & TOXICOL CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT ENVIRONM SCI,LAB HEPATOBIOL & TOXICOL CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. FU NIEHS NIH HHS [5-T32ES-07126-13, ES-04325] NR 36 TC 44 Z9 44 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 1997 VL 10 IS 10 BP 1198 EP 1204 DI 10.1021/tx970079u PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA YB089 UT WOS:A1997YB08900019 PM 9348444 ER PT J AU Chen, YM Yang, WK Ting, CC Tsai, WY Yang, DM WhangPeng, J Perng, RP AF Chen, YM Yang, WK Ting, CC Tsai, WY Yang, DM WhangPeng, J Perng, RP TI Cross regulation by IL-10 and 1L-2/IL-12 of the helper T cells and the cytolytic activity of lymphocytes from malignant effusions of lung cancer patients SO CHEST LA English DT Article DE gamma-interferon (IFN-gamma); interleukin-2 (IL-2) ID ACTIVATED KILLER CELLS; RECOMBINANT INTERLEUKIN-2; PLEURAL EFFUSION; NATURAL-KILLER; RESPONSES; CYTOKINE AB Study objective: Our previous report demonstrated that there was impairment of local cellular immunity with elevated interleukin-10 (IL-10) and undetectable IL-12 in neoplastic pleural effusion. These findings suggest that the local immune reactions favor the T-helper type 2 (Th2) pathway instead of Th1 pathway. The present study was designed to examine whether local cellular immunity could be manipulated by IL-2 and/or IL-12 treatment, and to determine their effect on the helper T-cell pathways and the cytolytic activity of the effusion-associated lymphocytes (EALs). Design: Using malignant pleural effusions obtained from four patients suffering from adenocarcinoma of lung, we separated the tumor cells from the EALs with Ficol-Hypaque centrifugation, followed by Percoll density centrifugation. To test whether the cytolytic function of lymphocytes could be enhanced by culturing with IL-2 and/or IL-12, lymphocytes were incubated with recombinant IL-2 with/without IL-12 for 6 days. Following this, the tumoricidal activity was assessed in an overnight (51)chromium-release assay. Autologous tumor cells for measuring specific antitumor activity, Daudi cells susceptible to lymphokine-activated killer cells, and NK-susceptible K562 cells were used as target cells. Measurements and results: After treatment in vitro with IL-2, IL-12, or IL-2 plus IL-12, the Th pathway shifted from Th2 to Th1 type (increased gamma-interferon production). To further study the effect of cytokine treatment on the cytolytic activity of EALs, it was found that after 6-day culturing, the EALs failed to kill any of the three tumor targets, whereas the 6-day cultured peripheral blood lymphocytes (PBLs) gave low level of cytotoxicity against all three tumor targets. Stimulation with IL-2 alone partially restored the immunocompetence of EALs to kill the tumor targets. Stimulation with IL-12 alone showed no significant effect on their cytolytic activity. However, IL-12 synergized with IL-2 to increase the cytolytic activity of EALs and PBLs against autologous tumor targets. This synergistic effect was not found for Daudi cells and K562 cells. Conclusions: These result suggest that EALs activated with IL-12 in the presence of a low concentration of IL-2, which converted the EALs from Th2 pathway to Th1 pathway, could be an alternative source of antitumor effectors for adoptive immunotherapy of cancer. C1 VET GEN HOSP,CHEST DEPT,TAIPEI,TAIWAN. NATL HLTH RES INST,CANC CLIN RES CTR,TAIPEI,TAIWAN. NATL YANG MING UNIV,SCH MED,TAIPEI,TAIWAN. NCI,LAB IMMUNE CELL BIOL,NIH,BETHESDA,MD 20892. NR 20 TC 34 Z9 36 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD OCT PY 1997 VL 112 IS 4 BP 960 EP 966 DI 10.1378/chest.112.4.960 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA YA351 UT WOS:A1997YA35100018 PM 9377959 ER PT J AU Giacomini, M Kolobow, T RealiForster, C Trawoger, R Cereda, M AF Giacomini, M Kolobow, T RealiForster, C Trawoger, R Cereda, M TI Intratracheal pulmonary ventilation and continuous positive airway pressure in a sheep model of severe acute respiratory failure SO CHEST LA English DT Article DE acute respiratory failure; CPAP; intratracheal pulmonary ventilation (ITPV) ID END-EXPIRATORY PRESSURE; TRACHEAL GAS INSUFFLATION; LUNG INJURY AB Study objectives: Previously we have shown that optimal pulmonary gas exchange can be sustained at normal airway pressures in a model of severe acute respiratory failure (ARF), using intratracheal pulmonary ventilation (ITPV), with weaning to room air, In an identical model of ARF, we have now explored whether ITPV, combined with continuous positive airway pressure (CPAP), can sustain adequate ventilation, with weaning to room air. Design: Randomized study in sheep. Setting: Animal research laboratory at the National Institutes of Health. Interventions: ARF was induced in 12 sheep, using mechanical ventilation at peak inspiratory pressure of 50 cm H2O, bunt excluding 5 to 8% of lungs. Sheep were then randomized into two groups: the CPAP-ITPV group (n=6), in which ITPV was combined with a novel CPAP system; and a control group (n=6) in which the same CPAP circuit was used, hut without ITPV. Measurements and results: All sheep in the CPAP-ITPV group were weaned to room air in 38.7+/-14 h. PaO2/fraction of inspired oxygen (FIo(2)) progressively increased from 108.8+/-43 to 355.7+/-93.1; PaCO2 remained within normal range; respiratory rate (RR) ranged from 18 to 120 breaths/min, and tidal volume (VT) was as low as 1.1 mL/kg. All sheep in the control group (CPAP alone) developed severe respiratory-acidosis and hypoxemia after 4.8+/-4 h, PaO2/FIo(2) decreased from 126.6+/-58.2 to 107.2+/-52.5 mm Hg, with a final PaCO2 of 166.8-73.3 mm Hg. Conclusions: All sheep treated with CPAP-ITPV maintained good gas exchange without hypercapnia at high RR and at low VT, with weaning to room air. All control animals treated with CPAP alone developed severe hypercapnia, respiratory acidosis, and severe hypoxemia, and were killed. C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NR 16 TC 10 Z9 10 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD OCT PY 1997 VL 112 IS 4 BP 1060 EP 1067 DI 10.1378/chest.112.4.1060 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA YA351 UT WOS:A1997YA35100033 PM 9377918 ER PT J AU Appelbaum, M Batten, DA Belsky, J Booth, C Bradley, R Brownell, C Caldwell, B Campbell, S ClarkeStewart, A Cohn, J Cox, M Fendt, K Friedman, S HirshPasek, K Huston, A Knoke, B Marshall, N McCartney, K OBrien, M Owen, MT Phillips, D Ricciuti, H Spieker, S Vandell, DL Weinraub, M AF Appelbaum, M Batten, DA Belsky, J Booth, C Bradley, R Brownell, C Caldwell, B Campbell, S ClarkeStewart, A Cohn, J Cox, M Fendt, K Friedman, S HirshPasek, K Huston, A Knoke, B Marshall, N McCartney, K OBrien, M Owen, MT Phillips, D Ricciuti, H Spieker, S Vandell, DL Weinraub, M TI The effects of infant child care on infant-mother attachment security: Results of the NICHD study of early child care SO CHILD DEVELOPMENT LA English DT Article ID STRANGE SITUATION; TEMPERAMENT; EMPLOYMENT; EXPERIENCE; QUALITY AB The aims of this investigation were to determine whether Strange Situation attachment classifications were equally valid for infants with and without extensive child-care experience in the first year of life and whether early child-care experience, alone or in combination with mother/child factors, was associated with attachment security, and specifically with insecure-avoidant attachment. Participants were 1,153 infants and their mothers at the 10 sites of the NICHD Study of Early Child Care. Mothers were interviewed, given questionnaires, and observed in play and in the home when their infants were from 1 to 15 months of age; infants were observed in child care at 6 and 15 months and in the Strange Situation at 15 months. Infants with extensive child-care experience did not differ from infants without child care in the distress they exhibited during separations from mother in the Strange Situation or in the confidence with which trained coders assisted them attachment classifications. There were no significant main effects of child-care experience (quality, amount, age of entry, stability, or type of care) on attachment security or avoidance. There were, however, significant main effects of maternal sensitivity and responsiveness. Significant interaction effects revealed that infants were less likely to be secure when low maternal sensitivity/responsiveness was combined with poor quality child care, more than minimal amounts of child care, or more than one care arrangement. In addition, boys experiencing many hours in care and girls in minimal amounts of care were somewhat less likely to he securely attached. C1 PENN STATE UNIV,UNIVERSITY PK,PA 16802. TEMPLE UNIV,PHILADELPHIA,PA 19122. UNIV ARKANSAS,LITTLE ROCK,AR 72204. UNIV CALIF IRVINE,IRVINE,CA 92717. UNIV KANSAS,LAWRENCE,KS 66045. UNIV NEW HAMPSHIRE,DURHAM,NH 03824. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV TEXAS,DALLAS,TX 75230. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV WISCONSIN,MADISON,WI 53706. VANDERBILT UNIV,NASHVILLE,TN 37240. WELLESLEY COLL,WELLESLEY,MA 02181. RP Appelbaum, M (reprint author), NICHHD,CDBB,BLDG 61E,4B05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Marshall, Nancy/C-3428-2012 NR 51 TC 313 Z9 316 U1 8 U2 34 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD OCT PY 1997 VL 68 IS 5 BP 860 EP 879 PG 20 WC Psychology, Educational; Psychology, Developmental SC Psychology GA YB560 UT WOS:A1997YB56000009 ER PT J AU Chen, ZX Breitman, TR AF Chen, ZX Breitman, TR TI Effects of prostaglandin E-2 and all-trans retinoic acid combination on induced differentiation of human acute promyelocytic leukemia NB4 cells SO CHINESE MEDICAL JOURNAL LA English DT Article ID ORAL PROSTAGLANDIN-E2; BINDING PROTEIN; HL-60; RESISTANCE; THERAPY; LINES; U-937 AB Objective A human promyelocytic leukemia (APL) cell line NE, was used to demonstrate the synergistic effects between all-trans retinoic acid (ATRA) and prostaglandin E-2 (PGE(2)) on growth inhibition and cytodifferentiation induction. Methods NB4 cells were cultured in the presence of either ATRA or PGE(2) as a single agent or in combinations at various ratio. Cell growth was measured and myeloid differentiation was tested on consecutive days over the whole course of culture. Results PGE(2) and ATRA synergistically induced the myeloid differentiation of NB4 cells. In comparison with ATRA alone, the combination of PGE(2) with ATRA caused an almost 20-fold decrease of effective concentration of ATRA. Conclusion The combination of ATRA and PGE(2) at an appropriate ratio may provide a convenient oral regimen of combined differentiation therapy for a better clinical outcome in APL patients. C1 NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. RP Chen, ZX (reprint author), SUZHOU UNIV,JIANGSU INST HEMATOL,AFFILIATED HOSP 1,SUZHOU 215006,JIANGSU PROVINC,PEOPLES R CHINA. NR 19 TC 5 Z9 5 U1 0 U2 0 PU CHINESE MEDICAL ASSOCIATION PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD OCT PY 1997 VL 110 IS 10 BP 783 EP 788 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YA990 UT WOS:A1997YA99000017 PM 9642310 ER PT J AU Elin, RJ Fried, MW Sampson, M Ruddel, M Kleiner, DE DiBisceglie, AM AF Elin, RJ Fried, MW Sampson, M Ruddel, M Kleiner, DE DiBisceglie, AM TI Assessment of monoethylglycinexylidide as measure of liver function for patients with chronic viral hepatitis SO CLINICAL CHEMISTRY LA English DT Article ID LIDOCAINE METABOLITE FORMATION; CIRRHOSIS; TRANSPLANTATION; RECIPIENT; DISEASE; DONORS; MEGX AB The liver metabolizes lidocaine by oxidative deethylation to form monoethylglycinexylidide (MEGX), an analyte proposed as an index of liver function. We determined MEGX and lidocaine serum concentrations with the TDx (Abbott Laboratories) at baseline and 15, 30, 60, and 90 min after the intravenous administration of lidocaine (1 mg/kg), analyzing specimens from 12 apparently healthy volunteers and 40 patients with chronic viral hepatitis diagnosed by liver biopsy and serum tests, The patients were grouped on the basis of the histology activity index. The following]laboratory tests were performed on serum specimens from all subjects: albumin (ALE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, and prothrombin time. The results showed no significant difference among the four groups for the concentrations of MEGX, lidocaine, and lidocaine/MEGX at the four time points. However, the concentrations of ALB, ALT, AST, AST/ALT, and prothrombin time were substantially different among the four groups. Thus, we conclude that assay of MEGX in our patients with chronic viral hepatitis did not contribute to the assessment of liver function when compared with 1 apparently healthy volunteers and traditional tests of liver function. C1 NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NIDDKD, DIGEST DIS BRANCH, NIH, BETHESDA, MD 20892 USA. RP Elin, RJ (reprint author), NIH, WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL, BLDG 10,RM 2C-306, 10 CTR DR, MSC 1508, BETHESDA, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 NR 27 TC 9 Z9 10 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 1997 VL 43 IS 10 BP 1952 EP 1957 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA YA359 UT WOS:A1997YA35900023 PM 9342018 ER PT J AU Gniewek, RA Sandbulte, C Fox, PC AF Gniewek, RA Sandbulte, C Fox, PC TI Comparison of antinuclear antibody testing methods by ROC analysis with reference to disease diagnosis SO CLINICAL CHEMISTRY LA English DT Letter C1 ARTHRIT CTR,LINCOLN,NE 68506. NIDR,NIH,BETHESDA,MD 20892. RP Gniewek, RA (reprint author), BIORAD LABS,4000 ALFRED NOBEL DR,HERCULES,CA 94547, USA. NR 14 TC 9 Z9 10 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 1997 VL 43 IS 10 BP 1987 EP 1989 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA YA359 UT WOS:A1997YA35900030 PM 9342025 ER PT J AU Mozes, E Alling, D Miller, MW Payne, SM Zinger, H Via, CS Shearer, GM AF Mozes, E Alling, D Miller, MW Payne, SM Zinger, H Via, CS Shearer, GM TI Genetic analysis of experimentally induced lupus in mice SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID AUTOANTIBODY PRODUCTION; MURINE MODEL; HOST DISEASE; ERYTHEMATOSUS; INDUCTION; MANIFESTATIONS; SUSCEPTIBILITY; IDIOTYPE; RECEPTOR; LINKAGE AB The DBA/2 and C57BL/6 mouse strains, as well as the BXD RI lines derived from these strains, were used to map the genes controlling experimentally induced systemic lupus erythematosus (SLE). SLE was induced using two immunologic approaches: (1) immunization with the human monoclonal anti-DNA antibody expressing the 16/6Id, to which the DBA/2 strain is susceptible (responder) and the C57BL/6 strain is resistant (nonresponder); and (2) induction of autoimmune GVHD in B6D2F1 hosts by inoculation of parental DBA/2 (induces SLE) or C57BL/6 (does not induce SLE) T cells. By both approaches the BXD RI lines could be divided into distinct DBA/2-like and C57BL/6-like categories. Concordance of SLE induced by both methods was observed for susceptibility and resistance in 13/15 BXD lines (P < 0.005). The results suggest that at least two non-H-2 genes control susceptibility and resistance to experimentally induced SLE, one mapping to chromosome 7 and the other mapping to chromosome 14. (C) 1997 Academic Press. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE,MD 21201. RP Mozes, E (reprint author), WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. NR 19 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD OCT PY 1997 VL 85 IS 1 BP 28 EP 34 DI 10.1006/clin.1997.4423 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA YA706 UT WOS:A1997YA70600004 PM 9325066 ER PT J AU Masur, H Kaplan, JE Holmes, KK Baker, AC Barr, D Benson, C Brosgart, C Chaisson, R Cooper, E Crumpacker, C Decker, C Drew, L Eisinger, R ElSadr, W Freedberg, K Goldberger, M Gordin, F Greaves, W Gross, P Hafner, R Havlir, D Horsburgh, R Jabs, D Kitahata, M Kovacs, J Martone, W Mayers, D Melnick, D Mofenson, L Neaton, J Nelson, C Oldfield, E Phair, J Polis, M Polsky, B Powderly, W Rimland, D Sloand, E Solomon, L Spector, S Sperling, R Trapnell, CB VanDyke, R Whitley, R Wright, T Belay, E Butler, JC Castro, KG Dykewicz, C Edlin, BR Ellerbrock, T Hajjeh, RA Jaffe, HW Juranek, D McNeil, M Miller, B Pellett, PE Reeves, W Schluter, WW Spiegel, RA Stewart, JA Styrt, B Vernon, SD Ward, J AF Masur, H Kaplan, JE Holmes, KK Baker, AC Barr, D Benson, C Brosgart, C Chaisson, R Cooper, E Crumpacker, C Decker, C Drew, L Eisinger, R ElSadr, W Freedberg, K Goldberger, M Gordin, F Greaves, W Gross, P Hafner, R Havlir, D Horsburgh, R Jabs, D Kitahata, M Kovacs, J Martone, W Mayers, D Melnick, D Mofenson, L Neaton, J Nelson, C Oldfield, E Phair, J Polis, M Polsky, B Powderly, W Rimland, D Sloand, E Solomon, L Spector, S Sperling, R Trapnell, CB VanDyke, R Whitley, R Wright, T Belay, E Butler, JC Castro, KG Dykewicz, C Edlin, BR Ellerbrock, T Hajjeh, RA Jaffe, HW Juranek, D McNeil, M Miller, B Pellett, PE Reeves, W Schluter, WW Spiegel, RA Stewart, JA Styrt, B Vernon, SD Ward, J TI Preface to the 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with Human Immunodeficiency Virus SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID MYCOBACTERIUM-AVIUM COMPLEX; PNEUMOCYSTIS-CARINII PNEUMONIA; 2 CONTROLLED TRIALS; CD4 CELL COUNTS; HIV-INFECTION; RIFABUTIN PROPHYLAXIS; KAPOSIS-SARCOMA; TRIMETHOPRIM-SULFAMETHOXAZOLE; DNA-SEQUENCES; CYTOMEGALOVIRUS RETINITIS C1 NIH, BETHESDA, MD 20892 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. NATL ASSOC PERSONS AIDS, WASHINGTON, DC USA. GAY MENS HLTH CRISIS INC, WASHINGTON, DC USA. RUSH MED COLL, CHICAGO, IL 60612 USA. E BAY AIDS CTR, BERKELEY, CA USA. JOHNS HOPKINS UNIV, BALTIMORE, MD USA. BETH ISRAEL HOSP, BOSTON, MA 02215 USA. NATL NAVAL MED CTR, BETHESDA, MD USA. UNIV CALIF SAN FRANCISCO, MT ZION MED CTR, SAN FRANCISCO, CA 94143 USA. COLUMBIA UNIV COLL PHYS & SURG, HARLEM HOSP CTR, NEW YORK, NY 10032 USA. BOSTON MED CTR, BOSTON, MA USA. US FDA, ROCKVILLE, MD 20857 USA. VET ADM MED CTR, WASHINGTON, DC 20422 USA. HOWARD UNIV HOSP, WASHINGTON, DC USA. HACKENSACK MED CTR, HACKENSACK, NJ 07604 USA. EMORY UNIV, ATLANTA, GA 30322 USA. NATL FDN INFECT DIS, BETHESDA, MD USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. KAISER PERMANENTE, SPRINGFIELD, VA USA. UNIV MINNESOTA, MINNEAPOLIS, MN USA. NATL MINOR AIDS COUNCIL, WASHINGTON, DC USA. EASTERN VIRGINIA MED SCH, NORFOLK, VA 23501 USA. NORTHWESTERN UNIV, SCH MED, CHICAGO, IL USA. WASHINGTON UNIV, ST LOUIS, MO 63130 USA. MARYLAND DEPT HLTH & MENTAL HYGIENE, BALTIMORE, MD USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. TULANE UNIV, SCH MED, NEW ORLEANS, LA 70112 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. COLUMBIA UNIV, COLL PHYS & SURG, NEW YORK, NY USA. RP Masur, H (reprint author), CDC, NATL AIDS CLEARINGHOUSE, POB 6003, ROCKVILLE, MD 20849 USA. RI Belay, Ermias/A-8829-2013 NR 106 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1997 VL 25 SU 3 BP S299 EP + PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YF067 UT WOS:A1997YF06700001 ER PT J AU Masur, H Kaplan, JE Holmes, KK Armstrong, D Baker, AC Barr, D Benson, C Brosgart, C Chaisson, R Cooper, E Crumpacker, C Decker, C Drew, L Eisinger, R ElSadr, W Freedberg, K Goldberger, M Gordin, F Greaves, W Gross, P Hafner, R Havlir, D Horsburgh, R Jabs, D Kitahata, M Kovacs, J Martone, W Mayers, D Melnick, D Mofenson, L Neaton, J Nelson, C Oldfield, E Phair, J Polis, M Polsky, B Powderly, W Rimland, D Sloand, E Solomon, L Spector, S Sperling, R Trapnell, CB VanDyke, R Whitley, R Wright, T Belay, E Butler, JC Castro, KG Dykewicz, C Edlin, BR Ellerbrock, T Hajjeh, RA Jaffe, HW Juranek, D McNeil, M Miller, B Pellett, PE Reeves, W Schluter, WW Spiegel, RA Stewart, JA Styrt, B Vernon, SD Ward, J AF Masur, H Kaplan, JE Holmes, KK Armstrong, D Baker, AC Barr, D Benson, C Brosgart, C Chaisson, R Cooper, E Crumpacker, C Decker, C Drew, L Eisinger, R ElSadr, W Freedberg, K Goldberger, M Gordin, F Greaves, W Gross, P Hafner, R Havlir, D Horsburgh, R Jabs, D Kitahata, M Kovacs, J Martone, W Mayers, D Melnick, D Mofenson, L Neaton, J Nelson, C Oldfield, E Phair, J Polis, M Polsky, B Powderly, W Rimland, D Sloand, E Solomon, L Spector, S Sperling, R Trapnell, CB VanDyke, R Whitley, R Wright, T Belay, E Butler, JC Castro, KG Dykewicz, C Edlin, BR Ellerbrock, T Hajjeh, RA Jaffe, HW Juranek, D McNeil, M Miller, B Pellett, PE Reeves, W Schluter, WW Spiegel, RA Stewart, JA Styrt, B Vernon, SD Ward, J TI 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: Disease-specific recommendations SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 CDC, NATL AIDS CLEARINGHOUSE, ROCKVILLE, MD 20849 USA. NATL INST HLTH, BETHESDA, MD USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. NATL ASSOC PERSONS AIDS, WASHINGTON, DC USA. GAY MENS HLTH CRISIS INC, WASHINGTON, DC USA. RUSH MED COLL, CHICAGO, IL 60612 USA. E BAY AIDS CTR, BERKELEY, CA USA. JOHNS HOPKINS UNIV, BALTIMORE, MD USA. BETH ISRAEL HOSP, BOSTON, MA 02215 USA. NATL NAVAL MED CTR, BETHESDA, MD USA. UNIV CALIF SAN FRANCISCO, MT ZION MED CTR, SAN FRANCISCO, CA 94143 USA. COLUMBIA UNIV COLL PHYS & SURG, HARLEM HOSP CTR, NEW YORK, NY 10032 USA. BOSTON MED CTR, BOSTON, MA USA. US FDA, ROCKVILLE, MD 20857 USA. VET ADM MED CTR, WASHINGTON, DC 20422 USA. HOWARD UNIV HOSP, WASHINGTON, DC USA. HACKENSACK MED CTR, HACKENSACK, NJ 07604 USA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. EMORY UNIV, ATLANTA, GA 30322 USA. NATL FDN INFECT DIS, BETHESDA, MD USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. KAISER PERMANENTE, SPRINGFIELD, VA USA. UNIV MINNESOTA, MINNEAPOLIS, MN USA. NATL MINOR AIDS COUNCIL, WASHINGTON, DC USA. W VIRGINIA SCH MED, NORFOLK, VA USA. WASHINGTON UNIV, ST LOUIS, MO 63130 USA. VET ADM MED CTR, ATLANTA, GA 30033 USA. MARYLAND DEPT HLTH & MENTAL HYG, BALTIMORE, MD USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. TULANE UNIV, SCH MED, NEW ORLEANS, LA 70112 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. COLUMBIA UNIV, COLL PHYS & SURG, NEW YORK, NY USA. RI Belay, Ermias/A-8829-2013 NR 15 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1997 VL 25 SU 3 BP S313 EP S335 PG 23 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YF067 UT WOS:A1997YF06700002 ER PT J AU Ruchkin, DS Berndt, RS Johnson, R Ritter, W Grafman, J Canoune, HL AF Ruchkin, DS Berndt, RS Johnson, R Ritter, W Grafman, J Canoune, HL TI Modality-specific processing streams in verbal working memory: evidence from spatio-temporal patterns of brain activity SO COGNITIVE BRAIN RESEARCH LA English DT Article DE working memory; short-term memory; verbal; modality; auditory; visual; event-related potential; slow wave ID POSITRON EMISSION TOMOGRAPHY; EVENT-RELATED POTENTIALS; SHORT-TERM-MEMORY; MISMATCH NEGATIVITY; INFORMATION; ACTIVATION; REHEARSAL; ARTIFACTS; STORAGE; MODELS AB The present study was concerned with whether there are separate, modality-specific processing "streams" in verbal working memory for information that is heard or read. We used event-related brain potentials (ERPs) recorded from scalp of normal humans to show between-modality differences in spatio-temporal patterns of brain activity during retention in working memory of aurally or visually presented verbal information. The ERP patterns suggested that a sustained, automatically maintained auditory store was activated by auditory presentation and a transient, visual-verbal store was activated by visual presentation. In addition to these modality-specific differences, the ERPs indicated that the phonological loop was activated in both modalities and further suggested that the onset of phonological loop activation was earlier for auditory presentation. (C) 1997 Elsevier Science B.V. C1 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA. NINDS, Med Neurol Branch, Cognit Neurosci Sect, Bethesda, MD USA. RP Ruchkin, DS (reprint author), Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. EM druchkin@umabnet.ab.umd.edu OI Grafman, Jordan H./0000-0001-8645-4457 NR 49 TC 62 Z9 65 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD OCT PY 1997 VL 6 IS 2 BP 95 EP 113 DI 10.1016/S0926-6410(97)00021-9 PG 19 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA YP326 UT WOS:000071265700003 ER PT J AU Mirsky, AF AF Mirsky, AF TI Pediatric neuropsychology in the medical setting - Baron,IS, Fennell,EB, Voeller,KKS SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP Mirsky, AF (reprint author), NIMH,SECT CLIN & EXPT NEUROPSYCHOL,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD OCT PY 1997 VL 42 IS 10 BP 915 EP 916 PG 2 WC Psychology, Multidisciplinary SC Psychology GA XZ236 UT WOS:A1997XZ23600025 ER PT J AU McMahon, RP Waclawiw, MA Geller, NL Barton, FB Terrin, ML Bonds, DR AF McMahon, RP Waclawiw, MA Geller, NL Barton, FB Terrin, ML Bonds, DR TI An extension of stochastic curtailment for incompletely reported and classified recurrent events: The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) SO CONTROLLED CLINICAL TRIALS LA English DT Article DE conditional power; interim monitoring; Poisson process; clinical trials; simulation ID CLINICAL-TRIALS AB The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), a double-blind randomized clinical trial, compared the frequency of acute vaso-occlusive (painful) crises during 2 yr of follow-up in 299 patients randomly assigned to hydroxyurea or placebo. Most patients had more than one crisis; all crises reported were included in the primary outcome analysis. A total of 7,229 follow up medical contact reports were classified as crises/not crises by a Crisis Review Committee. Because of the time required to report, document, and classify contacts, interim analyses were prepared with incomplete data. If a stopping boundary were crossed, early termination could be advised only after assessing the potential impact of the incomplete data. In an extension of stochastic curtailment methods, simulation procedures were used to estimate the probability of detecting differences when group crisis rates projected to the end of the study were compared using a rank test. To account for medical contacts not yet reported and the future occurrence of crises, Poisson process models assuming no treatment effect on crisis rates were used for these simulations. The number of unclassified contacts that would be classified as crises was simulated as a binomial random variable. These methods may be useful for interim monitoring in other studies of recurrent events with ongoing event reporting and classification. (C) Elsevier Science Inc. 1997. C1 NHLBI,BETHESDA,MD 20892. RP McMahon, RP (reprint author), MARYLAND MED RES INST,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. RI McMahon, Robert/C-5462-2009 FU NHLBI NIH HHS [U01-HL45692, U01-HL45696] NR 9 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 1997 VL 18 IS 5 BP 420 EP 430 DI 10.1016/S0197-2456(97)00014-7 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XY548 UT WOS:A1997XY54800003 PM 9315425 ER PT J AU Pollack, MM Patel, KM Ruttimann, UE AF Pollack, MM Patel, KM Ruttimann, UE TI Pediatric critical care training programs have a positive effect on pediatric intensive care mortality SO CRITICAL CARE MEDICINE LA English DT Article DE quality of care; severity of illness; intensive care; pediatric intensive care; medical training programs; pediatrics; PRISM; children; fellowship ID HOSPITAL CHARACTERISTICS; TEACHING HOSPITALS; QUALITY; VOLUME; MULTICENTER; SUPERVISION; EXPERIENCE; OUTCOMES; IMPACT; RATES AB Objective: Comparison of severity and diagnosis adjusted mortality rates from pediatric intensive care units (ICUs) staffed by physicians training in pediatric critical care, as well as pediatric residents, with mortality rates from pediatric ICUs staffed with only pediatric residents. Design: Cohort study. Setting: Sixteen volunteer pediatric ICUs, eight with critical care fellowships, and eight without such programs. Patients: Consecutive admissions until at least 14 deaths oc curred at each site. Interventions: None. Measurements and Main Results: Descriptive data and Pediatric Risk of Mortality scores were collected. Severity and diagnosis-adjusted mortality risk for each patient was computed by a predictor developed in an independent sample. The effect of fellowship programs was analyzed at the institution level by ranking the pediatric ICUs in terms of observed/predicted mortality rates, and, at the patient level, by including a training factor into the predictor model. The use of monitoring and therapeutic modalities was com pared in the two types of pediatric ICUs by severity-adjusted odds ratios. There were 2,744 admissions (145 deaths) to the eight fellowship pediatric ICUs and 3,006 admissions (150 deaths) to the eight nonfellowship pediatric ICUs. Institutional characteristics were not different between the two pediatric ICU sets. The raw mortality rates were similar (fellowship 5.28%; nonfellowship 4.99%, p = .714). Institution-level analyses indicated that fellowship pediatric ICUs performed better than nonfellowship pediatric ICUs; fellow ship pediatric ICUs ranked better than pediatric ICUs without Such programs (Wilcoxon rank sum test, p = .020). However, both the best and the worst ranked pediatric ICUs had fellowships. Patient-level analyses also indicated that outcome was significantly influenced by the fellowship status of the pediatric ICU. Using two different patient level analytic approaches, the odds of dying in a fellowship pediatric ICU vs. a nonfellowship pediatric ICU were 0.592 (95% confidence interval 0.468 to 0.749, p = .0001) and 0.714 (95% confidence interval 0.529 to 0.964, p = .028). Pediatric ICUs with fellowship programs performed more (p < .05) invasive monitoring, including intra-arterial catheters and central venous pressure catheters, and more technological therapies such as mechanical ventilation. Conclusions: Pediatric ICUs with critical care fellowship programs are generally associated with better risk-adjusted mortality rates than pediatric ICUs without such fellowship training pro grams. The cause for this effect requires a more in-depth study. The presence or absence of such training programs does not guarantee superior or inferior performance. C1 CHILDRENS NATL MED CTR, WASHINGTON, DC 20010 USA. CHILDRENS RES INST, CTR HLTH SERV & CLIN RES, WASHINGTON, DC USA. NIAAA, NIH, WASHINGTON, DC USA. RP Pollack, MM (reprint author), GEORGE WASHINGTON UNIV, SCH MED, WASHINGTON, DC 20007 USA. NR 32 TC 42 Z9 46 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 1997 VL 25 IS 10 BP 1637 EP 1642 DI 10.1097/00003246-199710000-00011 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA YA235 UT WOS:A1997YA23500011 PM 9377876 ER PT J AU Geusz, ME Fletcher, C Block, GD Straume, M Copeland, NG Jenkins, NA Kay, SA Day, RN AF Geusz, ME Fletcher, C Block, GD Straume, M Copeland, NG Jenkins, NA Kay, SA Day, RN TI Long-term monitoring of circadian rhythms in c-fos gene expression from suprachiasmatic nucleus cultures SO CURRENT BIOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; IMMEDIATE EARLY GENE; SPATIAL EXPRESSION; FIREFLY LUCIFERASE; PHOTIC REGULATION; MESSENGER-RNA; REPORTER GENE; INDUCTION; LIGHT; RAT AB Background: The AP-1 family of transcription factors has been implicated in the control of the expression of many genes in response to environmental signals. Previous studies have provided temporal profiles for c-fos expression by taking measurements from many animals at several points in time, but these studies provide limited information about dynamic changes in expression. Here, we have devised a method of continuously measuring c-fos expression. Results: A transgenic mouse line expressing the human c-fos promoter linked to the firefly luciferase reporter gene (fos/luc) was generated to continuously monitor c-fos gene expression. A second transgenic mouse line expressing luciferase under the control of the cytomegalovirus promoter (CMV/luc) served as a control. Luminescence originating from identifiable brain regions was imaged from fos/luc brain slice cultures. Expression of the fos/luc transgene accurately reflected transcriptional responses of the endogenous c-fos gene. Dynamic changes in fos/luc expression in suprachiasmatic nuclei (SCN) explant cultures were monitored continuously, and luminescence showed almost 24 hour rhythms lasting up to five circadian cycles. In contrast, bioluminescence monitored from CMV/luc SCN explant cultures was not rhythmic. Conclusion: The fos/luc transgenic mouse will be useful for long-term, non-invasive monitoring of c-fos transcriptional responses to the changing cellular environment. Circadian rhythms in c-fos expression can be monitored non-invasively in real time from the SCN, clearly demonstrating that c-fos transcription is regulated by the circadian clock. (C) Current Biology Ltd ISSN 0960-9822. C1 NCI, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. Scripps Res Inst, DEPT CELL BIOL, LA JOLLA, CA 92037 USA. RP Geusz, ME (reprint author), UNIV VIRGINIA, NSF CTR BIOL TIMING, GILMER HALL, CHARLOTTESVILLE, VA 22903 USA. RI Kay, Steve/F-6025-2011 OI Kay, Steve/0000-0002-0402-2878 FU NIMH NIH HHS [MH51573] NR 44 TC 33 Z9 34 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 1 PY 1997 VL 7 IS 10 BP 758 EP 766 DI 10.1016/S0960-9822(06)00334-4 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YB583 UT WOS:A1997YB58300031 PM 9368758 ER PT J AU Germain, RN AF Germain, RN TI T-cell signaling: The importance of receptor clustering SO CURRENT BIOLOGY LA English DT Article ID ANTIGEN RECEPTOR; BINDING-SITE; KINASE-ACTIVITY; CD4; TRANSDUCTION; ACTIVATION; COMPLEXES; AFFINITY; KINETICS; BETA AB T-cell receptors bound to peptide-MHC molecules undergo higher-order oligomerization in solution. This observation, the low-affinity-recognition properties of T-cell receptors, and other indications that such receptors undergo rapid, serial engagement by a single ligand suggest a dynamic clustering model of T-cell signaling. (C) Current Biology Ltd ISSN 0960-9822. RP Germain, RN (reprint author), NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 29 TC 65 Z9 66 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 1 PY 1997 VL 7 IS 10 BP R640 EP R644 DI 10.1016/S0960-9822(06)00323-X PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YB583 UT WOS:A1997YB58300020 PM 9368747 ER PT J AU Koonin, EV AF Koonin, EV TI A conserved ancient domain joins the growing superfamily of 3'-5' exonucleases SO CURRENT BIOLOGY LA English DT Letter ID DNA-POLYMERASE-I; ESCHERICHIA-COLI; ACTIVE-SITE RP Koonin, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894, USA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 1 PY 1997 VL 7 IS 10 BP R604 EP R606 DI 10.1016/S0960-9822(06)00311-3 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YB583 UT WOS:A1997YB58300009 PM 9368736 ER PT J AU Koonin, EV AF Koonin, EV TI Genome sequences: Genome sequence of a model prokaryote SO CURRENT BIOLOGY LA English DT Article ID ESCHERICHIA-COLI GENOME; REGION AB The complete Escherichia coli genome sequence is now known; it should greatly facilitate the analysis of other genomes, but a lot remains to be learnt about E. coli itself. About half the genes were previously uncharacterized, but expanding databases and improving analysis methods will help predict their functions. (C) Current Biology Ltd ISSN 0960-9822. RP Koonin, EV (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. NR 24 TC 9 Z9 9 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 1 PY 1997 VL 7 IS 10 BP R656 EP R659 DI 10.1016/S0960-9822(06)00328-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YB583 UT WOS:A1997YB58300025 PM 9368752 ER PT J AU Mitton, KP Hess, JL Bunce, GE AF Mitton, KP Hess, JL Bunce, GE TI Free amino acids reflect impact of selenite-dependent stress on primary metabolism in rat lens SO CURRENT EYE RESEARCH LA English DT Article DE amino acids; glutathione; lens; oxidative stress; pentose pathway; selenite; rat ID INDUCED CATARACT; GLUTATHIONE; CALCIUM; HEPATOCYTES; TRANSPORT; MECHANISM; REDUCTASE; DAMAGE; INJURY AB Purpose. A decrease in phase separation temperature, prior to nuclear cataract, has been correlated with elevated free amino acid content. Hence, we determined how selenite-induced stress alters free amino acid pools in the rat lens, following a single subcutaneous dose of sodium selenite (30 nmol g(-1) body weight) in 10- to 14-day-old Sprague Dawley rats. Result. Oxidative stress was evident in lenses 24 h after rats were treated with selenite. Glutathione content was decreased by 60% in the lens cortex and nucleus; the flux of glucose through the pentose phosphate pathway was increased; and glycerol-3-phosphate content was elevated. Amino acid transport, evaluated as C-14-cycloleucine uptake, was not altered, although C-14-glutamine was oxidized at a slower rate. Lenses from treated animals displayed, among the free amino acids, increased glutamine, proline, serine, glycine and the branched chain amino acids, while aspartate, glutamate, and taurine were less. Conclusions. A systemic delivery of sodium selenite caused oxidative stress in the rat lens. Direct effects on primary metabolism altered free amino acid pools that may contribute to transient and permanent changes in lens transparency. C1 VIRGINIA POLYTECH INST & STATE UNIV,DEPT BIOCHEM,BLACKSBURG,VA 24061. NEI,NIH,LAB MECH OCULAR DIS,BETHESDA,MD 20892. FU NEI NIH HHS [EY06123] NR 31 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 1997 VL 16 IS 10 BP 997 EP 1005 DI 10.1076/ceyr.16.10.997.9016 PG 9 WC Ophthalmology SC Ophthalmology GA XX775 UT WOS:A1997XX77500005 PM 9330851 ER PT J AU Carroll, MW Moss, B AF Carroll, MW Moss, B TI Poxviruses as expression vectors SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID RECOMBINANT VACCINIA VIRUSES; BACTERIOPHAGE-T7 RNA-POLYMERASE; GENE-EXPRESSION; MAMMALIAN-CELLS; FOWLPOX VIRUS; ACTIVE IMMUNOTHERAPY; CONSTRUCTION; REPLICATION; SELECTION; CANCER AB Poxviruses are widely used for the cytoplasmic expression of recombinant genes in mammalian cells. Recent improvements allow high expression and simplify the integration of multiple foreign genes. Vaccinia virus mutants and other poxviruses that undergo abortive infection in mammalian cells are receiving special attention because of their diminished cytopathic effects and increased safety. New replicating and 'non-replicating' vectors, encoding the bacteriophage T7 RNA polymerase for transcription of recombinant genes, have been engineered. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. RP Carroll, MW (reprint author), OXFORD BIOMED UK LTD,MEDAWAR CTR,OXFORD SCI PK,OXFORD OX4 4GA,ENGLAND. NR 52 TC 64 Z9 70 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD OCT PY 1997 VL 8 IS 5 BP 573 EP 577 DI 10.1016/S0958-1669(97)80031-6 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YA136 UT WOS:A1997YA13600007 PM 9353230 ER PT J AU Vinetz, JM AF Vinetz, JM TI Leptospirosis SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID POLYMERASE CHAIN-REACTION; DIAGNOSIS; PCR; POLYMORPHISMS; DISEASE AB Leptospirosis has recently been recognized as another reemerging infectious disease, both as epidemic in developing countries (Nicaragua, India) and as endemic in industrialized countries (USA), Molecular techniques have been successfully used for speciation, but have not replaced the gold standard serological techniques for identifying leptospires to the serovar level. Polymerase chain reaction is becoming the ideal diagnostic test, because leptospiral DNA can be detected bath on the initial presentation of clinical illness and even months later, and results are rapidly available, Modern techniques of cellular and molecular biology are beginning to unravel the pathogenesis and pathophysiology of leptospirosis. Treatment continues to rely on penicillins and tetracyclines, but morbidity and mortality should decline as improvements in rapid diagnostic techniques become widely adopted and the disease becomes more widely recognized. RP Vinetz, JM (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Vinetz, Joseph/0000-0001-8344-2004 NR 30 TC 15 Z9 15 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD OCT PY 1997 VL 10 IS 5 BP 357 EP 361 PG 5 WC Infectious Diseases SC Infectious Diseases GA YC477 UT WOS:A1997YC47700006 ER PT J AU Kruth, HS AF Kruth, HS TI The fate of lipoprotein cholesterol entering the arterial wall SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; HUMAN ATHEROSCLEROTIC LESIONS; MONOCYTE-DERIVED MACROPHAGES; RICH LIPID PARTICLES; HUMAN APOLIPOPROTEIN-E; FOAM CELLS; RABBIT AORTA; IN-VIVO; PERITONEAL-MACROPHAGES; CHYLOMICRON REMNANTS AB Recent findings have helped to explain the fate of cholesterol entering the arterial wall. LDL can undergo both fusion and aggregation. These changes may cause increased retention of LDL in lesion connective tissue matrix and LDL uptake by macrophages. In the cornea, apparent fusion of LDL occurs in the absence of macrophages. Mast cells may be important in LDL fusion, as mast cell-derived proteases can induce fusion of LDL through proteolysis of apolipoprotein B. LDL in arterial wall atherosclerotic lesions was found to be sialic acid-poor and ceramide-enriched. These chemical changes promote LDL aggregation. Processes that may function to remove cholesterol from the arterial wall have been reported. Macrophage-produced apolipoprotein E can mediate macrophage cholesterol efflux and macrophages can convert cholesterol to 27-oxygenated products that macrophages excrete. Alternately, another oxygenated sterol, 7-ketocholesterol, impairs macrophage cholesterol efflux. In addition, mast-cell derived chymase proteolyses HDL and reduces its capacity to stimulate cholesterol efflux. RP Kruth, HS (reprint author), NHLBI,SECT EXPT ATHEROSCLEROSIS,NIH,BLDG 10,ROOM 5N-113,10 CTR DR MSC-1422,BETHESDA,MD 20892, USA. NR 70 TC 42 Z9 43 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD OCT PY 1997 VL 8 IS 5 BP 246 EP 252 DI 10.1097/00041433-199710000-00002 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA YA239 UT WOS:A1997YA23900002 PM 9335947 ER PT J AU LippincottSchwartz, J Smith, CL AF LippincottSchwartz, J Smith, CL TI Insights into secretory and endocytic membrane traffic using green fluorescent protein chimeras SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID MEDIATED GENE-TRANSFER; LIVING CELLS; ENDOPLASMIC-RETICULUM; MAMMALIAN-CELLS; EXPRESSION; NEURONS; MUTATIONS; TRANSPORT; VECTORS; TOOL AB Green fluorescent fusion proteins, which can be visualized in the unperturbed environment of a living cell, have become important reporter molecules for studying protein localization and trafficking within secretory and endocytic membranes of living cells. They have been used in a wide variety of applications, including time-lapse imaging, double-labeling and photobleach experiments. Results from such work are clarifying the steps involved in the formation, translocation and fusion of transport intermediates, are defining the roles for microtubules in membrane transport, and are providing insights into the mechanisms of protein retention and localization within organelles. In so doing, they have changed our thinking about the temporal and spatial relationships between subcellular membrane structures and the morphogenesis of secretory and endocytic organelles. C1 NINCDS,NIH,BETHESDA,MD 20892. RP LippincottSchwartz, J (reprint author), NICHHD,CELL BIOL & METAB BRANCH,NIH,BLDG 18,ROOM 101,18 LIB DR,BETHESDA,MD 20892, USA. NR 64 TC 44 Z9 46 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD OCT PY 1997 VL 7 IS 5 BP 631 EP 639 DI 10.1016/S0959-4388(97)80082-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YG690 UT WOS:A1997YG69000006 PM 9384543 ER PT J AU Egan, MF Weinberger, DR AF Egan, MF Weinberger, DR TI Neurobiology of schizophrenia SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID DOPAMINE-D3 RECEPTOR GENE; PREFRONTAL CORTEX; SUSCEPTIBILITY GENES; VULNERABILITY LOCUS; HIPPOCAMPAL DAMAGE; CHROMOSOME 6P24-22; POTENTIAL LINKAGE; EXPRESSION; NEURONS; POSTMORTEM AB Schizophrenia appears to be a neurodevelopmental disorder involving dysfunctional prefrontal and temporal cortical neural systems. Recent data implicate presynaptic changes in subcortical dopamine neurotransmission, as well as alterations in cortical glutamatergic and GABAergic systems. Functional neuroimaging studies, combined with tests of neuropsychological function, suggest that cortical abnormalities underlie the cognitive deficits associated with schizophrenia. These deficits appear to account for much of the psychosocial dysfunction of schizophrenia and are particularly treatment refractory. Genetic studies have implicated several minor susceptibility loci; however, the clinical impact of these loci on the neurobiology of schizophrenia is still unclear. The use of neurobiological traits as phenotypes, such as cognitive deficits and cortical abnormalities, in genetic linkage studies may facilitate the identification of loci that underlie the most debilitating features of schizophrenia. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NEUROSCI RES CTR,WASHINGTON,DC 20032. RP Egan, MF (reprint author), NIMH,CLIN RES SERV,NEUROSCI RES CTR,2700 ML KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 52 TC 121 Z9 122 U1 4 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD OCT PY 1997 VL 7 IS 5 BP 701 EP 707 DI 10.1016/S0959-4388(97)80092-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA YG690 UT WOS:A1997YG69000016 PM 9384552 ER PT J AU Sivakumar, K Dalakas, MC AF Sivakumar, K Dalakas, MC TI Inclusion body myositis and myopathies SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID PRECURSOR PROTEIN GENE; INFLAMMATORY MYOPATHIES; MUSCULAR-DYSTROPHY; DISTAL MYOPATHY; MUSCLE-FIBERS; DERMATOMYOSITIS; POLYMYOSITIS; QUADRICEPS; EXPRESSION; FILAMENTS AB Sporadic inclusion body myositis is a frequent, acquired, adult-onset vacuolar myopathy affecting proximal and distal muscles with a distinct, easily identifiable clinical pattern. Although its primary cause is still unknown, autoimmune, viral, and degenerative processes, alone or in combination, are being considered. A uniform and sustained therapeutic response using the currently available immunomodulatory agents has not yet been achieved. Hereditary, inherited noninflammatory rimmed vacuolar myopathies with similar histologic features, collectively called hereditary inclusion body myopathies, are being redefined with the use of molecular genetics, The implications of the recent advances in clinical and basic sciences are discussed in the present review. C1 NINCDS,NEUROMUSCULAR DIS SECT,NIH,BETHESDA,MD 20892. NR 57 TC 28 Z9 29 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD OCT PY 1997 VL 10 IS 5 BP 413 EP 420 DI 10.1097/00019052-199710000-00010 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XZ175 UT WOS:A1997XZ17500010 PM 9330888 ER PT J AU Bax, A Ealick, SE AF Bax, A Ealick, SE TI Biophysical methods SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID PROTEINS C1 CORNELL UNIV,SECT BIOCHEM & CELL BIOL,ITHACA,NY 14853. RP Bax, A (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD OCT PY 1997 VL 7 IS 5 BP 669 EP 671 DI 10.1016/S0959-440X(97)80076-0 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YB579 UT WOS:A1997YB57900010 ER PT J AU Smith, MR Kung, HF Durum, SK Colburn, NH Sun, Y AF Smith, MR Kung, HF Durum, SK Colburn, NH Sun, Y TI TIMP-3 induces cell death by stabilizing TNF-alpha receptors on the surface of human colon carcinoma cells SO CYTOKINE LA English DT Article DE cell death; apoptosis; matrix metalloproteinases; tissue inhibitor of metalloproteinases; TNF-alpha; TNF-alpha receptors ID TUMOR-NECROSIS-FACTOR; HUMAN TISSUE INHIBITOR; METALLOPROTEINASES (TIMP)-3; MOLECULAR-CLONING; SOLUBLE FORM; GENE FAMILY; EXPRESSION; MEMBER; LYMPHOCYTES; ACTIVATION AB Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) regulate the structural integrity of the extracellular matrix (ECM). Constitutive expression of human TIMP3 in human DLD colon carcinoma cells renewed serum-responses and inhibited tumour formation in nude mice, To elucidate the mechanism of TIMP-3-mediated tumour suppression, we compared parental DLD and TIMP-3 expressing DLD cells (TIMP-3/DLD), finding them to be significantly different, TIMP-3/DLD cultures have fewer mitotic cells, are delayed in G(1), and die after serum starvation, TIMP-3/DLD conditioned media activates cell death on fibroblast cells, The cell death induced by serum starvation and conditioned media was inhibited by 70%, in the presence of neutralizing tumour necrosis factor alpha (TNF-alpha) antibody, TIMP-3/DLD whole cell lysate contained p55 TNF-alpha receptor, while vector/DLD lysate had p55 TNF-alpha receptor and p46 soluble TNF-alpha inhibitor, Vector/DLD conditioned media had p46, while no soluble TNF-alpha receptor,vas detected in TIMP-3/DLD conditioned media, In addition, FAGS analysis revealed that TIMP-3/DLD cells have more TNF-alpha surface binding sites, suggesting a direct correlation between TIMP-3 expression and surface receptors, The mechanism of tumorigenic reversion induced by TIMP-3 in DLD cells may involve protection of receptors from the proteolytic activity of MMPs. Putative TIMP-3-mediated inhibition of MMPs restores the TNF-alpha p55 signalling pathway and the carcinoma cell is killed by autocrine TNF-alpha, Thus, DLD cells have specific ECM MMPs that cleave cytokines and cytokine receptors, TIMP-3 specifically inhibits MMPs involved in receptor shedding. (C) 1997 Academic Press Limited. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,DIV BASIC SCI,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,DIV BASIC SCI,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CELL BIOL SECT,LAB BIOCHEM PHYSIOL,DIV BASIC SCI,FREDERICK,MD 21702. PARKE DAVIS PHARMACEUT RES,DIV MOL BIOL,ANN ARBOR,MI 48105. RP Smith, MR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702, USA. NR 34 TC 144 Z9 146 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 1997 VL 9 IS 10 BP 770 EP 780 DI 10.1006/cyto.1997.0233 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA YG161 UT WOS:A1997YG16100009 PM 9344510 ER PT J AU Meigs, JB DAgostino, RB Wilson, PWF Cupples, LA Nathan, DM Singer, DE AF Meigs, JB DAgostino, RB Wilson, PWF Cupples, LA Nathan, DM Singer, DE TI Risk variable clustering in the insulin resistance syndrome - The Framingham Offspring Study SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; CORONARY-HEART-DISEASE; BODY-FAT DISTRIBUTION; SYNDROME SYNDROME-X; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; METABOLIC SYNDROME; HYPERINSULINEMIA AB Insulin resistance has been hypothesized to unify the clustering of hypertension, glucose intolerance, hyperinsulinemia, increased levels of triglyceride and decreased HDL cholesterol, and central and overall obesity We tested this hypothesis with factor analysis, a statistical technique that should identify one factor if a single process underlies the clustering of these risk variables, From 2,458 nondiabetic subjects of the Framingham Offspring Study, we collected clinical data, fasting and 2-h postchallenge glucose and insulin levels, and fasting lipid levels, We performed factor analyses separately for men and women in the entire population and among subgroups with features of the insulin resistance syndrome, Subjects ranged in age from 26 to 82 years (mean age 54); 53% were women, 13.4% had impaired glucose tolerance, 27.6% had hypertension, 40% were obese, and 11.6% mere hyperinsulinemic, defined by elevated fasting insulin levels. Underlying the clustering of these risk variables were three factors, Fasting and 2-h postchallenge insulin levels, fasting triglyceride and HDL cholesterol levels, BMI, and waist-to-hip ratio were associated with one factor, Fasting and 2-h levels of glucose and insulin were associated with a second factor, Systolic blood pressure, diastolic blood pressure, and BMI were associated with a third factor, Results were similar for men and women and for all subgroups, These results were consistent with more than one independent physiological process underlying risk variable clustering: a central metabolic syndrome (characterized by hyperinsulinemia, dyslipidemia, and obesity), glucose intolerance, and hypertension. Glucose intolerance and hypertension were linked to the central syndrome through shared correlations with insulin levels and obesity insulin resistance (reflected by hyperinsulinemia) alone did not appear to underlie all features of the insulin resistance syndrome. C1 MASSACHUSETTS GEN HOSP,DEPT MED,DIABET UNIT,BOSTON,MA 02114. BOSTON UNIV,DEPT MATH STAT,BOSTON,MA 02215. BOSTON UNIV,CONSULTING UNIT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. BOSTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA. BOSTON UNIV,SCH MED,BOSTON,MA. NHLBI,NIH,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. RP Meigs, JB (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT S50 9,DEPT MED,BOSTON,MA 02114, USA. NR 61 TC 367 Z9 384 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1997 VL 46 IS 10 BP 1594 EP 1600 DI 10.2337/diabetes.46.10.1594 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XX800 UT WOS:A1997XX80000010 PM 9313755 ER PT J AU Matsuoka, N Ogawa, Y Hosoda, K Matsuda, J Masuzaki, H Miyawaki, T Azuma, N Natsui, K Nishimura, H Yoshimasa, Y Nishi, S Thompson, DB Nakao, K AF Matsuoka, N Ogawa, Y Hosoda, K Matsuda, J Masuzaki, H Miyawaki, T Azuma, N Natsui, K Nishimura, H Yoshimasa, Y Nishi, S Thompson, DB Nakao, K TI Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity SO DIABETOLOGIA LA English DT Article DE leptin; leptin receptor; Ob-R; obesity; sequence variant ID FATTY FA/FA RATS; MOLECULAR-CLONING; MISSENSE MUTATION; MESSENGER-RNA; DB/DB MICE; MOUSE; IDENTIFICATION; HYPOTHALAMUS; EXPRESSION; ABSENCE AB Leptin is an adipocyte-derived bloodborne satiety factor that acts on its cognate leptin receptor (Ob-R) in the hypothalamus, thereby regulating food intake and energy expenditure. To explore whether mutations in the Ob-R gene cause obesity in humans, we have searched for mutations in the gene for Ob-Rb, a biologically active receptor isoform, in obese Japanese subjects. We have also examined associations between such mutants and obesity in the Japanese. Genomic DNAs were used as templates in polymerase chain reaction (PCR) with primers selected to amplify exons 2 to 20 of the human Ob-Rb gene. Direct sequence analysis of the PCR products revealed 7 nucleotide sequence variants (Lys109Arg, Gln223Arg, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the Ob-Rb coding region from 17 obese Japanese subjects with a family history of obesity (BMI 39.3+/-8.4 kg/m(2)). No missense and nonsense mutations were found such as those in Zucker fatty (fa/fa) rats and Koletsky (fa(k)/fa(k)) rats. Nucleotide substitutions occurred at relatively high frequencies at codons 109, 223, 976, and 1019 (79, 91, 100, and 85 %, respectively). Allele frequency of each variant determined by PCR-RFLP and PCR-single strand conformation polymorphism analyses showed no significant differences between 47 obese (BMI 35.1 +/- 6.5 kg/m(2)) and 68 non-obese (BMI 21.6 +/- 2.2 kg/m(2)) subjects. The present study represents the first report of sequence variants of the Ob-Rb gene in the Japanese and provides evidence against either obesity-causing mutations or association of sequence variants with obesity in obese Japanese subjects. C1 KYOTO UNIV,GRAD SCH HUMAN & ENVIRONM STUDIES,KYOTO 606,JAPAN. KYOTO UNIV,GRAD SCH MED,DEPT MED & CLIN SCI,SAKYO KU,KYOTO 606,JAPAN. NIDDKD,CLIN DIABET & NUTR SECT,NIH,PHOENIX,AZ 85016. NR 35 TC 108 Z9 132 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1997 VL 40 IS 10 BP 1204 EP 1210 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XY788 UT WOS:A1997XY78800013 PM 9349603 ER PT J AU Koike, J Yamada, K Takano, S Kikuchi, Y Hemmi, H Koi, M Tsujita, K Yanagita, K Yoshio, T Shimatake, H AF Koike, J Yamada, K Takano, S Kikuchi, Y Hemmi, H Koi, M Tsujita, K Yanagita, K Yoshio, T Shimatake, H TI Undetectable expression of hMLH1 protein in sporadic colorectal cancer with replication error phenotype SO DISEASES OF THE COLON & RECTUM LA English DT Article DE colorectal cancer; hereditary nonpolyposis colorectal cancer; replication error; microsatellite instability; hMSH2; hMLH1; antibody; immunoblot ID NONPOLYPOSIS COLON-CANCER; MISMATCH REPAIR DEFICIENCY; MICROSATELLITE INSTABILITY; GENOMIC INSTABILITY; REPEATED SEQUENCES; PROXIMAL COLON; TUMOR-CELLS; MUTATIONS; GENE; HOMOLOG AB PURPOSE: Four DNA mismatch repair genes have been identified as being susceptible genes for hereditary nonpolyposis colorectal cancer. Deficiency of one of the mis match repair genes causes the replication error phenotype in more than 80 percent of patients with hereditary nonpolyposis colorectal cancer and in 10 to 30 percent of patients with sporadic colorectal cancer. To determine which mismatch repair gene is lacking the function in patients with replication error-positive colorectal cancer, several approaches have been used at the nucleic acid and protein levels. We studied replication error in 40 samples of randomly selected colorectal cancers and expression of hMSH2 and hMLH1 proteins analyzed by immunoblot in the tumor and normal tissues of the replication error-positive and replication error-negative samples, MATERIALS AND METHODS: Frozen tumor and normal tissues were obtained from 40 Japanese patients who had colorectal cancer. According to the Amsterdam criteria, those patients were classified as having 39 sporadic and 1 unknown colorectal cancers. Genomic DNA was extracted from tumor and normal tissues for determining replication error with eight microsatellite markers. Expression of hMSH2 and hMLH1 proteins in cell lysates of tumor and normal tissues of 16 patients was analyzed by immunoblot. RESULTS: The replication error phenotype was found in 6 (15 percent) of the 39 sporadic cases. hMLH1 protein was not detected in two of the six replication error-positive tumor tissues and not in the normal tissues, indicating that the tumor cells of the two patients had severe mutations in both alleles of the hMLH1 gene. Another four replication error-positive and ten replication error-negative tumors and normal tissues expressed hMLH1 protein. hMSH2 protein was detected in all samples. CONCLUSION: hMLH1 protein was undetectable in the two tumor tissues of the six replication error-positive samples of sporadic colorectal cancer. The detection procedure used here may have potential use for determining a dysfunctional mismatch repair gene product. C1 TOHO UNIV,SCH MED,DEPT MOL BIOL,TOKYO 143,JAPAN. BIOMED LABS,R&D CTR,SAITAMA,JAPAN. NIEHS,MOL CARCINOGENESIS LAB,NIH,RES TRIANGLE PK,NC 27709. RP Koike, J (reprint author), TOHO UNIV,SCH MED,DEPT SURG 1,OTA KU,6-11-1 OMORI NISHI,TOKYO 143,JAPAN. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014 NR 36 TC 12 Z9 12 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD OCT PY 1997 VL 40 IS 10 SU S BP S23 EP S28 DI 10.1007/BF02062016 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA YA761 UT WOS:A1997YA76100005 PM 9378008 ER PT J AU Weigmann, N Trieschmann, L Bustin, M AF Weigmann, N Trieschmann, L Bustin, M TI Enhancement of the transcription potential of nascent chromatin by chromosomal proteins HMG-14/-17 is coupled to nucleosome assembly and not DNA synthesis SO DNA AND CELL BIOLOGY LA English DT Article ID RNA POLYMERASE-III; ARCHITECTURAL ELEMENTS; ACTIVE CHROMATIN; REPLICATION; HMG-17; INVITRO; ELONGATION; INITIATION; HISTONES; COMPLEX AB We have previously demonstrated that in Xenopus egg extracts, which support DNA strand synthesis and chromatin assembly, incorporation of chromosomal proteins HMG-14/-17 into nascent nucleosomes increases the transcriptional potential of a chromatin template carrying the Xenopus 5S RNA gene. Here me use the single-stranded and double-stranded forms of a plasmid carrying a 5S RNA maxigene, to test whether the effect of HMG-14/-17 on transcription requires DNA synthesis and whether these proteins will affect transcription through a region containing nucleosomes. We find that most of the transcripts were about 350 nucleotides long, suggesting that HMG-14/-17 enhance transcription through a region that could contain nucleosomes. HMG-14/-17 enhance transcription of chromatin templates assembled onto double-stranded DNA, in the absence of DNA synthesis. Single-round transcription assays suggest that HMG-14/-17 increase transcription from templates assembled onto both single-and double-stranded DNA by increasing the specific activity, and not the number, of transcriptionally active templates. We conclude that the effect of HMG-14/-17 on the transcriptional potential of chromatin is linked to nucleosome assembly and is not linked to DNA synthesis. C1 NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 NR 46 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 1997 VL 16 IS 10 BP 1207 EP 1216 DI 10.1089/dna.1997.16.1207 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA YE464 UT WOS:A1997YE46400008 PM 9364931 ER PT J AU Daly, JW Shi, D Padgett, WL Ji, XD Jacobson, KA AF Daly, JW Shi, D Padgett, WL Ji, XD Jacobson, KA TI Riboflavin: Inhibitory effects on receptors, G-proteins, and adenylate cyclase SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE adenylate cyclase; P-site; adenosine analogs; xanthines; forskolin; C-proteins; A(1)-adenosine receptors ID RAT-BRAIN MEMBRANES; ADENOSINE RECEPTORS; CEREBRAL-ISCHEMIA; BINDING; DERIVATIVES; STIMULATION AB Riboflavin inhibited binding of both agonist and antagonist radioligands to rat brain A(1)-adenosine receptors with K-i values of approximately 10 mu M. In an adenylate cyclase assay with membrane preparations from either rat adipocytes or DDT MF-2 cells, both of which contain A(1)-adenosine receptors, riboflavin inhibited isoproterenol-stimulated cyclase activity with an IC50 of approximately 20 mu M. However, the inhibition of cyclase by riboflavin was not reversed by an A(1)-selective antagonist, nor by pretreatment with pertussis toxin. Thus, neither A(1)-receptors nor G(1)-proteins appear critically involved in the inhibition of cyclase by riboflavin. Riboflavin did block the stimulation by an adenosine analog of [S-35]GTP gamma S binding in rat cerebral cortical membranes. However, riboflavin also inhibited the stimulation by fMLP of [S-35]GTP gamma S binding in HL-60 cell membranes. Riboflavin inhibited forskolin-stimulated cyclase in membranes from DDT MF-2 cells > rat adipocytes > PC12 cells, hamster CHO M2 cells, and wild-type S49 cells. There was virtually no inhibition of forskolin-stimulated cyclase in membranes of human platelets, rat cerebral cortex, or cyc(-)S49 cells lacking G(s)-proteins. The calcium-stimulated cyclase in rat cerebral cortical membranes was inhibited by riboflavin. A preincubation of membranes with riboflavin markedly enhanced the inhibition for DDT MF-2 and wild-type and cyc(-)S49 membranes. The extent of inhibition in the different cell lines was dependent on the agent used to stimulate cyclase. Riboflavin, like the P-site inhibitor 2',5'-dideoxyadenosine, was more potent and efficacious when manganese instead of forskolin was used as the stimulant. However, unlike the P-site inhibitor, riboflavin did not markedly inhibit GppNHp-or fluoride-stimulated cyclase. Riboflavin at low micromolar concentrations appears to have three possibly interrelated effects on second messenger systems subserved by C-proteins. These are antagonism at A(1)-adenosine receptors, inhibition of turnover of guanyl nucleotides at C-proteins, and inhibition of adenylate cyclase. (C) 1997 Wiley-Liss, Inc.* C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bldg 8,Room B1A17, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 20 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 1997 VL 42 IS 2 BP 98 EP 108 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZD985 UT WOS:000072745500006 PM 22772360 ER PT J AU Samii, A Wassermann, EM Hallett, M AF Samii, A Wassermann, EM Hallett, M TI Post-exercise depression of motor evoked potentials as a function of exercise duration SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE fatigue; motor evoked potentials; transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; LONG-TERM POTENTIATION; FATIGUE; CORTEX; EXCITABILITY; HIPPOCAMPUS; MODULATION; RESPONSES; BRAIN AB Post-exercise facilitation and post-exercise depression are phenomena described in motor evoked potentials (MEPs) elicited to transcranial magnetic stimulation. Brief, non-fatiguing muscle activation produces post-exercise facilitation, and prolonged fatiguing muscle activation produces post-exercise depression. We studied 12 normal subjects to determine whether post-exercise depression occurs before fatigue is reached. We recorded MEPs from the resting extensor carpi radialis muscle after increasing the duration of isometric wrist extension, at 50% of maximum voluntary contraction, until the muscle fatigued. Fatigue was defined as the inability to maintain that force. The mean exercise duration before the muscle fatigued was 130 s, and post-exercise depression occurred only beyond 90 s of exercise. We conclude that post-exercise depression is detectable only after prolonged muscle activation. (C) 1997 Elsevier Science Ireland Ltd. C1 NINCDS, HUMAN MOTOR CONTROL SECT, MED NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 25 TC 51 Z9 51 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD OCT PY 1997 VL 105 IS 5 BP 352 EP 356 DI 10.1016/S0924-980X(97)00033-7 PG 5 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA YD586 UT WOS:A1997YD58600004 PM 9362999 ER PT J AU Yazawa, S Shibasaki, H Ikeda, A Terada, K Nagamine, T Honda, M AF Yazawa, S Shibasaki, H Ikeda, A Terada, K Nagamine, T Honda, M TI Cortical mechanism underlying externally cued gait initiation studied by contingent negative variation SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE gait initiation; contingent negative variation; sensorimotor association; supplementary motor area; primary motor cortex ID SUPPLEMENTARY MOTOR AREA; MOVEMENT-RELATED POTENTIALS; PARKINSONS-DISEASE; PREMOTOR CORTEX; STIMULATION; LOCOMOTION; MODULATION; RESPONSES; WALKING; MONKEYS AB In order to clarify the cortical mechanism underlying gait initiation, we examined the scalp distribution of the contingent negative variation (CNV) preceding externally cued gait initiation in a simple reaction-time paradigm in 10 healthy right-handed men, and compared the results with the CNV preceding simple foot dorsiflexion. A pair of auditory stimuli was given with an interstimulus (S1-S2) interval of 2 s and gait consisting of at least 3 steps was initiated with the right footstep as fast as possible in response to S2. Brisk dorsiflexion of the right foot was employed as a control task. It was found that the late CNV in the gait initiation task started about 1 s before S2, and was largest at Ct (-9.3 +/- 3.1 mu V) without clear asymmetry over the scalp. However, it was ill defined in the parietal area. In the foot dorsiflexion task, the late CNV was maximal at Ct (-7.1 +/- 2.9 mu V), and clearly seen also over the parietal area. The late CNV at Ct was significantly (P < 0.01) larger in the gait initiation than in the simple foot dorsiflexion. The amplitude of the late CNV preceding the foot dorsiflexion task was not significantly different between the sitting and the standing posture. In view of the results of previous invasive studies in both humans and animals which showed some frontal areas, including the supplementary motor area (SMA) and the primary motor cortex, as the generators of the late CNV, it is suggested that the cerebral cortex is active in initiation of externally triggered gait in a different way from the simple foot movement, and that bilateral SMAs may play a more important role in gait initiation than in simple foot movement. (C) 1997 Elsevier Science Ireland Ltd. C1 KYOTO UNIV,SCH MED,DEPT BRAIN PATHOPHYSIOL,SAKYO KU,KYOTO 60601,JAPAN. NINCDS,HUMAN MOTOR CONTROL SECT,NIH,BETHESDA,MD 20892. OI Ikeda, Akio/0000-0002-0790-2598 NR 52 TC 40 Z9 40 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD OCT PY 1997 VL 105 IS 5 BP 390 EP 399 DI 10.1016/S0924-980X(97)00034-9 PG 10 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA YD586 UT WOS:A1997YD58600010 PM 9363005 ER PT J AU Yarmola, E Chrambach, A AF Yarmola, E Chrambach, A TI Improved sensitivity of detection with the commercial automated gel electrophoresis (HPGE-1000) apparatus through modification of its optical system SO ELECTROPHORESIS LA English DT Article DE fluorescence optics; HPGE-1000 apparatus; signal; noise ratio; mirrored incident light; effect of mirror blackening; detection sensitivity AB In a representative application to a fluorescently detectable protein of commercial automated gel electrophoresis apparatus (HPGE-1000, LabIntelligence, Belmont, CA) the sensitivity of detection by fluorescence was significantly increased by elimination of the mirror below the gel tray. That increase in detection sensitivity is due to a decrease of fluorescent background noise by nearly one order of magnitude, overcompensating a decrease in signal by a factor of two. The resulting increase in signal/noise ratio, i.e., detection sensitivity, should allow for lowered sample loads by which the band width is reduced with benefits to resolution. C1 NICHHD,MACROMOL ANAL SECT,LAB CELLULAR & MOL BIOPHYS,NIH,BETHESDA,MD 20892. RUSSIAN ACAD SCI,VA ENGELHARDT MOL BIOL INST,LAB BIOPOLYMER PHYS,MOSCOW,RUSSIA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1997 VL 18 IS 11 BP 1951 EP 1954 DI 10.1002/elps.1150181112 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YJ957 UT WOS:A1997YJ95700011 PM 9420151 ER PT J AU Weiss, GH Kiefer, JE AF Weiss, GH Kiefer, JE TI Some properties of a measure of resolution in gel electrophoresis and capillary zone electrophoresis SO ELECTROPHORESIS LA English DT Article DE Gaussian peaks; capillary electrophoresis; gel electrophoresis; resolution AB The most commonly used measure of resolution for chromatographic and electrophoretic separations does not take into account the possibility of there being different amounts of each of the molecular species. A modification of a measure of resolution recently suggested by Aldroubi and Garner (BioTechniques 1992, 13, 620-624) can incorporate this effect explicitly. Their criterion for resolution is based on the time to observe a valley of specified magnitude separating two peaks. We examine how this measure depends on different physically relevant parameters that characterize the system. RP Weiss, GH (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 2 U1 3 U2 4 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1997 VL 18 IS 11 BP 2008 EP 2011 DI 10.1002/elps.1150181121 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YJ957 UT WOS:A1997YJ95700020 PM 9420160 ER PT J AU Hohjoh, H Singer, MF AF Hohjoh, H Singer, MF TI Sequence-specific single-strand RNA binding protein encoded by the human LINE-1 retrotransposon SO EMBO JOURNAL LA English DT Article DE human high affinity binding site; LINE-1 (L1Hs); non-LTR retrotransposon; RNA binding protein; ribonucleoprotein complex ID HUMAN TRANSPOSABLE ELEMENT; EMBRYONAL CARCINOMA-CELLS; DNA; TRANSLATION; EXPRESSION; DIVERSITY; FAMILY AB Previous experiments using human teratocarcinoma cells indicated that p40, the protein encoded by the first open reading frame (ORF) of the human LINE-1 (L1Hs) retrotransposon, occurs in a large cytoplasmic ribonucleoprotein complex in direct association with L1Hs RNA(s), the p40 RNP complex. We have now investigated the interaction between partially purified p40 and L1Hs RNA in vitro using an RNA binding assay dependent on co-immunoprecipitation of p40 and bound RNA, These experiments identified two p40 binding sites on the full-length sense strand L1Hs RNA. Both sites are in the second ORF of the 6000 nt RNA: site A between residues 1999 and 2039 and site B between residues 4839 and 4875. The two RNA segments share homologous regions. Experiments involving UV cross-linking followed by immunoprecipitation indicate that p40 in the in vitro complex is directly associated with L1Hs RNA, as it is in the p40 RNP complex found in teratocarcinoma cells. Binding and competition experiments demonstrate that p40 binds to single-stranded RNA containing a p40 binding site, but not to single-stranded or double-stranded DNA, double-stranded RNA or a DNA-RNA hybrid containing a binding site sequence. Thus, p40 appears to be a sequence-specific, single-strand RNA binding protein. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. CARNEGIE INST WASHINGTON,WASHINGTON,DC 20005. NR 29 TC 129 Z9 133 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 1 PY 1997 VL 16 IS 19 BP 6034 EP 6043 DI 10.1093/emboj/16.19.6034 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YB245 UT WOS:A1997YB24500024 PM 9312060 ER PT J AU Rodriguez-Pena, MS Collins, R Woodard, C Spiegel, AM AF Rodriguez-Pena, MS Collins, R Woodard, C Spiegel, AM TI Decreased insulin content and secretion in RIN 1046-38 cells overexpressing alpha(2)-adrenergic receptors SO ENDOCRINE LA English DT Article DE RIN cells; alpha(2)-adrenergic receptor; G-protein ID G-PROTEINS; IDENTIFICATION; INHIBITION; ISLETS; EPINEPHRINE; MUTATIONS; SUBTYPES; BINDING; CYCLASE; ACID AB Several G(i)-protein-coupled receptors normally expressed in islet beta-cells inhibit insulin secretion on binding of their respective agonists. To study the effect of supraphysiologic expression of such a receptor in insulin-secreting beta-cells, we stably transfected cDNA encoding the mouse alpha(2a)-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected, each overexpressing the alpha(2a)-adrenergic receptor to varying degrees. Cell lines showing the highest level of receptor expression showed significantly reduced insulin content, and reduced basal and stimulated insulin secretion. Pertussis toxin (PTX) treatment of cells was able to reverse partially the reduced insulin secretory response. Our results suggest that overexpression of a G(i)-protein-coupled receptor in beta-cells causes tonic inhibition of both insulin synthesis and secretion. Abnormalities in expression or function of such receptors could be a contributory factor in the impaired insulin secretion present in type II diabetes. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Spiegel, AM (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Rm 9N-222, Bethesda, MD 20892 USA. EM allens@amb.niddk.nih.gov NR 20 TC 8 Z9 8 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD OCT PY 1997 VL 7 IS 2 BP 255 EP 260 DI 10.1007/BF02778148 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YT586 UT WOS:000071621900015 PM 9549052 ER PT J AU Barr, VA Malide, D Zarnowski, MJ Taylor, SI Cushman, SW AF Barr, VA Malide, D Zarnowski, MJ Taylor, SI Cushman, SW TI Insulin stimulates both leptin secretion and production by rat white adipose tissue SO ENDOCRINOLOGY LA English DT Article ID OB MESSENGER-RNA; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; OBESE GENE; 3T3-L1 ADIPOCYTES; IN-VITRO; EXPRESSION; PROTEIN; HUMANS; CELLS AB Leptin, the peptide encoded by the obese gene, is secreted by adipose cells and plays a role in regulating food intake, energy expenditure, and adiposity. Because earlier studies suggested that insulin increases the expression of leptin, we investigated the effect of insulin on leptin secretion by adipose tissue. Epididymal fat pads were incubated in vitro in the presence or absence of insulin over a 4-h time course. Insulin increased leptin secretion by about 80% at all time points studied. After 10 min of insulin treatment, the amount of tissue-associated leptin was lower in insulin-stimulated tissue, presumably due to the increased secretion. At later times, bath tissue-associated leptin and total leptin production were higher in insulin-treated tissue. In untreated, isolated adipose cells, immunostaining of leptin was detected in the endoplasmic reticulum by confocal microscopy. After insulin treatment, there were two populations of cells. In many cells, leptin staining became fainter and was restricted to a narrow band near the plasma membrane. However, in other cells the leptin-staining pattern was unchanged. Leptin did not colocalize with GLUT4, the glucose transporter isoform found primarily in insulin-responsive cells, in either basal or insulin-stimulated adipose cells. In this study, insulin increased both secretion and production of leptin by adipose tissue fragments. Interestingly, insulin appeared to stimulate the transport of leptin from the endoplasmic reticulum rather than acting on a pool of regulated secretory vesicles. C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. NR 43 TC 186 Z9 193 U1 0 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1997 VL 138 IS 10 BP 4463 EP 4472 DI 10.1210/en.138.10.4463 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XX545 UT WOS:A1997XX54500055 PM 9322964 ER PT J AU Lucarelli, E Kaplan, D Thiele, CJ AF Lucarelli, E Kaplan, D Thiele, CJ TI Activation of trk-A but not trk-B signal transduction pathway inhibits growth of neuroblastoma cells SO EUROPEAN JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT Meeting on Advances in Neuroblastoma Research - 1996 CY MAY 22-25, 1996 CL PHILADELPHIA, PENNSYLVANIA DE neuroblastoma; trk-A; trk-B; NGF; BDNF ID RECEPTOR; DIFFERENTIATION; EXPRESSION; ASSOCIATION; PROGNOSIS AB In neuroblastoma tumours, the expression of high levels of trk-A mRNA, which encodes the high-affinity nerve growth factor (NGF) receptor, is associated with good prognosis. Constitutive expression of brain-derived neurotrophic factor (BDNF) and variable expression of its receptor trk-B are frequently detected in tumours from patients with a poor prognosis. To evaluate the biological consequences of activation of the trk-A or trk-B signal transduction pathways in neuroblastoma cells, the trk-A or trk-B gene was transfected into the trk negative 15N neuroblastoma cell line. Clones expressing trk-A or trk-B were treated with specific ligands and evaluated for growth and differentiation. Both ligands induced neurite extension. Treatment of the 15N-trk-A clones with NGF inhibited proliferation (80-90% decrease), while treatment of the 15N-trk-B clone with BDNF had no effect (< 10% decrease). NGF-induced growth inhibition was concentration dependent. Such studies indicate that differential trk expression may affect the biology of neuroblastoma tumours and contribute to differences in the clinical course of patients. (C) 1997 Elsevier Science Ltd. C1 NCI, Cellular & Mol Biol Sect, Pediat Branch, NIH, Bethesda, MD 20892 USA. NCI, Eukaryot Signal Transduct Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Thiele, CJ (reprint author), NCI, Cellular & Mol Biol Sect, Pediat Branch, NIH, Bldg 10,Room 13C218,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Lucarelli, Enrico/G-3588-2015 OI Lucarelli, Enrico/0000-0002-6681-6374 NR 16 TC 37 Z9 40 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 1997 VL 33 IS 12 BP 2068 EP 2070 DI 10.1016/S0959-8049(97)00266-9 PG 3 WC Oncology SC Oncology GA YM917 UT WOS:000071114800034 PM 9516854 ER PT J AU Gaetano, C Kitajima, Y Matsumoto, K Matsuo, T Thiele, CJ AF Gaetano, C Kitajima, Y Matsumoto, K Matsuo, T Thiele, CJ TI Identification of a novel thyroid hormone receptor responsive element in the human trk-B promoter SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. Ist Regina Elena, I-00161 Rome, Italy. 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 1997 VL 33 IS 12 BP 2138 EP 2138 PG 1 WC Oncology SC Oncology GA YM917 UT WOS:000071114800055 ER PT J AU Kitajima, Y Matsumoto, K Morrill, M Thiele, CJ AF Kitajima, Y Matsumoto, K Morrill, M Thiele, CJ TI Human trk-B promotor: Isolation and characterisation reveals novel retinoic acid inducible transcription unit involving INR and 3 ' direct repeat element SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Cell & Mol Biol Sect, Pediat Branch, 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 1997 VL 33 IS 12 BP 2138 EP 2138 PG 1 WC Oncology SC Oncology GA YM917 UT WOS:000071114800054 ER PT J AU Gomez, DE Alonso, DF Yoshiji, H Thorgeirsson, UP AF Gomez, DE Alonso, DF Yoshiji, H Thorgeirsson, UP TI Tissue inhibitors of metalloproteinases: Structure, regulation and biological functions SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Review DE tissue inhibitor of metalloproteinases; extracellular matrix; tissue remodeling; cell biology; physiopathology ID ERYTHROID-POTENTIATING ACTIVITY; MATRIX-DEGRADING METALLOPROTEINASES; FIBROBLAST COLLAGENASE INHIBITOR; RECOMBINANT CATALYTIC DOMAIN; HUMAN ALVEOLAR MACROPHAGES; GROWTH-PROMOTING ACTIVITY; MESSENGER-RNA EXPRESSION; HUMAN 72-KDA GELATINASE; B16-F10 MELANOMA-CELLS; IN-SITU HYBRIDIZATION AB Four members of the tissue inhibitor of metalloproteinases (TIMP) family have been characterized so far, designated as TIMP-1, TIMP-2, TIMP-3, and TIMP-4. TIMP-1 and TIMP-2 are capable of inhibiting the activities of all known matrix metalloproteinases (MMPs) and as such play a key role in maintaining the balance between extracellular matrix (ECM) deposition and degradation in different physiological processes, Accelerated breakdown of ECM occurs in various pathological processes, including inflammation, chronic degenerative diseases and tumor invasion. TIMP-1 and TIMP-2 can inhibit tumor growth, invasion, and metastasis in experimental models which has been associated with their MMP inhibitory activity, Recent developments in TIMP research suggest that TIMP-1 and TIMP-2 are multifunctional proteins with diverse actions, Both inhibitors exhibit growth factor-like activity and can inhibit angiogenesis. Structure-function studies have separated the MMP inhibitory activity of TIMP-1 from its growth promoting effect. TIMP-1 has also been implicated in gonadal steroidogenesis and as a cellular elongation factor. TIMP-3 is the only member of the TIMP family which is found exclusively in the extracellular matrix (ECM). It is regulated in a cell cycle-dependent fashion in certain cell types and may serve as a marker for terminal differentiation. The most recently discovered TIMP, TIMP-4, may function in a tissue-specific fashion in extracellular matrix hemostasis, The main aim of this article is to review recent literature on TIMPs with special emphasis on their biological activities and the possibility that they may have paradoxical roles in tumor progression. C1 NCI,TUMOR BIOL & CARCINOGENESIS SECT,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,BETHESDA,MD 20892. QUILMES NATL UNIV,DEPT SCI & TECHNOL,ONCOL MOL LAB,BUENOS AIRES,DF,ARGENTINA. OI Gomez, Daniel E/0000-0002-8629-0787 NR 176 TC 1136 Z9 1204 U1 3 U2 28 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD OCT PY 1997 VL 74 IS 2 BP 111 EP 122 PG 12 WC Cell Biology SC Cell Biology GA YA326 UT WOS:A1997YA32600001 PM 9352216 ER PT J AU Ariel, A Hershkoviz, R Cahalon, L Williams, DE Akiyama, SK Yamada, KM Chen, C Alon, R Lapidot, T Lider, O AF Ariel, A Hershkoviz, R Cahalon, L Williams, DE Akiyama, SK Yamada, KM Chen, C Alon, R Lapidot, T Lider, O TI Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix-bound interleukin-7 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokine; integrin; inflammation; blood vessel walls ID GROWTH-FACTOR; HUMAN IL-7; TYROSINE PHOSPHORYLATION; TERMINAL DOMAIN; RECEPTOR; LYMPHOCYTES; CYTOKINES; PROLIFERATION; FIBRONECTIN; EXPRESSION AB The putative effects of interleukin (IL)-7, operating in the context of extracellular matrix (ECM), on the adhesion of human T cells were examined. Recombinant human IL-7 was found to bind ECM or fibronectin (FN) with IC50 values of 10-100 nM. Nanogram amounts of both soluble and, especially, FN- or ECM-bound IL-7, which differentially affected the morphologies of FN-adherent T cells, induced the adhesion of resting CD4(+) and CD8(+) T cells in dose-dependent and beta 1 integrin-dependent manners. Under static and flow conditions, soluble IL-7 also induced the binding of unstimulated T cells to vascular cell adhesion molecule-1, suggesting that this cytokine can also modulate integrin binding to endothelial cell ligands. The effects of affinity modulation by IL-7 of FN-specific beta 1 integrins depend on the presence of soluble FN, which inhibited T cell adhesion to FN induced by FN-bound IL-7 or by an integrin-specific affinity-modulating monoclonal antibody, but not by soluble IL-7 or phorbol 12-myristate 13-acetate. These findings provide an example of a major ECM integrin ligand, FN, which is capable of modulating its adhesive interactions with specific immune cells by associating with and presenting a cytokine in a bio-active state. C1 WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. IMMUNEX CORP,SEATTLE,WA. RI Lapidot, Tsvee/A-1812-2010; OI Yamada, Kenneth/0000-0003-1512-6805 NR 44 TC 48 Z9 52 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1997 VL 27 IS 10 BP 2562 EP 2570 DI 10.1002/eji.1830271015 PG 9 WC Immunology SC Immunology GA YB498 UT WOS:A1997YB49800014 PM 9368611 ER PT J AU Velasco, PT Lukas, TJ Murthy, SNP DouglasTabor, Y Garland, DL Lorand, L AF Velasco, PT Lukas, TJ Murthy, SNP DouglasTabor, Y Garland, DL Lorand, L TI Hierarchy of lens proteins requiring protection against heat-induced precipitation by the alpha crystallin chaperone SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE thermal aggregation; lens enzymes; alpha crystallin; chaperone; cataract ID MOLECULAR CHAPERONE; ALDEHYDE DEHYDROGENASE; NUCLEOTIDE-SEQUENCE; B-CRYSTALLIN; LOCALIZATION; AGGREGATION; TISSUES; GENE AB Gel filtration of the water-soluble extract from bovine lens yields a group of proteins, emerging between the peaks of beta(H) and beta(L) crystallins, which show a considerably greater sensitivity to heat-induced aggregation/precipitation than the far more abundant beta and gamma crystallins. However, the small heat shock protein: alpha crystallin was effective in protecting these trace constituents of the lens from precipitating out of solution at 55 degrees C (measured under the standard conditions in a pH 7.5 buffer containing 50 mM sodium phosphate, 100 mM NaCl, 1 mM EDTA and 0.05% NaN3). Prominent components of the precipitate, formed in the absence of a recombinant alpha B crystallin chaperone could be resolved by one- and two-dimensional electrophoresis. Identification by amino acid sequencing revealed that the heat-sensitive group of lens proteins comprised glyceraldehyde-3-phosphate dehydrogenase (M-r similar to 39 kDa), enolase (similar to 48 kDa), leucine aminopeptidase (similar to 52 kDa) and aldehyde dehydrogenase (similar to 53 kDa). These findings indicate for the first time that the aggregation of such minor lens constituents could possibly contribute to initiating the process of opacification in the development of cataracts. (C) 1997 Academic Press Limited. C1 NORTHWESTERN UNIV,SCH MED,DEPT CELL & MOL BIOL,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT MOL PHARMACOL & BIOCHEM,CHICAGO,IL 60611. NEI,LAB MECHANISMS OCULAR DIS,BETHESDA,MD 20892. FU NEI NIH HHS [EY-03942] NR 29 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 1997 VL 65 IS 4 BP 497 EP 505 DI 10.1006/exer.1997.0358 PG 9 WC Ophthalmology SC Ophthalmology GA YA785 UT WOS:A1997YA78500004 PM 9464183 ER PT J AU Wellmann, A Doseeva, V Butscher, W Raffeld, M Fukushima, P StetlerStevenson, M Gardner, K AF Wellmann, A Doseeva, V Butscher, W Raffeld, M Fukushima, P StetlerStevenson, M Gardner, K TI The activated anaplastic lymphoma kinase increases cellular proliferation and oncogene up-regulation in rat 1a fibroblasts SO FASEB JOURNAL LA English DT Article DE plasmid vector; gene expression; cytosolic membrane; antibody; PTK ID NON-HODGKINS-LYMPHOMA; DNA-BINDING ACTIVITY; TRANSFORMING ACTIVITY; KI-1 LYMPHOMA; KAPPA-B; T-CELLS; PROTEIN; PHOSPHORYLATION; TRANSLOCATION; ONCOPROTEIN AB More than 60% of anaplastic large-cell lymphomas (Ki-1 lymphoma) are associated with a t(2;5)(p23;q35) translocation that produces an 80 kDa hyperphosphorylated chimeric protein (p80) derived from the fusion of the anaplastic lymphoma kinase (ALK) with nucleophosmin (NPM). The NPM-ALK chimeric gene is an activated tyrosine kinase that has been shown to be a potent oncogene, We have developed a cellular model for the study of p80 action in rat 1a fibroblasts, Expression of cDNA's encoding NPM-ALK (p80) in rat 1a fibroblasts induces anchorage-independent growth in soft agar and promotes foci formation in culture, Cells expressing exogenous p80 showed significantly increased proliferation characterized by accelerated cell cycle entry into S-phase. Consistent with increased G(0)/G(1) to S-phase transition, there is also marked up-regulation of cyclin A and cyclin D1 expression, In addition, p80 transformed cells showed elevated expression of several immediate early genes involved in cellular proliferation, including fos, jun, and c-myc, DNA binding analysis of nuclear extracts prepared from p80 transformed cells reveal marked up-regulation of AP-1 DNA binding activity, Functional AP-1-specific transfection assays also show up-regulation of AP-1-dependent transcriptional activation, These finding demonstrate that p80 transformed rat 1a fibroblast can be a highly useful model system for the molecular and biochemical characterization of the mechanisms of action of this interesting new oncogene. C1 NIH,PATHOL LAB,BETHESDA,MD 20892. NR 28 TC 49 Z9 51 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 1997 VL 11 IS 12 BP 965 EP 972 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA YA724 UT WOS:A1997YA72400006 PM 9337149 ER PT J AU Roilides, E Kadiltsoglou, I Dimitriadou, A Hatzistilianou, M Manitsa, A Karpouzas, J Pizzo, PA Walsh, TJ AF Roilides, E Kadiltsoglou, I Dimitriadou, A Hatzistilianou, M Manitsa, A Karpouzas, J Pizzo, PA Walsh, TJ TI Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article; Proceedings Paper CT 8th Immunocompromised-Host-Society Meeting CY JUN, 1994 CL DAVOS, SWITZERLAND SP Immunocompromised Host Soc DE interleukin-4; monocyte/macrophage; uptake; cytokine; Candida ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; NORMAL HUMAN-MONOCYTES; INTERFERON-GAMMA; FACTOR-ALPHA; IFN-GAMMA; MACROPHAGE ACTIVATION; GENE-EXPRESSION; FUNCTIONAL-PROPERTIES; SUPEROXIDE PRODUCTION AB Pathogenesis of invasive candidiasis may involve regulatory activities of Th2 immunity on phagocytic host defenses. The effects of interleukin (IL)-4 on antifungal capacity of human mononuclear phagocytes against Candida albicans were studied. Incubation of adherent mononuclear-leukocytes from healthy donors with IL-4 (1-5 ng ml(-1)) at 37 degrees C for 2-4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P less than or equal to 0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-gamma (0.25-25 ng ml(-1)), granulocyte-macrophage colony-stimulating factor (CSF, 20 ng ml(-1)), macrophage-CSF (15 ng ml(-1)) but not IL-10 (100 ng ml(-1)) somewhat counteracted the suppressive effect of IL-4. In contrast, mannose receptor-mediated uptake of blastoconidia in the absence of serum was increased by IL-4. Killing of conidia was decreased after incubation of morphonuclear leukocytes with IL-4 for 2 days (P < 0.05). While superoxide anion production in response ro phorbol myristate acetate was decreased by IL-4 (P < 0.05), it was not altered in response to blastoconidia and pseudohyphae. Morphonuclear leukocyte-induced pseudohyphal damage also remained unaltered. These findings suggest that IL-4 plays its detrimental role in invasive candidiasis by predominantly suppressing uptake and killing of blastoconidia by morphonuclear leukocytes. Anti-IL-4, IFN-gamma, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. UNIV THESSALONIKI,DEPT PEDIAT,GR-54642 THESSALONIKI,GREECE. HIPPOKRATIO GEN HOSP,DEPT TRANSFUS MED,GR-54642 THESSALONIKI,GREECE. NR 54 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD OCT PY 1997 VL 19 IS 2 BP 169 EP 180 DI 10.1111/j.1574-695X.1997.tb01086.x PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YD551 UT WOS:A1997YD55100009 PM 9395062 ER PT J AU Morgan, DL Mahler, JF Wilson, RE Moorman, MP Price, HC OConnor, RW AF Morgan, DL Mahler, JF Wilson, RE Moorman, MP Price, HC OConnor, RW TI Toxicity of divinylbenzene-55 for B6C3F1 mice in a two-week inhalation study SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID F344 RATS; STYRENE; SUSCEPTIBILITY AB Divinylbenzene (DVB) is a crosslinking monomer used primarily for copolymerization with styrene to produce ion-exchange resins. The toxicity of inhaled DVB was investigated because of the potential for worker exposure and the structural similarity of DVB to styrene, a potential carcinogen. Male and female B6C3F1 mice were exposed to 0, 25, 50, or 75 ppm DVB for 6 hr/day, 5 days/week for up to 2 weeks. Six mice/sex/dose group were killed after 3, 5, and 10 exposures and six mice/sex in the 75 ppm group were killed 7 days after 10 exposures. The most severe effects occurred in the nasal cavity and liver, with less severe effects occurring in the kidneys. In the nasal cavity olfactory epithelium acute necrosis and inflammation were present at early time points followed by regeneration, architectural reorganization, and focal respiratory metaplasia by 7 days after the last exposure. Olfactory epithelial changes were concentration-dependent with extensive involvement at 75 ppm and peripheral sparing at 25 ppm. There was also necrosis and regeneration of olfactory-associated Bowman's glands as well as the lateral nasal (Steno's) glands. Hepatocellular centrilobular (CL) necrosis was observed only in the 75 ppm dose group and was similar to that caused by styrene. A time-dependent progression was observed, characterized by CL degeneration after 1 exposure, necrosis after 3 and 5 exposures, and chronic inflammation with CL karyomegaly after 10 exposures and 7 days after the 10th exposure. Hepatic GSH levels were decreased in a dose-dependent manner. In the kidneys, transient tubular damage was observed in some male mice exposed to 75 ppm, and appeared to be a response to DVB-induced tubular epithelial injury. C1 MANTECH ENVIRONM TECHNOL INC,RES TRIANGLE PK,NC 27709. RP Morgan, DL (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1997 VL 39 IS 2 BP 89 EP 100 DI 10.1006/faat.1997.2362 PG 12 WC Toxicology SC Toxicology GA YH051 UT WOS:A1997YH05100002 PM 9344621 ER PT J AU Okuda, M Minehata, K Setoguchi, A Cho, KW Nakamura, N Nishigaki, K Watari, T Cevario, S OBrien, SJ Tsujimoto, H Hasegawa, A AF Okuda, M Minehata, K Setoguchi, A Cho, KW Nakamura, N Nishigaki, K Watari, T Cevario, S OBrien, SJ Tsujimoto, H Hasegawa, A TI Cloning and chromosome mapping of the feline genes p21WAF1 and p27Kip1 SO GENE LA English DT Article DE cyclin-dependent kinase inhibitors; feline tumor; molecular cloning; chromosomal mapping ID DEPENDENT KINASE INHIBITOR; LEUKEMIA-VIRUS; DOMESTIC CAT; POTENTIAL MEDIATOR; MYC GENE; CELL; TUMORS; MUTATIONS; IDENTIFICATION; REARRANGEMENT AB For investigation of the relation of cell cycle regulation with tumorigenesis in cats, we carried out molecular cloning of feline p21WAF1 and p27Kip1 cDNAs and chromosomal mapping of these genes on the cat genome, The feline p21WAF1 cDNA clone obtained in this study encoded 164 amino acids (aa) showing 83.5% and 76.8% sequence similarity with those of the human and mouse counterparts, respectively. The cat p27Kip1 cDNA clone isolated here encoded 198 aa, showing sequence similarities of 93.4% and 90.4% with its human and mouse counterparts, respectively. Using a panel of feline x rodent somatic cell hybrids, the feline CDKN1A (p21WAF1) and CDKN1B (p27Kip1) loci were assigned to feline chromosomes B2 and B4, respectively. Southern-blot analyses of 17 feline spontaneous leukemia and lymphoma cases using these cDNAs as probes did not reveal any rearrangements in either the p21WAF1 or the p27Kip1 gene. RT-PCR/SSCP (single strand conformation polymorphism) analysis of p27Kip1 cDNA did not uncover any amino acid substitutions in the 10 feline leukemia and lymphoma cases that were examined. (C) 1997 Elsevier Science B.V. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB GENOM DIVERS,FREDERICK,MD 21702. RP Okuda, M (reprint author), UNIV TOKYO,FAC AGR,DEPT VET INTERNAL MED,1-1-1 YAYOI,TOKYO 113,JAPAN. NR 26 TC 6 Z9 8 U1 0 U2 0 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 1997 VL 198 IS 1-2 BP 141 EP 147 DI 10.1016/S0378-1119(97)00304-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA YA834 UT WOS:A1997YA83400018 PM 9370275 ER PT J AU Lin, ZC Yang, SH Mallavia, LP AF Lin, ZC Yang, SH Mallavia, LP TI Codon usage and nucleotide composition in Coxiella burnetii SO GENE LA English DT Article DE Rickettsia; Q fever; chromosome; plasmid; G+C content; nucleotide co-occurrence ID ESCHERICHIA-COLI; SEQUENCE-ANALYSIS; MOLECULAR-CLONING; PLASMID QPH1; RICKETTSIA-TSUTSUGAMUSHI; CITRATE SYNTHASE; BASE COMPOSITION; ENCODING GENE; G+C-CONTENT; PROTEIN AB Coxiella burnetii, the causative agent of Q fever, is an obligate intracellular bacterium. With the development of molecular biology techniques, there have been increasing efforts on gene cloning and other genetic analyses of this organism. In this report, we tabulate the codon usage (CU) and nucleotide (nt) co-occurrence in C. burnetii, based on available nt sequence data. The average G+C content of the C. burnetii genome is 42.4%, where the G+C content is 42.7% for the chromosome and 38.7% for the plasmid. In comparison to Escherichia coli, there is biased CU. Some codons are frequently used in C. burnetii, but rarely used in E. coli and vice versa. Plasmid genes prefer A or T at the first or third position of a codon. However, TAA remains the most used stop codon. In the AT-rich DNA of C. burnetii, A or T tend to occur together, forming A or T tracks. (C) 1997 Elsevier Science B.V. C1 WASHINGTON STATE UNIV,DEPT MICROBIOL,PULLMAN,WA 99164. NIDA,ARC,NIH,BALTIMORE,MD 21224. FU NIAID NIH HHS [AI20190] NR 52 TC 2 Z9 2 U1 0 U2 0 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 1997 VL 198 IS 1-2 BP 171 EP 180 DI 10.1016/S0378-1119(97)00312-0 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA YA834 UT WOS:A1997YA83400022 PM 9370279 ER PT J AU Bharathi, A Ghosh, A Whalen, WA Yoon, JH Pu, R Dasso, M Dhar, R AF Bharathi, A Ghosh, A Whalen, WA Yoon, JH Pu, R Dasso, M Dhar, R TI The human RAE1 gene is a functional homologue of Schizosaccharomyces pombe rae1 gene involved in nuclear export of Poly(A)(+) RNA SO GENE LA English DT Article DE fission yeast; mRNA export; human homologue ID MESSENGER-RNA; NUCLEOCYTOPLASMIC TRANSPORT; BINDING-PROTEINS; CONDITIONAL ALLELE; YEAST; CYTOPLASM; COMPLEX; MUTATION; DEFECTS; PATHWAY AB A Schizosaccharomyces pombe temperature-sensitive mutant, rae1-1, was previously identified by us as being defective in nuclear export of Poly(A)(+) RNA when grown at restrictive temperature. Here, we report the isolation of the human homologue of the S. pombe rae1 gene. The RAE1 genes are highly conserved in evolution in both structure and function. The human RAE1 cDNA, when expressed from the CMV-promoter, can suppress partially the temperature sensitivity of the rae1-1 mutant. This is also reflected by increased Poly(A)+ RNA export at a restrictive temperature. An epitope tagged human Rae1p localizes to both the nucleus and the cytoplasm in transiently transfected HeLa cells. We discuss the potential role of Rae1p in nuclear cytoplasmic trafficking in yeast and higher eukaryotic cells. (C) 1997 Elsevier Science B.V. C1 NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. OI Dasso, Mary/0000-0002-5410-1371 NR 47 TC 39 Z9 40 U1 1 U2 1 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 1997 VL 198 IS 1-2 BP 251 EP 258 DI 10.1016/S0378-1119(97)00322-3 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA YA834 UT WOS:A1997YA83400032 PM 9370289 ER PT J AU Hong, SB Kim, SJ Noh, MJ Lee, YM Kim, Y Yoo, OJ AF Hong, SB Kim, SJ Noh, MJ Lee, YM Kim, Y Yoo, OJ TI Identification of the transcription termination site of the mouse nkx-1.2 gene: involvement of sequence-specific factors SO GENE LA English DT Article DE GT repeat; transcription regulation; RNA polymerase II ID RNA POLYMERASE-II; DNA-SEQUENCE; GASTRIN GENE; EXPRESSION; ENHANCER; BINDING AB We have identified a transcription termination site in the 3' flanking region of the mouse nkx-1.2 gene. A downstream transcription regulatory element in the mouse nkx-1.2 gene was characterized by transferring its 3'-fragment into a chloramphenicol acetyl transferase (CAT) expression vector. Analysis of recombinant plasmids transfected into mouse NIH3T3 cells by CAT assay showed the possible region of regulation. There were two direct repeat structures containing poly(dG-dT)poly(dC-dA) sequences (GT repeats) in this region. The precise location of transcription termination was mapped by nuclease S1 analysis of the transcripts from recombinant plasmids transfected into COSM6 cells. It was approximately 20 nucleotides upstream of the first GT repeat within the 5' sequences of the first element of the two direct repeats. Gel mobility shift assay and footprinting analysis demonstrated that nuclear DNA binding proteins bound specifically to the sequences where the termination occurred as well as the other sequences in the second element of the direct repeats. Southwestern analysis showed that 90-, 54-, 36- and 15-kDa nuclear proteins bound to the region of the termination. It is possible that one or more of those proteins are involved in blocking the elongation of the mouse nkx-1.2 gene transcript and then result in termination. (C) 1997 Elsevier Science B.V. C1 KOREA ADV INST SCI & TECHNOL,DEPT BIOL SCI,YUSONG GU,TAEJON 305701,SOUTH KOREA. NHLBI,MOL CARDIOL LAB,NIH,BETHESDA,MD 20892. KOREAN RES INST BIOSCI & BIOTECHNOL,PLANT & ANIM CELL TECHNOL RES DIV,TAEJON 305333,SOUTH KOREA. RI Yoo, Ook Joon/C-1860-2011 NR 22 TC 3 Z9 3 U1 0 U2 0 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 1997 VL 198 IS 1-2 BP 373 EP 378 DI 10.1016/S0378-1119(97)00340-5 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA YA834 UT WOS:A1997YA83400047 PM 9370304 ER PT J AU Sullivan, DM Jensen, TG Taichman, LB Csaky, KG AF Sullivan, DM Jensen, TG Taichman, LB Csaky, KG TI Ornithine-delta-aminotransferase expression and ornithine metabolism in cultured epidermal keratinocytes: toward metabolic sink therapy for gyrate atrophy SO GENE THERAPY LA English DT Article DE gene therapy; adenoviridae; metabolic diseases; skin ID MEDIATED GENE-TRANSFER; GLUTAMINE-SYNTHETASE; SKIN FIBROBLASTS; LIVER; HEPATOCYTES; ADENOVIRUS; DEFICIENCY; ARGININE; PATHWAY; PROLINE AB There is now strong evidence that the chorioretinal degeneration associated with ornithine-delta-aminotransferase (OAT) deficiency is a consequence of hyperornithinemia. Therefore development of a metabolic system for clearing ornithine from the circulation is being pursued as a potential treatment. The skin is considered an attractive location for such a metabolic system because autologous cells can be safely and easily utilized. This study was undertaken to determine the ornithine metabolizing capacity of epidermal keratinocytes expressing normal and superphysiologic amounts of OAT. The data show the overexpression of OAT in keratinocytes cultured from a gyrate atrophy patient restores ornithine metabolism and results in a rate of ornithine disappearance from the medium that is significantly higher than the rate of disappearance from the medium bathing normal keratinocytes. In addition, OAT activity determined in soluble protein prepared from sonicates suggests that the capacity to maintain plasma ornithine within the normal range is contained within an accomplishable graft of keratinocytes overexpressing OAT. However, the actual rate of ornithine disappearance from the media was significantly less than predicted from enzyme activity assays. Following ornithine metabolite production by intact cells suggests that ornithine metabolism is limited primarily by clearance of downstream metabolites, as opposed to substrate delivery. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. SUNY STONY BROOK,SCH MED,DEPT ORAL BIOL & PATHOL,STONY BROOK,NY 11794. FU NIDCR NIH HHS [R37 DE04511]; NIDDK NIH HHS [R01 DK49093] NR 32 TC 30 Z9 30 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 1997 VL 4 IS 10 BP 1036 EP 1044 DI 10.1038/sj.gt.3300505 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XZ210 UT WOS:A1997XZ21000006 PM 9415309 ER PT J AU Simons, A Janssen, IM Suijkerbuijk, RF Veth, RPH Pruszczynski, M HulsbergenvandeKaa, CA duManoir, S vanKessel, AG AF Simons, A Janssen, IM Suijkerbuijk, RF Veth, RPH Pruszczynski, M HulsbergenvandeKaa, CA duManoir, S vanKessel, AG TI Isolation of osteosarcoma-associated amplified DNA sequences using representational difference analysis SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN SARCOMAS; OSTEO-SARCOMA; AMPLIFICATION; GENE; LOSSES; TUMORS; IDENTIFICATION; GAINS AB Comparative genomic hybridization analysis of a primary osteosarcoma and its metastasis revealed two regions of DNA amplification, one at 17p11.2-12 and one at 19q12-13. Subsequent representational difference analysis of the primary tumor resulted in the isolation of two distinct tumor-amplified DNA fragments originating from chromosome 19. A YAC clone corresponding to one of the two isolated DNA fragments was used for fluorescence in situ hybridization on normal human lymphocyte metaphases and tumor-derived nuclei. This resulted in the localization of this YAC to 19q12-13.1 and confirmed the amplification status of the isolated fragment in the tumors, The availability of such RDA-isolated sequences may be instrumental in the seal-ch for genes relevant for tumor development. (C) 1997 1997 Wiley-Liss, Inc. C1 UNIV NIJMEGEN HOSP,DEPT ORTHOPED,NL-6500 HB NIJMEGEN,NETHERLANDS. UNIV NIJMEGEN HOSP,DEPT PATHOL,NL-6500 HB NIJMEGEN,NETHERLANDS. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Simons, A (reprint author), UNIV NIJMEGEN HOSP,DEPT HUMAN GENET,POB 9101,NL-6500 HB NIJMEGEN,NETHERLANDS. RI Geurts van Kessel, Ad/A-2810-2010; Hulsbergen-van de Kaa, C.A./L-4399-2015 NR 24 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 1997 VL 20 IS 2 BP 196 EP 200 DI 10.1002/(SICI)1098-2264(199710)20:2<196::AID-GCC10>3.0.CO;2-P PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA XZ209 UT WOS:A1997XZ20900010 PM 9331570 ER PT J AU Ouellette, BFF Boguski, MS AF Ouellette, BFF Boguski, MS TI Database divisions and homology search files: A guide for the perplexed SO GENOME RESEARCH LA English DT Article ID SEQUENCE RP Ouellette, BFF (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 8 TC 36 Z9 37 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD OCT PY 1997 VL 7 IS 10 BP 952 EP 955 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YC515 UT WOS:A1997YC51500004 PM 9331365 ER PT J AU Winfield, SL Tayebi, N Martin, BM Ginns, EI Sidransky, E AF Winfield, SL Tayebi, N Martin, BM Ginns, EI Sidransky, E TI Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: Implications for Gaucher disease SO GENOME RESEARCH LA English DT Article ID TARGETED DISRUPTION; CODING REGIONS; MOUSE; THROMBOSPONDIN-3; MUTATIONS; ORGANIZATION; PSEUDOGENE; SEQUENCES; PHENOTYPE; METAXIN AB Gaucher disease results from the deficiency of the lysosomal enzyme glucocerebrosidase (EC 3.2.1.45). Although the functional gene for glucocerebrosidase (GBA) and its pseudogene (psGBA), located in close proximity on chromosome 1q21, have been studied extensively, the flanking sequence has not been well characterized. The recent identification of human metaxin (MTX) immediately downstream of psGBA prompted a closer analysis of the sequence of the entire region surrounding the GBA gene. We now report the genomic DNA sequence and organization of a 75-kb region around GBA, including the duplicated region containing GBA and MTX. The origin and endpoints of the duplication leading to the pseudogenes for GBA and MTX are now clearly established. We also have identified three new genes within the 32 kb of sequence upstream to GBA, all of which are transcribed in the same direction as CBA. OF these three genes, the gene most distal to GBA is a protein kinase (clk2). The second gene, propin1, has a 1.5-kb cDNA and shares homology to a rat secretory carrier membrane protein 37 (SCAMP37). Finally, cote1, a gene of unknown function lies most proximal to GBA. The possible contributions of these closely arrayed genes to the more atypical presentations of Gaucher disease is now under investigation. C1 NIMH,CLIN NEUROSCI BRANCH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NR 36 TC 65 Z9 74 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD OCT PY 1997 VL 7 IS 10 BP 1020 EP 1026 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YC515 UT WOS:A1997YC51500011 PM 9331372 ER PT J AU Luo, G Leroy, E Kozak, CA Polymeropoulos, MH Horowits, R AF Luo, G Leroy, E Kozak, CA Polymeropoulos, MH Horowits, R TI Mapping of the gene (NRAP) encoding N-RAP in the mouse and human genomes SO GENOMICS LA English DT Article ID MAP AB N-RAP is a nebulin-related actin-binding protein found at the myotendon junction in skeletal muscle and at the intercalated disks in cardiac muscle. We mapped the NRAP gene to mouse chromosome 19 using interspecific crosses and to human chromosome 10 using radiation hybrid panels. Comparative analysis of the mouse and human genomes indicates that the NRAP gene is located in regions of conserved synteny between the two species. (C) 1997 Academic Press. C1 NIAMSD,NIH,BETHESDA,MD 20892. NHGRI,NIH,BETHESDA,MD 20892. NIAID,NIH,BETHESDA,MD 20892. NR 13 TC 5 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 1 PY 1997 VL 45 IS 1 BP 229 EP 232 DI 10.1006/geno.1997.4917 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YA721 UT WOS:A1997YA72100029 PM 9339382 ER PT J AU Stone, AL AF Stone, AL TI Heparin: The turning point SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NICHHD,DEV & MOL IMMUN LAB,NIMH,NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1997 VL 7 IS 7 BP 54 EP 54 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA478 UT WOS:A1997YA47800070 ER PT J AU Orvisky, E StJohn, E Parker, M Sidransky, E Martin, BM Ginns, EI Krasnewich, D AF Orvisky, E StJohn, E Parker, M Sidransky, E Martin, BM Ginns, EI Krasnewich, D TI Carbohydrate-deficient Glycoprotein Syndrome correlation of in vitro 2(H-3)mannose metabolic labelling studies with phosphomannomutase activity (PMM); PMM determined by direct analysis of mannose-1-phosphate to mannose-6-phosphate interconversion SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NIMH,NS,NIH,BETHESDA,MD 20892. NHGRI,MGB,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1997 VL 7 IS 7 BP 92 EP 92 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA478 UT WOS:A1997YA47800107 ER PT J AU Hanover, JA Wu, W Caracciolo, MR Krause, M Lubas, WA AF Hanover, JA Wu, W Caracciolo, MR Krause, M Lubas, WA TI O-linked GlcNAc transferase molecular features of a highly conserved signaling molecule SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NIDDK,LAB CELL BIOCHEM & BIOL,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1997 VL 7 IS 7 BP 110 EP 110 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YA478 UT WOS:A1997YA47800126 ER PT J AU Naliboff, BD Munakata, J Fullerton, S Gracely, RH Kodner, A Harraf, F Mayer, EA AF Naliboff, BD Munakata, J Fullerton, S Gracely, RH Kodner, A Harraf, F Mayer, EA TI Evidence for two distinct perceptual alterations in irritable bowel syndrome SO GUT LA English DT Article DE irritable bowel syndrome; visceral hypersensitivity; pain threshold ID RECTAL SENSITIVITY; DISTENSION; MOTILITY; PAIN AB Background and aims-Visceral hyperalgesia has been implicated as a factor contributing to symptom generation in irritable bowel syndrome (IBS). However, previous studies using intestinal balloon distension have used psychophysical procedures which do not provide adequate and unbiased measures of visceral sensitivity. Methods-Three psychophysical tasks were examined in 45 patients with IBS (positive Rome criteria) and 14 controls using rectal balloon distension with a computerised distension device. Discomfort threshold and tolerance were assessed during an ascending series of phasic pressure stimuli and during an interactive threshold tracking procedure. In addition, stimulus response functions were generated from intensity and unpleasantness ratings of the rectal distensions. Results-Discomfort threshold and tolerance for the ascending stimuli were significantly lower for the patients with IBS compared with the controls. In contrast, discomfort thresholds during the tracking procedure and stimulus response curves for the ascending series were not different between the groups. A factor analysis of the psychophysical data was consistent with the presence of two distinct and unrelated perceptual alterations related to rectal distension: hypervigilance for visceral stimuli, manifested as lowered response criteria for using the descriptor ''discomfort''; and rectal hypersensitivity, manifested as a lower discomfort threshold and left shift of the stimulus response curves. Conclusions-Patients with IBS as a group have a greater propensity to label visceral sensations negatively and show a lower tolerance for rectal balloon distension. A subgroup of patients also have baseline rectal hypersensitivity, assessed by unbiased measures of discomfort threshold and stimulus intensity judgements. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90073. NIDR,NAB,DEPT MED,NIH,BETHESDA,MD 20892. NIDR,NAB,DEPT PHYSIOL,NIH,BETHESDA,MD 20892. NIDR,NAB,DEPT PSYCHOL,NIH,BETHESDA,MD 20892. NIDR,NAB,NEUROPATH PAIN & PAIN ASSESSMENT SECT,NIH,BETHESDA,MD 20892. RP Naliboff, BD (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CURE DIGEST DIS RES CTR,NEUROENTER DIS PROGRAM,LOS ANGELES,CA 90073, USA. FU NIDDK NIH HHS [DK48351] NR 32 TC 278 Z9 281 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD OCT PY 1997 VL 41 IS 4 BP 505 EP 512 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YB236 UT WOS:A1997YB23600018 PM 9391250 ER PT J AU FernandezRodriguez, CM Prada, IR Prieto, J Montuenga, L Elssasser, T Penas, J Casal, M Medina, J Cuttita, F AF FernandezRodriguez, CM Prada, IR Prieto, J Montuenga, L Elssasser, T Penas, J Casal, M Medina, J Cuttita, F TI Circulating adrenomedullin and peripheral arterial vasodilatation in cirrhosis SO GUT LA English DT Meeting Abstract C1 HOSP XERAL VIGO,VIGO,SPAIN. UNIV NAVARRA,E-31080 PAMPLONA,SPAIN. NCI,DCS,NIH,ROCKVILLE,MD. ARS,USDA,BELTSVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD OCT PY 1997 VL 41 SU 3 BP A232 EP A232 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YB966 UT WOS:A1997YB96600988 ER PT J AU Miyake, M Hirayama, T Wada, A Padilla, PI Moss, J Kato, I Noda, M AF Miyake, M Hirayama, T Wada, A Padilla, PI Moss, J Kato, I Noda, M TI An arginine-specific (ADP-ribosyl) transferase activity in Helicobacter pylori SO GUT LA English DT Meeting Abstract C1 CHIBA UNIV,SCH MED,DEPT MICROBIOL 2,CHIBA 280,JAPAN. NAGASAKI UNIV,INST TROP MED,NAGASAKI 852,JAPAN. NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD OCT PY 1997 VL 41 SU 3 BP A20 EP A21 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YB966 UT WOS:A1997YB96600084 ER PT J AU SimonsMorton, BG Donohew, L AF SimonsMorton, BG Donohew, L TI Combining communication theory, research, and practice in substance abuse prevention among minority populations - Introduction SO HEALTH EDUCATION & BEHAVIOR LA English DT Editorial Material C1 UNIV KENTUCKY,LEXINGTON,KY 40506. RP SimonsMorton, BG (reprint author), NICHHD,PREVENT RES BRANCH,DESPR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 1997 VL 24 IS 5 BP 543 EP 543 DI 10.1177/109019819702400502 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XW953 UT WOS:A1997XW95300001 ER PT J AU SimonsMorton, BG Donohew, L Crump, AD AF SimonsMorton, BG Donohew, L Crump, AD TI Health communication in the prevention of alcohol, tobacco, and drug use SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID SUBSTANCE-ABUSE PREVENTION; SCHOOL; DRINKING AB Research on substance abuse prevention programs indicates that effectiveness is greater when multiple intervention approaches that address the specific vocabulary, perceptions, and values of the target population are employed. The field of health communication provides unique perspectives on media that can be applied to increase the salience and effectiveness of substance abuse prevention programs. Well-designed and Well-delivered health communications have the capacity for reaching remote audiences, changing health attitudes and behavior, shaping social norms, changing the way health issues are portrayed by the popular media, and influencing decisions about legislation and policies. Health communication approaches are generally employed within the broad context of health promotion programs, along with education, community development, empowerment, and social change approaches. This article describes the role of health communication in substance abuse prevention, reviews major conceptualizations of health communication, and introduces the unique features of the four articles included in this special section of Health Education Br Behavior. C1 UNIV KENTUCKY,DEPT COMMUN,LEXINGTON,KY 40506. UNIV KENTUCKY,CTR PREVENT RES,LEXINGTON,KY 40506. RP SimonsMorton, BG (reprint author), NICHHD,PREVENT RES BRANCH,DESPR,6100 EXECUT BLVD,ROOM 7B05,BETHESDA,MD 20852, USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 45 TC 15 Z9 15 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 1997 VL 24 IS 5 BP 544 EP 554 DI 10.1177/109019819702400503 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XW953 UT WOS:A1997XW95300002 PM 9307892 ER PT J AU Jensen, RH Zhang, SZ Wang, ZY Wang, WL Boice, J AF Jensen, RH Zhang, SZ Wang, ZY Wang, WL Boice, J TI Glycophorin a somatic cell mutation frequencies in residents of Tibet at high altitudes SO HEALTH PHYSICS LA English DT Article DE radiation, atmospheric; dose; health effects; exposure, radiation ID ATOMIC-BOMB SURVIVORS; RADIATION EXPOSURE; A LOCUS; MORTALITY; ERYTHROCYTES; WORKERS; PILOTS; CANCER; ASSAY; RISK AB Since cosmic radiation is absorbed by the atmosphere surrounding the Earth, people who live at high altitude receive significantly larger amounts of cosmic radiation exposure than do those who live at low altitude, The glycophorin A-based somatic mutation assay was performed on 36 blood samples from two populations of Tibet inhabitants to determine whether residents at high altitude (4,300 m) accumulate more somatic mutations than do those who Live at low altitude (1,500-1,900 m), These two populations differ in estimated cumulative lifetime cosmic radiation dose, with high altitude residents having received a mean of 111 mSv while low altitude residents received a mean of 27 mSv, Results showed no significant difference in peripheral blood variant erythrocyte frequency between these two populations and no difference from results of a previous study on Finnish workers who live at very low altitude (< 500 m). C1 UNIV CALIF SAN FRANCISCO, DEPT LAB MED, DIV MOL CYTOMETRY, SAN FRANCISCO, CA 94143 USA. MINIST PUBL HLTH, DIV RADIAT INJURY, BEIJING 100088, PEOPLES R CHINA. NCI, RADIAT EPIDEMIOL BRANCH, BETHESDA, MD 20852 USA. FU NCI NIH HHS [CP-40578] NR 24 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD OCT PY 1997 VL 73 IS 4 BP 663 EP 667 DI 10.1097/00004032-199710000-00012 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA XX080 UT WOS:A1997XX08000012 PM 9314228 ER PT J AU Taylor, GN Lloyd, RD Mays, CW Miller, SC Jee, WSS Mori, S Shabestari, L Li, XJ AF Taylor, GN Lloyd, RD Mays, CW Miller, SC Jee, WSS Mori, S Shabestari, L Li, XJ TI Relationship of natural incidence and radiosensitivity for bone cancer in dogs SO HEALTH PHYSICS LA English DT Article DE cancer; dogs; radiation effects; skeleton ID TUMORS; PU-239; BEAGLES AB A comparison of the risk coefficients for Pu-239- or Ra-226-induced hone cancer in two canine breeds, one with a relatively low (beagle) and the other with a very high (St, Bernard) natural incidence, indicated only slightly higher risk in the giant breed, The differences in risk for skeletal malignancy in Pu-239 and Ra-226 dogs were nonsignificant (p > 0.05). Likewise, the values of the Pu-239:Ra-226 ''toxicity ratios'' for these respective breeds, using bone cancer as the endpoint, were not significantly different at the 0.05 level, The anatomical distribution of the radiation-induced bone tumors tended to be a function of both the bone mass and the skeletal distribution of the radionuclide, not the site of predilection for naturally occurring bone neoplasia, Although the etiology of the higher natural incidence of bone cancer in the St, Bernard was not determined, several possible factors, including a higher osteoblastic activity level in the St, Bernards, are presented. These data suggest that making extrapolations of radiation-induced bone cancer risk from animals to humans is valid. C1 UNIV UTAH, RADIOBIOL LAB, SALT LAKE CITY, UT 84112 USA. NCI, BETHESDA, MD 20892 USA. UNIV UTAH, ANIM SERV, SALT LAKE CITY, UT 84112 USA. NR 26 TC 9 Z9 9 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD OCT PY 1997 VL 73 IS 4 BP 679 EP 683 DI 10.1097/00004032-199710000-00014 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA XX080 UT WOS:A1997XX08000014 PM 9314230 ER PT J AU Park, HJ Niedzielski, AS Wenthold, RJ AF Park, HJ Niedzielski, AS Wenthold, RJ TI Expression of the nicotinic acetylcholine receptor subunit, alpha 9, in the guinea pig cochlea SO HEARING RESEARCH LA English DT Article DE hair cell; efferent receptor; in situ hybridization; immunocytochemistry; kanamycin; ototoxicity ID OUTER HAIR-CELLS; MESSENGER-RNA; CHOLINE-ACETYLTRANSFERASE; OLIVOCOCHLEAR NEURONS; INSITU HYBRIDIZATION; AUDITORY-SYSTEM; RAT; IMMUNOREACTIVITY; ORGAN; LOCALIZATION AB Acetylcholine is a major neurotransmitter of the cochlear efferent system. Based on its high level of expression in hair cells, the recently cloned nicotinic receptor subunit, alpha 9 [Elgoyhen et al., Cell 79 (1994) 705-715], is likely to be the postsynaptic receptor for acetylcholine in hair cells either as a homomeric complex or with other subunits yet to be identified. To further study this receptor, we cloned and sequenced alpha 9 cDNA from the guinea pig organ of Corti library [Wilcox and Fex, Hear. Res. 62 (1992) 124-126]. The sequence of the guinea pig alpha 9 cDNA is similar to that of the rat, with identities of 85% and 89% al the nucleotide and amino acid levels, respectively. Most differences are in the cytoplasmic loop domain between the transmembrane segments 3 and 4. We also observed minor differences in the putative ligand binding regions. Pharmacological differences between acetylcholine receptors on outer hair cells of rat and guinea pig have been reported, and the minor structural changes we observe could account for these differences. Reverse transcription-polymerase chain reaction analysis showed a high expression of alpha 9 in the organ of Corti while expression was low or not detected in the spiral ganglion. In situ hybridization histochemistry showed expression of alpha 9 mRNA in both inner and outer hair cells, with much higher expression in outer hair cells than in inner hair cells. In the inner hair cell, silver grains were more abundant over the basal part of the cell than over the apical part. Immunocytochemistry showed a pattern of distribution of the alpha 9 protein similar to that seen for mRNA with in situ hybridization. Immunolabeling was most intense at the bases of both inner and outer hair cells. To determine the effect of hair cell loss on alpha 9 expression, hair cells were destroyed by either systemic or local application of kanamycin. This treatment led to a down regulation of alpha 9 in hair cells; this down regulation appeared to precede hair cell degeneration. In the spiral ganglion, a transient up regulation of alpha 9, as determined by RT-PCR, was seen 4-6 weeks after kanamycin treatment. C1 NIDCD,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NR 45 TC 34 Z9 34 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 1997 VL 112 IS 1-2 BP 95 EP 105 DI 10.1016/S0378-5955(97)00111-1 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA YB181 UT WOS:A1997YB18100009 PM 9367232 ER PT J AU Fricker, G Drewe, J Miller, D AF Fricker, G Drewe, J Miller, D TI Relevance of P-glycoprotein for the transport of cyclosporin A across intestine, liver and kidney SO HEPATOLOGY LA English DT Meeting Abstract C1 BIOPHARM,INST PHARM TECHNOL,HEIDELBERG,GERMANY. UNIV BASEL HOSP,CH-4031 BASEL,SWITZERLAND. NIEHS,RES TRIANGLE PK,NC 27709. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 13 EP 13 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400013 ER PT J AU Ratziu, V Kim, SJ Kim, YS Dang, O Wong, L Friedman, SL AF Ratziu, V Kim, SJ Kim, YS Dang, O Wong, L Friedman, SL TI A key role for ZF9 in hepatic fibrosis via its transcriptional activation of TGF beta 1 and types I and II TGF beta receptor genes in rat stellate cells. SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,LIVER CTR LAB,SAN FRANCISCO,CA 94143. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 227 EP 227 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400226 ER PT J AU Hu, ZY Zhang, ZS Doo, E Furusaka, A Huang, JK Liang, TJ AF Hu, ZY Zhang, ZS Doo, E Furusaka, A Huang, JK Liang, TJ TI Targeting of proteasome subunits by HBX leads to functional alteration of proteasome complex SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD 20892. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 390 EP 390 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400391 ER PT J AU Kadiiska, M Roussyn, I Mason, RP Raleigh, JA Thurman, RG AF Kadiiska, M Roussyn, I Mason, RP Raleigh, JA Thurman, RG TI Oxidative stress occurs in perfused rat liver under hypoxic conditions via mechanisms involving peroxynitrite. SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT RADIAT ONCOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. NIEHS,MOL BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Rusyn, Ivan/S-2426-2016 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 409 EP 409 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400409 ER PT J AU Baumert, TF Vergalla, J Thomson, M Ito, S Wong, DT Greenberg, HB Liang, TJ AF Baumert, TF Vergalla, J Thomson, M Ito, S Wong, DT Greenberg, HB Liang, TJ TI Hepatitis C virus-like particles synthesized in insect cells are highly immunogenic in vivo. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,ELECTRON MICROSCOPY FACIL,BOSTON,MA. STANFORD UNIV,SCH MED,PALO ALTO,CA 94304. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 515 EP 515 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400514 ER PT J AU Yanagi, M Emerson, SU Purcell, RH Bukh, J AF Yanagi, M Emerson, SU Purcell, RH Bukh, J TI Quasispecies of HCV: Analysis of complete ORFs of individual genomes. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID,HEPATITIS VIRUSES SECT,LID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 516 EP 516 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400516 ER PT J AU Kono, H Enomoto, N Connor, HD Bradford, BU Mason, RP Thurman, RG AF Kono, H Enomoto, N Connor, HD Bradford, BU Mason, RP Thurman, RG TI Saturated fat inhibits endotoxin-mediated activation of Kupffer cells in rats treated chronically with ethanol. SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHARMACOL,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 582 EP 582 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400583 ER PT J AU FernandezRodriguez, CM Prada, IR Prieto, J Montuenga, L Penas, J Elssasser, T Medina, J Cuttitta, F AF FernandezRodriguez, CM Prada, IR Prieto, J Montuenga, L Penas, J Elssasser, T Medina, J Cuttitta, F TI Circulating adrenomedullin and peripheral arterial vasodilatation in cirrhosis. SO HEPATOLOGY LA English DT Meeting Abstract C1 HOSP XERAL VIGO,VIGO,SPAIN. UNIV NAVARRA,NAVARRA,SPAIN. NCI,DCS,NIH,ROCKVILLE,MD. USDA ARS,BELTSVILLE,MD. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 619 EP 619 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400618 ER PT J AU Foms, X Bukh, J Purcell, RH Emerson, SU AF Foms, X Bukh, J Purcell, RH Emerson, SU TI Hepatitis C virus and molecular cloning: The risks of producing an artificial quasispecies. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID,HEPATITIS VIRUSES SECT,LID,NIH,BETHESDA,MD 20892. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 678 EP 678 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400679 ER PT J AU Baumert, TF Marrone, A Liang, TJ AF Baumert, TF Marrone, A Liang, TJ TI HBV core promotor mutations associated with fulminant hepatitis result in enhanced core protein expression. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 741 EP 741 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400741 ER PT J AU Thomas, DL Vlahov, D Alter, HJ Hunt, JC Marshall, R Astemborski, J Nelson, KE AF Thomas, DL Vlahov, D Alter, HJ Hunt, JC Marshall, R Astemborski, J Nelson, KE TI Association of antibody to GB Virus C with viral clearance and protection from reinfection. SO HEPATOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIH,BETHESDA,MD 20892. ABBOTT LABS,N CHICAGO,IL 60064. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 775 EP 775 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400774 ER PT J AU Tanaka, E Tacke, M Kobayashi, M Nakatsuji, Y Kiyosawa, K Schmolke, S Engel, AM Hess, G Alter, HJ AF Tanaka, E Tacke, M Kobayashi, M Nakatsuji, Y Kiyosawa, K Schmolke, S Engel, AM Hess, G Alter, HJ TI Past and present infections of hepatitis G virus in high-endemic area for hepatitis C; Comparison with nonendemic area. SO HEPATOLOGY LA English DT Meeting Abstract C1 SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 2,MATSUMOTO,NAGANO 390,JAPAN. BOEHRINGER MANNHEIM GMBH,PENZBERG,GERMANY. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 797 EP 797 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400797 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 High prevalence of hepatitis G virus (HGV) among patients with human immunodeficiency virus (HIV) infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD. NIAID,DEPT CRIT CARE MED,CTR CLIN,NIH,BETHESDA,MD. CHIRON DIAGNOST,EMERYVILLE,CA. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 800 EP 800 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400800 ER PT J AU Sakata, H Rubin, JS Miki, T AF Sakata, H Rubin, JS Miki, T TI Expression of proto-oncogene ect2 in S and G2/M phases of the cell cycle in regenerating mouse liver after partial hepatectomy. SO HEPATOLOGY LA English DT Meeting Abstract C1 ASAHIKAWA MED COLL,DEPT SURG 2,ASAHIKAWA,HOKKAIDO 078,JAPAN. NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 996 EP 996 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87400996 ER PT J AU Lau, DTY Doo, E Ghany, MG Kleiner, DE Park, Y Condreay, L Herion, D Liang, TJ Hoofnagle, JH AF Lau, DTY Doo, E Ghany, MG Kleiner, DE Park, Y Condreay, L Herion, D Liang, TJ Hoofnagle, JH TI Lamivudine for chronic hepatitis B with typical and atypical serology. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 1203 EP 1203 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87401202 ER PT J AU Hsia, CC Nakashima, Y Thorgeirsson, SS Harris, CC Wang, NJ Momosaki, S Tabor, E AF Hsia, CC Nakashima, Y Thorgeirsson, SS Harris, CC Wang, NJ Momosaki, S Tabor, E TI Correlation of immunohistochemical staining and mutations of p53 in human hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD 20014. NCI,NIH,BETHESDA,MD 20892. QIDONG CANC INST,QIDONG,PEOPLES R CHINA. 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1997 VL 26 IS 4 SU S BP 1320 EP 1320 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XY874 UT WOS:A1997XY87401320 ER PT J AU Macville, M Veldman, T PadillaNash, H Wangsa, D OBrien, P Schrock, E Ried, T AF Macville, M Veldman, T PadillaNash, H Wangsa, D OBrien, P Schrock, E Ried, T TI Spectral karyotyping, a 24-colour FISH technique for the identification of chromosomal rearrangements SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; DNA PROBES; CELLS; REGION AB Spectral karyotyping (SKY) is a new fluorescence in situ hybridisation (FISH) technique that refers to the molecular cytogenetic analysis of metaphase preparations by means of spectral microscopy. For SKY of human metaphase chromosomes, 24 chromosome-specific painting probes are used in just one FISH experiment. The probes are labelled by degenerate oligonucleotide-primed PCR using three fluorochromes and two haptens. Each probe is differentially labelled with one, two, three or four fluorescent dyes, resulting in a unique spectral signature for every chromosome. After in situ hybridisation and immunodetection, a spectral image is acquired using a conventional fluorescence light microscope equipped with a custom-designed triple-bandpass filter and the SpectraCube, which is able to retrieve spectral information for every pixel in a digital CCD image. The 24-colour display and chromosome classification are based on the unique emission spectra of the chromosomes. Together with chromosome banding information from an inverted DAPI or a G-banded metaphase, a comprehensive overview of chromosomal aberrations is presented. C1 NIH,GENOME TECHNOL BRANCH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. FU ADAMHA HHS [CRADA 9512-8] NR 23 TC 60 Z9 62 U1 2 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-5564 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD OCT-NOV PY 1997 VL 108 IS 4-5 BP 299 EP 305 DI 10.1007/s004180050169 PG 7 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA YF842 UT WOS:A1997YF84200003 PM 9387921 ER PT J AU Oosterwijk, JC Richard, G vanderWielen, MJR van de Vosse, E Harth, W Sandkuijl, LA Bakker, E vanOmmen, GJB AF Oosterwijk, JC Richard, G vanderWielen, MJR van de Vosse, E Harth, W Sandkuijl, LA Bakker, E vanOmmen, GJB TI Molecular genetic analysis of two families with keratosis follicularis spinulosa decalvans: refinement of gene localization and evidence for genetic heterogeneity SO HUMAN GENETICS LA English DT Article ID DISEASE; REGION; KFSD; MAP; HYP AB X-linked keratosis follicularis spinulosa decalvans (KFSD) is a rare disorder affecting both skin and eyes, In the two extended KFSD families analysed to date, the gene was mapped to Xp22.13-p22.2. By analyzing several new markers in this region, we were able to narrow the candidate region to a 1-Mb interval between DXS7161 and (DXS7593, DXS7105) in the large Dutch pedigree. In addition, we analyzed 23 markers in Xp21.2-p22.2 in a German family with KFSD, Haplotype and recombination analysis positioned the KFSD gene in this family most likely outside the candidate region on Xp22.13-p22.2. This finding is suggestive for genetic heterogeneity: in this pedigree there is either another locus on the X-chromosome, or KFSD is transmitted here as an autosomal dominant trait with variable expression. C1 UNIV LEIDEN HOSP, DEPT CLIN GENET, NL-2300 RC LEIDEN, NETHERLANDS. NIAMSD, SKIN BIOL LAB, NIH, BETHESDA, MD USA. LEIDEN UNIV, DEPT HUMAN GENET, MGC, NL-2300 RA LEIDEN, NETHERLANDS. GEN HOSP, DEPT DERMATOL, ERFURT, GERMANY. RP Oosterwijk, JC (reprint author), UNIV GRONINGEN, DEPT MED GENET, ANTONIUS DEUSINGLAAN 4, NL-9713 AW GRONINGEN, NETHERLANDS. RI van de Vosse, Esther/B-7285-2009; Bakker, Egbert/D-3525-2009; Oosterwijk, Jan C./G-5770-2011 OI van de Vosse, Esther/0000-0001-5199-3426; Bakker, Egbert/0000-0002-2843-7357; NR 27 TC 12 Z9 16 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 1997 VL 100 IS 5-6 BP 520 EP 524 DI 10.1007/s004390050546 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XY681 UT WOS:A1997XY68100007 PM 9341865 ER PT J AU Xue, W Luo, SY Adler, WH Schulze, DH Berman, JE AF Xue, W Luo, SY Adler, WH Schulze, DH Berman, JE TI Immunoglobulin heavy chain junctional diversity in young and aged humans SO HUMAN IMMUNOLOGY LA English DT Article ID GENE SEGMENT UTILIZATION; B-CELL REPERTOIRE; PREFERENTIAL UTILIZATION; PHOSPHORYLCHOLINE-ANTIBODY; BACTERIAL-ANTIGENS; PERIPHERAL-BLOOD; IMMUNE FUNCTION; MICE DIFFER; N-REGIONS; FETAL AB The causes of observed deficiencies in the humoral immune response-in aged humans are unknown. Since a major source of antibody diversity is generated at the V-H-D-J(H) junctional regions of the immunoglobulin heavy chain, we determined whether differences in junctional diversity are manifested with aging. We compared the CDR3 regions of IgM heavy chain transcripts isolated from young adult and aged humans. A PCR assay that measures CDR3 length in the majority of mu-heavy chains showed the same average size and normal range of CDRS length in aged individuals as observed in young adults. To characterize the features of junctional diversity of aged adults in more derail, we determined the CDRS sequences of a subset of the mu-heavy chain repertoire that utilizes members of the V(H)5 family. In general, CDR3 length, D family usage, and J(H) gene usage were similar in aged compared to young adults. Thus, in contrast to dramatic changes in heavy chain junctional diversity associated with fetal to adult development, no major differences were found between young and aged adults. Since the CDR3 repertoire generated in aged individuals appears ro be as diverse as that observed in younger adults, the decline in humoral immunocompetence with aging cannot be attributed to a restriction in heavy chain junctional diversification processes. (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc. C1 Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Dept Immunol & Microbiol, Baltimore, MD 21201 USA. Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Dept Mol Biol & Biophys, Baltimore, MD 21201 USA. Univ Maryland, Mol & Cellular Biol Program, Baltimore, MD 21201 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21222 USA. RP Berman, JE (reprint author), Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Dept Immunol & Microbiol, 725 W Lombard St, Baltimore, MD 21201 USA. FU NIA NIH HHS [AG-10207]; NIAID NIH HHS [AI-32590] NR 50 TC 22 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 1997 VL 57 IS 2 BP 80 EP 92 DI 10.1016/S0198-8859(97)00184-5 PG 13 WC Immunology SC Immunology GA YN916 UT WOS:000071221600002 PM 9438199 ER PT J AU Manasco, PK Umbach, DM Muly, SM Godwin, DC Negro-Vilar, A Culler, MD Underwood, LE AF Manasco, PK Umbach, DM Muly, SM Godwin, DC Negro-Vilar, A Culler, MD Underwood, LE TI Ontogeny of gonadotrophin and inhibin secretion in normal girls through puberty based on overnight serial sampling and a comparison with normal boys SO HUMAN REPRODUCTION LA English DT Article DE females; gonadotrophins; inhibin; males; puberty ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; HUMAN-SERUM; PATTERNS; GROWTH; ASSAYS AB We measured luteinizing hormone (LH) and follicle stimulating hormone (FSH) by immunofluorometric assays and alpha-inhibin by radioimmunoassay in serum sampled every 10 min throughout the night (2100-0500 h) from 44 normal girls. Mean overnight LH values rose log-linearly from a mean of 0.2 IU/l in prepubertal girls to 3.0 IU/l in late pubertal girls. Log(2) mean overnight FSH rose rapidly through early puberty and then remained, constant; mean FSH rose from 1.0 IU/l in prepubertal girls to -2.8 IU/l in Tanner III-V girls. Mean overnight inhibin increased through puberty, rising from 151 ng/l in prepubertal girls to 432 ng/l in fully pubescent girls. Within each of the first three Tanner stages, LH differed similar to 100-fold between the smallest and largest mean concentrations but differed <10-fold within stages IV or V. Such within-pubertal stage variability was less pronounced for FSH, which differed similar to 16-fold among Tanner I subjects and 4-10-fold at later stages, and for inhibin, which varied similar to 4-fold within each Tanner stage. The frequency of LH pulses during overnight sampling increased significantly during puberty, but the frequency of FSH and inhibin pulses remained constant. We compared the results from girls to those from 50 normal boys [Manasco et al. (1995) J. Clin, Endocrinol. Metab., SO, 2046-2052]. At each pubertal stage, girls had approximately the same mean overnight LH values as boys; girls had higher mean overnight FSH, particularly during Tanner stages II-IV; and boys had mean overnight alpha-inhibin immunoreactivity similar to 1.5 times that of girls at each pubertal stage. Still, hormone concentrations for individuals of both sexes intergraded at each pubertal stage. C1 NIEHS, Mol & Integrat Neurosci Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Dept Pediat, Div Pediat Endocrinol, Chapel Hill, NC 27599 USA. RP Manasco, PK (reprint author), Glaxo Wellcome Inc, CNS Clin Res, 5 Moore Dr,Main C3662, Res Triangle Pk, NC 27709 USA. FU NCRR NIH HHS [RROO46] NR 21 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD OCT PY 1997 VL 12 IS 10 BP 2108 EP 2114 DI 10.1093/humrep/12.10.2108 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA YR060 UT WOS:000071453900005 PM 9402263 ER PT J AU Hock, DL Huhn, RD Kemmann, E AF Hock, DL Huhn, RD Kemmann, E TI Leukocytosis in response to exogenous gonadotrophin stimulation SO HUMAN REPRODUCTION LA English DT Article DE cytokines; gonadotrophins; leukocytes; menotrophins; ovary ID OVARIAN HYPERSTIMULATION SYNDROME; INTERLEUKIN-6; LOCALIZATION; PREGNANCY; RECEPTOR AB Leukocytosis may develop in women undergoing ovulation induction. The production of blood leukocytes and their numbers in circulation are regulated by complex interactions involving endogenous haematopoietic cytokines, such as granulocyte-colony stimulating factor (G-CSF), monocyte-colony stimulating factor (M-CSF), and interleukins. The purpose of this prospective study was to explore the presence of leukocytosis in women who receive urinary menotrophins, and to determine whether haematopoietic cytokines are changed in the stimulation process. Controls were volunteers of the same age :range, not taking any medication, who received daily saline injections. Subjects underwent phlebotomy at defined points for determination of complete blood counts, G-CSF, M-CSF, and interleukin-6 concentrations. Baseline white blood cell (WBC) counts were similar in patients and controls. In menotrophin-treated patients the WBC counts rose significantly (4.19 +/- 0.28 to 6.37 +/- 0.71) during the stimulation and peaked in the luteal phase (P = 0.037). In contrast, WBC counts decreased in controls. Other leukocytic lineages were not affected. In treated patients G-CSF concentrations rose significantly (P = 0.028 versus controls), while changes in M-CSF and interleukin-6 were not significant. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet & Gynecol, Div Reprod Endocrinol, New Brunswick, NJ 08901 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Hock, DL (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet & Gynecol, Div Reprod Endocrinol, 303 George St, New Brunswick, NJ 08901 USA. NR 13 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD OCT PY 1997 VL 12 IS 10 BP 2143 EP 2146 DI 10.1093/humrep/12.10.2143 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA YR060 UT WOS:000071453900012 PM 9402270 ER PT J AU Cahill, CM AF Cahill, CM TI 5/22, 5/32, 5/2, 3/24 anti-porcine GH SO HYBRIDOMA LA English DT Article RP Cahill, CM (reprint author), NIA,BIOL CHEM LAB,NIH,4940 EASTERN AVE,R, 4B16,BLDG GRC,BALTIMORE,MD 21224, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD OCT PY 1997 VL 16 IS 5 BP 488 EP 488 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA YE707 UT WOS:A1997YE70700013 ER PT J AU Cahill, CM AF Cahill, CM TI 5/39, 1/197, 3/39, 5/7, 5/17 anti-porcine GH SO HYBRIDOMA LA English DT Article RP Cahill, CM (reprint author), NIA,BIOL CHEM LAB,NIH,4940 EASTERN AVE,RM 4B16,BLDG GRC,BALTIMORE,MD 21224, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD OCT PY 1997 VL 16 IS 5 BP 489 EP 489 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA YE707 UT WOS:A1997YE70700014 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Decreased vasodilator response to isoproterenol during nitric oxide inhibition in humans SO HYPERTENSION LA English DT Article; Proceedings Paper CT 69th Annual Scientific Session of the American-Heart-Association CY NOV 09-16, 1996 CL NEW ORLEANS, LA SP Amer Heart Assoc, Hoechst Marion Roussel Inc, Kansas City DE beta-adrenergic receptors; vasodilation; nitric oxide; endothelium; isoproterenol ID ENDOTHELIUM-DEPENDENT VASODILATION; SIGNAL-TRANSDUCTION PATHWAY; BETA-ADRENERGIC DILATION; ESSENTIAL-HYPERTENSION; CORONARY-ARTERIES; CYCLIC-GMP; VASCULAR RELAXATION; PROTEIN-KINASE; CONSCIOUS DOGS; MODULATION AB The vasodilator effect of beta-adrenergic agonists has traditionally been ascribed solely to a direct effect on vascular smooth muscle. Experimental studies, however, have suggested a role of endothelium-derived nitric oxide (NO) in beta-adrenergic-mediated vasodilation. The purpose of this investigation was to determine whether NO contributes to the vasodilator effect of beta-adrenergic stimulation in humans. We analyzed the forearm blood flow response to increasing doses of isoproterenol (50, 100, and 200 ng/min), a beta-adrenoceptor agonist, during the concomitant infusion of saline or N-G-monomethyl-L-arginine (L-NMMA; 4 mu mol/min), a blocker of NO synthesis, in 23 normal subjects (9 men and 14 women, aged 48+/-7 years). The effect of L-NMMA was also assessed during infusion of sodium nitroprusside (0.8, 1.6, and 3.2 mu g/min), an exogenous NO donor. Drugs were infused into the brachial artery, and forearm blood flow was measured by plethysmography. The vasodilator effect of isoproterenol was significantly blunted during the administration of L-NMMA compared with saline (maximum flow, 7.7+/-4 versus 11.2+/-5 mL . min(-1) . dL(-1), respectively; P<.001). In contrast, the vasodilator response to sodium nitroprusside was not significantly affected by the infusion of L-NMMA (maximum flow, 8.8+/-3.7 mL . min(-1) . dL(-1) during L-NMMA versus 8.3+/-3.2 mL . min(-1) . dL(-1) during saline; P=.25). These findings indicate that NO inhibition blunts the vasodilator effect of beta-adrenergic agonists in the human forearm and suggest that an abnormal response to adrenergic stimulation may occur in conditions associated with impaired NO activity. C1 NHLBI, CARDIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 35 TC 64 Z9 65 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 1997 VL 30 IS 4 BP 918 EP 921 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YC802 UT WOS:A1997YC80200023 PM 9336393 ER PT J AU Cohen, OJ Kinter, A Fauci, AS AF Cohen, OJ Kinter, A Fauci, AS TI Host factors in the pathogenesis of HIV disease SO IMMUNOLOGICAL REVIEWS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; CYTOTOXIC T-LYMPHOCYTES; LONG-TERM SURVIVORS; BLOOD MONONUCLEAR-CELLS; PERSISTENT GENERALIZED LYMPHADENOPATHY; PNEUMOCYSTIS-CARINII PNEUMONIA; SYNCYTIUM-INDUCING PHENOTYPE; INFECTED MONOCYTIC CELLS; CHEMOKINE RECEPTOR GENE AB Host factors play an important role in determining rates of disease progression in human immunodeficiency virus (HIV)-infected individuals. HIV is able to subvert the host immune system by infecting CD4(+) T cells that normally orchestrate immune responses and by inducing the secretion of proinflammatory cytokines that the virus can utilize to its own replicative advantage. The recognition that certain chemokine receptors serve as necessary co-factors for MV entry into its target cells as well as the fact that ligands for these receptors can modulate the efficiency of HN infection has expanded the number and scope of host factors that may impact the pathogenesis of HIV disease. This area of investigation will no doubt yield novel therapeutic strategies for intervention in HIV disease; however, caution is warranted in light of the enormous complexity of the pleiotropic cytokine and chemokine networks and the uncertainty inherent in manipulating these systems. HIV-infected long-term non-progressors represent an excellent model to study potential host factors involved in HN disease pathogenesis. Genetic factors certainly have a major impact on the immune responses mounted by the host. In this regard, a polymorphism in the gene for the HIV co-receptor CC chemokine receptor 5 (CCR5), which serves as a coreceptor for macrophage (M)-tropic strains of HIV, affords a high degree of protection against HIV infection in individuals homozygous for the genetic defect and some degree of protection against disease progression in HIV-infected heterozygotes. HIV-specific immune responses, including cytotoxic T-lymphocyte (CTL) responses and neutralizing antibody responses, also appear to play salutary roles in protecting against disease progression. RP Cohen, OJ (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,10 CTR DR,MSC 1876,ROOM 11B13,BETHESDA,MD 20892, USA. NR 264 TC 140 Z9 145 U1 0 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 1997 VL 159 BP 31 EP 48 DI 10.1111/j.1600-065X.1997.tb01005.x PG 18 WC Immunology SC Immunology GA YH429 UT WOS:A1997YH42900003 PM 9416501 ER PT J AU Alkhatib, G Murata, K Roder, JC AF Alkhatib, G Murata, K Roder, JC TI Cellular distribution of a natural killer cell tumour recognition-related surface antigen in purified human lymphocytes SO IMMUNOLOGY LA English DT Article ID EXPRESS; MECHANISM; RECEPTOR; INVIVO; ALPHA; GAMMA; GENES; BETA AB Natural killer (NK) cells are large granular lymphocytes capable of human leucocyte antigen (HLA) unrestricted killing of tumour cells. A putative NK cell tumour-recognition molecule (NK-TR) was previously isolated and cloned. The predicted primary structure of the NK-TR revealed that the amino terminus of the protein shared high homology with cyclophilin proteins. In this study, we used rabbit antibodies directed against synthetic peptides corresponding to amino acids 476-497 of the NK-TR protein, to examine the expression of the NK-TR antigen in freshly purified human lymphocytes. Cell-surface staining experiments using these peptide antibodies indicated the presence of the NK-TR protein on the surface of human CD3(+) T-cell populations purified from peripheral blood. There were individual donor differences in the levels of cell-surface expression of this antigen ranging from 35 to 90% in T lymphocytes and NK cells purified from different healthy volunteers. The immunoreactivity of our peptide antibodies in immunoprecipitation showed that the NK-TR-related protein expressed in purified T cells is similar to that expressed in NK cells in terms of its electrophoretic mobility. Cell-surface staining experiments using the peptide antibodies revealed that the NK-TR-related protein is more abundantly expressed on the surface of purified T cells compared with NK cells. Northern blot analysis of the mRNA species transcribed in human lymphocytes revealed abundant expression of NK-TR-specific mRNA species in purified T cells. Furthermore, another mRNA species smaller than 7 kb was detected in both NK and T-cell populations of lymphocytes freshly isolated from peripheral blood. Expression at the cell surface of a cyclophilin-homologous protein in purified human T lymphocytes may indicate another function for the reported NK-TR protein, that is, distinct from tumour-cell recognition and cytosis. C1 MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAM DEV & FETAL HLTH,TORONTO,ON M5G 1X5,CANADA. NYU,MED CTR,DEPT MED & MOL PARASITOL,NEW YORK,NY 10016. RP Alkhatib, G (reprint author), NIAID,VIRAL DIS LAB,NIH,9000 ROCKVILLE PK,BLDG 4,RM 236,BETHESDA,MD 20892, USA. RI Roder, John/G-6468-2013 NR 21 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD OCT PY 1997 VL 92 IS 2 BP 173 EP 179 DI 10.1046/j.1365-2567.1997.00332.x PG 7 WC Immunology SC Immunology GA YA903 UT WOS:A1997YA90300003 PM 9415023 ER PT J AU Knepper, B Heuer, I Meyer, TF VanPutten, JPM AF Knepper, B Heuer, I Meyer, TF VanPutten, JPM TI Differential response of human monocytes to Neisseria gonorrhoeae variants expressing pili and opacity proteins SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEINS; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; HUMAN EPITHELIAL-CELLS; HUMAN-NEUTROPHILS; GONOCOCCUS INFECTION; BORDETELLA-PERTUSSIS; VIRULENCE PROPERTIES; RESPIRATORY BURST; HUMAN PHAGOCYTES; PHASE VARIATION AB Experiments in vitro suggest that Neisseria gonorrhoeae surface variation plays a key role in gonococcal pathogenesis by providing the appropriate bacterial phenotypes to go through different stages of the infection. Here we report on the effects of phase and antigen variation of two major gonococcal adhesins, pill and opacity (Opal outer membrane proteins, on the interaction of the gonococci with human monocytes. Using a set of recombinants of gonococcus strain MS11 that each express 1 of 11 genetically defined Opa proteins or a defined type of pilus, we found that both Opa proteins and pill promote bacterial phagocytosis by monocytes in the absence of serum and that this feature largely depends on the type of protein that is expressed. One of the Opa proteins (Opa(50)) strongly promoted uptake by monocytes but had little effect on the interaction with polymorphonuclear leukocytes under the conditions employed. Similarly, the phagocytosis-promoting effect of the pill was much more pronounced in monocytes than in neutrophils (4-fold versus 22-fold stimulation of uptake, respectively). Only a subpopulation of both types of phagocytes actively ingested bacteria, as has been observed during natural infections. Measurements of luminol-enhanced chemiluminescence demonstrated that phagocytosis of opaque but not piliated gonococci was accompanied by an increase in oxygen-reactive metabolites. These findings demonstrate that the monocyte response towards gonococci is highly dependent on the bacterial phenotype and differs from the neutrophil response. This diversity in bacterial behavior towards various types of human phagocytic cells underlines the biological impact of gonococcal surface variation and may explain previous contradictory results on this subject. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,NIH,HAMILTON,MT 59840. MAX PLANCK INST BIOL,INFEKT BIOL ABT,D-72076 TUBINGEN,GERMANY. RI Meyer, Thomas F./J-2485-2013; OI Meyer, Thomas F./0000-0002-6120-8679; van Putten, Jos/0000-0002-4126-8172 NR 57 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1997 VL 65 IS 10 BP 4122 EP 4129 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XY522 UT WOS:A1997XY52200022 PM 9317017 ER PT J AU Gordon, VM Benz, R Fujii, K Leppla, SH Tweten, RK AF Gordon, VM Benz, R Fujii, K Leppla, SH Tweten, RK TI Clostridium septicum alpha-toxin is proteolytically activated by furin SO INFECTION AND IMMUNITY LA English DT Article ID BACTERIAL TOXINS; DIPHTHERIA-TOXIN; CELL-SURFACE; EXOTOXIN-A; CLEAVAGE; LOCALIZATION; PROTEASES; CARCINOMA; SITE AB Clostridium septicum alpha-toxin is secreted as an inactive 46,450-Da protoxin. The protoxin is activated by proteolytic cleavage near the C terminus, which eventually causes the release of a 45-amino-acid fragment, Proteoytic activation and loss of the propeptide allow alpha-toxin to oligomerize and form pores on the plasma membrane, which results in colloidal-osmotic lysis, Activation may be accomplished in vitro by cleavage with trypsin at Arg(367) (J, Ballard, Y, Sokolov, W, L, Yuan, B, L, Kagan, and R Ii, Tweten, Mol, Microbiol. 10:627-634, 1993), which is located within the sequence KKRRGKR(367)S. A conspicuous feature of this site is a recognition site (RGKR) for the eukaryotic protease furin, Pro-alpha-toxin (AT(pro)) that was digested with trypsin or recombinant soluble furin yielded the 41,327-Da active form (AT(act)). A mutated alpha-toxin in which the furin consensus site was altered to KKRSGSRS at the cleavage site (AT(SGSR)) was cleaved and activated by trypsin but not by furin, In cytotoxicity assays, wild-type Chinese hamster ovary (CHO) and furin-deficient CHO (FD11) cells were killed by AT(pro) but not by AT(SGSR), Both cell types were killed by AT(SGSR) that was preactivated with trypsin, Propidium iodide uptake assays revealed that FD11 cells were approximately 22% less sensitive to AT(pro) than were CHO cells, AT(pro)-induced cell lysis of FD11 cells, assessed by propidium iodide uptake,,vas partially prevented by leupeptin (5 mM) and completely prevented by antipain (2.5 mM). The inhibition by antipain suggested the presence of cysteine or serine proteases that could also activate AT(pro), These findings demonstrate that furin is involved in the activation of C, septicum alpha-toxin on the cell surface but that alternate eukaryotic proteases can also activate the toxin, Regardless of the activating protease, the furin consensus site appears to be essential for the activation of alpha-toxin on the cell surface. C1 UNIV OKLAHOMA,HLTH SCI CTR,DEPT MICROBIOL & IMMUNOL,OKLAHOMA CITY,OK 73190. NIDR,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [R01 AI032097, AI32097] NR 25 TC 36 Z9 38 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1997 VL 65 IS 10 BP 4130 EP 4134 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XY522 UT WOS:A1997XY52200023 PM 9317018 ER PT J AU Wolfner, MF Harada, HA Bertram, MJ Stelick, TJ Kraus, KW Kalb, JM Lung, YO Neubaum, DM Park, M Tram, U AF Wolfner, MF Harada, HA Bertram, MJ Stelick, TJ Kraus, KW Kalb, JM Lung, YO Neubaum, DM Park, M Tram, U TI New genes for male accessory gland proteins in Drosophila melanogaster SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Drosophila; reproduction; accessory gland; paragonia; peptide; glycoprotein; hormone; secretion; seminal fluid; toxin protease inhibitor ID SPIDER PHONEUTRIA-NIGRIVENTER; SEMINAL FLUID PROTEIN; SERPIN SUPERFAMILY; CONSENSUS SEQUENCE; PEPTIDE; FEMALE; INHIBITORS; SITES; EXPRESSION; VENOM AB The accessory gland of male insects produces components of the seminal fluid that alter the behavior, physiology and life span of the mated female, and contribute to her efficient storage and utilization of sperm. As a step towards understanding how this occurs, we have isolated genes encoding 12 previously unreported accessory gland-specific mRNAs from the fruit fly Drosophila melanogaster. We report here the restriction maps of the new genes, the chromosome positions - which are all autosomal - of the 11 non-repetitive genes, their expression patterns, and the sequences of the accessory gland proteins (Acps) encoded by nine of the genes. Eight of the proteins predicted from these sequences begin with putative secretion signals. Following their signal sequences, three of the predicted molecules are peptides and the other five are larger polypeptides with characteristics of cleavable prohormones. The ninth molecule, which has an N-terminal hydrophobic region but no consensus signal peptide cleavage site, is predicted to be a 716 amino acid glycoprotein. Of the nine proteins, two have intriguing similarities to sequences in protein databases. Acp76A is a 388 amino acid pro-protein which contains a signature sequence for the serpin class of protease inhibitors. The 115 amino acid Acp62F has a 28 amino acid region of high sequence similarity to a neurotoxin of the Brazilian armed spider Phoneutria nigriventer. Models are discussed in which Acp76A plays a role in the observed regulation of Acp proteolysis and/or in the coagulation of seminal fluid to form a mating plug, and in which Acp62F contributes to the reported toxicity of Drosophila seminal fluid. (C) 1997 Elsevier Science Ltd. All rights reserved. C1 Cornell Univ, Genet & Dev Sect, Ithaca, NY 14853 USA. Luther Coll, Dept Biol, Decorah, IA USA. Baylor Univ, Sch Med, Dept Cell Biol, Houston, TX 77030 USA. Univ Calgary, Dept Med Biochem, Calgary, AB, Canada. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wolfner, MF (reprint author), Cornell Univ, Genet & Dev Sect, Ithaca, NY 14853 USA. EM mfw5@cornell.edu RI Bertram, Michael/F-7501-2010; OI Bertram, Michael/0000-0002-1517-4025 NR 65 TC 91 Z9 103 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD OCT PY 1997 VL 27 IS 10 BP 825 EP 834 DI 10.1016/S0965-1748(97)00056-8 PG 10 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA YV176 UT WOS:000071797000003 PM 9474779 ER PT J AU Olumide, YM Dada, AJ Sogbanmu, IB Aruna, GA AF Olumide, YM Dada, AJ Sogbanmu, IB Aruna, GA TI Seroprevalence study of HIV-I, HIV-II and HTLV-I among patients at the Dermato-venereology clinic of the Lagos University Teaching Hospital SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; T-CELL LEUKEMIA; CUTANEOUS MANIFESTATIONS; AIDS AB Background Seroprevalence studies of HIV-I and HIV-II that have been reported in Nigeria were among commercial sex workers and blood donors. There are no data from STD patients and dermatologic patients. Methods A seroprevalence study of HIV-I, HIV-II and HTLV-I was prospectively conducted among STD clinic attendees and among patients with dermatoses which have been linked with HIV disease. The studies were done in 1992 and 1994. Results Some patients had more than one seropositive type. In 1992, the percentages of seropositive results to HIV-I, HIV-II and HTLV-I were 31, 19 and 50, respectively, and in 1994 the percentages of HIV-I and HTLV-I were 65 and 35, respectively. Conclusions Patients should be routinely screened for HTLV-I, in addition to HIV-I and HIV-II, among blood donors and also neurology clinic attendees in Nigeria. They should also be screened for retroviral infections when they present with dermatoses clinically suggestive of papular urticaria, onchodermatitis, or papulonecrotic tuberculids. C1 NIH,BETHESDA,MD 20892. RP Olumide, YM (reprint author), UNIV LAGOS,TEACHING HOSP,DEPT MED,PMB 12003,LAGOS,NIGERIA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD OCT PY 1997 VL 36 IS 10 BP 741 EP 744 DI 10.1046/j.1365-4362.1997.00338.x PG 4 WC Dermatology SC Dermatology GA YE850 UT WOS:A1997YE85000005 PM 9372347 ER PT J AU Steyn, K Steyn, M Swanepoel, AS Jordaan, PCJ Jooste, PL Fourie, JM Rossouw, JE AF Steyn, K Steyn, M Swanepoel, AS Jordaan, PCJ Jooste, PL Fourie, JM Rossouw, JE TI Twelve-year results of the Coronary Risk Factor Study (CORIS) SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE coronary risk factors; high-intensity intervention; low-intensity intervention; South Africa ID HEART-DISEASE; FOLLOW-UP; INTERVENTION; PREVENTION; PROGRAM; PROJECT; TRIAL; CHOLESTEROL; POPULATIONS AB Background. After 4 years a coronary heart disease risk factor intervention programme produced equally large and significantly reduced risk profiles in two intervention towns compared with a control town. intervention effects through community participation were assessed after cessation of the active intervention programme. The impact of secular trends was assessed in the control town and in two previously unstudied towns. Methods. Grass-sectional surveys were done in a random sample of 1620 participants aged 15-64 years in the three original towns 12 years after the initial quasi-experimental study. Two years later 327 subjects, aged 35-44 years, were studied in the original control town and in two non-intervention towns. Risk factor knowledge, smoking and medical histories were determined by questionnaire. Blood pressure, anthropometry and blood lipids were recorded. Data were compared across towns, and with previous surveys. Results. At 12 years the low intensity intervention town maintained a significantly better risk factor profile than the control town, while the high intensity intervention town now matched the control town. No differences in risk factor profiles were found between the control town and the two new towns. Deaths from coronary heart disease and strokes showed a downward trend in the study area. Conclusions. Outcome suggests large ongoing secular trends during the study could have overtaken the intervention effects in the high intensity town, but not in the low intensity intervention town, which showed an advantage over the control town. These results support the effectiveness of media-based, long term health promotion strategies to reduce cardiovascular disease risk profiles. C1 HUMAN SCI RES COUNCIL,GRP SOCIAL DYNAM,PRETORIA,SOUTH AFRICA. DEPT NATL HLTH SERV & POPULAT DEV,PRETORIA,SOUTH AFRICA. MRC,NATL RES PROGRAM NUTR INTERVENT,PAROWVALLEI,SOUTH AFRICA. NIH,OFF DIS PREVENT,BETHESDA,MD 20892. RP Steyn, K (reprint author), S AFRICAN MRC,CHRON DIS LIFESTYLE PROGRAM,POB 19070,ZA-7505 TYGERBERG,SOUTH AFRICA. NR 25 TC 24 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 1997 VL 26 IS 5 BP 964 EP 971 DI 10.1093/ije/26.5.964 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YH707 UT WOS:A1997YH70700007 PM 9363516 ER PT J AU Sinha, BK Song, KM AF Sinha, BK Song, KM TI Role of ras oncogene in adriamycin resistance in human prostate tumor cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE oncogenes; apoptosis; chemoresistance; prostate tumors ID C-MYC; FREE-RADICALS; INDUCED APOPTOSIS; ANTICANCER DRUGS; CANCER-CELLS; BCL-2; EXPRESSION; GENE; OVEREXPRESSION; SUSCEPTIBILITY AB We have previously isolated a drug-resistant, [PC3(R)], variant of human prostate PC3 cell line, which showed significant resistance (>10-fold) to adriamycin. No known mechanisms of drug resistance were found; however, resistant cells expressed more bcl2, c-myc, and ms oncogenes compared to the sensitive cells. In this study, we found that buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl-cysteine synthetase, decreased glutathione levels by 80-90% in both cell lines. BSO treatment down-modulated Ras protein only in PC3(R) cells and caused a 4-fold sensitization of PC3(R) cells to adriamycin without affecting PC3(W) cells. Farnesol treatment also inhibited expression of Ras protein and concomitantly reversed adriamycin resistance in PC3(R) cells, indicating that altered levels of ras expression plays an important role in drug resistance in PC3(R) cells. RP Sinha, BK (reprint author), NCI,DEPT DEV THERAPEUT,MED BRANCH,DIV CLIN SCI,NIH,BLDG 10,ROOM 6N-119,BETHESDA,MD 20892, USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1997 VL 11 IS 4 BP 819 EP 823 PG 5 WC Oncology SC Oncology GA XX586 UT WOS:A1997XX58600022 PM 21528280 ER PT J AU French, FE Whitcomb, RF Tully, JG Carle, P Bove, JM Henegar, RB Adams, JR Gasparich, GE Williamson, DL AF French, FE Whitcomb, RF Tully, JG Carle, P Bove, JM Henegar, RB Adams, JR Gasparich, GE Williamson, DL TI Spiroplasma lineolae sp. nov., from the horsefly Tabanus lineola (Diptera: Tabanidae) SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CLASS MOLLICUTES; GENUS SPIROPLASMA; CLASSIFICATION AB Spiroplasma strain TALS-2(T) from the viscera of the striped horsefly, Tabanus lineola, collected in Georgia was serologically distinct from other Spiroplasma species, groups, putative groups, and subgoups. Light and electron microscopy of cells of strain TALS-2(T) revealed helical motile cells surrounded only by a single cytoplasmic membrane, The organism grew in M1D and SP-4 liquid media, Growth also occurred in 1% serum fraction medium and in conventional horse serum medium, Growth in liquid media was serum dependent. The strain passed through 220-nm filter poles, but was retained in filters with 100-nm pores. The optimum temperature for growth was 30 degrees C. Multiplication occurred at temperatures from 20 to 37 degrees C, with a doubling time at the optimum temperature of 5.6 h in M1D broth, Strain TALS-2(T) catabolized glucose but hydrolyzed neither arginine nor urea. The guanine-plus-cytosine content of the DNA was 25 +/- 1 mol%. The genome size was 1,390 kbp. Six isolates serologically similar to strain TAS-2(T) were obtained from the same host in coastal Georgia. Three strains closely related to strain TALS-2(T) were isolated from the horsefly Poeciloderas quadripunctatus in Costa Rica, Strain TALS-2(T) (= ATCC 51749), a representative of group XXVII, is designated the type strain of a new species, Spiroplasma lineolae (Mollicutes: Entomoplasmatales). C1 GEORGIA SO UNIV,INST ARTHROPODOL & PARASITOL,STATESBORO,GA 30460. USDA,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. NIAID,MYCOPLASMA SECT,MOL MICROBIOL LAB,FREDERICK CANC RES FACIL,FREDERICK,MD 21702. INRA,BIOL CELLULAIRE & MOL LAB,F-33833 VILLENAVE DORNON,FRANCE. SUNY STONY BROOK,DEPT ANAT SCI,STONY BROOK,NY 11794. USDA,VEGETABLE LAB,BELTSVILLE,MD 20705. RP French, FE (reprint author), GEORGIA SO UNIV,DEPT BIOL,STATESBORO,GA 30460, USA. NR 32 TC 7 Z9 8 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1997 VL 47 IS 4 BP 1078 EP 1081 PG 4 WC Microbiology SC Microbiology GA YB183 UT WOS:A1997YB18300023 PM 9336909 ER PT J AU Rao, PV Robison, WG Bettelheim, F Lin, LR Reddy, VN Zigler, JS AF Rao, PV Robison, WG Bettelheim, F Lin, LR Reddy, VN Zigler, JS TI Role of small GTP-binding proteins in lovastatin-induced cataracts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE 3-hydroxy-3-methylglutaryl CoA reductase; isoprenylation; lens; lovastatin; small GTP-binding proteins ID LENS EPITHELIAL-CELLS; COA REDUCTASE INHIBITORS; ACTIN STRESS FIBERS; CHOLESTEROL CONTENT; GROWTH-FACTORS; ORGAN-CULTURE; OCULAR LENS; RHO-FAMILY; RAT LENS; DIFFERENTIATION AB Purpose. To investigate the biochemical mechanisms involved in the cataract induced by lovastatin, a commonly used cholesterol-lowering agent. Methods. The effects of lovastatin on lens transparency and on lens epithelial cell proliferation and structure have been investigated using organ-cultured rat lenses and cultured epithelial cells from human and rabbit lenses, respectively. Lens histologic and morphologic changes were recorded microscopically. Small GTP-binding protein profiles were determined by [alpha-P-32] GTP overlay assays. Results. Rat lenses organ cultured for 7 days with lovastatin, a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, developed frank subcapsular opacity. Lens epithelial cells (both human and rabbit) demonstrated extensive morphologic changes and inhibition of proliferation when treated with lovastatin. Histologic sections of lovastatin-treated lenses showed partial to complete degeneration of the central epithelium, distortion of elongating epithelial cells, and extensive vacuole formation in the equatorial regions of the cortex. Supplementation of the medium with DL-mevalonic acid (a precursor of isoprenoids whose synthesis is inhibited by lovastatin) prevented the lovastatin-induced changes in whole lenses or in lens epithelial cell cultures, whereas supplementation with cholesterol had no such effect. GTP-binding proteins accumulated in the soluble fi-actions of lovastatin-treated lens epithelial cells. This was consistent with a blockade in isoprenylation preventing normal association with membranes. Conclusions. The findings suggest that impairment of the function of small GTP-binding proteins, due to a lovastatin-induced blockade in their isoprenylation, affects lens cell structure and proliferation in tissue culture and induces lens opacity in organ culture. These findings are consistent with the proposed roles of small GTP-binding proteins as molecular switches that regulate fundamental cellular processes, including growth, differentiation, and maintenance of cell structure. C1 OAKLAND UNIV,EYE RES INST,ROCHESTER,MI. RP Rao, PV (reprint author), NEI,LAB MECHANISMS OCULAR DIS,NIH,6 CTR DR,MSC 2735,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY 05230] NR 45 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 1997 VL 38 IS 11 BP 2313 EP 2321 PG 9 WC Ophthalmology SC Ophthalmology GA YC228 UT WOS:A1997YC22800016 PM 9344354 ER PT J AU Hecht, FM Wheat, J Korzun, AH Hafner, R Skahan, KJ Larsen, R Limjoco, MT Simpson, M Schneider, D Keefer, MC Clark, R Lai, KK Jacobson, JM Squires, K Bartlett, JA Powderly, W AF Hecht, FM Wheat, J Korzun, AH Hafner, R Skahan, KJ Larsen, R Limjoco, MT Simpson, M Schneider, D Keefer, MC Clark, R Lai, KK Jacobson, JM Squires, K Bartlett, JA Powderly, W TI Itraconazole maintenance treatment for histoplasmosis in AIDS: A prospective, multicenter trial SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE histoplasmosis; AIDS; itraconazole; clinical trial ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AMPHOTERICIN-B THERAPY; CAPSULATUM ANTIGEN; HEPATIC-INJURY; DIAGNOSIS; RELAPSE; GRISEOFULVIN; FLUCONAZOLE; PREVENTION; SERUM AB Purpose: To study the efficacy and safety of maintenance treatment with itraconazole for disseminated histoplasmosis in patients with AIDS. Patients and Methods: This was a prospective, multicenter, open-label study conducted at university-based hospitals participating in the AIDS Clinical Trial Group (ACTG). Forty-six AIDS patients with mild to moderate disseminated histoplasmosis who had successfully completed 12 weeks of induction treatment with itraconazole were treated with itraconazole, 200 mg once daily (42 patients) or 400 mg once daily (4 patients). Patients were followed at monthly intervals with clinical and laboratory assessment for relapse or toxicity. Primary outcome measures were relapse of histoplasmosis and survival. Secondary outcome measures included drug-limiting toxicity and changes in serum and urine Histoplasma polysaccharide antigen (HPA) levels. Results: Two patients relapsed during a median follow-up period of 87 weeks. The 1-year relapse-free rate was estimated to be 95.3% (95% CI, 85.3%-99.7%). One relapse may have been related to poor adherence to treatment and the second to concurrent administration of rifampin. From the start of maintenance treatment, the estimated 1-year survival rate was 73.0% (95% CI, 67.5%-77.9%). Five patients discontinued treatment because of suspected drug toxicity, three of whom had possible or probable hepatotoxicity. Median serum and urine HPA levels declined significantly during treatment. The only patient in whom antigen levels rose >2 U developed clinical relapse 1 week later; antigen levels were unavailable in the other relapsing patient. Conclusions: Itraconazole, 200 mg daily, is effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. It is generally well tolerated, but clinicians should be alert for drug interactions and possible hepatotoxicity. C1 ALBERT EINSTEIN COLL MED,BRONX,NY 10467. INDIANA UNIV,INDIANAPOLIS,IN 46204. ROUDEBUSH DEPT VET AFFAIRS MED CTR,INDIANAPOLIS,IN. AIDS CLIN TRIALS GRP,STAT & DATA ANAL CTR,BOSTON,MA. NIAID,DIV AIDS,ROCKVILLE,MD. UNIV CINCINNATI,CINCINNATI,OH. UNIV SO CALIF,LOS ANGELES,CA. UNIV MINNESOTA,MINNEAPOLIS,MN. FRONTIER SCI TECH & RES FDN,AMHERST,NY. UNIV ROCHESTER,ROCHESTER,NY. TULANE UNIV,NEW ORLEANS,LA 70118. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. MT SINAI SCH MED,NEW YORK,NY. CORNELL UNIV,NEW YORK,NY. DUKE UNIV,DURHAM,NC. WASHINGTON UNIV,ST LOUIS,MO. NR 26 TC 32 Z9 38 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1997 VL 16 IS 2 BP 100 EP 107 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YE048 UT WOS:A1997YE04800005 PM 9358104 ER PT J AU Rantanen, T Heikkinen, E AF Rantanen, T Heikkinen, E TI Preservation of muscle strength with maintenance of habitual physical activity from age 80 to 85 years SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Meeting Abstract C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,BETHESDA,MD 20892. UNIV JYVASKYLA,DEPT HLTH SCI,JYVASKYLA,FINLAND. UNIV JYVASKYLA,FINNISH CTR INTERDISCIPLINARY GERONTOL,JYVASKYLA,FINLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD OCT PY 1997 VL 5 IS 4 BP 385 EP 385 PG 1 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA XY033 UT WOS:A1997XY03300042 ER PT J AU Vliagoftis, H Worobec, AS Metcalfe, DD AF Vliagoftis, H Worobec, AS Metcalfe, DD TI The protooncogene c-kit and c-kit ligand in human disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID CONSTITUTIVELY ACTIVATING MUTATIONS; RECEPTOR TYROSINE KINASE; HUMAN MAST-CELL; PERIPHERAL-BLOOD; MASTOCYTOSIS; GROWTH RP Vliagoftis, H (reprint author), NIAID,ALLERG DIS LAB,NIH,BLDG 10,RM 11C205,10 CTR DR MSC 1881,BETHESDA,MD 20892, USA. RI Vliagoftis, Harissios/C-6480-2013 NR 11 TC 93 Z9 97 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 1997 VL 100 IS 4 BP 435 EP 440 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA YA529 UT WOS:A1997YA52900001 PM 9338533 ER PT J AU Cone, EJ Oyler, J Darwin, WD AF Cone, EJ Oyler, J Darwin, WD TI Cocaine disposition in saliva following intravenous, intranasal, and smoked administration SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID MASS-SPECTROMETRY; CHROMATOGRAPHY; COCAETHYLENE; PLASMA; DRUGS; BLOOD RP Cone, EJ (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 16 TC 50 Z9 51 U1 0 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 1997 VL 21 IS 6 BP 465 EP 475 PG 11 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA XZ141 UT WOS:A1997XZ14100010 PM 9323527 ER PT J AU Kapteyn, JC Ram, AFJ Groos, EM Kollar, R Montijn, RC VandenEnde, H Llobell, A Cabib, E Klis, FM AF Kapteyn, JC Ram, AFJ Groos, EM Kollar, R Montijn, RC VandenEnde, H Llobell, A Cabib, E Klis, FM TI Altered extent of cross-linking of beta 1,6-glucosylated mannoproteins to chitin in Saccharomyces cerevisiae mutants with reduced cell wall beta 1,3-glucan content SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ALKALI-SOLUBLE GLUCAN; GLYCOSYL-PHOSPHATIDYLINOSITOL; CANDIDA-ALBICANS; ALPHA-AGGLUTININ; PROTEIN-KINASE; YEAST; IDENTIFICATION; PATHWAY; GLUCOMANNOPROTEINS; STAUROSPORINE AB The yeast cell wall contains beta 1,3-glucanase-extractable and beta 1,3-glucanase-resistant mannoproteins. The beta 1,3-glucanase-extractable proteins are retained in the cell wall by attachment to a beta 1,6-glucan moiety, which in its turn is linked to beta 1,3-glutan (J. C. Kapteyn, R C. Montijn, E. Vink, J. De La Cruz, A. Llobell, J. E. Douwes, H. Shimoi, P. N. Lipke, and F. M. Klis, Glycobiology 6:337-345, 1996). The pl,3-glucanase-resistant protein fraction could be largely released by exochitinase treatment and contained the same set of beta 1,6-glucosylated proteins, including Cwp1p, as the beta 1,3-glucanase-extractable fraction. Chitin was linked to the proteins in the beta 1,3-glucanase-resistant fraction through a beta 1,6-glucan moiety. In wild-type cell walls, the beta 1,3-glucanase-resistant protein fraction represented only 1 to 2% of the covalently linked cell wall proteins, ,whereas in cell walls of fks1 and gas1 deletion strains, which contain much less beta 1,3-glucan but more chitin, beta 1,3-glucanase-resistant proteins represented about 40% of the total. We propose that the increased crosslinking of cell wall proteins via beta 1,6-glucan to chitin represents a cell mall repair mechanism in yeast, which is activated in response to cell wall weakening. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. UNIV SEVILLA,CSIC,INST BIOQUIM VEGETAL & FOTOSINTESIS,E-41080 SEVILLE,SPAIN. RP Kapteyn, JC (reprint author), UNIV AMSTERDAM,CTR FUNGAL CELL WALL RES,IMCB,BIOCTR,KRUISLAAN 318,NL-1098 SM AMSTERDAM,NETHERLANDS. RI Klis, Frans/B-9085-2008; OI Klis, Frans/0000-0003-0079-9492; Llobell Gonzalez, Antonio/0000-0002-6605-9027 NR 49 TC 116 Z9 119 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1997 VL 179 IS 20 BP 6279 EP 6284 PG 6 WC Microbiology SC Microbiology GA YA937 UT WOS:A1997YA93700009 PM 9335273 ER PT J AU Bax, A Tjandra, N AF Bax, A Tjandra, N TI High-resolution heteronuclear NMR of human ubiquitin in an aqueous liquid crystalline medium SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE alignment; bicelle; dipolar coupling; Lipid; liquid crystal; N-15 relaxation ID PROTEINS; RELAXATION; MEMBRANES AB A mixture of dihexanoyl phosphatidylcholine and dimyristoyl phosphatidylcholine in water forms disc-shaped particles, often referred to as bicelles [Sanders and Schwonek (1992) Biochemistry, 31, 8898-8905]. These adopt an ordered, liquid crystalline phase, which can be maintained at very low concentrations of the bicelles (down to 3% w/v). At this concentration the spacing between individual bicelles, on average, exceeds 300 Angstrom. The bicelles are shown to have a negligible effect on the rotational diffusion of ubiquitin as judged by the N-15 T-1 rho values of the backbone amides relative to those in isotropic aqueous solution. The protein exhibits a residual degree of alignment which is proportional to the bicelle concentration, and approximately collinear with ubiquitin's rotational diffusion tenser. The degree of alignment obtained offers unique opportunities for studying the protein's structure and dynamics. C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Bax, A (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 2,BETHESDA,MD 20892, USA. NR 22 TC 195 Z9 196 U1 1 U2 10 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD OCT PY 1997 VL 10 IS 3 BP 289 EP 292 DI 10.1023/A:1018308717741 PG 4 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA YG934 UT WOS:A1997YG93400010 PM 9390407 ER PT J AU Wu, AJ Chen, ZJ Kan, EC Baum, BJ AF Wu, AJ Chen, ZJ Kan, EC Baum, BJ TI Interferon-gamma-induced JAK2 and STAT1 signalling in a human salivary gland cell line SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID SJOGRENS-SYNDROME; TARGETED DISRUPTION; EPITHELIAL-CELLS; EXPRESSION; RECEPTOR; PROTEIN; STIMULATION; ACTIVATION; INDUCTION; PATHWAYS AB We have used a human salivary gland cell line (HSG) as a possible in vitro model to evaluate the effects of IFN-gamma on human salivary gland epithelium (Wu et al., 1994, 1996, 1997). In the present study, we examined the JAK-STAT signal-transduction pathway in IfN-gamma-treated HSG cells. We demonstrate that JAK2 and Stat1 are phosphorylated at tyrosine residues in a time-and concentration-dependent manner following exposure to IFN-gamma. In addition, we show that activation of this signalling pathway is decreased by the addition of a blocking antibody to the IFN-gamma receptor. The same maneuver is also able to reduce by approximately 50-70% the surface expression of two IFN-gamma-induced immunoregulatory molecules: HLA-DR and ICAM-1. These results demonstrate that the JAK2 and Stat1 signalling pathway is active in salivary-derived epithelial cells and may contribute to their immunopathologic destruction. (C) 1997 Wiley-Liss, Inc. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. NR 24 TC 15 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 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 1997 VL 173 IS 1 BP 110 EP 114 DI 10.1002/(SICI)1097-4652(199710)173:1<110::AID-JCP13>3.0.CO;2-M PG 5 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XY745 UT WOS:A1997XY74500013 PM 9326455 ER PT J AU Stoleru, S Nottelmann, ED Belmont, B Ronsaville, D AF Stoleru, S Nottelmann, ED Belmont, B Ronsaville, D TI Sleep problems in children of affectively ill mothers SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE bipolar affective disorder; depression; sleep disorders; adolescence; pre-school children; schoolchildren; maternal depression ID STRUCTURED PSYCHIATRIC INTERVIEW; EARLY-CHILDHOOD; PREPUBERTAL CHILDREN; DEPRESSIVE SYMPTOMS; MATERNAL DEPRESSION; 3-YEAR-OLD CHILDREN; PRESCHOOL-CHILDREN; BEHAVIOR PROBLEMS; MAJOR DEPRESSION; YOUNG-CHILDREN AB The objective of the study was to determine whether the frequency and severity of sleep problems were greater in children of affectively ill mothers than in children of control mothers. Sleep problems were studied in children of mothers with a diagnosis of unipolar (N = 38) and bipolar (N = 23) affective illness and children of mothers with no current or past psychiatric diagnosis (N = 24). Mothers' reports on the Child Behavior Checklist (CBCL) were obtained three times, 4 years apart, on sibling pairs (ages 1.5-3.5 and 5-8 years, respectively, at first assessment). In addition, on the third assessment, the Diagnostic Interview for Children and Adolescents was filled out by mothers and children. In both siblings, sleep problems, as assessed through the CBCL, were more frequent and severe in children of affectively ill mothers. In younger siblings, the persistence of sleep problems was more frequent in children of affectively ill mothers. Co-occurrence of sleep problems among siblings was more frequent in children of affectively ill mothers than in those of control mothers. C1 INSERM,F-94275 LE KREMLIN BICETR,FRANCE. NIMH,BETHESDA,MD 20892. NR 73 TC 56 Z9 56 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD OCT PY 1997 VL 38 IS 7 BP 831 EP 841 DI 10.1111/j.1469-7610.1997.tb01601.x PG 11 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA YE692 UT WOS:A1997YE69200011 PM 9363582 ER PT J AU Lombardi, WJ Sirocco, KY Andreason, PJ George, DT AF Lombardi, WJ Sirocco, KY Andreason, PJ George, DT TI Effects of triazolam and ethanol on proactive interference: Evidence for an impairment in retrieval inhibition SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID TEMPORAL-LOBE LESIONS; EXPLICIT MEMORY; AMNESIC PATIENTS; IMPLICIT MEMORY; HIPPOCAMPAL LTP; ANGIOTENSIN-II; FRONTAL-LOBE; DIAZEPAM; ALCOHOL; DISSOCIATION AB The effects of two memory-impairing drugs, ethanol and triazolam, on proactive interference (PI) in memory were studied. Following ingestion of either one of these drugs or a placebo, subjects studied an A-B list ((e.g., BEE-WASP) of paired associates, followed by an A-C list (e.g., BEE-HONEY) on the interference trial, and a D-E list (e.g., KING-QUEEN) followed by an A-C list on the control trial. A PI effect was found in the data, such that subjects produced fewer correct second list targets on the interference trial than on the control trial. Neither ethanol nor triazolam was found to influence the size of the PI effect. However, both drugs were found to increase B intrusions on the test of the A-C list, to impair subjects' ability to produce more than one studied response for each cue word, and to impair the subjective experience of retrieved memory information. These data suggest that ethanol and triazolam impair an inhibitory process that normally operates as one component of intentional retrieval, playing an important role in the suppression of unwanted information during a memory task. C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. NR 48 TC 6 Z9 6 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD OCT PY 1997 VL 19 IS 5 BP 698 EP 712 DI 10.1080/01688639708403755 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA YJ694 UT WOS:A1997YJ69400007 PM 9408800 ER PT J AU Leibenluft, E Schmidt, PJ Turner, EH Danaceau, MA Ashman, SB Wehr, TA Rubinow, DR AF Leibenluft, E Schmidt, PJ Turner, EH Danaceau, MA Ashman, SB Wehr, TA Rubinow, DR TI Effects of leuprolide-induced hypogonadism and testosterone replacement on sleep, melatonin, and prolactin secretion in men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CENTRAL PRECOCIOUS PUBERTY; PLASMA MELATONIN; HYPOGONADOTROPIC HYPOGONADISM; CIRCADIAN-RHYTHM; DELAYED PUBERTY; SERUM MELATONIN; WOMEN; ESTROGEN; AMPLIFICATION; AMENORRHEA AB The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has received relatively little attention despite the importance of the topic to several clinical syndromes. Pharmacologically induced hypogonadism, with and without gonadal steroid replacement, provides an opportunity to examine these questions within a controlled experimental design. We used leuprolide acetate, with and without testosterone replacement, to study the role of testosterone in the regulation of sleep and of melatonin, PRL, and TSH secretion in men. Results from 10 men revealed significant decreases in 24-h PRL levels and in the percentage and time of stage 4 sleep in the hypogonadal state compared with testosterone replacement. There were no differences in melatonin or TSH secretion or in the timing or duration of sleep between the two hormonal conditions. These results indicate that testosterone has relatively specific and discrete effects on sleep and hormonal rhythms in men. C1 NIMH, CLIN PSYCHOBIOL BRANCH, BETHESDA, MD 20892 USA. NIMH, BEHAV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 38 TC 25 Z9 29 U1 1 U2 1 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 1997 VL 82 IS 10 BP 3203 EP 3207 DI 10.1210/jc.82.10.3203 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YA002 UT WOS:A1997YA00200005 PM 9329339 ER PT J AU Vgontzas, AN Bixler, EO Papanicolaou, DA Kales, A Stratakis, CA VelaBueno, A Gold, PW Chrousos, GP AF Vgontzas, AN Bixler, EO Papanicolaou, DA Kales, A Stratakis, CA VelaBueno, A Gold, PW Chrousos, GP TI Rapid eye movement sleep correlates with the overall activities of the hypothalamic-pituitary-adrenal axis and sympathetic system in healthy humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BIOCHEMICAL MANIFESTATIONS; REM-SLEEP; DEPRESSION; CORTISOL; STRESS; NEUROBIOLOGY AB To assess the association of the overall amount of rapid eye movement (REM sleep and the activities of the hypothalamic-pituitary-adrenal axis and sympathetic system, Re performed polysomnography and measured 24-h urinary free cortisol and catecholamine excretion in 21 healthy adults. After an adaptation night, each subject was recorded in the sleep laboratory for 3 consecutive nights while 24-h urine specimens were collected. Urinary free cortisol, epinephrine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid levels were significantly and positively correlated with the average values of percent REM sleep (P < 0.05). There were no correlations between hormone values and REM latency, other variables of REM distribution, or REM density, an index of phasic activity during REM sleep. The positive correlations between stress system activity and REM sleep are consistent with hormonal and sleep alterations in melancholic depression, a state characterized by increased cortisol and catecholamine secretion. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Vgontzas, AN (reprint author), PENN STATE UNIV, DEPT PSYCHIAT, SLEEP RES & TREATMENT CTR, 500 UNIV DR, HERSHEY, PA 17033 USA. NR 19 TC 22 Z9 23 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1997 VL 82 IS 10 BP 3278 EP 3280 DI 10.1210/jc.82.10.3278 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YA002 UT WOS:A1997YA00200019 PM 9329353 ER PT J AU Silver, K Walston, J Plotnick, L Taylor, SI Kahn, CR Shuldiner, AR AF Silver, K Walston, J Plotnick, L Taylor, SI Kahn, CR Shuldiner, AR TI Molecular scanning of beta-3-adrenergic receptor gene in total congenital lipoatrophic diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RECEPTOR; THERMOGENESIS; MUTATIONS AB Total congenital lipoatrophic diabetes is characterized by absence of subcutaneous adipose tissue, hypertriglyceridemia, and insulin resistance. We hypothesized that mutations in the beta-3-adrenergic receptor (beta 3AR) gene might result in the lipoatrophic phenotype by preventing triglyceride storage in adipocytes; thereby, resulting in secondary insulin resistance. We screened the beta 3AR gene in 7 subjects with total congenital lipoatropic diabetes. We found a heterozygous substitution of a guanine to cytosine at position -153 (G-153C) in the 5'-untranslated region of 3 African-American lipoatrophic siblings and 1 sibling without lipoatrophy but with insulin resistance. To determine whether the base change was related to the lipoatrophic phenotype, we genotyped 69 African-Americans without lipoatrophy and found the G-153C substitution in 2 control subjects (allele frequency = 0.01). No other single-stranded polymorphism variants were found in any of the 7 lipoatrophic subjects. Direct sequencing of both alleles of 1 lipoatrophic subject demonstrated a thymidine insertion at position -300 in both alleles. All lipoatrophic subjects along with 20 African-American control subjects were homozygous for the base insertion, suggesting an error in the published sequence. In conclusion, mutations in the beta 3AR gene do not appear to be involved in the development of congenital total lipoatrophy. C1 JOHNS HOPKINS UNIV, SCH MED, DIV ENDOCRINOL & METAB, BALTIMORE, MD 21287 USA. JOHNS HOPKINS UNIV, SCH MED, DIV GERIATR MED & GERONTOL, BALTIMORE, MD 21287 USA. JOHNS HOPKINS UNIV, SCH MED, DIV PEDIAT ENDOCRINOL, BALTIMORE, MD 21287 USA. NIDDKD, DIABET BRANCH, NIH, BETHESDA, MD 20892 USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [1F32DK09340-01] NR 16 TC 10 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1997 VL 82 IS 10 BP 3395 EP 3398 DI 10.1210/jc.82.10.3395 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YA002 UT WOS:A1997YA00200042 PM 9329375 ER PT J AU Forns, X Tan, D Alter, HJ Purcell, RH Bukh, J AF Forns, X Tan, D Alter, HJ Purcell, RH Bukh, J TI Evaluation of commercially available and in-house reverse transcription PCR assays for detection of hepatitis G virus or GB virus C SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; SEQUENCE; HETEROGENEITY; GENOTYPES; REGION AB Serum samples from 96 Spanish hemodialysis patients, as well as serial dilutions of RNA extracted from a reference strain of hepatitis G virus (HGV), were tested for HGV or GB virus C (GBV-C) RNA, Two different reverse transcription (RT)-PCR-based methods of detection were compared for the ability to detect RNA extracted from the samples: an RT-nested PCR assay with primers derived from the 5' noncoding region (5'NC) or nonstructural region 3 (NS3) sequences and a commercially available RT-PCR assay with primers derived from the 5'NC or NS5A sequences. When RT-nested PCR was performed on 10-fold serial dilutions of RNA from the HGV reference strain, the last positive dilution was 10(-7) to 10(-8). With the commercial RT-PCR assay the last positive dilution was 10(-6) to 10(-7). When equal amounts of RNA extracted from serum samples from 96 hemodialysis patients were tested for HGV or GBV-C RNA, 25 patients (26%) were positive hy the RT-nested PCR. However only 21 (84%) of these 25 positive patients were positive for HGV or GBV-C by the commercial RT-PCR assay. Analysis of the 5'NC and NS3 sequences amplified by RT-nested PCR demonstrated that all hut two positive patients had unique HGV or GBV-C sequences. In summary, RT-nested PCR and a commercially available RT-FCR assay for HGV or GBV-C gave concordant results for 96% of the patients tested. C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP Forns, X (reprint author), NIAID,LID,NIH,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 205,7 CTR DR,MSC 0740,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO-56000] NR 16 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1997 VL 35 IS 10 BP 2698 EP 2702 PG 5 WC Microbiology SC Microbiology GA XX182 UT WOS:A1997XX18200057 PM 9316941 ER PT J AU Tellier, R Bukh, J Emerson, SU Miller, RH Purcell, RH AF Tellier, R Bukh, J Emerson, SU Miller, RH Purcell, RH TI Long PCR and its application to hepatitis viruses: Amplification of hepatitis A, hepatitis B, and hepatitis C virus genomes (vol 34, pg 3086, 1996) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Correction, Addition RP Tellier, R (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1997 VL 35 IS 10 BP 2713 EP 2713 PG 1 WC Microbiology SC Microbiology GA XX182 UT WOS:A1997XX18200063 ER PT J AU Bloch, M Stager, S Braun, A Calis, KA Turcasso, NM Grothe, DR Rubinow, DR AF Bloch, M Stager, S Braun, A Calis, KA Turcasso, NM Grothe, DR Rubinow, DR TI Pimozide-induced depression in men who stutter SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PARKINSONS-DISEASE; CHRONIC-SCHIZOPHRENIA; INDUCED DYSPHORIA; NEUROLEPTICS; HYPOTHESIS; AKATHISIA; SYMPTOMS AB Background: Neuroleptic-related dysphoric reactions are well recognized in the context of psychiatric disorders, especially in association with extrapyramidal side effects. Very few controlled data exist regarding the effects of neuroleptics on the mood of psychiatrically ''normal'' subjects. In this study, the depressogenic effect of the neuroleptic drug pimozide was assessed in men without psychiatric disorders. Method: Eight men with developmental stuttering but no past or present psychiatric illness participated in a double-blind, placebo-controlled study assessing the effect of 6 weeks of pimozide treatment on speech fluency and mood. Results: Four of the seven subjects who were compliant with the treatment developed marked depressive symptoms. No clear association was found between these reactions and pimozide dose, blood level, or degree of neurologic side effects. Symptoms abated soon after drug discontinuation. Conclusion: Pimozide induced significant depressive symptoms in this group of psychiatrically normal men who stutter. Neuroleptic drugs may have a causal effect in the induction of depression in psychiatrically normal subjects, ostensibly independent of dose or severity of neurologic side effects. C1 NIDOCD,NIH,BETHESDA,MD. NIH,CTR CLIN,BETHESDA,MD 20892. RP Bloch, M (reprint author), NIMH,DEPT HLTH & HUMAN SERV,NIH,BLDG 10,ROOM 3N238,10 CTR DR MSC 1276,BETHESDA,MD 20892, USA. OI Stager, Sheila/0000-0002-4294-2114 NR 25 TC 6 Z9 7 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 1997 VL 58 IS 10 BP 433 EP 436 DI 10.4088/JCP.v58n1004 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA YE226 UT WOS:A1997YE22600004 PM 9375593 ER PT J AU Hartman, TJ McCarthy, PR Park, RJ Schuster, E Kushi, LH AF Hartman, TJ McCarthy, PR Park, RJ Schuster, E Kushi, LH TI Results of a community-based low-literacy nutrition education program SO JOURNAL OF COMMUNITY HEALTH LA English DT Article ID LOW-FAT; CHOLESTEROL; PATTERNS; INTERVENTION; HOMEMAKERS; IMPACT; DIETS AB A nutrition intervention focused on low-fat eating pattern changes was conducted among low-literacy participants in a Twin Cities Metropolitan area Expanded Food and Nutrition Education Program (EFNEP), A total of 134 EFNEP participants who participated in the intervention were compared to 70 comparison participants who received EFNEP nutrition education materials. Associations between changes in outcome variables specific to the intervention were evaluated using mixed-model regression analyses, The principal effects seen for this program were related to changes in eating pattern scales. More modest effects were seen in scales related to attitudes of lowfat eating, and although changes in dietary fat intake as measured by 24-hour dietary interviews suggested a positive intervention effect, this did not approach statistical significance. C1 UNIV MINNESOTA,DEPT EDUC,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT NUTR,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,MINNESOTA EXPANDED FOOD & NUTR EDUC PROGRAM,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. MCCARTHY & ASSOCIATES INC,ST PAUL,MN. RP Hartman, TJ (reprint author), NCI,BETHESDA,MD 20892, USA. OI Kushi, Lawrence/0000-0001-9136-1175 FU NHLBI NIH HHS [R01-HL-46781] NR 33 TC 23 Z9 23 U1 2 U2 7 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD OCT PY 1997 VL 22 IS 5 BP 325 EP 341 DI 10.1023/A:1025123519974 PG 17 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YC676 UT WOS:A1997YC67600002 PM 9353681 ER PT J AU Huffman, LC Pedersen, FA DelCarmen, R Bryan, YE AF Huffman, LC Pedersen, FA DelCarmen, R Bryan, YE TI Infant cry acoustics and maternal reactivity to cries: Contributors to mother-infant interaction SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 1997 VL 18 IS 5 BP 361 EP 361 DI 10.1097/00004703-199710000-00031 PG 1 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA YA865 UT WOS:A1997YA86500019 ER PT J AU Slootweg, MC Swolin, D Netelenbos, JC Isaksson, OGP Ohlsson, C AF Slootweg, MC Swolin, D Netelenbos, JC Isaksson, OGP Ohlsson, C TI Estrogen enhances growth hormone receptor expression and growth hormone action in rat osteosarcoma cells and human osteoblast-like cells SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BONE-MINERAL CONTENT; FACTOR-I; BINDING-PROTEIN; LONG-TERM; PARATHYROID-HORMONE; GENE-EXPRESSION; RETINOIC ACID; ESTRADIOL; 17-BETA-ESTRADIOL; GH AB Postmenopausal bone loss is primarily due to estrogen deficiency. Recent clinical observations demonstrate that GH increases bone mass in GH deficient patients. The present study investigates whether estrogen regulates GH action and GH receptor expression in osteoblasts. 17 beta-estradiol or GH added to the culture medium as single substances did not influence rat osteosarcoma cell proliferation nor human osteoblast-like (hOB) cell proliferation. However, together they synergistically induced osteoblast proliferation (rat osteosarcoma cells 160.1 +/- 15.5% of control cells; human osteoblast-like cells 159.6 +/- 5.1% of control cells). 17 beta-estradiol stimulated I-125-GH binding and GH receptor (GHR) mRNA levels in rat osteosarcoma cells. The stimulatory effect of estradiol was time dependent, reaching a peak after 8 h of incubation with 17 beta-estradiol (binding 216.9 +/- 27.8% and mRNA 374.6 +/- 30.8% of control). The finding that estradiol stimulated I-125-GH binding was confirmed in human osteoblast-like cells. In these cells, 17 beta-estradiol (10-(12) hi) increased I-125-GH binding to 203.8 +/- 3.6% of control levels. We conclude that estrogen stimulates GH activity as well as GH binding and GHR mRNA levels in osteoblasts. These findings indicate that estrogen potentiates the effect of GH at the receptor level. C1 SAHLGRENS UNIV HOSP,RES CTR ENDOCRINOL & METAB,S-41345 GOTHENBURG,SWEDEN. FREE UNIV AMSTERDAM HOSP,RES INST ENDOCRINOL REPROD & METAB,NL-1007 MB AMSTERDAM,NETHERLANDS. FREE UNIV AMSTERDAM HOSP,CENT CHEM LAB,NL-1007 MB AMSTERDAM,NETHERLANDS. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. NR 47 TC 40 Z9 42 U1 0 U2 2 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 1997 VL 155 IS 1 BP 159 EP 164 DI 10.1677/joe.0.1550159 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XZ433 UT WOS:A1997XZ43300019 PM 9390018 ER PT J AU Blackwell, KT Vogl, TP Dettmar, HP Brown, MA Barbour, GS Alkon, DL AF Blackwell, KT Vogl, TP Dettmar, HP Brown, MA Barbour, GS Alkon, DL TI Identification of faces obscured by noise: comparison of an artificial neural network with human observers SO JOURNAL OF EXPERIMENTAL & THEORETICAL ARTIFICIAL INTELLIGENCE LA English DT Article DE artificial neural network; face recognition; correlated noise ID UNFAMILIAR FACES; HERMISSENDA-CRASSICORNIS; RECOGNITION; MEMORY; MODEL; MECHANISMS; PERCEPTION; FEATURES; CELLS; UNITS AB Face identification is easily accomplished by humans but is an exceptionally difficult task for machine vision algorithms. This report is the first to directly compare the face identification performance of humans with that of an artificial neural network, Dystal, using digitized images of the faces of eight individuals in an eight-alternative forced-response paradigm. The test images differed from the training images in facial expression, head tilt and rotation, amount and correlation of added noise, and the presence of a stocking mask in some of the images. The images were deliberately not preprocessed by a feature extraction algorithm to avoid confounding the performance of Dystal with the performance of the feature extraction algorithm. While human observers outperform Dystal at low noise levels, at high levels of correlated noise Dystal outperforms human observers, who score just above the chance level. The greater sensitivity to noise exhibited by human observers is attributed to the local feature extraction performed by human observers, but not by Dystal. C1 ENVIRONM RES INST MICHIGAN, ARLINGTON, VA 22209 USA. NINCDS, LAB ADAPT SYST, NIH, BETHESDA, MD 20892 USA. OI Blackwell, Kim/0000-0003-4711-2344 NR 42 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0952-813X J9 J EXP THEOR ARTIF IN JI J. Exp. Theor. Artif. Intell. PD OCT-DEC PY 1997 VL 9 IS 4 BP 491 EP 508 DI 10.1080/095281397147004 PG 18 WC Computer Science, Artificial Intelligence SC Computer Science GA YJ423 UT WOS:A1997YJ42300003 ER PT J AU Stern, MD Pizarro, G Rios, E AF Stern, MD Pizarro, G Rios, E TI Local control model of excitation-contraction coupling in skeletal muscle SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE ion channels; sarcoplasmic reticulum; calcium release; signal transduction ID RETICULUM CALCIUM-RELEASE; CUT TWITCH FIBERS; SARCOPLASMIC-RETICULUM; CA2+ RELEASE; RYANODINE RECEPTOR; CARDIAC-MUSCLE; ELEMENTARY EVENTS; CHARGE MOVEMENT; BINDING SITES; FROG-MUSCLE AB This is a quantitative model of control of Ca2+ release from the sarcoplasmic reticulum in skeletal muscle, based on dual control of release channels (ryanodine receptors), primarily by voltage, secondarily by Ca2+ (Rios, E., and G. Pizarro. 1988. NIPS. 3:223-227). Channels are positioned in a double row array of between 10 and 60 channels, where exactly half face voltage sensors (dihydropyridine receptors) in the transverse (t) tubule membrane (Block, B.A., T. Imagawa, K.P. Campbell, and C. Franzini-Armstrong. 1988. J. Cell Biol. 107:2587-2600). We calculate the flux of Ca2+ release upon different patterns of pulsed t-tubule depolarization by explicit stochastic simulation of the states of all channels in the array. Channels are initially opened by voltage sensors, according to an allosteric prescription (Rios, E., M. Karhanek,J. Ma, A. Gonzalez. 1993. J. Gen. Physiol. 102:449-482). Ca2+ permeating the open channels, diffusing in the junctional gap space, and interacting with fixed and mobile buffers produces defined and changing distributions of Ca2+ concentration. These concentrations interact with activating and inactivating channel sites to determine the propagation of activation and inactivation within the array. The model satisfactorily simulates several whole-cell observations, including kinetics and voltage dependence of release flux, the ''paradox of control,'' whereby Ca2+-activated release remains under voltage control, and, most surprisingly, the ''quantal'' aspects of activation and inactivation (Pizarro, G., N. Shirokova, A. Tsugorka, and E. Rios. 1997. J. Physiol. 501:289-303). Additionally, the model produces discrete events of activation that resemble Ca2+ sparks (Cheng, H., M.B. Cannell, and W.J. Lederer. 1993. Science (Wash. DC). 262:740-744). All these properties result fr om the intersection of stochastic channel properties, control by local Ca2+, and, most importantly, the one dimensional geometry of the array and its mesoscopic scale. Our calculations support the concept that the release lease channels associated with one face of one junctional t-tubule segment, with its voltage sensor, constitute a functional unit, termed the ''couplon.'' This unit is fundamental: the whole cell behavior can be synthesized as that of a set of couplons, rather than a set of independent channels. C1 UNIV REPUBLICA, FAC MED, DEPT BIOFIS, MONTEVIDEO, URUGUAY. RUSH UNIV, SCH MED, DEPT MOL PHYSIOL & BIOPHYS, CHICAGO, IL 60612 USA. RP Stern, MD (reprint author), NIA, CARDIOVASC SCI LAB, CTR GERONTOL RES, NIH, 4940 EASTERN AVE, BALTIMORE, MD 21214 USA. NR 71 TC 149 Z9 151 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD OCT PY 1997 VL 110 IS 4 BP 415 EP 440 DI 10.1085/jgp.110.4.415 PG 26 WC Physiology SC Physiology GA YA244 UT WOS:A1997YA24400008 PM 9379173 ER PT J AU An, P Wei, L Wu, XY Yuhki, N OBrien, SJ Winkler, C AF An, P Wei, L Wu, XY Yuhki, N OBrien, SJ Winkler, C TI Evolutionary analysis of the 5'-terminal region of hepatitis G virus isolated from different regions in China SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID A-E-HEPATITIS; MOLECULAR-CLONING; GBV-C; SEQUENCES; GENOME; ASSOCIATION; PATIENT; PCR AB We have determined the nucleotide sequence of the 5'-terminal region of the hepatitis G virus (HGV) genome in 11 hepatitis patients from three cities in China. Phylogenetic analyses revealed that the Chinese isolates were genetically distinct from previously described West African isolates (type 1) and American, European and East African isolates (type 2), with a mean sequence divergence of approximately 10%. The mean divergence between isolates from Lanzhou, in the northwest of China, and those from Shanghai and Nanjing, on the east coast of China, was 5 % (range 3-7 %). The isolates from Shanghai and Nanjing were closely related to a common strain in Japan, while some of those from Lanzhou were closely related to a southeast Asian type 3 isolate. Thus, the Chinese isolates belong to the type 3 variant of HGV. C1 NCI, FREDERICK CANC RES & DEV CTR, INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,NIH, FREDERICK, MD 21702 USA. NCI, LAB GEN DIVERS, FREDERICK, MD 21702 USA. NR 20 TC 17 Z9 20 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 1997 VL 78 BP 2477 EP 2482 PN 10 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA YA164 UT WOS:A1997YA16400010 PM 9349467 ER PT J AU Watkins, BA Crowley, R Davis, AE Louie, AT Reitz, MS AF Watkins, BA Crowley, R Davis, AE Louie, AT Reitz, MS TI Syncytium formation induced by human immunodeficiency virus type 1 isolates correlates with affinity for CD4 SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID T-CELL LINES; V3 LOOP; HIV TYPE-1; MT-2 CELLS; MONONUCLEAR PHAGOCYTES; SURFACE GLYCOPROTEIN; GP120 GLYCOPROTEIN; ENVELOPE GENE; HTLV-III; TROPISM AB Different strains of human immunodeficiency virus type 1 (HIV-1) show considerable divergence in genetic content and biological properties. One property that has been closely correlated with clinical prognosis is the ability to induce syncytia formation in susceptible cells. This ability had been correlated with the V3 loop sequence of major envelope glycoprotein, gp120, but recent reports have questioned this connection. We investigated the contributions of different regions of the env gene to syncytia induction using chimeric viruses that contain part of the genome of a strain that lacks this ability (HIV-1(Ba-L)) within the genome of a virus that can form syncytia (HIV-1(HXB-2)). When tested in two cell lines susceptible to both parental viruses, as well as in primary cells, these chimeric viruses demonstrated that the ability to induce syncytia formation was determined by regions of env outside the V3 loop, which encompass residues that contribute to the binding of CD4 by gp120. Further investigation failed to show any difference in the expression of gp120 on the cell surface or cell adhesion molecules by cells infected with SI or NSI variants that would explain the observed differences in the ability to form syncytia. Assays of relative affinity for CD4 indicated that gp120 from SI variants showed a significantly higher affinity for CD4 than gp120 from NSI variants. These observations suggest that areas of the HIV-1 env gene contributing to the CD4 binding site may also contribute to the determination of syncytium-inducing (SI) and non-syncytium-inducing (NSI) phenotypes. C1 NCI,DIV BASIC SCI,NIH,BETHESDA,MD 20892. US FDA,MOL VIROL LAB,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. UNIV MARYLAND,INST HUMAN VIROL,BALTIMORE,MD 21201. NR 47 TC 12 Z9 12 U1 0 U2 0 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 1997 VL 78 BP 2513 EP 2522 PN 10 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA YA164 UT WOS:A1997YA16400015 PM 9349472 ER PT J AU Egwuagu, CE Charukamnoetkanok, P Gery, I AF Egwuagu, CE Charukamnoetkanok, P Gery, I TI Thymic expression of autoantigens correlates with resistance to autoimmune disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETINOID-BINDING PROTEIN; MYELIN BASIC-PROTEIN; S-ANTIGEN; T-CELLS; TOLERANCE; UVEITIS; MICE; IRBP; PREVENTION; SEQUENCES AB Experimental autoimmune uveoretinitis (EAU), an animal model for human intraocular inflammation (uveitis), is induced by immunization with retinal proteins such as S-Ag or interphotoreceptor retinoid binding protein, Marked differences exist among different animal species and strains in their susceptibility to EAU induction, but the cause of these differences is not completely clear, Here we show for the first time a correlation between constitutive expression of ocular autoantigens in the thymus (mRNA and protein) and resistance to EAU, This correlation was noted both at the species (mice vs rats or monkeys) and the subspecies (differences among strains) level, The data thus provide a novel mechanistic explanation for the differences in susceptibility to autoimmune diseases, suggesting that resistance to an organ-specific autoimmune disease may be regulated at least in part by capacity to establish central tolerance to the relevant autoantigen. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,NATL INST HLTH RES SCHOLARS PROGRAM,BETHESDA,MD 20814. NR 32 TC 139 Z9 140 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1997 VL 159 IS 7 BP 3109 EP 3112 PG 4 WC Immunology SC Immunology GA XY461 UT WOS:A1997XY46100005 PM 9317106 ER PT J AU Hirunpetcharat, C Tian, JH Kaslow, DC vanRooijen, N Kumar, S Berzofsky, JA Miller, LH Good, MF AF Hirunpetcharat, C Tian, JH Kaslow, DC vanRooijen, N Kumar, S Berzofsky, JA Miller, LH Good, MF TI Complete protective immunity induced in mice by immunization with the 19-kilodalton carboxyl-terminal fragment of the merozoite surface protein-1 (MSP1(19)) of Plasmodium yoelii expressed in Saccharomyces cerevisiae - Correlation of protection with antigen-specific antibody titer, but not with effector CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHABAUDI-ADAMI MALARIA; AOTUS MONKEYS; INDEPENDENT IMMUNITY; RODENT MALARIA; DEFICIENT MICE; LYMPHOCYTES-T; NITRIC-OXIDE; INFECTION; GENE; ELIMINATION AB The 19-kDa carboxyl-terminal fragment of the merozoite surface proiein-1 (MSP1) is a leading malaria vaccine candidate but is unable to induce immunity in all monkeys or all strains of mice, The mechanism of immunity is unclear, although data show that cell-mediated immunity plays a critical role following immunization with the larger mature MSP1 protein, We optimized a vaccine protocol using the MSP1(19) fragment of Plasmodium yoelii expressed in Saccharomyces cerevisiae, such that following exposure of mice to parasites, they remained undetectable in peripheral blood, whereas control animals all died at very high parasitemia within 10 days, We then depleted the vaccinated mice of >99% of CD4(+) a cells by anti-CD4 mAb treatment and could show that infections in most animals remained subpatent following challenge, furthermore, mice in which the gene for the mu-chain of Ig had been disrupted could not be immunized with MSP1(19). Immunity in normal mice did not depend on the presence of an intact spleen nor production of nitric oxide, persisting unabated when >70% of splenic macrophages were depleted, Thus, while effector CD4(+) T cells may contribute to immunity, neither they nor factors associated with a Th1-type cell mediated immune response appeared to play the major role in MSP1(19)-induced protection in normal mice, Furthermore, T cells were not sufficient for immunity in mice lacking B cells, In normal mice, protection correlated with a very high titer of MSP1(19)-specific Abs (>6,400,000), predominantly G1 and G2b, which may function by merozoite neutralization. C1 QUEENSLAND INST MED RES,BRISBANE,QLD 4006,AUSTRALIA. NCI,MOL IMMUNOGENET & VACCINE RES SECT,NIH,BETHESDA,MD. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD. VRIJE UNIV AMSTERDAM,FAC MED,DEPT CELL BIOL & IMMUNOL,AMSTERDAM,NETHERLANDS. NR 34 TC 155 Z9 159 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1997 VL 159 IS 7 BP 3400 EP 3411 PG 12 WC Immunology SC Immunology GA XY461 UT WOS:A1997XY46100038 PM 9317139 ER PT J AU Pollack, M Ohl, CA Golenbock, DT DiPadova, F Wahl, LM Koles, NL Guelde, G Monks, BG AF Pollack, M Ohl, CA Golenbock, DT DiPadova, F Wahl, LM Koles, NL Guelde, G Monks, BG TI Dual effects of LPS antibodies on cellular uptake of LPS and LPS-induced proinflammatory functions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MONOCLONAL-ANTIBODIES; LIPOPOLYSACCHARIDE LPS; HUMAN-MONOCYTES; BACTERIAL LIPOPOLYSACCHARIDE; HUMAN-NEUTROPHILS; FACTOR SECRETION; BINDING-PROTEIN; FACTOR-ALPHA; CD14 AB Human phagocytes recognize bacterial LPS (endotoxin) through membrane CD14 (mCD14), a proinflammatory LPS receptor, This study tested the hypothesis that anti-LPS Abs neutralize endotoxin by blocking cellular uptake through mCD14, Ab-associated changes in the uptake and cellular distribution of FITC-LPS were assessed by flow cytometry and laser scanning confocal microscopy in human CD14-transfected Chinese hamster ovary fibroblasts (CHO-CD14 cells) and human peripheral blood monocytes, LPS core- and O-side chain-specific mAbs inhibited mCD14-mediated LPS uptake by both cell types in the presence of serum, O-side chain-specific mAb concurrently enhanced complement-dependent LPS uptake by monocytes through complement receptor-1 (CR1) and uptake by CHO-CD14 cells involving another heat-labile serum factor(s) and cell-associated recognition molecule(s), Core-specific mAb inhibited mCD14-mediated uptake of homologous and heterologous LPS, while producing less concurrent enhancement of non-mCD14-mediated LPS uptake, The modulation by anti-LPS mAbs of mCD14-mediated LPS uptake was associated with inhibition of LPS-induced nuclear factor-kappa B (NF-kappa B) translocation and TNF-alpha secretion in CHO-CD14 cells and monocytes, respectively, while mAb enhancement of non-mCD14-mediated LPS uptake stimulated these activities, LPS-specific Abs thus mediate anti-inflammatory and proinflammatory functions, respectively, by preventing target cell uptake of LPS through mCD14 and augmenting uptake through CR1 or other cell receptors. C1 MAXWELL FINLAND LAB INFECT DIS, BOSTON, MA 02118 USA. NOVARTIS PHARMA AG, CH-4002 BASEL, SWITZERLAND. NIDA, NIH, BETHESDA, MD 20892 USA. RP Pollack, M (reprint author), UNIFORMED SERV UNIV HLTH SCI, DEPT MED, F EDWARD HEBERT SCH MED, 4301 JONES BRIDGE RD, BETHESDA, MD 20814 USA. RI Monks, Brian/B-8362-2015 OI Monks, Brian/0000-0003-4008-3093 FU NIAID NIH HHS [AI-22706] NR 39 TC 20 Z9 21 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1997 VL 159 IS 7 BP 3519 EP 3530 PG 12 WC Immunology SC Immunology GA XY461 UT WOS:A1997XY46100050 PM 9317151 ER PT J AU Ludviksson, BR Ehrhardt, RO Strober, W AF Ludviksson, BR Ehrhardt, RO Strober, W TI TGF-beta production regulates the development of the 2,4,6-trinitrophenol-conjugated keyhole limpet hemocyanin-induced colonic inflammation in IL-2-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; MYELIN BASIC-PROTEIN; CD4(+) T-CELLS; ORAL TOLERANCE; INTERFERON-GAMMA; TRANSFORMING GROWTH-FACTOR-BETA-1; AUTOIMMUNE ENCEPHALOMYELITIS; INTERLEUKIN-2-DEFICIENT MICE; ULCERATIVE-COLITIS; DOWN-REGULATION AB A severe, Th1-mediated experimental colitis with similarities to inflammatory bowel disease in humans can be induced by a single injection of 2,4,6-trinitrophenol (TNP)-substituted protein plus adjuvant in IL-2(-/-) mice, To determine the early events involved in the pathogenesis of IL-2(-/-) colitis, we compared the function of lamina propria (LP) T cells from IL-2(-/-) and IL-2(+/+) mice subjected to disease-inducing (TNP-conjugated keyhole limpet hemocyanin (TNP-KLH)) and disease-inhibiting (anti-CD3) immunization protocols, We show that LP T cells in TNP-KLH-immunized IL-2(-/-) mice fail to produce TGF-beta early (day 2), whereas LP T cells in TNP-KLH-immunized IL-2(+/+) mice exhibit an approximately eightfold rise in TGF-beta secretion, The critical importance of local TGF-beta production was further substantiated by the following findings, 1) LP T cells from TNP-KLH-immunized IL-2(-/-) mice administered anti-CD3 (i.p.) exhibit a significant rise in TGF-beta production but fail to produce IFN-gamma, and such mice do not develop colitis. 2) TNP-KLH-immunized IL-2(-/-) mice administered anti-CD3 and coadministered anti-TGF-beta mAb again give rise to IFN-gamma-producing LP cells, and such mice develop colitis, 3) TNP-KLH-immunized IL-2(+/+) mice administered anti-TGF-beta mAb exhibit pockets of mononuclear cell infiltrates in the LP. These results indicate that the disposition of IL-2(-/-) mice to develop chronic colonic inflammation is due to a Th1 cell response in the LP that is not appropriately counter-regulated by the production of the suppressor cytokine, TGF-beta. RP Ludviksson, BR (reprint author), NIAID,MUCOSAL IMMUN SECT,CLIN INVEST LAB,NIH,BLDG 10,ROOM 11N238,BETHESDA,MD 20892, USA. OI Ludviksson, Bjorn/0000-0002-6445-148X NR 32 TC 60 Z9 61 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1997 VL 159 IS 7 BP 3622 EP 3628 PG 7 WC Immunology SC Immunology GA XY461 UT WOS:A1997XY46100061 PM 9317162 ER PT J AU Xie, H Zhang, BW Matsumoto, Y Li, Q Notkins, AL Lan, MS AF Xie, H Zhang, BW Matsumoto, Y Li, Q Notkins, AL Lan, MS TI Autoantibodies to IA-2 and IA-2 beta in insulin-dependent diabetes mellitus recognize conformational epitopes - Location of the 37- and 40-kDa fragments determined SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; FIRST-DEGREE RELATIVES; ISLET-CELL ANTIGEN; TRANSMEMBRANE PROTEIN; MOLECULAR-CLONING; TRYPTIC FRAGMENTS; GLUTAMATE-DECARBOXYLASE; AUTOANTIGEN; DISTINCT; IDDM AB IA-2 and IA-2 beta are major autoantigens in insulin-dependent diabetes mellitus (IDDM) and the precursors, respectively, of a 40- and 37-kDa tryptic fragment that reacts with IDDM sera, In the present study, by amino acid sequencing of recombinant IA-2 and IA-2 beta, we determined the tryptic cleavage sites involved in the generation of these fragments, Both cleavage sites are immediately after an arginine residue at position 653 for IA-2 and position 679 for IA-2 beta, The resulting tryptic fragments are 326 and 307 amino acids in length and retain their ability to react with IDDM sera, In contrast to IA-2 and IA-2 beta, other members of the protein tyrosine phosphatase (PTP) family (i.e., RPTP kappa, RPTP mu, NU-3, SHP, and 3CH134) are completely susceptible to digestion by trypsin, Sequence analysis revealed five conserved cysteine residues in IA-2 and IA-2 beta that are not present in other PTPs. Reduction and alkylation of IA-2 and IA-2 beta recombinant proteins resulted in loss of bath resistance to digestion by trypsin and reactivity with autoantibodies in IDDM sera, It is concluded that disulfide bond formation plays a critical role in the maintenance of antigenic structure and that the autoantibodies to IA-2/IA-2 beta in IDDM sera recognize conformational epitopes. C1 NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. NR 35 TC 33 Z9 34 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1997 VL 159 IS 7 BP 3662 EP 3667 PG 6 WC Immunology SC Immunology GA XY461 UT WOS:A1997XY46100066 PM 9317167 ER PT J AU Svare, EI Kjaer, SK Nonnenmacher, B Worm, AM Moi, H Christensen, RB vandenBrule, AJC Walboomers, JMM Meijer, CJLM Hubbert, NL Lowy, DR Schiller, JT AF Svare, EI Kjaer, SK Nonnenmacher, B Worm, AM Moi, H Christensen, RB vandenBrule, AJC Walboomers, JMM Meijer, CJLM Hubbert, NL Lowy, DR Schiller, JT TI Seroreactivity to human papillomavirus type 16 virus-like particles is lower in high-risk men than in high-risk women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; POLYMERASE CHAIN-REACTION; GENITAL WARTS; CANCER; INFECTION; DETERMINANTS; ANTIBODIES; SCRAPES; DNA; GENOTYPES AB Seroreactivity to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) in men attending clinics for sexually transmitted diseases (STDs) in Denmark (n = 219) and Greenland (n = 88) was compared with seroreactivity in women attending the same clinics and was furthermore related to epidemiologic variables and concurrent HPV DNA detection. Risk factors for male seropositivity in Denmark were lifetime number of sex partners, a history of STDs, and sexual preference and in Greenland were ever having had syphilis and years at school. Although men reported significantly more sex partners, the mean seroreactivity was significantly lower in men than in women: 0.50 and 0.75, respectively, in Denmark and 0.53 and 0.86 in Greenland (P = .0001). Male seropositivity was not correlated with concurrent HPV DNA detection, but only 15 Danish and 6 Greenlandic men had HPV-16 DNA. Presence of HPV-16 VLP antibodies appears to be a biomarker for exposure to genital HPVs in men but is less sensitive than in women. C1 RUDOLPH BERGHS HOSP,COPENHAGEN OUTPATIENT VENEREAL CLIN,COPENHAGEN,DENMARK. NIH,CELLULAR ONCOL LAB,BETHESDA,MD 20892. DRONNING INGRIDS HOSP,VENEREAL CLIN,NUUK,GREENLAND. UNIV HOSP VRIJE UNIV,DEPT PATHOL,AMSTERDAM,NETHERLANDS. RP Svare, EI (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,STRANDBOULEVARDEN 49,DK-2100 COPENHAGEN,DENMARK. NR 28 TC 53 Z9 55 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1997 VL 176 IS 4 BP 876 EP 883 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XZ465 UT WOS:A1997XZ46500005 PM 9333144 ER PT J AU Pilgrim, AK Pantaleo, G Cohen, OJ Fink, LM Zhou, JY Zhou, JT Bolognesi, DP Fauci, AS Montefiori, DC AF Pilgrim, AK Pantaleo, G Cohen, OJ Fink, LM Zhou, JY Zhou, JT Bolognesi, DP Fauci, AS Montefiori, DC TI Neutralizing antibody responses to human immunodeficiency virus type 1 in primary infection and long-term-nonprogressive infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID COMPLEMENT-ACTIVATING ANTIBODIES; PRIMARY HIV-1 INFECTION; T-CELL; IMMUNE-RESPONSES; RHESUS-MONKEYS; IN-VIVO; PLASMA; SERA; SEROCONVERSION; PROGRESSION AB The role of neutralizing antibodies in human immunodeficiency virus type 1 (HIV-I) infection is poorly understood and was assessed by evaluating responses at different stages of infection. Undiluted sera from long-term nonprogressors (LTNP) had broad neutralizing antibodies against heterologous primary isolates and were more likely to neutralize the contemporaneous autologous isolate than were sera from short-term nonprogressors and progressors. In primary infection, envelope-specific IgG was detected before the initial decline in plasma viremia, but neutralizing antibodies developed more slowly. Here, neutralizing antibodies against strains SF-2 and MN were sometimes the first to be detected, but titers were low for at least 17 weeks from onset of symptoms. Neutralizing antibodies against the early autologous isolate were detected for 4 patients by 5-40 weeks but were undetectable in 2 additional patients for 27-45 weeks. The results indicate that neutralizing antibody responses are slow to develop during primary infection and are uniquely broad in LTNP. C1 DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. HOP BEAUMONT,LAB AIDS PATHOGENESIS,LAUSANNE,SWITZERLAND. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. RI Pantaleo, Giuseppe/K-6163-2016 FU NIAID NIH HHS [AI-28662, AI-45218] NR 44 TC 264 Z9 269 U1 1 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1997 VL 176 IS 4 BP 924 EP 932 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XZ465 UT WOS:A1997XZ46500011 PM 9333150 ER PT J AU Breman, JG vanderGroen, G Peters, CJ Heymann, DL AF Breman, JG vanderGroen, G Peters, CJ Heymann, DL TI International Colloquium on Ebola Virus Research: Summary report SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID HEMORRHAGIC-FEVER VIRUSES; MARBURG VIRUS; MONKEYS; POPULATIONS; INFECTIONS; FILOVIRUS; ANTIGENS; AFRICA; ZAIRE; LASSA C1 INST TROP MED, DEPT MICROBIOL, B-2000 ANTWERP, BELGIUM. CTR DIS CONTROL & PREVENT, NATL CTR INFECT DIS, ATLANTA, GA USA. WHO, DIV EMERGING & OTHER COMMUNICABLE DIS SURVEILLANC, CH-1211 GENEVA, SWITZERLAND. RP Breman, JG (reprint author), NIH, FOGARTY INT CTR,BLDG 31,ROOM B2C39,31 CTR DR, MSC 2220, BETHESDA, MD 20892 USA. NR 43 TC 7 Z9 7 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1997 VL 176 IS 4 BP 1058 EP 1063 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XZ465 UT WOS:A1997XZ46500028 PM 9333167 ER PT J AU Roden, RBS Lowy, DR Schiller, JT AF Roden, RBS Lowy, DR Schiller, JT TI Papillomavirus is resistant to desiccation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XV International Papillomavirus Workshop CY DEC, 1996 CL BRISBANE, AUSTRALIA ID VIRUS-LIKE PARTICLES; INFECTIONS; FOMITES AB There is strong epidemiologic evidence for sexual transmission of high-risk genital human papillomavirus (HPV) types. However, it is unclear if infection may also be transmitted indirectly via fomites. To assess this possibility, the in vitro infectivity after desiccation was compared for pseudotype HPV-16 virions, a model for high-risk type genital HPV, and bovine papillomavirus type 1 (BPV-1), a papillomavirus known to be transmitted via fomites. The 2 viruses had similar resistance to desiccation in cell extracts, retaining similar to 100%, 50%, and 30% of infectivity when dehydrated for 1, 3, and 7 days, respectively, at room temperature. Pseudotype HPV-16 and BPV in cell extracts were completely inactivated by autoclave treatment and susceptible to 70% ethanol but were resistant to EDTA or incubation at 56 degrees C for 1 h. The data suggest that further study of nonsexual spread of high-risk genital HPV via fomites is warranted. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 17 TC 65 Z9 69 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1997 VL 176 IS 4 BP 1076 EP 1079 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XZ465 UT WOS:A1997XZ46500032 PM 9333171 ER PT J AU Fleischmajer, R Kuhn, K Sato, Y MacDonald, ED Perlish, JS Pan, TC Chu, ML Kishiro, Y Oohashi, T Bernier, S Yamada, Y Ninomiya, Y AF Fleischmajer, R Kuhn, K Sato, Y MacDonald, ED Perlish, JS Pan, TC Chu, ML Kishiro, Y Oohashi, T Bernier, S Yamada, Y Ninomiya, Y TI There is temporal and spatial expression of alpha 1 (IV), alpha 2 (IV), alpha 5 (IV), alpha 6 (IV) collagen chains and beta 1 integrins during the development of the basal lamina in an ''in vitro'' skin model SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE collagen IV ID BASEMENT-MEMBRANE COLLAGEN; EXTRACELLULAR-MATRIX COMPONENTS; LINKED ALPORT SYNDROME; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODIES; SERTOLI CELLS; GENE; IDENTIFICATION; KERATINOCYTES; LOCALIZATION AB Temporal and spatial expression of alpha 1 (IV), alpha 2 (IV), alpha 3 (IV), alpha 4 (IV), alpha 5 (IV), and alpha 6 (IV) collagen chains was studied during the formation of the basal lamina in an ''in vitro'' skin model. A sequential study was performed at 7-d and 14-d cultures (lamina densa absent) and at 28-, 36-, and 56-d cultures (lamina densa present). Expression of beta 1, beta 4, alpha 1, alpha 2, alpha 3, alpha 5, alpha 6 integrin subunits and co-localization with collagen IV was studied by regular and laser confocal indirect immunofluorescence microscopy. mRNA expression of alpha 2 (IV) and alpha 6 (IV) chains was estimated by northern blots. The earliest expression of alpha 1 (IV) and alpha 2 (IV) collagen chains was noted in 7-d cultures restricted to basal keratinocytes. At 14-d cultures, alpha 1 (IV) and alpha 2 (IV) chains were noted in basal keratinocytes and as a broad band (10 mu m) in the adjacent dermis. At this stage 80% of the alpha 2 (IV) mRNA was expressed in the dermis and 20% in the epidermis. At 28-, 36-, and 56-d cultures the alpha 1 (IV) and alpha 2 (IV) chains were present in a linear distribution at the epidermo-dermal junction and in the upper dermis. The alpha 6 (IV) collagen chains were expressed much later at 36-d cultures and the alpha 5 (IV) at 56 d, both mostly in a linear distribution but also in the adjacent dermis. alpha 6 (IV) mRNA was demonstrated in the dermis of 36-d cultures. There was co-localization of collagen IV and beta 1 integrin subunits in 14-d cultures at the matrix site of keratinocytes. Functional perturbation studies with AIIB2 monoclonal antibody (anti-beta 1 subunits) and competitive inhibition with a collagen cyanogen bromide digestion derived fragment (CB3[IV]) that contains the collagen IV ligand for alpha 1 beta 1, alpha 2 beta 1 integrins, altered the pattern of collagen IV deposition. C1 MAX PLANCK INST BIOCHEM,MUNICH,GERMANY. OKAYAMA UNIV,SCH MED,DEPT MOL BIOL & BIOCHEM,OKAYAMA,JAPAN. THOMAS JEFFERSON UNIV,DEPT BIOCHEM & MOL BIOL,PHILADELPHIA,PA. THOMAS JEFFERSON UNIV,DEPT DERMATOL,PHILADELPHIA,PA. NIH,DEV BIOL LAB,BETHESDA,MD 20892. RP Fleischmajer, R (reprint author), MT SINAI SCH MED,DEPT DERMATOL,BOX 1047,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. RI OOHASHI, Toshitaka/B-1599-2011 NR 44 TC 38 Z9 40 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1997 VL 109 IS 4 BP 527 EP 533 DI 10.1111/1523-1747.ep12336696 PG 7 WC Dermatology SC Dermatology GA XY217 UT WOS:A1997XY21700005 PM 9326385 ER PT J AU Sanford, KK Parshad, R Price, FM Tarone, RE Thompson, J Guerry, D AF Sanford, KK Parshad, R Price, FM Tarone, RE Thompson, J Guerry, D TI Radiation-induced chromatid breaks and DNA repair in blood lymphocytes of patients with dysplastic nevi and/or cutaneous melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE deficient DNA repair ID G2 PHASE; GROUP-C; CANCER; DAMAGE; ABERRATIONS; FIBROBLASTS; CELLS; PREDISPOSITION; PRECURSORS; GENE AB Each chromatid contains a single continuous molecule of double-stranded DNA, so chromatid breaks represent unrepaired DNA double-strand breaks. Frequencies of chromatid breaks after G(2) phase x-irradiation were determined in phytohemagglutinin-stimulated blood lymphocytes from normal subjects and from four categories of patients with dysplastic nevi with or without cutaneous melanoma or with melanoma alone. Some cells were treated with an inhibitor of DNA repair replication to determine enzymatic incision activity at damaged sites after exposure to x-rays, UVC, or fluorescent light. Whereas one of 16 normal controls had deficient DNA repair, all 17 patients from families with hereditary dysplastic nevi with or without melanoma (category I) had a deficiency in repair of radiation-induced DNA damage, manifested as an abnormally high frequency of chromatid breaks after x-irradiation or a reduced capacity to incise the damaged sites after UV exposure. Four of 11 patients with sporadic dysplastic nevi alone (category II) and eight of 12 with sporadic dysplastic nevi and melanoma (category III) showed deficient DNA repair after x-irradiation. One of two patients with sporadic melanoma and no dysplastic nevi (category IV) was also deficient in repair of x-ray-induced damage. Deficient DNA repair thus appears to be associated with hereditary dysplastic nevi with or without melanoma. It also characterizes some patients with sporadic dysplastic nevi or melanoma. C1 HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC. UNIV PENN,CTR CANC,PIGMENTED LES GRP,PHILADELPHIA,PA 19104. RP Sanford, KK (reprint author), NCI,NATL CANC INST,CELLULAR & MOL BIOL LAB,BIOSTAT BRANCH,NIH,ROOM 1E24,BLDG 37,BETHESDA,MD 20892, USA. NR 20 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1997 VL 109 IS 4 BP 546 EP 549 DI 10.1111/1523-1747.ep12336789 PG 4 WC Dermatology SC Dermatology GA XY217 UT WOS:A1997XY21700008 PM 9326388 ER PT J AU Hsu, R Lazarova, Z Yee, C Yancey, KB AF Hsu, R Lazarova, Z Yee, C Yancey, KB TI Noncomplement fixing, IgG(4) autoantibodies predominate in patients with anti-epiligrin cicatricial pemphigoid SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE autoimmunity; bullous disease; laminin ID IMMUNE-COMPLEXES; MONOCLONAL-ANTIBODIES; SUBCLASS DISTRIBUTION; SEROLOGIC ASPECTS; IGG4 ANTIBODIES; SKIN; COMPLEMENT; LIGAND; IMMUNOFLUORESCENCE; SPECIFICITY AB This study characterized the specific reactivity, IgG subclass, and complement fixing ability of anti-laminin-5 IgG from 12 patients with anti-epiligrin cicatricial pemphigoid. Circulating IgG from all patients bound the dermal side of 1 M NaCl split skin, immunoprecipitated laminin-5 produced by biosynthetically radiolabeled human keratinocytes, and (in 10 of 12 cases) immunoblotted the laminin-alpha 3 subunit. Analysis of the distribution of IgG subclasses in these patients' circulating anti-laminin-5 autoantibodies by semiquantitative indirect immunofluorescence microscopy using the HP series of subclass-specific monoclonal antibodies revealed: (i) IgG(4) predominant autoantibodies in seven of 11 sera; (ii) IgG(1) and IgG(2) at substantially lower levels in a smaller number of sera; and (iii) no specific IgG(3) anti-laminin-5 autoantibodies in any patients. The same IgG(4)-dominant profile of anti-laminin-5 autoantibodies was found in enzyme-linked immunosorbent assay studies of purified human laminin 5. Direct immunofluorescence microscopy of six skin biopsies from three patients found that IgG(4) was also the predominant subclass of IgG in epidermal basement membranes in situ. Consistent with these findings, sera from 11 of 11 patients with anti-laminin-5 IgG autoantibodies did not fur C3 to epidermal basement membranes in vitro. These immunochemical studies suggest that complement activation does not play a major role in the pathophysiology of this disease and that subepidermal blisters in these patients may develop via a direct effect of anti-laminin-5 IgG itself. C1 NCI,DERMATOL BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NR 27 TC 31 Z9 31 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1997 VL 109 IS 4 BP 557 EP 561 DI 10.1111/1523-1747.ep12337073 PG 5 WC Dermatology SC Dermatology GA XY217 UT WOS:A1997XY21700010 PM 9326390 ER PT J AU Weinberg, WC Yuspa, SH AF Weinberg, WC Yuspa, SH TI An antibody to p53 recognizes soluble keratins in epidermal keratinocyte cultures under differentiating, but not proliferating, conditions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID MONOCLONAL-ANTIBODIES; SIMIAN VIRUS-40; PROTEIN; EXPRESSION; TRANSFORMATION; ANTIGENS RP Weinberg, WC (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009 NR 17 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1997 VL 109 IS 4 BP 611 EP 612 DI 10.1111/1523-1747.ep12337539 PG 2 WC Dermatology SC Dermatology GA XY217 UT WOS:A1997XY21700019 PM 9326399 ER PT J AU Ding, YS Liang, F Fowler, JS Kuhar, MJ Carroll, FI AF Ding, YS Liang, F Fowler, JS Kuhar, MJ Carroll, FI TI Synthesis of [F-18]norchlorofluoroepibatidine and its N-methyl derivative: New PET ligands for mapping nicotinic acetylcholine receptors SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE nicotinic acetylcholine receptors; epibatidine; fluorine-18; positron emission tomography ID NUCLEOPHILIC AROMATIC-SUBSTITUTION; POISON FROG; EPIBATIDINE; (+/-)-EPIBATIDINE AB Fluorine-18 labeled norchlorofluoroepibatidine (NFEP), a high-affinity nicotinic acetylcholine receptor ligand, was prepared by a one-pot, two-step synthesis: nucleophilic heteroaromatic substitution of a tert-Boc protected precursor (7-tert-butyloxycarbonyl-exo-2-(2'-N,N,N-trimethylammonium-5'-pyridinyl)-7-[2.2.1]heptane iodide) using no-carrier-added [F-18]fluoride followed by deprotection with trifluoroacetic acid. Subsequent reductive N-methylation with formaldehyde and sodium cyanoborohydride afforded fluorine-lb labeled N-methyl-norchlorofluoroepibatidine (N-methyl-NFEP). The unusually high radiochemical yield for the first step (70%) and the quantitative conversions in the deprotection and N-methylation steps afforded overall radiochemical yields of 55-65% (decay corrected based on starting [F-18]fluoride) for [F-18]NFEP (synthesis time 65 min) and 45-55% for [F-18]N-methyl-NFEP (synthesis time 75 min), with a specific activity of 2-9 Ci/mu mole (EOB). C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP Ding, YS (reprint author), BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973, USA. NR 21 TC 24 Z9 25 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD OCT PY 1997 VL 39 IS 10 BP 827 EP 832 DI 10.1002/(SICI)1099-1344(199710)39:10<827::AID-JLCR29>3.3.CO;2-Z PG 6 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA XZ102 UT WOS:A1997XZ10200005 ER PT J AU Gabel, SA Luck, LA Werbelow, LG London, RE AF Gabel, SA Luck, LA Werbelow, LG London, RE TI Dynamic frequency shifts of complexed ligands: An NMR study of D-[1-C-13,1-H-2]glucose complexed to the Escherichia coli periplasmic glucose/galactose receptor SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID PORPHOBILINOGEN SYNTHASE; 280000-DALTON PROTEIN; RELAXATION; METHYLENE; CARBONS; DIPOLAR; NUCLEI AB The C-13 multiplet structure of D-[1-C-13,1-H-2] glucose complexed to the Escherichia coli periplasmic glucose/galactose receptor has been studied as a function of temperature. Asymmetric multiplet patterns observed are shown to arise from dynamic frequency shifts. Multiplet asymmetry contributions resulting from shift anisotropy-dipolar cross correlations were found to be small, with optimal fits of the data corresponding to small, negative values of the correlation factor, chi(CD-CSA). Additional broadening at higher temperatures most-probably results from ligand exchange between free and complexed states. Effects of internal motion are also considered theoretically, and indicate that the order parameter for the bound glucose is greater than or equal to 0.9. (C) 1997 Academic Press. C1 CLARKSON UNIV, DEPT BIOL, CTR SCI, POTSDAM, NY 13699 USA. NEW MEXICO INST MIN & TECHNOL, DEPT CHEM, SOCORRO, NM 87801 USA. RP Gabel, SA (reprint author), NIEHS, STRUCT BIOL LAB, MR01, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 19 TC 4 Z9 4 U1 1 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 1997 VL 128 IS 2 BP 101 EP 104 DI 10.1006/jmre.1997.1223 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA YG965 UT WOS:A1997YG96500001 PM 9356263 ER PT J AU Duyn, JH Yang, YH AF Duyn, JH Yang, YH TI Fast spiral magnetic resonance imaging with trapezoidal gradients SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE fast MRI; spiral MRI; gradient slew rate; duty cycle ID FMRI AB A modified spiral imaging technique is presented, in which the conventional sinusoidal gradient waveforms are replaced by trapezoidal ones. In addition to allowing a reduced data acquisition time, the new waveforms circumvent specific hardware restrictions on the minimum scan repetition time. (C) 1997 Academic Press. RP Duyn, JH (reprint author), NIH,LAB DIAGNOST RADIOL RES,OIR,BLDG 10,ROOM BIN-256,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010 NR 16 TC 13 Z9 13 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD OCT PY 1997 VL 128 IS 2 BP 130 EP 134 DI 10.1006/jmre.1997.1237 PG 5 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA YG965 UT WOS:A1997YG96500004 PM 9356266 ER PT J AU Bocchinfuso, WP Korach, KS AF Bocchinfuso, Wayne P. Korach, Kenneth S. TI Mammary Gland Development and Tumorigenesis in Estrogen Receptor Knockout Mice SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE Wnt-1; breast cancer; hyperplasia; progesterone; prolactin; cyclin D1 AB Estrogens are important for the development of the mammary gland and strongly associated with oncogenesis in this tissue. The biological effects of estrogens are mediated through the estrogen receptor (ER),(3) a member of the nuclear receptor superfamily. The estrogen/ER signaling pathway plays a central role in mammary gland development, regulating the expression and activity of other growth factors and their receptors. The generation of the ER knockout (ERKO) mouse has made it possible to directly understand the contribution of ER in mammary development and has provided an unique opportunity to study estrogen action in carcinogenesis. A mammary oncogene (Wnt-1) was introduced into the ERKO background to determine if the absence of the ER would affect the development of tumors induced by oncogenic stimulation. The development, hyperplasia, and tumorigenesis in mammary glands from the ERKO/Wnt-1 mouse line are described. These studies provide the impetus to evaluate the effect of other oncogenes in mammary tumorigenesis in the absence of estrogen/ER signaling. C1 [Korach, Kenneth S.] NIEHS, Environm Dis & Med Program, Receptor Biol Sect, Lab Reprod & Dev Toxicol,NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Environm Dis & Med Program, Receptor Biol Sect, Lab Reprod & Dev Toxicol,NIH, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 66 TC 225 Z9 231 U1 2 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD OCT PY 1997 VL 2 IS 4 BP 323 EP 334 DI 10.1023/A:1026339111278 PG 12 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA V25HI UT WOS:000208468700002 PM 10935020 ER PT J AU Humphreys, RC Lydon, JP O'Malley, BW Rosen, JM AF Humphreys, Robin C. Lydon, John P. O'Malley, Bert W. Rosen, Jeffrey M. TI Use of PRKO Mice to Study the Role of Progesterone in Mammary Gland Development SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE Progesterone receptor; gene knockout; reciprocal transplantation; ductal and lobuloalveolar development; stromal-epithelial interactions AB To better understand the distinct physiological roles played by progesterone and estrogen receptors (PR amd ER)(4) as well as to study directly PR function in an in vivo context, a novel mutant mouse strain, the PR knockout (PRKO) mouse, was generated carrying a germline loss of function mutation at the PR locus. Mouse mammary gland development has been examined in PRKO mice using reciprocal transplantation experiments to investigate the effects of the stromal and epithelial PRs on ductal and lobuloalveolar development. The absence of PR in transplanted donor epithelium, but not in recipient stroma, prevented normal lobuloalveolar development in response to estrogen and progesterone treatment. Conversely, the presence of PR in the transplanted donor epithelium, but not in the recipient stroma, revealed that PR in the stroma may be necessary for ductal development. Stimulation of ductal development by the PR may, therefore, be mediated by an unknown secondary signaling molecule, possibly a growth factor. The continued stimulation of the stromal PR appears to be dependent on reciprocal signal(s) from the epithelium. Thus, the combination of gene knockout and reciprocal transplantation technologies has provided some new insights into the role of stromal-epithelial interactions and steroid hormones in mammary gland development. C1 [Lydon, John P.; O'Malley, Bert W.; Rosen, Jeffrey M.] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. [Humphreys, Robin C.] NIH, Dev Biol Sect, Biochem & Metab Lab, Bethesda, MD USA. RP Rosen, JM (reprint author), Baylor Coll Med, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM jrosen@bcm.tmc.edu FU National Institutes of Health [CA64255]; USAMRMC [DAMD17-94-J-4253] FX The authors thank Dr. Susanne Krnacik for critical comments. This work was supported by grant CA64255 from the National Institutes of Health and DAMD17-94-J-4253 from the USAMRMC to J. M. R. NR 62 TC 54 Z9 54 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD OCT PY 1997 VL 2 IS 4 BP 343 EP 354 DI 10.1023/A:1026343212187 PG 12 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA V25HI UT WOS:000208468700004 PM 10935022 ER PT J AU Hennighausen, L Robinson, GW Wagner, KU Liu, XW AF Hennighausen, Lothar Robinson, Gertraud W. Wagner, Kay-Uwe Liu, Xiuwen TI Developing a Mammary Gland is a Stat Affair SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE Prolactin signaling; Stat5; mammary development; alveoli; milk secretion AB The mammary gland is a recent acquisition on the phylogenetic scale of organ evolution and is characterized by an unparalleled regenerative capacity. With each pregnancy an expanded lobulo-alveolar compartment rises on the ductal compartment and differentiates to secrete large amounts of milk during lactation. After weaning of the young the entire alveolar compartment undergoes apoptosis and is remodeled to return to a virgin-like state. Evolution recruited old hands from existing signaling pathways to guide and accomplish the extraordinary task of repeatedly building and destroying this highly specialized tissue. Seventy years ago it was known that the presence of estrogen, progesterone, and prolactin (PRL)(3) was essential for ductal and alveolar development. The recent ability to generate mice from which genes have been deleted by homologous recombination has made it possible to gain molecular insight into the signaling pathways used by these hormones to effect mammary differentiation. In the cast of characters progesterone and PRL are on center stage. After binding to its receptor, PRL activates the JAK-STAT pathway leading to transcription of genes which induce alveolar proliferation and differentiation. In vivo experiments have shown that JAK-Stat signaling is mandatory for adult mammary gland development and lactation. Two Stat molecules, Stat3 and Stat5, appear to have opposite functions and their relative activity may serve to control developmental cycles of mammary tissue. While Stat5 activity has been linked to alveolar proliferation and function, Stat3 activity correlates with the loss of alveolar function, cell death and the initiation of mammary tissue remodeling. C1 [Hennighausen, Lothar; Robinson, Gertraud W.; Wagner, Kay-Uwe; Liu, Xiuwen] NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDK, Biochem & Metab Lab, NIH, Bldg 10,Rm 9N113, Bethesda, MD 20892 USA. EM mam-mary@nih.gov NR 39 TC 45 Z9 45 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD OCT PY 1997 VL 2 IS 4 BP 365 EP 372 DI 10.1023/A:1026347313096 PG 8 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA V25HI UT WOS:000208468700006 PM 10935024 ER PT J AU Sidransky, E Ginns, EI AF Sidransky, E Ginns, EI TI Gaucher disease plus SO JOURNAL OF MEDICAL GENETICS LA English DT Letter ID MUTATION; GENE RP Sidransky, E (reprint author), NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892, USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD OCT PY 1997 VL 34 IS 10 BP 876 EP 877 DI 10.1136/jmg.34.10.876-a PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XZ443 UT WOS:A1997XZ44300022 PM 9350830 ER PT J AU Policastro, PF Munderloh, UG Fischer, ER Hackstadt, T AF Policastro, PF Munderloh, UG Fischer, ER Hackstadt, T TI Rickettsia rickettsii growth and temperature-inducible protein expression in embryonic tick cell lines SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID SPOTTED-FEVER RICKETTSIAE; PLAQUE-FORMATION; INFECTION; VIRULENCE; CULTURES; ESTABLISHMENT; CLEAVAGE; STRAINS AB Rickettsia rickettsii has limited adverse effects on its arthropod vector, but causes severe disease in man, To model differences in host-parasite interaction, R, rickettsii growth and protein expression were examined at temperatures reflective of host environment in the tick cell lines DALBE3 and IDE2, the human endothelial cell line ECV304, and the African green monkey kidney cell line Vero76, At low multiplicities of infection, rickettsial titres increased 10(2)-10(3)-fold in all cell lines after incubation for 3 days at 34 degrees C, At higher multiplicites and with extended incubation, R, rickettsii showed enhanced survival in tick versus mammalian cells, No difference in rickettsial ultrastructure or protein profiles was detected between different host cell types, Rickettsial proteins of 42, 43, 48, 75 and 100 kDa are induced in tick cells shifted from 28 degrees to 34 degrees C, but not in cells maintained at 28 degrees C, This temperature response may be associated with expression of rickettsial determinants that are pathogenic to mammalian hosts. C1 NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,NIH,HAMILTON,MT 59840. UNIV MINNESOTA,DEPT ENTOMOL,ST PAUL,MN 55180. RP Policastro, PF (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,NIH,HAMILTON,MT 59840, USA. NR 32 TC 33 Z9 33 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD OCT PY 1997 VL 46 IS 10 BP 839 EP 845 PG 7 WC Microbiology SC Microbiology GA YA858 UT WOS:A1997YA85800006 PM 9364140 ER PT J AU Sotir, M Switzer, W Schable, C Schmitt, J Vitek, C Khabbaz, RF AF Sotir, M Switzer, W Schable, C Schmitt, J Vitek, C Khabbaz, RF TI Risk of occupational exposure to potentially infectious nonhuman primate materials and to simian immunodeficiency virus SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE injuries; needlestick; mucocutaneous; infection ID HEPATITIS-B VIRUS; RHESUS-MONKEYS; LABORATORY WORKER; MACAQUE MONKEYS; RETROVIRUS; DISEASE; BLOOD; AIDS; TRANSMISSION; PREVALENCE AB Five hundred fifty persons who worked with nonhuman primates (NHP) or with NHP material in 13 North American research institutions were surveyed for potential occupational exposures and tested for antibodies to simian immunodeficiency virus (SIV). Needlesticks and mucocutaneous exposures were reported more frequently among persons who handled SIV-negative or SIV-status-unknown (SIV-N/U) animals (36% and 35%) or who worked with SIV-N/U material in the laboratory (18% and 17%) than among persons who handled SIV-positive NHP (SIV-P) (9% and 4%) or worked with SIV-P material (6% and 8%), The risk for needlesticks when working with both SIV-N/U and SIV-P animals and the risk for mucocutaneous exposures from SIV-N/U animals increased with the number of years working with NHP. Persons who performed invasive tasks (e.g., obtaining blood samples, performing surgery/autopsies) were more likely than others to sustain needlesticks (adjusted OR = 3.55, 95% CI = 1.40-9.02). Two (0.4%) of 550 persons had antibodies to SIV. One appears to be infected with SIV, as previously reported. These data suggest that persons who work with NHP or with NHP material are at risk for occupational exposure to potentially infectious materials including SIV. Prevention strategies are needed to reduce the risk for needlesticks and mucocutaneous exposures around all NHP, and safety guidelines should emphasize prevention options for invasive tasks performed with animals. C1 CTR DIS CONTROL & PREVENT,DIV VIRAL & RICKETTSIAL DIS,STD,TB LAB RES,NATL CTR INFECT DIS,ATLANTA,GA 30333. CTR DIS CONTROL & PREVENT,DIV AIDS,STD,TB LAB RES,NATL CTR INFECT DIS,ATLANTA,GA 30333. EMORY UNIV,ROLLINS SCH PUBL HTH,DEPT EPIDEMIOL,ATLANTA,GA 30322. NIH,DIV SAFETY,BETHESDA,MD 20892. NR 32 TC 19 Z9 19 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 1997 VL 26 IS 5 BP 233 EP 240 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA YH410 UT WOS:A1997YH41000002 PM 9437261 ER PT J AU Chatterjee, R Tsarev, S Pillot, J Coursaget, P Emerson, SU Purcell, RH AF Chatterjee, R Tsarev, S Pillot, J Coursaget, P Emerson, SU Purcell, RH TI African strains of hepatitis E virus that are distinct from Asian strains SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE enteric viral hepatitis; HEV sequence analysis ID TRANSMITTED NON-A; NON-B HEPATITIS; CYNOMOLGUS MONKEYS; MOLECULAR-CLONING; PROTOTYPE STRAIN; SEQUENCE; ISOLATE; HEV AB Partial genomic sequences of four hepatitis E virus (HEV) strains from Africa (Morocco and Tunisia) and one from Central Asia (Tashkent, Uzbekistan) were obtained. The reverse transcriptase-polymerase chain reaction was used to amplify 5' and hypervariable regions of open reading frame 1 (ORF1) and a region overlapping all 3 ORFs. Sequence analysis of these regions revealed the African strains to be quite distinct from all known Asian strains but more similar to them than to the Mexican strain. Sequence analysis of the Tashkent strain revealed almost complete identity with another central Asian strain from Osh, Kirgizia. These results thus fur ther confirm the geographical origin of HEV strain divergence. (C) 1997 Wiley-Liss, Inc. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,NIH,BETHESDA,MD 20892. INST PASTEUR,UNITE IMMUNOL MICROBIENNE,PARIS,FRANCE. FAC PHARM PHILIPPE MAUPAS,LAB IMMUNOL MALAD INFECTIEUSES,TOURS,FRANCE. FU NIAID NIH HHS [N01-AI-45180, N01-AI-52705] NR 11 TC 44 Z9 45 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD OCT PY 1997 VL 53 IS 2 BP 139 EP 144 DI 10.1002/(SICI)1096-9071(199710)53:2<139::AID-JMV5>3.3.CO;2-O PG 6 WC Virology SC Virology GA XZ466 UT WOS:A1997XZ46600005 PM 9334924 ER PT J AU Jaeger, MMM Kalinec, G Dodane, V Kachar, B AF Jaeger, MMM Kalinec, G Dodane, V Kachar, B TI A collagen substrate enhances the sealing capacity of tight junctions of A6 cell monolayers SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE tight junction; intercellular junctions; transepithelial permeability; transepithelial electrical resistance (TER); A6 epithelial cell cultures; collagen ID CANINE KIDNEY-CELLS; TRANS-EPITHELIAL PERMEABILITY; OCCLUDING JUNCTIONS; ZONULA-OCCLUDENS; RAT-LIVER; 2 STRAINS; ZO-1; RESISTANCE; MODULATION; CYTOSKELETON AB A6 cells, a kidney derived epithelial cell line, when cultured either on a collagen-coated substrate or on polycarbonate substrate without collagen form confluent monolayers that are similar in cell density and overall morphology. However, the transepithelial electrical resistance (TER) of monolayers grown on the collagen-coated substrate is ninefold higher than that of monolayers grown without collagen. A comparative freeze-fracture study showed that this large difference in TER is not related to the length or number of tight junction strands but to differences in the specific conductance of individual strands. This conductance was obtained considering the TER, the linear junctional density and the mean number of tight junction strands. We estimated the specific linear conductance of the tight junction strands to be 2.56 x 10(-7) S/cm for cells grown on collagen and 30.3 x 10(-7) S/cm for the cells grown without collagen. We also examined changes in distribution and phosphorylation states of the zonula occludens associated protein, ZO-1, during monolayer formation. Immunocytochemistry reveals that the distribution of ZO-1 follows a similar time course and pattern independent of the presence or absence of collagen. While the amount of ZO-1 expression is identical in cells grown on both substrates, this protein is phosphorylated to a greater extent during the initial stages of confluence in cells cultured on collagen. We suggest that the phosphorylation levels of ZO-1 in A6 cells at the early stages of monolayer formation may determine the final molecular structure and specific conductance of the tight junctions strands. C1 NIDCD,LAB CELLULAR BIOL,NIH,BETHESDA,MD 20892. UNIV SAO PAULO,SCH DENT,DEPT ORAL PATHOL,SAO PAULO,BRAZIL. RI Marques, Marcia/F-3780-2012 OI Marques, Marcia/0000-0002-9398-1252 NR 38 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD OCT 1 PY 1997 VL 159 IS 3 BP 263 EP 270 DI 10.1007/s002329900289 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA XX151 UT WOS:A1997XX15100009 PM 9312215 ER PT J AU Bolander, FF Ginsburg, E Vonderhaar, BK AF Bolander, FF Ginsburg, E Vonderhaar, BK TI The regulation of mammary prolactin receptor metabolism by a retroviral envelope protein SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID TUMOR VIRUS RECEPTOR; EPITHELIAL-CELLS; HORMONE RECEPTORS; DOWN-REGULATION; GLAND EXPLANTS; BINDING; INTERNALIZATION; MECHANISMS; ACID AB In a previous study, infection with the mouse mammary tumor virus (MMTV) was shown to increase the sensitivity of the mammary epithelium toward prolactin (PRL); furthermore, this effect could be mimicked by the binding of the MMTV envelope protein (gp52) to its cell receptor. The present work has investigated the possibility that gp52-induced changes in the PRL receptor (PRLR) were responsible for this phenomenon. In vitro, gp52 doubled the PRLR concentration in the plasmalemma of mammary epithelium without affecting the affinity. The origins of these PRLRs were twofold: first, gp52 stimulated PRLR mRNA nearly fivefold, suggesting that some of the receptors were newly synthesized. Second, there was a redistribution of PRLRs within the mammary cell: PRLRs were shifted from an internal pool to the plasma membrane. This relocation was very rapid, occurring within 30 min. There did not appear to be any contribution from alterations in PRLR degradation, since the half-life of PRLR was not affected by gp52. In summary, the MMTV increases the PRL sensitivity of mouse mammary epithelium by elevating PRLRs through both enhanced synthesis and recruitment from microsomes. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP Bolander, FF (reprint author), UNIV S CAROLINA,DEPT BIOL SCI,COLUMBIA,SC 29208, USA. FU NCI NIH HHS [CA 42009] NR 32 TC 7 Z9 7 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD OCT PY 1997 VL 19 IS 2 BP 131 EP 136 DI 10.1677/jme.0.0190131 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YA161 UT WOS:A1997YA16100004 PM 9343305 ER PT J AU Cabot, EL Angeletti, B Usdin, K Furano, AV AF Cabot, EL Angeletti, B Usdin, K Furano, AV TI Rapid evolution of a young L1 (LINE-1) clade in recently speciated Rattus taxa SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE molecular sequence data; retrotransposon; L1; LINE-1; repeated DNA; rodent; evolution ID INTERSPERSED REPEATED DNA; MOUSE L1; RIBONUCLEOPROTEIN-PARTICLES; TRANSPOSABLE ELEMENT; SEQUENCES; FAMILY; PROTEIN; IDENTIFICATION; PROMOTER; MICE AB L1 elements are retrotransposons that have been replicating and evolving in mammalian genomes since before the mammalian radiation. Rattus norvegicus shares the young L1(m1vi2) clade only with its sister taxon, Rattus cf moluccarius. Here we compared the L1(m1vi2) clade in these recently diverged species and found that it evolved rapidly into closely related but distinct clades: the L1(m1vi2-rm) clade (or subfamily), characterized here from R. cf moluccarius, and the L1(m1vi2-rn) clade, originally described in R. norvegicus. In addition to other differences, these clades are distinguished by a cluster of amino acid replacement substitutions in ORF I. Both rat species contain the L1(m1vi2-rm) clade, but the L1(m1vi2-rn) clade is restricted to R. norvegicus. Therefore, the L1(m1vi2-rm) clade arose prior to the divergence of R. norvegicus and R. cf moluccarius, and the L1(m1vi2-rn) clade amplified after their divergence. The total number of L1(m1vi2-rm) elements in R. cf moluccarius is about the same as the sum of the L1(m1vi2-rm) and L1(m1vi2-rn) elements in R. norvegicus. The possibility that L1 amplification is in some way limited so that the two clades compete for replicative supremacy as well as the implications of the other distinguishing characteristic of the L1(m1vi2-rn) and L1(m1vi2-rm) clades are discussed. C1 NIDDK,SECT GENOM STRUCT & FUNCT,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 47 TC 23 Z9 23 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD OCT PY 1997 VL 45 IS 4 BP 412 EP 423 DI 10.1007/PL00006246 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA XX824 UT WOS:A1997XX82400010 PM 9321420 ER PT J AU Verneau, O Catzeflis, F Furano, AV AF Verneau, O Catzeflis, F Furano, AV TI Determination of the evolutionary relationships in Rattus sensu lato (Rodentia:Muridae) using L1 (LINE-2) amplification events SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE LINE-1; repeat DNA; Rattus; rodent; phylogeny; evolution ID INTERSPERSED REPEATED DNA; PHYLOGENETIC HISTORY; MURINE RADIATION; FAMILY; SEQUENCES; MAMMALIA; ELEMENTS; ACOMYS; MOUSE; TREES AB We determined similar to 215 bp of DNA sequence from the 3'-untranslated region (UTR) of 240 cloned L1 (LINE-1) elements isolated from 22 species of Rattus sensu late and Rattus sensu stricto murine rodents. The sequences were sorted into different L1 subfamilies, and oligonucleotides cognate to them were hybridized to genomic DNA of various taxa. From the distribution of the L1 subfamilies in the various species, we inferred the partial phylogeny of Rattus sensu late. The four Maxomys species comprise a well-defined clade separate from a monophyletic cluster that contains the two Leopoldamys and four Niviventer species. The Niviventer/Leopoldamys clade, in turn, shares a node with the clade that contains Berylmys, Sundamys, Bandicota, and Rattus sensu stricto. The evolutionary relationships that we deduced agree with and significantly extend the phylogeny of Rattus sensu lato established by other molecular criteria. Furthermore, the L1 amplification events scored here produced a unique phylogenetic tree, that is, in no case did a character (a given L1 amplification event) appear on more than one branch. The lack of homoplasy found in this study supports the robustness of L1 amplification events as phylogenetic markers for the study of mammalian evolution. C1 NIDA, SECT GENOM STRUCT & FUNCT, CELLULAR & MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. RI VERNEAU, Olivier/A-6631-2010 NR 52 TC 23 Z9 25 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD OCT PY 1997 VL 45 IS 4 BP 424 EP 436 DI 10.1007/PL00006247 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA XX824 UT WOS:A1997XX82400011 PM 9321421 ER PT J AU Schuler, GD AF Schuler, GD TI Pieces of the puzzle: expressed sequence tags and the catalog of human genes SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article ID HUMAN GENOME PROJECT; MAP; DISCOVERY; PATTERNS; MICROARRAY; DIVERSITY; CANCER; DBEST RP Schuler, GD (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 40 TC 275 Z9 307 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD OCT PY 1997 VL 75 IS 10 BP 694 EP 698 DI 10.1007/s001090050155 PG 5 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA YB371 UT WOS:A1997YB37100003 PM 9382993 ER PT J AU Wei, Q Wu, XF Hammer, JA AF Wei, Q Wu, XF Hammer, JA TI The predominant defect in dilute melanocytes is in melanosome distribution and not cell shape, supporting a role for myosin V in melanosome transport SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID UNCONVENTIONAL MYOSIN; SACCHAROMYCES-CEREVISIAE; COAT COLOR; LOCUS; GENE; LOCALIZATION; PROTEINS; GROWTH; MYO2 AB Mice with mutations at the dilute locus, which encodes the heavy chain of a type V unconventional myosin, exhibit a reduction in coat colour intensity. This defect is thought to be caused by the absence in dilute melanocytes of the extensive dendritic arbor through which these sells normally deliver pigment-laden melanosomes to keratinocytes. The data on which this conclusion has been based can also be explained, however, by a defect in the outward transport of melanosomes within melanocytes of normal shape. To resolve this question, we compared the shape and pigment distribution within melanocytes present in primary cultures prepared from the epidermis of C57BL/6J pups that were either wild type (D/D) at dilute or homozygous for the dilute null allele d(120J). These same comparisons were also performed on melanocytes in situ, where antibodies to the membrane tyrosine kinase receptor cKIT were used to visualize melanocyte cell shape independent of pigment distribution. Wild type melanocytes were found to be dendritic and to have melanosomes distributed throughout their dendrites both in vitro and in situ. Mutant melanocytes were also found to be dendritic in both cases, but their melanosomes were highly concentrated in the cell body and largely excluded from dendrites. We conclude, therefore, that the predominant defect in dilute melanocytes is in melanosome distribution, not cell shape. These results argue that the myosin V isoform Encoded by the dilute locus functions in dendritic extensions to move melanosomes from their site of formation within the cell body to their site of intercellular transfer at dendritic tips. This conclusion is consistent with our recent demonstration by immunolocalization that the dilute myosin V isoform associates with melanosomes in mouse melanocytes. C1 NHLBI,CELL BIOL LAB,SECT MOL CELL BIOL,NIH,BETHESDA,MD 20892. NR 37 TC 58 Z9 58 U1 2 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD OCT PY 1997 VL 18 IS 5 BP 517 EP 527 DI 10.1023/A:1018659117569 PG 11 WC Cell Biology SC Cell Biology GA YA169 UT WOS:A1997YA16900002 PM 9350005 ER PT J AU Kirkpatrick, B Litman, D Kim, JW Vladar, K Breier, A Buchanan, RW AF Kirkpatrick, B Litman, D Kim, JW Vladar, K Breier, A Buchanan, RW TI Failure of fusion of the septum pellucidum and the heterogeneity of schizophrenia SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID DEFICIT SYNDROME; ABNORMALITIES; DISORDERS; PATTERNS C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. RP Kirkpatrick, B (reprint author), UNIV MARYLAND,MARYLAND PSYCHIAT RES CTR,POB 21247,BALTIMORE,MD 21228, USA. FU NIMH NIH HHS [MH-00925, MH44801, MH-40279] NR 22 TC 6 Z9 6 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 1997 VL 185 IS 10 BP 639 EP 641 DI 10.1097/00005053-199710000-00008 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YB974 UT WOS:A1997YB97400008 PM 9345255 ER PT J AU Hsiao, JK AF Hsiao, JK TI Schizophrenia - Hirsch,SR, Weinberger,DR SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP Hsiao, JK (reprint author), NIMH,SCHIZOPHRENIA RES BRANCH,NEUROIMAGING PROGRAM,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 1997 VL 185 IS 10 BP 650 EP 651 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YB974 UT WOS:A1997YB97400015 ER PT J AU Heyes, MP Saito, K Chen, CY Proescholdt, MG Nowak, TS Li, J Beagles, KE Proescholdt, MA Zito, MA Kawai, K Markey, SP AF Heyes, MP Saito, K Chen, CY Proescholdt, MG Nowak, TS Li, J Beagles, KE Proescholdt, MA Zito, MA Kawai, K Markey, SP TI Species heterogeneity between gerbils and rats: Quinolinate production by microglia and astrocytes and accumulations in response to ischemic brain injury and systemic immune activation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE kynurenine pathway; immune activation; ischemic brain injury; endotoxin; microglia; astrocytes; gerbil; rat; species differences ID CENTRAL-NERVOUS-SYSTEM; INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY; KYNURENINE PATHWAY METABOLISM; TRANSIENT FOREBRAIN ISCHEMIA; NITRIC-OXIDE PRODUCTION; CONVERT L-TRYPTOPHAN; CEREBRAL-ISCHEMIA; CEREBROSPINAL-FLUID; INTERFERON-GAMMA; ACID FORMATION AB Quinolinic acid is an excitotoxic kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared quinolinate responses to systemic and brain immune activation in gerbils and rats. Global cerebral ischemia in gerbils, but not rats, increased hippocampus indoleamine-2,3-dioxygenase activity and quinolinate levels 4 days postinjury. In a rat focal ischemia model, small increases in quinolinate concentrations occurred in infarcted regions on days 1, 3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an intraperitoneal injection of endotoxin (1 mg/kg of body weight) increased quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3-dioxygenase activity at 24 h postinjection. In rats, however, no significant quinolinate content changes occurred, whereas lung indoleamine-2,3-dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [C-13(6)]quinolinate from L-[C-13(6)]tryptophan. Gerbil astrocytes produced relatively small quantities of quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine-2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert L-tryptophan to quinolinate. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. UNIV TENNESSEE,COLL MED,DEPT NEUROL,MEMPHIS,TN. GIFU UNIV,DEPT LAB MED,GIFU,JAPAN. UNIV TOKYO,DEPT NEUROSURG,TOKYO 113,JAPAN. RP Heyes, MP (reprint author), NIMH,LAB NEUROTOXICOL,BLDG 10,ROOM 3D40,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 69 TC 55 Z9 57 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1997 VL 69 IS 4 BP 1519 EP 1529 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XX057 UT WOS:A1997XX05700021 PM 9326281 ER PT J AU Sommer, N Martin, R McFarland, HF Quigley, L Cannella, B Raine, CS Scott, DE Loschmann, PA Racke, MK AF Sommer, N Martin, R McFarland, HF Quigley, L Cannella, B Raine, CS Scott, DE Loschmann, PA Racke, MK TI Therapeutic potential of phosphodiesterase type 4 inhibition in chronic autoimmune demyelinating disease SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE cytokine; experimental autoimmune encephalomyelitis; multiple sclerosis; phosphodiesterase type 4; rolipram; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; RECEPTOR ALPHA-CHAIN; T-CELLS; ROLIPRAM; PREVENTION; ANTIBODY; MICE; EXPRESSION AB It was recently demonstrated that selective phosphodiesterase type 4 (PDE4) inhibition suppresses the clinical manifestations of acute experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and inhibits the production of tumor necrosis factor-alpha (TNF-alpha), a pathogenetically central cytokine. Since the most common presentation of MS in humans is a relapsing-remitting course, we investigated the therapeutic potential of PDE4 inhibition in the relapsing-remitting EAE model of the SJL mouse. Administration of rolipram. the prototypic PDE4 inhibitor, reduced the clinical signs of EAE during both the initial episode of disease and subsequent relapses. In parallel, there was marked reduction of demyelination and also less inflammation throughout the central nervous system (CNS) of rolipram-treated animals. Gene expression of proinflammatory cytokines in the CNS was reduced in most of the rolipram-treated animals. Additional experiments demonstrated that PDE I inhibition acted principally by inhibiting the secretion of Thl cytokines, however, the encephalitogenic potential of myelin basic protein-specific T cells was not impaired. Our findings suggest that PDE4 inhibitors are a promising cytokine-directed therapy in chronic demyelinating disease. (C) 1997 Elsevier Science B.V. C1 UNIV TUBINGEN,DEPT NEUROL,D-72076 TUBINGEN,GERMANY. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PATHOL NEUROPATHOL,BRONX,NY 10461. US FDA,BETHESDA,MD 20892. RP Sommer, N (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892, USA. FU NINDS NIH HHS [NS 11920, NS 08952, NS 07098] NR 33 TC 59 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT PY 1997 VL 79 IS 1 BP 54 EP 61 DI 10.1016/S0165-5728(97)00111-2 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA YC021 UT WOS:A1997YC02100007 PM 9357447 ER PT J AU Fields, RD Eshete, F Stevens, B Itoh, K AF Fields, RD Eshete, F Stevens, B Itoh, K TI Action potential-dependent regulation of gene expression: Temporal specificity in Ca2+ cAMP-responsive element binding proteins, and mitogen-activated protein kinase signaling SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CREB phosphorylation; calcium; c-fos; signal transduction; activity-dependent plasticity; LTP; MAP kinase; SRE ID LONG-TERM FACILITATION; IMMEDIATE-EARLY GENES; APLYSIA SENSORY NEURONS; C-FOS TRANSCRIPTION; NERVOUS-SYSTEM; INTRACELLULAR CALCIUM; CREB PHOSPHORYLATION; HIPPOCAMPAL-NEURONS; ELECTRICAL-ACTIVITY; NEURAL IMPULSES AB Specific patterns of neural impulses regulate genes controlling nervous system development and plasticity, but it is not known how intracellular signaling cascades and transcriptional activation mechanisms can regulate specific genes in response to specific patterns of action potentials. Studies using electrical stimulation of mouse dorsal root ganglion neurons in culture show that the temporal dynamics of intracellular signaling pathways are an important factor, Expression of c-fos varied inversely with the interval between repeated bursts of action potentials, Transcription was not dependent on a large or sustained increase in intracellular Ca2+, and high Ca2+ levels separated by long interburst intervals (5 min) produced minimal increases in c-fos expression. Levels of the transcription factor cAMP-responsive element binding protein (CREB), phosphorylated at Ser-133, increased rapidly in response to brief action potential stimulation but remained at high levels several minutes after an action potential burst. These kinetics limited the fidelity with which P-CREB could follow different patterns of action potentials, and P-CREB levels were not well correlated with c-fos expression, The extracellular-regulated kinase (ERK) mitogen-activated protein kinases (MAPK) also were stimulated by action potentials of appropriate temporal patterns, Bursts of action potentials separated by long intervals (5 min) did not activate MAPK effectively, but they did increase CREB phosphorylation. This was a consequence of the more rapid dephosphorylation of MAPK in comparison to CREB, High expression of c-fos was dependent on the combined activation of the MAPK pathway and phosphorylation of CREB, These observations show that temporal features of action potentials (and associated Ca2+ transients) regulate expression of neuronal genes by activating specific intracellular signaling pathways with appropriate temporal dynamics. RP Fields, RD (reprint author), NICHHD,DEV NEUROBIOL LAB,NEUROCYTOL & PHYSIOL UNIT,NIH,BLDG 49,ROOM 5A38,BETHESDA,MD 20892, USA. NR 71 TC 208 Z9 209 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 1997 VL 17 IS 19 BP 7252 EP 7266 PG 15 WC Neurosciences SC Neurosciences & Neurology GA XX358 UT WOS:A1997XX35800009 PM 9295372 ER PT J AU Safieddine, S Wenthold, RJ AF Safieddine, S Wenthold, RJ TI The glutamate receptor subunit delta 1 is highly expressed in hair cells of the auditory and vestibular systems SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cochlea; vestibular end organ; hair cells; spiral ganglion neurons; PCR; in situ hybridization; Western blot; immunocytochemistry ID GUINEA-PIG COCHLEA; POTASSIUM-INDUCED RELEASE; SPIRAL GANGLION NEURONS; IMMUNOCYTOCHEMICAL LOCALIZATION; MESSENGER-RNAS; PURKINJE-CELL; RAT-BRAIN; NON-NMDA; NEUROACTIVE SUBSTANCES; OLIVOCOCHLEAR NEURONS AB In the inner ear, fast excitatory synaptic transmission is mediated by ionotropic glutamate receptors, including AMPA, kainate, and NMDA receptors. The recently identified delta 1 and delta 2 glutamate receptors share low homology with the other three types, and no clear response or ligand binding has been obtained from cells transfected with delta alone or in combination with other ionotropic receptors. Studies of mice lacking expression of delta 2 show that this subunit plays a crucial role in plasticity of cerebellar glutamatergic synapses. In addition, these mice show a deficit in vestibular compensation. These findings and the nature of glutamatergic synapses between vestibulocochlear hair cells and primary afferent dendrites suggest that delta receptors may be functionally important in the inner ear and prompted us to investigate the expression of delta receptors in the cochlea and peripheral vestibular system. Reverse transcription and DNA amplification by PCR combined with immunocytochemistry and in situ hybridization were used. Our results show that the expression of delta 1 in the organ of Corti is intense and restricted to the inner hair cells, whereas delta 1 is expressed in all spiral ganglion neurons as well as in their satellite glial cells. In the vestibular end organ, delta 1 was highly expressed in both hair cell types and also was expressed in the vestibular ganglion neurons. The prominent expression of delta 1 in inner hair cells and in type I and type II vestibular hair cells suggests a functional role in hair cell neurotransmission. RP Safieddine, S (reprint author), NATL INST DEAFNESS & OTHER COMMUNICAT DISORDERS,NIH,NEUROCHEM LAB,36 CONVENT DR MSC-4162,BETHESDA,MD 20892, USA. NR 72 TC 36 Z9 38 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 1997 VL 17 IS 19 BP 7523 EP 7531 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XX358 UT WOS:A1997XX35800034 PM 9295397 ER PT J AU Olson, BR Gumowski, J Rubino, D Oldfield, EH AF Olson, BR Gumowski, J Rubino, D Oldfield, EH TI Pathophysiology of hyponatremia after transsphenoidal pituitary surgery SO JOURNAL OF NEUROSURGERY LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the Endocrine-Society CY JUN 14-17, 1995 CL WASHINGTON, DC SP Endocrine Soc, Minist Educ, Sci & Culture Japan, Dtsch ForschGemeinsch DE hyponatremia; pituitary tumor; thirst; natriuresis; antidiuresis ID INAPPROPRIATE SECRETION; ANTIDIURETIC-HORMONE; VASOPRESSIN SECRETION; OSMOREGULATION; EXCRETION; DIAGNOSIS; HUMANS; TUMORS; WATER AB Hyponatremia after pituitary surgery is presumed to be due to antidiuresis; however, detailed prospective investigations of water balance that would define its pathophysiology and true incidence have not been established. In this prospective study, the authors documented water balance in patients for 10 days after surgery, monitored any sodium dysregulation, further characterized the pathophysiology of hyponatremia, and correlated the degree of intraoperative stalk and posterior pituitary damage with water balance dysfunction. Ninety-two patients who underwent transsphenoidal pituitary surgery were studied. To evaluate posterior pituitary damage, a questionnaire was completed immediately after surgery in 61 patients. To examine the osmotic regulation of vasopressin secretion in normonatremic patients, water loads were administered 7 days after surgery. Patients were categorized on the basis of postoperative plasma sodium patterns. After pituitary surgery, 25% of the patients developed spontaneous isolated hyponatremia (Day 7 +/- 0.4). Twenty percent of the patients developed diabetes insipidus and 46% remained normonatremic. Plasma arginine vasopressin (AVP) was not suppressed in hyponatremic patients during hypoosmolality or in two-thirds of the normonatremic patients after water-load testing. Only one-third of the normonatremic patients excreted the water load and suppressed AVP normally. Hyponatremic patients were more natriuretic, had lower dietary sodium intake, and had similar fluid intake and cortisol and atrial natriuretic peptide (ANP) levels compared with normonatremic patients. Normonatremia, hyponatremia, and diabetes insipidus were associated with increasing degrees of surgical manipulation of the posterior lobe and pituitary stalk during surgery. The pathophysiology of hyponatremia after transsphenoidal surgery is complex. It is initiated by pituitary damage that produces AVP secretion and dysfunctional osmoregulation in most surgically treated patients. Additional events that act together to promote the clinical expression of hyponatremia include nonatrial natriuretic peptide-related excess natriuresis, inappropriately normal fluid intake and thirst, as well as low dietary sodium intake. Patients should be monitored closely for plasma sodium, plentiful dietary sodium replacement, mild fluid restriction, and attention to symptoms of hyponatremia during the First 2 weeks after transsphenoidal surgery. C1 WATERBURY HOSP & HLTH CTR,DEPT MED,WATERBURY,CT. NIH,WARREN G MAGNUSON CLIN CTR,DEPT NURSING,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. NR 25 TC 59 Z9 63 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1997 VL 87 IS 4 BP 499 EP 507 DI 10.3171/jns.1997.87.4.0499 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XX492 UT WOS:A1997XX49200002 PM 9322839 ER PT J AU Tedeschi, G Lundbom, N Raman, R Bonavita, S Duyn, JH Alger, JR DiChiro, G AF Tedeschi, G Lundbom, N Raman, R Bonavita, S Duyn, JH Alger, JR DiChiro, G TI Increased choline signal coinciding with malignant degeneration of cerebral gliomas: a serial proton magnetic resonance spectroscopy imaging study SO JOURNAL OF NEUROSURGERY LA English DT Article DE primary brain tumor; cerebral glioma; malignant degeneration; tumor recurrence; magnetic resonance spectroscopy; proton magnetic resonance spectroscopy imaging; choline ID POSITRON EMISSION TOMOGRAPHY; HUMAN BRAIN-TUMORS; H-1 MR SPECTROSCOPY; LOW-GRADE ASTROCYTOMA; F-18 FLUORODEOXYGLUCOSE; IN-VITRO; FDG-PET; H-1-NMR SPECTROSCOPY; INTRACRANIAL TUMORS; GLUCOSE CONSUMPTION AB The authors tested the hypothesis that proton magnetic resonance spectroscopy (H-1-MRS) imaging can be used as a supportive diagnostic tool to differentiate clinically stable brain tumors from those progressing as a result of low-to high-grade malignant transformation or posttherapeutic recurrence. Twenty-seven patients with cerebral gliomas verified on histological examination were studied repeatedly with H-1-MRS imaging over a period of 3.5 years. At the time of each H-1-MRS imaging study, clinical examination, MR imaging, positron emission tomography with F-18-fluorodeoxyglucose, and biopsy findings (when available) were used to categorize each patient as having tither stable or progressive disease. Measures of the percentage changes in the choline (Cho) H-1-MRS imaging signal intensity between studies, which were obtained without knowledge of the clinical categorization, allowed the investigators to segregate the groups with a high degree of statistical significance. All progressive cases showed a Cho signal increase between studies of more than 45%, whereas all stable cases showed an elevation of less than 35%, no changer or even a decreased signal. The authors conclude that increased Cho levels coincide with malignant degeneration of cerebral gliomas and therefore may possibly be used as a supportive indicator of progression of these neoplasms. C1 NIH,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,BRAIN RES INST,DEPT RADIOL SCI,LOS ANGELES,CA 90024. RP Tedeschi, G (reprint author), NINCDS,NEUROIMAGING BRANCH,NIH,BLDG 10,ROOM 1C227,9002 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010 NR 57 TC 202 Z9 218 U1 2 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1997 VL 87 IS 4 BP 516 EP 524 DI 10.3171/jns.1997.87.4.0516 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XX492 UT WOS:A1997XX49200005 PM 9322842 ER PT J AU Laske, DW Morrison, PF Lieberman, DM Corthesy, ME Reynolds, JC StewartHenney, PA Koong, SS Cummins, A Paik, CH Oldfield, EH AF Laske, DW Morrison, PF Lieberman, DM Corthesy, ME Reynolds, JC StewartHenney, PA Koong, SS Cummins, A Paik, CH Oldfield, EH TI Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with single-photon emission computerized tomography imaging SO JOURNAL OF NEUROSURGERY LA English DT Article DE brain; drug delivery; single-photon emission computerized tomography; Macaca mulatta ID FLUID; ANTIBODY; DELIVERY; FLOW AB High-flow interstitial infusion into the brain, which uses bulk fluid flow to achieve a relatively homogeneous-drug distribution in the extracellular space of the brain, has the potential to perfuse large volumes of brain. The authors report reproducible long-term delivery of In-111-diethylenetriamine pentaacetic acid-apontransferrin (In-111-DTPA-Tf) (molecular mass 81 kD) to Macaca mulatta brain and monitoring with single-photon emission computerized tomography (SPECT). The In-111-DTPA-Tf was infused at 1.9 mu l/minute over 87 hours into the frontal portion of the centrum semiovale using a telemetry-controlled fully implanted pump. On Days 1, 3, 4, 8, 11, and 15 after beginning the infusion, planar and SPECT scans of In-111-DTPA-Tf were obtained. Spread of protein in the brain ranged from 2 to 3 cm and infusion volumes ranged from 3.9 to 6.7 cm(3). Perfusion of over one-third of the white matter of the infused hemisphere was achieved. From brain SPECT images of Tc-99m-hexamethylpropyleneamine oxime, which was administered intravenously before each In-111 scan, the authors also found that blood perfusion in the infused region was reduced by less than 5% relative to corresponding noninfused regions. Histological, examination at 30 days revealed only mild gliosis limited to the area immediately surrounding the needle tract. These findings indicate that long-term interstitial brain infusion is effective for the delivery of drugs on a multicentimeter scale In the primate brain. The results also indicate that it should be possible to perfuse targeted regions of the brain for extended intervals to investigate the potential utility of neurotrophic factors, antitumor agents, and other materials for the treatment of central nervous system disorders. C1 NINCDS,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. RI Kipke, Daryl/A-2167-2009 NR 19 TC 112 Z9 113 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1997 VL 87 IS 4 BP 586 EP 594 DI 10.3171/jns.1997.87.4.0586 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XX492 UT WOS:A1997XX49200010 PM 9322847 ER PT J AU Keir, SD Miller, J Yu, G Hamilton, R Samulski, RJ Xiao, XA Tornatore, C AF Keir, SD Miller, J Yu, G Hamilton, R Samulski, RJ Xiao, XA Tornatore, C TI Efficient gene transfer into primary and immortalized human fetal glial cells using adeno-associated virus vectors: establishment of a glial cell line with a functional CD4 receptor SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE gene expression; adeno-associated virus; dependovirus; glia ID HUMAN POLYOMAVIRUS; NONDIVIDING CELLS; MAMMALIAN BRAIN; SPINAL-CORD; EXPRESSION; INTEGRATION; REPLICATION; ENGRAFTMENT; ASTROCYTES; PATTERNS AB Adeno associated virus (AAV) is a non-pathogenic dependent parvovirus with a broad host range, capable of high levels of transduction and stable integration into the host cell genome. We have investigated the potential for using AAV as a vector for gene transfer into glial cells of the human fetal nervous system. Recombinant AAV vectors expressing either the reporter gene beta galactosidase or a human CD4 receptor were able to transduce both primary glial cells of the human fetal nervous system and an SV40 immortalized human fetal glial cell line (SVG). No difference in transduction efficiency was observed between the primary cells and the cell line which in both cases was as high as 95%. Stable transfectants of the glial cell line expressing the CD4 receptor were selected. An SVG/CD4 expressing line was then established. The presence of the CD4 receptor was confirmed by immunohistochemistry, Westerm immune-blotting and flow cytometric analysis. The CD4 receptor was shown to be functional by infection of the SVG/CD4 cell line with the human immunodeficiency virus (HIV). Upon infection, the SVG/CD4 cells produced 20-fold higher levels of the HIV intracellular core antigen P24 than the CD4 negative parental cells and in addition formed syncytia. The use of AAV vectors should prove useful in biological investigations of human glial cells and offers promise as a means of ex vivo and in vivo gene delivery. C1 NHLBI,CLIN HEMATOL BRANCH,NIH,BETHESDA,MD 20892. UNIV N CAROLINA,GENE THERAPY CTR,CHAPEL HILL,NC. SOMATIX THERAPY CORP,ALAMEDA,CA 94501. RP Keir, SD (reprint author), NINCDS,LAB MOL MED & NEUROSCI,NIH,BLDG 36,RM 5W21,BETHESDA,MD 20892, USA. NR 28 TC 19 Z9 20 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 1997 VL 3 IS 5 BP 322 EP 330 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA YF288 UT WOS:A1997YF28800002 PM 9372453 ER PT J AU Kovacs, G Akhtar, M Beckwith, BJ Bugert, P Cooper, CS Delahunt, B Eble, JN Fleming, S Ljungberg, B Medeiros, LJ Moch, H Reuter, VE Ritz, E Roos, G Schmidt, D Srigley, JR Storkel, S VandenBerg, E Zbar, B AF Kovacs, G Akhtar, M Beckwith, BJ Bugert, P Cooper, CS Delahunt, B Eble, JN Fleming, S Ljungberg, B Medeiros, LJ Moch, H Reuter, VE Ritz, E Roos, G Schmidt, D Srigley, JR Storkel, S VandenBerg, E Zbar, B TI The Heidelberg classification of renal cell tumours SO JOURNAL OF PATHOLOGY LA English DT Editorial Material DE kidney; renal cell neoplasms; classification; genetics ID CARCINOMA; TUMORS; CYTOGENETICS; PAPILLARY; KIDNEY AB This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996, The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic to the kidneys, The proposed classification subdivides renal cell tumours into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most commonly documented genetic abnormalities, Benign rumours are subclassified into metanephric adenoma and adenofibroma, papillary renal cell adenoma, and renal oncocytoma, Malignant tumours are subclassified into common or conventional renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and renal cell carcinoma, unclassified, This classification is based on current genetic knowledge, correlates with recognizable histological findings, and is applicable to routine diagnostic practice, (C) 1997 John Wiley & Sons, Ltd. C1 KING FAISAL SPECIALIST HOSP & RES CTR,RIYADH 11211,SAUDI ARABIA. LOMA LINDA UNIV,LOMA LINDA,CA 92350. INST CANC RES,SUTTON,SURREY,ENGLAND. WELLINGTON SCH MED,NEWTOWN,NEW ZEALAND. ROUDEBUSH VAMC,INDIANAPOLIS,IN. UNIV EDINBURGH,SCH MED,EDINBURGH,MIDLOTHIAN,SCOTLAND. UMEA UNIV,UMEA,SWEDEN. CITY HOPE NATL MED CTR,DUARTE,CA 91010. UNIV BASEL,BASEL,SWITZERLAND. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. INST PATHOL,MANNHEIM,GERMANY. UNIV TORONTO,TORONTO,ON,CANADA. UNIV WITTEN HERDECKE,WUPPERTAL,GERMANY. UNIV GRONINGEN,GRONINGEN,NETHERLANDS. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RP Kovacs, G (reprint author), UNIV HEIDELBERG,DEPT UROL,ONCOL MOL LAB,IM NEUENHEIMER FELD 365,D-69120 HEIDELBERG,GERMANY. NR 16 TC 859 Z9 875 U1 1 U2 11 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 1997 VL 183 IS 2 BP 131 EP 133 DI 10.1002/(SICI)1096-9896(199710)183:2<131::AID-PATH931>3.0.CO;2-G PG 3 WC Oncology; Pathology SC Oncology; Pathology GA YA170 UT WOS:A1997YA17000003 PM 9390023 ER PT J AU Pollack, MM Patel, KM Ruttimann, UE AF Pollack, MM Patel, KM Ruttimann, UE TI The pediatric risk of mortality .3. Acute physiology score (PRISM III APS): A method of assessing physiologic instability for pediatric intensive care unit patients SO JOURNAL OF PEDIATRICS LA English DT Article ID HEAD-INJURY; CHILDREN; PREDICTION; SEVERITY; AGE; CHILDHOOD; INFANTS; COMA AB Objective: To develop a physiology-based measure of physiologic instability for use in pediatric patients that has an expanded scale compared with the Pediatric Risk of Mortality (PRISM) III score. Study design: Data were collected from consecutive admissions to 32 pediatric ICUs (11,165 admission, 543 deaths). Patient-level data included physiologic data, outcomes, descriptive information, and diagnoses. Physiologic data included the most abnormal values in the first 24 hours of pediatric ICU stay from 27 variables. Initially, ranges of each physiologic variable were evaluated for their association with mortality. A multivariate logistic regression analysis was used to determine the final variables and their ranges. Integer scores reflecting the relative contribution to mortality risk were assigned to the variable ranges. Results: A total of 59 ranges of 21 physiologic variables were selected. This score is called the Pediatric Risk of Mortality III-Acute Physiology Score (PRISM III-APS). Mortality increased as the PRISM III-APS score increased. Most patients have PRISM III-APS scores less than 10, and these patients have a mortality risk of less than 1%. At the other extreme, the mortality rate of the 137 patients with a PRISM III-APS score of greater than 80 was greater than 97%. Conclusion: The PRISM III-APS score is an expanded measure of physiologic instability that has been validated against mortality. Compared with PRISM III, PRISM III-APS should be more sensitive to small changes in physiologic status. C1 NIAAA, NIH, WASHINGTON, DC USA. RP Pollack, MM (reprint author), GEORGE WASHINGTON UNIV, CHILDRENS NATL MED CTR, SCH MED, CTR HLTH SERV & CLIN RES, WASHINGTON, DC 20010 USA. NR 25 TC 99 Z9 102 U1 1 U2 4 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 1997 VL 131 IS 4 BP 575 EP 581 DI 10.1016/S0022-3476(97)70065-9 PG 7 WC Pediatrics SC Pediatrics GA YG843 UT WOS:A1997YG84300018 PM 9386662 ER PT J AU Mills, JL Fears, TR Robison, LL Nicholson, HS Sklar, CA Byrne, J AF Mills, JL Fears, TR Robison, LL Nicholson, HS Sklar, CA Byrne, J TI Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia SO JOURNAL OF PEDIATRICS LA English DT Article ID CRANIAL IRRADIATION; OVARIAN-FUNCTION; PUBERTAL GROWTH; RADIATION; GIRLS; THERAPY AB Objective: As more children survive acute lymphoblastic leukemia (ALL), questions are raised regarding how the disease and its therapy affect their pubertal development. Study design: The National Institute of Child Health and Human Development-National Cancer Institute-Children's Cancer Group Leukemia Follow-Up Study used a historical cohort design to investigate menarche in 188 ALL survivors who were premenarchal at diagnosis, aged at least 18 years, at least 2 years after diagnosis, alive, and in remission. Female siblings of ALL survivors (n = 215) served as control subjects. Results: Menarche occurred within the normal age range in 92% of survivors and 96% of the control subjects (p = 0.09). Early menarche occurred in four survivors (2%) and three control subjects (1%). Delayed, absent, or medically induced menarche was reported by 12 survivors (6%) and six control subjects (3%). Compared with the control subjects, survivors of ALL who received 1500 cGy cranial radiation before the age of 8 years had significantly earlier menarche, relative hazard (RH) of 2.2 (95% confidence interval: 1.4, 3.4 [p = 0.0003]). Survivors receiving 2400 cGy of craniospinal radiation with or without abdominal radiation had significantly later menarche than the control subjects, RH 0.4 (95% confidence interval: 0.3, 0.7 [p = 0.0002]). Conclusions: In this large cohort of ALL survivors, the risk of disordered menarche was low. However, younger subjects receiving 1800 cCy cranial radiation and those receiving 2400 cCy below the diaphragm required careful monitoring. C1 NCI, BIOSTAT BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV MINNESOTA, DEPT PEDIAT, MINNEAPOLIS, MN 55455 USA. CHILDRENS NATL MED CTR, DEPT HEMATOL ONCOL, WASHINGTON, DC 20010 USA. MEM SLOAN KETTERING CANC CTR, DEPT PEDIAT, NEW YORK, NY 10021 USA. RP Mills, JL (reprint author), NICHHD, PEDIAT EPIDEMIOL SECT, DIV EPIDEMIOL STAT & PREVENT RES,NIH,6100 BLDG, MSC 7510, ROOM 7B03, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA 05436, CA 02971, CA 13539] NR 21 TC 35 Z9 38 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 1997 VL 131 IS 4 BP 598 EP 602 DI 10.1016/S0022-3476(97)70069-6 PG 5 WC Pediatrics SC Pediatrics GA YG843 UT WOS:A1997YG84300022 PM 9386666 ER PT J AU Albandar, JM Brown, LJ Loe, H AF Albandar, JM Brown, LJ Loe, H TI Putative periodontal pathogens in subgingival plaque of young adults with and without early-onset periodontitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE periodontitis; early-onset/pathogenesis; periodontitis, early-onset/microbiology ID LOCALIZED JUVENILE PERIODONTITIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; BACTEROIDES-GINGIVALIS; EIKENELLA-CORRODENS; BACTERIA; DISEASE; MICROBIOLOGY; ADOLESCENTS; CULTURE AB THIS STUDY ASSESSED THE ASSOCIATIONS between putative periodontal pathogens and early-onset periodontitis (EOP) in a population of 248 subjects, 13 to 19 years of age at baseline, derived from a representative sample of U.S. young adults. The subjects were selected based on the presence or absence of attachment loss at baseline. The attachment level was assessed clinically at baseline and at a 6-year follow-up examination, and the presence of 7 bacterial species was assessed at follow-up using DNA probes. The individuals were classified into generalized, localized, incidental EOP, and no-periodontitis groups based on the extent and severity of attachment loss; and classified as having rapid, moderate, slow, and no progression based on the rate of periodontal progression during the 6 preceding years. In the EOP groups there were significantly higher percentages of individuals with detectable levels of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus, and Treponema denticola. In addition, the EOP group had significantly higher levels of these 5 microorganisms compared to the no-periodontitis group. There were also higher percentages of individuals with these species and higher levels of bacteria in the group showing disease progression than the group without progression. In a descending order of importance, P. gingivalis, T. denticola, and P. intermedia were the microorganisms significantly associated with the generalized and/or rapidly progressing disease. F. nucleatum and C. rectus were also associated with EOP, but to a lesser degree. In the present population Actinobacillus actinomycetemcomitans was not significantly associated with EOP, though it was recovered more often from subjects with localized EOP. Eikenella corrodens was present equally in subjects with and without disease. The results show that several bacterial species are associated with EOP, and that P. gingivalis and T. denticola are of particular importance and may play a significant role in the more severe and progressive forms of EOP. C1 AMER DENT ASSOC,CHICAGO,IL. UNIV CONNECTICUT,CTR HLTH,SCH DENT MED,DEPT PERIODONTOL,FARMINGTON,CT. RP Albandar, JM (reprint author), NIDR,NATCHER BLDG,ROOM 4AS-19B,45 CTR DR,BETHESDA,MD 20892, USA. OI Albandar, Jasim M./0000-0001-7801-3811 NR 30 TC 96 Z9 98 U1 0 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD OCT PY 1997 VL 68 IS 10 BP 973 EP 981 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YE202 UT WOS:A1997YE20200007 PM 9358364 ER PT J AU GeterDouglass, B Katz, JL Alling, K Acri, JB Witkin, JM AF GeterDouglass, B Katz, JL Alling, K Acri, JB Witkin, JM TI Characterization of unconditioned behavioral effects of dopamine D-3/D-2 receptor agonists SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SQUIRREL-MONKEYS; D-3 RECEPTORS; PHARMACOLOGICAL CHARACTERIZATION; STEREOTYPED BEHAVIOR; LOCOMOTOR-ACTIVITY; MOLECULAR-BIOLOGY; SELECTIVE LIGAND; MICE SUGGEST; COCAINE; RAT AB A series of experiments examined the ability of dopamine D-3/D-2 receptor agonists [(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H -[1]benzopyrano-[4,3-b]-1, oxazin-9-ol hydrochloride (PD 128,907), (+/-)-7-hydroxy-dipropylaminotetralin hydrobromide (7-OH-DPAT), quinpirole and bromocriptine] to produce a variety of dopaminergically mediated behaviors. The effects of these drugs with selectivity for D-3/D-2 receptors over D-1 receptors were compared with those produced by the selective D-1 agonists [(+/-)-Phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol hydrochloride (SKF 38393), (+/-)-6-Chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro -1H-3-benzazepine hydrobromide (SKF 82958)], a nonselective dopaminergic agonist (apomorphine), and an indirect dopamine agonist (cocaine). The D-3/D-2 agonists decreased locomotor activity, had no effect on gnawing and only inconsistently induced climbing in mice. Further, these agonists dose-dependently produced scratching in squirrel monkeys. In contrast, the D-1 agonists, SKF 82958 and SKF 38393, did not produce scratching in squirrel monkeys, Whereas the full D-1 agonist, SKF 82958, produced increases in locomotor activity and in climbing and gnawing, the partial D-1 agonist, SKF 38393, did not increase the frequencies of these behaviors. The nonselective dopamine agonist, apomorphine, produced decreases in locomotor activity and increases in climbing and gnawing in mice. Apomorphine dose-dependently produced scratching in squirrel monkeys. The indirect dopamine agonist, cocaine, produced increases in locomotor activity and climbing, but had no effect on climbing or gnawing in mice and did not produce scratching in squirrel monkeys. These findings suggest that D-3/D-2 agonists can be distinguished on various behavioral measures from the nonselective agonist, apomorphine (gnawing), D-1 agonists (scratching) and the indirect agonist, cocaine (locomotor activity and scratching). Behaviors once attributed to stimulation of D-2 (locomotor activity and scratching) or D-1/D-2 (climbing and gnawing) receptors may also involve dopamine D-3 receptors. RP GeterDouglass, B (reprint author), NIDA,DRUG DEV GRP,PRECLIN PHARMACOL LAB,ADDICT RES CTR,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 64 TC 24 Z9 25 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1997 VL 283 IS 1 BP 7 EP 15 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YC301 UT WOS:A1997YC30100002 PM 9336302 ER PT J AU Wolff, DJ Gauld, DS Neulander, MJ Southan, G AF Wolff, DJ Gauld, DS Neulander, MJ Southan, G TI Inactivation of nitric oxide synthase by substituted aminoguanidines and aminoisothioureas SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID POTENT INHIBITORS; L-ARGININE; MECHANISM; ISOFORM; ISOTHIOUREAS; HEMOGLOBIN; ENZYME; RAT AB A series of substituted aminoguanidines and amino-substituted isothioureas have been examined as inhibitors of nitric oxide (NO) synthase (NOS) isoforms. Each of the agents produced a time-and concentration-dependent inactivation of the NO-forming activity of the affinity-purified NOS isoforms. These inactivations required exposure of NOS to the drug under conditions that supported catalysis, consistent with the proposal that they act as alternate substrate, mechanism-based inactivators. Of the aminoguanidines examined, 2-ethylaminoguanidine was the most efficient inactivator, exhibiting vs. iNOS an apparent K-l value of 120 mu M as measured at 100 mu M arginine and a k(inact max) value of 0.48 min(-1) and thus an apparent second-order rate constant for inactivation of 4.0 mM(-1)min(-1). 2-Ethylaminoguanidine displayed a high isoform selectivity for the iNOS compared with the nNOS and eNOS isoforms. 2-Ethylaminoguanidine inactivated NO synthetic activity in cytokine-induced RAW 264.7 cells as measured at 100 mu M extracellular arginine with an apparent K-l value of 55 mu M and a k(inact max) value of 0.09 min(-1). The inactivated RAW 264.7 cell NO synthetic capability was restored over a 3-hr period after drug removal to a value 60% of its pretreatment value. This recovery occurred despite the presence of cycloheximide sufficient to inhibit protein synthesis by > 99%. 1-Amino-S-methylisothiourea by contrast with the aminoguanidines was identified as a mechanism-based inactivator selective for the nNOS isoform. In contrast to S-isopropylisothiourea, which was found to be both cell penetrant and reversible, 1-amino-S-methylisothiourea appeared cell impermeable and inhibited NOS enzyme ''irreversibly.'' C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD. RP Wolff, DJ (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PHARMACOL,PISCATAWAY,NJ 08854, USA. FU NHLBI NIH HHS [HL54768] NR 39 TC 51 Z9 53 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1997 VL 283 IS 1 BP 265 EP 273 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YC301 UT WOS:A1997YC30100032 PM 9336332 ER PT J AU Pickworth, WB Fant, RV Henningfield, JE AF Pickworth, WB Fant, RV Henningfield, JE TI Inhibition of prostaglandin synthesis and effects of ethanol and pentobarbital humans SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CYCLOOXYGENASE INHIBITORS; TIME COURSE; ALCOHOL; PERFORMANCE; BLOCKADE; ASPIRIN; INTOXICATION; SYNTHETASE; ANTAGONIZE; FLUOXETINE AB Results from animal research suggest that pretreatment with prostaglandin synthesis inhibitors (PGSIs) may inhibit physiological and behavioral effects of moderate ethanol ingestion. We examined the effects of ethanol and pentobarbital in humans with and without pretreatment with indomethacin, a potent PGSI. Ten male subjects with histories of recreational use of ethanol and sedative/hypnotics participated in this inpatient study. The effects of indomethacin alone (0.66 mg/kg), indomethacin (0, 0.17, 0.33, 0.66 and 1.33 mg/kg) in combination with ethanol (0 and I g/kg) and indomethacin (0 and 0.66 mg/kg) in combination with pentobarbital (0, 1.33 and 4 mg/kg) were tested. On test days, subjects swallowed capsules containing indomethacin or placebo. One hour later, they swallowed capsules that contained pentobarbital or placebo and a large drink (500 ml) of tonic water that contained ethanol or placebo (tonic water with 2 ml of ethanol floated on top). Both ethanol and pentobarbital affected subjective ratings, performance measures and heart rate. However, indomethacin pretreatment had no influence on drug-induced changes to ethanol and pentobarbital. The results of this study illustrate the relationship between depressant drugs and human performance, but they do not support the hypothesis that inhibition of prostaglandin synthesis diminishes the effects of ethanol and pentobarbital in humans. C1 JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD USA. PINNEY ASSOCIATES, BETHESDA, MD USA. RP NIDA, ADDICT RES CTR, INTRAMURAL RES PROGRAM, POB 5180, BALTIMORE, MD 21224 USA. NR 37 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1997 VL 283 IS 1 BP 274 EP 280 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YC301 UT WOS:A1997YC30100033 PM 9336333 ER PT J AU Tuttleman, M Pillemer, SR Tilley, BC Fowler, SE Buckley, LM Alarcon, GS Trentham, DE Neuner, R Clegg, DO Leisen, JCC Heyse, SP AF Tuttleman, M Pillemer, SR Tilley, BC Fowler, SE Buckley, LM Alarcon, GS Trentham, DE Neuner, R Clegg, DO Leisen, JCC Heyse, SP TI A cross sectional assessment of health status instruments in patients with rheumatoid arthritis participating in a clinical trial SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; SF-36; M-HAQ; health status instruments; clinical trial; quality of life ID IMPACT MEASUREMENT SCALES; QUALITY-OF-LIFE; ASSESSMENT QUESTIONNAIRE; PHYSICAL-DISABILITY; OUTCOME MEASURES AB Objective. To (I) validate die Short-Form Health Sun ey (SF-36) as a generic functional health status measure in patients with rheumatoid arthritis CRA), and (2) assess correlations between the SF-36 and other outcome measures used in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. Methods. We conducted a cross sectional analysis of the final visit outcome measures from the 48 week, multicenter; placebo controlled double blind MIRA trial. Multitrait scaling analyses assessed convergent and discriminant validity and internal consistency reliability of the SF-36 in the study patients. Responses to comparable items on the SF-36 and modified Health Assessment Questionnaire (M-HAQ) regarding physical functioning were compared and questions from both instruments were also compared to other RA outcome measures. Results. In patients with RA, the SF-36 had high internal consistency and reliability, high discriminant and high convergent validity. Moderate correlations were observed (r = -0.46 to -0.61, p < 0.01 in each case) for comparable items on the SF-36 and M-HAQ regarding dressing, walking, and bending. Joint tenderness score correlations with items on the M-HAQ and SF-36, and joint tenderness score correlations with the SF-36 scales were higher than for joint swelling scores. Physician and patient global assessments were mast highly correlated (r = 0.58 and 0.66, p < 0.01, respectively) with the SF-36 bodily pain item. Conclusion. The SF-36 is a valid Instrument for this RA population. The SF-36 correlates with the M-HAQ and the physician and patient global assessments. The usefulness of the SF-36 in measuring change in RA clinical trials requires testing in longitudinal studies. C1 NIAMSD, NIH, BETHESDA, MD 20892 USA. HENRY FORD HLTH SCI CTR, DIV BIOSTAT & RES EPIDEMIOL, DETROIT, MI USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT INTERNAL MED, RICHMOND, VA 23298 USA. UNIV ALABAMA, DEPT MED, DIV CLIN IMMUNOL & RHEUMATOL, BIRMINGHAM, AL 35294 USA. BETH ISRAEL HOSP, DIV RHEUMATOL, BOSTON, MA 02215 USA. US FDA, ROCKVILLE, MD 20857 USA. UNIV UTAH, DEPT INTERNAL MED, DIV RHEUMATOL, SALT LAKE CITY, UT 84112 USA. HENRY FORD HOSP, DIV RHEUMATOL, DETROIT, MI 48202 USA. RP Tuttleman, M (reprint author), NIAID, BMB,DMID,NIH,SOLAR BLDG, ROOM 3A28, 6003 EXECUT BLVD, BETHESDA, MD 20892 USA. FU NIAMS NIH HHS [N01-AR-1-2202, N01-AR-1-2203, N01-AR-1-2205] NR 22 TC 56 Z9 58 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 1997 VL 24 IS 10 BP 1910 EP 1915 PG 6 WC Rheumatology SC Rheumatology GA XY693 UT WOS:A1997XY69300011 PM 9330931 ER PT J AU Ernst, M Cohen, RM Liebenauer, LL Jons, PH Zametkin, AJ AF Ernst, M Cohen, RM Liebenauer, LL Jons, PH Zametkin, AJ TI Cerebral glucose metabolism in adolescent girls with attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE fluorodeoxyglucose; positron emission tomography; adolescent; attention-deficit/hyperactivity disorder; sexual maturation ID DEFICIT HYPERACTIVITY DISORDER; QUANTITATIVE MORPHOLOGY; SUSTAINED ATTENTION; BRAIN METABOLISM; CAUDATE-NUCLEUS; CORPUS-CALLOSUM; CHILDREN; ASYMMETRY; ADHD; DYSFUNCTION AB Objective: Low cerebral metabolic rates for glucose (CMRglc) have been reported in a small sample of girls with attention-deficit/hyperactivity disorder (ADHD). This study was an effort to replicate this finding in a larger independent sample. Method: Using positron emission tomography and [F-18]fluorodeoxyglucose, CMRglc were compared between 10 girls with ADHD (14.10 +/- 1.91 years) and 11 normal girls (14.3 +/- 1.70 years). Results: Global CMRglc was similar between ADHD and control girls. Lateralization of normalized CMRglc differed significantly between ADHD and control girls in parietal and subcortical regions, with rCMRglc lower on the left than on the right side in girls with ADHD, and conversely in control girls. The sylvian area of the parietal region and the anterior putamen of the subcortical region were the main contributors to this effect. Normalized rCMRglc of the hippocampus was higher in ADHD than in control girls. Sexual maturation was the only clinical characteristic that differed between present and previous samples, and it correlated with global CMRglc. Conclusions: Although failing to confirm abnormally low CMRglc in girls with ADHD, this study suggested that (1) functional interactions between sex and brain development may contribute to ADHD pathophysiology, and (2) sexual maturation should be controlled in future CMRglc studies of adolescent girls. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 43 TC 58 Z9 59 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 1997 VL 36 IS 10 BP 1399 EP 1406 DI 10.1097/00004583-199710000-00022 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA XZ473 UT WOS:A1997XZ47300024 PM 9334553 ER PT J AU Albandar, JM Brown, LJ Loe, H AF Albandar, JM Brown, LJ Loe, H TI Clinical features of early-onset periodontitis SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID JUVENILE PERIODONTITIS; PREVALENCE; ADOLESCENTS; PROGRESSION; DISEASE AB The authors estimate the prevalence of early-onset periodontitis, or EOP, in U.S. adolescents and describe the clinical features that occur at an early stage in those who have EOP. In 1986 and 1987, about 10.0 percent of African-American, 5.0 percent of Hispanic and 1.3 percent of white U.S. adolescents had ECP. Clinical features that may be useful in the early detection of EOP include overt gingival inflammation, dental calculus and a high rate of caries, restorations and tooth loss. C1 UNIV CONNECTICUT,CTR HLTH,SCH DENT MED,FARMINGTON,CT. AMER DENT ASSOC,HLTH POLICY RESOURCE CTR,CHICAGO,IL. NIDR,NIH,BETHESDA,MD 20892. RP Albandar, JM (reprint author), UNIV BERGEN,FAC DENT,BERGEN,NORWAY. OI Albandar, Jasim M./0000-0001-7801-3811 NR 18 TC 45 Z9 49 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1997 VL 128 IS 10 BP 1393 EP 1399 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XZ252 UT WOS:A1997XZ25200014 PM 9332140 ER PT J AU Slavkin, HC AF Slavkin, HC TI Benefit-to-risk ratio: The challenge of antibiotic drug resistance SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1997 VL 128 IS 10 BP 1447 EP 1451 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XZ252 UT WOS:A1997XZ25200022 PM 9332148 ER PT J AU Travis, LB Curtis, RE Storm, H Hall, P Holowaty, E VanLeeuwen, FE Kohler, BA Pukkala, E Lynch, CF Andersson, M Bergfeldt, K Clarke, EA Wiklund, T Stoter, G Gospodarowicz, M Sturgeon, J Fraumeni, JF Boice, JD AF Travis, LB Curtis, RE Storm, H Hall, P Holowaty, E VanLeeuwen, FE Kohler, BA Pukkala, E Lynch, CF Andersson, M Bergfeldt, K Clarke, EA Wiklund, T Stoter, G Gospodarowicz, M Sturgeon, J Fraumeni, JF Boice, JD TI Risk of second malignant neoplasms among long-term survivors of testicular cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GERM-CELL TUMORS; PEUTZ-JEGHERS SYNDROME; NON-HODGKINS-LYMPHOMA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GASTROINTESTINAL CANCER; 2ND MALIGNANCIES; OVARIAN-CANCER; FOLLOW-UP; CHEMOTHERAPY AB Background: We have quantified the site-specific risk of second malignant neoplasms among nearly 29 000 survivors (greater than or equal to 1 year) of testicular cancer, taking into account the histologic type of initial cancer and the primary therapy used to treat it, Methods: The study cohort consisted of 28 843 men identified within 16 population-based tumor registries in North America and Europe; over 3300 men had survived more than 20 years, New invasive cancers were identified through a search of registry files, Results: Second cancers were reported in 1406 men (observed-to-expected ratio [O/E] = 1.43; 95% confidence interval 1.36-1.51), with statistically significant excesses noted for acute lymphoblastic leukemia (O/E = 5.20), acute nonlymphocytic leukemia (O/E = 3.07), melanoma (O/E = 1.69), non-Hodgkin's lymphoma (O/E = 1.88), and cancers of the stomach (O/E 1.95), colon (O/E = 1.27), rectum (O/E = 1.41), pancreas (O/E = 2.21), prostate (O/E = 1.26), kidney (O/E = 1.50), bladder (O/E = 2.02), thyroid (O/E = 2.92), and connective tissue (O/E = 3.16), Overall risk was similar after seminomas (O/E 1.42) or nonseminomatous tumors (O/E = 1.50), Risk of solid tumors increased with time since the diagnosis of testicular cancer, yielding an O/E = 1.54 (O = 369) among 20-year survivors (two-sided P for trend = .00002), Secondary leukemia was associated with both radiotherapy and chemotherapy, whereas excess cancers of the stomach, bladder, and, possibly, pancreas were associated mainly with radiotherapy, Conclusions: Men with testicular cancer continue to be at significantly elevated risk of second malignant neoplasms for more than two decades following initial diagnosis, Patterns of excess second cancers suggest that many factors may be involved, although the precise roles of treatment, natural history, diagnostic surveillance, and other influences are yet to be clarified. C1 DANISH CANC SOC,COPENHAGEN,DENMARK. KAROLINSKA UNIV HOSP,STOCKHOLM,SWEDEN. CANC CARE ONTARIO,TORONTO,ON,CANADA. NETHERLANDS CANC INST,AMSTERDAM,NETHERLANDS. FINNISH CANC REGISTRY,FIN-00170 HELSINKI,FINLAND. UNIV IOWA,IOWA CITY,IA 52242. UNIV HELSINKI,CENT HOSP,HELSINKI,FINLAND. DR DANIEL DEN HOED CANC CTR,NL-3008 AE ROTTERDAM,NETHERLANDS. UNIV TORONTO,PRINCESS MARGARET HOSP,TORONTO,ON,CANADA. RP Travis, LB (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,RM 408,BETHESDA,MD 20892, USA. RI Bergfeldt, Kjell/C-3581-2012 NR 71 TC 321 Z9 324 U1 0 U2 7 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 1 PY 1997 VL 89 IS 19 BP 1429 EP 1439 DI 10.1093/jnci/89.19.1429 PG 11 WC Oncology SC Oncology GA XY455 UT WOS:A1997XY45500010 PM 9326912 ER PT J AU Vortmeyer, AO Lubensky, IA Merino, MJ Wang, CY Pham, T Furth, EE Zhuang, ZP AF Vortmeyer, AO Lubensky, IA Merino, MJ Wang, CY Pham, T Furth, EE Zhuang, ZP TI Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL UNDIFFERENTIATED CARCINOMA; COLON; TUMORIGENESIS; RECTUM AB Background: The histopathologic spectrum of colorectal neuroendocrine tumors ranges from benign to highly malignant, In this spectrum, poorly differentiated neuroendocrine carcinoma (PDNC) is the most aggressive type, characterized bg early dissemination and a rapidly fatal course. Since it is unclear whether PDNC originates from neoplastic transformation of preexisting neuroectodermal cells, pluripotent epithelial stem cells, or adenocarcinoma precursor cells, we investigated the histogenesis of this type sf cancer by performing genetic analyses on a series of colorectal tumors, Methods: Archived histologic sections of colorectal PDNC from nine patients were analyzed; gastrointestinal carcinoid tumor specimens from four patients were used as controls, The specimens were deparaffinized, microdissected, and analyzed genetically, After DNA extraction, polymerase chain reaction amplification was performed to investigate alteration (i.e., loss of heterozygosity [LOH]) of the APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma), and p53 (also known as TP53) genes, Results: LOH of the APC, DCC, or p53 genes was observed in six of eight-informative PDNC tumors; no LOH was detected in the carcinoid control specimens. Four of five informative PDNC tumors had associated adenocarcinoma; LOH of the APC and p53 genes in these tumors involved the same allele in both tissue components, Four of the five tumors with associated adenocarcinoma showed LOH of the DCC gene; in three adenomatous components showed LOW of the same allele, Conclusions: PDNC and associated adenocarcinoma appear to be derived from the same cell of origin, which is most likely either a pluripotent epithelial stem cell ar an adenocarcinoma precursor cell. C1 NCI,DIV CLIN PATHOL,PATHOL LAB,NIH,BETHESDA,MD 20892. HOSP UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. NR 17 TC 93 Z9 96 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 1 PY 1997 VL 89 IS 19 BP 1448 EP 1453 DI 10.1093/jnci/89.19.1448 PG 6 WC Oncology SC Oncology GA XY455 UT WOS:A1997XY45500012 PM 9326914 ER PT J AU Clow, WH Lindblad, P Gridley, G Nyren, O McLaughlin, JK Linet, MS Pennello, GA Adami, HO Fraumeni, JF AF Clow, WH Lindblad, P Gridley, G Nyren, O McLaughlin, JK Linet, MS Pennello, GA Adami, HO Fraumeni, JF TI Risk of urinary tract cancers following kidney or ureter stones SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; RENAL PELVIS; BLADDER-CANCER; CARCINOGENESIS; INFECTION; MELAMINE; DISEASE; RATS AB Background: A relationship has been suggested between kidney or ureter stones and the development of urinary tract cancers, In this study, a population-based cohort of patients hospitalized for kidney or ureter stones in Sweden was followed for up to 25 years to examine subsequent risks for developing renal cell? renal pelvis/ureter, or bladder cancer, Methods: I)ata from the national Swedish In-patient Register and the national Swedish Cancer Registry were linked to follow 61 144 patients who were hospitalized for kidney or ureter stones from 1965 through 1983. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were computed on the basis of nationwide cancer incidence rates, after adjustment for age, sex, and calendar year. Results: Risk of renal cell cancer was not elevated in this cohort. Significant excesses of renal pelvis/ureter cancer (SIR = 2.5; 95% CI = 1.8-3.3) and bladder cancer (SIR = 1.4; 95% CI 1.3-1.6) were observed, but the SIRs for women were more than twice those for men. Risks varied little by age or duration of follow-up. Risks of renal pelvis/ureter cancer and bladder cancer among patients with an associated diagnosis of urinary tract infection were more than double those among patients without such infection, although the risks were significantly elevated in both groups, Conclusions: Individuals hospitalized for kidney or ureter stones are at increased risk of developing renal pelvis/ureter or bladder cancer? even beyond 10 years of follow-up, Chronic irritation and infection may play a role, since kidney or ureter stones were located on the same side of the body as the tumors in most patients with renal pelvis/ureter cancer evaluated in our study. C1 KAROLINSKA INST,DEPT MED EPIDEMIOL,STOCKHOLM,SWEDEN. SUNDSVALL HOSP,DEPT UROL,SUNDSVALL,SWEDEN. INT EPIDEMIOL INST,ROCKVILLE,MD. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Clow, WH (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,RM 418,BETHESDA,MD 20892, USA. NR 28 TC 0 Z9 2 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 1 PY 1997 VL 89 IS 19 BP 1453 EP 1457 PG 5 WC Oncology SC Oncology GA XY455 UT WOS:A1997XY45500013 ER PT J AU Solomon, SD AF Solomon, SD TI Obituary: Elizabeth Mary Smith (1939-1997) SO JOURNAL OF TRAUMATIC STRESS LA English DT Item About an Individual RP Solomon, SD (reprint author), NIH,OFF BEHAV & SOCIAL SCI RES,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 1997 VL 10 IS 4 BP 705 EP 707 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA YE637 UT WOS:A1997YE63700018 ER PT J AU Nowak, MA Lloyd, AL Vasquez, GM Wiltrout, TA Wahl, LM Bischofberger, N Williams, J Kinter, A Fauci, AS Hirsch, VM Lifson, JD AF Nowak, MA Lloyd, AL Vasquez, GM Wiltrout, TA Wahl, LM Bischofberger, N Williams, J Kinter, A Fauci, AS Hirsch, VM Lifson, JD TI Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VIVO; POPULATION-DYNAMICS; IMMUNE-RESPONSES; HIV-1 INFECTION; PLASMA; RNA; MACAQUES; IMMUNIZATION; QUANTITATION; LYMPHOCYTES AB Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis, We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance hair-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 H weeks were approximately twofold greater than those obtained just prier to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R-0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated, This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,AIDS VACCINE PROGRAM,LAB RETROVIRAL PATHOGENESIS,FREDERICK,MD 21702. UNIV OXFORD,DEPT ZOOL,MATH BIOL GRP,OXFORD OX1 3PS,ENGLAND. GILEAD SCI INC,FOSTER CITY,CA 94404. MAGAININ PHARMACEUT INC,PLYMOUTH MEETING,PA 19462. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20852. NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. RI Nowak, Martin/A-6977-2008; Lloyd, Alun/H-4944-2012 FU Wellcome Trust NR 38 TC 196 Z9 198 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1997 VL 71 IS 10 BP 7518 EP 7525 PG 8 WC Virology SC Virology GA XW142 UT WOS:A1997XW14200045 PM 9311831 ER PT J AU Wickham, TJ Lee, GM Titus, JA Sconocchia, G Bakacs, T Kovesdi, I Segal, DM AF Wickham, TJ Lee, GM Titus, JA Sconocchia, G Bakacs, T Kovesdi, I Segal, DM TI Targeted adenovirus-mediated gene delivery to T cells via CD3 SO JOURNAL OF VIROLOGY LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; PENTON BASE; RECEPTOR; EXPRESSION; ATTACHMENT; INFECTION; INTEGRIN; BINDING; COMPLEX; THERAPY AB T cells are primary targets in numerous gene therapy protocols. However, the use of subgroup C adenovirus serotype 2 or 5 (Ad2 or Ad5) as a vector to transduce T cells is limited by its poor transduction efficiency for these cells. In this report we show that poor T-cell transduction results from these cells lacking both the primary Ad2-Ad5 receptor, used in attachment, and the secondary Ad receptor, which mediates entry of most adenovirus serotypes. These deficiencies,were overcome by using a bispecific antibody (bsAb) with specificities for human CD3 and for a FLAG epitope genetically introduced into Ad5 (Ad,FLAG) to redirect the virus to human T cells, The anti-FLAG x anti-CD3 bsAb increased Ad,FLAG binding 30-fold, induced the efficient uptake of Ad.FLAG into the cells? and led to a 100- to 500-fold increase in the transduction of resting T cells. Moreover, fluorescence-activated cell sorter analysis showed that 25 to 90% of the T cells were transduced by the bsAb-complexed Ad,FLAG at multiplicities of infection between 20 and 100 active particles per cell, These results demonstrate that bsAbs can target Ad to non-Ad receptors on cells that are normally resistant to Ad, resulting in their efficient and specific transduction. C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. NATL INST ONCOL,DEPT IMMUNOL,BUDAPEST,HUNGARY. RP Wickham, TJ (reprint author), GENVEC INC,ROCKVILLE,MD 20852, USA. NR 33 TC 89 Z9 90 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1997 VL 71 IS 10 BP 7663 EP 7669 PG 7 WC Virology SC Virology GA XW142 UT WOS:A1997XW14200063 PM 9311849 ER PT J AU Wang, KN Pesnicak, L Straus, SE AF Wang, KN Pesnicak, L Straus, SE TI Mutations in the 5' end of the herpes simplex virus type 2 latency-associated transcript (LAT) promoter affect LAT expression in vivo but not the rate of spontaneous reactivation of genital herpes SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; INFECTED NEURONS; MESSENGER-RNA; GUINEA-PIGS; GENE; REGION; ESTABLISHMENT; HSV-1; FREQUENCY; ELEMENT AB The primary hel pes simplex virus type 2 (HSV-2) latency-associated transcript (LAT) promoter influences LAT expression and rates of virus reactivation. We explored the biological importance of particular neuronally responsive regions within the promoter by creating new recombinant viruses bearing a targeted deletion (236 bp [strain 524]) or a point mutation (2 bp [strain 167]) in this region, These recombinant viruses grew efficiently in vitro and in vivo, caused acute genital disease in guinea pigs, and, as measured by quantitative-competitive (QC) DNA PCR, established latency, all as well as did the wild-type parental HSV 2 strain 333, the rescuant strain 524R, and the previously described 624-bp LAT(-) promoter deletion mutant. By QC-reverse transcriptase PCR of RNA from latently infected ganglia, mutant 167 expressed wild-type levels of LAT and the deletion mutant 524 expressed 9- to 15-fold less LAT than normal, while the LAT expression of the LAT(-) mutant was undetectable or at least 5 log units less than that of the wild type. The rates of recurrence of genital lesions were normal for recombinant viruses 524 and 167 but reduced (as expected) for the LAT(-) mutant. Alteration of a subset of LAT promoter elements reduced LAT expression by 1 log unit but did not influence the rate of spontaneous disease reactivation in vivo, Far greater reductions in LAT expression are necessary before reactivation rates are noticeably changed. RP Wang, KN (reprint author), NIAID,LCI,MED VIROL SECT,NIH,BLDG 10,ROOM 11N228,10 CTR DR,MSC 1888,BETHESDA,MD 20892, USA. NR 30 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1997 VL 71 IS 10 BP 7903 EP 7910 PG 8 WC Virology SC Virology GA XW142 UT WOS:A1997XW14200094 PM 9311880 ER PT J AU Chaudry, GJ Eiden, MV AF Chaudry, GJ Eiden, MV TI Mutational analysis of the proposed gibbon ape leukemia virus binding site in Pit1 suggests that other regions are important for infection SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR RECEPTOR; HAMSTER-CELLS; HIV-1 ENTRY; SUBGROUP-B; RETROVIRUS; GENE; LOCALIZATION; COFACTOR; RESIDUE; CLONING AB Region A of Pit1 (residues 550 to 558 in domain IV) and related receptors has remained the only sequence implicated in gibbon ape leukemia virus (GALV) infection, and an acidic residue at the first position appeared indispensable, The region has also been proposed to be the GALV binding site, but this lacks empirical support. Whether an acidic residue at the first position in this sequence is a definitive requirement for GALV infection has also remained unclear; certain receptors retain function even in the absence of this acidic residue, We report here that in Pit1 an acidic residue is dispensable not only at position 550 but also at 553 alone and at both positions, Further, the virus requires no specific residue at either position, Mutations generated a collection of region A sequences, often with fundamentally different physicochemical properties (overall hydrophobicity or hydrophilicity and net charge of -1, or 0, or +1), and yet Pit1 remained an efficient GALV receptor. A comparison of these sequences and a few previously published ones from highly efficient GALV receptors revealed that el en position in region A can vary without affecting GALV entry. Even Pit2 is nonfunctional for GALV only because it has lysine at the first position in its region A, which is otherwise highly diverse from region A of Pit1. We propose that region A itself is not the GALV binding motif and that Ether sequences are required for virus entry, Indeed, certain Pit1/Pit2 chimeras revealed that sequences outside domain IV are specifically important for GALV infection. C1 NIMH,UNIT MOL VIROL,LAB CELLULAR & MOL REGULAT,BETHESDA,MD 20892. RI Chaudry, Ghulam/F-9761-2011 NR 33 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1997 VL 71 IS 10 BP 8078 EP 8081 PG 4 WC Virology SC Virology GA XW142 UT WOS:A1997XW14200122 PM 9311908 ER PT J AU Gu, L Zhou, M Jurickova, I Yeager, AM Kreitman, RJ Phillips, CN Findley, HW AF Gu, L Zhou, M Jurickova, I Yeager, AM Kreitman, RJ Phillips, CN Findley, HW TI Expression of interleukin-6 receptors by pediatric acute lymphoblastic leukemia cells with the t(4;11) translocation: a possible target for therapy with recombinant IL6-Pseudomonas exotoxin SO LEUKEMIA LA English DT Article DE interleukin-6 receptor; ALL; IL6-Pseudomonas exotoxin ID BONE-MARROW TRANSPLANTATION; MIXED-LINEAGE LEUKEMIA; 11Q23 TRANSLOCATIONS; GROWTH-FACTOR; PROLIFERATION; T(4-11)(Q21-Q23); IMMUNOTOXINS; CHILDREN; PROTEIN; GENES AB We have detected expression of interleukin-6 receptors (IL-6R) by primary leukemic cells from three of six patients with t(4;11)+ ALL. Scatchard analysis revealed from 960 to 2100 high-affinity IL-6R/cell on these cells (median, 1560; mean, 1540). All three IL-6R+ cases also expressed CD33, which was not expressed on IL-6R-negative cases. To determine if these receptors could serve as a target for a recombinant ligand-toxin, we examined the sensitivity of primary IL-6R+ ALL cells to a recombinant IL6 - Pseudomonas exotoxin (IL6-PE4E) fusion protein, in which the toxicity and specificity of the chimeric toxin was enhanced by substitution of four glutamine residues for naturally occurring amino acids in PE domain I. Primary cells from IL-6R+ cases were sensitive to IL6-PE4E in a 48-h cytotoxicity assay, with ID50 values (concentrations causing 50% decrease in viability) ranging from 23 ng/ml to 92 ng/ml (median, 61; mean, 58). Furthermore, incubation of these cells with 10(3) ng/ml IL6-toxin for 24 h prevented their subsequent engraftment in SCID mice. Thus, IL6-PE4E may be useful for ex vivo purging of IL-6R+ leukemic cells in an autologous bone marrow transplantation setting and possibly for therapy of residual, chemotherapy-resistant disease. C1 EMORY UNIV,SCH MED,DIV PEDIAT HEMATOL ONCOL BMT,DEPT PEDIAT,ATLANTA,GA 30322. EMORY UNIV HOSP,ONCOL CYTOGENET LAB,ATLANTA,GA 30322. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [R29 CA72020] NR 37 TC 2 Z9 2 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1997 VL 11 IS 10 BP 1779 EP 1786 DI 10.1038/sj.leu.2400757 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA YA291 UT WOS:A1997YA29100026 PM 9324301 ER PT J AU Kreitman, RJ AF Kreitman, RJ TI Getting plant toxins to fuse SO LEUKEMIA RESEARCH LA English DT Article ID B-CHAIN MUTANTS; PSEUDOMONAS EXOTOXIN; FUSION TOXIN; ELONGATION FACTOR-2; GALACTOSE-BINDING; DIPHTHERIA-TOXIN; CHIMERIC TOXIN; RICIN; CELLS; PROTEIN RP Kreitman, RJ (reprint author), NCI,MOL BIOL LAB,DIV CANC BIOL,NIH,37-4E16,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 24 TC 16 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD OCT PY 1997 VL 21 IS 10 BP 997 EP 999 DI 10.1016/S0145-2126(97)00083-0 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA YJ332 UT WOS:A1997YJ33200011 PM 9403010 ER PT J AU Isomoto, S Horio, Y Matsumoto, S Kondo, C Yamada, M Gilbert, DJ Copeland, NG Jenkins, NA Kurachi, Y AF Isomoto, S Horio, Y Matsumoto, S Kondo, C Yamada, M Gilbert, DJ Copeland, NG Jenkins, NA Kurachi, Y TI Sur2 and Kcnj8 genes are tightly linked on the distal region of mouse Chromosome 6 SO MAMMALIAN GENOME LA English DT Article ID LOCALIZATION; EXPRESSION; CHANNELS; MUSCLE; FAMILY C1 OSAKA UNIV,FAC MED,DEPT PHARMACOL 2,SUITA,OSAKA 565,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 10 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 1997 VL 8 IS 10 BP 790 EP 791 DI 10.1007/s003359900573 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XY081 UT WOS:A1997XY08100023 PM 9321483 ER PT J AU Yamada, KM AF Yamada, KM TI Integrin signaling SO MATRIX BIOLOGY LA English DT Review DE cell adhesion; cytoskeleton; extracellular matrix; integrin; signal transduction ID CELL-MATRIX INTERACTIONS; TRANSDUCTION; ADHESION; PROTEINS; BINDING; ACTIVATION; RECEPTOR; KINASES; COMPLEX AB Integrins provide dynamic links between cells and extracellular matrix molecules. Although integrins were originally viewed as relatively simple adhesion molecules, it soon became clear that intracellular signal transduction initiated by integrins is centrally involved in many cellular processes. In fact, a remarkable number of classical signaling pathways are now known to be activated or modified by the interactions of cells with matrix proteins via integrins. These integrin signaling responses can also involve many other extracellular and intracellular molecules. The following mini-reviews were solicited from some of the future leaders in the field of integrin signaling. They examine selected important portions of this field, provide conceptual syntheses from a large and confusing literature, and then propose novel testable ideas. These ideas should encourage dialogue and open new avenues of research in this rapidly expanding, exciting field. RP Yamada, KM (reprint author), NIDR,CRANIOFACIAL DEV BIOL & REGENERAT BRANCH,NIH,BLDG 30,ROOM 421,30 CONVENT DR,MSC 4370,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 49 TC 79 Z9 79 U1 1 U2 5 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD OCT PY 1997 VL 16 IS 4 BP 137 EP 141 DI 10.1016/S0945-053X(97)90001-9 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YF329 UT WOS:A1997YF32900001 PM 9402002 ER PT J AU Chute, JP Venzon, DJ Hankins, L Okunieff, P Frame, JN Ihde, DC Johnson, BE AF Chute, JP Venzon, DJ Hankins, L Okunieff, P Frame, JN Ihde, DC Johnson, BE TI Outcome of patients with small-cell lung cancer during 20 years of clinical research at the US National Cancer Institute SO MAYO CLINIC PROCEEDINGS LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; BRONCHOGENIC-CARCINOMA; THORACIC RADIOTHERAPY; PROGNOSTIC FACTORS; COMBINATION CHEMOTHERAPY; INDUCTION CHEMOTHERAPY; ETOPOSIDE-CISPLATIN; RADIATION-THERAPY; RANDOMIZED TRIAL; DOSE ETOPOSIDE AB Objective: To determine the outcome of all patients with small-cell lung cancer (SCLC) treated at the US National Cancer Institute between April 1973 and April 1993. Design: We retrospectively analyzed a series of 594 consecutive patients with SCLC treated at a single institution during a 20-year period to assess changes in duration of survival and toxicity related to various treatment regimens. Material and Methods: For analysis, patients were grouped by decade, and the duration of survival of patients with limited-and extensive-stage SCLC was examined to assess whether patients treated during the first decade of the study (1973 through 1983), when cyclophosphamide-based regimens were used, had different outcomes than those treated during the second decade (1983 through 1993), when cisplatin-based regimens were used. Patients had a minimal follow-up of 2 years. Results: No significant difference was found in the survival of patients with limited-or extensive-stage SCLC treated during the second decade in comparison with during the first decade of the study. Among patients with extensive-stage SCLC, performance status 3 or 4 and metastatic lesions of the liver and central nervous system had a significant adverse effect on survival in both the first and the second decade. Among patients with limited-stage disease, performance status 3 or 4 had the most significant adverse influence on survival during the overall study period. In addition, in a multivariate analysis, etoposide-cisplatin plus twice-daily chest radiotherapy was significantly associated with prolonged survival (P = 0.003). Conclusion: We noted no significant change in the duration of survival of patients with either limited-or extensive-stage SCLC treated at our institution during a 20-year period. A multivariate analysis showed that patients with limited-stage SCLC given a cisplatin-based regimen plus chest radiotherapy lived modestly longer than similar patients given cyclophosphamide regimens at our institution. No evidence was found of changes in pretreatment factors that would affect survival. C1 NATL NAVAL MED CTR, NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. NCI, MED BRANCH, BETHESDA, MD 20892 USA. NCI, RADIAT ONCOL BRANCH, DIV CLIN SCI, BETHESDA, MD 20892 USA. WASHINGTON UNIV, SCH MED, DIV MED ONCOL, ST LOUIS, MO USA. RI Venzon, David/B-3078-2008 NR 52 TC 34 Z9 34 U1 0 U2 1 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 1997 VL 72 IS 10 BP 901 EP 912 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA YC252 UT WOS:A1997YC25200002 PM 9379691 ER PT J AU Schmidt, HHJ Gregg, RE Shamburek, R Brewer, BHB Zech, LA AF Schmidt, HHJ Gregg, RE Shamburek, R Brewer, BHB Zech, LA TI Erdheim-Chester disease: Low low-density lipoprotein levels due to rapid catabolism SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID APOLIPOPROTEIN-A-I; XANTHOMA-DISSEMINATUM; DIABETES-INSIPIDUS; CHOLESTEROL; ATHEROSCLEROSIS; DEPOSITION; METABOLISM; XANTHOGRANULOMATOSIS; HISTIOCYTOSIS; INVOLVEMENT AB We have identified a 44-year-old patient with symmetrically excessive xanthomatosis, called Erdheim-Chester disease (ECD), and simultaneously decreased levels of low-density lipoprotein (LDL) cholesterol. Clinically, this patient presents lipoidgranulomatosis of numerous long and flat bones with involvement of the liver, spleen, pericardium, pleura, thyroid, skin, conjunctiva, and gingiva. However, the patient does not have any signs of atherosclerosis. So far, the underlying defect has not been elucidated, We performed a LDL-apolipoprotein B (apoB) kinetic study in the ECD patient and a normal control to determine the etiology of the low LDL level in ECD. LDL was isolated from both subjects, radioiodinated with either I-131 or I-125, and injected simultaneously into the ECD patient and the normal control. Normal and ECD LDL was catabolized at the same rate after injection into the control subject (fractional catabolic rate [FCR], 0.43/d and 0.46/d, respectively). Therefore, LDL isolated from an ECD subject is metabolically normal, In contrast, autologous LDL injected into the ECD subject showed a markedly increased catabolism (FCR, 0.69/d) compared with that in the control subject (FCR, 0.43/d). This is the first report about increased catabolism of LDL cholesterol in a patient. C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NR 39 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 1997 VL 46 IS 10 BP 1215 EP 1219 DI 10.1016/S0026-0495(97)90220-1 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XY568 UT WOS:A1997XY56800022 PM 9322810 ER PT J AU Venkatakrishnan, V Fisher, WR Zech, LA AF Venkatakrishnan, V Fisher, WR Zech, LA TI Determination of the radiation dose from administered apolipoprotein tracers in humans SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT National-Institute-of-Health Symposium on In Vivo Tracer Kinetics and Modeling CY MAY 03, 1996 CL NATL INST OF HLTH, BETHESDA, MD SP NIH HO NATL INST OF HLTH ID LIPOPROTEINS AB Radioactive tracers are routinely used in investigation of the metabolism of apolipoprotein kinetics. Here, metabolic studies of apolipoprotein tracers labelled with radioiodine were analysed to determine the absorbed radiation dose received by the subject. This analysis used compartmental modelling techniques to evaluate the radiation dose to various organs and the total body resulting from radioiodinated tracer injection. In this approach, we combined the published kinetic models of iodine and those of specific apolipoproteins. From the solution of the integrated compartmental models, residence times of the radiation in various source organs, in particular the thyroid, whole body, bladder, and red bone marrow, have been determined for the apolipoproteins apoA-I, apoA-II, very-low-density lipoprotein (VLDL)-apoB, and low-density lipoprotein (LDL)-apoB, each labelled with iodine 123, 133, 124, 131, 126, and 125. These tabulated values were used to calculate radiation doses to the different target organs. The thyroid is the organ that receives the largest dose of delivered radiation, and the importance of the duration of administration of iodine salts in blocking radiation to the thyroid is demonstrated. Optimal block times of 28 days for I-131 and 42 days for I-125-labeled apolipoprotein tracers are proposed. When such a protocol is followed, the radiation dose to the thyroid and other organs is small by comparison to radiation doses allowed for workers whose occupation exposes them to radiation. The importance of frequent voiding to reduce the radiation dose to the bladder has also been demonstrated. Copyright (C) 1997 by W.B. Saunders Company. C1 UNIV FLORIDA,JHMHSC,DEPT NUCL ENGN SCI,GAINESVILLE,FL 32610. UNIV FLORIDA,DEPT MED,GAINESVILLE,FL 32610. NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. FU NCRR NIH HHS [M01RR00082]; NHLBI NIH HHS [HL-29394] NR 11 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 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 1997 VL 46 IS 10 BP 1231 EP 1239 DI 10.1016/S0026-0495(97)90223-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XY568 UT WOS:A1997XY56800025 PM 9322813 ER PT J AU Sherman, ME Sturgeon, S Brinton, LA Potischman, N Kurman, RJ Berman, ML Mortel, R Twiggs, LB Barrett, RJ Wilbanks, GD AF Sherman, ME Sturgeon, S Brinton, LA Potischman, N Kurman, RJ Berman, ML Mortel, R Twiggs, LB Barrett, RJ Wilbanks, GD TI Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 11-17, 1995 CL TORONTO, CANADA SP US & Canadian Acad Pathol DE endometrial carcinoma; endometrioid; hormones; pathogenesis; risk; serous ID PAPILLARY CARCINOMA; POSTMENOPAUSAL WOMEN; CANCER; P53; EPIDEMIOLOGY; RECURRENCE; RECEPTORS; MUTATION; ESTROGEN; UTERUS AB We performed a multi-institutional, incident case-control study of 328 endometrioid and 26 serous carcinomas to assess whether risk factors and circulating hormone levels in women with serous carcinoma differ from the expected profile for endometrial carcinoma. We also evaluated exposures potentially related to endometrial cancer risk, anthropometric measurements, and circulating levels of sex hormones and related carrier proteins. Histopathologic specimens were reviewed without knowledge of the other data. As expected, a statistically significant association was observed for high body mass index (BMI) (relative risk, 3.5) and use of menopausal estrogens (relative risk, 2.4) in the endometrioid carcinoma cases, whereas serous carcinomas were not strongly associated with these factors. Smoking and oral contraceptive use decreased risk for both tumor types. For five of six sex hormones tested, age-adjusted mean serum levels in patients with serous carcinoma were significantly lower than those in women with endometrioid carcinoma. After adjustment for BMI, these differences were narrowed, but levels of albumin-bound estradiol and estrone remained significantly lower in the serous cases. Age and BMI-adjusted levels of sex hormone-binding globulin were significantly higher in patients with serous carcinoma than in women with endometrioid carcinomas. In conclusion, risk factors and sex hormone levels in patients with uterine serous carcinoma seem to differ from those in women with endometrioid carcinoma, suggesting that there may be at least two different pathways of endometrial carcinogenesis. C1 JOHNS HOPKINS MED INST,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21205. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. UNIV CALIF IRVINE,IRVINE MED CTR,DEPT OBSTET & GYNECOL,ORANGE,CA 92668. MILTON S HERSHEY MED CTR,DEPT OBSTET & GYNECOL,HERSHEY,PA. UNIV MINNESOTA,HLTH SCI CTR,DEPT OBSTET & GYNECOL,MINNEAPOLIS,MN 55455. BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC. RUSH MED COLL,DEPT OBSTET & GYNECOL,CHICAGO,IL 60612. RP Sherman, ME (reprint author), JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 39 TC 74 Z9 77 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 1997 VL 10 IS 10 BP 963 EP 968 PG 6 WC Pathology SC Pathology GA YB118 UT WOS:A1997YB11800001 PM 9346174 ER PT J AU Chang, CP Jacobs, Y Nakamura, T Jenkins, NA Copeland, NG Cleary, ML AF Chang, CP Jacobs, Y Nakamura, T Jenkins, NA Copeland, NG Cleary, ML TI Meis proteins are major in vivo DNA binding partners for wild-type but not chimeric Pbx proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN PROTOONCOGENE PBX1; HOX-2.4 HOMEOBOX GENE; HOMEODOMAIN PROTEIN; MYELOID-LEUKEMIA; HOX PROTEINS; TRANSCRIPTIONAL ACTIVATOR; COOPERATIVE INTERACTIONS; NUCLEAR-LOCALIZATION; PRE-B; EXTRADENTICLE AB The Pbx1 and Meis1 proto-oncogenes code for divergent homeodomain proteins that are targets for oncogenic mutations in human and murine leukemias, respectively, and implicated by genetic analyses to functionally collaborate with Hox proteins during embryonic development and/or oncogenesis. Although Pbx proteins have been shown to dimerize with Hox proteins and modulate their DNA binding properties in vitro, the biochemical compositions of endogenous Pbx-containing complexes have not been determined. In the present study, we demonstrate that Pbx and Meis proteins form abundant complexes that comprise a major Pbx-containing DNA binding activity in nuclear extracts of cultured cells and mouse embryos. Pbx1 and Meis1 dimerize in solution and cooperatively bind bipartite DNA sequences consisting of directly adjacent Pbx and Meis half sites. Pbx1-Meis1 heterodimers display distinctive DNA binding specificities and cross-bind to a subset of Pbx-Hox sites, including those previously implicated as response elements for the execution of Pbx-dependent Hox programs in vivo. Chimeric oncoprotein E2a-Pbx1 is unable to bind DNA with Meis1, due to the deletion of amino-terminal Pbx1 sequences following fusion with E2a. We conclude that Meis proteins are preferred in vivo DNA binding partners for wild-type Pbx1, a relationship that is circumvented by its oncogenic counterpart E2a-Pbx1. C1 STANFORD UNIV,MED CTR,DEPT PATHOL,STANFORD,CA 94305. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [CA42971, CA09151] NR 53 TC 179 Z9 183 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1997 VL 17 IS 10 BP 5679 EP 5687 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XX658 UT WOS:A1997XX65800002 PM 9315626 ER PT J AU Goodier, JL Fan, H Maraia, RJ AF Goodier, JL Fan, H Maraia, RJ TI A carboxy-terminal basic region controls RNA polymerase III transcription factor activity of human La protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID 2 FUNCTIONAL COMPONENTS; SACCHAROMYCES-CEREVISIAE; SMALL RIBONUCLEOPROTEINS; INITIATION-FACTOR; CYTOPLASMIC RNAS; RIBOSOMAL-RNA; INVITRO; EXPRESSION; BINDING; GENE AB Human La protein has been shown to serve as a transcription factor for RNA polymerase III (pol III) by facilitating transcription termination and recycling of transcription complexes. In addition, La binds to the 3' oligo(U) ends common to all nascent pol III transcripts, and in the case of B1-Alu RNA, protects it from 3'-end processing (R. J. Maraia, D. J. Kenan, and J. D. Keene, Mol. Cell. Biol. 14:2147-2158, 1994). Others have previously dissected the La protein into an N-terminal domain that binds RNA and a C-terminal domain that does not. Here, deletion and substitution mutants of La were examined for general RNA binding, RNA 3'-end protection, and transcription factor activity. Although some La mutants altered in a C-terminal basic region bind RNA in mobility shift assays, they are defective in RNA 3'-end protection and do not support transcription, while one C-terminal substitution mutant is defective only in transcription. Moreover, a C-terminal fragment lacking RNA binding activity appears able to support low levels of transcription by pol m. While efficient multiround transcription is supported only by mutants that bind RNA and contain a C-terminal basic region, These analyses indicate that RNA binding contributes to but is not sufficient for La transcription factor activity and that the C-terminal domain plays a role in transcription that is distinguishable from simple RNA binding, The transcription factor activity of La can be reversibly inhibited by RNA, suggesting the potential for feedback inhibition of pol III transcription. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NR 47 TC 61 Z9 61 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1997 VL 17 IS 10 BP 5823 EP 5832 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XX658 UT WOS:A1997XX65800016 PM 9315640 ER PT J AU Ding, HF Bustin, M Hansen, U AF Ding, HF Bustin, M Hansen, U TI Alleviation of histone H1-mediated transcriptional repression and chromatin compaction by the acidic activation region in chromosomal protein HMG-14 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; NEWBORN GUINEA-PIGS; ACTIVE CHROMATIN; NUCLEOSOME CORES; IN-VIVO; BINDING; DNA; GENES; COMPLEX; REPLICATION AB Histone H1 promotes the generation of a condensed, transcriptionally inactive, higher order chromatin structure. Consequently histone H1 activity must be antagonized in order to convert chromatin to a transcriptionally competent, more extended structure. Using simian virus 40 minichromosomes as a model system, we now demonstrate that the nonhistone chromosomal protein HMG-14, which is known to preferentially associate with active chromatin, completely alleviates histone H1-mediated inhibition of transcription by RNA polymerase II. HMG-14 also partially disrupts histone H1-dependent compaction of chromatin. Bath the transcriptional enhancement and chromatin-unfolding activities of HMG-14 are mediated through its acidic, C-terminal region. Strikingly, transcriptional and structural activities of HMG-14 are maintained upon replacement of the C-terminal fragment by acidic regions from either GAL4 or HMG-2. These data support the model that the acidic C terminus of HMG-14 is involved in unfolding higher-order chromatin structure to facilitate transcriptional activation of mammalian genes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOL GENET,B411,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 FU NCI NIH HHS [5T32CA0936] NR 74 TC 70 Z9 73 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1997 VL 17 IS 10 BP 5843 EP 5855 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XX658 UT WOS:A1997XX65800018 PM 9315642 ER PT J AU Lee, YH Sauer, B Johnson, PF Gonzalez, FJ AF Lee, YH Sauer, B Johnson, PF Gonzalez, FJ TI Disruption of the c/ebp alpha gene in adult mouse liver SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; SITE-SPECIFIC RECOMBINATION; CYCLIN-DEPENDENT KINASES; ENHANCER-BINDING PROTEIN; FACTOR-I GENE; CRE RECOMBINASE; TRANSCRIPTIONAL REGULATION; TRANSFERRIN PROMOTER; MOLECULAR-CLONING; NUCLEAR FACTORS AB The liver-enriched transcription factor C/EBP alpha has been implicated in the regulation of numerous liver-specific genes, It was previously reported that mice carrying a homozygous null mutation at the c/ebp alpha locus died as neonates due to the absence of hepatic glycogen and the resulting hypoglycemia. However, the lethal phenotype precluded further analysis of the role of C/EBP alpha in hepatic gene regulation in adult mice, To circumvent this problem, we constructed a conditional knockout allele of c/ebp alpha by using the Cre/loxP recombination system. Homozygous c/ebp-loxP mice, (c/ebp alpha(fl/fl); fl, flanked by loxP sites) were found to be indistinguishable from their wild-type counterparts, However, when Cre recombinase was delivered to hepatocytes of adult c/ebp alpha(fl/fl) mice by infusion of a recombinant adenovirus carrying the cre gene, more than 80% of the c/ebp alpha(fl/fl) genes were deleted specifically in liver and C/EBP alpha expression was reduced by 90%. This condition resulted in a reduced level of bilirubin UDP-glucuronosyltransferase expression in the liver. After several days, the knockout mice del eloped severe jaundice due to an increase in unconjugated serum bilirubin. The expression of genes encoding phosphoenolpyruvate carboxykinase, glycogen synthase, and factor IX was also strongly reduced in adult conditional-knockout animals, while the expression of transferrin, apolipoprotein B, and insulin-like growth factor I genes was not affected. These results establish C/EBP alpha as an essential transcriptional regulator of genes encoding enzymes involved in bilirubin detoxification and gluconeogenesis in adult mouse liver. C1 NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. NCI,LAB METAB,NIH,BETHESDA,MD 20892. NCI,EUKARYOT TRANSCRIPT REGULAT GRP,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 45 TC 146 Z9 147 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1997 VL 17 IS 10 BP 6014 EP 6022 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XX658 UT WOS:A1997XX65800036 PM 9315660 ER PT J AU deMora, JF Porras, A Ahn, N Santos, E AF deMora, JF Porras, A Ahn, N Santos, E TI Mitogen-activated protein kinase activation is not necessary for, but antagonizes, 3T3-L1 adipocytic differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-I; MAP KINASE; TRANSCRIPTION FACTOR; RAF-1 KINASE; RESPONSIVENESS INVITRO; HORMONE RECEPTORS; MAPK/RSK CASCADE; GENE-EXPRESSION; C-FOS AB In 3T3-L1 fibroblasts, Ras proteins mediate both insulin-induced differentiation to adipocytes and its activation of cytosolic serine/threonine kinases, including Raf-1 kinase, mitogen-activated protein kinase (MAPK), and Rsk. Here, we report that insulin-and Ras-induced activation of MAPK is not required for the differentiation process and in fact antagonizes it, The treatment of 3T3-L1 preadipocytes with MEK-specific inhibitor PD98059 blocked insulin- and Ras-induced MAPK activation but had no effect on or slightly enhanced adipocytic differentiation. Tumor necrosis factor alpha (TNF-alpha), an inhibitor of insulin stimulated adipogenesis, activated MAPK in 3T3-L1 cells. PD98059 treatment blocked MAPK activation by TNF-alpha and reversed the blockade of adipogenesis mediated bg low (1 ng/ml) TNF-alpha concentrations. 3T3-L1 transfectants containing hyperactivated MEK1 or overexpressed MAPK displayed impaired adipocytic differentiation, PD98059 treatment also reversed the blockade of differentiation in MEK1 transfectants. These results indicate that MAPK does not promote but can contribute to inhibition of the process of adipocytic differentiation of 3T3-L1 cells. C1 NCI, CELLULAR & MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. UNIV COLORADO, DEPT CHEM & BIOCHEM, HOWARD HUGHES MED INST, BOULDER, CO 80309 USA. RI Porras, Almudena/N-2121-2015 OI Porras, Almudena/0000-0002-6495-3308 NR 57 TC 134 Z9 134 U1 0 U2 2 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 1997 VL 17 IS 10 BP 6068 EP 6075 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XX658 UT WOS:A1997XX65800042 ER PT J AU Pu, RT Dasso, M AF Pu, RT Dasso, M TI The balance of RanBP1 and RCC1 is critical for nuclear assembly and nuclear transport SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; GTPASE-ACTIVATING PROTEIN; CELL-CYCLE PROGRESSION; LAEVIS EGG EXTRACTS; BINDING-PROTEIN; DNA-REPLICATION; RAN/TC4 GTPASE; IMPORT; YEAST; REGULATOR AB Ran is a small GTPase that is essential for nuclear transport, mRNA processing, maintenance of structural integrity of nuclei, and cell cycle control. RanBP1 is a highly conserved Ran guanine nucleotide dissociation inhibitor. We sought to use Xenopus egg extracts for the development of an in vitro assay for RanBP1 activity in nuclear assembly, protein import, and DNA replication. Surprisingly, when we used anti-RanBP1 antibodies to immunodeplete RanBP1 from Xenopus egg extracts, we found that the extracts were also depleted of RCC1, Ran's guanine nucleotide exchange factor, suggesting that these proteins form a stable complex. In contrast to previous observations using extracts that had been depleted of RCC1 only, extracts lacking both RanBP1 and RCC1 (codepleted extracts) did not exhibit defects in assays of nuclear assembly, nuclear transport, or DNA replication. Addition of either recombinant RanBP1 or RCC1 to codepleted extracts to restore only one of the depleted proteins caused abnormal nuclear assembly and inhibited nuclear transport and DNA replication in a manner that could be rescued by further addition of RCC1 or RanBP1, respectively. Exogenous mutant Ran proteins could partially rescue nuclear function in extracts without RanBP1 or without RCC1, in a manner that was correlated with their nucleotide binding state. These results suggest that little RanBP1 or RCC1 is required for nuclear assembly, nuclear import, or DNA replication in the absence of the other protein. The results further suggest that the balance of GTP-and GDP-Ran is critical for proper nuclear assembly and function in vitro. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. OI Dasso, Mary/0000-0002-5410-1371 NR 48 TC 31 Z9 33 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 1997 VL 8 IS 10 BP 1955 EP 1970 PG 16 WC Cell Biology SC Cell Biology GA YB663 UT WOS:A1997YB66300010 PM 9348536 ER PT J AU Maroulakou, IG Shibata, MA Jorcyk, CL Chen, XX Green, JE AF Maroulakou, IG Shibata, MA Jorcyk, CL Chen, XX Green, JE TI Reduced p53 dosage associated with mammary tumor metastases in C3(1)/T-AG transgenic mice SO MOLECULAR CARCINOGENESIS LA English DT Article DE p53; transgenic mice; simian virus 40 large-T antigen; mammary cancer; tumor progression; metastases ID LARGE T-ANTIGEN; SUPPRESSOR GENE; BREAST-CANCER; MUTATIONS; PROTEIN; PROGRESSION; EXPRESSION; PROSTATE; SPECTRUM AB Transgenic mice expressing the simian virus 40 large T-antigen (T-AG) under the regulatory control of the rat prostatic steroid binding protein C3(1) gene develop mammary carcinomas (in females) and prostate carcinomas (in males). The development of carcinomas occurs several months after the appearance of dysplastic lesions, suggesting that T-AG is necessary but insufficient for tumor formation and that other genetic events are involved in this process. T-AG is known to bind to p53 and to result in its functional inactivation, which is believed to be a critical step in T-AG-induced transformation. We investigated whether the T-AG-p53 interaction is rate limiting in the development of phenotypic changes in these transgenic mice by crossing C3(1)/T-AG transgenics with mice carrying null mutations of the p53 gene. T-AG-expressing animals with a p53(+/-) genotype developed much more aggressive mammary tumors, as evidenced by increased numbers and size of metastases, than did T-AG-expressing animals carrying two wild-type p53 alleles. While p53 was expressed in primary tumors, p53 expression appeared to be reduced or lost in many metastases in mice carrying either the p53(+/+) or p53(+/-) genotypes. The tumorigenic process did not appear to be due to the loss of the second wild-type p53 allele or the gain of dominant oncogenic mutations in p53, as no mutations were detected in either primary or metastatic tumors by polymerase chain reaction-single-strand conformation polymorphism analyses. These findings suggest that despite the presence of T-AG, p53 levels influence the characteristics of the late stages of mammary tumor growth and accelerate metastases. Functional loss of p53 and not p53 mutations participates in T-AG-induced mammary carcinoma development and progression. (C) 1997 Wiley-Liss, Inc. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,OFF LAB ANIM SCI,FREDERICK,MD 21701. NR 29 TC 15 Z9 15 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 1997 VL 20 IS 2 BP 168 EP 174 DI 10.1002/(SICI)1098-2744(199710)20:2<168::AID-MC3>3.0.CO;2-J PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA YE254 UT WOS:A1997YE25400003 PM 9364206 ER PT J AU Warner, DR Gejman, PV Collins, RM Weinstein, LS AF Warner, DR Gejman, PV Collins, RM Weinstein, LS TI A novel mutation adjacent to the switch III domain of G(S alpha) in a patient with pseudohypoparathyroidism SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HETEROTRIMERIC G-PROTEIN; BETA-GAMMA SUBUNIT; ADENYLATE-CYCLASE; HEREDITARY OSTEODYSTROPHY; REGULATORY COMPONENT; CRYSTAL-STRUCTURE; GTP HYDROLYSIS; ALPHA-SUBUNIT; RECEPTOR; GENE AB A novel G(s alpha) mutation encoding the substitution of arginine for serine 250 (G(s alpha) S250R) was identified in a patient with pseudohypoparathyroidism type Ia. Both G(s) activity and G(s alpha) expression were decreased by about 50% in erythrocyte membranes from the affected patient. The cDNA of this G(s alpha) mutant, as well as one in which the S250 residue is deleted (G(s alpha)-Delta S250), was generated, and the biochemical properties of the products of in vitro transcription/translation were examined. Both mutants had a sedimentation coefficient similar to that of wild type G(s alpha) (similar to 3.7S) when kept at 0 C after synthesis. However when maintained for 1-2 h at 30-37 C, both mutants aggregated to a material sedimenting at similar to 6.3S or greater (G(s alpha)-S250R to a greater extent than G(s alpha)-Delta S250), while wild type G(s alpha) sedimented at similar to 3.7S, suggesting that the mutants were thermolabile. Incubation in the presence of high doses of guanine nucleotide partially prevented heat denaturation of G(s alpha) Delta S250 but had no protective effect on G(s alpha)-S250R. Sucrose density gradient centrifugation at 0 C in the presence and absence of beta gamma-dimers demonstrated that, in contrast to wild type G(s alpha), neither mutant could interact with beta gamma. Trypsin protection assays revealed no protection of G(s alpha)-S250R by GTP gamma S or AlF4- at any temperature. GTP gamma S conferred modest protection of G(s alpha)-Delta S250 (similar to 50% of wild-type G(s alpha)) at 30 C but none at 37 C, while AlF4- conferred slight protection at 20 C but none at 30 C or above. Consistent with this result, G(s alpha)-Delta S250 was able to stimulate adenylyl cyclase at 30 C when reconstituted with cyc(-) membranes in the presence of GTP gamma S but not in the presence of AlF4-. G(s alpha)-S250R showed no ability to stimulate adenylyl cyclase in the presence of either agent. Stable transfection of mutant and wild-type G(s alpha) into cyc(-) S49 lymphoma cells revealed that the majority of wild type G(s alpha) localized to membranes, while little or no membrane localization occurred for either mutant. Modeling of G(s alpha) based upon the crystal structure of G(t alpha) or G(i alpha) suggests that Ser(250) interacts with several residues within and around the conserved NKXD motif, which directly interacts with the guanine ring of bound GDP or GTP. It is therefore possible that substitution or deletion of this residue may alter guanine nucleotide binding, which could lead to thermolability and impaired function. C1 NIMH, CLIN NEUROGENET BRANCH, NIH, BETHESDA, MD 20892 USA. NIDDKD, METAB DIS BRANCH, NIH, BETHESDA, MD 20892 USA. RP Warner, DR (reprint author), NINCDS, MEMBRANE BIOCHEM SECT, MOL & CELLULAR NEUROBIOL LAB,NIH,BLDG 49, ROOM 2A28, BETHESDA, MD 20892 USA. NR 37 TC 43 Z9 45 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1997 VL 11 IS 11 BP 1718 EP 1727 DI 10.1210/me.11.11.1718 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XY295 UT WOS:A1997XY29500014 PM 9328353 ER PT J AU Tsai, HF Washburn, RG Chang, YC KwonChung, KJ AF Tsai, HF Washburn, RG Chang, YC KwonChung, KJ TI Aspergillus fumigatus arp1 modulates conidial pigmentation and complement deposition SO MOLECULAR MICROBIOLOGY LA English DT Article ID CRYPTOCOCCUS-NEOFORMANS; COLLETOTRICHUM-LAGENARIUM; PULMONARY ASPERGILLOSIS; GENE; VIRULENCE; NIDULANS; RESISTANCE; TRANSFORMATION; BIOSYNTHESIS; TRICYCLAZOLE AB Aspergillus fumigatus is an important pathogen causing invasive pulmonary aspergillosis in immunocompromised patients. The fungus propagates by conidia, which are the infectious structures inhaled by the human host. Opsonophagocytosis is thought to contribute to clearance of the inhaled conidia, a process that is facilitated by complement deposition on conidial surfaces. We now show that conidial colour mutants exhibit significant increases in C3 binding capacity compared with wild type. A reddish-pink mutation that led to enhanced C3 binding was complemented by a cosmid clone. A 3.3 kb DNA fragment from the subsequently rescued cosmid was sufficient to restore the bluish-green conidial pigment. The bluish-green transformant exhibited a level of C3 binding similar to that of the parental strain. A gene, designated arp1, was responsible for the complementation. Comparison of the genomic and cDNA sequences of arp1 revealed that it has two introns and encodes a putative protein of 168 amino acids. Arp1 is very similar to scytalone dehydratase, an enzyme involved in 1,8-dihydroxynaphthalene-melanin synthesis in Colletotrichum lagenarium and Magnaporthe grisea. Northern hybridization analysis revealed that arp1 is developmentally regulated, being expressed during conidiation. Disruption of arp1 resulted in reddish-pink conidia and increased C3 binding. Our studies suggest that arp1 modulates the bluish-green pigmentation of conidia as well as complement deposition. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,INFECT DIS SECT,WINSTON SALEM,NC 27103. FU NIAID NIH HHS [AI-01036] NR 51 TC 69 Z9 78 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1997 VL 26 IS 1 BP 175 EP 183 DI 10.1046/j.1365-2958.1997.5681921.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YB786 UT WOS:A1997YB78600015 PM 9383199 ER PT J AU Dibbens, JA Muraiso, K Chattoraj, DK AF Dibbens, JA Muraiso, K Chattoraj, DK TI Chaperone-mediated reduction of RepA dimerization is associated with RepA conformational change SO MOLECULAR MICROBIOLOGY LA English DT Article ID P1 PLASMID REPLICATION; PHAGE-LAMBDA-REPRESSOR; SHOCK PROTEINS DNAJ; INITIATOR PROTEIN; ESCHERICHIA-COLI; OPERATOR BINDING; LIGAND-BINDING; COPY NUMBER; ORIGIN; DIMERS AB RepA, the initiator protein of plasmid P1, binds to multiple sites (iterons) in the origin, The binding normally requires participation of chaperones, DnaJ, DnaK and GrpE. When purified, RepA appears dimeric and is inactive in iteron binding, On reaction with chaperones, a species active in iteron binding is formed and found to be monomeric. To test whether the chaperones can reduce dimerization, RepA was used to replace the dimerization domain of the lambda repressor. The hybrid protein repressed the lambda operator efficiently, indicating that RepA can dimerize in vivo. A further increase in repressor activity was seen in dnaJ mutant cells, These results are consistent with a chaperone-mediated reduction of RepA dimerization, We also found that RepA mutants defective in dimerization still depend on DnaJ for iteron binding, Conversely, RepA mutants that no longer require chaperones for iteron binding remain dimerization proficient, These results indicate that the chaperone dependence of RepA activity is not solely owing to RepA dimerization, Our results are most simply explained by a chaperone-mediated conformational change in RepA protomer that activates iteron binding. This conformational change also results in reduced RepA dimerization. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 46 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1997 VL 26 IS 1 BP 185 EP 195 DI 10.1046/j.1365-2958.1997.5691920.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YB786 UT WOS:A1997YB78600016 PM 9383200 ER PT J AU Berg, DE Strausbaugh, L Shaw, KJ Zhang, JH AF Berg, DE Strausbaugh, L Shaw, KJ Zhang, JH TI Claire Berg, 1937-1997 - In memoriam SO MOLECULAR MICROBIOLOGY LA English DT Item About an Individual C1 UNIV CONNECTICUT,STORRS,CT. SCHERING PLOUGH RES INST,KENILWORTH,NJ. NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. RP Berg, DE (reprint author), WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1997 VL 26 IS 2 BP 409 EP 410 PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YF447 UT WOS:A1997YF44700017 ER PT J AU Kowalski, RJ Giannakakou, P Gunasekera, SP Longley, RE Day, BW Hamel, E AF Kowalski, RJ Giannakakou, P Gunasekera, SP Longley, RE Day, BW Hamel, E TI The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (Taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID GUANINE-NUCLEOTIDES; POLYMERIZATION; PROTEINS; MECHANISM; ANALOGS; 5'-TRIPHOSPHATE; CYTOTOXICITY; DYNAMICS; INVITRO; ABSENCE AB The lactone-bearing polyhydroxylated alkatetraene (+)-discodermolide, which was isolated from the sponge Discodermia dissoluta, induces the polymerization of purified tubulin with and without microtubule-associated proteins or GTP, and the polymers formed are stable to cold and calcium. These effects are similar to those of paclitaxel (Taxol), but discodermolide is more potent. We confirmed that these properties represent hypernucleation phenomena; we obtained lower tubulin critical concentrations and shorter polymers with discodermolide than paclitaxel under a variety of reaction conditions. Furthermore, we demonstrated that discodermolide is a competitive inhibitor with [H-3]paclitaxel in binding to tubulin polymer, with an apparent K-i value of 0.4 mu M. Multidrug-resistant human colon and ovarian carcinoma cells overexpressing P-glycoprotein, which are 900- and 2800-fold resistant to paclitaxel, respectively, relative to the parental lines, retained significant sensitivity to discodermolide (25- and 89-fold more resistant relative to the parental lines). Ovarian carcinoma cells that are 20-30-fold more resistant to paclitaxel than the parental line on the basis of expression of altered beta-tubulin polypeptides retained nearly complete sensitivity to discodermolide. The effects of discodermolide on the reorganization of the microtubules of Potorous tridactylis kidney epithelial cells were examined at different times. Intracellular microtubules were reorganized into bundles in interphase cells much more rapidly after discodermolide treatment compared with paclitaxel treatment. A variety of spindle aberrations were observed after treatment with both drugs. The proportions of the different types of aberration were different for the two drugs and changed with the length of drug treatment. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,DIV CLIN SCI,MED BRANCH,NIH,BETHESDA,MD 20892. HARBOR BRANCH OCEANOG INST INC,DIV BIOMED MARINE RES,FT PIERCE,FL 34946. UNIV PITTSBURGH,INST CANC,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15238. UNIV PITTSBURGH,INST CANC,DEPT PHARMACEUT SCI,PITTSBURGH,PA 15238. NR 40 TC 197 Z9 202 U1 2 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1997 VL 52 IS 4 BP 613 EP 622 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YA268 UT WOS:A1997YA26800009 PM 9380024 ER PT J AU Licinio, J AF Licinio, J TI Biomedicine '98 - Call for abstracts SO MOLECULAR PSYCHIATRY LA English DT Editorial Material RP Licinio, J (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BLDG 10,RM 2D46,BETHESDA,MD 20892, USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 1 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT-NOV PY 1997 VL 2 IS 6 BP 429 EP 429 DI 10.1038/sj.mp.4000337 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA YD107 UT WOS:A1997YD10700001 ER PT J AU Negrao, AB AF Negrao, AB TI Mood disorders across the continents SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID DEPRESSION; EPIDEMIOLOGY AB A large cross-national epidemiological study of mood disorders reveals consistent clinical patterns that might help with the localization of genetic markers. RP Negrao, AB (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BLDG 10,RM 2D46,10 CTR DR MSC 1284,BETHESDA,MD 20892, USA. RI Negrao, Andre Brooking/C-9526-2014 OI Negrao, Andre Brooking/0000-0002-8133-6723 FU NIMH NIH HHS [MH37592] NR 11 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT-NOV PY 1997 VL 2 IS 6 BP 439 EP 441 DI 10.1038/sj.mp.4000318 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA YD107 UT WOS:A1997YD10700006 PM 9399683 ER PT J AU Stratakis, CA Sarlis, NJ Berrettini, WH Badner, JA Chrousos, GP Gershon, ES DeteraWadleigh, SD AF Stratakis, CA Sarlis, NJ Berrettini, WH Badner, JA Chrousos, GP Gershon, ES DeteraWadleigh, SD TI Lack of linkage between the corticotropin-releasing hormone (CRH) gene and bipolar affective disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE corticotropin-releasing hormone (CRH) gene; linkage; bipolar disorder; stress; chromosome 8q13; dinucleotide repeat polymorphism ID OLD-ORDER AMISH; MANIC-DEPRESSIVE ILLNESS; PEDIGREE-MEMBER METHOD; SUSCEPTIBILITY LOCUS; BIOCHEMICAL MANIFESTATIONS; PREDISPOSING LOCUS; STRESS SYSTEM; DNA MARKERS; NEUROENDOCRINOLOGY; CHROMOSOME-11P AB Corticotropin-releasing hormone (CRH) plays a key role in the regulation of the stress response. Abnormalities in CRH secretion have been documented in both the depression and manic phases of bipolar disorder (BPD). In the present study, we investigated genetic linkage between the CRH gene and BPD in 22 pedigrees. A highly informative, short tandem repeat (STR) polymorphism adjacent to the CRH gene on human chromosomal region 8q13 was used to examine linkage. Affected sibling pair (ASP) and the likelihood-based disequilibrium tests revealed nonsignificant values. We conclude that the CRH gene is not linked to BPD; if genes involved in the regulation of stress response are indeed linked to BPD, the search should be directed towards those that regulate CRH secretion or its effects on target tissues. C1 NIDDK,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. NIMH,CLIN NEUROGENET BRANCH,NIH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT & HUMAN BEHAV,PHILADELPHIA,PA 19107. GEORGETOWN UNIV,CHILDRENS MED CTR,WASHINGTON,DC 20007. RP Stratakis, CA (reprint author), NICHHD,DEB,NIH,BLDG 10,RM 10 N 262,10 CTR DR,MSC 1862,BETHESDA,MD 20892, USA. NR 39 TC 7 Z9 7 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT-NOV PY 1997 VL 2 IS 6 BP 483 EP 485 DI 10.1038/sj.mp.4000268 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA YD107 UT WOS:A1997YD10700016 PM 9399692 ER PT J AU Bergen, AW Peterson, R Kokoszka, J Long, JC Virkkunen, M Linnoila, M Goldman, D AF Bergen, AW Peterson, R Kokoszka, J Long, JC Virkkunen, M Linnoila, M Goldman, D TI mu opioid receptor gene variants: lack of association with alcohol dependence SO MOLECULAR PSYCHIATRY LA English DT Article DE OPRM1; mu opioid receptor; polymorphism; alcoholism; substance ID OPIATE RECEPTOR; CHROMOSOMAL ASSIGNMENT; SIGNAL-TRANSDUCTION; HEALTHY-VOLUNTEERS; VIOLENT OFFENDERS; BETA-ENDORPHIN; MESSENGER-RNA; FIRE SETTERS; NALTREXONE; EXPRESSION AB The mu opioid receptor is implicated in the reward, tolerance and withdrawal effects of alcohol and other drugs of abuse.(1,2) This hypothesis is supported by the effects of alcohol on beta-endorphin release,(3) of mu opioid receptor agonists and antagonists on alcohol consumption,(4,5) and by the activation of the dopaminergic reward system by both alcohol and opiates.(6) In addition, the murine mu opioid receptor locus, Oprm, is implicated as the major quantitative trait locus (QTL) affecting the different levels of morphine consumption between two inbred mouse strains that also exhibit differences in alcohol and cocaine consumption.(7,8) Detection of genetic variation affecting OPRM1 expression or mu opioid receptor function would be an important step towards understanding the origins of inter-individual variation in response to mu opioid receptor ligands and in diseases of substance dependence.(9-12) We directly sequenced the human mu opioid receptor locus, OPRM1,(13-15) to detect natural variation that might affect function and/or be associated with psychiatric phenotypes related to opioid function. Four DNA sequence variants were found: three non-synonymous substitutions (Ala6Val [rare], Asn40Asp, [0.10-0.16], Ser147Cys [rare]) and one intronic variant (IVS2+691G/C [0.55-0.63]). OPRM1 alleles, genotypes and haplotypes from three psychiatrically characterized population samples (US Caucasian [USC, n = 100], Finnish Caucasian [FC, n = 324] and Southwestern American Indian [SAI, n = 367]), were used to perform association and sib-pair linkage analyses with alcohol and drug dependence diagnoses. No significant association of OPRM1 genetic variation to phenotype was observed. This analysis has 80% power to detect a small to moderate effect of OPRM1 variation on alcohol dependence and 100% power to detect effects of the magnitude of the ALDH2*2 variant. While these data do not support a role of the mu opioid receptor in susceptibility to alcohol dependence, the potential relationship between OPRM1 genetic variation and response to endogenous opioids and exogenous opiates can now be investigated. C1 UNIV HELSINKI,DEPT PSYCHIAT,HELSINKI 001810 18,FINLAND. NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. RP Bergen, AW (reprint author), NIAAA,NEUROGENET LAB,12501 WASHINGTON AVE,FLOW BLDG,ROOM 2,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644 NR 42 TC 197 Z9 207 U1 2 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT-NOV PY 1997 VL 2 IS 6 BP 490 EP 494 DI 10.1038/sj.mp.4000331 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA YD107 UT WOS:A1997YD10700018 PM 9399694 ER PT J AU Hurd, YL Herman, MM Hyde, TM Bigelow, LB Weinberger, DR Kleinman, JE AF Hurd, YL Herman, MM Hyde, TM Bigelow, LB Weinberger, DR Kleinman, JE TI Prodynorphin mRNA expression is increased in the patch vs matrix compartment of the caudate nucleus in suicide subjects SO MOLECULAR PSYCHIATRY LA English DT Article DE opioid neuropeptides; limbic; striatum; depression; human; in situ hybridization; enkephalin; dopamine receptors ID IN-SITU HYBRIDIZATION; SCHIZOPHRENIC-PATIENTS; MESSENGER-RNA; CEREBROSPINAL-FLUID; GENE-EXPRESSION; BINDING-SITES; HUMAN-BRAIN; RECEPTORS; DOPAMINE; POSTMORTEM AB Experimental and clinical studies suggest an involvement of the opioid neuropeptide system in psychiatric disorders. Notably, opioid peptide immunoreactivity is altered in the cerebrospinal fluid of chronic schizophrenics and manic-depressive subjects.(1-3) Despite these clinical findings, few postmortem investigations(4,5) have examined the association of endogenous opioid neuropeptides with schizophrenia and suicide. Anatomically, a tight interaction exists within the neostriatum between the opioid peptide (dynorphin and enkephalin) system and classical neurotransmitters such as dopamine(6) which has been implicated in both the psychotic symptoms and the cognitive deficits that characterize schizophrenia (see review).(7) The neostriatum is differentially organized into patch and matrix neurochemical mosaic compartments anatomically connected to limbic-and sensorimotor-related brain regions, respectively.(6,8) Moreover, the human neostriatum is characterized by a heterogenous expression of the prodynorphin opioid gene: high in the patch, but low in the matrix compartment.(9,10) The present results show for the first time a differential alteration of prodynorphin within distinct striatal compartments in postmortem tissue from nonschizophrenic suicide subjects. The prodynorphin patch/matrix mRNA expression was elevated in the caudate nucleus of suicide subjects as compared to normal controls and schizophrenics in which no alterations in opioid peptides or D-1 and D-2 mRNA expression were apparent. Altogether the findings suggest that discrete dysfunction of the endogenous opioid dynorphin system might contribute to depression and the risk of suicide in nonschizophrenic subjects. C1 ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP Hurd, YL (reprint author), KAROLINSKA INST,KAROLINSKA HOSP,DEPT CLIN NEUROSCI,PSYCHIAT SECT,S-17176 STOCKHOLM,SWEDEN. NR 29 TC 28 Z9 29 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT-NOV PY 1997 VL 2 IS 6 BP 495 EP 500 DI 10.1038/sj.mp.4000319 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA YD107 UT WOS:A1997YD10700019 PM 9399695 ER PT J AU Esterling, LE Matise, TC Sanders, AR Yoshikawa, T Overhauser, J Gershon, ES Moskowitz, MT DeteraWadleigh, SD AF Esterling, LE Matise, TC Sanders, AR Yoshikawa, T Overhauser, J Gershon, ES Moskowitz, MT DeteraWadleigh, SD TI An integrated physical map of 18p11.2: a susceptibility region for bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE chromosome 18; radiation hybrid; YAC; somatic cell hybrid ID HUMAN GENOME; CHROMOSOME-18; LINKAGE; DENSITY; GENE AB The reported linkage between bipolar disorder and a large pericentric portion of chromosome 18 has been replicated in an independent study. Further examination of this region showed that 18p11.2 had the greatest allele sharing in our pedigrees and increased sharing in other independently ascertained pedigree series permitting refinement of the region of significance. To facilitate positional cloning of a susceptibility gene, we used a combination of mapping reagents, including a subchromosomal somatic cell hybrid panel, a contig of clones in yeast artificial chromosomes (YAC), and a radiation hybrid (RH) panel, to construct a high resolution physical map of the region including sequence tag sites (STSs) and expressed sequence tags (ESTs). This approach generated the interlocus distance and order of 15 STSs and 16 ESTs including four novel transcripts, with an average of similar to 200 kb between loci, over a similar to 6-Mb region. This high resolution integrated map will be an important tool in providing loci for contig construction, and positional candidates for mutation screening. C1 NATL INST DEAFNESS & OTHER COMMUN DISORDERS,GENET MOL LAB,NIH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOL BIOL & MED GENET,PHILADELPHIA,PA 19107. ROCKEFELLER UNIV,LAB STAT GENET,NEW YORK,NY 10021. RP Esterling, LE (reprint author), NIMH,UNIT GENE MAPPING & EXPRESS,CLIN NEUROGENET BRANCH,NIH,BLDG 10,ROOM 3N218,BETHESDA,MD 20892, USA. FU NHGRI NIH HHS [HG00151]; NIMH NIH HHS [MH44292] NR 16 TC 11 Z9 11 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT-NOV PY 1997 VL 2 IS 6 BP 501 EP 504 DI 10.1038/sj.mp.4000317 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA YD107 UT WOS:A1997YD10700020 PM 9399696 ER PT J AU Spector, SA Lemmer, JT Koffman, BM Fleisher, TA Feuerstein, IM Hurley, BF Dalakas, MC AF Spector, SA Lemmer, JT Koffman, BM Fleisher, TA Feuerstein, IM Hurley, BF Dalakas, MC TI Safety and efficacy of strength training in patients with sporadic inclusion body myositis SO MUSCLE & NERVE LA English DT Article DE inclusion body myositis; exercise; immune function; muscle injury ID ACUTE-PHASE RESPONSE; LYMPHOCYTE SUBPOPULATIONS; INFLAMMATORY MYOPATHIES; NEUROMUSCULAR DISORDERS; CIRCULATING LEUKOCYTE; RESISTANCE EXERCISE; SKELETAL-MUSCLE; POLYMYOSITIS; DERMATOMYOSITIS; DISEASE AB We studied the effects of a 12-week progressive resistance strength training program in weakened muscles of 5 patients with sporadic inclusion body myositis (IBM). Strength was evaluated with Medical Research Council (MRC) scale ratings and quantitative isometric and dynamic tests. Changes in serum creatine kinase (CK), lymphocyte subpopulations, muscle size (determined by magnetic resonance imaging), and histology in repeated muscle biopsies were examined before and after training, After 12 weeks, the values of repetition maximum improved in the least weakened muscles, 25-120% from baseline. This dynamic effect was not captured by MRC or isometric muscle strength measurements. Serum CK, B cells, T-cell subsets, and NK cells remained unchanged, Repeat muscle biopsies did not reveal changes in the number and degree of degenerating fibers or inflammation. The size of the trained muscles did not change. We conclude that a supervised progressive resistance training program in IBM patients can lead to gains in dynamic strength of the least weak muscles without causing muscle fatigue and muscle injury or serological, histological, and immunological abnormalities. Even though the functional significance of these gains is unclear, this treatment modality is a safe and perhaps overlooked means of rehabilitation of IBM patients, (C) 1997 John Wiley & Sons, Inc. C1 NINCDS,NEUROMUSCULAR DIS SECT,NIH,BETHESDA,MD 20892. NIH,DEPT IMMUNOL,CTR CLIN,BETHESDA,MD 20892. NIH,DEPT RADIOL,CTR CLIN,BETHESDA,MD 20892. UNIV MARYLAND,DEPT KINESIOL,EXERCISE SCI LAB,COLLEGE PK,MD 20742. NR 35 TC 72 Z9 77 U1 1 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 1997 VL 20 IS 10 BP 1242 EP 1248 DI 10.1002/(SICI)1097-4598(199710)20:10<1242::AID-MUS6>3.0.CO;2-C PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XY297 UT WOS:A1997XY29700006 PM 9324080 ER PT J AU Englander, EW Howard, BH AF Englander, EW Howard, BH TI Alu-mediated detection of DNA damage in the human genome SO MUTATION RESEARCH-DNA REPAIR LA English DT Review DE DNA damage; Alu repeat; genomic integrity; UV-photoproduct; PCR ID GENE-SPECIFIC REPAIR; CHAIN-REACTION ASSAY; NUCLEOSOME CORE DNA; PYRIMIDINE DIMERS; XERODERMA-PIGMENTOSUM; POLYMERASE; CISPLATIN; CELLS; PHOTOPRODUCTS; CHROMATIN AB A new approach to monitoring UV damage and repair in the human genome has been developed. The proposed approach is based on a combination of features unique to interspersed repetitive Alu elements, and the ability of certain DNA lesions to block Tag polymerase-mediated DNA synthesis: namely, the extraordinary abundance of Alu repeats throughout the human genome in conjunction with distinct sequence motifs comprising long runs of T residues which are likely targets for formation of UV lesions. Hence, Tag polymerase-mediated extension synthesis with Alu specific primers was employed to visualize formation of discrete predicted adducts within the element. Several variations of the Alu-primer driven amplification protocol were developed to monitor the following aspects of damage: (i) induction of UV-photoproducts at predicted sites within the Alu sequence, (ii) modification of extension synthesis profiles, (iii) UV dose dependent, quantitative inhibition of Alu-primer driven amplification. The assays reveal sites of predicted Tag polymerase blockage within the Alu sequence, a global decrease in the mean length of extension products, and a measurable reduction in the quantity of extension products that is inversely proportional to UV dose. Thus, the exceptional abundance of Alu repeats and their primary sequence features, in combination with the ability of UV lesions to block elongation by Tag polymerase, provide a novel and sensitive system for detecting UV damage in the human genome. The system detects UV damage at levels that are compatible with cellular DNA repair, and provides a unique amplification-based protocol for probing the overall integrity of human DNA. (C) 1997 Elsevier Science B.V. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NR 32 TC 11 Z9 11 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD OCT PY 1997 VL 385 IS 1 BP 31 EP 39 DI 10.1016/S0921-8777(97)00036-0 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YE075 UT WOS:A1997YE07500004 PM 9372846 ER PT J AU Henninghausen, L AF Henninghausen, L TI Transgenic factor VIII: The milky way and beyond SO NATURE BIOTECHNOLOGY LA English DT News Item ID PLASMINOGEN-ACTIVATOR; PROTEIN; MOUSE; EXPRESSION RP Henninghausen, L (reprint author), NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 1997 VL 15 IS 10 BP 945 EP 946 DI 10.1038/nbt1097-945 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA XZ285 UT WOS:A1997XZ28500016 PM 9335038 ER PT J AU Moldin, SO AF Moldin, SO TI The maddening hunt for madness genes SO NATURE GENETICS LA English DT Editorial Material ID PAIR LINKAGE ANALYSIS; SUSCEPTIBILITY LOCUS; VULNERABILITY LOCUS; COMPLEX TRAITS; SCHIZOPHRENIA; DISEQUILIBRIUM; CHROMOSOME-22; ASSOCIATION; 8P C1 GEORGETOWN UNIV,MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20007. RP Moldin, SO (reprint author), NIMH,DIV BASIC & CLIN NEUROSCI RES,GENET RES BRANCH,NIH,ROCKVILLE,MD 20857, USA. NR 26 TC 59 Z9 59 U1 1 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1997 VL 17 IS 2 BP 127 EP 129 DI 10.1038/ng1097-127 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA XZ555 UT WOS:A1997XZ55500003 PM 9326920 ER PT J AU Marlhens, F Bareil, C Griffoin, JM Zrenner, E Amalric, P Eliaou, C Liu, SY Harris, E Redmond, TM Arnaud, B Claustres, M Hamel, CP AF Marlhens, F Bareil, C Griffoin, JM Zrenner, E Amalric, P Eliaou, C Liu, SY Harris, E Redmond, TM Arnaud, B Claustres, M Hamel, CP TI Mutations in RPE65 cause Leber's congenital amaurosis SO NATURE GENETICS LA English DT Letter ID RETINAL-PIGMENT EPITHELIUM; MICROSOMAL PROTEIN; GENE; DYSTROPHY C1 HOP ST CHARLES,LAB NEUROBIOL AUDIT PLAST SYNAPT,INSERM,U254,F-34295 MONTPELLIER 5,FRANCE. INST BIOL,BIOCHIM GENET LAB,MONTPELLIER,FRANCE. UNIV TUBINGEN,HOSP EYE,TUBINGEN,GERMANY. CABINET OPTHALMOL,ALBI,FRANCE. HOP GUI DE CHAULIAC,SERV OPTALMOL,MONTPELLIER,FRANCE. NEI,RETINAL CELL & MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI BAREIL, Corinne/A-8387-2008; LABO, U827/A-8632-2008; OI Redmond, T. Michael/0000-0002-1813-5291 NR 13 TC 387 Z9 395 U1 3 U2 16 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1997 VL 17 IS 2 BP 139 EP 141 DI 10.1038/ng1097-139 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA XZ555 UT WOS:A1997XZ55500013 PM 9326927 ER PT J AU Grimsby, J Toth, M Chen, K Kumazawa, T Klaidman, L Adams, JD Karoum, F Gal, J Shih, JC AF Grimsby, J Toth, M Chen, K Kumazawa, T Klaidman, L Adams, JD Karoum, F Gal, J Shih, JC TI Increased stress response and p-phenylethylamine in MAOB-deficient mice SO NATURE GENETICS LA English DT Article ID MONOAMINE-OXIDASE-A; NORRIE DISEASE; GENES; ASSOCIATION; INHIBITORS; SEROTONIN; BEHAVIOR; DOPAMINE; CLONING; PATIENT AB MAOA and MAOB are key iso-enzymes that degrade biogenic and dietary amines(1-5). MAOA preferentially oxidizes serotonin (5-hydroxytryptamine, or 5-HT) and norepinephrine (NE), whereas MAOB preferentially oxidizes beta-phenylethylamine (PEA). Both forms can oxidize dopamine (DA). A mutation in MAOA results in a clinical phenotype characterized by borderline mental retardation and impaired impulse control(6,7). X-chromosomal deletions which include MAOB were found in patients suffering from atypical Norrie's disease(8,9), which is characterized by blindness and impaired hearing. Reduced MAOB activity has been found in type-II alcoholism and in cigarette smokers(10,11). Because most alcoholics smoke, the effects of alcohol on MAOB activity remain to be determined. Here we show that targetted inactivation of MAOB in mice increases levels of PEA but not those of 5-HT, NE and DA, demonstrating a primary role for MAOB in the metabolism of PEA. PEA has been implicated in modulating mood and affect(12,13). Indeed, MAOB-deficient mice showed an increased reactivity to stress. In addition, mutant mice were resistant to the neurodegenerative effects of MPTP, a toxin that induces a condition reminiscent of Parkinson's disease. C1 UNIV SO CALIF,SCH PHARM,DEPT MOL PHARMACOL & TOXICOL,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT CELL & NEUROBIOL,LOS ANGELES,CA 90033. CORNELL UNIV MED COLL,DEPT PHARMACOL,NEW YORK,NY 10021. NIMH,ST ELIZABETHS HOSP,DEPT PSYCHOL & PHARMACOL,WASHINGTON,DC 20032. FU NIMH NIH HHS [R01 MH37020, K05 MH00796, R37 MH39085] NR 30 TC 161 Z9 164 U1 1 U2 7 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1997 VL 17 IS 2 BP 206 EP 210 DI 10.1038/ng1097-206 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XZ555 UT WOS:A1997XZ55500030 PM 9326944 ER PT J AU Smith, MW Carrington, M Winkler, C Lomb, D Dean, M Huttley, G OBrien, SJ AF Smith, MW Carrington, M Winkler, C Lomb, D Dean, M Huttley, G OBrien, SJ TI CCR2 chemokine receptor and AIDS progression SO NATURE MEDICINE LA English DT Letter C1 NCI,FREDERICK CANC RES & DEV CTR,LAB GENOM DIVERS,FREDERICK,MD 21702. RP Smith, MW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702, USA. RI Smith, Michael/B-5341-2012; Huttley, Gavin/G-5169-2015; OI Huttley, Gavin/0000-0001-7224-2074; Dean, Michael/0000-0003-2234-0631 NR 8 TC 79 Z9 79 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 1997 VL 3 IS 10 BP 1052 EP 1053 DI 10.1038/nm1097-1052c PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XZ287 UT WOS:A1997XZ28700005 PM 9334699 ER PT J AU Ng, ST Zhou, JA Adesanya, OO Wang, J LeRoith, D Bondy, CA AF Ng, ST Zhou, JA Adesanya, OO Wang, J LeRoith, D Bondy, CA TI Growth hormone treatment induces mammary gland hyperplasia in aging primates SO NATURE MEDICINE LA English DT Article ID FACTOR-I; BREAST-CANCER; GENE-EXPRESSION; PROLACTIN; SYSTEM; PROLIFERATION; THERAPY AB The decline of growth hormone (CH) and insulin-like growth factor I (ICF-I) production during aging has been likened to the decrease in gonadal steroids in menopause. The repletion of GH/IGF-I levels in aging individuals is suggested to restore the lean tissue anabolism characteristic of youth(1). In addition to anabolic effects on musculoskeletal tissues, CH also stimulates mammary glandular growth in some species(2-4), although its effects on primate mammary growth remain unclear(5). Some clinical observations implicate GH in human mammary growth, for example, gynecomastia occurs in some children treated with CH (ref. 6), and tall stature and acromegaly are associated with an increased incidence of breast cancer(7,8). To investigate the effects of GH/ICF-I augmentation on mammary tissue in a model relevant to aging humans, we treated aged female rhesus monkeys with CH, IG F-l, GH + ICF-I or saline diluent for 7 weeks. ICF-I treatment was associated with a twofold increase, GH with a three-to fourfold increase, and GH + IGF-I with a four-to fivefold increase in mammary glandular size and epithelial proliferation index. These mitogenic effects were directly correlated with circulating GH and IGF-I levels, suggesting that either CH or its downstream effector ICF-I stimulates primate mammary epithelial proliferation. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. NR 23 TC 139 Z9 141 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 1997 VL 3 IS 10 BP 1141 EP 1144 DI 10.1038/nm1097-1141 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XZ287 UT WOS:A1997XZ28700042 PM 9334728 ER PT J AU Clore, GM Gronenborn, AM AF Clore, GM Gronenborn, AM TI NMR structures of proteins and protein complexes beyond 20,000 M-r SO NATURE STRUCTURAL BIOLOGY LA English DT Review ID MAGNETIC-RESONANCE SPECTROSCOPY; RESOLUTION 3-DIMENSIONAL STRUCTURE; DIRECT REFINEMENT; CHEMICAL-SHIFTS; HETERONUCLEAR; IMPACT; THIOREDOXIN AB Recent advances in multidimensional NMR to obtain resonance assignments, interproton distance and torsion angle restraints, and restraints that characterize long range order, coupled with new methods of structure refinement, have permitted solution structures of proteins in excess of 250 residues to be solved. RP Clore, GM (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 2,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 32 TC 71 Z9 71 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD OCT PY 1997 VL 4 SU S BP 849 EP 853 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YA764 UT WOS:A1997YA76400003 PM 9377157 ER PT J AU Esposito, C Striker, LJ Striker, GE AF Esposito, C Striker, LJ Striker, GE TI Molecular analysis of glomerular diseases in renal biopsies SO NEPHROLOGY LA English DT Article; Proceedings Paper CT International Symposium on IgA Nephropathy - Molecular Approach and Clinical Practice CY NOV 25-26, 1996 CL TOKYO, JAPAN SP Japan Intractable Dis Res Fdn, Minist Hlth & Welf Japan, Special Study Grp DE diabetic nephropathy; gene expression; glomerulosclerosis; membranous glomerulonephritis; mRNA analysis; renal biopsy; type collagen IV ID BASEMENT-MEMBRANE COLLAGEN; IV COLLAGEN; DIFFERENTIAL EXPRESSION; DIABETIC NEPHROPATHY; ALPORT SYNDROME; CELL; GLOMERULOSCLEROSIS; CHAINS; ADULT AB The purpose of this study was to determine the pattern of gene expression of type IV collagen alpha chains in several chronic human glomerular diseases using micro dissected glomeruli and assessment of mRNA by competitive polymerase chain reaction (PCR). After showing that the level of a2 type IV collagen mRNA was elevated in sclerotic glomeruli isolated from nephrectomies, we undertook a preliminary cross-sectional study of type IV collagen alpha chain mRNA in renal biopsies in two of the leading causes of glomerulosclerosis: (i) diabetic nephropathy; and (ii) membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels alterations were disease-specific. The relative levels of the individual cc-chains of type IV collagen depended on the anatomic site of the glomerular lesions. The alpha-2IV/alpha-3IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with that obtained in experimental animals, suggest that a defective basement collagen synthesis is associated with progressive glomerular scarring. If these conclusions are verified in studies of repeat biopsies, the risk of progressive glomerulosclerosis in individual patients could be estimated, leading to the means to assess therapeutic responses. C1 NIDDK,RENAL CELL BIOL SECT,NIH,BETHESDA,MD 20892. NR 14 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD OCT PY 1997 VL 3 SU 2 BP S683 EP S689 DI 10.1111/j.1440-1797.1997.tb00285.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA YE162 UT WOS:A1997YE16200011 ER PT J AU Striker, GE AF Striker, GE TI Summary and closing remarks SO NEPHROLOGY LA English DT Editorial Material RP Striker, GE (reprint author), NIH,DIV KIDNEY UROL & HEMATOL DIS,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD OCT PY 1997 VL 3 SU 2 BP S759 EP S761 DI 10.1111/j.1440-1797.1997.tb00297.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA YE162 UT WOS:A1997YE16200023 ER PT J AU Kawai, N Yamamoto, T Yamamoto, H McCarron, RM Spatz, M AF Kawai, N Yamamoto, T Yamamoto, H McCarron, RM Spatz, M TI Functional characterization of endothelin receptors on cultured brain capillary endothelial cells of the rat SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID SIGNAL-TRANSDUCTION; COTRANSPORT; INHIBITION; TRANSPORT; VESSELS; HYPOXIA; BINDING; SODIUM; KINASE; CA2+ AB This report describes the effects of endothelins (ET-1 and ET-3) on ion transport systems expressed on cultured rat brain capillary endothelial cells (RBEC) and includes investigation of pharmacological properties of ET receptors, their reactivity and induction of signal transduction pathways. ET-1 stimulated IP3 formation and Ca2+ uptake with half-maximal effective concentrations (EC50) of 0.68 and 0.93 nM, respectively; the effects of ET-3 on these responses were much weaker. ET-1-stimulated IP3 formation and Ca2+ uptake were inhibited by an ETA antagonist (BQ123) and a phospholipase C (PLC) inhibitor (U73122), indicating the presence of ETA receptors coupled to PLC. ET-1 stimulated K+ efflux (through a quinine-sensitive mechanism) and K+ uptake (through both ouabain-sensitive and bumetanide-sensitive mechanisms) with EC50 of 0.59 and 0.68 nM, respectively. The potencies of ET-3 on these responses were considerably lower than those of ET-1. By contrast, ET-1 or ET-3 stimulated Na+ uptake with similarly high potencies (EC50 = 0.80 and 1.89 nM, respectively) through EIPA (a Na+/H+ exchange inhibitor)-sensitive mechanisms. ET-stimulated K+ efflux, K+ uptake and Na+ uptake activities were all inhibited by BQ123 (but not by BQ788), suggesting the involvement of ETA (and not ETB) receptors in all these responses. ET-1 stimulated K+ uptake and efflux were inhibited by either U73122 or an intracellular Ca2+ chelator, suggesting that these two responses were mediated via PLC. In contrast, ET stimulation of Na+ uptake was unaffected by PLC inhibition or intracellular Ca2+ chelation. These data suggest the presence of two distinct subtypes of ETA receptors on RBEC; one appears to be a typical ETA receptor which is coupled to PLC and has higher binding affinity for ET-1 than ET-3. The other (ETA-like) receptor is similarly activated by ET-1 and ET-3 with high potencies but is independent of PLC. This possibility was further confirmed by the [I-125]ET-1 binding studies demonstrating the presence of high- and low-affinity ET-3 binding sites. (C) 1997 Elsevier Science Ltd. C1 NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. YOKOHAMA CITY UNIV,GRAD SCH INTEGRATED SCI,LAB MOL RECOGNIT,YOKOHAMA,KANAGAWA,JAPAN. TOKYO INST PSYCHIAT,DEPT PSYCHOPHARMACOL,TOKYO,JAPAN. NR 27 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD OCT PY 1997 VL 31 IS 4 BP 597 EP 605 DI 10.1016/S0197-0186(97)00018-1 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XW582 UT WOS:A1997XW58200013 PM 9308010 ER PT J AU Prinster, A Pierpaoli, C Turner, R Jezzard, P AF Prinster, A Pierpaoli, C Turner, R Jezzard, P TI Simultaneous measurement of Delta R2 and Delta R2* in cat brain during hypoxia and hypercapnia SO NEUROIMAGE LA English DT Article ID BLOOD OXYGENATION; FUNCTIONAL MRI; SENSORY STIMULATION; SIGNAL CHANGES; MOTOR CORTEX; 1.5 T; CONTRAST; ECHO; ACTIVATION; EPI AB One of the most important issues in blood-oxygen-level-dependent (BOLD)-based brain functional magnetic resonance imaging is the understanding of the vascular structures that are responsible for the signal changes observed, The T2*-related signal changes observed during variations in susceptibility-induced magnetic field gradients are a function both of non-refocusable mechanisms, such as diffusion, and of refocusable effects such as field inhomogeneities. Conversely, T2-related signal changes are only a function of non-refocusable effects, It has been suggested that T2-weighted images could be less sensitive to blood susceptibility changes in a macrovascular environment than T2*-weighted images and could thus be more accurate in identifying the ''activation'' of the parenchyma rather than ''draining vein'' effects, In this study we use hypoxia and hypercapnia challenges in cats to provide a change in blood deoxyhemoglobin concentration (as a model for classic BOLD changes and not as a model for neuronal activation), A combined gradient echo and spin echo echo-planar-imaging (EPI) pulse sequence was used to map Delta R2 (i.e., Delta(1/T2)) and Delta R2* (i.e., Delta(1/T2*)) changes during the challenges, Our experiments demonstrate that: (i) the acquisition of T2-weighted EPI data does not in itself differentiate signal changes in the parenchyma from those occurring in regions around larger vessels, but that (ii) the simultaneous acquisition of T2- and T2*-weighted images could be useful in identifying microvascular regions in gray matter by analyzing the ratio Delta R2/Delta R2*. This value seems independent of the degree of deoxyhemoglobin concentration change, but is related to properties of the vascular environment. The suggest a possible application of the results to the study of brain function in humans. (C) 1997 Academic Press. C1 NIMH,UNIT MRI PHYS,LBC,NIH,LAB CARDIAC ENERGET,BETHESDA,MD 20892. UNIV MILAN,INST HS RAFFAELE,INB CNR,MILAN,ITALY. NINCDS,NEUROIMAGING BRANCH,NIH,BETHESDA,MD 20892. WELLCOME DEPT COGNIT NEUROL,INST NEUROL,LONDON,ENGLAND. RI Turner, Robert/C-1820-2008; Pierpaoli, Carlo/E-1672-2011; Prinster, Anna/B-8414-2015 OI Prinster, Anna/0000-0003-2706-3071 FU Wellcome Trust NR 27 TC 31 Z9 32 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT PY 1997 VL 6 IS 3 BP 191 EP 200 DI 10.1006/nimg.1997.0288 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YE484 UT WOS:A1997YE48400005 PM 9344823 ER PT J AU Perry, JR DeAngelis, LM Schold, SC Burger, PC Brem, H Brown, MT Curran, WJ Scott, CB Prados, MD Kaplan, R Cairncross, JG AF Perry, JR DeAngelis, LM Schold, SC Burger, PC Brem, H Brown, MT Curran, WJ Scott, CB Prados, MD Kaplan, R Cairncross, JG TI Challenges in the design and conduct of phase III brain tumor therapy trials SO NEUROLOGY LA English DT Article ID RECURSIVE PARTITIONING ANALYSIS; RECURRENT MALIGNANT GLIOMA; RADIATION-THERAPY; CLINICAL-TRIALS; ANAPLASTIC GLIOMAS; ADJUVANT CHEMOTHERAPY; FUNCTIONAL ASSESSMENT; PROGNOSTIC IMPORTANCE; ONCOLOGY GROUP-83-02; INITIAL MANAGEMENT C1 UNIV TORONTO,TORONTO,ON,CANADA. TORONTO SUNNYBROOK REG CANC CTR,TORONTO,ON,CANADA. MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. UNIV TEXAS,SW MED CTR,DEPT NEUROL,DALLAS,TX 75235. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSURG & ONCOL,BALTIMORE,MD. DUKE UNIV,MED CTR,NEUROONCOL SECT,DURHAM,NC. THOMAS JEFFERSON UNIV,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19107. AMER COLL RADIOL,RADIAT THERAPY ONCOL GRP,PHILADELPHIA,PA. UNIV CALIF SAN FRANCISCO,DEPT NEUROONCOL,SAN FRANCISCO,CA 94143. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. UNIV WESTERN ONTARIO,LONDON,ON,CANADA. LONDON REG CANC CTR,LONDON,ON N6A 4L6,CANADA. NR 51 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1997 VL 49 IS 4 BP 912 EP 917 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA YC431 UT WOS:A1997YC43100003 PM 9339667 ER PT J AU Chen, R Wassermann, EM Canos, M Hallett, M AF Chen, R Wassermann, EM Canos, M Hallett, M TI Impaired inhibition in writer's cramp during voluntary muscle activation SO NEUROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Neurological-Association CY OCT 13-16, 1996 CL MIAMI, FL SP Amer Neurol Assoc ID TRANSCRANIAL MAGNETIC STIMULATION; MOTOR CORTEX STIMULATION; RECIPROCAL INHIBITION; CORTICAL STIMULATION; FOREARM MUSCLES; SILENT PERIOD; SYMPTOMATIC HEMIDYSTONIA; PREMOTOR CORTEX; PRIMATE MOTOR; BASAL GANGLIA AB We used paired transcranial magnetic stimulation (TMS) to evaluate inhibitory mechanisms in eight patients with writer's cramp during rest and isometric wrist extension. Both stimuli were 110% of the motor threshold; the interstimulus intervals (ISIs) were 20 to 200 ms in increments of 10 ms. Surface EMG was recorded from wrist extensors. In the symptomatic hemisphere, there was no significant difference in the amplitude of the test (second) motor evoked-potential (MEP) between patients and age-matched controls at rest. However, with voluntary muscle activation, inhibition of the test MEP by the conditioning MEP was significantly less in writer's cramp patients than in controls (p = 0.02). The difference was most prominent at ISIs of 60 to 80 ms in which inhibition is maximum. In the asymptomatic hemisphere, there was no significant difference between patients and controls in both rest and active conditions. The silent period was shorter in patients than controls on the symptomatic side (p = 0.003) but not on the asymptomatic side. We conclude that the inhibitory effects induced by magnetic stimulation are reduced in patients with writer's cramp, but only on the symptomatic side during muscle activation. This may relate to the overflow of muscle activity that characterizes this condition. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 47 TC 145 Z9 146 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1997 VL 49 IS 4 BP 1054 EP 1059 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA YC431 UT WOS:A1997YC43100025 PM 9339689 ER PT J AU Calabresi, PA Pelfrey, CM Tranquill, LR Maloni, H McFarland, HF AF Calabresi, PA Pelfrey, CM Tranquill, LR Maloni, H McFarland, HF TI VLA-4 expression on peripheral blood lymphocytes is downregulated after treatment of multiple sclerosis with interferon beta SO NEUROLOGY LA English DT Article ID RESONANCE-IMAGING LESIONS; ADHESION MOLECULE-1; ENDOTHELIAL-CELLS; T-CELLS; ENCEPHALOMYELITIS; ACTIVATION; INTEGRIN; SIGNS AB Adhesion molecules are likely to play a critical role in the immunopathogenesis of multiple sclerosis (MS). The interaction of vascular cell adhesion molecule-1 (VCAM-1) with its lymphocyte Ligand very late antigen-4 (VLA-4) may mediate migration of lymphocytes into the CNS. We have previously demonstrated that MS patients treated with interferon beta (IFN-beta) have a significant increase in soluble VCAM-1 (sVCAM-1) soon after the initiation of treatment, and this effect correlated with the resolution of contrast-enhancing MRI lesions. We studied the cell surface expression of VLA-4 by flow cytometry in 10 MS patients before and during IFN-beta treatment. We found a significant decrease in mean VLA-4 fluorescence of MS patients' lymphocytes on treatment and no change in untreated controls. In vitro treatment of lymphocytes with IFN-beta did not reproduce this effect, but the addition of sVCAM-1 did result in a decrease in VLA-4 expression. These data indicate that the previously identified increase in sVCAM-1 may lead to a decrease in VLA-4 expression and that this effect may partially explain the mechanism of action of IFN-beta. C1 CASE WESTERN RESERVE UNIV,DEPT PATHOL,CLEVELAND,OH 44106. RP Calabresi, PA (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,BLDG 10,ROOM 5B-16,10 CTR DR MSC-1400,BETHESDA,MD 20892, USA. OI Pelfrey, Clara/0000-0002-6108-7555 NR 31 TC 90 Z9 91 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1997 VL 49 IS 4 BP 1111 EP 1116 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA YC431 UT WOS:A1997YC43100034 PM 9339698 ER PT J AU Hemmer, B Vergelli, M Tranquill, L Conlon, P Ling, N McFarland, HF Martin, R AF Hemmer, B Vergelli, M Tranquill, L Conlon, P Ling, N McFarland, HF Martin, R TI Human T-cell response to myelin basic protein peptide (83-99): Extensive heterogeneity in antigen recognition, function, and phenotype SO NEUROLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; MULTIPLE-SCLEROSIS PATIENTS; RECEPTOR ANTAGONISTS; FINE SPECIFICITY; IMMUNE DEVIATION; LYMPHOCYTES-T; THERAPY; CLONES AB Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, and myelin proteins are the most likely candidate autoantigens. Based on experiments performed in experimental allergic encephalomyelitis (EAE), innovative immunotherapies have been developed that target either the specific trimolecular: complex of encephalitogenic T cells, consisting of T-cell receptor (TCR), major histocompatibility complex (MHC; HLA in humans) class II molecule, and autoantigenic peptide, or the effector functions of these cells. To provide the basis for the transfer of these specific immunotherapies to MS, we extensively characterized the human T-cell response to one major myelin epitope, the myelin basic protein peptide (83-99). We analyzed restriction element, TCR usage and affinity, fine specificity, cytokine production, cytolytic activity, and expression of surface molecules on 41 T-cell clones (TCCs) derived from MS patients and normal controls. We demonstrate a high degree of complexity of recognition patterns as well as of functional phenotypes among T cells responding to the same epitope. In contrast to results from animal models, these findings indicate that the design of epitope-based specific immunotherapies for MS is more difficult than previously thought. C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV TUBINGEN,SCH MED,DEPT NEUROL,TUBINGEN,GERMANY. NEUROCRINE BIOSCI INC,SAN DIEGO,CA. NR 56 TC 35 Z9 35 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1997 VL 49 IS 4 BP 1116 EP 1126 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA YC431 UT WOS:A1997YC43100035 PM 9339699 ER PT J AU Petrovitch, H Nelson, J Snowdon, D Davis, DG Ross, GW Li, CY White, L AF Petrovitch, H Nelson, J Snowdon, D Davis, DG Ross, GW Li, CY White, L TI Microscope field size and the neuropathologic criteria for Alzheimer's disease SO NEUROLOGY LA English DT Article ID CONSORTIUM; ESTABLISH; REGISTRY; CERAD C1 UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. DEPT VET AFFAIRS,HONOLULU,HI. LOUISIANA STATE UNIV,DEPT PATHOL,NEW ORLEANS,LA. UNIV KENTUCKY,SANDERS BROWN CTR AGING,DEPT PREVENT MED,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT PATHOL & LAB MED,LEXINGTON,KY 40536. NIA,NIH,BETHESDA,MD 20892. RP Petrovitch, H (reprint author), KUAKINI MED CTR,HONOLULU ASIA AGING STUDY,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NIA NIH HHS [N01-AG-4-2149] NR 5 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1997 VL 49 IS 4 BP 1175 EP 1176 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA YC431 UT WOS:A1997YC43100053 PM 9339717 ER PT J AU Borchelt, DR Ratovitski, T vanLare, J Lee, MK Gonzales, V Jenkins, NA Copeland, NG Price, DL Sisodia, SS AF Borchelt, DR Ratovitski, T vanLare, J Lee, MK Gonzales, V Jenkins, NA Copeland, NG Price, DL Sisodia, SS TI Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins SO NEURON LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; BETA-PROTEIN; A-BETA; SENILE PLAQUES; IN-VIVO; MISSENSE MUTATIONS; DOWN-SYNDROME; GENE; A-BETA-42(43); LOCUS AB Missense mutations in two related genes, termed presenilin 1 (PS1) and presenilin 2 (PS2), cause dementia in a subset of early-onset familiar Alzheimer's disease (FAD) pedigrees. In a variety of experimental in vitro and in vivo settings, PAD-linked presenilin variants influence the processing of the amyloid precursor protein (APP), leading to elevated levels of the highly fibrillogenic A beta 1-42 peptides that are preferentially deposited in the brains of Alzheimer Disease (AD) patients. In this report, we demonstrate that transgenic animals that coexpress an PAD-linked human PS1 variant (A246E) and a chimeric mouse/human APP harboring mutations linked to Swedish PAD kindreds (APP swe) develop numerous amyloid deposits much earlier than age-matched mice expressing APP swe and wild-type Hu PS1 or APP swe alone. These results provide evidence for the view that one pathogenic mechanism by which PAD-linked mutant PS1 causes AD is to accelerate the rate of beta-amyloid deposition in brain. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. RI Lee, Michael/D-9491-2013 OI Lee, Michael/0000-0001-5865-9682 FU NIA NIH HHS [AG05146, AG14248]; NINDS NIH HHS [NS 20471] NR 51 TC 668 Z9 689 U1 1 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 1997 VL 19 IS 4 BP 939 EP 945 DI 10.1016/S0896-6273(00)80974-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA YD189 UT WOS:A1997YD18900020 PM 9354339 ER PT J AU Ali, SO Denicoff, KD Ketter, TA SmithJackson, EE Post, RM AF Ali, SO Denicoff, KD Ketter, TA SmithJackson, EE Post, RM TI Psychosensory symptoms in bipolar disorder SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE bipolar disorder; psychosensory; diagnosis; lithium; carbamazepine ID AFFECTIVE-ILLNESS; PARTIAL SEIZURES; CARBAMAZEPINE; PHENOMENOLOGY; RELIABILITY; PSYCHOSIS; RATIONALE; EPILEPSY; VALIDITY; LITHIUM AB This study investigated psychosensory symptoms and their relationship to retrospective and prospective courses of illness, as well as therapeutic outcomes, in patients with bipolar disorder. Using the Silberman-Post Psychosensory Rating Scale (SP-PSRS), psychosensory symptoms were assessed in 51 patients who met Diagnostic and Statistical Manual, 3rd Edition-Revised (DSM-III-R) criteria for bipolar disorder and in 39 healthy, normal controls. Patients with bipolar disorder were enrolled in a 3-year, double-blind, randomized study comparing the prophylactic efficacy of lithium or carbamazepine in the first year, a crossover to the other drug in the second year, and the combination of both medications in the third year. Psychosensory scores from patients with bipolar disorder were compared with scores from healthy controls and with a variety of retrospective and prospective course of illness and treatment variables. Psychosensory symptoms occurred frequently in patients with bipolar I and II disorders, but were rare in healthy controls. When depressed, patients with bipolar II disorder (n = 23) reported more psychosensory symptoms when compared to patients with bipolar I disorder (n = 28), and those with a history of rapid cycling (n = 29) reported more psychosensory symptoms when compared to patients without a history of rapid cycling (n = 21). Psychosensory symptoms were not related to response to carbamazepine, lithium, or the combination of both drugs. Although the presence of psychosensory symptoms is associated with some bipolar subtypes (patients with bipolar II disorder and patients with a history of rapid cycling), they do not appear to predict treatment response. Further studies are needed to assess the pathophysiologic implications of the presence of psychosensory symptoms and their potential implications, if any, for directing therapeutics. C1 NIMH,BIOL PSYCHIAT BRANCH,SECT PSYCHOBIOL,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA 94305. OI Ali, Syed/0000-0003-3131-3299 NR 45 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD OCT PY 1997 VL 10 IS 4 BP 223 EP 231 PG 9 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA YD472 UT WOS:A1997YD47200001 PM 9359118 ER PT J AU Arnett, PA Rao, SM Grafman, J Bernardin, L Luchetta, T Binder, JR Lobeck, L AF Arnett, PA Rao, SM Grafman, J Bernardin, L Luchetta, T Binder, JR Lobeck, L TI Executive functions in multiple sclerosis: An analysis of temporal ordering, semantic encoding, and planning abilities SO NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the International-Neuropsychological-Society CY FEB 02-06, 1994 CL CINCINNATI, OH SP Int Neuropsychol Soc ID FRONTAL-LOBE LESIONS; SORTING TEST-PERFORMANCE; COGNITIVE DYSFUNCTION; MEMORY IMPAIRMENT; AMNESIC PATIENTS; PATTERNS; DEFICITS; DAMAGE AB Previous studies have consistently demonstrated impairments in conceptual reasoning and set-shifting abilities in patients with multiple sclerosis (MS). Other executive functions have been less frequently examined. We compared 44 MS patients and 48 demographically matched controls on a temporal-ordering and semantic-encoding task and on a test of planning (Tower of Hanoi). Compared with controls, MS patients experienced deficient semantic encoding and planning but unimpaired temporal-order memory. For both tasks, post hoc analyses indicated that chronic-progressive MS patients contributed most to the group differences. A combination of poor planning and slowed information-processing speed was hypothesized to have contributed to MS patients' impaired Tower of Hanoi performance. Further research is needed to explore the possible relationship between semantic-encoding and planning deficits in MS and social and occupational disabilities. C1 NINCDS,COGNIT NEUROSCI SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. MED COLL WISCONSIN,DEPT NEUROL,MILWAUKEE,WI. RP Arnett, PA (reprint author), WASHINGTON STATE UNIV,DEPT PSYCHOL,POB 644820,PULLMAN,WA 99164, USA. RI Rao, Stephen/A-2460-2010; OI Rao, Stephen/0000-0002-6463-7460; Grafman, Jordan H./0000-0001-8645-4457; Binder, Jeffrey/0000-0002-2233-5640 FU NINDS NIH HHS [R01 NS22128] NR 46 TC 88 Z9 89 U1 3 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD OCT PY 1997 VL 11 IS 4 BP 535 EP 544 DI 10.1037/0894-4105.11.4.535 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA YA337 UT WOS:A1997YA33700008 PM 9345697 ER PT J AU Brady, DR Mufson, EJ AF Brady, DR Mufson, EJ TI Parvalbumin-immunoreactive neurons in the hippocampal formation of Alzheimer's diseased brain SO NEUROSCIENCE LA English DT Article DE immunocytochemistry; degeneration; Ca2+-buffering agent; subiculum; presubiculum; dentate gyrus ID BINDING PROTEIN PARVALBUMIN; CHANDELIER CELL AXONS; CEREBRAL-CORTEX; NEUROPEPTIDE-Y; SENILE DEMENTIA; NERVOUS-SYSTEM; FASCIA-DENTATA; MONKEY; NEOCORTEX; GYRUS AB The number and topographic distribution of immunocytochemically stained parvalbumin interneurons was determined in the hippocampal formation of control and Alzheimer's diseased brain. In control hippocampus, parvalbumin interneurons were aspiny and pleomorphic, with extensive dendritic arbors. In dentate gyrus, parvalbumin cells, as well as a dense plexus of fibers and puncta, were associated with the granule cell laver. A few cells also occupied the molecular layer. In strata oriens and pyramidale of CA1-CA3 subfields, parvalbumin neurons gave rise to dendrites that extended into adjacent strata. Densely stained puncta and beaded fibers occupied stratum pyramidale, with less dense staining in adjacent strata oriens and radiatum. Virtually no parvalbumin profiles were observed in stratum lacunosum-moleculare or the alveus. Numerous polymorphic parvalbumin neurons and a dense plexus of fibers and puncta characterized the deep layer of the subiculum and the lamina principalis externa of the presubiculum. In Alzheimer's diseased hippocampus, there was an approximate 60% : decrease in the number of parvalbumin interneurons in the dentate gyrus/CA4 subfield (P<0.01) and subfields CA1-CA2 (P<0.01). In contrast, parvalbumin neurons did not statistically decline in subfields CA3, subiculum or presubiculum in Alzheimer's diseased brains relative to controls. Concurrent staining with Thioflavin-S histochemistry did not reveal degenerative changes within parvalbumin-stained profiles. These findings reveal that parvalbumin interneurons within specific hippocampal subfields are selectively vulnerable in Alzheimer's disease. This vulnerability may be related to their differential connectivity, e.g., those regions connectionally related to the cerebral cortex (dentate gyrus and CA1) are more vulnerable than those regions connectionally related to subcortical loci (subiculum and presubiculum). C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,ALZHEIMERS DIS RES CTR,DEPT NEUROL SCI,CHICAGO,IL 60612. FU NIA NIH HHS [AG 10688, AG 11482]; NINDS NIH HHS [NS 26146] NR 45 TC 43 Z9 44 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1997 VL 80 IS 4 BP 1113 EP 1125 DI 10.1016/S0306-4522(97)00068-7 PG 13 WC Neurosciences SC Neurosciences & Neurology GA XR557 UT WOS:A1997XR55700012 PM 9284064 ER PT J AU Ou, JH Carlos, TM Watkins, SC Saavedra, JE Keefer, LK Kim, YM Harbrecht, BG Billiar, TR AF Ou, JH Carlos, TM Watkins, SC Saavedra, JE Keefer, LK Kim, YM Harbrecht, BG Billiar, TR TI Differential effects of nonselective nitric oxide synthase (NOS) and selective inducible NOS inhibition on hepatic necrosis, apoptosis, ICAM-1 expression, and neutrophil accumulation during endotoxemia SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE nitric oxide; NOS inhibitors; liver; necrosis; apoptosis; neutrophil; adhesion molecule ID INTERCELLULAR-ADHESION MOLECULE-1; PROGRAMMED CELL-DEATH; L-ARGININE; MONOCLONAL-ANTIBODY; MURINE ENDOTOXEMIA; REPERFUSION INJURY; LEUKOCYTE ADHESION; HEPATOCYTE INJURY; ENDOTHELIAL-CELL; NITROGEN-OXIDES AB The roles of nitric oxide derived from either the constitutive endothelial NO synthase (eNOS or NOS3) or the inducible NOS (iNOS or NOS2) in hepatic injury during endotoxemia remain controversial. To investigate this further, rats received a bolus of lipopolysaccharide (LPS) following implantation of osmotic pumps containing one of two nonselective NOS inhibitors (NMA or NAME), one of two inducible NOS inhibitors (NIL or AG), or saline, The inhibitors were infused continuously into the Liver via the portal vein. Treatment of LPS-injected rats with NMA and NAME resulted in 106 and 227% increases, respectively, in circulating hepatic enzyme levels compared to LPS-treated control rats. In contrast, infusion of the iNOS-selective inhibitors had no effect on the LPS-induced hepatic necrosis. In rats receiving NAME, LPS induced greater neutrophil infiltration and ICAM-1 expression than in the LPS + saline group, whereas NIL infusion did not. The increased hepatic necrosis and PMN infiltration in the LPS + NAME group was partially prevented by a simultaneous infusion of a liver-selective NO donor. Inhibition of PMN accumulation using an anti-ICAM-1 antibody or by PMN depletion using vinblastine pretreatment, however, did not reverse the increased necrosis with NAME infusion during endotoxemia. In contrast to the assessment for necrosis, increased apoptosis was observed in the livers of LPS-treated rats receiving infusions of either NAME or NIL, but not with LPS alone. These data indicate that NO produced by eNOS may be adequate to prevent necrosis by a mechanism independent of PMN, while induced NO appears to prevent apoptosis. (C) 1997 Academic Press. C1 Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15231 USA. Univ Pittsburgh, Dept Med, Div Hematol, Pittsburgh, PA 15231 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15231 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15231 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Billiar, TR (reprint author), A1010 Presbyterian Univ Hosp, Dept Surg, 200 Lothrop St, Pittsburgh, PA 15213 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NIGMS NIH HHS [R01-GM-37753, R01-GM-44100] NR 60 TC 93 Z9 95 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD OCT PY 1997 VL 1 IS 5 BP 404 EP 416 DI 10.1006/niox.1997.0136 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG184 UT WOS:000072975600004 PM 9441911 ER PT J AU Buchhop, S Gibson, MK Wang, XW Wagner, P Sturzbecher, HW Harris, CC AF Buchhop, S Gibson, MK Wang, XW Wagner, P Sturzbecher, HW Harris, CC TI Interaction of p53 with the human Rad51 protein SO NUCLEIC ACIDS RESEARCH LA English DT Article ID WILD-TYPE P53; DNA-BINDING FUNCTION; CELL-CYCLE CHECKPOINT; ESCHERICHIA-COLI RECA; T7 RNA-POLYMERASE; TUMOR-SUPPRESSOR; GENETIC-RECOMBINATION; INDUCED APOPTOSIS; STRAND TRANSFER; NUCLEIC-ACIDS AB p53 is thought to function in the maintenance of genomic stability by modulating transcription and interacting with cellular proteins to influence the cell cycle, DNA repair and apoptosis. p53 mutations occur in >50% of human cancers, and cells which lack wild type p53 accumulate karyotypic abnormalities such as amplifications, deletions, inversions and translocations, We propose that p53 hinders these promiscuous recombinational events by interacting with cellular recombination and repair machinery. We recently reported that p53 can directly bind in vivo to human Rad51 (hRad51) protein and in vitro to its bacterial homologue RecA. We used GST-fusion and his-tagged protein systems to further investigate the physical interaction between p53 and hRad51, homologue of the yeast Rad51 protein that is involved in recombination and DNA double strand repair. The hRad51? binds to wild-type p53 and to a lesser extent, point mutants 135Y, 249S and 273H. This binding is not mediated by a DNA or RNA intermediate, Mapping studies using a panel of p53 deletion mutants indicate that hRad51 could bind to two regions of p53; one between amino acids 94 and 160 and a second between 264 and 315, Addition of anti-p53 antibody PAb421 (epitope 372-381 amino acids) inhibited the interaction with hRad51. In contrast, p53 interacts with the region between aa 125 and 220 of hRad51, which is highly conserved among Rad51 related proteins from bacteria to human, In Escherichia coli RecA protein, this region is required for homo-oligomerization, suggesting that p53 might disrupt the interaction between RecA and Rad51 subunits, thus inhibiting biochemical functions of Rad51 like proteins, These data are consistent with the hypothesis that p53 interaction with hRAD51 may influence DNA recombination and repair and that additional modifications of p53 by mutation and protein binding may affect this interaction. C1 NCI, HUMAN CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. UNIV LUBECK, INST HUMANGENET, D-23538 LUBECK, GERMANY. UNIV SAARLAND, D-66421 HOMBURG, GERMANY. RI Wang, Xin/B-6162-2009 NR 62 TC 159 Z9 162 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 1 PY 1997 VL 25 IS 19 BP 3868 EP 3874 DI 10.1093/nar/25.19.3868 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XZ398 UT WOS:A1997XZ39800017 PM 9380510 ER PT J AU Stein, C Schafer, M Cabot, PJ Carter, L Zhang, Q Zhou, L Gasior, M AF Stein, C Schafer, M Cabot, PJ Carter, L Zhang, Q Zhou, L Gasior, M TI Peripheral opioid analgesia SO PAIN REVIEWS LA English DT Review ID ARTHROSCOPIC KNEE SURGERY; DORSAL-ROOT-GANGLIA; CORTICOTROPIN-RELEASING-FACTOR; RAT SENSORY NEURONS; SUBSTANCE-P RELEASE; IMMUNOREACTIVE BETA-ENDORPHIN; BLOOD MONONUCLEAR-CELLS; INTRAARTICULAR MORPHINE ANALGESIA; PROENKEPHALIN-DERIVED PEPTIDES; STIMULATED ADENYLATE-CYCLASE C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NIDA,PRECLIN PHARMACOL LAB,BALTIMORE,MD. RI Cabot, Peter/B-2424-2013; OI Cabot, Peter/0000-0003-1778-3753; Stein, Christoph/0000-0001-5240-6836 NR 175 TC 2 Z9 2 U1 0 U2 2 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON, ENGLAND NW1 3BH SN 0968-1302 J9 PAIN REV JI Pain Rev. PD OCT PY 1997 VL 4 IS 3 BP 173 EP 187 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA YG205 UT WOS:A1997YG20500003 ER PT J AU Pimenta, PFP Modi, GB Pereira, ST Shahabuddin, M Sacks, DL AF Pimenta, PFP Modi, GB Pereira, ST Shahabuddin, M Sacks, DL TI Novel role for the peritrophic matrix in protecting Leishmania from the hydrolytic activities of the sand fly midgut SO PARASITOLOGY LA English DT Article DE chitinase; Leishmania; peritrophic membrane; sand fly; allosamidin ID PHLEBOTOMUS-PAPATASI DIPTERA; AEDES-AEGYPTI L; MEXICANA-AMAZONENSIS; VECTOR COMPETENCE; LIPOPHOSPHOGLYCAN; PSYCHODIDAE; MOSQUITO; MEMBRANE; TRANSMISSION; INSECTS AB The role of the peritrophic matrix (PM) in the development of Leishmania major infections in a natural vector, Phlebotomus papatasi, was investigated by addition of exogenous chitinase to the bloodmeal, which completely blocked PM formation. Surprisingly, the absence of the PM was associated with the loss of midgut infections. The chitinase was not directly toxic to the parasite, nor were midgut infections lost due to premature expulsion of the bloodmeal. Most parasites were killed in chitinase-treated flies within the first 4 h after feeding. Substantial early killing was also observed in control flies, suggesting that the lack of PM exacerbates lethal conditions which normally exist in the blood-fed midgut. Early parasite mortality was reversed by soybean trypsin inhibitor. Allosamadin, a specific inhibitor of chitinase, led to a thickening of the PM, and also prevented the early parasite mortality seen in infected flies. Susceptibility to gut proteases was extremely high in transitional-stage parasites, while amastigotes and fully transformed promastigotes were relatively resistant. A novel role for the PM in promoting parasite survival is suggested, in which the PM creates a barrier to the rapid diffusion of digestive enzymes, and limits the exposure of parasites to these enzymes during the time when they are especially vulnerable to proteolytic damage. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. UNIV ESTADUAL NORTE FLUMINENSE,CTR BIOCENCIAS & BIOTECHNOL,LAB BIOL CELULAR & TECIDUAL,BR-28015620 RIO JANEIRO,BRAZIL. NR 36 TC 76 Z9 80 U1 2 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0031-1820 J9 PARASITOLOGY JI Parasitology PD OCT PY 1997 VL 115 BP 359 EP 369 DI 10.1017/S0031182097001510 PN 4 PG 11 WC Parasitology SC Parasitology GA YD864 UT WOS:A1997YD86400003 PM 9364562 ER PT J AU Mitchell, H Senturia, Y Gergen, P Baker, D Joseph, C McNiffMortimer, K Wedner, HJ Crain, E Eggleston, P Evans, R Kattan, M Kercsmar, C Leickly, F Malveaux, F Smartt, E Weiss, K AF Mitchell, H Senturia, Y Gergen, P Baker, D Joseph, C McNiffMortimer, K Wedner, HJ Crain, E Eggleston, P Evans, R Kattan, M Kercsmar, C Leickly, F Malveaux, F Smartt, E Weiss, K TI Design and methods of the National Cooperative Inner-City Asthma Study SO PEDIATRIC PULMONOLOGY LA English DT Article DE asthma; children; inner-city ID DUST MITE ALLERGEN; DER-P-I; CHILDHOOD ASTHMA; NITROGEN-DIOXIDE; MONOCLONAL-ANTIBODIES; IGE ANTIBODIES; CHILDREN; EXPOSURE; PURIFICATION; DERMATOPHAGOIDES AB The National Cooperative Inner-City Asthma Study (NCICAS) was established to identify and then intervene on those factors which are related to asthma morbidity among children in the inner-city. This paper describes the design and methods of the broad-based initial Phase I epidemiologic investigation. Eight research centers enrolled 1,528 children, 4 to 9 years of age, from English-or Spanish-speaking families, all of whom resided in major metropolitan inner-city areas. The protocol included an eligibility assessment and an extensive baseline visit, during which symptom data, such as wheezing, lost sleep, changes in activities of daily living, inpatient admissions, and emergency department and clinic visits were collected. A comprehensive medical history for each child was taken and adherence to the medical regimen was assessed. Access, as well as barriers, to the medical system were addressed by a series of questions including the location, availability, and consistency of treatment for asthma attacks, follow-up care, and primary care. The psychological health of the caretaker and of the child was also measured. Asthma knowledge of the child and caretaker was determined. Sensitization to allergens was assessed by skin-prick allergen testing and exposure to cigarette smoke and the home environment were assessed by questionnaire-For more than a third of the families, in-home visits were conducted with dust sample allergen collection and documentation of the home environment, such as the presence of pets and evidence of smoking, mildew, and roaches. Urine specimens were collected to measure passive smoke exposure by cotinine assays, blood samples were drawn for banking, and children age 6 to 9 years were given spirometric lung function assessment. At 3, 6 and 9 months following the baseline assessment, telephone interviews were conducted to ask about the child's symptoms, unscheduled emergency department or clinic visits, and hospitalizations. At this time, peak flow measurements with 2-week diary symptom records were collected. (C) 1997 Wiley-Liss, Inc. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. CHILDRENS MEM HOSP,CHICAGO,IL 60614. NIAID,DAIT,NIH,BETHESDA,MD 20892. MT SINAI SCH MED,NEW YORK,NY. HENRY FORD HOSP,DETROIT,MI 48202. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. JOHNS HOPKINS SCH MED,BALTIMORE,MD. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. HOWARD UNIV,COLL MED,WASHINGTON,DC. FU PHS HHS [UO1 A1-30751, UO1 A1-30752, UO1 A1-30756] NR 33 TC 112 Z9 113 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 1997 VL 24 IS 4 BP 237 EP 252 PG 16 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA YE566 UT WOS:A1997YE56600003 PM 9368258 ER PT J AU Kattan, M Mitchell, H Eggleston, P Gergen, P Crain, E Redline, S Weiss, K Evans, R Kaslow, R Kercsmar, C Leickly, F Malveaux, F Wedner, HJ AF Kattan, M Mitchell, H Eggleston, P Gergen, P Crain, E Redline, S Weiss, K Evans, R Kaslow, R Kercsmar, C Leickly, F Malveaux, F Wedner, HJ TI Characteristics of inner-city children with asthma: The National Cooperative Inner-City Asthma Study SO PEDIATRIC PULMONOLOGY LA English DT Article DE asthma; children; inner-city ID CHILDHOOD ASTHMA; UNITED-STATES; HEALTH-SERVICES; BIRTH-WEIGHT; PREVALENCE; MORTALITY; TRENDS; HOSPITALIZATION; POVERTY; FREQUENCY AB Asthma morbidity has increased dramatically in the past decade, especially among poor and minority children in the inner cities. The National Cooperative inner-City Asthma Study (NCICAS) is a multicenter study designed to determine factors that contribute to asthma morbidity in children in the inner cities. A total of 1,528 children with asthma, ages 4 to 9 years old, were enrolled in a broad-based epidemiologic investigation of factors which were thought to be related to asthma morbidity. Baseline assessment included morbidity, allergy evaluation, adherence and access to care, home visits, and pulmonary function. interval assessments were conducted at 3, 6, and 9 months after the baseline evaluations. Over the one-year period, 83% of the children had no hospitalizations and 3.6% had two or more. The children averaged 3 to 3.5 days of wheeze for each of the four two-week recall periods. The pattern of skin test sensitivity differed from other populations in that positive reactions to cockroach were higher (35%) and positive reactions to house dust mite were lower (31%). Caretakers reported smoking in 39% of households of children with asthma, and cotinine/ creatinine ratios exceeded 30 ng/mg in 48% of the sample. High exposure (>40 ppb) to nitrogen dioxide was found in 24% of homes. Although the majority of children had insurance coverage, 53% of study participants found it difficult to get follow-up asthma care. The data demonstrate that symptoms are frequent but do not result in hospitalization in the majority of children. These data indicate a number of areas which are potential contributors to the asthma morbidity in this population, such as environmental factors, lack of access to care, and adherence to treatment. Interventions to reduce asthma morbidity are more likely to be successful ii they address the many different asthma risks found in the inner cities. (C) 1997 Wiley-Liss, Inc. C1 MT SINAI SCH MED, NEW YORK, NY USA. NEW ENGLAND RES INST, WATERTOWN, MA 02172 USA. JOHNS HOPKINS SCH MED, BALTIMORE, MD USA. NIAID, DAIT, NIH, BETHESDA, MD 20892 USA. ALBERT EINSTEIN COLL MED, BRONX, NY 10467 USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CHILDRENS MEM HOSP, CHICAGO, IL 60614 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. HENRY FORD HOSP, DETROIT, MI 48202 USA. HOWARD UNIV, COLL MED, WASHINGTON, DC USA. WASHINGTON UNIV, SCH MED, ST LOUIS, MO USA. FU PHS HHS [UO1 A1-30751, UO1 A1-30752, UO1 A1-30756] NR 29 TC 263 Z9 265 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 1997 VL 24 IS 4 BP 253 EP 262 DI 10.1002/(SICI)1099-0496(199710)24:4<253::AID-PPUL4>3.0.CO;2-L PG 10 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA YE566 UT WOS:A1997YE56600004 PM 9368259 ER PT J AU Wade, S Weil, C Holden, G Mitchell, H Evans, R KruszonMoran, D Bauman, L Crain, E Eggleston, P Kattan, M Kercsmar, C Leickly, F Malveaux, F Wedner, HJ AF Wade, S Weil, C Holden, G Mitchell, H Evans, R KruszonMoran, D Bauman, L Crain, E Eggleston, P Kattan, M Kercsmar, C Leickly, F Malveaux, F Wedner, HJ TI Psychosocial characteristics of inner-city children with asthma: A description of the NCICAS psychosocial protocol SO PEDIATRIC PULMONOLOGY LA English DT Article DE asthma; children; inner-city; psychosocial ID DEPENDENT DIABETES-MELLITUS; HEALTH-CARE SERVICES; LIFE EVENTS; SELF-MANAGEMENT; PERCEIVED COMPETENCE; PSYCHOLOGICAL ADJUSTMENT; PSYCHIATRIC-DISORDERS; CAGE QUESTIONNAIRE; METABOLIC CONTROL; CHILDHOOD ASTHMA AB Previous research has demonstrated a significant reciprocal relationship between psychosocial factors and asthma morbidity in children. The National Cooperative Inner-City Asthma Study investigated both asthma-specific and non-specific psychosocial variables, including asthma knowledge beliefs and management behavior, caregiver and child adjustment, life stress, and social support. This article presents these psychosocial characteristics in 1,528 4-9-year-old asthmatic urban children and their caretakers. Caretakers demonstrated considerable asthma knowledge, averaging 84% correct responses on the Asthma Information Quiz. However, respondents provided less than one helpful response for each hypothetical problem situation involving asthma care, and most respondents had more than one undesirable response, indicating a potentially dangerous or maladaptive action. Both adults and children reported multiple caretakers responsible for asthma management (adult report: average 3.4, including the child); in addition, children rated their responsibility for self-care significantly higher than did adults. Scores on the Child Behavior Checklist indicated increased problems compared to normative samples (57.3 vs. 50, respectively), and 35% of children met the criteria for problems of clinical severity. On the Brief Symptom Inventory, adults reported elevated levels of psychological distress (56.02 vs norm of 50); 50% of caretakers had symptoms of clinical severity. Caretakers also experienced an average of 8.13 undesirable life events in the 12 months preceding the baseline interview. These findings suggest that limited asthma problem-solving skills, multiple asthma managers, child and adult adjustment problems, and high levels of life stress are significant concerns for this group and may place the inner-city children in this study population at increased risk for problems related to adherence to asthma management regimens and for asthma morbidity. (C) 1997 Wiley-Liss, Inc. C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. CHILDRENS MEM HOSP,CHICAGO,IL 60614. MT SINAI SCH MED,NEW YORK,NY. NEW ENGLAND RES INST,WATERTOWN,MA 02172. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. JOHNS HOPKINS SCH MED,BALTIMORE,MD. HENRY FORD HOSP,DETROIT,MI 48202. HOWARD UNIV,COLL MED,WASHINGTON,DC. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. RP Wade, S (reprint author), NIA,DAIT,NIH,SOALR BLDG,ROOM 4A42,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Holden, Gary/A-2290-2008; OI Holden, Gary/0000-0002-7227-3652 FU PHS HHS [UO1 A1-30751, UO1 A1-30752, UO1 A1-30756] NR 65 TC 123 Z9 127 U1 2 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 1997 VL 24 IS 4 BP 263 EP 276 DI 10.1002/(SICI)1099-0496(199710)24:4<263::AID-PPUL5>3.0.CO;2-L PG 14 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA YE566 UT WOS:A1997YE56600005 PM 9368260 ER PT J AU Mancilla, EE DeLuca, F Ray, K Winer, KK Fan, GF Baron, J AF Mancilla, EE DeLuca, F Ray, K Winer, KK Fan, GF Baron, J TI A Ca2+-sensing receptor mutation causes hypoparathyroidism by increasing receptor sensitivity to Ca2+ and maximal signal transduction SO PEDIATRIC RESEARCH LA English DT Article; Proceedings Paper CT 10th International Congress of Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CA ID CALCIUM-SENSING RECEPTOR; AUTOSOMAL-DOMINANT; MOLECULAR-CLONING; HYPOCALCEMIA; EXPRESSION; KIDNEY AB Activating mutations of the Ca2+-sensing receptor (caR) gene cause autosomal dominant hypoparathyroidism. Functional expression studies have been reported for several mutations, but have produced conflicting results. Thus, the mechanism by which these mutations activate the receptor is unclear. We describe here a new family with autosomal dominant hypoparathyroidism. The mother and three daughters experienced muscle spasms and/or seizures from early childhood. They were treated with oral calcium and vitamin D analogs, and all four patients developed hypercalciuria, nephrocalcinosis, and renal insufficiency. In this family, we identified a heterozygous missense mutation (F612S) involving the extracellular region of the CaR. The mutation cosegregated with disease. It was not present in 50 normal control individuals, We used site-directed mutagenesis to introduce this mutation into the caR cDNA, and then expressed the mutant receptor in human embryonic kidney (HEK)-293 cells. In these cells, the accumulation of inositol phosphates was measured as a function of extracellular Ca2+ concentration. compared with the wild-type receptor, the mutant receptor showed a left-shift in the concentration-response curve and an increase in the maximal response to high Ca2+ concentrations. These effects did not appear to be mediated by changes in levels of receptor expression, as judged by ELISA, or by changes in receptor glycosylation, as judged by Western analysis. We conclude that this CaR mutation causes hypoparathyroidism by a dual increase in receptor sensitivity to extracellular Ca2+ and maximal signal transduction capacity. C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NR 18 TC 24 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 1997 VL 42 IS 4 BP 443 EP 447 DI 10.1203/00006450-199710000-00004 PG 5 WC Pediatrics SC Pediatrics GA XX215 UT WOS:A1997XX21500004 PM 9380434 ER PT J AU Rauchschwalbe, R Brenner, RA Smith, GS AF Rauchschwalbe, R Brenner, RA Smith, GS TI The role of bathtub seats and rings in infant drowning deaths SO PEDIATRICS LA English DT Article DE drowning; submersion; infant; bathtub ID UNITED-STATES; CHILD-ABUSE; COUNTY; PREVENTION; ACCIDENTS; BRISBANE; INJURY; POOLS AB Objective. To describe deaths due to drowning that involve the use of an infan Design. Case series, cases reported to the US Consumer Product Safety Commission data systems. Setting. United States, 1983-1995. Main Outcome Measures. Death in which an infant bathtub seat or ring was in use at the time of deathand the primary cause of death was drowning. Results. Thirty-two drowning deaths involving bath seats/rings were identified and investigated by the Consumer Product Safety Commission over a 13-year period. The majority of deaths (84%) occurred from 1991-1995, with more than 50% occurring in the 2 most recent years. The victims' ages at the time of the incident ranged from 5 to 15 months with a mean and median age of 8 months. In more than 90% of incidents there was a reported lapse in adult supervision, with a mean reported lapse of 6 minutes and a median lapse of 4 minutes. Focus groups with parents found that while making bathing somewhat easier, bath seats/rings are useful for a relatively short time period, as the child rapidly outgrows the product. They also suggested that care givers are more likely to leave a child unattended in the tub if one of these products is in use. Conclusion. Bath seats/rings are associated with an increasing number of reported infant drowning deaths. The use of such products may increase the risk of drowning among infants by increasing the likelihood that an infant will be left alone in the tub. However, in the absence of exposure data in a suitable comparison group it is difficult to assess the overall risk inherent in their use. Educational efforts reinforcing the need for continuous adult supervision of infants and children around all bodies of water should now also include a reminder that bath seats/rings are not safety items and are not a substitute for adult supervision. Infants and toddlers should never be left in the bathtub unsupervised, even for brief moments. C1 NICHHD, DIV EPIDEMIOL STAT & PREVENT RES, BETHESDA, MD 20892 USA. US CONSUMER PROD SAFETY COMMISS, BETHESDA, MD USA. JOHNS HOPKINS UNIV, CTR INJURY RES & POLICY, BALTIMORE, MD 21218 USA. SCH HYG & PUBL HLTH, BALTIMORE, MD USA. FU NIAAA NIH HHS [R29AA07700] NR 25 TC 14 Z9 14 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1997 VL 100 IS 4 BP art. no. EP e1 DI 10.1542/peds.100.4.e1 PG 5 WC Pediatrics SC Pediatrics GA XZ079 UT WOS:A1997XZ07900022 PM 9310534 ER PT J AU London, SJ SullivanKlose, T Daly, AK Idle, JR AF London, SJ SullivanKlose, T Daly, AK Idle, JR TI Lung cancer risk in relation to the CYP2C9 genetic polymorphism among Caucasians in Los Angeles County SO PHARMACOGENETICS LA English DT Article DE cytochrome P4502C9; cytochrome P4502C; CYP2C; susceptibility; epidemiology ID ALLELIC VARIANT; BENZOPYRENE; METABOLISM C1 NIEHS,LAB PHARMACOL & CHEM,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. MED SCH NEWCASTLE UPON TYNE,DEPT PHARMACOL SCI,NEWCASTLE TYNE NE2 4HH,TYNE & WEAR,ENGLAND. MEDISINSK TEKNISK SENTER,INST CANC RES & MOL BIOL,N-7005 TRONDHEIM,NORWAY. RP London, SJ (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Daly, Ann/H-3144-2011; OI Daly, Ann/0000-0002-7321-0629; Idle, Jeff/0000-0002-6143-1520; London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [N01-CN-25403] NR 9 TC 31 Z9 32 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1997 VL 7 IS 5 BP 401 EP 404 DI 10.1097/00008571-199710000-00010 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA YA646 UT WOS:A1997YA64600010 PM 9352577 ER PT J AU Metcalfe, DD Baram, D Mekori, YA AF Metcalfe, DD Baram, D Mekori, YA TI Mast cells SO PHYSIOLOGICAL REVIEWS LA English DT Review ID BASOPHILIC LEUKEMIA-CELLS; TUMOR-NECROSIS-FACTOR; FC-EPSILON-RI; C-KIT LIGAND; HIGH-AFFINITY RECEPTOR; MOUSE BONE-MARROW; DELAYED-TYPE HYPERSENSITIVITY; COLONY-STIMULATING FACTOR; CONNECTIVE-TISSUE-TYPE; PROTEIN-TYROSINE KINASE AB Mast cells are found resident in tissues throughout the body, particularly in association with structures such as blood vessels and nerves, and in proximity to surfaces that interface the external environment. Mast cells are bone marrow-derived and particularly depend upon stem cell factor for their survival. Mast cells express a variety of phenotypic features within tissues as determined by the local environment. Withdrawal of required growth factors results in mast cell apoptosis. Mast cells appear to be highly engineered cells with multiple critical biological functions. They may be activated by a number of stimuli that are bath Fc(epsilon)RI dependent and Fc(epsilon)RI independent. Activation through various receptors leads to distinct signaling pathways. After activation, mast cells may immediately extrude granule-associated mediators and generate lipid-derived substances that induce immediate allergic inflammation, Mast cell activation may also be followed by the synthesis of chemokines and cytokines, Cytokine and chemokine secretion, which occurs hours later, may contribute to chronic inflammation. Biological functions of mast cells appear to include a role in innate immunity, involvement in host defense mechanisms against parasitic infestations, immunomodulation of the immune system, and tissue repair and angiogenesis. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT MED,IL-69978 TEL AVIV,ISRAEL. RP Metcalfe, DD (reprint author), NIAID,ALLERG DIS LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 590 TC 1340 Z9 1385 U1 12 U2 88 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD OCT PY 1997 VL 77 IS 4 BP 1033 EP 1079 PG 47 WC Physiology SC Physiology GA YC320 UT WOS:A1997YC32000004 PM 9354811 ER PT J AU Azarya-Sprinzak, E Naor, D Wolfson, HJ Nussinov, R AF Azarya-Sprinzak, E Naor, D Wolfson, HJ Nussinov, R TI Interchanges of spatially neighbouring residues in structurally conserved environments SO PROTEIN ENGINEERING LA English DT Article DE compensatory interchanges; correlated interchanges; protein design; structural motifs; structure comparison ID PROTEIN STRUCTURES; BACTERIOPHAGE-T4 LYSOZYME; AROMATIC INTERACTIONS; CORRELATED MUTATIONS; DATA-BANK; SEQUENCE; STABILITY; EVOLUTION; PACKING; POTENTIALS AB The question of whether interchanges of spatially neighboring residues are coupled, or whether they change independently of each other, has been addressed repeatedly over the last few years. Utilizing a residue order-independent structural comparison tool, we investigated interchanges of spatially adjacent residue pairs in conserved 3D environments in globally dissimilar protein structures. We define spatially adjacent pairs to be non-local neighboring residues which are in spatial contact, though separated along the backbone, to exclude backbone effects. A dataset of unrelated structures is extensively compared, constructing a matrix of all 400x400 interchanges of residue pairs. Our study indicates that (i) interchanges of residues which are spatial neighbors are indepedent of each other. With the exception of a few pairs, the pattern of interchanges of pairs of adjacent residues resembles that expected from interchanges of single residues. However, clustering residues of similar characteristics, serves to enhance secondary trends. Hence, (ii) clustering the hydrophobic, aliphatic and, separately, the aromatic, and comparing them with the charged, and the polar, indicates that hydrophobic pairs are favorably replaced by hydrophobic, and charged/polar by charged/polar. The most strongly conserved are the charged. Interestingly, the type of charge (like or opposite) plays no role. Interchanges between the hydrophobic and hydrophilic classes are unfavorable. (iii) Clustering by volume indicates that the most highly conserved are the (Small, Small) pairs. The least favorable are interchanges of the type (Small, Small) <---->, (Large, Large). Interchanges of the type (Large, Small) <----> (Large, Large) are less favorable than (Large, Small) <----> (Small, Small). Compensatory interchanges of the type (Large, Small) <----> (Small, Large) are unfavorable. (iv) Inspection of the trends in the interchanges of the clustered small residues versus clustered large rigid, and separately versus clustered large flexible, illustrates clear differences. Consistently, within all hydrophobic, large and small, the flexible aliphatic differ from the more rigid aromatic. The flexible aliphatic residue pairs are unfavorably replaced by other residue types. Furthermore, (v) the unique properties of the aromatics, conferred by the electronic configuration of their benzene rings, are transformed into clear trends. Replacements of polar residues by aromatics, while unfavorable, are nevertheless consistently more favorable than into aliphatics. We address these issues and their direct implications to protein design and to fold recognition. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, SAIC, Frederick, MD 21702 USA. Tel Aviv Univ, Fac 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, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, SAIC, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 47 TC 17 Z9 18 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD OCT PY 1997 VL 10 IS 10 BP 1109 EP 1122 DI 10.1093/protein/10.10.1109 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YV403 UT WOS:000071819500002 PM 9488136 ER PT J AU Hwang, SR Palkovits, M Hook, VYH AF Hwang, SR Palkovits, M Hook, VYH TI High level expression and characterization of recombinant human hippocampus phenol sulfotransferase: A novel phenol-sulfating form of phenol sulfotransferase SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID HUMAN LIVER; HUMAN-BRAIN; KINETIC CHARACTERIZATION; BACTERIAL EXPRESSION; MOLECULAR-CLONING; CDNA CLONING; IDENTIFICATION; PURIFICATION; GENES AB Phenol sulfotransferases (PSTs) represent a family of sulfotransferase enzymes that modify the biologic activities and excretion of phenolic compounds and monoamines. A novel human hippocampal PST (H-PST) cDNA with homology to phenol (P) and monoamine (M) forms of PST was previously isolated from brain, To compare the biochemical properties of H-PST with that of phenol (P-PST) and monoamine (M-PST) sulfotransferases, high level expression of recombinant H-PST was achieved in this study with the pET3c vector in BL21(DE3) Escherichia coli cells. Expression was demonstrated by isopropyl beta-n-thiogalactopyranoside induction of 34-kDa H-PST that represented 5-10% of total E. coli proteins. Purification by ion-exchange chromatography on DEAE-Sepharose yielded more than 2 mg of H-PST, Characterization showed that H-PST exists as a homodimer of 60-65 kDa by gel filtration chromatography, H-PST prefers p-nitrophenol as substrate and does not sulfate dopamine or neuropeptide substrates, Kinetic studies showed that H-PST possessed K-m(app) and V-max(app) values of 3 mu M p-nitrophenol and 160 nmol/min/mg, respectively. H-PST was sensitive to inhibition by DCNP (2,6-dichloro-4-nitrophenol). H-PST is thermolabile since its activity was reduced upon preincubation at 37 degrees C. These results indicate that H-PST shows similarities and differences compared to. P-PST and M-PST sulfotransferases, P-PST prefers p-nitrophenol as substrate, is sensitive to inhibition by DCNP, and is thermostable; in contrast, M-PST prefers monoamines as substrate, is not sensitive to DCNP, and is thermolabile. The distinct profile of biochemical properties of H-PST, and its primary sequence homology to P-PST and M-PST, suggests that H-PST represents a novel allelic variant of human phenol sulfotransferases. Importantly, this study demonstrates that high level expression of H-PST allows determination of distinguishing characteristics of variant forms of PSTs. (C) 1997 Academic Press. C1 UNIV CALIF SAN DIEGO, DEPT MED 0822, LA JOLLA, CA 92093 USA. SEMMELWEIS UNIV MED, SCH MED, DEPT ANAT 1, H-1085 BUDAPEST, HUNGARY. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 28 TC 2 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD OCT PY 1997 VL 11 IS 1 BP 125 EP 134 DI 10.1006/prep.1997.0782 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XY802 UT WOS:A1997XY80200016 PM 9325148 ER PT J AU Raghunathan, G Jernigan, RL AF Raghunathan, G Jernigan, RL TI Ideal architecture of residue packing and its observation in protein structures SO PROTEIN SCIENCE LA English DT Article DE equivalent sphere packing model; ideal packing; long-range interactions; packing geometry, protein lattices; residue packing ID KNOWLEDGE-BASED POTENTIALS; MONTE-CARLO SIMULATIONS; ACID SIDE-CHAINS; LATTICE MODEL; FOLDING PROBLEM; CORE-PACKING; ENERGY; CONFORMATIONS; SEQUENCE; DENSITY AB A simple model of sphere packing has been investigated as an ideal model for long-range interactions for the packing of non-bonded residues in protein structures. By superposing all residues, the geometry of packing around a central residue is investigated. It is found that all residues conform almost perfectly to this lattice model for sphere packing when a radius of 6.5 Angstrom is used to define non-bonded (virtual) interacting residues. Side-chain positions with respect to sequential backbone segments are relatively regular as well. This lattice can readily be used in conformation simulations to reduce the conformational space. C1 NCI,MOL STRUCT SECT,LAB EXPT & COMPUTAT BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012 NR 44 TC 40 Z9 40 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD OCT PY 1997 VL 6 IS 10 BP 2072 EP 2083 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YB609 UT WOS:A1997YB60900003 PM 9336831 ER PT J AU Bahar, I Atilgan, AR Jernigan, RL Erman, B AF Bahar, I Atilgan, AR Jernigan, RL Erman, B TI Understanding the recognition of protein structural classes by amino acid composition SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE non-bonded contacts; coordination of amino acids; Kirchhoff matrices; lattice models; singular value decomposition; secondary structure content prediction; contact patterns ID SECONDARY STRUCTURE; CLASS PREDICTIONS; NEURAL NETWORKS; FOLDING TYPE; CHARACTERS; CLASSIFICATION; INFORMATION; POTENTIALS AB (K)nowledge of amino acid composition, alone, is verified here to be sufficient for recognizing the structural class, alpha, beta, alpha + beta, or alpha/beta of a given protein with an accuracy of 81%. This is supported by results from exhaustive enumerations of all conformations for all sequences of simple, compact lattice models consisting of two types (hydrophobic and polar) of residues. Different compositions exhibit strong affinities for certain folds. Within the limits of validity of the lattice models, two factors appear to determine the choice of particular folds: 1) the coordination numbers of individual sites and 2) the size and geometry of non-bonded clusters. These two properties, collectively termed the distribution of nonbonded contacts, are quantitatively assessed by an eigenvalue analysis of the so-called Kirchhoff or adjacency matrices obtained by considering the non-bonded interactions on a lattice. The analysis permits the identification of conformations that possess the same distribution of non-bonded contacts. Furthermore, some distributions of non-bonded contacts are favored entropically, due to their high degeneracies. Thus, a competition between enthalpic and entropic effects is effective in determining the choice of a distribution for a given composition, Based on these findings, an analysis of non-bonded contacts in protein structures was made. The analysis shows that proteins belonging to the four distinct folding classes exhibit significant differences in their distributions of non-bonded contacts, which more directly explains the success in predicting structural class from amino acid composition. (C) 1997 Wiley-Liss, Inc.dagger C1 NCI,MOL STRUCT SECT,LAB EXPT & COMPUTAT BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892. BOGAZICI UNIV,POLYMER RES CTR,TR-80815 BEBEK,ISTANBUL,TURKEY. TUBITAK ADV POLYMER MAT RES CTR,TR-80815 BEBEK,ISTANBUL,TURKEY. RI Atilgan, Ali Rana/A-7805-2011; Jernigan, Robert/A-5421-2012; OI ERMAN, BURAK/0000-0002-2496-6059 NR 33 TC 112 Z9 113 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD OCT PY 1997 VL 29 IS 2 BP 172 EP 185 DI 10.1002/(SICI)1097-0134(199710)29:2<172::AID-PROT5>3.0.CO;2-F PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XZ547 UT WOS:A1997XZ54700005 PM 9329082 ER PT J AU ElKabbani, O Carper, DA McGowan, MH Devedjiev, Y ReesMilton, KJ Flynn, TG AF ElKabbani, O Carper, DA McGowan, MH Devedjiev, Y ReesMilton, KJ Flynn, TG TI Studies on the inhibitor-binding site of porcine aldehyde reductase: Crystal structure of the holoenzyme-inhibitor ternary complex SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE aldo-keto reductase; diabetic complications; drug design; site-directed mutagenesis; alpha/beta-barrel; X-ray crystallography ID HUMAN ALDOSE REDUCTASE; DIABETIC COMPLICATIONS; ACTIVE-SITE; ENZYME; SUBSTRATE; MUTAGENESIS; MECHANISM AB Aldehyde reductase is an enzyme capable of metabolizing a wide variety of aldehydes to their corresponding alcohols. The tertiary structures of aldehyde reductase and aldose reductase are similar and consist of an alpha/beta-barrel with the active site located at the carboxy terminus of the strands of the barrel. We have determined the X-ray crystal structure of porcine aldehyde reductase holoenzyme in complex with an aldose reductase inhibitor, tolrestat, at 2.4 Angstrom resolution to obtain a picture of the binding conformation of inhibitors to aldehyde reductase. Tolrestat binds in the active site pocket of aldehyde reductase and interacts through van der Waals contacts with Arg 312 and Asp 313. The carboxylate group of tolrestat is within hydrogen bonding distance with His 113 and Trp 114. Mutation of Arg 312 to alanine in porcine aldehyde reductase alters the potency of inhibition of the enzyme by aldose reductase inhibitors. Our results indicate that the structure of the inhibitor-binding site of aldehyde reductase differs from that of aldose reductase due to the participation of nonconserved residues in its formation. A major difference is the participation of Arg 312 and Asp 313 in lining the inhibitor-binding site in aldehyde reductase but not in aldose reductase. (C) 1997 Wiley-Liss, Inc. C1 NEI,NIH,BETHESDA,MD 20892. UNIV ALABAMA,CTR MACROMOL CRYSTALLOG,BIRMINGHAM,AL 35294. QUEENS UNIV,DEPT BIOCHEM,KINGSTON,ON K7L 3N6,CANADA. RP ElKabbani, O (reprint author), MONASH UNIV,VICTORIAN COLL PHARM,DEPT MED CHEM,381 ROYAL PARADE,PARKVILLE,VIC 3052,AUSTRALIA. NR 33 TC 35 Z9 36 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD OCT PY 1997 VL 29 IS 2 BP 186 EP 192 DI 10.1002/(SICI)1097-0134(199710)29:2<186::AID-PROT6>3.0.CO;2-B PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XZ547 UT WOS:A1997XZ54700006 PM 9329083 ER PT J AU Berenbaum, SA Resnick, SM AF Berenbaum, SA Resnick, SM TI Early androgen effects on aggression in children and adults with congenital adrenal hyperplasia SO PSYCHONEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT XIIIth Biennial Meeting of the International-Society-for-the-Study-of-Behavioural-Development CY JUN 28-JUL 02, 1994 CL AMSTERDAM, NETHERLANDS SP Int Soc Study Behav Dev DE sex differences; aggression; gonadal hormones; congenital adrenal hyperplasia; 21-hydroxylase deficiency; psychosexual development ID EARLY HORMONAL INFLUENCES; GENDER-RELATED BEHAVIOR; SEX-DIFFERENCES; HUMANS; PROGESTERONE; TESTOSTERONE; PREFERENCES; ORIENTATION; ADOLESCENT; ATTITUDES AB Males are more likely than females to show aggressive behavior across species, ages, and situations, and these differences may be partly influenced by early hormones. We studied aggression in three samples of subjects with congenital adrenal hyperplasia (CAH), who were exposed to high levels of androgen in the prenatal and early postnatal periods. Controls were siblings and first cousins similar in age. In Sample 1, adolescents and adults completed the Multidimensional Personality Questionnaire (MPQ), which includes an Aggression scale. In Sample 2, adolescents and adults completed the MPQ and a paper-and-pencil version of Reinisch's Aggression Inventory. In Sample 3, parents rated the aggression of children aged 3-12, using a modification of Reinisch's Inventory. In all three samples, control males had higher aggression scores than control females. Further, as predicted, females with CAH had higher aggression than control females, but the difference was significant only in adolescents and adults. These results suggest that early androgens contribute to variability in human aggression. Published by Elsevier Science Ltd. C1 NIA,LAB PERSONAL & COGNIT,BALTIMORE,MD 21224. RP Berenbaum, SA (reprint author), SO ILLINOIS UNIV,SCH MED,DEPT SOCIAL & BEHAV SCI,CARBONDALE,IL 62901, USA. FU NICHD NIH HHS [R01 HD019644, HD19644] NR 39 TC 105 Z9 106 U1 3 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD OCT PY 1997 VL 22 IS 7 BP 505 EP 515 DI 10.1016/S0306-4530(97)00049-8 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA YE716 UT WOS:A1997YE71600003 PM 9373884 ER PT J AU Funk, D Post, RM Pert, A AF Funk, D Post, RM Pert, A TI Role of central dopaminergic and 5-hydroxytryptaminergic projections in the behavioral responses elicited by thyrotropin-releasing hormone in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE thyrotropin-releasing hormone; dopamine; 5-hydroxytryptamine; vagus nerve; locomotor activity; behavior; microdialysis ID RECEPTOR MESSENGER-RNA; CENTRAL NERVOUS-SYSTEM; SPINAL-CORD; NUCLEUS-ACCUMBENS; SUBSTANCE-P; TRH; BRAIN; SEROTONIN; INVOLVEMENT; NEURONS AB The systemic administration of thyrotropin-releasing hormone (TRH) to rats elicits locomotor activation wet dog shakes, jaw movements, paw licking and tail rattle. Central dopamine (DA) and 5-hydroxytryptamine (5-HT) systems and peripheral vagal afferents have been implicated in these responses. To define this circuitry further, the effects of lesions of these pathways on the behavioral responses elicited by intraperitoneal (IF) injections of TRH were assessed in rats. Lesions of the DAergic innervation of the nucleus accumbens did not affect the locomotor activation, wet dog shakes, paw licking, jaw movements or tail rattle elicited by TRH. This is consistent with our in vivo microdialysis finding that TRH did not affect the release of DA in the nucleus accumbens at a dose that strongly increased locomotor activity. Depletion of spinal 5-HT significantly decreased the wet dog shakes induced by TRH, while depletion of forebrain 5-HT had no effect on any behavior. Bilateral vagotomy did not affect the locomotor response to TRH or any of the other behaviors measured. Taken together, these results suggest that the DAergic mesolimbic, the 5-HTergic projections to the forebrain and vagal afferent systems are not mediators of the behavioral responses to systemic TRH. In contrast, the raphe-spinal 5-HTergic projection system may serve to modulate the wet dog shakes elicited by this peptide. RP Funk, D (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 38 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1997 VL 133 IS 4 BP 356 EP 362 DI 10.1007/s002130050414 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YC397 UT WOS:A1997YC39700007 PM 9372535 ER PT J AU Leidy, NK AF Leidy, NK TI Validation research and the life cycle of health outcome measures SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 MEDTAP INT INC,BETHESDA,MD. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT-DEC PY 1997 VL 6 IS 7-8 BP 220 EP 220 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YH504 UT WOS:A1997YH50400220 ER PT J AU McCabe, M AF McCabe, M TI Making quality of life a meaningful end-point in cancer clinical trials SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT-DEC PY 1997 VL 6 IS 7-8 BP 238 EP 238 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YH504 UT WOS:A1997YH50400238 ER PT J AU Curbow, B Bowie, JV Martin, AC Lopez, SG Campbell, JF Phillips, PH McCabe, MS Varricchio, C AF Curbow, B Bowie, JV Martin, AC Lopez, SG Campbell, JF Phillips, PH McCabe, MS Varricchio, C TI Quality of life in cancer chemotherapy randomized trials SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. EMMES CORP,POTOMAC,MD. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT-DEC PY 1997 VL 6 IS 7-8 BP 239 EP 239 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YH504 UT WOS:A1997YH50400239 ER PT J AU Trimble, EL AF Trimble, EL TI Collecting and analysing quality of life data in cancer treatment trials SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT-DEC PY 1997 VL 6 IS 7-8 BP 392 EP 392 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YH504 UT WOS:A1997YH50400392 ER PT J AU Varicchio, C AF Varicchio, C TI The necessary components of a quality of life end-point evaluation in a clinical trial SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT-DEC PY 1997 VL 6 IS 7-8 BP 403 EP 403 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YH504 UT WOS:A1997YH50400403 ER PT J AU Courcoutsakis, NA Chow, CK Shawker, TH Carney, JA Stratakis, CA AF Courcoutsakis, NA Chow, CK Shawker, TH Carney, JA Stratakis, CA TI Syndrome of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas (Carney complex): Breast imaging findings SO RADIOLOGY LA English DT Article DE breast neoplasms, diagnosis; breast neoplasms, MR; breast neoplasms, radiography; breast neoplasms, US; Carney complex; gadolinium ID SPECIAL ASSOCIATIONS; DUCTAL ADENOMA; FIBROADENOMA AB PURPOSE: To study the imaging appearances of breast lesions in female patients with Carney complex. MATERIALS AND METHODS: Seven patients with Carney complex underwent mammography (n = 5), ultrasound (US) (n = 6), or magnetic resonance (MR) imaging (n = 6) in a prospective study. Previous breast images in three patients were reviewed. Mammograms in two additional patients were retrospectively reviewed. Thus, nine patients aged 16-61 were included in this study. RESULTS: Mammograms showed well-defined, iso-or hypodense masses; most were not calcified. Two lesions contained calcifications; both were biopsy-proved ductal adenomas. US demonstrated solid, hypoechoic, well-circumscribed masses in six patients and complex cystic masses (myxoid fibroadenomas) in one patient. MR imaging with a fat-suppressed, fast spin-echo, T2-weighted sequence demonstrated high-signal-intensity lesions (n = 5). Fat-suppressed, spoiled gradient-recalled-echo MR images demonstrated hypointense lesions with variable contrast material enhancement (n = 5). Five of seven patients in the prospective review had multiple breast lesions on at least one study. Mammograms and US scans were negative in three patients each. Chest and breast MR images were negative in only one patient. CONCLUSION: Female patients with Carney complex often have multiple breast masses with variable imaging appearances that probably represent myxoid fibroadenomas or ductal adenomas. MR imaging showed the most lesions. These lesions all demonstrate benign characteristics and should not prompt multiple biopsies. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. MAYO CLIN,DEPT LAB MED & PATHOL,ROCHESTER,MN. NICHHD,DEV ENDOCRINOL BRANCH,UNIT GENET ENDOCRINOL,SECT PEDIAT ENDOCRINOL,BETHESDA,MD 20892. GEORGETOWN UNIV,CHILDRENS MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. NR 19 TC 28 Z9 29 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1997 VL 205 IS 1 BP 221 EP 227 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XX266 UT WOS:A1997XX26600039 PM 9314989 ER PT J AU Strober, W Coffman, RL AF Strober, W Coffman, RL TI Tolerance and immunity in the mucosal immune system - Introduction SO RESEARCH IN IMMUNOLOGY LA English DT Editorial Material C1 Natl Inst Hlth, Mucosal Immun Sect, Clin Invest Lab, Bethesda, MD 20892 USA. DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA. RP Strober, W (reprint author), Natl Inst Hlth, Mucosal Immun Sect, Clin Invest Lab, 10 Ctr Dr,MSC 1890,Bldg 10,Room 11 N 234-244, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 5 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD OCT-DEC PY 1997 VL 148 IS 8-9 BP 489 EP 490 DI 10.1016/S0923-2494(98)80141-7 PG 2 WC Immunology SC Immunology GA ZG972 UT WOS:000073058500001 PM 9588826 ER PT J AU Kelsall, BL Strober, W AF Kelsall, BL Strober, W TI Peyer's patch dendritic cells and the induction of mucosal immune responses SO RESEARCH IN IMMUNOLOGY LA English DT Article ID INTESTINAL M-CELLS; MONOCLONAL-ANTIBODY; FOLLICLE EPITHELIUM; LANGERHANS CELLS; MOUSE SPLEEN; IN-VIVO; MICE; INFECTION; GAMMA; IDENTIFICATION C1 NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. RP Kelsall, BL (reprint author), NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bldg 10,Room 11C216,10 Ctr Dr, Bethesda, MD 20892 USA. NR 65 TC 17 Z9 17 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD OCT-DEC PY 1997 VL 148 IS 8-9 BP 490 EP 498 DI 10.1016/S0923-2494(98)80142-9 PG 9 WC Immunology SC Immunology GA ZG972 UT WOS:000073058500002 PM 9588827 ER PT J AU Marth, T Strober, W AF Marth, T Strober, W TI Oral tolerance and its modulation by anti-cytokines SO RESEARCH IN IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELLS; IMMUNE-RESPONSES; IMMUNOLOGICAL RESPONSES; PEYERS-PATCHES; IN-VIVO; INFLAMMATORY CYTOKINES; ADMINISTERED PROTEIN C1 Univ Saarland, D-66421 Homburg, Germany. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Marth, T (reprint author), Univ Saarland, D-66421 Homburg, Germany. NR 64 TC 4 Z9 4 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD OCT-DEC PY 1997 VL 148 IS 8-9 BP 554 EP 561 DI 10.1016/S0923-2494(98)80149-1 PG 8 WC Immunology SC Immunology GA ZG972 UT WOS:000073058500009 PM 9588834 ER PT J AU Ehrhardt, RO Ludviksson, B AF Ehrhardt, RO Ludviksson, B TI Induction of colitis in IL2-deficient-mice: the role of thymic and peripheral dysregulation in the generation of autoreactive T cells SO RESEARCH IN IMMUNOLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; RESIDENT INTESTINAL FLORA; INTERLEUKIN-2 RECEPTORS; INTERFERON-GAMMA; TRANSGENIC RATS; CROHNS-DISEASE; LYMPHOCYTES-T; GROWTH-FACTOR; MUTANT MICE; TOLERANCE C1 Prot Design Labs Inc, Mt View, CA 94043 USA. NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bethesda, MD USA. RP Ehrhardt, RO (reprint author), Prot Design Labs Inc, Mt View, CA 94043 USA. OI Ludviksson, Bjorn/0000-0002-6445-148X NR 61 TC 9 Z9 9 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD OCT-DEC PY 1997 VL 148 IS 8-9 BP 582 EP 588 DI 10.1016/S0923-2494(98)80153-3 PG 7 WC Immunology SC Immunology GA ZG972 UT WOS:000073058500013 PM 9588838 ER PT J AU Tedeschi, G Lundbom, N Raman, R Bonavita, S Duyn, JH Alger, JR DiChiro, G AF Tedeschi, G Lundbom, N Raman, R Bonavita, S Duyn, JH Alger, JR DiChiro, G TI Increased choline signal coincides with malignant degeneration of cerebral gliomas: a serial proton magnetic resonance spectroscopic imaging study SO RIVISTA DI NEURORADIOLOGIA LA Italian DT Article; Proceedings Paper CT XIVth National Congress of the Associazione-Italiana-di-Neuroradiologia CY OCT 16-18, 1997 CL CONSENTIA, ITALY SP Assoc Italiana Neuroradiol DE primary brain tumors; cerebral gliomas; malignant degeneration; tumor recurrence; MR-spectroscopy; proton MR-spectroscopic imaging; choline AB We tested the hypothesis that proton magnetic resonance spectroscopic imaging (H-1-MRSI) can be used as a supportive diagnostic tool to differentiate clinically stable brain tumors from those progressing as a result of either low-to-high grade malignant transformation or of post-therapeutic recurrence. Twenty-seven patients with histologically verified cerebral gliomas were studied repeatedly with H-1-MRSI or er a period of 3.5 tears. At the time of each H-1-MRSI study, clinical examination, MRI, positron emission tomography (PET) with F-18-fluorodeoxyglucose (FDG), and biopsy findings (when available) were used to categorize each patient as being either <> or <>. Measures of the between-studies percent changes in the choline H-1-MRSI signal intensity, obtained without our knowledge of the clinical categorization, segregated the groups with a high degree of statistical significance. All progressive cases showed a between-studies choline signal increase of more than 45%, while all stable cases showed an elevation of less than 35%, no change, or even a decreased signal. We conclude that increased choline coincides with malignant degeneration of cerebral gliomas, and therefore, may possibly be used as a supportive indicator of malignant degeneration of these neoplasms. C1 NINCDS,NEUROIMAGING BRANCH,NIH,BETHESDA,MD 20892. NINCDS,LAB DIAGNOST RADIOL,NIH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,BRAIN RES INST,DEPT RADIOL SCI,LOS ANGELES,CA 90024. RI Duyn, Jozef/F-2483-2010 NR 4 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI CENTAURO PI BOLOGNA PA VIA DEL PRATELLO, 8, 40122 BOLOGNA, ITALY SN 1120-9976 J9 RIV NEURORADIOL JI Riv. Neuroradiol. PD OCT PY 1997 VL 10 SU 2 BP 18 EP 19 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YE854 UT WOS:A1997YE85400003 ER PT J AU Matzner, Y Malech, HL AF Matzner, Y Malech, HL TI Introduction: Neutrophil pathophysiology SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material C1 NIH,BETHESDA,MD 20892. RP Matzner, Y (reprint author), HADASSAH MED ORG,JERUSALEM,ISRAEL. 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 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1997 VL 34 IS 4 BP 265 EP 266 PG 2 WC Hematology SC Hematology GA YA415 UT WOS:A1997YA41500001 PM 9347576 ER PT J AU Malech, HL Nauseef, WM AF Malech, HL Nauseef, WM TI Primary inherited defects in neutrophil function: Etiology and treatment SO SEMINARS IN HEMATOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; CHEDIAK-HIGASHI-SYNDROME; LEUKOCYTE ADHESION DEFICIENCY; BONE-MARROW TRANSPLANTATION; NADPH OXIDASE; GRANULE DEFICIENCY; MYELOPEROXIDASE DEFICIENCY; PREVALENCE; MUTATION; LFA-1 C1 VET ADM MED CTR,DEPT MED,INFLAMMAT PROGRAM,IOWA CITY,IA 52240. UNIV IOWA,IOWA CITY,IA 52242. RP Malech, HL (reprint author), NIAID,HOST DEF LAB,NIH,BLDG 10,RM 11N113,10 CTR DR,MSC 1886,BETHESDA,MD 20892, USA. FU BLRD VA [I01 BX000513] NR 62 TC 65 Z9 65 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1997 VL 34 IS 4 BP 279 EP 290 PG 12 WC Hematology SC Hematology GA YA415 UT WOS:A1997YA41500003 PM 9347578 ER PT J AU Murphy, PM AF Murphy, PM TI Neutrophil receptors for interleukin-8 and related CXC chemokines SO SEMINARS IN HEMATOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; IL-8 RECEPTOR; GRO-ALPHA; CHEMOTACTIC CYTOKINES; ACTIVATING PEPTIDE-2; PHOSPHOLIPASE-D; BINDING; CELLS; PROTEIN; BETA RP Murphy, PM (reprint author), NIAID,HOST DEF LAB,NIH,BLDG 10,RM 11N113,BETHESDA,MD 20892, USA. NR 67 TC 148 Z9 149 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1997 VL 34 IS 4 BP 311 EP 318 PG 8 WC Hematology SC Hematology GA YA415 UT WOS:A1997YA41500006 PM 9347581 ER PT J AU Malech, HL Bauer, TR Hickstein, DD AF Malech, HL Bauer, TR Hickstein, DD TI Prospects for gene therapy of neutrophil defects SO SEMINARS IN HEMATOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; APE LEUKEMIA-VIRUS; LEUKOCYTE ADHESION DEFICIENCY; PERIPHERAL-BLOOD PROGENITORS; COLONY-STIMULATING FACTOR; INTEGRIN CD18 SUBUNIT; NADPH OXIDASE; SUPEROXIDE GENERATION; MEDIATED EXPRESSION; RETROVIRAL VECTORS C1 UNIV WASHINGTON,SCH MED,DIV ONCOL,VET ADM PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98195. RP Malech, HL (reprint author), NIAID,HOST DEF LAB,NIH,BLDG 10,RM 11N113,10 CTR DR MSC 1886,BETHESDA,MD 20892, USA. NR 43 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1997 VL 34 IS 4 BP 355 EP 361 PG 7 WC Hematology SC Hematology GA YA415 UT WOS:A1997YA41500011 PM 9347586 ER PT J AU Grem, JL AF Grem, JL TI Systemic treatment options in advanced colorectal cancer: Perspectives on combination 5-fluorouracil plus leucovorin SO SEMINARS IN ONCOLOGY LA English DT Review ID DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY; HIGH-DOSE LEUCOVORIN; PHASE-III TRIAL; BLOOD MONONUCLEAR-CELLS; BIOCHEMICAL MODULATION; RANDOMIZED TRIAL; ONCOLOGY-GROUP; POPULATION CHARACTERISTICS; INFUSION FLUOROURACIL; INTERFERON ALFA-2A C1 NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,Natl Naval Med Ctr, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 50 TC 15 Z9 16 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1997 VL 24 IS 5 SU 18 BP 8 EP 18 PG 11 WC Oncology SC Oncology GA YP511 UT WOS:000071285100003 ER PT J AU Takimoto, CH AF Takimoto, CH TI Antifolates in clinical development SO SEMINARS IN ONCOLOGY LA English DT Review ID THYMIDYLATE SYNTHASE INHIBITOR; PHASE-II TRIAL; CELL LUNG-CANCER; METASTATIC BREAST-CANCER; SOFT-TISSUE SARCOMA; ADVANCED PANCREATIC ADENOCARCINOMA; SOLUBLE FOLATE ANTAGONIST; NECK-CANCER; DIHYDROFOLATE-REDUCTASE; ORAL PIRITREXIM C1 Bethesda Naval Hosp, NCI, Div Clin Sci, Dev Therapeut Dept,Med Branch, Bethesda, MD 20889 USA. RP Takimoto, CH (reprint author), Bethesda Naval Hosp, NCI, Div Clin Sci, Dev Therapeut Dept,Med Branch, Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 134 TC 8 Z9 8 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1997 VL 24 IS 5 SU 18 BP 40 EP 51 PG 12 WC Oncology SC Oncology GA YP511 UT WOS:000071285100007 ER PT J AU Zahm, SH Fraumeni, JF AF Zahm, SH Fraumeni, JF TI The epidemiology of soft tissue sarcoma SO SEMINARS IN ONCOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; MALIGNANT FIBROUS HISTIOCYTOMA; CANCER FAMILY SYNDROME; HEPATIC ANGIOSARCOMA; KAPOSIS-SARCOMA; BREAST-CANCER; PHENOXY HERBICIDES; FORESTRY WORKERS; UNITED-STATES; CASE-REFERENT RP Zahm, SH (reprint author), NATL CANC INST,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,418N,6130 EXECUT BLVD,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 153 TC 101 Z9 104 U1 2 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1997 VL 24 IS 5 BP 504 EP 514 PG 11 WC Oncology SC Oncology GA YB531 UT WOS:A1997YB53100003 PM 9344316 ER PT J AU Grem, JL AF Grem, JL TI Mechanisms of action and modulation of fluorouracil SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID ADVANCED COLORECTAL-CANCER; COLON-CARCINOMA-CELLS; METASTATIC GASTROINTESTINAL ADENOCARCINOMA; CONTINUOUS-INFUSION 5-FLUOROURACIL; MASS-SPECTROMETRIC METHOD; PLUS CALCIUM LEUCOVORIN; HIGH-DOSE LEUCOVORIN; MOUSE FM3A CELLS; THYMIDYLATE SYNTHASE; PHASE-I RP Grem, JL (reprint author), NCI,NATL NAVAL MED CTR,DEV THERAPEUT DEPT,MED BRANCH,DIV CLIN SCI,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 100 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 1997 VL 7 IS 4 BP 249 EP 259 DI 10.1016/S1053-4296(97)80023-9 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YB859 UT WOS:A1997YB85900002 ER PT J AU Booth, V Carr, TW Erneux, T AF Booth, V Carr, TW Erneux, T TI Near-threshold bursting is delayed by a slow passage near a limit point SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE bursting; delay; slow passage ID DEPENDENT BIFURCATION PARAMETER; JUMP TRANSITION; ACID REACTION; OSCILLATIONS; MODEL; DYNAMICS; SYSTEMS AB In a general model for square-wave bursting oscillations, we examine the fast transition between the slowly varying quiescent and active phases. In this type of bursting, the transition occurs at a saddle-node (SN) bifurcation point of the fast-variable subsystem when the slow variable is taken to be the bifurcation parameter. A critical case occurs when the SN bifurcation point is also a steady solution of the full bursting system. In this case near the bursting threshold, the transition suffers a large delay. We propose a first investigation of this critical case that has been noted accidentally but never explored. We present an asymptotic analysis local to the SN point of the fast subsystem and quantitatively describe the slow passage near the SN point underlying the transition delay. Our analysis reveals that bursting solutions showing the longest delays and, correspondingly, the bursting threshold appear near but not exactly at the SN point, as is commonly assumed. C1 NIDDKD,MATH RES BRANCH,NIH,BETHESDA,MD 20814. USN,RES LAB,SPECIAL PROJECT NONLINEAR SCI,WASHINGTON,DC 20375. FREE UNIV BRUSSELS,B-1050 BRUSSELS,BELGIUM. NR 16 TC 17 Z9 18 U1 0 U2 1 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 SN 0036-1399 J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD OCT PY 1997 VL 57 IS 5 BP 1406 EP 1420 PG 15 WC Mathematics, Applied SC Mathematics GA XZ056 UT WOS:A1997XZ05600010 ER PT J AU Follmann, D AF Follmann, D TI Adaptively changing subgroup proportions in clinical trials SO STATISTICA SINICA LA English DT Article DE Bayesian statistics; decision theory; interim monitoring; interaction; strata ID DESIGNS AB During the course of a fixed sample size clinical trial, differences in the size of the treatment effect between strata may become pronounced. If rejecting the null hypothesis of no treatment effect is of paramount concern, it may make sense to increase representation of the more responsive stratum to increase power of the trial. Additionally, strata in which treatment is harmful may need to be dropped for ethical reasons. This paper provides conditions under which such adaptation does not affect the type I error rate. The change in power resulting from adaptation under Various strategies is investigated. Frequentist and Bayesian approaches to decision making are explored and a simulation is used to provide guidelines as to whether stratum proportions should be altered. A clinical trial with an early and substantial between stratum difference is reanalyzed under adaptation. C1 NHLBI,OFF BIOSTAT RES,ROCKLEDGE CTR 2,BETHESDA,MD 20892. NR 16 TC 7 Z9 7 U1 0 U2 0 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD OCT PY 1997 VL 7 IS 4 BP 1085 EP 1102 PG 18 WC Statistics & Probability SC Mathematics GA YF243 UT WOS:A1997YF24300018 ER PT J AU Palosuo, T Virtamo, J Haukka, J Taylor, PR Aho, K Puurunen, M Vaarala, O AF Palosuo, T Virtamo, J Haukka, J Taylor, PR Aho, K Puurunen, M Vaarala, O TI High antibody levels to prothrombin imply a risk of deep venous thrombosis and pulmonary embolism in middle-aged men - A nested case-control study SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; SYSTEMIC LUPUS-ERYTHEMATOSUS; BINDING PLASMA-PROTEINS; ANTIPHOSPHOLIPID ANTIBODIES; ANTICARDIOLIPIN ANTIBODIES; CAROTID ATHEROSCLEROSIS; ANTICOAGULANT ACTIVITY; MYOCARDIAL-INFARCTION; BETA-2-GLYCOPROTEIN-I; PHOSPHOLIPIDS AB Antibodies against phospholipid-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)-GPI) and prothrombin, are associated with thromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases. We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids (cardiolipin), to phospholipid-binding plasma proteins beta(2)-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis. The antibodies were measured in stored serum samples from 265 cases of deep venous thrombosis of the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls. The study subjects were middle-aged men participating in a cancer prevention trial of alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified from nationwide Hospital Discharge Register. The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies. As adjusted for body mass index, number of daily cigarettes and history of chronic bronchitis, myocardial infarction and heart failure al baseline, the odds ratio per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0). The seven highest individual optical density-unit values of antiprothrombin antibodies were all confined to subjects with thromboembolic episodes. In conclusion, the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of deep venous thrombosis and pulmonary embolism and could be involved in the development of the thrombotic processes. C1 NCI,BETHESDA,MD 20892. RP Palosuo, T (reprint author), NATL PUBL HLTH INST,MANNERHEIMINTIE 166,FIN-00300 HELSINKI,FINLAND. RI Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 37 TC 68 Z9 69 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD OCT PY 1997 VL 78 IS 4 BP 1178 EP 1182 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YA269 UT WOS:A1997YA26900004 PM 9364981 ER PT J AU Kraiem, Z Lahat, N Sadeh, O Blithe, DL Nisula, BC AF Kraiem, Z Lahat, N Sadeh, O Blithe, DL Nisula, BC TI Desialylated and deglycosylated human chorionic gonadotropin are superagonists of native human chorionic gonadotropin in human thyroid follicles SO THYROID LA English DT Article ID HAMSTER OVARY CELLS; HUMAN THYROTROPIN RECEPTOR; CULTURED HUMAN THYROCYTES; DR ANTIGEN EXPRESSION; HUMAN TSH RECEPTORS; IODIDE UPTAKE; SIGNAL-TRANSDUCTION; GAMMA-INTERFERON; HORMONE; HCG AB Highly purified human chorionic gonadotropin (hCG) interacts with the thyrotropin (TSH) receptor and stimulates triiodothyronine (T-3) secretion, iodide uptake and organification, and cyclic adenosine monophosphate (cAMP) formation in human thyroid follicles. Because of interest in the role of the carbohydrate component in the structure-function relationships of hCG we undertook to deplete hCG of its sialic acid or carbohydrate residues and assess the thyrotropic activity of the carbohydrate-modified forms. For this purpose, we used our assay system consisting of human thyroid follicles cultured and suspended in collagen gel in serum-free medium. Under these conditions, the cells are organized as follicular three-dimensional structures with normal polarity, enabling enhanced responsiveness to hormonal stimulation, and T-3 secretion can be measured as a response parameter. Desialylated (ds)-hCG and deglycosylated (dg)-hCG dose-dependently stimulated T-3 secretion, iodide uptake and organification, and in each case did so with about twice the intrinsic activity of native hCG. Indeed, removal of the sialic acid or carbohydrate residues from native hCG transformed it into a thyroid stimulator that elicited a maximal response in terms of iodide uptake, organification and T-3 secretion by human thyroid follicles as high as TSH and almost twice as high as native hCG. Not only were ds-hCG and dg-hCG more intrinsically active than hCG, they were more than five times as potent. As with hCG, both ds-hCG and dg-hCG managed to elicit such responses in human thyrocytes while evoking minimal amounts of cAMP, illustrating the concept of cAMP superfluity and highlighting the potential pitfalls of using cAMP as a measure of hormonal bioactivity. hCG, and to a greater extent ds-hCG and dg-hCG, inhibited, as did TSH, gamma-interferon-induced human leukocyte antigen-DR (HLA-DR) expression in human thyrocytes, again reflecting the intrinsic thyrotropic activity of native hCG and its variants depleted of sialic acid or carbohydrate residues. In conclusion, this is the first report on the thyrotropic activity of ds-hCG and dg-hCG using the physiologically relevant hormonal end-point response, thyroid hormone secretion. The study was conducted in a serum-free culture system of human thyroid follicles and shows that removal of the sialic acid or carbohydrate residues from native hCG transform hCG variants into thyroid stimulating superagonists. The hCG variants inhibited, as did TSH, gamma-interferon-induced HLA-DR expression. C1 CARMEL HOSP, RES IMMUNOL UNIT, IL-34362 HAIFA, ISRAEL. TECHNION ISRAEL INST TECHNOL, FAC MED, HAIFA, ISRAEL. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Kraiem, Z (reprint author), CARMEL HOSP, ENDOCRINE RES UNIT, 7 MICHAL ST, IL-34362 HAIFA, ISRAEL. NR 33 TC 14 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD OCT PY 1997 VL 7 IS 5 BP 783 EP 788 DI 10.1089/thy.1997.7.783 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YD729 UT WOS:A1997YD72900015 PM 9349585 ER PT J AU Coogan, TP Shiraishi, N Waalkes, MP AF Coogan, TP Shiraishi, N Waalkes, MP TI Metallothionein gene expression in the reproductive tissues of the male Wistar rat: Effects of treatment with metals or glucocorticoids SO TOXIC SUBSTANCE MECHANISMS LA English DT Article ID DIETARY ZINC-DEFICIENCY; DOSE-RESPONSE ANALYSIS; CADMIUM CARCINOGENESIS; CRL-(WI)BR RATS; TUMOR-INDUCTION; INJECTION SITE; PROSTATE; CELLS; PRETREATMENT; TOXICITY AB The male reproductive tissues appear to be particularly sensitive to the toxic metal cadmium. The basis of this sensitivity may involve the expression of the metallothionein (MT) gene. This series of experiments sought to define the expression of the MT gene in the major lobes of the rat prostate (dorsolateral and ventral) and in the testes under both normal circumstances and after exposure to agents that are known to upregulate hepatic MT gene expression, such as zinc, cadmium, and glucocorticoids. The hepatic MT system was selected because it has a well-defined activity and responsiveness to including stimuli, while dexamethasone was selected as the glucocorticoid because it has been shown to induce MT both in vitro and in vivo. Male Wistar rats were treated with cadmium (2.5, 20, and 40 mu mol/kg, sc), zinc (2 mmol/kg, sc), or dexamethasone (0.2, 2, or 20 mu mol/kg, sc) as a single dose. Controls received saline. Rats were sacrificed 24 h after exposure, and a single liver (-250 mg) sample, both testes, and the entire ventral or dorsolateral lobes of the prostate were removed and quick frozen in liquid nitrogen. RNA was then extracted, blotted, and probed for MT-I gene expression using a P-32-labeled cDNA probe specific for the rat MT-I gene. Blots were quantified by densitometry. The dorsolateral lobe of the prostate had very high basal levels of MT mRNA, much higher than ventral prostate (15.3-fold), fiver (15.1-fold), or testes (4.6-fold). Cadmium treatment markedly increased the expression of the MT gene in the liver but had little, if any, effect on the gene in the testes or in the ventral or dorsolateral prostate. Dexamethasone treatment also increased the expression of the MT gene in the liver but had no effect on the expression in the testes or dorsolateral prostate. In the ventral prostate the glucocorticoid stimulated MT gene expression minimally, if at all. Zinc had a marked effect on MT gene expression in the liver, increasing it 4.2-fold over control levels, but expression. in the ventral prostate was not modified. Snail increases in expression occurred with zinc exposure in the dorsolateral prostate where levels of MT gene expression increased 1.7-fold, which was one of the quantitatively larger increases detected in this study given the high basal expression in ths tissue. The results of the present study indicate wide variability in basal or induced expression of the MT gene in various tissues of the Wistar rat. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702. NR 37 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 1076-9188 J9 TOX SUBST MECH JI Tox. Subst. Mech. PD OCT-DEC PY 1997 VL 16 IS 4 BP 357 EP 370 PG 14 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA XX261 UT WOS:A1997XX26100005 ER PT J AU McKenna, IM Waalkes, MP Chen, LC Gordon, T AF McKenna, IM Waalkes, MP Chen, LC Gordon, T TI Comparison of inflammatory lung responses in Wistar rats and C57 and DBA mice following acute exposure to cadmium oxide fumes SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 1996 CL BARCELONA, SPAIN SP Natl Ctr Toxicol Res, Food & Drug Adm, NCI, Assoc Reg Enseignement & Rech Sci Champagne Ardenne, Int Res Inst Metal Ions, Univ Rovira Virgili, Univ Barcelona, Escola Profess Med Treball, Direcc Gen Investigac Cient & Tecn, Commiss Univ Rec CIRIT Generalitat Catalunya ID CELL NUCLEAR ANTIGEN; ALVEOLAR MACROPHAGES; PULMONARY CARCINOGENICITY; BRONCHOALVEOLAR LAVAGE; RESPIRATORY-TRACT; METALLOTHIONEIN; INJURY; CHLORIDE; TOXICITY; PROLIFERATION AB Inhalation of cadmium oxide (CdO) is a significant form of human exposure to cadmium (Cd). Furthermore, there is epidemiological and experimental data relating Cd inhalation with lung cancer. Animal studies indicate that rats are more susceptible to Cd-induced lung cancer than mice, but interstrain sensitivity differences to Cd-induced pulmonary inflammation or carcinogenesis have not been addressed in either species. We compared pulmonary inflammatory processes in Wistar Furth (WF) rats with those in C57 and DBA mice exposed to freshly generated CdO fumes in nose-only inhalation chambers. Animals were exposed to 1 mg Cd/m(3) for 3 hr and terminated immediately or 1, 3, and 5 days after exposure. Control animals were exposed to air/argon furnace gases. Cd-induced lung injury was assessed by bronchoalveolar lavage fluid (BALF) analyses, histopathology, and immunohistochemical detection of cell proliferation. Inhalation of CdO resulted in pulmonary inflammatory processes that varied widely across species and strains. C57 mice responded with faster and greater influx of neutrophils and proliferation of alveolar macrophages, type II epithelial cells, and bronchiolar epithelial cells compared to DBA mice or WF rats. DBA mice retained a greater percentage of inhaled Cd in the lungs and presented higher levels of BALF protein than C57 mice or rats. In comparison to mice, WF rats responded with a more transient inflammatory response in BALF parameters and higher degree of acute inflammation in lung tissue. The more pronounced proliferation of alveolar and bronchiolar epithelial cells observed in C57 mice might indicate higher susceptibility of this mice strain to Cd-induced lung carcinogenesis compared to DBA mice or WF rats. Furthermore, the present results of fewer inflammatory cells and lower proliferation of epithelial cells in DBA mice in association with our previous observation of higher Cd-induced metallothionein protein in this strain suggest that DBA might be less susceptible to the pulmonary carcinogenic effects of inhaled Cd than C57 mice or WF rats. We conclude that mice might not necessarily be more resistant than rats to the carcinogenic effects of inhaled Cd, since intraspecies susceptibility differences are strongly suggested by the present data. An extrapolation of this conclusion is that genetic variations in the human population may determine individual sensitivity differences to inhaled Cd. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NYU,INST ENVIRONM MED,MED CTR,TUXEDO PK,NY 10987. RI Cjem, Lung-Chi/H-5030-2012 NR 41 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT PY 1997 VL 146 IS 2 BP 196 EP 206 DI 10.1006/taap.1997.8241 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YD923 UT WOS:A1997YD92300004 PM 9344887 ER PT J AU Mathews, JM Raymer, JH Etheridge, AS Velez, GR Bucher, JR AF Mathews, JM Raymer, JH Etheridge, AS Velez, GR Bucher, JR TI Do endogenous volatile organic chemicals measured in breath reflect and maintain CYP2E1 levels in vivo? SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID LIPID-PEROXIDATION; GENETIC POLYMORPHISMS; PROTEIN STABILIZATION; IN-VIVO; RAT; METABOLISM; INDUCTION; ACETONE; CYTOCHROMES-P-450; HEPATOTOXICITY AB The effect of trans-1,2-dichloroethylene (DCE), an inhibitor of cytochrome P450 (P450) 2E1 (CYP2E1), on the composition and quantity of volatile organic chemicals (VOCs) expired in the breath of male F-344 rats was determined in parallel with hepatic P450 activity and content. Hepatic microsomes were prepared from groups of rats prior to dosing and at 2, 5, 12, and 24 hr postdosing with DCE (100 mg/kg ip), and total P450 content and the activity of CYP2E1 was determined. Breath was collected from parallel groups of rats predose and at several intervals that encompassed the time points for rats euthanized for microsome preparation. Over 100 breath components were identified by GC/MS and quantitated by GC/FID. The overall change in the profile of breath VOCs resulting from administration of DCE was striking. An increase of approximately 1000% was measured in the mass of non-DCE-derived VOCs exhaled 4-6 hr after dosing, but there was no increase in hepatic lipid peroxidation. In addition to hexane, short-chain methyl ketones were particularly affected, and percentage increases in response to inhibition were inversely related to chain length, with acetone and 2-butanone > 2-pentanone much greater than 2-hexanone > 2-heptanone. There were no statistically significant decreases in total content of P450, but the activity of CYP2E1 was diminished about 65% at 2 and 5 hr after DCE treatment. However, 24 hr after inhibitor administration the total mass of VOCs expired was only marginally elevated above baseline and CYP2E1 activity was not significantly different from that of untreated rats. The compounds most markedly increased upon inhibition of CYP2E1 are also excellent inducers of that isozyme, and this finding is consistent with the hypothesis that these chemicals are important to the normal homeostasis of CYP2E1. The increase in breath components observed following inhibition of CYP2E1 suggests that VOCs in breath can reflect the activity of that isozyme in vivo. (C) 1997 Academic Press. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Mathews, JM (reprint author), RES TRIANGLE INST,POB 12194,3040 CORNWALLIS RD,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-4-5380] NR 33 TC 11 Z9 11 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT PY 1997 VL 146 IS 2 BP 255 EP 260 DI 10.1006/taap.1997.8257 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YD923 UT WOS:A1997YD92300010 PM 9344893 ER PT J AU Moroff, G Leitman, SF Luban, NLC AF Moroff, G Leitman, SF Luban, NLC TI Principles of blood irradiation, dose validation, and quality control SO TRANSFUSION LA English DT Review ID VERSUS-HOST DISEASE; MEDIATED GRAFT-REJECTION; ULTRAVIOLET-IRRADIATION; RADIATION; TRANSPLANTATION; PREVENTION; DOSIMETRY; STORAGE C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLOOD SERV SECT,BETHESDA,MD. NATL CHILDRENS HOSP,MED CTR,DEPT LAB MED,WASHINGTON,DC. RP Moroff, G (reprint author), AMER RED CROSS,JEROME H HOLLAND LAB BIOMED SCI,15601 CRABBS BRANCH WAY,ROCKVILLE,MD 20855, USA. NR 27 TC 36 Z9 43 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1997 VL 37 IS 10 BP 1084 EP 1092 DI 10.1046/j.1537-2995.1997.371098016450.x PG 9 WC Hematology SC Hematology GA YC865 UT WOS:A1997YC86500016 PM 9354830 ER PT J AU Saitoh, H Pu, RT Dasso, M AF Saitoh, H Pu, RT Dasso, M TI SUMO-1: wrestling with a new ubiquitin-related modifier SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID CONJUGATING ENZYME UBC9; HUMAN HOMOLOG; PROTEIN; INTERACTS; TRANSPORT; GENE RP Saitoh, H (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BLDG 18,ROOM 106,18 LIB DR,MSC-5431,BETHESDA,MD 20892, USA. OI Dasso, Mary/0000-0002-5410-1371 NR 20 TC 118 Z9 120 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD OCT PY 1997 VL 22 IS 10 BP 374 EP 376 DI 10.1016/S0968-0004(97)01102-X PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YC858 UT WOS:A1997YC85800003 PM 9357311 ER PT J AU OBrien, SJ Wienberg, J Lyons, LA AF OBrien, SJ Wienberg, J Lyons, LA TI Comparative genomics: lessons from cats SO TRENDS IN GENETICS LA English DT Review ID GENETIC-LINKAGE MAP; DOMESTIC CAT; ZOO-FISH; CONSERVATION; MAMMALS; MOUSE; BIOLOGY; PROJECT; PORCINE; LOCI AB The genomics era, spearheaded by dazzling technological developments in human and mouse gene mapping, has additionally provoked extensive comparative gene mapping projects for domestic species of several vertebrate orders. As the human genome project promises a one dimensional string of 100 000 genes and sequences, comparative mapping will extend that inference to a second dimension representing index species of the 20 living mammalian orders and to a third dimension by phylogenetic description of the genomes of mammal ancestors. We review here the remarkable extent of genome homology conservation among mammals illustrated by technology applications in the feline genome project. C1 UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QR,ENGLAND. RP OBrien, SJ (reprint author), NCI,LAB GENOM DIVERS,FREDERICK,MD 21702, USA. NR 51 TC 99 Z9 100 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 1997 VL 13 IS 10 BP 393 EP 399 DI 10.1016/S0168-9525(97)01297-3 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA YB671 UT WOS:A1997YB67100005 PM 9351340 ER PT J AU Forozan, F Karhu, R Kononen, J Kallioniemi, A Kallioniemi, OP AF Forozan, F Karhu, R Kononen, J Kallioniemi, A Kallioniemi, OP TI Genome screening by comparative genomic hybridization SO TRENDS IN GENETICS LA English DT Review ID MOLECULAR CYTOGENETIC ANALYSIS; UNIVERSAL DNA-AMPLIFICATION; GENE-EXPRESSION PATTERNS; BREAST-CANCER; SOLID TUMORS; HUMAN-CHROMOSOMES; CELL LYMPHOMA; COPY NUMBER; GAINS; MICROARRAY AB Comparative genomic hybridization (CGH) provides a molecular cytogenetic approach for genome-wide scanning of differences in DNA sequence copy number. The technique is now attracting wide-spread interest, especially among cancer researchers. The rapidly expanding database of CGH publications already covers about 1500 tumors and is beginning to reveal genetic abnormalities that are characteristic of certain tumor types or stages of tumor progression. Six novel gene amplifications, as well as a locus for a cancer-predisposition syndrome, have been discovered based on CGH data. CGH has now been established as a first-line screening technique for cancer researchers and will serve as a basis for ongoing efforts to develop high-resolution next-generation genome scanning, such as the microarray technology. C1 TAMPERE UNIV HOSP,FIN-33521 TAMPERE,FINLAND. TAMPERE UNIV,INST MED TECHNOL,CANC GENET LAB,FIN-33521 TAMPERE,FINLAND. RP Forozan, F (reprint author), NIH,NATL HUMAN GENOME RES INST,CANC GENET LAB,BETHESDA,MD 20892, USA. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 43 TC 195 Z9 203 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 1997 VL 13 IS 10 BP 405 EP 409 DI 10.1016/S0168-9525(97)01244-4 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA YB671 UT WOS:A1997YB67100009 PM 9351342 ER PT J AU ODonovan, MJ Rinzel, J AF ODonovan, MJ Rinzel, J TI Synaptic depression: a dynamic regulator of synaptic communication with varied functional roles SO TRENDS IN NEUROSCIENCES LA English DT News Item ID SPINAL-CORD; POSTSYNAPTIC POTENTIALS; MOTONEURONS; NEOCORTEX; INVITRO C1 NIDDK,MATH RES BRANCH,NIH,BETHESDA,MD 20892. RP ODonovan, MJ (reprint author), NINCDS,SECT DEV NEUROBIOL,NEURAL CONTROL LAB,NIH,BETHESDA,MD 20892, USA. NR 24 TC 81 Z9 81 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD OCT PY 1997 VL 20 IS 10 BP 431 EP 433 DI 10.1016/S0166-2236(97)01124-7 PG 3 WC Neurosciences SC Neurosciences & Neurology GA XZ028 UT WOS:A1997XZ02800001 PM 9347607 ER PT J AU LaCroix, AZ Newton, KM Leveille, SG Wallace, J AF LaCroix, AZ Newton, KM Leveille, SG Wallace, J TI Healthy aging - A women's issue SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID BONE-MINERAL DENSITY; CORONARY HEART-DISEASE; PHYSICAL-ACTIVITY; HIP FRACTURE; POSTMENOPAUSAL WOMEN; OLDER ADULTS; OSTEOPOROTIC FRACTURES; MAINTAINING MOBILITY; ESTROGEN REPLACEMENT; RANDOMIZED TRIAL AB The life expectancy of women currently exceeds that of men by almost seven years, yet women spend approximately twice as many years disabled prior to death as their male counterparts. The diseases that account for death and health care utilization in older women (heart disease, cancer, stroke, fracture, pneumonia, osteoarthritis, cataracts) are also major contributors to disability. This paper reviews the scientific evidence that supports specific recommendations for older women that may prevent or delay these conditions for as long as possible. Risk factors for falls and fractures should be assessed and, where possible, modified. Adequate intakes of calcium, vitamin D, fruits, and vegetables should be encouraged. Weight should be monitored and weight loss discouraged for most women. Screening for B12 deficiency is recommended. Engaging women in a shared decision-making process about the use of hormone replacement therapy for longterm prevention of heart disease and fractures is important, as is regular screening for breast and cole-rectal cancer. Women should be encouraged to engage in enjoyable physical activities, including walking, for 30 minutes daily. These interventions have the potential to delay the onset and improve the course of many chronic conditions that prevail in later life. C1 FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,SEATTLE,WA 98104. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SCH MED,DEPT MED,DIV GERIATR,SEATTLE,WA 98195. RP LaCroix, AZ (reprint author), GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,1730 MINOR AVE,STE 1600,SEATTLE,WA 98101, USA. NR 62 TC 31 Z9 31 U1 6 U2 7 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD OCT PY 1997 VL 167 IS 4 BP 220 EP 232 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA YB464 UT WOS:A1997YB46400005 PM 9348751 ER PT J AU Ershler, WB Gravenstein, S AF Ershler, WB Gravenstein, S TI Successful aging calls for more than drugs SO WESTERN JOURNAL OF MEDICINE LA English DT Article C1 EASTERN VIRGINIA MED SCH,GLENNAN CTR GERIATR & GERONTOL,NORFOLK,VA 23501. RP Ershler, WB (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Gravenstein, Stefan/G-1681-2011 NR 0 TC 1 Z9 1 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD OCT PY 1997 VL 167 IS 4 BP 238 EP 239 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YB464 UT WOS:A1997YB46400007 PM 9348753 ER PT J AU Muir, MM Kosteretz, KG Lech, JJ AF Muir, MM Kosteretz, KG Lech, JJ TI Localization, depuration, bioaccumulation and impairment of ion regulation associated with cationic polymer exposure in rainbow trout (Oncorhynchus mykiss) SO XENOBIOTICA LA English DT Article ID HUMIC-ACID; TOXICITY AB 1. Static exposure of rainbow trout, Oncorhynchus mykiss, to three commercial C-14-labelled cationic polymers (EDP, epichlorhydrin-dimethylamine; CYT, polyacrylamide ester; and STK, polyacrylamide amide) resulted in C-14 being concentrated only in gill tissue. 2. Depuration studies examining the effect of humic acid (HA) cn cationic polymer bound in gill tissue indicate that the binding is reversible with exposure to polymer-free water and polymer-free water with HA for each of the three polymers. 3. Analysis of blood pH, Na+, K+, total NH3 and Cl- after static water exposures to EDP (m.w. 50 000) at 7.5 mg EDP/1 revealed a treatment related decrease in blood pH, from 7.1 to 6.6, accompanied by an increase in blood NH3 and evidence of severe impairment of ion regulation. 4. Repeated exposure to the cationic polymers did not result in increases in the C-14 concentration in gill tissue suggesting that bioaccumulation of the polymers does not occur. 5. These data suggest that the gill is the site of toxicity for these cationic polymers and that their toxic effects involve gill function and ion regulation rather than systemic actions on internal organs. C1 MED COLL WISCONSIN,DEPT PHARMACOL & TOXICOL,MILWAUKEE,WI 53226. NIEHS,MARINE & FRESHWATER BIOMED SCI CORE CTR,MILWAUKEE,WI 53204. NR 13 TC 5 Z9 5 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD OCT PY 1997 VL 27 IS 10 BP 1005 EP 1014 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YC599 UT WOS:A1997YC59900003 PM 9364738 ER PT J AU Bilski, P Holt, RN Chignell, CF AF Bilski, P Holt, RN Chignell, CF TI Properties of singlet molecular oxygen O-2((1)Delta(g)) in binary solvent mixtures of different polarity and proticity SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY LA English DT Article DE singlet molecular oxygen; phosphorescence; radiative deactivation; nonradiative deactivation; polarity; proticity; solvent mixtures ID INFRARED LUMINESCENCE; RATE-CONSTANT; DECAY; DEACTIVATION; TRANSITION; 1-DELTA-G; STATE AB We have measured O-1(2) lifetimes (tau) and radiative rate constants (k(tau)) for O-1(2) phosphorescence in a number of binary solvent mixtures with components of water, deuterium oxide, acetonitrile (AN), 1,4-dioxane (D), propylene carbonate (PC), or ethylene carbonate (EC). We have correlated k(r) and tau with the mixtures' composition, polarizability, polarity and proticity. Our data show that O-1(2) properties are independent of both solvent polarity and solvent proticity, and confirm that the radiative rate constant k(tau) for O-1(2) phosphorescence best correlates with solvent polarizability. The prevailing trend is that k(tau) values increase with the increasing polarizability of solvent medium; in 1,4-dioxane mixtures, this increase is almost Linear. However, for other solvents the correlation with polarizability is more solvent specific. For example, polarizability remains virtually unchanged over a wide composition range in AN-H2O mixtures, but the k(tau) value increases by almost a factor of 5. In H2O-D2O mixtures, polarizability decreases with increasing D2O concentration while the value of k(tau) increases twofold. This divergence suggests that, besides collision complexes, the interaction of O-1(2) with these solvents may involve a more specific interaction such as exciplex formation. Such specific interactions are probably responsible for considerable scattering that is usually observed in plots that relate k(r) values measured in chemically different solvents to macroscopic polarizability. The best way to obtain accurate k(tau) and k(d)(tau) values for O-1(2) in mixed solvents is still to measure them experimentally. We present here measured values of k(tau) and tau in a variety of mixed solvents; these values can be helpful in calculating O-1(2) yields from measurements of steady state phosphorescence. (C) 1997 Elsevier Science S.A. RP Bilski, P (reprint author), NIEHS,MOL BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 30 Z9 30 U1 1 U2 8 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1010-6030 J9 J PHOTOCH PHOTOBIO A JI J. Photochem. Photobiol. A-Chem. PD SEP 30 PY 1997 VL 109 IS 3 BP 243 EP 249 DI 10.1016/S1010-6030(97)00147-0 PG 7 WC Chemistry, Physical SC Chemistry GA XY975 UT WOS:A1997XY97500008 ER PT J AU Kingan, TG Zitnan, D Jaffe, H Beckage, NE AF Kingan, TG Zitnan, D Jaffe, H Beckage, NE TI Identification of neuropeptides in the midgut of parasitized insects: FLRFamides as candidate paracrines SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE tobacco hornworm; Manduca sexta; gut endocrine cells; FLRFamide; wasp; Cotesia congregata; enzyme immunoassay ID FMRFAMIDE-LIKE PEPTIDES; ENTERIC NERVOUS-SYSTEM; MANDUCA-SEXTA; ENDOCRINE-CELLS; TOBACCO HORNWORM; SCHISTOCERCA-GREGARIA; COTESIA-CONGREGATA; EXPRESSION; MOTH; COCKROACH AB Parasitism of Manduca sexta (Lepidoptera: Sphingidae) larvae by the braconid wasp Cotesia congregata (Hymenoptera: Braconidae) leads to accumulation of peptides in host neurons and neurosecretory cells of the central nervous system (CNS) and neurons and endocrine/paracrine cells of the midgut. This accumulation has now facilitated the characterization of two new members of the FLRFamide family from midguts of parasitized larvae. The peptides, given the names F24 and F39, are 24 and 39 amino acids in length with the sequences VRDYPQLLDSGMKRQDVVHSFLRFamide and YAEAAGEQVPEYQALVRDYPQLLDSGMKRQDVVHSFLRFamide. The sequence of F24 is identical to the C-terminal 24 amino acids of F39. The C-terminal 10-mer of each is identical to a previously characterized decapeptide neurohormone (F10). This sequence is preceded by a potential processing site. In nonparasitized insects F39 was present at several-fold the amount of F24. In parasitized insects F24 and F39 accumulate in the middle and posterior regions of the midgut, which are enriched in endocrine/paracrine cells reacting with FLRFamide antisera. In the combined brain and subesophageal ganglion F39 was not detected and the amount of F24 never exceeded 2 fmol per Br/SEG. Of the three peptides, only F10 was found in the hemolymph. Thus, F24 and F39 may be intermediates in the biosynthesis of F10 and may themselves be released locally from endocrine/paracrine cells in the midgut epithelium. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV CALIF RIVERSIDE,DEPT ENTOMOL,RIVERSIDE,CA 92521. SLOVAK ACAD SCI,INST ZOOL,BRATISLAVA 84206,SLOVAKIA. NINCDS,LNC,NIH,BETHESDA,MD 20892. RP Kingan, TG (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,INSECT NEUROBIOL & HORMONE LAB,E BLDG 306,RM 322,BELTSVILLE,MD 20705, USA. NR 42 TC 47 Z9 48 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD SEP 30 PY 1997 VL 133 IS 1 BP 19 EP 32 DI 10.1016/S0303-7207(97)00140-8 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA XZ790 UT WOS:A1997XZ79000003 PM 9359469 ER PT J AU Dey, S Ramachandra, M Pastan, I Gottesman, MM Ambudkar, SV AF Dey, S Ramachandra, M Pastan, I Gottesman, MM Ambudkar, SV TI Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE multidrug transporter; cis(Z)-flupentixol; photoaffinity labeling; [I-125]iodoarylazidoprazosin; ATP hydrolysis ID MULTIDRUG-RESISTANT CELLS; NUCLEOTIDE-BINDING SITES; SUBSTRATE-SPECIFICITY; MONOCLONAL-ANTIBODIES; ATPASE ACTIVITY; LABELING SITES; INSECT CELLS; TRANSPORTER; VINBLASTINE; EXPRESSION AB Human P-glycoprotein (Pgp) confers multidrug resistance to cancer cells by ATP-dependent extrusion of a great many structurally dissimilar hydrophobic compounds, The manner in which Pgp recognizes these different substrates is unknown. The protein shows internal homology between its N- and C-terminal halves, each comprised of six putative transmembrane helices and a consensus ATP binding/utilization site, Photoactive derivatives of certain Pgp substrates specifically label two regions, one on each half of the protein, In this study, using [I-125]iodoarylazidoprazosin ([I-125]IAAP), a photoactive analog of prazosin, we have demonstrated the presence of two nonidentical drug-interaction sites within Pgp. Taking advantage of a highly susceptible trypsin cleavage site in the linker region of Pgp, we characterized the [I-125]IAAP binding to the Nand C-terminal halves, cis(Z)-Flupentixol, a modulator of Pgp function, preferentially increased the affinity of [I-125]IAAP for the C-terminal half of the protein (C-site) by reducing the K-d from 20 to 6 nM without changing the labeling or affinity (K-d = 42-46 nM) of the N-terminal half (N-site), Also, the concentration of vinblastine (Pgp substrate) and cyclosporin A (Pgp modulator) required for 50% inhibition of [I-125]IAAP binding to the C-site was increased 5- to 6-fold by cis(Z)-flupentixol without any effect on the N-site, In addition, [I-125]IAAP binding to the N-site was less susceptible than to C-site to inhibition by vanadate which blocks ATP hydrolysis and drug transport, These data demonstrate the presence of at least two nonidentical substrate interaction sites in Pgp. C1 NCI,CELL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Ambudkar, Suresh/B-5964-2008 NR 42 TC 304 Z9 305 U1 2 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 10594 EP 10599 DI 10.1073/pnas.94.20.10594 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800022 PM 9380680 ER PT J AU Weng, NP Granger, L Hodes, RJ AF Weng, NP Granger, L Hodes, RJ TI Telomere lengthening and telomerase activation during human B cell differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GERMINAL-CENTERS; MEMORY-B; T-CELLS; HEMATOPOIETIC-CELLS; HUMAN FIBROBLASTS; HUMAN-LYMPHOCYTES; SOMATIC MUTATION; ANTIGEN RECEPTOR; RNA COMPONENT; BONE-MARROW AB The function of the immune system is highly dependent on cellular differentiation and clonal expansion of antigen-specific lymphocytes, However, little is known about mechanisms that may have evolved to protect replicative potential in actively dividing lymphocytes during immune differentiation and response. Here we report an analysis of telomere length and telomerase expression, factors implicated in the regulation of cellular replicative lifespan, in human B cell subsets. In contrast to previous observations, in which telomere shortening and concomitant loss of replicative potential occur in the process of somatic cell differentiation and cell division, it was found that germinal center (GC) B cells, a compartment characterized by extensive clonal expansion and selection, had significantly longer telomeric restriction fragments than those of precursor naive B cells. Furthermore, it was found that telomerase, a telomere-synthesizing enzyme, is expressed at high levels in GC B cells (at least 128-fold higher than those of naive and memory B cells), correlating with the long telomeres in this subset of B cells. Finally, both naive and memory B cells were capable of upregulating telomerase activity in vitro in response to activation signals through the B cell antigen receptor in the presence of CD40 engagement and/or interleukin 4. These observations suggest that a novel process of telomere lengthening, possibly mediated by telomerase, functions in actively dividing GC B lymphocytes and may play a critical role in humoral immune response by maintaining the replicative potential of GC and descendant memory B cells. C1 NIA,NIH,BETHESDA,MD 20892. RP Weng, NP (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B17,10 CTR DR,MSC 1360,BETHESDA,MD 20892, USA. NR 63 TC 182 Z9 187 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 10827 EP 10832 DI 10.1073/pnas.94.20.10827 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800063 PM 9380719 ER PT J AU NobenTrauth, N Shultz, LD Brombacher, F Urban, JF Gu, H Paul, WE AF NobenTrauth, N Shultz, LD Brombacher, F Urban, JF Gu, H Paul, WE TI An interleukin 4 (IL-4)-independent pathway for CD4(+) T cell IL-4 production is revealed in IL-4 receptor-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STIMULATORY FACTOR-I; GAMMA-CHAIN; FUNCTIONAL COMPONENT; FC-EPSILON; MAST-CELLS; RESPONSES; GENE; EXPRESSION; LYMPHOKINE; PROTEINS AB IL-4 receptor alpha chain (IL-4R alpha)-deficient mice were generated by gene-targeting in BALB/c embryonic stem cells. Mutant mice showed a loss of IL-4 signal transduction and functional activity. The lack of IL-4R alpha resulted in markedly diminished, but not absent, TH2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis. CD4(+), CD62L-high, and CD62L-low T cell populations from uninfected TL-4R alpha(-/-) mice were isolated by cell sorting, Upon primary stimulation by T cell receptor cross-linkage, the CD62L-low, bur not the CD62L-high, cells secreted considerable amounts of IL-4, which was strikingly enhanced upon 4-day culture with anti-CDS in the presence or absence of IL-4. CD62L-low cells isolated from IL-4R alpha(-/-), beta(2)-microglobulin(-/-) double homozygous mice produced less IL-4 than did either IL-4R alpha(-/-) or wild-type mice. These results indicate that an IL-4-independent, beta(2)-microglobulin-dependent pathway exists through which the CD62L-low CD4(+) population has acquired IL-4-producing capacity in vivo, strongly suggesting that these cells are NK T cells. C1 JACKSON LAB, BAR HARBOR, ME 04609 USA. MAX PLANCK INST IMMUNBIOL, D-79108 FREIBURG, GERMANY. USDA, IMMUNOL & DIS RESISTANCE LAB, BELTSVILLE, MD 20705 USA. RP NobenTrauth, N (reprint author), NIAID, IMMUNOL LAB,NIH,TWINBROOK 2,ROOM 125, 12441 PARKLAWN DR, ROCKVILLE, MD 20852 USA. OI Urban, Joseph/0000-0002-1590-8869 FU NCI NIH HHS [CA20408] NR 48 TC 237 Z9 241 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 10838 EP 10843 DI 10.1073/pnas.94.20.10838 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800065 PM 9380721 ER PT J AU Ahlers, JD Takeshita, T Pendleton, CD Berzofsky, JA AF Ahlers, JD Takeshita, T Pendleton, CD Berzofsky, JA TI Enhanced immunogenicity of HIV-1 vaccine construct by modification of the native peptide sequence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOTOXIC-T-CELLS; MHC CLASS-II; LYMPHOCYTES-T; IN-VIVO; NEUTRALIZING ANTIBODY; MOLECULAR ANALYSIS; SYNTHETIC PEPTIDE; ENVELOPE PROTEIN; PARTIAL AGONISTS; HELPER EPITOPES AB Viral proteins are not naturally selected for high affinity major histocompatibility complex (MHC) binding sequences; indeed, if there is any selection, it is;likely to be negative in nature, Thus, one should be able to increase viral peptide binding to MHC in the rational design of synthetic peptide vaccines. The TI helper peptide front the HIV-I envelope protein was made more immunogenic for inducing T cell proliferation to the native sequence by replacing a residue that exerts an adverse influence on peptide binding to an MHC class II molecule, Mice immunized with vaccine constructs combining the more potent Th helper (Th) epitope with a cytotoxic T lymphocyte (CTL) determinant developed greatly enhanced CTL responses, Use of class II MHC-congenic mice confirmed that the enhancement of CTL response was due to class II-restricted help, Thus, enhanced T cell help is key for optimal induction of CTL, and, by modification of the native immunogen to increase binding to MHC, it is possible to develop second generation vaccine constructs that enhance both Th cell activation and CTL induction. C1 NCI,METAB BRANCH,MOL IMMUNOGENET & VACCINE RES SECT,NIH,BETHESDA,MD 20892. NR 52 TC 64 Z9 64 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 10856 EP 10861 DI 10.1073/pnas.94.20.10856 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800068 PM 9380724 ER PT J AU Becker, KJ McCarron, RM Ruetzler, C Laban, O Sternberg, E Flanders, KC Hallenbeck, JM AF Becker, KJ McCarron, RM Ruetzler, C Laban, O Sternberg, E Flanders, KC Hallenbeck, JM TI Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NEURON-SPECIFIC ENOLASE; GROWTH-FACTOR-BETA; TUMOR-NECROSIS-FACTOR; BRAIN-BARRIER PERMEABILITY; CENTRAL-NERVOUS-SYSTEM; ORAL TOLERANCE; ARTERY OCCLUSION; TGF-BETA AB Immune mechanisms contribute to cerebral ischemic injury. Therapeutic immunosuppressive options are limited due to systemic side effects. We attempted to achieve immunosuppression in the brain through oral tolerance to myelin basic protein (MBP). Lewis rats were fed low-dose bovine MBP or ovalbumin (1 mg, five times) before 3 h of middle cerebral artery occlusion (MCAO). A third group of animals was sensitized to MBP but did not survive the post-stroke period. Infarct size at 24 and 96 h after ischemia was significantly less in tolerized animals, Tolerance to MBP was confirmed in vivo by a decrease in delayed-type hypersensitivity to MBP, Systemic immune responses, characterized in vitro by spleen cell proliferation to Con A, lipopolysaccharide, and MBP, again confirmed antigen-specific immunologic tolerance, Immunohistochemistry revealed transforming growth factor pi production by T cells in the brains of tolerized but not control animals. Systemic transforming growth factor pi levels were equivalent in both groups. Corticosterone levels 24 h after surgery were elevated in all sham operated animals and ischemic control animals but not in ischemic tolerized animals. These results demonstrate that antigen-specific modulation of the immune response decreases infarct size after focal cerebral ischemia and that sensitization to the same antigen may actually worsen outcome. C1 NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. NIMH,CLIN ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. NR 89 TC 115 Z9 122 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 10873 EP 10878 DI 10.1073/pnas.94.20.10873 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800071 PM 9380727 ER PT J AU Zhao, CQ Young, MR Diwan, BA Coogan, TP Waalkes, MP AF Zhao, CQ Young, MR Diwan, BA Coogan, TP Waalkes, MP TI Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID B6C3F1 MOUSE-LIVER; HEAT-SHOCK; RAT-LIVER; C-MYC; HEPATOCELLULAR TUMORS; METALLOTHIONEIN GENE; S-ADENOSYLMETHIONINE; CYTO-TOXICITY; METHYLATION; CADMIUM AB Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming s-adenosyl-methionine (SAM) in the process, The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion, The hypothesis was tested by first inducing transformation in a rat liver epithelial cell line by chronic exposure to low levels of arsenic, as confirmed by the development of highly aggressive, malignant tumors after inoculation of cells into Nude mice, Global DNA hypomethylation occurred concurrently with malignant transformation and in the presence of depressed levels of S-adenosyl-methionine Arsenic-induced DNA hypomethylation was a function of dose and exposure duration, and remained constant even after withdrawal of arsenic, Hyperexpressibility of the MT gene, a gene for which expression is clearly controlled by DNA methylation, was also detected in transformed cells, Acute arsenic or arsenic at nontransforming levels did not induce global hypomethylation of DNA, Whereas transcription of DNA MeTase was elevated, the MeTase enzymatic activity was reduced with arsenic transformation. Taken together, these results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis. C1 NIEHS,NCI,INORGAN CARCINOGENESIS SECT,COMPARAT CARCINOGENESIS LAB,NIH,RES TRIANGLE PK,NC 27709. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP FREDERICK,FREDERICK,MD 21702. NR 51 TC 329 Z9 361 U1 1 U2 20 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 10907 EP 10912 DI 10.1073/pnas.94.20.10907 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800077 PM 9380733 ER PT J AU Fidock, DA Wellems, TE AF Fidock, DA Wellems, TE TI Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THYMIDYLATE SYNTHASE GENE; PLASMODIUM-FALCIPARUM MALARIA; MYCOBACTERIUM-AVIUM COMPLEX; IN-VITRO ACTIVITIES; PYRIMETHAMINE RESISTANCE; ANTIMALARIAL ACTIVITY; STABLE TRANSFECTION; MOLECULAR-BASIS; PS-15; METHOTREXATE AB Increasing resistance of Plasmodium falciparum malaria parasites to chloroquine and the dihydrofolate reductase (DHFR) inhibitors pyrimethamine and cycloguanil have sparked renewed interest in the antimalarial drugs WR99210 and proguanil, the cycloguanil precursor. To investigate suggestions that WR99210 and proguanil act against a target other than the reductase moiety of the P. falciparum bifunctional DHFR-thymidylate synthase enzyme, we have transformed P. falciparum with a variant form of human DHFR selectable by methotrexate. Human DHFR was found to fully negate the antiparasitic effect of WR99210, thus demonstrating that the only significant action of WR99210 is against parasite DHFR, Although the human enzyme also resulted in greater resistance to cycloguanil, no decrease was found in the level of susceptibility of transformed parasites to proguanil, thus providing evidence of intrinsic activity of this parent compound against a target other than DHFR, The transformation system described here has the advantage that P. falciparum drug-resistant lines are uniformly sensitive to methotrexate and will complement transformation with existing pyrimethamine-resistance markers in functional studies of P. falciparum genes, This system also provides an approach for screening and identifying novel DHFR inhibitors that will be important in combined chemotherapeutic formulations against malaria. C1 NIAID,PARASIT DIS LAB,MOL GENET SECT,NIH,BETHESDA,MD 20892. INST PASTEUR,LAB PARASITOL BIOMED,F-75724 PARIS 15,FRANCE. OI Fidock, David/0000-0001-6753-8938 NR 51 TC 333 Z9 334 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 10931 EP 10936 DI 10.1073/pnas.94.20.10931 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800081 PM 9380737 ER PT J AU Quan, N Whiteside, M Kim, L Herkenham, M AF Quan, N Whiteside, M Kim, L Herkenham, M TI Induction of inhibitory factor kappa B alpha mRNA in the central nervous system after peripheral lipopolysaccharide administration: An in situ hybridization histochemistry study in the rat SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; MESSENGER-RNA; TNF-ALPHA; ACTIVATION; EXPRESSION; CYTOKINES; BRAIN; GENE; ASTROCYTES AB In this study we investigate the mRNA expression of inhibitory factor kappa B alpha (I kappa B alpha) in cells of the rat brain induced by an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), I kappa B controls the activity of nuclear factor kappa B, which regulates the transcription of many immune signal molecules, The detection of I kappa B induction, therefore, would reveal the extent and the cellular location of brain-derived immune molecules in response to peripheral immune challenges, Low levels of I kappa B alpha mRNA were found in the large blood vessels and in circumventricular organs (CVOs) of saline-injected control animals, After an i.p. LPS injection (2.5 mg/kg), dramatic induction of I kappa B alpha mRNA occurred in four spatio-temporal patterns, Induced signals were first detected at 0.5 hr in the lumen of large blood vessels and in blood vessels of the choroid plexus and CVOs, Second, at 1-2 hr, labeling dramatically increased in the CVOs and choroid plexus and spread to small vascular and glial cells throughout the entire brain; these responses peaked at 2 hr and declined thereafter, Third, cells of the meninges became activated at 2 hr and persisted until 12 hr after the LPS injection, Finally, only at 12 hr, induced signals were present in ventricular ependyma, Thus, I kappa B alpha mRNA is induced in brain after peripheral LPS injection, beginning in cells lining the blood side of the blood-brain barrier and progressing to cells inside brain, The spatiotemporal patterns suggest that cells of the blood-brain barrier synthesize immune signal molecules to activate cells inside the central nervous system in response to peripheral LPS, The cerebrospinal fluid appears to be a conduit for these signal molecules. RP Quan, N (reprint author), NIMH,FUNCT NEUROANAT SECT,BLDG 36,ROOM 2D15,BETHESDA,MD 20892, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 28 TC 114 Z9 115 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 10985 EP 10990 DI 10.1073/pnas.94.20.10985 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800090 PM 9380746 ER PT J AU Shughrue, PJ Lubahn, DB NegroVilar, A Korach, KS Merchenthaler, I AF Shughrue, PJ Lubahn, DB NegroVilar, A Korach, KS Merchenthaler, I TI Responses in the brain of estrogen receptor alpha-disrupted mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; BREAST-CANCER; MOUSE; RAT; GENE; AUTORADIOGRAPHY; CELLS AB These studies sought to determine if neurons in the estrogen receptor-ct knockout (ER alpha KO) mouse brain concentrated 16 alpha-[I-125]iodo-11 beta-methoxy-17 beta-estradiol (I-125-estrogen), and if so, whether estrogen binding augmented the expression of progesterone receptor (PR) mRNA. Mice were injected with I-125-estrogen and cryostat sections thaw mounted onto emulsion-coated glides. After 30-90 days of exposure, cells with a nuclear uptake and retention of I-125-estrogen were observed in a number of ER alpha KO mouse brain regions including the preoptic nucleus and arcuate nucleus of the hypothalamus, bed nucleus of the stria terminalis, and amygdala, although the number of labeled cells and intensity of nuclear concentration was markedly attenuated when compared with wild-type littermates. Competition studies with excess 17 beta-estradiol, diethylstilbestrol, or moxestrol, But not with R5020 or dihydrotestosterone, prevented the nuclear concentration of I-125-estrogen. To determine if the low level of estrogen binding was capable of regulating gene expression, in situ hybridization was used to evaluate PR mRNA in the brain, ER alpha KO and wild-type mice were ovariectomized and treated with vehicle or 17 beta-estradiol, and brains were sectioned and hybridized with a PR cRNA probe, Analysis of hybridization signal revealed a similar, low level of PR mRNA in ovariectomized wild-type and homozygous mice, and a marked increase in expression after treatment of ovariectomized animals with 17 beta-estradiol, with the level of hybridization signal being significantly higher in wild-type animals when compared with ER alpha KO mice, The results demonstrate that estrogen binds in the ER alpha KO brain and is capable of modulating PR gene expression, thus supporting the presence and functionality of a nonclassical estrogen receptor. C1 UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. NIEHS,LAB REPROD TOXICOL,NIH,RES TRIANGLE PK,NC 27709. NIEHS,LAB DEV TOXICOL,NIH,RES TRIANGLE PK,NC 27709. RP Shughrue, PJ (reprint author), WYETH AYERST RES,WOMENS HLTH RES INST,145 KING PRUSSIA RD,RADNOR,PA 19087, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 27 TC 82 Z9 85 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 30 PY 1997 VL 94 IS 20 BP 11008 EP 11012 DI 10.1073/pnas.94.20.11008 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XY998 UT WOS:A1997XY99800094 PM 9380750 ER PT J AU Whalen, WA Bharathi, A Danielewicz, D Dhar, R AF Whalen, WA Bharathi, A Danielewicz, D Dhar, R TI Advancement through mitosis requires rae1 gene function in fission yeast SO YEAST LA English DT Article DE Schizosaccharomyces pombe; rae1-1 mutant; mitosis ID MESSENGER-RNA TRANSPORT; SPINDLE POLE BODY; CELL-CYCLE; SCHIZOSACCHAROMYCES-POMBE; SUBCELLULAR-LOCALIZATION; NUCLEAR-ENVELOPE; DNA-REPLICATION; PROTEIN-KINASE; ACTIVATION; IMPORT AB Growth of the rae1-1 mutant of Schizosaccharomyces pombe at restrictive temperature results in accumulation of poly(A)(+) RNA in the nucleus and a cell cycle arrest at the G2/M boundary. We demonstrate here that rae1 function is required for a process other than mRNA export which is essential for advancement through mitosis. Cells lacking rae1 function arrest with elevated Cdc2p kinase levels at a step before the formation of a mitotic spindle and without separation of the spindle pole bodies. Rae1p was localized to the nuclear periphery, consistent with a role in nucleocytoplasmic trafficking, which could include protein import. We propose a model where rae1 functions in cell cycle progression through trafficking of proteins required for mitosis. (C) 1997 John Wiley & Sons, Ltd. C1 NCI, MOL VIROL LAB, NIH, BETHESDA, MD 20892 USA. NR 46 TC 29 Z9 30 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD SEP 30 PY 1997 VL 13 IS 12 BP 1167 EP 1179 DI 10.1002/(SICI)1097-0061(19970930)13:12<1167::AID-YEA154>3.0.CO;2-O PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA XU744 UT WOS:A1997XU74400005 PM 9301023 ER PT J AU Altieri, AS Mazzulla, MJ Zhou, HJ Costantino, N Court, DL Byrd, RA AF Altieri, AS Mazzulla, MJ Zhou, HJ Costantino, N Court, DL Byrd, RA TI Sequential assignments and secondary structure of the RNA-binding transcriptional regulator NusB SO FEBS LETTERS LA English DT Article DE antitermination; Nus factor; NusB; RNA-binding protein; secondary structure; nuclear magnetic resonance ID RIBOSOMAL-PROTEIN S10; CHEMICAL-SHIFT INDEX; NMR-SPECTROSCOPY; PHAGE-LAMBDA; ANTITERMINATION FACTORS; N-15-ENRICHED PROTEINS; IMPROVED SENSITIVITY; CRYSTAL-STRUCTURE; NEURAL NETWORKS; C-PROTEINS AB The NusB protein is involved in transcriptional regulation in bacteriophage lambda. NusB binds to the RNA form of the nut site and along with N, NusA, NusE and NusG, stabilizes the RNA polymerase transcription complex and allows stable, persistent antitermination, NusB contains a 10 residue Arg-rich RNA-binding motif (ARM) at the N-terminus but is not sequentially homologous to any other proteins. In contrast to other known ARM-containing proteins, NusB forms a stable structure in solution in the absence of RNA, NMR spectroscopy was used to determine that NusB contains six alpha-helices: R10-Q21, I27-F34, V45-L65, Q79-S93, Y100-F114 and D118-L127. The structure of NusB makes it a member of a newly emerging class of alpha-helical RNA-binding proteins. (C) 1997 Federation of European Biochemical Societies. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL CONTROL & GENET SECT,FREDERICK,MD 21702. RP Altieri, AS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOL NMR SECT,POB B,BLDG 538,FREDERICK,MD 21702, USA. RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 NR 63 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 29 PY 1997 VL 415 IS 2 BP 221 EP 226 DI 10.1016/S0014-5793(97)01128-9 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YB592 UT WOS:A1997YB59200021 PM 9351000 ER PT J AU Kauppila, T Jyvasjarvi, E Murtomaki, S Mansikka, H Pertovaara, A Virtanen, I Liesi, P AF Kauppila, T Jyvasjarvi, E Murtomaki, S Mansikka, H Pertovaara, A Virtanen, I Liesi, P TI Use of paper for treatment of a peripheral nerve trauma in the rat SO NEUROREPORT LA English DT Article DE hyperalgesia; nerve regeneration; neuropathic pain; paper; rat ID SCIATIC-NERVE; GROWTH-FACTOR; NEUROPATHIC PAIN; REGENERATION; INFLAMMATION AB REINNERVATION Of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves. C1 UNIV TURKU,DEPT PHYSIOL,SF-20500 TURKU,FINLAND. UNIV HELSINKI,INST BIOMED,DEPT PHYSIOL,FIN-00014 HELSINKI,FINLAND. UNIV HELSINKI,INST BIOMED,DEPT ANAT,FIN-00014 HELSINKI,FINLAND. NIH,CELLULAR & MOL NEUROBIOL LAB,ALCOHOL ABUSE RES CTR,ROCKVILLE,MD. RP Kauppila, T (reprint author), UNIV AALBORG,SMI,FR BAHERS VEJ 7-D3,DK-9220 AALBORG,DENMARK. OI Pertovaara, Antti/0000-0002-8590-7220 NR 19 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 29 PY 1997 VL 8 IS 14 BP 3151 EP 3155 DI 10.1097/00001756-199709290-00029 PG 5 WC Neurosciences SC Neurosciences & Neurology GA XX910 UT WOS:A1997XX91000031 PM 9331932 ER PT J AU Alexander, J SchartonKersten, TM Yap, G Roberts, CW Liew, FY Sher, A AF Alexander, J SchartonKersten, TM Yap, G Roberts, CW Liew, FY Sher, A TI Mechanisms of innate resistance to Toxoplasma gondii infection SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Discussion Meeting of the Royal-Society-of-London on Immune Effector Mechanisms in Parasitic Infections CY FEB 19-20, 1997 CL LONDON, ENGLAND SP Royal Soc London ID TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; ANTI-MICROBIAL ACTIVITY; ENDOGENOUS IFN-GAMMA; INTERFERON-GAMMA; NITRIC-OXIDE; FACTOR-ALPHA; MURINE TOXOPLASMOSIS; ACCESSORY CELLS; T-CELLS AB The interaction of protozoan parasites with innate host defences is critical in determining the character of the subsequent infection. The initial steps in the encounter of Toxoplasma gondii with the vertebrate immune system provide a striking example of this important aspect of the host-parasite relationship. In immunocompetent individuals this intracellular protozoan produces an asymptomatic chronic infection as part of its strategy for transmission. Nevertheless, T. gondii is inherently a highly virulent pathogen. The rapid induction by the parasite of a potent cell-mediated immune response that both limits its growth and drives conversion to a dormant cyst stage explains this apparent paradox. Studies with gene-deficient mice have demonstrated the interleukin-12 (IL-12)-dependent production of interferon gamma (IFN-gamma) to be of paramount importance in controlling early parasite growth. However, this seems to be independent of nitric oxide production as mice deficient in inducible nitric oxide synthase (iNOS) and tumour necrosis factor receptor were able to control early growth of T. gondii, although they later succumbed to infection. Nitric oxide does, however, seem to be important in controlling persistent infection; treating chronic infection with iNOS metabolic inhibitors results in disease reactivation. Preliminary evidence implicates neutrophils in effector pathways against this parasite distinct from that described for macrophages. Once initiated, IL-12-dependent IFN-gamma production in synergy with other proinflammatory cytokines can positively feed back on itself to induce 'cytokine shock'. Regulatory cytokines, particularly IL-10, are essential to down-regulate inflammation and limit host pathology. C1 NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. UNIV GLASGOW,DEPT IMMUNOL,GLASGOW G11 6NT,LANARK,SCOTLAND. RP Alexander, J (reprint author), UNIV STRATHCLYDE,DEPT IMMUNOL,31 TAYLOR ST,GLASGOW G4 0NR,LANARK,SCOTLAND. RI Alexander, James/A-4238-2009; Roberts, Craig/B-8016-2008 OI Roberts, Craig/0000-0002-0653-835X NR 52 TC 47 Z9 50 U1 0 U2 4 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD SEP 29 PY 1997 VL 352 IS 1359 BP 1355 EP 1359 PG 5 WC Biology SC Life Sciences & Biomedicine - Other Topics GA YA544 UT WOS:A1997YA54400009 PM 9355127 ER PT J AU Nash, TE AF Nash, TE TI Antigenic variation in Giardia lamblia and the host's immune response SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Discussion Meeting of the Royal-Society-of-London on Immune Effector Mechanisms in Parasitic Infections CY FEB 19-20, 1997 CL LONDON, ENGLAND SP Royal Soc London ID EXPERIMENTAL HUMAN INFECTIONS; SURFACE-PROTEINS; ANIMAL-MODEL; ZINC-BINDING; GENE; ERYTHROCYTES; EXPRESSION; GERBILS; MICE; VARIABILITY AB Giardia lamblia, a protozoan parasite of the small intestine of humans and other animals, undergoes surface antigenic variation. The antigens involved belong to a family of variant-specific surface proteins (VSPs), which are unique, cysteine-rich zinc finger proteins. The patterns of infection in humans and animals fail to show the expected cyclical waves of increasing and decreasing numbers of parasites expressing unique VSPs. Nevertheless, changes in VSP expression occur within the population in vivo owing to selection of VSPs by both immune and non-immune mechanisms. After inoculation of a single G. lamblia clone (able to persist in the absence of immune pressure) expressing one VSP (greater than or equal to 90%) into mice or humans, the original VSP continues to be expressed until 2 weeks post inoculation (p.i.), when many other VSPs gradually replace it. Selection by immune-mediated processes is suggested because switching occurs at the same time that humoral responses are first detected. In most mouse strains, switching also occurs at about two weeks. Almost all trophozoites are eliminated at three weeks (p.i.), but a barely detectable infection persists over months. In neonatal mice, apparent self-cure is delayed until the sixth or seventh week. Antigenic switching does not occur in adult or neonatal severe combined immunodeficiency disease (SCID) mice, but does occur in neonatal nude mice, thus implicating B-cell-mediated mechanisms in immune switching. Not all VSPs are expressed to the same degree in vivo. Some VSPs appear to be preferentially selected whereas others are eliminated on a non-immune basis. In infections in which immunity does not play a role, such as in SCID mice, and during the first week of infection in immunocompetent mice or gerbils, persisting VSPs are preferentially expressed and maintained whereas non-persisting VSPs are replaced within the first week of infection. The purpose of antigenic variation may be presentation of a wide assortment of VSPs to hosts, increasing the chance of a successful initial infection or reinfection. Immune selection of variants comes into play following biological selection. RP Nash, TE (reprint author), NIH,PARASIT DIS LAB,GASTROINTESTINAL PARASITES SECT,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 61 TC 43 Z9 45 U1 0 U2 1 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD SEP 29 PY 1997 VL 352 IS 1359 BP 1369 EP 1375 DI 10.1098/rstb.1997.0122 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA YA544 UT WOS:A1997YA54400011 PM 9355129 ER PT J AU Knable, MB Heinz, A Raedler, T Weinberger, DR AF Knable, MB Heinz, A Raedler, T Weinberger, DR TI Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE I-123-IBZM; SPECT; neuroleptics; antipsychotics; schizophrenia ID SCHIZOPHRENIC-PATIENTS; PARKINSONS-DISEASE; ATYPICAL NEUROLEPTICS; D-2; CLOZAPINE; PET; EFFICACY; BLOCKADE; BINDING; SAFETY AB Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [I-123]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects. (C) 1997 Elsevier Science Ireland Ltd. RP Knable, MB (reprint author), NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 35 TC 74 Z9 76 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD SEP 29 PY 1997 VL 75 IS 2 BP 91 EP 101 DI 10.1016/S0925-4927(97)00023-1 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YC318 UT WOS:A1997YC31800003 PM 9351491 ER PT J AU Yamada, KM AF Yamada, KM TI Hot papers - Cell biology - Integrin function: Molecular hierarchies of cytoskeletal and signaling molecules by S. Miyamoto, H. Teramoto, O.A. Coso, J.S. Gutkind, P.D. Burbelo, S.K. Akiyama, K.M. Yamada - Comments SO SCIENTIST LA English DT Editorial Material C1 NIDR,ORAL & PHARYNGEAL CANC BRANCH,BETHESDA,MD 20892. RP Yamada, KM (reprint author), NIDR,CRANIOFACIAL DEV BIOL & REGENERAT BRANCH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD SEP 29 PY 1997 VL 11 IS 19 BP 14 EP 14 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA XX685 UT WOS:A1997XX68500012 ER PT J AU Tobin, GJ Li, GH Fong, SE Nagashima, K Gonda, MA AF Tobin, GJ Li, GH Fong, SE Nagashima, K Gonda, MA TI Chimeric HIV-1 virus-like particles containing gp120 epitopes as a result of a ribosomal frameshift elicit Gag- and SU-specific murine cytotoxic T-lymphocyte activities SO VIROLOGY LA English DT Article ID INFECTED INSECT CELLS; LONG-TERM SURVIVORS; LOW VIRAL LOAD; RECOMBINANT BACULOVIRUS; TYPE-1 INFECTION; IMMUNE-RESPONSE; SEROPOSITIVE INDIVIDUALS; NEUTRALIZING ANTIBODIES; EXPRESSION SYSTEM; IN-VIVO AB insect cell expression of the HIV-1 Gag precursor protein by recombinant baculoviruses results in the assembly and budding of noninfectious virus-like particles (VLPs). The VLPs resemble immature virus in ultrastructural morphology and can be purified by conventional retroviral techniques. The virus-like appearance of the particles suggested that they could be used to package additional peptides. The retroviral frameshift mechanism was used to translate the pol gene products by expressing additional genetic information as chimeric Gag-Pol fusion proteins. Sequences encoding the carboxy[ 65% of the HIV-1 surface glycoprotein (gp120, SU) were inserted into the Gag-Pol reading frame immediately downstream of the Gag stop codon. The assembly and budding of large quantities of Gag and chimeric Gag-SU VLPs were observed by standard transmission electron microscopy. The presence of gp120 epitopes in the Gag-SU VLPs was confirmed by immunoelectron microscopy and Western blot analysis using monoclonal anti-gp120 antibodies. Mice inoculated with the Gag-SU pseudovirions developed cytotoxic lymphocyte responses to both HIV-1 Gag and Env epitopes yet humoral immune responses only to Gag epitopes. The chimeric Gag-SU particles may have applications as vaccines or immunotherapeutic treatments for HIV-1 infection. In addition, the frameshift mechanism can be applied to the packaging of other Viral or cellular proteins. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB CELL & MOL STRUCT,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO56000] NR 57 TC 15 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 29 PY 1997 VL 236 IS 2 BP 307 EP 315 DI 10.1006/viro.1997.8745 PG 9 WC Virology SC Virology GA XZ359 UT WOS:A1997XZ35900009 PM 9325238 ER PT J AU Pickar, D Malhotra, AK Rooney, W Breier, A Goldman, D AF Pickar, D Malhotra, AK Rooney, W Breier, A Goldman, D TI Apolipoprotein E epsilon 4 and clinical phenotype in schizophrenia SO LANCET LA English DT Article C1 NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. RP Pickar, D (reprint author), NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 5 TC 22 Z9 22 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 27 PY 1997 VL 350 IS 9082 BP 930 EP 931 DI 10.1016/S0140-6736(05)63266-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XY672 UT WOS:A1997XY67200015 PM 9314875 ER PT J AU Luo, Y Hawver, DB Iwasaki, K Sunderland, T Roth, GS Wolozin, B AF Luo, Y Hawver, DB Iwasaki, K Sunderland, T Roth, GS Wolozin, B TI Physiological levels of beta-amyloid peptide stimulate protein kinase C in PC12 cells SO BRAIN RESEARCH LA English DT Article DE protein kinase C; Alzheimer's disease; signal transduction ID NERVE GROWTH-FACTOR; ALZHEIMERS-DISEASE; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; PRECURSOR PROTEIN; LIMITED PROTEOLYSIS; NEURITE OUTGROWTH; BRAIN; TRANSLOCATION; INHIBITION AB Alzheimer's beta-amyloid peptide (A beta) is normally present at nanomolar concentrations in body fluids and in the medium of cultured cells. In vitro experiments have shown that A beta has neurotrophic effects and can promote neuronal adhesion and elongation of axon-like processes. In an attempt to understand the molecular mechanisms underlying such effects, we have recently reported that nanomolar doses of A beta can stimulate protein tyrosine phosphorylation and activate phosphatidylinositol-3-kinase in neuronal cells. Here we show evidence that A beta can also activate protein kinase C, a serine/threonine kinase, in PC12 cells. First, using a serine-containing S6 peptide as an exogenous substrate, we found that nanomolar levels of A beta peptides 1-40 or 1-42 significantly stimulated an S6 phosphorylating kinase activity, whereas the A beta(40-1) reverse sequence peptide had no effect. Down-regulation of PKC by prolonged (18 h) treatment with 1 mu M PMA prevented the A beta-induced S6 phosphorylation. Using a more specific PKC substrate, N-terminal acetylated peptide (4-14) from myelin basic protein, we then demonstrated that A beta indeed increased PKC activity and that this activity could be blocked by the PKC inhibitor, staurosporine. Finally, immunoblotting experiments showed that A beta induced translocation of PKC gamma from cytosol to membrane and also significantly reduced cytosolic PKC alpha levels. Taken together, these data suggest that physiological levels of A beta can regulate PKC activity. (C) 1997 Elsevier Science B.V. C1 NIMH, SECT GERIATR PSYCHIAT, BETHESDA, MD 20892 USA. LOYOLA UNIV, MED CTR, DEPT PHARMACOL, MAYWOOD, IL 60153 USA. NIA, GERONTOL RES CTR, MOL NEUROBIOL UNIT, BALTIMORE, MD 21224 USA. RP Luo, Y (reprint author), NIA, GERONTOL RES CTR, MOL PHYSIOL & GENET SECT, 4940 EASTERN AVE, 4E02, BALTIMORE, MD 21224 USA. NR 50 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD SEP 26 PY 1997 VL 769 IS 2 BP 287 EP 295 DI 10.1016/S0006-8993(97)00718-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA YC393 UT WOS:A1997YC39300011 PM 9374197 ER PT J AU Mann, H Ladenheim, B Hirata, H Moran, TH Cadet, JL AF Mann, H Ladenheim, B Hirata, H Moran, TH Cadet, JL TI Differential toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout mice SO BRAIN RESEARCH LA English DT Article DE P-glycoprotein; neurotoxicity; methamphetamine; methylenedioxymethamphetamine; blood-brain barrier; dopamine; striatum; nucleus accumbens; cancer ID DISMUTASE TRANSGENIC MICE; BACTERIAL TRANSPORT PROTEINS; P-GLYCOPROTEIN GENE; RAT-BRAIN; SUPEROXIDE RADICALS; UPTAKE SITES; MOUSE; NEUROTOXICITY; DOPAMINE; FAMILY AB The toxic effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/kg) and methylenedioxymethamphetamine (MDMA) (5.0, 10.0 and 20.0 mg/kg) on dopaminergic systems were assessed in the striatum and of the nucleus accumbens in mdr1a wild-type and knockout mice. METH caused significant dose-dependent decreases of dopamine (DA) and DA transporters (DAT) in the striatum and the nucleus accumbens (NAc) of both wild-type and knockout mice. The lowest doses of METH (2.5 mg/kg) caused only small changes in the wild-type, but marked decreases in the mdr1a knockout mice. The two higher doses (5 mg/kg and 10 mg/kg) caused similar changes in both strains of mice. In contrast to METH, MDMA caused greater percentage decreases in DAT in the wild-type mice. For example, the lowest dose (5 mg/kg) caused significant decreases in DAT in the NAc of wild-type but not of mdr1a knockout mice. The highest dose (20 mg/kg) caused similar changes in both the strains. These results suggest that METH and MDMA interact differentially with P-glycoproteins. These observations document, for the first time, a role for these proteins in the entry of METH and MDMA into the brain via the blood-brain barrier, with P-glycoprotein possibly facilitating the entry of MDMA but interfering with that of METH into the brain. (C) 1997 Elsevier Science B.V. C1 NIDA,ADDICT RES CTR,MOL NEUROPSYCHIAT SECT,IRP,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. FU NICHD NIH HHS [HD 24605] NR 36 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 26 PY 1997 VL 769 IS 2 BP 340 EP 346 DI 10.1016/S0006-8993(97)00754-3 PG 7 WC Neurosciences SC Neurosciences & Neurology GA YC393 UT WOS:A1997YC39300018 PM 9374204 ER PT J AU Price, KN Tuinman, A Baker, DC Chisena, C Cysyk, RL AF Price, KN Tuinman, A Baker, DC Chisena, C Cysyk, RL TI Isolation and characterization by electrospray-ionization mass spectrometry and high-performance anion-exchange chromatography of oligosaccharides derived from hyaluronic acid by hyaluronate lyase digestion: Observation of some heretofore unobserved oligosaccharides that contain an odd number of units SO CARBOHYDRATE RESEARCH LA English DT Article DE hyaluronan; hyaluronic acid; electrospray-ionization mass spectrometry; high-performance anion-exchange chromatography (HPAEC); pulsed amperometric detection (PAD); glycosaminoglycans ID PULSED AMPEROMETRIC DETECTION; OLIGOGALACTURONIC ACIDS; LIQUID-CHROMATOGRAPHY; TUMOR-CELLS; CD44; CARBOHYDRATE; BINDING; RECEPTORS; PROTEOGLYCANS; EXPRESSION AB Hyaluronic acid was degraded with hyaluronate lyase (E.C. 4.2.2.1, from Streptomyces hyalurolyticus), and the resulting oligosaccharides up to dp 16 were characterized by electrospray-ionization mass spectrometry (ESIMS) and high-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection (PAD). In accordance with the known regiospecificity of the enzyme, the products included even-numbered oligosaccharides of structure beta-D-4en-thrHexpA-(1 --> 3)-[beta-D-GlcpNAc-(1 --> 4)-beta-D-GlcpA](n)-(1 --> 3)-D-GlcpNAc. Minor amounts of novel and unexpected odd-numbered oligomers, having the structure beta-D-4en-thrHexpA-(1 --> 3)-[beta-D-GlcpNAc-(1 --> 4)-D-GlcpA](n), were also isolated and characterized. This study, in addition to others beginning to appear in the literature, demonstrates the usefulness of ESIMS and HPAEC-PAD in the analysis and characterization of anionic glycosaminoglycan-type oligosaccharides. (C) 1997 Elsevier Science Ltd. C1 UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996. NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 45 TC 44 Z9 45 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 26 PY 1997 VL 303 IS 3 BP 303 EP 311 DI 10.1016/S0008-6215(97)00171-7 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA YC520 UT WOS:A1997YC52000007 PM 9373935 ER PT J AU Godwin, DA Michniak, BB Player, MR Sowell, JW AF Godwin, DA Michniak, BB Player, MR Sowell, JW TI Transdermal and dermal enhancing activity of pyrrolidinones in hairless mouse skin SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE transdermal drug delivery; pyrrolidinones; hairless mouse; percutaneous penetration; hydrocortisone; skin retention ID IN-VITRO EVALUATION; PENETRATION ENHANCERS; AZONE ANALOGS; PYRROLIDONE DERIVATIVES; DRUG DELIVERY; HYDROCORTISONE; PERMEATION; SERIES; 1-ALKYL-2-PYRROLIDONES; INDOMETHACIN AB The transdermal penetration-enhancing abilities of 16 pyrrolidinones were tested against the model drug hydrocortisone using a hairless mouse skin model in vitro. Skins were pretreated for I h with the enhancer in propylene glycol before application of the drug also in propylene glycol. Enhancement ratios (ER) were calculated for permeability coefficient (P), 24-h receptor concentration (Q(24)), and skin content of drug (SC) and compared to control values (no enhancer present). N-Dodecyl-2-pyrrolidinone and 2-pyrrolidinone-1-acetic acid dodecyl ester were found to produce the greatest enhancement for all the parameters calculated with ER for Q(24) of 23.11 and 11.68, respectively. These same enhancers also produced high ERs for P with 42.95 and 41.07, respectively. These values exceed Atone's enhancement ratios for the same parameters and hence these enhancers are candidates for further development as penetration enhancers. (C) 1997 Elsevier Science B.V. C1 UNIV S CAROLINA,COLL PHARM,DEPT BASIC PHARMACEUT SCI,COLUMBIA,SC 29208. NIDDKD,MED CHEM LAB,SECT BIOMED CHEM,NIH,BETHESDA,MD 20892. RP Godwin, DA (reprint author), UNIV NEW MEXICO,COLL PHARM,DEPT BASIC PHARMACEUT SCI,ALBUQUERQUE,NM 87131, USA. NR 23 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD SEP 26 PY 1997 VL 155 IS 2 BP 241 EP 250 DI 10.1016/S0378-5173(97)00163-4 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XX711 UT WOS:A1997XX71100009 ER PT J AU Gong, DW He, YF Karas, M Reitman, M AF Gong, DW He, YF Karas, M Reitman, M TI Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta 3-adrenergic agonists, and leptin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BROWN ADIPOSE-TISSUE; PROTON TRANSPORT; FAT; EXPRESSION; CLONING; OBESITY; MICE; GENE; MECHANISM; C57BL/6J AB Mitochondrial uncoupling proteins (UCPs) are transporters that are important for thermogenesis, The net result of their activity is the exothermic movement of protons through the inner mitochondrial membrane, uncoupled from ATP synthesis, We have cloned a third member of the UCP family, UCP3. UCP3 is expressed at high levels in muscle and rodent brown adipose tissue, Overexpression in yeast reduced the mitochondrial membrane potential, showing that UCP3 is a functional uncoupling protein, UCP3 RNA levels are regulated by hormonal and dietary manipulations, In contrast, levels of UCP2, a widely expressed UCP family member, showed little hormonal regulation, In particular, muscle UCP3 levels were decreased 3-fold in hypothyroid rats and increased B-fold in hyperthyroid rats, Thus UCP3 is a strong candidate to explain the effects of thyroid hormone on thermogenesis. White adipose UCP3 levels were greatly increased by treatment with the beta 3-adrenergic agonist, CL214613, suggesting another pathway for increasing thermogenesis, UCP3 mRNA levels were also regulated by dexamethasone, leptin, and starvation, albeit differently in muscle and brown adipose tissue. Starvation caused increased muscle and decreased BAT UCP3, suggesting that muscle assumes a larger role in thermoregulation during starvation, The UCP3 gene is located close to that encoding UCP2, in a chromosomal region implicated in previous linkage studies as contributing to obesity. RP Gong, DW (reprint author), NIDDK,DIABET BRANCH,NIH,BLDG 10,RM 8N-250,10 CTR DR,MSC 1770,BETHESDA,MD 20892, USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 36 TC 653 Z9 679 U1 3 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 26 PY 1997 VL 272 IS 39 BP 24129 EP 24132 DI 10.1074/jbc.272.39.24129 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY515 UT WOS:A1997XY51500009 PM 9305858 ER PT J AU Li, WQ Zhang, JC Bottaro, DP Li, W Pierce, JH AF Li, WQ Zhang, JC Bottaro, DP Li, W Pierce, JH TI Identification of serine 643 of protein kinase C-delta as an important autophosphorylation site for its enzymatic activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATP BINDING MUTANT; TYROSINE PHOSPHORYLATION; IN-VIVO; ACTIVATION; CELLS; PATHWAY; PKC; DIFFERENTIATION; TRANSFORMATION; STIMULATION AB To investigate the role of serine/threonine autophosphorylation of protein kinase C-delta (PMC-delta), we mutated serine 643 of PKC-delta to an alanine residue (PKC-delta S643A). Two different expression vectors containing PKC-delta S643A mutant cDNAs were transfected and expressed in 32D myeloid progenitor cells. In vitro autophosphorylation assays demonstrated 65-83% reduction in autophosphorylation of PKC-delta S643A in comparison to wild type PKC-delta (PKC-delta WT). The enzymatic activity of PKC-delta S643A mutant as measured by phosphorylating the PKC-delta pseudosubstrate region-derived substrate was also reduced more than 70% in comparison to that of PRC-delta WT. In vivo labeling and subsequent two-dimensional phosphopeptide analysis demonstrated that at least one phosphopeptide was absent in PKC-delta S643A when compared with PRC-delta WT, further substantiating that serine 643 is phosphorylated in vivo, Localization and 12-O-tetradecanoylphorbol-13-acetate-dependent translocation and tyrosine phosphorylation of PKC-delta S643A were not altered in comparison to PRC-delta WT, indicating that mutagenesis did not affect the structural integrity of the mutant protein, 12-O-Tetradecanoylphorbol-13-acetate-mediated monocytic differentiation of 32D cells overexpressing PKC-delta S643A mutant protein was impaired in comparison to that of PRC-delta WT transfectant, Taken together, oar results demonstrate that serine 643 of PRC-delta is a major autophosphorylation site, and phosphorylation of this site plays an important role in controlling its enzymatic activity and biological function. C1 UNIV CHICAGO,BEN MAY INST CANC RES,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,CHICAGO,IL 60637. RP Li, WQ (reprint author), NCI,MOL & CELLULAR BIOL LAB,NIH,BLDG 37,RM 1E24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 31 TC 59 Z9 60 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 26 PY 1997 VL 272 IS 39 BP 24550 EP 24555 DI 10.1074/jbc.272.39.24550 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY515 UT WOS:A1997XY51500071 PM 9305920 ER PT J AU Radko, SP Weiss, GH Chrambach, A AF Radko, SP Weiss, GH Chrambach, A TI Protein band spreading in capillary zone electrophoresis - Effects of sample zone length and presence of polymer SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 9th International Symposium on High Performance Capillary Electrophoresis and Related Microscale Techniques CY JAN 26-30, 1997 CL ORLANDO, FL DE band profiles; buffer composition; proteins ID HIGH-PERFORMANCE ELECTROPHORESIS; GEL-ELECTROPHORESIS; DISPERSION; RESOLUTION; MECHANISMS AB It is commonly accepted that intra-column zone dispersion in CZE rests on multiple mechanisms, viz, diffusion, interaction of analyte with the capillary walls, Joule heat and conductivity differences between sample zone and the surrounding buffer. The most important extra-column contributor to bandwidth is thought to be the starting zone width, The present study shows that the length of the starting zone above 10 mm is linearly related to the bandwidth of R-phycoerythrin (M-t 290.10(3)). Below that length, bandwidth demonstrates a plateau preceded by a slight rise. Within the 'plateau range', the ratio of bandwidth to effective capillary length is close to constant while it is independent of electric field strength in the range of 37 to 370 V cm(-1) and of protein concentration in the range of 0.1 to 1000 mu g ml(-1). The experimental observations support the notion that the analyte-wall interaction is the determining source of intra-column zone dispersion, A slight rise observed at initial zone lengths of less than 2 mm was accounted for by a diffusion model taking into account a non-local initial concentration of analyte. The presence of polyethyleneglycol in the buffer within a concentration range up to 6% does not affect bandwidth, Above that concentration, the level of constant bandwidth is raised. (C) 1997 Elsevier Science B.V. C1 NIH,PHYS SCI LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Radko, SP (reprint author), NICHHD,MACROMOL ANAL SECT,LAB CELLULAR & MOL BIOPHYS,NIH,BLDG 10,ROOM 6C215,BETHESDA,MD 20892, USA. NR 20 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 26 PY 1997 VL 781 IS 1-2 BP 277 EP 286 DI 10.1016/S0021-9673(97)00730-9 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YC198 UT WOS:A1997YC19800031 PM 9368390 ER PT J AU Ding, JM Szeliga, J Dipple, A Vouros, P AF Ding, JM Szeliga, J Dipple, A Vouros, P TI Application of mixed mobile phases and a step gradient method in capillary electrochromatography for the separation of isomeric polycyclic aromatic hydrocarbon-deoxyribonucleoside adduct mixtures prepared in vitro SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 9th International Symposium on High Performance Capillary Electrophoresis and Related Microscale Techniques CY JAN 26-30, 1997 CL ORLANDO, FL DE polynuclear aromatic hydrocarbons; deoxyribonucleosides; nucleosides; DNA; electrochromatography; mobile phase composition ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DIOL-EPOXIDES; MOUSE SKIN; 11,12-DIHYDRODIOL 13,14-EPOXIDE; NEWBORN MICE; DNA; 5,6-DIMETHYLCHRYSENE; TUMORIGENICITY; BENZOCHRYSENE; METABOLISM AB Capillary electrochromatography (CEC) was used for the analysis of mixtures of neutral isomeric compounds derived from the reaction of carcinogenic hydrocarbon (benzo[g]chrysene and 5,6-dimethylchrysene) dihydrodiol epoxides with calf thymus deoxyribonucleic acid (DNA). The CEC analysis demonstrated higher resolution, greater speed and lower analyte consumption than high-performance liquid chromatography (HPLC) in the analysis of the same samples using the same type of stationary phase. Proper selection of the mixed mobile phases was critical for the separation of these complex mixtures with enhanced speed and selectivity. The use of a step gradient further improved the speed of the CEC analysis resulting in electrochromatograms that required only 25-70% of the corresponding HPLC analysis times. (C) 1997 Elsevier Science B.V. C1 NORTHEASTERN UNIV,DEPT CHEM,BOSTON,MA 02115. NORTHEASTERN UNIV,BARNETT INST,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [1RO1CA 69390-01] NR 27 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 26 PY 1997 VL 781 IS 1-2 BP 327 EP 334 DI 10.1016/S0021-9673(97)00529-3 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YC198 UT WOS:A1997YC19800036 PM 9368395 ER PT J AU Choy, HE Hanger, RR Aki, T Mahoney, M Murakami, K Ishihama, A Adhya, S AF Choy, HE Hanger, RR Aki, T Mahoney, M Murakami, K Ishihama, A Adhya, S TI Repression and activation of promoter-bound RNA polymerase activity by Gal repressor SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcription; RNA polymerase; alpha subunit; repression ID INITIAL TRANSCRIBING COMPLEX; COLI GALACTOSE OPERON; ALPHA-SUBUNIT; LAC REPRESSOR; TRANSCRIPTIONAL ACTIVATION; PROTEIN P4; DNA; BINDING; GENE; COMMUNICATION AB By binding to the DNA site O-E at position -60.5 in the gal operon, the GalR protein activates transcription from the P2 promoter located on the opposite face of DNA (position -5) and represses transcription from the P1 promoter located on the same face (position +1). GalR increases RNA polymerase binding at P2 and inhibits isomerization at P1 by forming a GalR-DNA-RNA polymerase ternary complex in each case. The specific effect of GalR at one promoter is independent of the presence of the other promoter. The enhancement or repression is also not the intrinsic property of a promoter; the regulation can be reversed by switching the angular orientation of the promoters relative to O-E. Both enhancement and repression appear to require the same interaction between RNA polymerase alpha-subunit and GalR and/or the same interaction between RNA polymerase alpha-subunit and DNA in the ternary complexes. We have discussed how GalR might exert opposite effects in the steps involved in the formation of the open complex from free RNA polymerase and DNA. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NATL INST GENET,DEPT MOL GENET,MISHIMA,SHIZUOKA 411,JAPAN. RI Aki, Tsunehiro/B-6719-2012 OI Aki, Tsunehiro/0000-0001-9753-2043 NR 34 TC 34 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 26 PY 1997 VL 272 IS 3 BP 293 EP 300 DI 10.1006/jmbi.1997.1221 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY531 UT WOS:A1997XY53100001 PM 9325090 ER PT J AU Sasaki, T Chang, MCJ AF Sasaki, T Chang, MCJ TI N-arachidonylethanolamine (anandamide) formation from N-arachidonylphosphatidylethanolamine in rat brain membranes SO LIFE SCIENCES LA English DT Article DE anandamide; N-arachidonylphosphatidylethanolamine; brain membranes ID MICROSOMAL PHOSPHOLIPASE-D; CANNABINOID RECEPTOR; ENZYMATIC-SYNTHESIS; HIPPOCAMPAL SLICES; STIMULATION; INVOLVEMENT; ACTIVATION; FORSKOLIN; LIGAND AB Labeled L-N-arachidonylphosphatidylethanolamine (L-N-arachidonyl PE), a likely precursor of N-arachidonylethanolamine (anandamide), as well as its D-isomer, were synthesized using [C-14]arachidonic acid. Anandamide was formed by incubating L-N-arachidonyl PE and rat brain membrane with phenylmethylsulfonyl fluoride (PMSF), an inhibitor of anandamide amidohydrolase. Formation of anandamide from L-N-arachidonyl PE was inhibited by p-chloromercuriphenylsulfonic acid (p-CMPS), sulfhydryl reagent, and heat inactivate pre-treatment. D-N-Arachidonyl PE, an unnatural analog for N-arachidonyl PE, did not form anandamide. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 22 TC 20 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD SEP 26 PY 1997 VL 61 IS 18 BP 1803 EP 1810 DI 10.1016/S0024-3205(97)00804-7 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XZ551 UT WOS:A1997XZ55100008 PM 9365227 ER PT J AU Allen, DD Galdzicki, Z Brining, SK Fukuyama, R Rapoport, SI Smith, QR AF Allen, DD Galdzicki, Z Brining, SK Fukuyama, R Rapoport, SI Smith, QR TI Beta-amyloid induced increase in choline flux across PC12 cell membranes SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; beta-amyloid; choline; transport; cholinergic vulnerability; acetylcholine; PC12 cells ID ALZHEIMERS-DISEASE; POSSIBLE MECHANISM; TOXICITY; PROTEIN; CHANNELS AB Beta-amyloid peptide is the main constituent of senile plaques and is implicated in the pathogenesis of Alzheimer's disease. It has been shown to be both neurotoxic and neurotrophic in vivo, and its effects have been suggested to be mediated in part by alterations in membrane transport. In the present study, we investigated the effect of beta-amyloid (1-40) on choline transport in cultured PC12 cells. We found that exposure to 46 or 92 mu M beta-amyloid (1-40) increased [C-14]choline flux in PC12 cells in a concentration-dependent manner, whereas exposure to reverse sequence beta-amyloid (40-1) had no effect. If there is a similar effect in vivo, the increased beta-amyloid dependent permeability to choline could lead to depletion of cellular choline stores and could contribute to the selective vulnerability of cholinergic neurons in Alzheimer's disease. (C) 1997 Elsevier Science Ireland Ltd. C1 TEXAS TECH UNIV,HSC,SCH PHARM,DEPT PHARMACEUT SCI,AMARILLO,TX 79106. RP Allen, DD (reprint author), NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892, USA. NR 18 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 26 PY 1997 VL 234 IS 1 BP 71 EP 73 PG 3 WC Neurosciences SC Neurosciences & Neurology GA YA879 UT WOS:A1997YA87900019 PM 9347949 ER PT J AU Tang, LH Luque, EA Efstathiou, JA Bortecen, KH Kidd, M Tarasova, NI Modlin, IM AF Tang, LH Luque, EA Efstathiou, JA Bortecen, KH Kidd, M Tarasova, NI Modlin, IM TI Gastrin receptor expression and function during rapid transformation of the enterochromaffin-like cells in an African rodent SO REGULATORY PEPTIDES LA English DT Article DE ECL cells; carcinoids; mastomys; hypergastrinemia; histamine; loxtidine ID RAT PANCREATIC ACINI; B RECEPTOR; MASTOMYS-NATALENSIS; CCK-B; ALPHA-1B-ADRENERGIC RECEPTOR; GENE-EXPRESSION; PARIETAL-CELLS; AMINO-ACID; ECL CELLS; CHOLECYSTOKININ AB The enterochromaffin-like cell (ECL) cells of the stomach are principally regulated by gastrin via a gastrin/CCKB, receptor (G(R),) which modulates both histamine secretion and cell proliferation. In the African rodent (mastomys) hypergastrinemia generated by the histamine-2 receptor antagonist (loxtidine) results in ECL cell hyperplasia and neoplasia at 8 and 16 weeks respectively. The expression, structure and function of the G(R) during transformation is however unknown. We utilized a pure (similar to 90%) preparation of ECL cells to evaluate alterations in the G(R) utilizing immunocytochemistry, Western blot analysis, reverse transcription polymerase chain reaction (RT-PCR), 5-bromo-2-deoxyuridine uptake and phosphorylation site analysis. Although the expression of ECL cell G(R) was upregulated at both mRNA (PT-PCR) and protein (Western analysis) level, its affinity to gastrin was decreased in the hyperplastic phase and lost during transformation. The coding sequence of the G(R) of mastomys tumor ECL cells was identical to that of normal ECL cells, parietal cells and the brain. However, the mRNA sequence of the third introcytoplasmic loop of the G(R) was significantly different to other species. In addition, the G(R) exhibited phosphorylation site on serine residue(s). We have thus noted a direct correlation between hypergastrinemia and G(R) alteration and function during ECL cell transformation. It is possible that the unique mastomys gastrin receptor mediated ECL cell transformation involves the novel phosphorylation sites and a divergence in the introcytoplasmic domain. (C) 1997 Elsevier Science B.V. C1 YALE UNIV, SCH MED, DEPT SURG, GASTR PATHOBIOL RES GRP, NEW HAVEN, CT 06520 USA. DEPT VET AFFAIRS MED CTR, NEW HAVEN, CT 06520 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOL ASPECT DRUG DESIGN SECT, FREDERICK, MD 21702 USA. FU NIDDK NIH HHS [DK48820] NR 43 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 26 PY 1997 VL 72 IS 1 BP 9 EP 18 DI 10.1016/S0167-0115(97)01025-2 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA YG381 UT WOS:A1997YG38100002 PM 9404728 ER PT J AU Cottler, LB Hasin, D Grant, BF AF Cottler, LB Hasin, D Grant, BF TI The cross-cultural nosological issues in drug and alcohol use disorders - Overview SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10027. NIAAA,DIV EPIDEMIOL & EPIDEMIOL,ROCKVILLE,MD 20852. RP Cottler, LB (reprint author), WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 25 PY 1997 VL 47 IS 3 BP 159 EP 159 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XV657 UT WOS:A1997XV65700001 ER PT J AU Ustun, B Compton, W Mager, D Babor, T Baiyewu, O Chatterji, S Cottler, L Gogus, A Mavreas, V Peters, L Pull, C Saunders, J Smeets, R Stipec, MR Vrasti, R Hasin, D Room, R VandenBrink, W Regier, D Blaine, J Grant, BF Sartorius, N AF Ustun, B Compton, W Mager, D Babor, T Baiyewu, O Chatterji, S Cottler, L Gogus, A Mavreas, V Peters, L Pull, C Saunders, J Smeets, R Stipec, MR Vrasti, R Hasin, D Room, R VandenBrink, W Regier, D Blaine, J Grant, BF Sartorius, N TI WHO Study on the reliability and validity of the alcohol and drug use disorder instruments: overview of methods and results SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE WHO study; alcohol; drug use; reliability; validity; dependence; harmful use ID CIDI AB The WHO Study on the reliability and validity of the alcohol and drug use disorder instruments is an international study which has taken place in 12 centres in ten countries, aiming to test the reliability and validity of three diagnostic instruments for alcohol and drug use disorders: the Composite International Diagnostic Interview (CIDI), the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and a special version of the Alcohol Use Disorder and Associated Disabilities Interview schedule-alcohol/drug-revised (AUDADIS-ADR). The purpose of the reliability and validity (R&V) study is to further develop the alcohol and drug sections of these instruments so that a range of substance-related diagnoses can be made in a systematic, consistent, and reliable way. The study focuses on new criteria proposed in the tenth revision of the International Classification of Diseases (ICD-10) and the fourth revision of the diagnostic and statistical manual of mental disorders (DSM-IV) for dependence, harmful use and abuse categories for alcohol and psychoactive substance use disorders. A systematic study including a scientifically rigorous measure of reliability (i.e. 1 week test-retest reliability) and validity (i.e. comparison between clinical and non-clinical measures) has been undertaken. Results have yielded useful information on reliability and validity of these instruments at diagnosis, criteria and question level. Overall the diagnostic concordance coefficients (kappa, kappa) were very good for dependence disorders (0.7-0.9), but were somewhat lower for abuse and harmful use categories. The comparisons among instruments and independent clinical evaluations and debriefing interviews gave important information about possible sources of unreliability, and provided useful clues on the applicability and consistency of nosological concepts across cultures. (C) 1997 Elsevier Science Ireland Ltd. C1 WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. UNIV CONNECTICUT,CTR HLTH,DEPT PSYCHIAT,FARMINGTON,CT 06032. UNIV COLL IBADAN HOSP,DEPT PSYCHIAT,IBADAN,NIGERIA. UNIV ATHENS,DEPT PSYCHIAT,ATHENS,GREECE. HACETTEPE UNIV,DEPT PSYCHIAT,ANKARA,TURKEY. ST VINCENTS HOSP,CLIN RES UNIT ANXIETY DISORDERS,DARLINGHURST,NSW 2010,AUSTRALIA. CTR HOSP LUXEMBOURG,SERV NEUROPSYCHIAT,LUXEMBOURG,LUXEMBOURG. ROYAL PRINCE ALFRED HOSP,DEPT PSYCHIAT,CAMPERDOWN,NSW 2050,AUSTRALIA. MINIST HLTH WELF & SPORTS,INSPECTORATE HLTH CARE,RIJSWIJK,NETHERLANDS. BEHAV SCI RES INST,OFF DEAN ACAD AFFAIRS,SAN JUAN,PR. HOSP PSYCHIAT,TIMIS,ROMANIA. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY. ADDICT RES FDN,TORONTO,ON M5S 2S1,CANADA. UNIV AMSTERDAM,AMSTERDAM INST ADDICT RES,AMSTERDAM,NETHERLANDS. NIMH,DIV EPIDEMIOL & SERV RES,ROCKVILLE,MD 20857. NIDA,DIV CLIN RES,ROCKVILLE,MD. NIAAA,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD 20852. UNIV GENEVA,DEPT PSYCHIAT,GENEVA,SWITZERLAND. RP Ustun, B (reprint author), WHO,DIV MENTAL HLTH & PREVENT SUBSTANCE ABUSE,UNIT EPIDEMIOL CLASSIFICAT & ASSESSMENT,CH-1211 GENEVA 27,SWITZERLAND. OI Peters, Lorna/0000-0003-2704-0531 FU NIMH NIH HHS [UO1MH35883] NR 19 TC 202 Z9 203 U1 7 U2 17 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 25 PY 1997 VL 47 IS 3 BP 161 EP 169 DI 10.1016/S0376-8716(97)00087-2 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XV657 UT WOS:A1997XV65700002 PM 9306042 ER PT J AU Chatterji, S Saunders, JB Vrasti, R Grant, BF Hasin, D Mager, D AF Chatterji, S Saunders, JB Vrasti, R Grant, BF Hasin, D Mager, D TI Reliability of the alcohol and drug modules of the alcohol use disorder and associated disabilities interview schedule alcohol/drug-revised (AUDADIS-ADR): an international comparison SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE alcohol use disorder; disabilities; drug AB The purpose of the present study was to examine the test-retest reliability of the alcohol and drug modules of the AUDADIS-ADR in three sites: Bangalore, India, Jebel, Romania and Sydney, Australia. The overall reliability of ICD-10, DSM-IV and DSM-III-R dependence diagnoses was found to be good to excellent for each substance, including alcohol, for each time frame, regardless of whether the total sample or user subsample figured into the calculations. Reliability associated with corresponding harmful use and abuse diagnoses were mixed, but generally lower. Reliability statistics for Bangalore were generally lower than those of the Jebel and Sydney sites, particularly for alcohol diagnostic criteria. Implications of these results are discussed, in conjunction with results from the discrepancy interview protocol analyses within sites, in terms of future revisions to the AUDADIS-ADR and its training procedures tailored to developing countries. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV SYDNEY,CTR DRUG & ALCOHOL STUDIES,ROYAL PRINCE ALFRED HOSP,DEPT PSYCHOL MED,SYDNEY,NSW 2050,AUSTRALIA. HOSP PSYCHIAT,JEBEL TIMIS 1922,ROMANIA. NIAAA,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY 10032. COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY 10032. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. RP Chatterji, S (reprint author), NATL INST MENTAL HLTH & NEUROSCI,POST BAG 2900,BANGALORE 560029,KARNATAKA,INDIA. NR 16 TC 215 Z9 215 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 25 PY 1997 VL 47 IS 3 BP 171 EP 185 DI 10.1016/S0376-8716(97)00088-4 PG 15 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XV657 UT WOS:A1997XV65700003 PM 9306043 ER PT J AU Cottler, LB Grant, BF Blaine, J Mavreas, V Pull, C Hasin, D Compton, WM RubioStipec, M Mager, D AF Cottler, LB Grant, BF Blaine, J Mavreas, V Pull, C Hasin, D Compton, WM RubioStipec, M Mager, D TI Concordance of DSM-IV alcohol and drug use disorder criteria and diagnoses as measured by AUDADIS-ADR, CIDI and SCAN SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of College-on-Problems-of-Drug-Dependence CY 1993 CL SCOTTSDALE, AZ SP Coll Problems Drug Dependence DE diagnoses; DSM-IV alcohol; drug ID INTERVIEW SCHEDULE; RELIABILITY; SAM AB This study was designed to examine the agreement of DSM-IV alcohol and drug use disorder diagnoses generated by three WHO/NIH diagnostic instruments, the AUDADIS-ADR, the CIDI, and the SCAN. This substudy, conducted in three countries, Greece; Luxembourg, and the United States: was parr of the larger joint project on diagnosis and classification of mental disorders and alcohol and drug-related problems, which was initiated to evaluate the cross-cultural applicability of the instruments and the criteria. Overall, concordance among the three assessments was good for alcohol and opiate dependence, fair to good for cocaine and sedative dependence, and low for amphetamine dependence. Cannabis dependence concordance was significantly more discrepant than any other substance. Agreement on abuse was low for all substances examined. In addition, the concordance of DSM-IV criteria for each substance was examined. Finally, reasons for discrepancies in responses among assessments were examined: based on discrepancy interview protocol methodology. Further investigation will help to refine these instruments in order to provide a more thorough understanding of alcohol and drug abuse diagnoses. (C) 1997 Elsevier Science Ireland Ltd. C1 NIAAA,BIOMETRY BRANCH,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD 20852. NIDA,TREATMENT RES BRANCH,DIV CLIN & SERV RES,ROCKVILLE,MD 20857. UNIV ATHENS,SCH MED,EGINIT HOSP,DEPT PSYCHIAT,ATHENS 11528,GREECE. CTR HOSP LUXEMBOURG,SERV NEUROPSYCHIAT,L-1210 LUXEMBOURG,LUXEMBOURG. COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK STATE PSYCHIAT INST,DEPT PSYCHIAT,NEW YORK,NY 10032. UNIV PUERTO RICO,BEHAV SCI RES INST,DEPT PSYCHIAT,SAN JUAN,PR 00936. RP Cottler, LB (reprint author), WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,40 N KINGS HIGHWAY,SUITE 4,ST LOUIS,MO 63108, USA. NR 22 TC 236 Z9 237 U1 5 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 25 PY 1997 VL 47 IS 3 BP 195 EP 205 DI 10.1016/S0376-8716(97)00090-2 PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XV657 UT WOS:A1997XV65700005 PM 9306045 ER PT J AU Pull, CB Saunders, JB Mavreas, V Cottler, LB Grant, BF Hasin, DS Blaine, J Mager, D Ustun, BT AF Pull, CB Saunders, JB Mavreas, V Cottler, LB Grant, BF Hasin, DS Blaine, J Mager, D Ustun, BT TI Concordance between ICD-10 alcohol and drug use disorder criteria and diagnoses as measured by the AUDADIS-ADR, CIDI and SCAN: results of a cross-national study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE ICD-10 alcohol; drug; diagnoses ID INTERVIEW SCHEDULE AB Agreement between the AUDADIS-ADR, CIDI and SCAN in case identification for ICD-10 alcohol and drug use disorders and diagnostic criteria was investigated in three countries, Luxembourg, Greece and the US. Overall, agreement for ICD-10 dependence diagnoses between the three instruments was fair to good for alcohol, opioids and cocaine, but generally lower for dependence diagnoses for other substance. In contrast, concordance between instruments for harmful use diagnoses was extremely poor for all substances. Implications of these major findings are discussed in terms of the relationship between prevalence, reliability and concordance and indications and cautions regarding cross-instrument comparisons. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV SYDNEY,CTR DRUG & ALCOHOL STUDIES,ROYAL PRINCE ALFRED HOSP,DEPT PSYCHOL MED,SYDNEY,NSW 2050,AUSTRALIA. UNIV ATHENS,EGINIT HOSP,SCH MED,DEPT PSYCHIAT,GR-11528 ATHENS,GREECE. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. NIAAA,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. NIDA,DIV CLIN & SERV RES,ROCKVILLE,MD 20857. WHO,EPIDEMIOL & MANAGERIAL SUPPORT DIV MENTAL HLTH,CH-1211 GENEVA 27,SWITZERLAND. RP Pull, CB (reprint author), CTR HOSP LUXEMBOURG,SERV NEUROPSYCHIAT,4 RUE BARBLE,L-1210 LUXEMBOURG,LUXEMBOURG. NR 19 TC 166 Z9 168 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 25 PY 1997 VL 47 IS 3 BP 207 EP 216 DI 10.1016/S0376-8716(97)00091-4 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XV657 UT WOS:A1997XV65700006 PM 9306046 ER PT J AU Hasin, D Grant, BF Cottler, L Blaine, J Towle, L Ustun, B Sartorius, N AF Hasin, D Grant, BF Cottler, L Blaine, J Towle, L Ustun, B Sartorius, N TI Nosological comparisons of alcohol and drug diagnoses: a multisite, multi-instrument international study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE alcohol dependence; drug dependence; alcohol abuse; drug abuse; harmful use; substance use disorders ID SUBSTANCE USE DISORDERS; UNITED-STATES 1988; DSM-III-R; DEPENDENCE; ABUSE AB International nosological research was conducted to determine cross-system agreement on alcohol and drug dependence and harmful use (abuse). ICD-10, DSM-IV and DSM-III-R diagnoses were compared in 1811 subjects from a variety of treatment and other types of settings from 12 sites around the world. Three diagnostic instruments were used: the Alcohol Use Disorders and Associated Disabilities Interview Schedule-Alcohol/Drug-Revised (AUDADIS-ADR), the composite international diagnostic interview (CIDI), and the schedules for clinical assessment in neuropsychiatry (SCAN). At seven of the study sites, two or more of these instruments were used. Results for dependence diagnoses showed excellent cross-system agreement across sites and instruments, especially for current diagnoses. Cross-system agreement for harmless use (abuse) was much lower and less consistent. Geographic location or culture appeared to have little influence on the results for either dependence or harmful use. (C) 1997 Elsevier Science Ireland Ltd. C1 COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY 10032. NIAAA,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. NIDA,DIV CLIN & SERV RES,ROCKVILLE,MD 20857. NIAAA,BETHESDA,MD 20892. WHO,EPIDEMIOL & MANAGERIAL SUPPORT,DIV MENTAL HLTH & PREVENT SUBSTANCE ABUSE,CH-1211 GENEVA 27,SWITZERLAND. WHO,DIV MENTAL HLTH,CH-1211 GENEVA 27,SWITZERLAND. RP Hasin, D (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,722 W 168TH ST,BOX 123,NEW YORK,NY 10032, USA. NR 25 TC 141 Z9 141 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 25 PY 1997 VL 47 IS 3 BP 217 EP 226 DI 10.1016/S0376-8716(97)00092-6 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XV657 UT WOS:A1997XV65700007 PM 9306047 ER PT J AU Steinbach, OC Wolffe, AP Rupp, RAW AF Steinbach, OC Wolffe, AP Rupp, RAW TI Somatic linker histones cause loss of mesodermal competence in Xenopus SO NATURE LA English DT Article ID GENE-TRANSCRIPTION; MYOD EXPRESSION; EARLY RESPONSE; IN-VIVO; EMBRYOS; INDUCTION; LAEVIS; PROTEIN; CELLS; EMBRYOGENESIS AB In Xenopus, cells from the animal hemisphere are competent to form mesodermal tissues from the morula through to the blastula stage(1). Loss of mesodermal competence at early gastrula is programmed cell-autonomously, and occurs even in single cells at the appropriate stage(2). To determine the mechanism by which this occurs, we have been investigating a concomitant, global change in expression of H1 linker histone subtypes. H1 histones are usually considered to be general repressors of transcription(3), but in Xenopus they are increasingly thought to have selective functions in transcriptional regulation(4-6). Xenopus eggs and embryos at stages before the midblastula transition(7) are deficient in histone H1 protein, but contain an oocyte-specific variant called histone B4 or H1M. After the midblastula transition, histone B4 is progressively substituted by three somatic histone H1 variants, and replacement is complete by early neurula(8,9). Here we report that accumulation of somatic H1 protein is rate limiting for the loss of mesodermal competence. This involves selective transcriptional silencing of regulatory genes required for mesodermal differentiation pathways, like muscle, by somatic, but not maternal, H1 protein. C1 MAX PLANCK GESELL, FRIEDRICH MIESCHER LAB, D-72076 TUBINGEN, GERMANY. NICHHD, MOL EMBRYOL LAB, NIH, BETHESDA, MD 20892 USA. NR 29 TC 148 Z9 152 U1 0 U2 4 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 25 PY 1997 VL 389 IS 6649 BP 395 EP 399 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX675 UT WOS:A1997XX67500056 PM 9311783 ER PT J AU Ladenson, PW Braverman, LE Mazzaferri, EL BruckerDavis, F Cooper, DS Garber, JR Wondisford, FE Davies, TF DeGroot, LJ Daniels, GH Ross, DS Weintraub, BD AF Ladenson, PW Braverman, LE Mazzaferri, EL BruckerDavis, F Cooper, DS Garber, JR Wondisford, FE Davies, TF DeGroot, LJ Daniels, GH Ross, DS Weintraub, BD TI Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HAMSTER OVARY CELLS; SERUM THYROGLOBULIN; STIMULATING HORMONE; CANCER; I-131; BIOACTIVITY; DIAGNOSIS AB Background To detect recurrent disease in patients who have had differentiated thyroid cancer, periodic withdrawal of thyroid hormone therapy may be required to raise serum thyrotropin concentrations to stimulate thyroid tissue so that radioiodine (iodine-131) scanning can be performed. However, withdrawal of thyroid hormone therapy causes hypothyroidism. Administration of recombinant human thyrotropin stimulates thyroid tissue without requiring the discontinuation of thyroid hormone thera py. Methods One hundred twenty-seven patients with thyroid cancer underwent whole-body radioiodine scanning by two techniques: first after receiving two doses of thyrotropin while thyroid hormone therapy was continued, and second after the withdrawal of thyroid hormone therapy. The scans were evaluated by reviewers unaware of the conditions of scanning. The serum thyroglobulin concentrations and the prevalence of symptoms of hypothyroidism and mood disorders were also determined. Results Sixty-two of the 127 patients had positive whole-body radioiodine scans by one or both techniques. The scans obtained after stimulation with thyrotropin were equivalent to the scans obtained after withdrawal of thyroid hormone in 41 of these patients (66 percent), superior in 3 (5 percent), and inferior in 18 (29 percent). When the 65 patients with concordant negative scans were included, the two scans were equivalent in 106 patients (83 percent). Eight patients (13 percent of those with at least one positive scan) were treated with radioiodine on the basis of superior scans done after withdrawal of thyroid hormone. Serum thyroglobulin concentrations increased in 15 of 35 tested patients: 14 after withdrawal of thyroid hormone and 13 after administration of thyrotropin. Patients had more symptoms of hypothyroidism (P<0.001) and dysphoric mood states (P<0.001) after withdrawal of thyroid hormone than after administration of thyrotropin. Conclusions Thyrotropin stimulates radioiodine uptake for scanning in patients with thyroid cancer, but the sensitivity of scanning after the administration of thyrotropin is less than that after the withdrawal of thyroid hormone. Thyrotropin scanning is associated with fewer symptoms and dysphoric mood states. (C) 1997, Massachusetts Medical Society. C1 JOHNS HOPKINS UNIV, SCH MED, DIV ENDOCRINOL & METAB, BALTIMORE, MD USA. JOHNS HOPKINS UNIV, SCH MED, THYROID TUMOR CTR, BALTIMORE, MD USA. UNIV MASSACHUSETTS, MED CTR, DIV ENDOCRINOL & METAB, WORCESTER, MA USA. OHIO STATE UNIV, DEPT INTERNAL MED, COLUMBUS, OH 43210 USA. NIDDKD, NIH, BETHESDA, MD 20892 USA. SINAI HOSP, DIV ENDOCRINOL & METAB, BALTIMORE, MD 21215 USA. BETH ISRAEL HOSP, THYROID UNIT, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, DIV ENDOCRINOL & METAB, BOSTON, MA 02215 USA. UNIV CHICAGO, MED CTR, THYROID STUDY UNIT, CHICAGO, IL 60637 USA. MASSACHUSETTS GEN HOSP, THYROID UNIT, BOSTON, MA 02114 USA. MT SINAI MED CTR, DIV ENDOCRINOL & METAB, NEW YORK, NY 10029 USA. RI Sgouros, George/A-6767-2008 NR 26 TC 281 Z9 289 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 25 PY 1997 VL 337 IS 13 BP 888 EP 896 DI 10.1056/NEJM199709253371304 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA XX302 UT WOS:A1997XX30200004 PM 9302303 ER PT J AU Kramer, BS Klausner, RD AF Kramer, BS Klausner, RD TI Grappling with cancer - Defeatism versus the reality of progress SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID UNITED-STATES RP Kramer, BS (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 29 Z9 30 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 25 PY 1997 VL 337 IS 13 BP 931 EP 934 DI 10.1056/NEJM199709253371312 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XX302 UT WOS:A1997XX30200012 PM 9302311 ER PT J AU Duh, FM Scherer, SW Tsui, LC Lerman, MI Zbar, B Schmidt, L AF Duh, FM Scherer, SW Tsui, LC Lerman, MI Zbar, B Schmidt, L TI Gene structure of the human MET proto-oncogene SO ONCOGENE LA English DT Article DE MET proto-oncogene; HGF/SF receptor; renal carcinoma ID RENAL-CELL CARCINOMA; TYROSINE KINASE; C-MET; GROWTH-FACTOR; HGF RECEPTOR; OVEREXPRESSION; SEQUENCE; MUTATION; LINE; KIT AB By direct sequencing of cosmids using primers designed from the known cDNA sequence, we identified 19 exons in the human MET proto-oncogene, and sequenced the corresponding 5' and 3' exon-intron junctions. By homology search in the database of the Washington University Genome Sequence Center (GSC), we identified one additional exon. These 20 exons, together with a previously reported exon, bring the total exon number of MET to 21. Oligonucleotide primers were designed to amplify each exon and adjacent intronic sequences to permit examination of each exon for mutations. By restriction mapping, we assembled a 110 kb genomic contig that covered almost the entire MET protooncogene, This information is relevant for the screening of recently reported mutations of the MET gene which cause hereditary papillary renal carcinomas and for the search for additional mutations of the same gene which may play a role in the pathogenesis of common human carcinomas including carcinomas of the breast, ovary and pancreas. C1 NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,IMMUNOBIOL LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. HOSP SICK CHILDREN,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. RI Tsui, Lap-chee/A-1081-2010; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 NR 17 TC 37 Z9 38 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 25 PY 1997 VL 15 IS 13 BP 1583 EP 1586 DI 10.1038/sj.onc.1201338 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XX369 UT WOS:A1997XX36900009 PM 9380410 ER PT J AU Gutmann, DH SaporitoIrwin, S DeClue, JE Wienecke, R Guha, A AF Gutmann, DH SaporitoIrwin, S DeClue, JE Wienecke, R Guha, A TI Alterations in the rap1 signaling pathway are common in human gliomas SO ONCOGENE LA English DT Article DE astrocytomas; tumor suppressor gene; tuberous sclerosis complex 2; tuberin ID CELL-LINES; GENE; AMPLIFICATION; TUMORS; PRODUCT; TUBERIN; CDK4; OVEREXPRESSION; NEUROBLASTOMA; EXPRESSION AB Several inherited predisposition to cancer syndromes are associated with the development of nervous system tumors. Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which affected individuals are at risk for developing astrocytomas. One of the genes responsible for this disorder is TSC2, located on chromosome 16p, and encoding a 180 kDa protein (tuberin) that functions in part as a negative regulator of rap1. Previous studies from our laboratory demonstrated that 30% of sporadic astrocytomas have reduced or absent tuberin expression, In addition to loss of tuberin in sporadic astrocytomas, aberrant rap1 mediated signaling may also result from overexpression of rap1. In this study, we test the hypothesis that alterations in the rap1 signaling pathway are frequently observed in certain subsets of gliomas compared to other tumors of the nervous system. Analysis of sporadic astrocytomas and ependymomas demonstrated either increased rap1 or reduced/absent tuberin protein expression in 50-60% of different cohorts of these gliomas, compared to 30-33% of sporadic schwannomas and meningiomas and none of eight oligodendrocyte tumors. These results suggest that alterations in the rap1 signaling pathway are important in the development of certain sporadic human gliomas. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. UNIV TORONTO,MT SINAI HOSP,SAMUEL LUNENFELD RES INST,DIV NEUROSURG,TORONTO,ON M5T 2S8,CANADA. UNIV TORONTO,TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. RP Gutmann, DH (reprint author), WASHINGTON UNIV,SCH MED,DEPT NEUROL,BOX 8111,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. NR 22 TC 31 Z9 31 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 25 PY 1997 VL 15 IS 13 BP 1611 EP 1616 DI 10.1038/sj.onc.1201314 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XX369 UT WOS:A1997XX36900013 PM 9380414 ER PT J AU Hilfiker, KA Brechbiel, MW Rogers, RD Planalp, RP AF Hilfiker, KA Brechbiel, MW Rogers, RD Planalp, RP TI Tricationic metal complexes ([ML][NO3](3), M=Ga,In) of N,N',N''-tris(2-pyridylmethyl)-cis-1,3,5-triaminocyclohexane: Preparation and structure SO INORGANIC CHEMISTRY LA English DT Article ID LIPOPHILIC HEXADENTATE ALUMINUM; LIGAND; 1,4,7-TRIAZACYCLONONANE-N,N',N''-TRIACETATE; GALLIUM; IONS; CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; INDIUM; DESIGN C1 UNIV NEW HAMPSHIRE,DEPT CHEM,DURHAM,NH 03824. UNIV ALABAMA,DEPT CHEM,TUSCALOOSA,AL 35487. NIH,DEPT CHEM,CHEM SECT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 24 TC 30 Z9 30 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD SEP 24 PY 1997 VL 36 IS 20 BP 4600 EP 4603 DI 10.1021/ic9614024 PG 4 WC Chemistry, Inorganic & Nuclear SC Chemistry GA XY361 UT WOS:A1997XY36100048 ER PT J AU Mercer, BM Miodovnik, M Thurnau, GR Goldenberg, RL Das, AF Ramsey, RD Rabello, YA Meis, PJ Moawad, AH Iams, JD VanDorsten, JP Paul, RH Bottoms, SF Merenstein, G Thom, EA Roberts, JM McNellis, D AF Mercer, BM Miodovnik, M Thurnau, GR Goldenberg, RL Das, AF Ramsey, RD Rabello, YA Meis, PJ Moawad, AH Iams, JD VanDorsten, JP Paul, RH Bottoms, SF Merenstein, G Thom, EA Roberts, JM McNellis, D TI Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ANTIMICROBIAL THERAPY; DOUBLE-BLIND; INTRAAMNIOTIC INFECTION; EXPECTANT MANAGEMENT; CLINICAL-TRIALS; GRAM STAIN; AMNIOCENTESIS; PROPHYLAXIS; AMPICILLIN AB Context.-Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent. Objective.-To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity. Design.-Randomized, double-blind, placebo-controlled trial. Setting.-University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Patients.-A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization. Interventions.-Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen, Group B streptococcus (GBS) carriers were identified and treated, Tocolysis and corticosteroids were prohibited after randomization. Main Outcome Measures.-The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth, These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed. Results.-In the total study population, the primary outcome (44.1% vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001). Conclusions.-We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity. C1 UNIV CINCINNATI,CINCINNATI,OH 45221. UNIV OKLAHOMA,OKLAHOMA CITY,OK. UNIV ALABAMA,BIRMINGHAM,AL. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. UNIV SO CALIF,LOS ANGELES,CA 90089. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV CHICAGO,CHICAGO,IL 60637. OHIO STATE UNIV,COLUMBUS,OH 43210. MED UNIV S CAROLINA,CHARLESTON,SC 29425. WAYNE STATE UNIV,DETROIT,MI 48202. UNIV COLORADO,DENVER,CO 80202. UNIV PITTSBURGH,PITTSBURGH,PA 15260. NICHHD,BETHESDA,MD 20892. RP Mercer, BM (reprint author), UNIV TENNESSEE,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,853 JEFFERSON AVE,SUITE E102,MEMPHIS,TN 38103, USA. FU NICHD NIH HHS [U10-HD-21434, U10-HD-27915, U10-HD-27917] NR 37 TC 259 Z9 278 U1 3 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 24 PY 1997 VL 278 IS 12 BP 989 EP 995 DI 10.1001/jama.278.12.989 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XX012 UT WOS:A1997XX01200029 PM 9307346 ER PT J AU Brown, P AF Brown, P TI The risk of bovine spongiform encephalopathy ('mad cow disease') to human health SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; VARIANT; TRANSMISSION AB Some human cases of the transmissible neurodegenerative disorder Creutzfeldt-Jakob disease recently seen in Great Britain are thought to have resulted from eating beef infected with the agent of bovine spongiform encephalopathy. Reasons for and against this presumption are explained, and the question of a similar situation occurring in countries other than Britain-in particular, the United States-is discussed in terms of the existence of scrapie (in sheep) or unrecognized bovine spongiform encephalopathy (in cattle), the practice of recycling nonedible sheep and cattle tissue for animal nutrition, and precautionary measures already taken or under consideration by government agencies. RP Brown, P (reprint author), NINCDS, CENT NERVOUS SYST STUDIES LAB, NIH, BLDG 36, ROOM 5B21, BETHESDA, MD 20892 USA. NR 18 TC 26 Z9 30 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 24 PY 1997 VL 278 IS 12 BP 1008 EP 1011 DI 10.1001/jama.278.12.1008 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XX012 UT WOS:A1997XX01200032 PM 9307349 ER PT J AU Schwenk, F Sauer, B Kukoc, N Hoess, R Muller, W Kocks, C Kuhn, R Rajewsky, K AF Schwenk, F Sauer, B Kukoc, N Hoess, R Muller, W Kocks, C Kuhn, R Rajewsky, K TI Generation of Cre recombinase-specific monoclonal antibodies, able to characterize the pattern of Cre expression in cre-transgenic mouse strains SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE conditional gene targeting; Cre recombinase; monoclonal antibodies ID SITE-SPECIFIC RECOMBINATION; B-CELL DEVELOPMENT; DNA RECOMBINATION; TISSUE-CULTURE; MICE; GENE; LINES; BACTERIOPHAGE-P1; LYMPHOCYTES; POLYMERASE AB Transgene-encoded Cre recombinase can target alteration of loxP-tagged genes to specific cell types and developmental stages in mice, depending on the pattern of transgene expression. To facilitate determination of the latter, we have generated monoclonal anti-Cre antibodies which are specific for distinct epitopes on the recombinase and detect Cre both on immunoblots and intracellularly by immunofluorescence. We demonstrate the usefulness of these antibodies by an analysis of Cre expression in mice carrying a cre-transgene under B cell-specific control. (C) 1997 Elsevier Science B.V. C1 NIDDK,NIH,BETHESDA,MD 20892. DUPONT CO INC,GENET & CANC GRP,WILMINGTON,DE 19880. RP Schwenk, F (reprint author), UNIV COLOGNE,INST GENET,WEYERTAL 121,D-50931 COLOGNE,GERMANY. RI Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 NR 36 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP 24 PY 1997 VL 207 IS 2 BP 203 EP 212 DI 10.1016/S0022-1759(97)00116-6 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA YC359 UT WOS:A1997YC35900011 PM 9368647 ER PT J AU Markovitz, JH Smith, D Raczynski, JM Oberman, A Williams, OD Knox, S Jacobs, DR AF Markovitz, JH Smith, D Raczynski, JM Oberman, A Williams, OD Knox, S Jacobs, DR TI Lack of relations of hostility, negative affect, and high-risk behavior with low plasma lipid levels in the coronary artery risk development in young adults study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Southeastern Lipid Conference CY SEP 06, 1996 CL CALLAWAY GARDENS, GA ID LOW SERUM-CHOLESTEROL; LOW BLOOD CHOLESTEROL; DEPRESSIVE SYMPTOMS; MORTALITY; MEN; SUICIDE; HYPOCHOLESTEROLEMIA; ASSOCIATIONS; PERSONALITY; AGGRESSION AB Background: Previous studies have suggested that low plasma cholesterol levels or cholesterol lowering may increase the risk of suicide and violent death. Increased aggression, risk-taking behavior, or depression has been associated with low cholesterol levels in some studies. Methods: A total of 4240 subjects of the Coronary Artery Risk Development in Young Adults study, aged 23 to 35 years, were included in the study. Analyses were stratified by race (black or white) and sex. Persons in the lowest 10% of plasma total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were compared with the other participants in each race/sex group, using standardized measures of hostility, anger suppression, depressive symptoms, and anxiety. The relations between 5-year change in hostility and 5-year change in lipid levels also were examined. The relations between lipid levels and high-risk behavior leg, violent arguments or having a gun at home) were examined in a subset of subjects. All analyses were adjusted for relevant covariates. Results: In cross-sectional analyses, low total cholesterol levels were not related to any of the psychological measures in any race/sex group. Among black women only, low low-density lipoprotein cholesterol was related to greater anxiety, and low triglycerides were related to lower anger suppression (P less than or equal to.002). Among white men only, increases in hostility during the 5-year follow-up were related to increases in triglycerides (P<.01), but changes in hostility were unrelated to changes in cholesterol levels. Among a subset of 371 subjects with initially elevated total cholesterol (greater than or equal to 5.17 mmol/L [greater than or equal to 200 mg/dL]) and a nonmedicated decrease of 0.52 mmol/L (greater than or equal to 20 mg/dL) or more during 5 years, hostility decreased in a univariate analysis (P<.001). High-risk behaviors also were not associated with low lipid levels. Conclusion: The results do not support a consistent relation between hostility, negative affect, or high-risk behaviors with low lipid levels or lipid-lowering among young adults. C1 UNIV ALABAMA,BEHAV MED UNIT,DEPT MED,BIRMINGHAM,AL 35205. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. RP Markovitz, JH (reprint author), UNIV ALABAMA,DIV PREVENT MED,DEPT MED,1717 11TH AVE S,ROOM 733,BIRMINGHAM,AL 35205, USA. NR 39 TC 26 Z9 26 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 22 PY 1997 VL 157 IS 17 BP 1953 EP 1959 DI 10.1001/archinte.157.17.1953 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XW984 UT WOS:A1997XW98400005 PM 9308507 ER PT J AU Ellenberg, J Siggia, ED Moreira, JE Smith, CL Presley, JF Worman, HJ LippincottSchwartz, J AF Ellenberg, J Siggia, ED Moreira, JE Smith, CL Presley, JF Worman, HJ LippincottSchwartz, J TI Nuclear membrane dynamics and reassembly in living cells: Targeting of an inner nuclear membrane protein in interphase and mitosis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LAMIN-B-RECEPTOR; DREIFUSS MUSCULAR-DYSTROPHY; GREEN FLUORESCENT PROTEIN; INTEGRAL PROTEIN; PORE COMPLEX; MITOTIC PHOSPHORYLATION; DROSOPHILA-MELANOGASTER; ENDOPLASMIC-RETICULUM; LATERAL DIFFUSION; ENVELOPE AB The mechanisms of localization and retention of membrane proteins in the inner nuclear membrane and the fate of this membrane system during mitosis were studied in living cells using the inner nuclear membrane protein, lamin B receptor, fused to green fluorescent protein (LBR-GFP). Photobleaching techniques revealed the majority of LBR-GFP to be completely immobilized in the nuclear envelope (NE) of interphase cells, suggesting a tight binding to heterochromatin and/or lamins. A subpopulation of LBR-GFP within ER membranes, by contrast, was entirely mobile and diffused rapidly and freely (D = 0.41 +/- 0.1 mu m(2)/s). High resolution confocal time-lapse imaging in mitotic cells revealed LBR-GFP redistributing into the interconnected ER membrane system in prometaphase, exhibiting the same high mobility and diffusion constant as observed in interphase ER membranes. LBR-GFP rapidly diffused across the cell within the membrane network defined by the ER, suggesting the integrity of the ER was maintained in mitosis, with little or no fragmentation and vesiculation. At the end of mitosis, nuclear membrane reformation coincided with immobilization of LBR-GFP in ER elements at contact sites with chromatin. LBR-GFP-containing ER membranes then wrapped around chromatin over the course of 2-3 min, quickly and efficiently compartmentalizing nuclear material. Expansion of the NE followed over the course of 30-80 min. Thus, selective changes in lateral mobility of LBR-GFP within the ER/NE membrane system form the basis for its localization to the inner nuclear membrane during interphase. Such changes, rather than vesiculation mechanisms, also underlie the redistribution of this molecule during NE disassembly and reformation in mitosis. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. CORNELL UNIV,DEPT PHYS,ITHACA,NY 14853. NINCDS,LIGHT IMAGING FACIL,NIH,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT ANAT & CELL BIOL,NEW YORK,NY 10032. RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X FU NCI NIH HHS [R01-CA66974] NR 62 TC 519 Z9 533 U1 0 U2 43 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 22 PY 1997 VL 138 IS 6 BP 1193 EP 1206 DI 10.1083/jcb.138.6.1193 PG 14 WC Cell Biology SC Cell Biology GA XX822 UT WOS:A1997XX82200002 PM 9298976 ER PT J AU Farias, MF Gattass, R Pinon, MC Ungerleider, LG AF Farias, MF Gattass, R Pinon, MC Ungerleider, LG TI Tangential distribution of cytochrome oxidase-rich blobs in the primary visual cortex of macaque monkeys SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE striate cortex; VI; modular organization; Macaca mulatta ID ELECTRON-MICROSCOPIC ANALYSIS; STRIATE CORTEX; MONOCULAR ENUCLEATION; QUANTITATIVE LIGHT; SQUIRREL-MONKEY; CEBUS-APELLA; ORGANIZATION; TOPOGRAPHY; PATCHES; HISTOCHEMISTRY AB We studied the tangential distribution of cytochrome c oxidase (CytOx)-rich blobs in four striate cortices of three normal monkeys (Macaca mulatta). The spatial density and cross-sectional area of blobs were analyzed in CytOx-reacted tangential sections of flat-mounted preparations of the striate cortex (V1). Well-delimited CytOx-rich blobs were found in the middle portion of cortical layer III of the V1. Throughout the binocular field representation, the spatial density of blobs was nearly constant with a mean value of four to five blobs per mm(2). In the monocular portions of V1, however, blob spatial density diminished. In all cases, the mean cross-sectional area of blobs was constant in the V1. The small variation of CytOx blob topography with visual field eccentricity contrasts with the variation described in previously published material. (C) 1997 Wiley-Liss, Inc. C1 UNIV FED RIO DE JANEIRO,INST BIOFIS CARLOS CHAGAS FILHO,DEPT NEUROBIOL,BR-21941 RIO JANEIRO,BRAZIL. NIMH,LAB BRAIN & COGNIT,BETHESDA,MD 20892. NR 35 TC 16 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 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 22 PY 1997 VL 386 IS 2 BP 217 EP 228 DI 10.1002/(SICI)1096-9861(19970922)386:2<217::AID-CNE4>3.0.CO;2-4 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA XV823 UT WOS:A1997XV82300004 PM 9295148 ER PT J AU Smrcina, M Majer, P Majerova, E Guerassina, TA Eissenstat, MA AF Smrcina, M Majer, P Majerova, E Guerassina, TA Eissenstat, MA TI Facile stereoselective synthesis of gamma-substituted gamma-amino acids from the corresponding alpha-amino acids SO TETRAHEDRON LA English DT Article ID CYTOCHALASAN SYNTHESIS; DERIVATIVES; INHIBITION; ANALOGS; GLUTAMATE; PEPSTATIN; SODIUM; PEPSIN AB A facile stereoselective method for the synthesis of gamma-substituted, gamma-amino acids from alpha-amino acids was developed. The key step of the procedure is complete reduction of the keto functionality of alpha-amino acyl Meldrum's acid by sodium acetoxyborohydride. The resulting amino alkyl Meldrum's acid undergoes thermal decarboxylative ring closure to a 5-substituted pyrrolidinone which yields, the corresponding gamma-amino acid after basic hydrolysis. The overall yield of the procedure ranges from 40 to 65%. (C) 1997 Elsevier Science Ltd. RP Smrcina, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 21 TC 57 Z9 57 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD SEP 22 PY 1997 VL 53 IS 38 BP 12867 EP 12874 DI 10.1016/S0040-4020(97)00840-5 PG 8 WC Chemistry, Organic SC Chemistry GA XW840 UT WOS:A1997XW84000004 ER PT J AU Keefer, MC Wolff, M Gorse, GJ Graham, BS Corey, L ClementsMann, ML VeraniKetter, N Erb, S Smith, CM Belshe, RB Wagner, LJ McElrath, MJ Schwartz, DH Fast, P Charron, K Reynolds, MJ Zimmerman, E Jones, K Harris, M Frey, SE Kennedy, DJ Israel, H Berry, C Read, B Spitz, T Pacatte, T Dolin, R Reichman, RC Lambert, J Demeter, L Roberts, NJ Pugliese, M Berger, D Burke, J Scott, T Blackstone, E Wright, PF Braeuner, M Rybczyk, GK Crumbo, K Battle, W Cornell, R Owens, D Jennings, M Harbison, MA Hensman, BJ Barr, P Stablein, DM Voss, T Pallas, S Lomax, N Koff, W Lawrence, D Johnston, M Savarese, B Wescott, SL AF Keefer, MC Wolff, M Gorse, GJ Graham, BS Corey, L ClementsMann, ML VeraniKetter, N Erb, S Smith, CM Belshe, RB Wagner, LJ McElrath, MJ Schwartz, DH Fast, P Charron, K Reynolds, MJ Zimmerman, E Jones, K Harris, M Frey, SE Kennedy, DJ Israel, H Berry, C Read, B Spitz, T Pacatte, T Dolin, R Reichman, RC Lambert, J Demeter, L Roberts, NJ Pugliese, M Berger, D Burke, J Scott, T Blackstone, E Wright, PF Braeuner, M Rybczyk, GK Crumbo, K Battle, W Cornell, R Owens, D Jennings, M Harbison, MA Hensman, BJ Barr, P Stablein, DM Voss, T Pallas, S Lomax, N Koff, W Lawrence, D Johnston, M Savarese, B Wescott, SL TI Safety profile of phase I and II preventive HIV type 1 envelope vaccination: Experience of the NIAID AIDS Vaccine Evaluation Group SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP160 RECOMBINANT VACCINIA; GLYCOPROTEIN GP120; CANDIDATE VACCINE; POSTVACCINAL SARCOMAS; IMMUNE-RESPONSES; NERVOUS-SYSTEM; PROTEIN GP120; NAIVE ADULTS; HEAVY-CHAINS AB The NIAID-sponsored AIDS Vaccine Evaluation Group was established in 1988 to perform phase I/II clinical trials with candidate preventive HIV-1 vaccines. This report includes safety data from 1398 HIV-negative, healthy volunteers who were enrolled into 25 phase I and 1 phase II multicentered, randomized, double-blind studies evaluating seven recombinant HIV-1 envelope vaccines, two V3 loop synthetic peptide vaccines, and two live poxvirus-vectored recombinant envelope vaccines. All studies but three were placebo controlled; the placebo was either the adjuvant alone or, in studies of recombinant poxvirus vaccines, it was the vector with no gene insert or a non-HIV gene insert, All candidate vaccines were generally well tolerated. The only adverse effects that were clearly related to vaccination were occasional acute local and systemic reactions that were associated with the adjuvants. Three adjuvants in particular were associated with moderate to severe local reactions: alum plus deoxycholate (ImmunoAg), MTP-PE (Biocine Corp.), and QS21 (Genentech, Inc.). MTP-PE was also associated with self-limited severe systemic reactions, There were no serious adverse laboratory toxicities and no evidence of significant immunosuppressive events after receipt of the candidate vaccines. A few volunteers experienced symptoms that might relate to an underlying immunopathologic mechanism (rash, hemolytic anemia, arthralgia), but their presentations were mild and their incidence was low. Eleven volunteers were diagnosed with malignancies during or after their participation, which was within the 95% confidence interval of the number of cases predicted by the National Cancer Institute SEER (Program for cancer surveillance, epidemiology, and end result reporting) database. In conclusion, the envelope-based recombinant or synthetic candidate HIV-1 vaccines appear to be safe and this work has prepared the way for the testing of increasingly complex candidate HIV-1 vaccines. C1 EMMES CORP,POTOMAC,MD 20854. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63110. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37232. UNIV WASHINGTON,SCH MED,SEATTLE,WA 98144. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. NIAID,DIV AIDS,ROCKVILLE,MD 20892. RP Keefer, MC (reprint author), UNIV ROCHESTER,MED CTR,SCH MED & DENT,DEPT MED,INFECT DIS UNIT,POB 689,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NIAID NIH HHS [N01-AI-05065, N01-AI-45208, N01-AI-05063] NR 66 TC 65 Z9 70 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 20 PY 1997 VL 13 IS 14 BP 1163 EP 1177 DI 10.1089/aid.1997.13.1163 PG 15 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XW124 UT WOS:A1997XW12400001 PM 9310283 ER PT J AU Li, YX Schaffner, AE Li, HR Nelson, R Barker, JL AF Li, YX Schaffner, AE Li, HR Nelson, R Barker, JL TI Proton-induced cation current in embryonic rat spinal cord neurons changes ion dependency over time in vitro SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE proton; calcium channel; sodium channel; rat embryo; spinal cord; neuron ID INDUCED SODIUM CURRENT; ROOT GANGLION NEURONS; CALCIUM CHANNELS; SENSORY NEURONS; TASTE CELLS; MECHANISM; PERMEATION; PATCHES AB A rapid increase in proton concentration [H+](o) induces Na+ conductance in a variety of cell types. Here we report that H+ trigger a cation-selective channel whose ion dependency changes over time in culture. Whole-cell recordings of ventral spinal cord neurons dissociated at E15 and cultured for up to 14 days revealed that more than 80% had H+-induced inward current responses exhibiting a rapid decay phase. The current response was activated beginning about pH 6.8. Following decay, several minutes were required for complete recovery. More modest decreases in pH, which by themselves failed to activate this current, depressed those triggered by effective changes in pH. The currents recorded from cells in culture for less than 7 days could be abolished completely in the absence of Ca2+ and persisted in Na+-free and Ba2+-containing solutions. Ensemble analysis of current fluctuations recorded at the peak of the current allowed us to estimate a unitary channel conductance of 7.0 pS and a mean open time of 4.1 ms. In neurons cultured 2 weeks or more, protons induced an inward current response with similar kinetic properties, but with [Na+](o) dependency. Thus, proton-activated cation conductance in embryonic rat spinal cord neurons is self-limiting and involves brief openings of cation-selective channels whose ion dependency changes over time in culture. (C) 1997 Elsevier Science B.V. C1 NINCDS,NEUROPHYSIOL LAB,NIH,BETHESDA,MD 20892. NR 23 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD SEP 20 PY 1997 VL 102 IS 2 BP 261 EP 266 DI 10.1016/S0165-3806(97)00102-8 PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA XZ455 UT WOS:A1997XZ45500012 ER PT J AU Liu, JM Young, NS Walsh, CE CottlerFox, M Carter, C Dunbar, C Barrett, AJ Emmons, R AF Liu, JM Young, NS Walsh, CE CottlerFox, M Carter, C Dunbar, C Barrett, AJ Emmons, R TI Retroviral mediated gene transfer of the Fanconi anemia complementation group C gene to hematopoietic progenitors of group C patients SO HUMAN GENE THERAPY LA English DT Article ID AUTOLOGOUS BONE-MARROW; STEM-CELLS; TRANSPLANTATION; EXPRESSION; MUTATION; FACC AB Fanconi anemia (FA) is a rare genetic disorder characterized by progressive pancytopenia, congenital abnormalities, and a predisposition to malignancy. Therapy is currently limited to allogeneic marrow transplantation; patients lacking a suitable donor usually die from aplasia or acute leukemia. Recently, mutation in a novel gene named FACC (Fanconi anemia C-complementing) has been identified as causing one type of FA. FACC mutations, which introduce splicing errors or stop codons, have been identified in similar to 15% of FA patients. We have recently been successful in functional complementation of four FA cell lines using retroviral vectors to transfer a copy of the normal FACC gene. We also analyzed the ability of our viral vectors to functionally correct hematopoietic progenitor cells from a patient bearing a splice donor mutation. As for the lymphoid cell lines, these CD34-enriched cells were extremely sensitive to MMC. After infection of these progenitor cells with viral vectors bearing normal FACC, the progenitors gave rise to increased numbers of colonies both in the absence and presence of up to 5 nM MMC, whereas control cells were completely destroyed by 1 nM MMC. In summary, we have demonstrated that: (1) retroviral vectors can be engineered to transfer a normal FACC gene to FA(C) lymphoid cell lines and primary hematopoietic cells; (2) introduction of a normal FACC gene into CD34(+) progenitors markedly enhances their growth in the absence and presence of MMC. This study is designed to determine whether hematopoietic progenitors transduced with the normal FACC gene can be reinfused safely into FA(C) patients. CD34(+) cells obtained from G-CSF mobilized peripheral blood will be transduced ex vivo over a 72-hour period in the presence of IL-3, IL-6, and Stem Cell Factor with the FACC retroviral vector. These transduced cells will be reinfused into FA(C) patients. Patients will be monitored for toxicities as well as evidence of successful gene transfer and expression. The procedure will be repeated up to a total of 4 times with each treatment 2-4 months apart. Theoretically, these rescued stem cells should have a selective growth advantage within the hypoplastic FA marrow environment in vivo. RP Liu, JM (reprint author), NHLBI,HEMATOL BRANCH,NIH,BLDG 10,RM 7C103,BETHESDA,MD 20892, USA. NR 20 TC 26 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP 20 PY 1997 VL 8 IS 14 BP 1715 EP 1730 DI 10.1089/hum.1997.8.14-1715 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XY914 UT WOS:A1997XY91400010 PM 9322874 ER PT J AU Linde, K Clausius, N Ramirez, G Melchart, D Eitel, N Hedges, LV Jonas, WB AF Linde, K Clausius, N Ramirez, G Melchart, D Eitel, N Hedges, LV Jonas, WB TI Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebo-controlled trials SO LANCET LA English DT Review ID HOMEOPATHIC PREPARATION; RHEUMATOID-ARTHRITIS; PUBLICATION BIAS; COMPLEMENTARY MEDICINE; GENERAL-PRACTITIONERS; ALTERNATIVE MEDICINE; SYSTEMATIC REVIEWS; GALPHIMIA GLAUCA; ARNICA-MONTANA; POLLINOSIS AB Background Homoeopathy seems scientifically implausible, but has widespread use. We aimed to assess whether the clinical effect reported in randomised controlled trials of homoeopathic remedies is equivalent to that reported for placebo. Methods We sought studies from computerised bibliographies and contacts with researchers, institutions, manufacturers, individual collectors, homoeopathic conference proceedings, and books. We included all languages. Double-blind and/or randomised placebo-controlled trials of clinical conditions were considered. Our review of 186 trials identified 119 that met the inclusion criteria. 89 had adequate data for meta-analysis, and two sets of trial were used to assess reproducibility. Two reviewers assessed study quality with two scales and extracted data for information on clinical condition, homoeopathy type, dilution, ''remedy'', population, and outcomes. Findings The combined odds ratio for the 89 studies entered into the main meta-analysis was 2.45 (95% CI 2.05, 2.93) in favour of homoeopathy. The odds ratio for the 26 good-quality studies was 1.66 (1.33, 2.08), and that corrected for publication bias was 1.78 (1.03, 3.10). Four studies on the effects of a single remedy on seasonal allergies had a pooled odds ratio for ocular symptoms at 4 weeks of 2.03 (1.51, 2.74). Five studies on postoperative ileus had a pooled mean effect-size-difference of -0.22 standard deviations (95% CI -0.36, -0.09) for flatus, and -0.18 SDs (-0.33, -0.03) for stool (both p<0.05). Interpretation The results of our meta-analysis are not compatible with the hypothesis that the clinical effects of homoeopathy are completely due to placebo. However, we found insufficient evidence from these studies that homoeopathy is clearly efficacious for any single clinical condition. Further research on homoeopathy is warranted provided it is rigorous and systematic. C1 NIH,OFF ALTERNAT MED,BETHESDA,MD 20892. TECH UNIV MUNICH,MUNCHENER MODELL,CTR COMPLEMENTARY MED RES,D-8000 MUNICH,GERMANY. UNIV N TEXAS,HLTH SCI CTR,DEPT PUBL HLTH & PREVENT MED,FT WORTH,TX. UNIV MUNICH,CHIRURG KLIN & POLIKLIN INNENSTADT,MUNICH,GERMANY. UNIV CHICAGO,DEPT EDUC,CHICAGO,IL 60637. OI Linde, Klaus/0000-0002-2902-970X NR 145 TC 519 Z9 529 U1 23 U2 131 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 20 PY 1997 VL 350 IS 9081 BP 834 EP 843 DI 10.1016/S0140-6736(97)02293-9 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA XX401 UT WOS:A1997XX40100009 PM 9310601 ER PT J AU Robbins, JB Towne, DW Gotschlich, EC Schneerson, R AF Robbins, JB Towne, DW Gotschlich, EC Schneerson, R TI ''Love's labours lost'': failure to implement mass vaccination against group A meningococcal meningitis in sub-Saharan Africa SO LANCET LA English DT Editorial Material ID GROUP-A; NEISSERIA-MENINGITIDIS; POLYSACCHARIDE VACCINE; CAPSULAR POLYSACCHARIDE; EPIDEMIC; DISEASE; ANTIBODY; CHILDREN; EFFICACY; AGE C1 ROCKEFELLER UNIV,NEW YORK,NY 10021. RP Robbins, JB (reprint author), NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD 20892, USA. NR 41 TC 53 Z9 53 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 20 PY 1997 VL 350 IS 9081 BP 880 EP 882 DI 10.1016/S0140-6736(97)03227-3 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA XX401 UT WOS:A1997XX40100048 PM 9310615 ER PT J AU Kostenis, E Gomeza, J Lerche, C Wess, J AF Kostenis, E Gomeza, J Lerche, C Wess, J TI Genetic analysis of receptor-G alpha(q) coupling selectivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; G-PROTEIN; MOLECULAR-CLONING; ADRENERGIC-RECEPTORS; TERMINAL MUTATIONS; SYNTHETIC PEPTIDES; LIGAND-BINDING; ALPHA-SUBUNIT; AMINO-ACID; ACTIVATION AB Many different G protein-linked receptors are preferentially coupled to G proteins of the G(q/11) family, To elucidate the molecular basis underlying this selectivity, different G(q/11)-coupled receptors (m3 muscarinic, V1a vasopressin, and gastrin-releasing peptide receptor) were coexpressed (in COS-7 cells) with mutant alpha(s) subunits in which residues present at the C terminus of alpha(s) were replaced with the corresponding alpha(q/11), residues, Remarkably, whereas none of the receptors was able to interact with wild type alpha(s) to a significant extent, all three receptors gained the ability to productively couple to a mutant alpha(s) subunit containing a single Glu --> Asn point mutation at position -3, Moreover, the m3 muscarinic and the Via vasopressin receptors but not the GRP receptor also gained the ability to interact with a mutant alpha(s) subunit containing a single Gln --> Glu point mutation at position -5, indicating that the alpha(q/11) residues present in these mutant G protein constructs play key roles in determining the selectivity of receptor recognition. To identify the site(s) on G(q/11)-coupled receptors that can functionally interact with the C terminus of alpha(q/11) subunits, we next analyzed the ability of a series of hybrid m2/m3 muscarinic receptors to interact with a mutant alpha(s) subunit (sq5) in which the last five amino acids of alpha(s) were replaced with the corresponding alpha(q/11) sequence, Similar to the wild type m2 and m3 muscarinic receptors, none of the investigated hybrid receptors was able to efficiently interact with wild type alpha(s). Interestingly, however, three mutant m2 receptors in which different segments of the second and third intracellular loops were replaced with the corresponding m3 receptor sequences were identified, which, in contrast to the G(i/o)-coupled wild type m2 receptor, gained the ability to efficiently activate the sq5 subunit, This observation suggests that multiple intracellular receptor domains form a binding pocket for the C terminus of G protein alpha(q/11) subunits. C1 NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NR 46 TC 60 Z9 61 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 19 PY 1997 VL 272 IS 38 BP 23675 EP 23681 DI 10.1074/jbc.272.38.23675 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100034 PM 9295309 ER PT J AU Malkov, VA Biswas, I CameriniOtero, RD Hsieh, P AF Malkov, VA Biswas, I CameriniOtero, RD Hsieh, P TI Photocross-linking of the NH2-terminal region of Taq MutS protein to the major groove of a heteroduplex DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CROSS-LINKING; ESCHERICHIA-COLI; MISMATCH REPAIR; MUTATION; HOMOLOG; IDENTIFICATION; CONTACT; RNA AB The MutS DNA mismatch repair protein recognizes heteroduplex DNAs containing mispaired or unpaired bases, To identify regions of MutS protein in close proximity to the heteroduplex DNA, we have utilized the photoactivated cross-linking moiety 5-iododeoxyuridine (5-IdUrd), Nucleoprotein complexes of Thermus aquaticus MutS protein bound to monosubstituted 5-IdUrd-containing heteroduplex DNAs were cross-linked with long-wavelength ultraviolet light, Positioning of the 5-IdUrd moiety at one of three positions within the DNA bulge, two nucleotides upstream or three nucleotides downstream of the unpaired base, resulted in an identical subset of cross-linked peptides as determined by proteolytic fingerprinting, The tryptic peptide cross linked to an unpaired 5-IdUrd residue was determined by peptide sequencing to correspond to a highly conserved region spanning residues 25-49. Cross-linking to the bulge nucleotide occurred at Phe-39, indicating that this residue contacts, or is in close proximity to, the unpaired base of a heteroduplex DNA. Site-directed mutagenesis resulting in the substitution of Ala for Phe-39 reduced the affinity of the mutant protein for heteroduplex DNA by roughly 3 orders of magnitude, but had no apparent effect on its ability to dimerize, its thermostability, or its ATPase activity, These results implicate the region in the vicinity of Phe-39 as being crucial for heteroduplex DNA binding by Tag MutS protein. C1 NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NR 21 TC 82 Z9 82 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 19 PY 1997 VL 272 IS 38 BP 23811 EP 23817 DI 10.1074/jbc.272.38.23811 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100053 PM 9295328 ER PT J AU Grenert, JP Sullivan, WP Fadden, P Haystead, TAJ Clark, J Mimnaugh, E Krutzsch, H Ochel, HJ Schulte, TW Sausville, E Neckers, LM Toft, DO AF Grenert, JP Sullivan, WP Fadden, P Haystead, TAJ Clark, J Mimnaugh, E Krutzsch, H Ochel, HJ Schulte, TW Sausville, E Neckers, LM Toft, DO TI The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-FREE SYSTEM; PROGESTERONE-RECEPTOR; IN-VIVO; GLUCOCORTICOID RECEPTOR; RETICULOCYTE LYSATE; TYROSINE KINASE; COMPLEX; HETEROCOMPLEX; ASSOCIATION; RAF AB Many functions of the chaperone, heat shock protein 90 (hsp90), are inhibited by the drug geldanamycin that specifically binds hsp90, We have studied an amino-terminal domain of hsp90 whose crystal structure has recently been solved and determined to contain a geldanamycin binding site. We demonstrate that, in solution, drug binding is exclusive to this domain. This domain also binds ATP linked to Sepharose through the gamma-phosphate. Binding is specific for ATP and ADP and is inhibited by geldanamycin, Mutation of four glycine residues within two proposed ATP binding motifs diminishes both geldanamycin binding and the ATP-dependent conversion of hsp90 to a conformation capable of binding the co-chaperone p23, Since p23 binding requires regions outside the 1-221 domain of hsp90, these results indicate a common site for nucleotides and geldanamycin that regulates the conformation of other hsp90 domains. C1 MAYO CLIN & MAYO FDN,DEPT BIOCHEM & MOL BIOL,ROCHESTER,MN 55905. NCI,NIH,BETHESDA,MD 20892. UNIV VIRGINIA,DEPT PHARMACOL,CHARLOTTESVILLE,VA 22908. FU NHLBI NIH HHS [HL 19242]; NICHD NIH HHS [HD 09140]; NIDDK NIH HHS [DK 46249] NR 57 TC 428 Z9 436 U1 2 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 19 PY 1997 VL 272 IS 38 BP 23843 EP 23850 DI 10.1074/jbc.272.38.23843 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100057 PM 9295332 ER PT J AU Vora, AC Chiu, R McCord, M Goodarzi, G Stahl, SJ Mueser, TC Hyde, CC Grandgenett, DP AF Vora, AC Chiu, R McCord, M Goodarzi, G Stahl, SJ Mueser, TC Hyde, CC Grandgenett, DP TI Avian retrovirus U3 and U5 DNA inverted repeats - Role of nonsymmetrical nucleotides in promoting full-site integration by purified virion and bacterial recombinant integrases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYELOBLASTOSIS VIRUS INTEGRASE; IN-VITRO; CONCERTED INTEGRATION; VIRAL-DNA; PROTEIN INVITRO; SEQUENCES; BINDING; WATER; CLEAVAGE; TERMINI AB The U3 and U5 termini of linear retrovirus DNA contain imperfect inverted repeats that are necessary for the concerted insertion of the termini into the host chromosome by viral integrase. Avian myeloblastosis virus integrase can efficiently insert the termini of retrovirus-like DNA donor substrates (480 base pairs) by a concerted mechanism (full-site reaction) into circular target DNA in vitro. The specific activities of virion-derived avian myeloblastosis virus integrase and bacterial recombinant Rous sarcoma virus (Prague A strain) integrase (similar to 50 nM or less) appear similar upon catalyzing the full-site reaction with 3'-OH recessed wild type or mutant donor substrates, We examined the role of the three nonsymmetrical nucleotides located at the 5th, 8th, and 12th positions in the U3 and U5 15-base pair inverted repeats for their ability to modify the full-site and simultaneously, the half-site strand transfer reactions. Our data suggest that the nucleotide at the 5th position appears to be responsible for the 3-5-fold preference for wild type U3 ends over wild type U5 ends by integrase for concerted integration. Additional mutations at the 5th or 6th position, or both, of U3 or U5 termini significantly increased (similar to 3 fold) the full-site reactions of mutant donors over wild type donors. C1 ST LOUIS UNIV,HLTH SCI CTR,INST MOL VIROL,ST LOUIS,MO 63110. NIAMS,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA16312] NR 30 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 19 PY 1997 VL 272 IS 38 BP 23938 EP 23945 DI 10.1074/jbc.272.38.23938 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100069 PM 9295344 ER PT J AU Modarress, KJ Opoku, J Xu, M Sarlis, NJ Simons, SS AF Modarress, KJ Opoku, J Xu, M Sarlis, NJ Simons, SS TI Steroid-induced conformational changes at ends of the hormone-binding domain in the rat glucocorticoid receptor are independent of agonist versus antagonist activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN PROGESTERONE-RECEPTOR; RETINOIC ACID RECEPTOR; LONG TERMINAL REPEAT; HEPATOMA-CELL LINES; ESTROGEN-RECEPTOR; DEXAMETHASONE 21-MESYLATE; NUCLEAR RECEPTORS; GENE-EXPRESSION; MODULATORY ELEMENT; FUNCTIONAL-GROUP AB The underlying molecular mechanism for the expression of agonist versus antagonist activity for a given receptor-steroid complex is still not known. One attractive hypothesis, based on data from progesterone receptors, is that agonist versus antagonist binding induces unique conformations at the C terminus of receptors, which can be detected by the different fragments produced by partial proteolysis. We now report that the determinants of glucocorticoid receptor (GR)-antagonist complex activity are more complex, Steroid binding did cause a conformational change in the GR that was detected by partial trypsin digestion, as described previously (Simons, S. S., Jr., Sistare, F. D., and Chakraborti, P. K. (1989) J. Biol. Chem. 264, 14493-14497). However, there was no uniformity in the digestion patterns of unactivated or activated receptors bound by a series of six structurally different antagonists including the affinity labeling antiglucocorticoid dexamethasone 21-mesylate, A total of four resistant bands were observed on SDS-polyacrylamide gels in the range of 30-27 kDa. Using a series of point mutations and epitope-specific antibodies, it was determined that the 30-kDa species represented the entire C-terminal sequence of amino acids 518-795, whereas the other bands arose from additional N-terminal and/or C-terminal cleavages, Bioassays with GRs containing various point and deletion mutations failed to reveal any C-terminal alterations that could convert antagonists into biologically active agonists, Thus, the presence or absence of C-terminal amino acids of the GR did not uniquely determine either the appearance of smaller trypsin-resistant fragments or the nature of the biological response of receptor-bound antisteroids. When compared with the current model of the ligand-binding domain, which is based on the x-ray structures of the comparable region of thyroid and retinoic acid receptors, the present results suggest that sequences outside of the model structure are relevant for the binding and biological activity of GRs. C1 NIDDK,STEROID HORMONES SECT,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 74 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 19 PY 1997 VL 272 IS 38 BP 23986 EP 23994 DI 10.1074/jbc.272.38.23986 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100075 PM 9295350 ER EF