FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Zarchin, N Meilin, S Kraut, A Mendelman, A Rifkind, J Mayevsky, A AF Zarchin, N Meilin, S Kraut, A Mendelman, A Rifkind, J Mayevsky, A TI Hemodynamic, metabolic, ionic and electrical changes during cerebral ischemia in aged rats SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Bar Ilan Univ, Dept Life Sci, Ramat Gan, Israel. NIA, LCMB, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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. PY 1997 SU 48 BP S55 EP S55 PG 1 WC Neurosciences SC Neurosciences & Neurology GA ZB328 UT WOS:000072460000226 ER PT J AU Shankar, L Ravindranath, V Boyd, MR Vistica, DT Shankar, SK AF Shankar, L Ravindranath, V Boyd, MR Vistica, DT Shankar, SK TI Histological, histochemical and autoradiographic evidence of in vitro neurotoxic effects of the novel antitumor agent, 9-methoxy-N-2-methylellipticinium acetate SO NEUROTOXICOLOGY LA English DT Article DE 9-methoxy-N-2-methylellipticinum acetate; ellipticines; brain; neurotoxicity; brain slices ID HUMAN BRAIN; CYTOTOXICITY AB 9-Methoxy-N-2-methylellipticinium acetate (MMEA) exhibits selective cytotoxicity towards glial-derived human brain tumor cell lines comprising the U.S. National Cancer Institute preclinical drug screen. Neurotoxic potential of MMEA has been demonstrated in an in vitro model employing sagittal slices of rat brain. Histochemical staining of rat brain slices for lactate dehydrogenase (LDH) activity revealed decreased staining intensity following incubation with increasing concentrations of MMEA (0.1 - 100 mu M). Cytological evaluation of paraffin sections stained with Cresyl Fast Violet revealed neuronal damage delineated by cytoplasmic vacuolation, and distention and fraying of the plasma membrane. No glial or vascular pathology could be discerned. Autoradiography, following exposure to C-14-MMEA, revealed distinct labelling of the large neurons of the brain stem, neurons in the thalamus and pyramidal neurons of the hippocampus, indicating neuronal uptake of the drug. (C) 1997 Intox Press, Inc. C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROPATHOL,BANGALORE 560029,KARNATAKA,INDIA. NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,BANGALORE 560029,KARNATAKA,INDIA. NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 13 TC 1 Z9 1 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PY 1997 VL 18 IS 1 BP 89 EP 95 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA XG646 UT WOS:A1997XG64600014 PM 9215991 ER PT J AU Sriram, K Boyd, MR Vistica, DT Ravindranath, V AF Sriram, K Boyd, MR Vistica, DT Ravindranath, V TI In vitro neurotoxicity of the antitumor agent 9-methoxy-N-2-methylellipticinium acetate (MMEA): Role of brain cytochrome P-450 SO NEUROTOXICOLOGY LA English DT Article DE 9-methoxy-N-2-methylellipticinium acetate; ellipticines; brain; cytochrome P-450; neurotoxicity; brain slices ID NADH-DEHYDROGENASE; INDUCED TOXICITY; DERIVATIVES; INVITRO; CYTOTOXICITY; POTENTIATION; ELLIPTICINE; PROTECTION; INHIBITORS; BINDING AB 9-Methoxy-N-2-methylellipticinium acetate (MMEA) is representative of a series of quaternized ellipticine derivatives that are selectively cytotoxic to human brain tumor cell lines derived from non-neuronal (glial) cells (Acton et al, 1994). In an attempt to determine whether MMEA may exhibit toxicity to normal brain cells, we have examined the effect of the drug, in vitro, using sagittal slices of rat brain. Incubation of rat brain slices in an artificial cerebrospinal fluid medium containing MMEA resulted in dose-dependent leakage of lactate dehydrogenase (LDH) into the surrounding medium. However, other subcellular marker enzymes such as Na+-K(+)ATPase (plasma membrane), cytochrome c oxidase, isocitrate dehydrogenase, NADH- dehydrogenase (mitochondrial), N-acetylglucosaminidase, acid phosphatase (lysosomal), glyceraldehyde-3-phosphate dehydrogenase and enolase (glycolytic enzymes) were unaffected even at the highest tested concentrations of MMEA (10 and 100 mu M). Preincubation of slices with reserpine (1 nM) or, dopamine or serotonin-specific reuptake inhibitors abolished MMEA-induced toxicity in brain slices. Pretreatment of slices with piperonyl butoxide and metyrapone, inhibitors of cytochrome P-450, also prevented the toxicity of MMEA. Further, brain slices prepared from phenobarbital-treated rats showed enhanced sensitivity to MMEA. C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,BANGALORE 560029,KARNATAKA,INDIA. NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,NIH,FREDERICK,MD 21701. NR 28 TC 3 Z9 3 U1 0 U2 1 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PY 1997 VL 18 IS 1 BP 97 EP 104 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA XG646 UT WOS:A1997XG64600015 PM 9215992 ER PT J AU Scortegagna, M Hanbauer, I AF Scortegagna, M Hanbauer, I TI The effect of lead exposure and serum deprivation on mesencephalic primary cultures SO NEUROTOXICOLOGY LA English DT Article DE Pb-2 toxicity; mesencephalic primary cultures; glia; neurons; serum deprivation ID BLOOD-BRAIN-BARRIER; CALCIUM CHANNELS; METAL-IONS; RAT-BRAIN; TOXICITY; CELLS; METALLOTHIONEIN; PROTEIN; NEURONS; ASTROCYTES AB The effect of Pb2+ was studied in embryonic mesencephalic primary cultures that contain neurons and glia. Pb2+ exposure in absence of serum, damaged more efficaciously the cultured cells than Pb2+ exposure in presence of serum. In serum-free medium, Pb2+ elicited mainly necrosis and apoptosis in maximally 13 % of the cells in culture. The glial fibrillary acidic protein (GFAP) content was decreased by Pb2+ exposure in serum-containing medium. The abundance of GFAP was also decreased by serum deprivation that was augmented by the addition of 12.5 mu M Pb2+ in, serum-free medium. A 6h exposure to 6 mu M Pb2+ in serum-free medium also lowered the low affinity H-3-D-aspartate uptake. A 6h exposure of mesencephalic cells to 3-25 mu M Pb2+ in serum-free medium failed to alter the number of tyrosine hydroxylase-and calretinin-immunoreactive cells, whereas, 50 mu M Pb2+ obliterated both cell types. A 6h exposure of cells to 3 mu M Pb2+ in serum-free medium decreased H-3-dopamine uptake by 50 % and 12.5 mu M Pb2+ obliterated it. Addition of albumin to serum-free medium failed to prevent the Pb2+-elicited inhibition of [H-3]-dopamine uptake suggesting that the serum-afforded delay of cell death may not be due to a removal of reactive Pb2+ by protein/chelate formation but rather to the Pb2+-scavenging function of glial cells. Serum deprivation may exacerbate the Pb2+-induced neurotoxicity presumably by impairing the metal scavenging function of astrocytes. (C) 1997 Inter Press, Inc. C1 NHLBI, LAB MOL IMMUNOL, BETHESDA, MD 20892 USA. NR 30 TC 22 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PY 1997 VL 18 IS 2 BP 331 EP 339 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA XU979 UT WOS:A1997XU97900003 PM 9291483 ER PT S AU Alexander, NJ Hecht, NB AF Alexander, NJ Hecht, NB BE Coutifaris, C Mastroianni, L TI Male contraception: future possibilities SO NEW HORIZONS IN REPRODUCTIVE MEDICINE SE INTERNATIONAL CONGRESS, SYMPOSIUM AND SEMINAR SERIES LA English DT Proceedings Paper CT IXth World Congress on Human Reproduction CY MAY 28-JUN 02, 1996 CL PHILADELPHIA, PA C1 NICHHD, Contracept Dev Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP Alexander, NJ (reprint author), NICHHD, Contracept Dev Branch, Populat Res Ctr, NIH, 6100 Execut Blvd,8B13G MSC 7510, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND SN 0969-2622 BN 1-85070-793-6 J9 I C S S PY 1997 VL 12 BP 91 EP 97 PG 7 WC Andrology; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA BK07Y UT WOS:000071091100013 ER PT B AU Bezrukov, SM Vodyanoy, I Pustovoit, MA AF Bezrukov, SM Vodyanoy, I Pustovoit, MA BE Claeys, C Simoen, E TI Noise-facilitated signal transduction in threshold-free non-dynamical systems: Theory and experiment. SO NOISE IN PHYSICAL SYSTEMS AND 1/F FLUCTUATIONS, PROCEEDINGS OF THE 14TH INTERNATIONAL CONFERENCE LA English DT Proceedings Paper CT 14th International Conference on Noise in Physical Systems and l/f Fluctuations (ICNF 97) CY JUL 14-18, 1997 CL LOUVAIN, BELGIUM SP IMEC, European Lab Electr Noise, European Union Network Noise AB We find stochastic resonance in a very general model - a random pulse train where the probability of pulse generation is exponentially dependent on an input which is composed of a sine-wave signal plus random noise. Thus, we demonstrate that SR is a fundamental property of a wide variety of 'kT-driven' systems ranging from semiconductor p-n junctions to modem mesoscopic electronic devices to voltage-dependent ion channels - 'elemental switches' of biological signal computing and sensing. Our results are supported by experiments with voltage-dependent ion channels and computer simulations. C1 NIH, DCRT, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NIH, DCRT, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-02-3141-5 PY 1997 BP 369 EP 372 PG 4 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied SC Acoustics; Engineering; Physics GA BK26Y UT WOS:000071639300081 ER PT J AU Choi, CW Barker, WC Buvat, I Carrasquillo, JA Bacharach, SL AF Choi, CW Barker, WC Buvat, I Carrasquillo, JA Bacharach, SL TI Implications of dual-energy-window (DEW) scatter correction inaccuracies for In-111 quantitative geometric mean imaging SO NUCLEAR MEDICINE COMMUNICATIONS LA English DT Article ID SPECT QUANTIFICATION; MONOCLONAL-ANTIBODY; COMPENSATION; CANCER; SCINTIGRAPHY; FRAGMENTS; CAMERA AB There is increasing clinical interest in the use of quantitative imaging for radiopharmaceuticals labelled with In-111. Dual-energy-window (DEW) scatter correction is a frequently used component of planar geometric mean quantitative imaging, but it is known that the scatter multiplier k suffers from significant dependence on the characteristics of the scatter medium. Phantom studies with a variety of source geometries were carried out to determine the clinical impact of this dependence on the quantitative accuracy of tumour imaging carried out in conjunction with attenuation correction. Spheres of various sizes (5-20 ml volumes) containing approximately 3.7 MBq (100 mu Ci) In-111 were imaged at a variety of depths (4.8-10.5 cm) within an elliptical water-filled phantom, as well as in air. Geometric mean emission images were acquired using a 20% photopeak window at 247 keV and a 10% scatter window at 205 keV. These emission images were corrected for attenuation using measured Tc-99(m) transmission data that were scaled to In-111 photon energies. Scatter correction was performed in two ways: (1) using the standard DEW method and (2) using a modified DEW method that takes into account benign scatter in the detector crystal. Errors in the activity estimates ranged from -4% to +3% for method 1 in water, and -5% to +3% for method 2 in water. In air, method 1 ranged from -13% to -5%, and method 2 ranged from -10% to -1%. Method 1 was found to yield an accuracy equivalent to that of method 2, except in conditions of very low patient scatter, when the modified method behaved significantly better. We conclude that in a variety of realistic geometries, variations in scatter fraction as determined by the DEW scatter correction method combined with appropriate attenuation correction need not inhibit accurate absolute quantitation of spherical 'tumours' labelled with In-111 when using planar imaging. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 25 TC 3 Z9 3 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0143-3636 J9 NUCL MED COMMUN JI Nucl. Med. Commun. PD JAN PY 1997 VL 18 IS 1 BP 79 EP 86 DI 10.1097/00006231-199701000-00016 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WJ116 UT WOS:A1997WJ11600016 PM 9061707 ER PT J AU Benson, DA Boguski, MS Lipman, DJ Ostell, J AF Benson, DA Boguski, MS Lipman, DJ Ostell, J TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The GenBank sequence database incorporates DNA sequences from all available public sources, primarily through the direct submission of sequence data from authors and from large-scale sequencing projects, Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive coverage, GenBank continues to focus on quality control and annotation while expanding data coverage and retrieval services, An integrated retrieval system, known as Entrez, incorporates data from the major DNA and protein sequence databases, along with genome maps and protein structure information, MEDLINE abstracts from published articles describing the sequences are also included as an additional source of biological annotation, Sequence similarity searching is offered through the BLAST family of programs, All of NCBI's services are offered through the World Wide Web, In addition, there are specialized server/client versions as well as FTP and e-mail sewer access. RP Benson, DA (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 9 TC 176 Z9 181 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1997 VL 25 IS 1 BP 1 EP 6 DI 10.1093/nar/25.1.1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD443 UT WOS:A1997WD44300001 PM 9016491 ER PT J AU Hainaut, P Soussi, T Shomer, B Hollstein, M Greenblatt, M Hovig, E Harris, CC Montesano, R AF Hainaut, P Soussi, T Shomer, B Hollstein, M Greenblatt, M Hovig, E Harris, CC Montesano, R TI Database of p53 gene somatic mutations in human tumors and cell lines: Updated compilation and future prospects SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BREAST CANCERS; SUPPRESSOR GENE; URANIUM MINERS; LUNG-CANCER; MUTANTS; WOMEN; TRANSACTIVATION; ETIOLOGY; HOTSPOT; PATTERN AB In recent years, there has been an exponential increase in the number of p53 mutations identified in human cancers, The p53 mutation database consists of a list of point mutations in the p53 gene of human tumors and cell lines, compiled from the published literature and made available through electronic media, The database is now maintained at the International Agency for Research on Cancer (IARC) and is updated twice a year, The current version contains records on 5091 published mutations and is expected to surpass the 6000 mark in the January 1997 release, The database is available in various formats through the European Bioinformatics Institute (EBI) ftp server at: ftp://ftp.ebi.ac.uk/pub/databases/p53/ or by request from IARC (p53database@iarc.fr) and will be searchable through the SRS system in the near future, This report provides a description of the criteria for inclusion of data and of the current formats, a summary of the relevance of p53 mutation analysis to clinical and biological questions, and a brief discussion of the prospects for future developments. C1 INT AGCY RES CANC,F-69372 LYON 08,FRANCE. INSERM,U301,F-75010 PARIS,FRANCE. EUROPEAN MOL BIOL LAB,OUTSTN EUROPEAN BIOINFORMAT INST,CAMBRIDGE CB10 1SD,ENGLAND. GERMAN CANC RES CTR,D-69120 HEIDELBERG,GERMANY. UNIV VERMONT,COLL MED,BURLINGTON,VT 05405. NORWEGIAN RADIUM HOSP,INST CANC RES,N-0310 OSLO,NORWAY. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Hovig, Eivind/H-2474-2011; Hainaut, Pierre /B-6018-2012; OI Hovig, Eivind/0000-0002-9103-1077; Hainaut, Pierre /0000-0002-1303-1610; soussi, thierry/0000-0001-8184-3293 NR 27 TC 253 Z9 259 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1997 VL 25 IS 1 BP 151 EP 157 DI 10.1093/nar/25.1.151 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD443 UT WOS:A1997WD44300037 PM 9016527 ER PT J AU Martinez, E Moore, DD Keller, E Pearce, D Robinson, V MacDonald, PN Simons, SS Sanchez, E Danielsen, M AF Martinez, E Moore, DD Keller, E Pearce, D Robinson, V MacDonald, PN Simons, SS Sanchez, E Danielsen, M TI The Nuclear Receptor Resource project SO NUCLEIC ACIDS RESEARCH LA English DT Article AB We have expanded the original Glucocorticoid Receptor Resource (GRR) database to include several individual resources as part of a larger project called the Nuclear Receptor Resource (NRR), In addition to the GRR, the NRR currently features the Thyroid Hormone Receptor Resource, the Androgen Receptor Resource, the Mineralocorticoid Receptor Resource, the Vitamin D Receptor Resource, and the Steroid Receptor Associated Proteins Resource, The goal of the NRR project is to provide a comprehensive resource for information on the nuclear receptor superfamily, and to provide a forum for the dissemination and discussion of both published and unpublished material on these proteins, Although the individual resources are managed from different servers, all the files are integrated and can be accessed through the project's Home Page, housed at http://nrr.georgetown.edu/nrr.html. In the near future, we hope to expand the project to contain information on other nuclear receptors and to better our electronic publication system, To accomplish this, we encourage the involvement of nuclear receptor investigators in the NRR. C1 GEORGETOWN UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT MOL BIOL & GENET,BOSTON,MA 02114. EASTERN VIRGINIA MED SCH,GLENNAN CTR,NORFOLK,VA 23507. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94110. ST LOUIS UNIV,HLTH SCI CTR,DEPT PHARMACOL & PHYSIOL SCI,ST LOUIS,MO 63104. NIDDK,STEROID HORMONES SECT,NIH,BETHESDA,MD 20892. MED COLL OHIO,DEPT PHARMACOL,TOLEDO,OH 43699. RI Danielsen, Mark/B-1606-2008 OI Danielsen, Mark/0000-0002-0923-9945 FU NIDDK NIH HHS [R01 DK43382]; PHS HHS [K04 02105] NR 0 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1997 VL 25 IS 1 BP 163 EP 165 DI 10.1093/nar/25.1.163 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD443 UT WOS:A1997WD44300039 PM 9016529 ER PT J AU Baxevanis, AD Landsman, D AF Baxevanis, AD Landsman, D TI Histone and histone fold sequences and structures: A database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ALIGNMENT; CHROMATIN; PROTEINS; TOOL; DNA AB A database of aligned histone protein sequences has been constructed based on the results of homology searches of the major public sequence databases. In addition, sequences of proteins identified as containing the histone fold motif and structures of all known histone and histone fold proteins have been included in the current release. Database resources include information on conflicts between similar sequence entries in different source databases, multiple sequence alignments, and links to the Entrez integrated information retrieval system at the National Center for Biotechnology Information (NCBI). The database currently contains over 1000 protein sequences. C1 NIH,COMPUTAT BIOL BRANCH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. NIH,NATL CTR HUMAN GENOME RES,GENOME TECHNOL BRANCH,BETHESDA,MD 20892. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 17 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1997 VL 25 IS 1 BP 272 EP 273 DI 10.1093/nar/25.1.272 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD443 UT WOS:A1997WD44300062 PM 9016552 ER PT J AU Tutonda, MG Fain, HD Buckheit, RW Broom, AD AF Tutonda, MG Fain, HD Buckheit, RW Broom, AD TI The role of hydrophobic versus hydrophilic base character in the anti-HIV activity of purine-containing polyribonucleotides SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; STRANDED POLYRIBONUCLEOTIDES; NUCLEOSIDES; INFECTION; THERAPY AB In contrast to the highly amphiphilic poly(1-methyl-6-thioinosinic acid), a potent anti-HIV agent, poly(1-amino-6-thioinosinic acid) (PATI) lacks the unique melting behavior characteristic of the amphiphilic polymers and is completely devoid of anti-HIV activity. This is consistent with the hypothesis that amphiphilic character and the ability to form an ordered secondary structure in solution are prerequisites for potent anti-HIV activity of single-stranded polynucleotides. C1 UNIV UTAH,COLL PHARM,DEPT MED CHEM,SALT LAKE CITY,UT 84112. FREDERICK CANC RES & DEV CTR,SO RES INST,VIROL RES DIV,FREDERICK,MD 21701. NR 15 TC 8 Z9 8 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 1-2 BP 173 EP 182 DI 10.1080/07328319708002531 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WL664 UT WOS:A1997WL66400016 ER PT J AU Eritja, R Adam, V Avino, A Diaz, AR Fabrega, C Ferrer, E Grotli, M Garcia, RG Hoffmann, M Marquez, VE Wiersma, M AF Eritja, R Adam, V Avino, A Diaz, AR Fabrega, C Ferrer, E Grotli, M Garcia, RG Hoffmann, M Marquez, VE Wiersma, M TI Preparation of oligonucleotides containing nonnatural base analogs. SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article ID DNA; DERIVATIVES; NUCLEOSIDE AB The preparation of oligonucleotides containing 5-amino-2'-deoxyuridine, 5-N-acetamido-2'-deoxyuridine, 5-aza-2'-deoxycytidine and N-2-substituted guanosine derivatives is described. In each case selection of the appropriate protective group, synthesis and deprotection conditions is discussed. C1 NCI,NIH,BETHESDA,MD 20892. RP Eritja, R (reprint author), EUROPEAN MOL BIOL LAB,MEYERHOFSTR 1,D-69117 HEIDELBERG,GERMANY. RI Grotli, Morten/A-8735-2010; eritja, ramon/B-5613-2008; Avino, Anna/N-5223-2015; Fabrega, MCarme/K-9847-2014 OI Grotli, Morten/0000-0002-0154-0151; eritja, ramon/0000-0001-5383-9334; Avino, Anna/0000-0003-3047-738X; Fabrega, MCarme/0000-0003-3816-7634 NR 14 TC 2 Z9 2 U1 0 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 5-6 BP 697 EP 702 DI 10.1080/07328319708002936 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP845 UT WOS:A1997XP84500026 ER PT J AU Agrawal, S Jiang, ZW Zhao, QY Shaw, D Sun, D Saxinger, C AF Agrawal, S Jiang, ZW Zhao, QY Shaw, D Sun, D Saxinger, C TI Mixed-backbone oligonucleotides containing phosphorothioate and methylphosphonate linkages as second generation antisense oligonucleotide SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA ID IMMUNODEFICIENCY-VIRUS TYPE-1; OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES; PHARMACOKINETICS; REPLICATION; ACTIVATION; MICE; RNA AB Antisense oligonucleotides are being studied as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have synthesized phosphorothioate oligonucleotides containing methylphosphonate linkages at the 5'-end, the 3'-end, or in the center, and have evaluated the impact of these linkages on the biophysical properties, biological properties, and some of the safety parameters. C1 UNIV ALABAMA,LURLEEN B WALLACE TUMOR INST,BIRMINGHAM,AL 35233. NCI,DIV BASIC SCI,BETHESDA,MD 20892. RP Agrawal, S (reprint author), HYBRIDON INC,1 INNOVAT DR,WORCESTER,MA 01605, USA. NR 19 TC 7 Z9 7 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 927 EP 936 DI 10.1080/07328319708006109 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000006 ER PT J AU Jeong, LS Bae, M Chun, MW Marquez, VE AF Jeong, LS Bae, M Chun, MW Marquez, VE TI Synthesis and anti-HIV activity of carbocyclic ring-enlarged 4',1'a-methano oxetanocin analogues SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA AB Synthesis of carbocyclic ring-enlarged 4',1'a-methano oxetanocin analogues via completely regioselective opening of cyclic sulfites by sodium azide or purine bases is described. C1 SEOUL NATL UNIV,COLL PHARM,SEOUL 151742,SOUTH KOREA. NCI,DIV BASIC SCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. RP Jeong, LS (reprint author), EWHA WOMANS UNIV,COLL PHARM,MED CHEM LAB,SEOUL 120750,SOUTH KOREA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1059 EP 1062 DI 10.1080/07328319708006132 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000029 ER PT J AU Eritja, R Marquez, VE Garcia, RG AF Eritja, R Marquez, VE Garcia, RG TI Synthesis and properties of oligonucleotides containing 5-aza-2'-deoxycytidine. SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA ID LABILE AB The preparation of a protected derivative of 5-aza-2'-deoxycytidine carrying the 2-(p-nitrophenyl)ethyl group is described. The new derivative is useful for the preparation of oligonucleotides containing 5-aza-2'-deoxycytidine using a special methodology that avoids the use of ammonia. C1 NCI,NIH,BETHESDA,MD 20892. RP Eritja, R (reprint author), EUROPEAN MOL BIOL LAB,MEYERHOFSTR 1,D-69117 HEIDELBERG,GERMANY. RI eritja, ramon/B-5613-2008 OI eritja, ramon/0000-0001-5383-9334 NR 8 TC 2 Z9 2 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1111 EP 1114 DI 10.1080/07328319708006144 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000041 ER PT J AU Cramer, H Torrence, PF AF Cramer, H Torrence, PF TI Synthesis of (2',5')-oligoadenylate antisense chimeras targeting steroid 5 alpha-reductase SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA ID 2-5A ANTISENSE; RNA TARGET AB 2-5A antisense chimeras have been synthesized which target human steroid 5 alpha-reductase mRNA. To enhance the stability of the chimera towards degradative enzymes the terminal phosphodiester bond was isomerized from 3',5' to 3',3' and the 5'-phosphate group was thiolated. C1 NIDDK,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 9 TC 0 Z9 0 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1201 EP 1204 DI 10.1080/07328319708006157 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000054 ER PT J AU Player, MR Maitra, R Silverman, R Torrence, PF AF Player, MR Maitra, R Silverman, R Torrence, PF TI Targeting HIV mRNA for degradation: 2,5-A antisense chimeras as potential chemotherapeutic agents for AIDS SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA AB We have identified a region within a 1 kb HIV gag RNA which can be ablated in vitro using a 2,5-A antisense chimera. The cleavage was specific and almost complete at a concentration of 100 nM chimera. C1 NIDDKD,NIH,BETHESDA,MD 20892. CLEVELAND CLIN RES FDN,CLEVELAND,OH 44195. NR 0 TC 1 Z9 1 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1221 EP 1222 DI 10.1080/07328319708006162 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000059 ER PT J AU Valette, G Girardet, JL Pompon, A Perigaud, C Gosselin, G Korba, B Hantz, O Imbach, JL AF Valette, G Girardet, JL Pompon, A Perigaud, C Gosselin, G Korba, B Hantz, O Imbach, JL TI The pronucleotide approach .3. Synthesis, anti-HBV activity and stability studies of the bis(S-pivaloyl-2-thioethyl) phosphotriester derivative of acyclovir SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA ID T-CELL CULTURE; INTRACELLULAR DELIVERY; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE AB The nucleoside analog Acyclovir (ACV) is used in the treatment of herpes simplex (HSV) and varicella-zoster (VZV) diseases. The possibility to extend the application field of ACV by using the bis[SATE] pronucleotide approach in order to deliver ACVMP inside the cell was investigated, And actually, the title compound has potent anti-hepatitis B activity in cell culture experiments. Here, we also report its synthesis and stability in various media. C1 UNIV MONTPELLIER 2,CNRS,UMR USTL 5625,CHIM BIOORGAN LAB,F-34095 MONTPELLIER 5,FRANCE. NIH,VIROL BRANCH,DMID,BETHESDA,MD 20892. SIDA & RETROVIRUS HUMAINS,INSERM,U 271,UNITE RECH HEPATITES,F-69424 LYON 3,FRANCE. NR 7 TC 6 Z9 6 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1331 EP 1335 DI 10.1080/07328319708006182 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000079 ER PT J AU Winter, H Maeda, Y Mitsuya, H Zemlicka, J AF Winter, H Maeda, Y Mitsuya, H Zemlicka, J TI Phosphodiester amidates of unsaturated nucleoside analogues as anti-HIV agents SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA ID INTRACELLULAR DELIVERY; ABSOLUTE-CONFIGURATION; ENANTIOSELECTIVITY; DERIVATIVES; PATHWAYS; ISODDA AB Lipophilic phosphodiester L-alaninates of acyclic unsaturated nucleoside analogues 1d, 1e, 2d, 2e, 3d, 3e, 4d and 5d were prepared and their antiretroviral activity was examined in ATH8 cell culture infected with HIV-1. A possible mechanism of action of these analogues is discussed. C1 WAYNE STATE UNIV,SCH MED,BARBARA ANN KARMANOS CANC INST,DETROIT,MI 48201. NCI,EXPT RETROVIROL SECT,MED BRANCH,NIH,BETHESDA,MD 20892. NR 11 TC 4 Z9 4 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1341 EP 1345 DI 10.1080/07328319708006184 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000081 ER PT J AU Charubala, R Maurinsh, J Rosler, A Melguizo, M Jungmann, O Gottlieb, M Lehbauer, J Hawkins, M Pfleiderer, W AF Charubala, R Maurinsh, J Rosler, A Melguizo, M Jungmann, O Gottlieb, M Lehbauer, J Hawkins, M Pfleiderer, W TI Pteridine nucleosides new - New versatile building blocks in oligonucleotide synthesis SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA ID LUMAZINE AB Chemical syntheses of 1-(2-deoxy-beta-D-ribofuranosyl)lumazines and isopterins as well as 8-(2-deoxy-beta-D-ribofuranosyl)-4-amino-7(8H)pteridones and -isoxanthopterins have been developed to make the structural analogs of the naturally occurring 2'-deoxyribonucleosides in the pteridine series available. The corresponding phosphoramidites have been used in machine-aided solid-support syntheses leading to new types of fluorescence labeled oligonucleotides. The effects of the various fluorophors on duplex formation and as labels for enzyme reactions is demonstrated. C1 NIH,BETHESDA,MD 20892. RP Charubala, R (reprint author), UNIV KONSTANZ,FAK CHEM,POSTFACH 5560,D-78434 CONSTANCE,GERMANY. RI Melguizo, Manuel/M-1273-2014 OI Melguizo, Manuel/0000-0002-2210-9547 NR 16 TC 12 Z9 12 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1369 EP 1378 DI 10.1080/07328319708006188 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000085 ER PT J AU Marquez, VE Ezzitouni, A Siddiqui, MA Russ, P Ikeda, H George, C AF Marquez, VE Ezzitouni, A Siddiqui, MA Russ, P Ikeda, H George, C TI Conformational analysis of nucleosides constructed on a bicyclo[3.1.0]hexane template. Structure-antiviral activity analysis for the northern and southern hemispheres of the pseudorotational cycle SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA ID CARBOCYCLIC THYMIDINE AB A conformational analysis of carbocyclic nucleosides built on a rigid bicyclo[3.1.0]hexane template (1-4, Northern and 5-8 Southern) showed that the Northern conformation prefers an anti glycosyl torsion angle whereas the Southern conformation favors the syn range. Antiviral activity was mostly associated with the Northern conformers. C1 USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. RP Marquez, VE (reprint author), NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. NR 4 TC 11 Z9 11 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1431 EP 1434 DI 10.1080/07328319708006199 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000096 ER PT J AU Zhang, WF Torrence, P AF Zhang, WF Torrence, P TI The synthesis of 2-5A antisense chimeras with various non-nucleoside components. SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA ID RNA AB We have synthesized a series of 2-5A chimeras in which the nature of the oligoadenylate-antisense linkage and the length of the 2',5'-oligoadenylate were varied. In addition, a branched linker was introduced to relocate the 2',5'-oligoadenylate with respect to the antisense domain. C1 NIDDKD,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1579 EP 1582 DI 10.1080/07328319708006234 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000131 ER PT J AU Xiao, W Li, GY Torrence, PF Cirino, NM Silverman, RH AF Xiao, W Li, GY Torrence, PF Cirino, NM Silverman, RH TI Inhibition of Respiratory Syncytial Virus by double termini-protected 2-5A antisense chimeras SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XII International Round Table on Nucleosides, Nucleotides and their Biological Applications - Making Drugs Out of Nucleosides and Oligonucleotides CY SEP 15-19, 1996 CL LA JOLLA, CA AB Respiratory syncytial virus (RSV) replication was reduced by greater than 90% after treatment of infected human tracheal epithelial cell line, 9HTE, with double termini-protected 2-5 A antisense chimeras. C1 NIDDK,SECT BIOMED CHEM,NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195. NR 5 TC 2 Z9 2 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 7-9 BP 1735 EP 1738 DI 10.1080/07328319708006266 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF530 UT WOS:A1997YF53000163 ER PT J AU Buolamwini, JK Barchi, JJ AF Buolamwini, JK Barchi, JJ TI Solution NMR conformational analysis of the potent equilibrative sensitive (ES) nucleoside transporter inhibitor, S-(4-nitrobenzyl)mercaptopurine riboside (NBMPR) SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article ID COUPLING-CONSTANTS; SUBSTITUENT ELECTRONEGATIVITIES; KARPLUS EQUATION; SUGAR RING; PROTEIN; BINDING; ANALOGS AB High resolution NMR analysis involving one-dimensional (1-D) H-1 and nuclear Overhauser (NOE) difference spectroscopy was applied to solutions of NBMPR in DMSO-d(6). Coupling constants were obtained at different temperatures between 285 and 353 K, and used to analyze the rotamer preferences about the C-4'-C-5' bond. The results revealed a rotamer distribution about the chi tortion angle that favors the high-anti range, a preponderance of the gamma(+) rotamer (at similar to 64%) with respect to the gamma torsion angle, and a higher population of the south (S) conformer, which was favored by as little as the 4% to as much as 31% over the north (N) conformer as calculated by the program PSEUROT 6.2. The high-anti glycosidic torsion orientation appears to be the major conformational difference between the solution structure of NBMPR determined in this study and the structure previously observed in the solid state. C1 Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Dept Med Chem, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Natl Ctr Dev Nat Prod, University, MS 38677 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Buolamwini, JK (reprint author), Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Dept Med Chem, University, MS 38677 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 19 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1997 VL 16 IS 12 BP 2101 EP 2110 DI 10.1080/07328319708002561 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YN745 UT WOS:000071202100002 ER PT S AU McCormick, KA AF McCormick, KA BE Gerdin, U Tallberg, M Wainwright, P TI Improving nursing documentation to include outcomes of care in computerized information systems SO NURSING INFORMATICS: THE IMPACT OF NURSING KNOWLEDGE ON HEALTH CARE INFORMATICS SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 6th Triennial International Congress of IMIA-NI on Nursing Informatics - The Impact of Nursing Knowledge on Health Care Informatics (NI 97) CY 1997 CL STOCKHOLM, SWEDEN SP Int Med Informat Assoc, Special Interest Grp Nursing Informat, No Nurses Federat, Swedish Nurses Assoc, Swedish Assoc Hlth Officers, Swedish Federat Cty Council, Stockholm Univ Coll Hlth Sci, Swedish Inst Hlth Serv Dev, S Stockholm Hlth Care Dist AB Oftentimes when models of information systems are developed, outcomes are either left out or described as an end product of treatment alone. However, in research demonstrating outcomes, evaluating whether outcomes are achieved can best be accomplished when the outcomes are integrated into the entire care process. This paper describes a model for nursing to consider when integrating outcomes during several components of nursing care delivery, and several nursing domains for achieving outcome of care. RP McCormick, KA (reprint author), AGCY HLTH CARE POLICY & RES,CTR INFORMAT TECHNOL,2101 E JEFFERSON ST,SUITE 602,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0926-9630 BN 90-5199-362-5 J9 ST HEAL T PY 1997 VL 46 BP 105 EP 110 PG 6 WC Medical Informatics; Nursing SC Medical Informatics; Nursing GA BJ94F UT WOS:A1997BJ94F00018 PM 10175380 ER PT J AU Grady, P AF Grady, P TI NINR and the nursing research community: The next 10 years ... The next century SO NURSING OUTLOOK LA English DT News Item RP Grady, P (reprint author), NIH,NINR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JAN-FEB PY 1997 VL 45 IS 1 BP 43 EP 43 DI 10.1016/S0029-6554(97)90059-2 PG 1 WC Nursing SC Nursing GA WJ887 UT WOS:A1997WJ88700010 PM 9139263 ER PT J AU Leidy, NK Abbott, RD Fedenko, KM AF Leidy, NK Abbott, RD Fedenko, KM TI Sensitivity and reproducibility of the dual-mode actigraph under controlled levels of activity intensity SO NURSING RESEARCH LA English DT Article; Proceedings Paper CT Sigma Theta Tau 33rd Biennial Convention CY NOV 05, 1995 CL DETROIT, MI SP Sigma Theta Tau ID PHYSICAL-ACTIVITY; PERCEIVED EXERTION; MOTOR-ACTIVITY; PLACEMENT; DISEASE; DESIGN AB The purpose of this study was to test the sensitivity and reproducibility of dual-made actigraphy as an objective measure of functional performance in healthy adults under controlled levels of activity intensity. Twenty subjects wore the instrument on the nondominant wrist while performing standardized tasks selected to represent day-to-day activities at three levels of intensity (five tasks in each level): light (1-2 metabolic equivalents), moderate (3-4 metabolic equivalents), and heavy (4-6 metabolic equivalents). Upon completion of each intensity level, subjects were asked to rate their level of exertion using Borg's 15-point rating of perceived exertion (RPE) scale. Eighteen subjects repeated the protocol within 7 days. Zero-crossing and time-above-threshold mades successfully differentiated between light and moderate and between light and heavy activity. Reproducibility correlation coefficients (r(s)) across activity levels were .80 and .66 for the two modes, respectively. Results suggest dual-mode actigraphy may be useful for the study of performance variation and structure in healthy and chronically ill individuals. C1 NATL INST NURSING RES,LAB STUDY HUMAN RESPONSES HLTH & ILLNESS,NIH,BETHESDA,MD. UNIV VIRGINIA,DEPT MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22903. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. NR 41 TC 17 Z9 17 U1 0 U2 1 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JAN-FEB PY 1997 VL 46 IS 1 BP 5 EP 11 DI 10.1097/00006199-199701000-00002 PG 7 WC Nursing SC Nursing GA WF263 UT WOS:A1997WF26300002 PM 9024418 ER PT J AU Morse, MA Kresty, LA Steele, VE Kelloff, GJ Boone, CW Balentine, DA Harbowy, ME Stoner, GD AF Morse, MA Kresty, LA Steele, VE Kelloff, GJ Boone, CW Balentine, DA Harbowy, ME Stoner, GD TI Effects of theaflavins on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID PHENETHYL ISOTHIOCYANATE; DNA METHYLATION; ELLAGIC ACID; BLACK TEA; RATS; CANCER; CONSUMPTION; INHIBITION; CHEMOPREVENTION; GREEN AB The purpose of this experiment was to compare the inhibitory effects of the polyphenol fraction of black tea, theaflavins (TF), the polyphenol fraction of green tea, and (-)-epigallocatechin-3-gallate (EGCG) in the rat esophageal tumor model. The tea fractions were administered in the drinking water at concentrations of 360 and 1,200 ppm for two weeks before administration of the esophageal carcinogen N-nitrosomethylbenzylamine (NMBA). NMBA was administered subcutaneously in 10% dimethyl sulfoxide three times weekly for five weeks. Additional groups of rats received only vehicle and plain drinking water or vehicle and drinking water containing 1,200 ppm of each tea fraction. Twenty-five weeks after NMBA administration began, the experiment was terminated and esophagi were excised and scored for tumors. Rats that were not dosed with NMBA had no tumors. Rats treated with NMBA only had an esophageal tumor incidence of 100% and a multiplicity of 3.3 +/- 0.4 tumors/rat. The proportion of rats developing tumors was not significantly reduced by any of the four tea fractions at the concentrations tested. However, the 1,200 ppm concentrations of each tea fraction in the drinking water produced some reduction in esophageal tumor multiplicity, although only TF significantly reduced tumor multiplicity compared with rats treated with NMBA only. The rates of esophageal tumor formation were significantly reduced at 360 and 1,200 ppm by TF and EGCG. C1 NCI,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. THOMAS J LIPTON TEA CO,ENGLEWOOD CLIFFS,NJ 07632. RP Morse, MA (reprint author), OHIO STATE UNIV,SCH PUBL HLTH,DIV ENVIRONM HLTH SCI,CHRI 1148,300 W 10TH AVE,COLUMBUS,OH 43210, USA. OI Harbowy, Matthew/0000-0003-4861-9411 FU NCI NIH HHS [N01-CN-25486-01] NR 28 TC 42 Z9 45 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1997 VL 29 IS 1 BP 7 EP 12 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA YF603 UT WOS:A1997YF60300002 PM 9383778 ER PT J AU Fu, YM Yu, ZX Ferrans, VJ Meadows, GG AF Fu, YM Yu, ZX Ferrans, VJ Meadows, GG TI Tyrosine and phenylalanine restriction induces G0/G1 cell cycle arrest in murine melanoma in vitro and in vivo SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID B-16 MELANOMA; NUCLEAR ANTIGEN; METASTATIC PHENOTYPE; MESSENGER-RNA; GROWTH-FACTOR; INHIBITION; SELECTION; CANCER; PROLIFERATION; ENHANCEMENT AB Tyr-Phe and Met limitation in vitro inhibited cell proliferation and proliferating cell nuclear antigen (PCNA) expression to a gl eater extent than serum limitation. Tyr-Phe and serum limitation arrested cells in the G0/GI phase; Met limitation blocked cells in the G0/GI and S phases. Tyr-Phe limitation progressively decreased cyclin D-1 expression to 30% of control within four days and did not affect expression of cyclin D-3 or cyclin-dependent kinase (CDK2, CDK4, and CDK5) expression. Met limitation decreased cyclin D-3 expression to 25% of control and CDK2 expression to 32% of control by Day 4 and did not affect expression of cyclin D-1, CDK4, and CDK5. Serum limitation inhibited cyclin D-1 and cyclin D-3 expression to 24% of control after four days and did not effect CDK expression. Expression of two CDK inhibitors, p21(WAF1/Cip1) and P27(Kip1), was not changed by amino acid or serum limitation. Dietary restriction of Tyr-Phe in mice bearing subcutaneous B16BL6 melanoma tumors decreased tumor growth rate compared with mice fed a normal diet. Tumors from Tyr-Phe-restricted mice exhibited decreased PCNA expression, G0/GI phase cell cycle arrest and reduced cyclin D-1 expression. These data indicate that decreased tumor growth in vivo associated with dietary restriction of Tyr and Phe is cell cycle specific. C1 Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Pullman, WA 99164 USA. Washington State Univ, Coll Pharm, Pharmacol & Toxicol Grad Program, Pullman, WA 99164 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. RP Meadows, GG (reprint author), Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Box 646510, Pullman, WA 99164 USA. FU NCI NIH HHS [R01-CA-42465] NR 34 TC 24 Z9 25 U1 1 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1997 VL 29 IS 2 BP 104 EP 113 PG 10 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA YM124 UT WOS:000071031100002 PM 9427972 ER PT J AU Breslow, RA Subar, AF Patterson, BH Block, G AF Breslow, RA Subar, AF Patterson, BH Block, G TI Trends in food intake: The 1987 and 1992 National Health Interview Surveys SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID CANCER PREVENTION; QUESTIONNAIRE; RECORDS; WOMEN; VALIDATION; FREQUENCY AB Tc, examine food intake trends in the US population, cross-sectional nationally representative food intake data were obtained from the 1987 and 1992 National Wealth Interview Survey Cancer control Supplements. In each of these years, approximately 10,000 respondents completed methodologically consistent food frequency questionnaires containing the same 57 food items. Between 1987 and 1992, the proportion of Americans consuming high-fat foods, including fried fish, fried chicken, bacon, eggs, whole milk, and butter, decreased. The proportion of Americans drinking alcoholic beverages also decreased: fewer drank wine and hard liquor in 1992. The proportion of fruit and vegetable consumers remained stable over time. These results are similar to those obtained from more detailed national surveys. National guidelines urge Americans to avoid intake of high-fat foods, increase consumption of fruits and vegetables, and practice moderation when drinking alcoholic beverages to prevent cancer and other chronic diseases. The direction of Americans' apparent changes in food usage between 1987 and 1992, evaluated using limited data from food frequency questionnaires, suggests greater behavioral changes in the direction of guidelines recommending avoidance of foods that may increase the risk of cancer than in the direction of guidelines recommending increased consumption of foods that may confer protection. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. RP Breslow, RA (reprint author), NCI,EPN 313,BIOMETRY BRANCH,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Block, Gladys/E-3304-2010 NR 32 TC 20 Z9 20 U1 1 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1997 VL 28 IS 1 BP 86 EP 92 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA XE795 UT WOS:A1997XE79500013 PM 9200155 ER PT J AU Shoff, SM Newcomb, PA Longnecker, MP AF Shoff, SM Newcomb, PA Longnecker, MP TI Frequency of eating and risk of colorectal cancer in women SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID COLON-CANCER; DIETARY FACTORS; BREAST-CANCER; LARGE-BOWEL; WISCONSIN AB Numerous dietary constituents have been extensively studied with regard to colorectal cancer risk, but food intake patterns have been studied less frequently. The purpose of these analyses was to describe associations between frequency of eating and colorectal cancer risk in women. Female Wisconsin residents aged 30-74 years with a diagnosis of colorectal cancer within two years were identified through the statewide tumor registry. Control subjects were randomly selected from lists of licensed drivers (<65 yrs old) and Medicare beneficiaries (65-74 yrs old). Meal and snack frequency was obtained on a subset of case (n = 189) and control (n = 322) subjects. Odds ratios and 95% confidence intervals (CIs) obtained from conditional logistic regression models were used to estimate multivariate-adjusted relative risks. Compared with women consuming three or four meat daily, women consuming one to two meals daily had an adjusted relative risk of 0.57 (95% CI = 0.34-0.94). Snacking frequency and frequency of meals + snacks were not associated with cancer risk. These results are consistent with other reports and suggest that meal frequency is associated with colorectal cancer risk. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP Shoff, SM (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,MED SCI CTR,ROOM 47660,1300 UNIV AVE,MADISON,WI 53706, USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [R25CA-47785] NR 16 TC 11 Z9 11 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1997 VL 27 IS 1 BP 22 EP 25 PG 4 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA VX321 UT WOS:A1997VX32100003 PM 8970177 ER PT S AU Hibbeln, JR Umhau, JC George, DT Salem, N AF Hibbeln, JR Umhau, JC George, DT Salem, N BE Simopoulos, AP Pavlou, KN TI Do plasma polyunsaturates predict hostility and depression? SO NUTRITION AND FITNESS: METABOLIC AND BEHAVIORAL ASPECTS IN HEALTH AND DISEASE SE World Review of Nutrition and Dietetics LA English DT Article; Proceedings Paper CT 3rd International Conference on Nutrition and Fitness CY MAY 24-27, 1996 CL ATHENS, GREECE ID FATTY-ACID METABOLISM; CEREBROSPINAL-FLUID; SERUM-CHOLESTEROL; 5-HYDROXYINDOLEACETIC ACID; SOCIAL-BEHAVIOR; HUMAN CSF; SEROTONIN; VIOLENT; DISEASE; MEN RP Hibbeln, JR (reprint author), NIAAA, LAB MEMBRANE BIOCHEM & BIOPHYS, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. NR 69 TC 45 Z9 48 U1 1 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 3-8055-6474-0 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 1997 VL 82 BP 175 EP 186 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BJ41E UT WOS:A1997BJ41E00012 PM 9270321 ER PT S AU Nolan, PJ Knepper, MA Packer, RK AF Nolan, PJ Knepper, MA Packer, RK BE ODonovan, DJ Endou, H Schoolwerth, AC Tizianello, A Walls, J TI Role of adrenal steroids in stimulating ammonium excretion during acute metabolic acidosis SO NUTRITIONAL AND ACID-BASE ASPECTS OF AMINO ACID METABOLISM SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article; Proceedings Paper CT 7th International Ammoniagenesis Workshop CY MAY 20-23, 1996 CL GALWAY, IRELAND SP Gambro Ltd, Shire Pharm Ltd, Janssen Cilag Ltd, Pfizer Corp, Univ Kyorin, Sch Med, Tokyo, Bord Failte, Conf Bur Ireland, Univ Coll, Galway ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE; INNER MEDULLA; RAT; CORTICOSTERONE; ACIDIFICATION; PURIFICATION; TRANSPORT; SEGMENTS; NEPHRON; CELLS C1 GEORGE WASHINGTON UNIV,DEPT BIOL SCI,WASHINGTON,DC 20052. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. NR 23 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 3-8055-6490-2 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 1997 VL 121 BP 55 EP 61 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA BJ75M UT WOS:A1997BJ75M00009 PM 9336698 ER PT S AU Tataranni, PA Ravussin, E AF Tataranni, PA Ravussin, E BE Anderson, GH Rolls, BJ Steffen, DG TI Effect of fat intake on energy balance SO NUTRITIONAL IMPLICATIONS OF MACRONUTRIENT SUBSTITUTES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Nutritional Implications of Macronutrient Substitutes CY OCT 27-29, 1996 CL ARLINGTON, VA SP New York Acad Sci, Int Life Sci Inst, N Amer Tech Comm Macronutrient Substitut ID DIETARY-FAT; PIMA-INDIANS; WEIGHT-GAIN; INSULIN-RESISTANCE; LIPOPROTEIN-LIPASE; OBESE SUBJECTS; CARBOHYDRATE; OXIDATION; EXPENDITURE; HUMANS RP Tataranni, PA (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, NIH, 4212 N 16TH ST, ROOM 541-A, PHOENIX, AZ 85016 USA. NR 48 TC 17 Z9 17 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-084-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 819 BP 37 EP 43 DI 10.1111/j.1749-6632.1997.tb51797.x PG 7 WC Food Science & Technology; Multidisciplinary Sciences; Nutrition & Dietetics SC Food Science & Technology; Science & Technology - Other Topics; Nutrition & Dietetics GA BH98L UT WOS:A1997BH98L00005 PM 9186759 ER PT S AU Wickstrom, E Tyson, FL AF Wickstrom, E Tyson, FL BE Chadwick, DJ Cardew, G TI Differential oligonucleotide activity in cell culture versus mouse models SO OLIGONUCLEOTIDES AS THERAPEUTIC AGENTS SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Oligonucleotides as Therapeutic Agents CY JAN 07-09, 1997 CL CIBA FDN, LONDON, ENGLAND HO CIBA FDN ID BREAST-CARCINOMA CELLS; ANTISENSE OLIGONUCLEOTIDES; NUDE-MICE; ONCOGENE AMPLIFICATION; DOWN-REGULATION; OVARIAN-CANCER; EXPRESSION; DNA; PHOSPHOROTHIOATE; INHIBITION AB The usual course of drug discovery begins with the demonstration of compound activity in cells and, usually, a lower level of activity in animals. Successive rounds of drug design may result in a compound with sufficient activity in animals to justify clinical trials. The basic endpoints of therapeutic oligonucleotide experiments include target antigen reduction, target messenger reduction and inhibition of transformed cell proliferation or viral replication. However, one should expect oligonucleotides to exhibit pleiotropic behaviour, as do all other drugs. In an animal oligonucleotides will necessarily bind to and dissociate from all macromolecules encountered in the blood, in tissues, on cell surfaces and within cellular compartments. Contrary to expectations, oligonucleotides designed to be complementary to certain transcripts have sometimes been found moderately effective in cell-free extracts, more effective in cell culture and most effective in animal models. If greater potency against standard endpoints is reported in mouse models than was observed in cell culture, critical examination must consider alternate modes of action in animals that may not apply in cell culture. This counterintuitive paradox will be examined, based on studies of Ha-ras expression in bladder cancer, Ki-ras expression in pancreatic cancer, erbB2 expression in ovarian cancer and c-myc expression in B cell lymphoma. C1 Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Wickstrom, E (reprint author), Thomas Jefferson Univ, Dept Microbiol & Immunol, 1025 Walnut St, Philadelphia, PA 19107 USA. FU NCI NIH HHS [CA42960, CA60139] NR 41 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND SN 0300-5208 BN 0-471-97279-7 J9 CIBA F SYMP PY 1997 VL 209 BP 124 EP 137 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, General & Internal SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; General & Internal Medicine GA BL63X UT WOS:000076141500018 PM 9383573 ER PT J AU Ren, QF VanGroeningen, CJ Hardcastle, A Aherne, GW Geoffroy, F Allegra, CJ Johnston, PG Grem, JL AF Ren, QF VanGroeningen, CJ Hardcastle, A Aherne, GW Geoffroy, F Allegra, CJ Johnston, PG Grem, JL TI Determinants of cytotoxicity with prolonged exposure to fluorouracil in human colon cancer cells SO ONCOLOGY RESEARCH LA English DT Article DE fluorouracil; DNA damage; thymidylate synthase; colon cancer ID METASTATIC COLORECTAL-CARCINOMA; THYMIDYLATE SYNTHASE INHIBITION; 5-FLUOROURACIL CYTO-TOXICITY; MOUSE FM3A CELLS; CONTINUOUS-INFUSION; HUMAN-BREAST; NUCLEAR-RNA; DNA-DAMAGE; LEUCOVORIN; RESISTANCE AB To explore the determinants of cytotoxicity during prolonged exposure to pharmacologically relevant concentrations of 5-fluorouracil (FUra), we studied the effects of FUra at concentrations ranging from 0.1 to 1 mu M in HCT 116 and HT 29 colon cancer cells grown in the presence of physiologic levels of leucovorin. A 5- and 7-day exposure to 1 mu M FUra reduced cell growth to 46% and 20% of control in HT 29 cells and to 74% and 38% of control in HCT 116 cells. Concurrent exposure to thymidine (10 or 20 mu M) or uridine (1 mM) provided partial protection against FUra toxicity in HT 29 cells, but did not protect HCT 116 cells. After a 24-h exposure to 1 mu M [H-3]FUra, free 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) and FUDP + FUTP levels were 0.7 and 144 pmol/10(6) cells in HT 29 cells, respectively, and 3.9 and 178 pmol/10(6) cells in HCT 116 cells. FdUMP and FUDP + FUTP pools increased by 5.7- and 2.0-fold in HT 29 cells and by 1.7- and 3.3-fold in HCT 116 cells over the next 48 h, but did not accumulate thereafter. After a 24-h exposure to 1 PM [H-3]FUra, FUra-RNA levels were 158 and 280 fmol/mu g in HT 29 and HCT 116 cells, respectively; FUra-RNA levels increased over time, and reached 700 and 1156 fmol/mu g at day 5. Concurrent exposure to 1 mM uridine for 72 h did not diminish [H-3]FUra-RNA incorporation. Upon removal of [H-3]FUra following a 24-h exposure, FUra-RNA levels remained relatively stable with 57-78% retained at 120 h. A low level of [H-3]FUra-DNA incorporation was detected in HT 29 cells. Thymidylate synthase (TS) catalytic activity in control cells was 2-fold higher in HCT 116 cells compared to HT 29 cells (47 vs. 23 pmol/min/mg). Total TS content increased 1.5- to 3-fold over control in both cell lines during FUra exposure, and ternary complex formation was evident for up to 96 h. dTTP pools were not depleted in FUra-treated cells, suggesting that residual TS catalytic activity was sufficient to maintain dTTP pools relative to demand. Surprisingly, the partial inhibition of TS was accompanied by a striking accumulation of immunoreactive ''dUMP'' pools in both lines; dUTP pools also increased 2- to 3-fold. In summary, the gradual and stable accumulation of FUra in RNA noted in both lines may account for the thymidine-insensitive component of FUra toxicity. Because dTTP pools were not appreciably diminished, the interference with nascent DNA chain elongation and induction of single-strand breaks in newly synthesized DNA in both cell lines may be due to misincorporation of deoxyuridine nucleotides. C1 NATL NAVAL MED CTR, NCI, MED BRANCH, DEV THERAPEUT DEPT, DIV CLIN SCI, BETHESDA, MD 20889 USA. NR 57 TC 16 Z9 16 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1997 VL 9 IS 2 BP 77 EP 88 PG 12 WC Oncology SC Oncology GA XA700 UT WOS:A1997XA70000005 PM 9167189 ER PT J AU Agbaria, R Kelley, JA Jackman, J Viola, JJ Ram, Z Oldfield, E Johns, DG AF Agbaria, R Kelley, JA Jackman, J Viola, JJ Ram, Z Oldfield, E Johns, DG TI Antiproliferative effects of cyclopentenyl cytosine (NSC 375575) in human glioblastoma cells SO ONCOLOGY RESEARCH LA English DT Article DE cyclopentenyl cytosine; CTP synthase; glioblastoma; intracerebral tumors; blood-brain barrier ID TRIPHOSPHATE; PENETRATION; METABOLISM; ANTITUMOR; INFUSION; BRAIN AB Cyclopentenyl cytosine (CPEC) exerts an antiproliferative effect against a wide variety of human and murine tumor lines, including a panel of human gliosarcoma and astrocytoma lines. This effect is produced primarily by the 5'-triphosphate metabolite CPEC-TP, an inhibitor of cytidine-5'-triphosphate (CTP) synthase (EC 6.3.4.2). Be cause previous studies with human glioma cell lines utilized cells in long-term tissue culture, we have undertaken to determine whether the activity of CPEC in such model systems is also demonstrable in freshly excised human glioblastoma cells. Glioma cells obtained at surgery and in log phase growth were exposed to the drug at levels ranging from 0.01 to 1 mu M for 24 h, and CPEC-TP and CTP levels were determined by HPLC. Dose-dependent accumulation of CPEC-TP was accompanied by a concomitant decrease in CTP pools, with 50% depletion of the latter being achieved at a CPEC lever of ca. 0.1 mu M. Human glioma cell proliferation was inhibited 50% by 24 h exposure to 0.07 mu M CPEC. Postexposure decay of CPEC-TP was slow, with a half-time of 30 h. DNA cytometry showed a dose-dependent shift in cell cycle distribution, with an accumulation of cells in S-phase. The pharmacological effects of CPEC on freshly excised glioblastoma cells are quantitatively similar to those seen in a range of established tissue culture lines, including human glioma, colon carcinoma, and MOLT-4 lymphoblasts, supporting the recommendation that the drug may be advantageous for the treatment of human glioblastoma. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. NR 20 TC 14 Z9 14 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1997 VL 9 IS 3 BP 111 EP 118 PG 8 WC Oncology SC Oncology GA XG611 UT WOS:A1997XG61100002 PM 9220496 ER PT J AU Varricchio, F Husain, SR Leland, P Gill, P Puri, RK AF Varricchio, F Husain, SR Leland, P Gill, P Puri, RK TI Interleukin-4 receptor expression in vivo on human AIDS-related Kaposi's sarcoma SO ONCOLOGY RESEARCH LA English DT Article DE Kaposi's sarcoma; interleukin-1 receptors; immunohistochemistry; basic fibroblast growth factor; S-100 ID RENAL-CELL-CARCINOMA; IMMUNODEFICIENCY-VIRUS TYPE-1; FIBROBLAST GROWTH-FACTOR; ADHESION MOLECULE-1 ICAM-1; LONG-TERM CULTURE; TAT PROTEIN; DIFFERENTIAL EXPRESSION; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; GENE-EXPRESSION AB We have investigated the expression of interleukin-4 receptors (IL-4R) in acquired immunodeficiency syndrome (AIDS)-related Kaposi's Sarcoma (KS) in situ by immunohistochemistry. Frozen and fixed sections from five patch stage and two nodular stage KS lesions were stained with anti-IL-4R monoclonal antibody with similar results. Skin biopsies from the clinically apparent lesions and adjacent clinically uninvolved skin were also examined. We observed that individual KS cells lining the irregular vascular spaces were stained with anti-IL-4R antibody, although the degree of staining was variable. The epithelioid and oval cells appear to stain more than the spindle cells in plaque stages or nodular lesions. The sections from nonclinically involved skin also contained a few cells with features of KS, singly or in clusters that also stained for IL-4R. Skin sections from four normal donors did not stain with IL-4R antibody except for hair follicles, sweat glands, and faint staining of blood vessels. KS sections were also stained with antibodies to basic fibroblast growth factor (FGF), S100, fibronectin, and von Willebrand factor. KS lesions from clinically involved and uninvolved skin sections were positive for all four antibodies. Thus, the differences between KS lesion and clinically uninvolved skin adjacent to a KS lesion may be more quantitative than qualitative. The IL-4 receptors on KS cells were functional as IL-4 modulated intercellular adhesion molecule 1 (ICAM-1) on these cells. Taken together, our results suggest that AIDS-KS cells express eleveated levels of IL-4R compared to normal endothelial and skin cells and, thus, the receptors for IL-4 on KS may serve as an attractive target for anticancer therapy. C1 US FDA, Dept Biostat & Epidemiol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ So Calif, Sch Med, Dept Hematol, Los Angeles, CA USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, HFM-530,Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 455, Bethesda, MD 20892 USA. EM PURI@A1.CBER.FDA.GOV NR 63 TC 9 Z9 9 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1997 VL 9 IS 9 BP 495 EP 503 PG 9 WC Oncology SC Oncology GA YX637 UT WOS:000072061200006 PM 9495455 ER PT J AU Takahashi, N Iwahori, A Breitman, TR Fukui, T AF Takahashi, N Iwahori, A Breitman, TR Fukui, T TI Tunicamycin in combination with retinoic acid synergistically inhibits cell growth while decreasing palmitoylation and enhancing retinoylation of proteins in the human breast cancer cell line MCF-7 SO ONCOLOGY RESEARCH LA English DT Article DE retinoylation; palmitoylation; tunicamycin; drug synergism; cell division ID ACUTE PROMYELOCYTIC LEUKEMIA; THERAPEUTIC ANTICANCER AGENTS; F9 TERATOCARCINOMA CELLS; BINDING-PROTEIN; CRABP-I; DIFFERENTIATION THERAPY; NUCLEAR RECEPTORS; EXPRESSION; CARCINOMA; 17-BETA-ESTRADIOL AB All-trans-Retinoic acid (RA) induces differentiation and inhibits growth of many tumor types. Whereas the RA nuclear receptors mediate genomic effects of RA, there also are many nongenomic effects that do not have defined mechanisms. Some nongenomic effects of RA may involve retinoylation (RA acylation), a posttranslational modification of proteins occurring in many eukaryotic cell lines including the human breast cancer cell line MCF-7. To gain further knowledge of the role(s) of retinoylation, we studied the effects of tunicamycin (TM), an inhibitor of both protein N-glycosylation and palmitoylation, on growth and retinoylation in MCF-7 cells. We found that RA or TM alone inhibited growth of MCF-7 cells. Combinations of RA and TM inhibited growth synergistically. TM increased retinoylation and decreased palmitoylation. These results suggest that increased retinoylation and decreased glycosylation and palmitoylation may play a role in the synergistic inhibition of cell growth by combinations of TM and RA in MCF-7 cells. Furthermore, our results suggest that combinations of TM and RA may have clinical utility. C1 Hoshi Univ, Dept Hlth Chem, Shinagawa Ku, Tokyo 142, Japan. NCI, Biol Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Takahashi, N (reprint author), Hoshi Univ, Dept Hlth Chem, Shinagawa Ku, 4-41 Ebara 2 Chome, Tokyo 142, Japan. NR 46 TC 10 Z9 10 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1997 VL 9 IS 10 BP 527 EP 533 PG 7 WC Oncology SC Oncology GA YY230 UT WOS:000072126300002 PM 9507530 ER PT J AU Song, KM Li, ZW Seth, P Cowan, KH Sinha, BK AF Song, KM Li, ZW Seth, P Cowan, KH Sinha, BK TI Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas SO ONCOLOGY RESEARCH LA English DT Article DE cis-platinum; drug resistance; p53 gene; adenovirus; gene therapy; ovarian carcinoma ID PROGRAMMED CELL-DEATH; IN-VIVO; DRUG-RESISTANCE; CANCER-CELLS; CISPLATIN RESISTANCE; POTENT INHIBITOR; LUNG-CANCER; APOPTOSIS; BCL-2; BAX AB Mutations of the tumor suppressor wild-type p53 gene have been implicated in the development of resistance to anticancer drugs. We have examined the role of wild-type p53 in resistance to cis-diamminedichloroplatinum (II) (CDDP) in human ovarian cancer cells using a recombinant adenovirus containing human wild-type p53 cDNA (Adwtp53). In this study we used the human ovarian A2780 tumor cells (wtp53), which are sensitive to CDDP and A2780/CP tumor cells (nonfunctional/mutant p53) and are resistant to CDDP. Studies show that introduction of wtp53 protein via adenovirus gene transfer into A2780/CP cells significantly sensitized these cells to CDDP cytotoxicity, indicating wtp53 was involved in resistance to CDDP. We found that introduction of wtp53 protein also resulted in growth arrest of A2780/CP tumor cells whereas the parent A2780 cells were significantly less sensitive to Adwtp53. This synthesis of wtp53 protein induced by Adwtp53 in A2780/CP cells resulted in a significant increase in the expression of Bax protein without significantly effecting the expression of bcl2 protein, and induced a dose-dependent increase in the nucleosomal DNA fragmentation. The presence of CDDP further enhanced this apoptosis, causing a 30-fold sensitization of A2780/CP cells to CDDP. These results indicate that mutation of p53 protein in A2780/CP ovarian tumor cells resulted in the resistance to CDDP and that combinations of wtp53 gene and CDDP may result in sensitization of mutant p53-containing tumors to chemogenetherapy. C1 NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Sinha, BK (reprint author), NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,NIH, Bldg 10,Room 12C-210, Bethesda, MD 20892 USA. EM bks@box-b.nih.gov NR 40 TC 28 Z9 28 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1997 VL 9 IS 11-12 BP 603 EP 609 PG 7 WC Oncology SC Oncology GA ZF081 UT WOS:000072860700006 PM 9563008 ER PT J AU Nussenblatt, R AF Nussenblatt, R TI Use of laser flare photometry to assess and monitor inflammation in uveitis - Discussion SO OPHTHALMOLOGY LA English DT Editorial Material RP Nussenblatt, R (reprint author), NEI,NIH,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 1997 VL 104 IS 1 BP 71 EP 72 PG 2 WC Ophthalmology SC Ophthalmology GA WE575 UT WOS:A1997WE57500022 ER PT S AU Zeffiro, TA Eden, GF Woods, RP VanMeter, JW AF Zeffiro, TA Eden, GF Woods, RP VanMeter, JW BE Villringer, A Dirnagl, U TI Intersubject analysis of fMRI data using spatial normalization SO OPTICAL IMAGING OF BRAIN FUNCTION AND METABOLISM 2: PHYSIOLOGICAL BASIS AND COMPARISON TO OTHER FUNCTIONAL NEUROIMAGING METHODS SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Symposium on Optical Imaging and Metabolism CY MAY 01-02, 1995 CL BERLIN, GERMANY SP Volkswagen Stift, Hertie Stift, Bayer, Fresenius, Hamamatsu Protonics, Sanofi Winthrop, IBM, Siemens AG ID POSITRON-EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; HUMAN BRAIN; PET IMAGES C1 NIH, LAB DIAGNOST RADIOL RES, OD, BETHESDA, MD 20892 USA. NIMH, SECT FUNCT BRAIN IMAGING, NIH, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, LOS ANGELES, CA 90024 USA. RP Zeffiro, TA (reprint author), SENSOR SYST INC, 103A CARPENTER DR, STERLING, VA 20163 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45585-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 413 BP 235 EP 240 PG 6 WC Medicine, Research & Experimental; Clinical Neurology; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ16K UT WOS:A1997BJ16K00026 PM 9238505 ER PT B AU Gandjbakhche, AH Chernomordik, V Bonner, RF Hebden, JC Nossal, R AF Gandjbakhche, AH Chernomordik, V Bonner, RF Hebden, JC Nossal, R BE Chance, B Alfano, RR TI Use of time-dependent contrast functions to discriminate between the scattering and absorption properties of abnormal regions hidden within a tissue-like phantom SO OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE: THEORY, INSTRUMENTATION, MODEL, AND HUMAN STUDIES II, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue - Theory, Instrumentation, Model, and Human Studies II CY FEB 09-12, 1997 CL SAN JOSE, CA SP Int Biomed Opt soc, Soc Photo Opt Instrumentat Engineers, Amer Soc Laser Med & Surg Inc AB The success of time-resolved imaging of an abnormal site embedded in thick tissue may rely on one's ability to quantify the absorption coefficient of the target as a specific spectroscopic signature. This task is particularly complicated when the scattering properties of the target differ from those of the surrounding tissue. Using data obtained from time-resolved transillumination experiments of abnormally absorbing and differentially scattering objects embedded in a tissue-like phantom, we show how a new deconvolution algorithm enables us to quantify the optical properties of the target. The algorithm is based on a photon random walk theory that expresses different time-dependent point spread functions to calculate the diffusive and absorptive contrasts obtained in time-of-flight measurements. RP Gandjbakhche, AH (reprint author), NIH,PHYS SCI LAB,DCRT,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 4 Z9 4 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2390-4 J9 P SOC PHOTO-OPT INS PY 1997 VL 2979 BP 211 EP 218 DI 10.1117/12.280246 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BJ71N UT WOS:A1997BJ71N00024 ER PT J AU Luyten, FP AF Luyten, FP TI A scientific basis for the biologic regeneration of synovial joints SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article; Proceedings Paper CT National-Institutes-of-Health Technology Assessment Conference on Management of Temporomandibular Disorders CY APR 29-MAY 01, 1996 CL BETHESDA, MD SP NIH, NIDR, NIH Off Med Applicat Res, NIAMSD, NINDS, NINR, NIH Off Res Women Hlth ID FACTOR-BETA SUPERFAMILY; PROTEIN; MEMBERS AB Temporomandibular joint disorders represent a large group of conditions involving a local or more generalized musculoskeletal disease process. The disorders have many features and many causes and may result in limited or more severe damage of the joint associated tissues including the disks, the articular surface, the underlying bone, and the ligamentous structures. As our understanding of the molecular processes guiding skeletal tissue formation progresses, new opportunities arise in the field of skeletal tissue and joint repair. Reconstruction of the temporomandibular joint by means of scientifically designed approaches will revolutionize surgical treatment modalities. RP Luyten, FP (reprint author), NIDR,DEV BIOL PROJECT,BONE RES BRANCH,NIH,BETHESDA,MD 20892, USA. NR 11 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 1997 VL 83 IS 1 BP 167 EP 169 DI 10.1016/S1079-2104(97)90109-8 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WD102 UT WOS:A1997WD10200034 PM 9007942 ER PT J AU Lipton, JA AF Lipton, JA TI Introduction: National institutes of health technology assessment conference on management of temporomandibular disorders SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article RP Lipton, JA (reprint author), NIDR, DIV EXTRAMURAL RES, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 1997 VL 83 IS 1 BP 49 EP 50 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WD102 UT WOS:A1997WD10200015 ER PT J AU Dionne, RA AF Dionne, RA TI Pharmacologic treatments for temporomandibular disorders SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article; Proceedings Paper CT National-Institutes-of-Health Technology Assessment Conference on Management of Temporomandibular Disorders CY APR 29-MAY 01, 1996 CL BETHESDA, MD SP NIH, NIDR, NIH Off Med Applicat Res, NIAMSD, NINDS, NINR, NIH Off Res Women Hlth ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CHRONIC NONMALIGNANT PAIN; LOW-DOSE AMITRIPTYLINE; SPLINT THERAPY; FACIAL-PAIN; PLACEBO; DYSFUNCTION; ANTIDEPRESSANTS; METAANALYSIS; MANAGEMENT AB Drugs are widely used in the management of acute and chronic orofacial pain. Whereas the use of analgesics for acute orofacial pain is well documented through hundreds of controlled clinical trials, the use of a broad spectrum of drugs for chronic pain is based on very few studies. In the absence of data supporting a therapeutic benefit for a drug used chronically for pain, toxicity associated with the drug can still occur. It is critical, therefore, to assess the balance between therapeutic benefit and safety. This article reviews current evidence supporting the use of several drug classes for temporomandibular disorders (TMD) and identifies therapeutic controversies in need of further research. C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH,NIH, CLIN PHARMACOL UNIT,DIV INTRAMURAL, BETHESDA, MD 20892 USA. NR 55 TC 57 Z9 59 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 1997 VL 83 IS 1 BP 134 EP 142 DI 10.1016/S1079-2104(97)90104-9 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WD102 UT WOS:A1997WD10200029 PM 9007937 ER PT S AU Rifkind, JM Ajmani, RS Heim, J AF Rifkind, JM Ajmani, RS Heim, J BE Harrison, DK Delpy, DT TI Impaired hemorheology in the aged associated with oxidative stress SO OXYGEN TRANSPORT TO TISSUE XIX SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 24th Scientific Meeting of the International-Society-on-Oxygen-Transport-to-Tissue CY AUG, 1996 CL UNIV DUNDEE, DUNDEE, SCOTLAND SP Int Soc Oxygen Transport Tissue, British Microcirculat Soc, Inst Phys & Engn Med, 6th World Congress Microcirculat, Alliance Pharm, Baxter Hlth Corp, Blood Substitutes Div, Dundee City Council, Dundee Teaching Hosp, Scottish Enterprise Tayside, Hamamatsu UK, Oxygen Sensors Inc, Pfizer UK, Pharmacia & Upjohn, Univ Dundee HO UNIV DUNDEE ID CORONARY HEART-DISEASE; PLASMA-FIBRINOGEN; HEMOGLOBIN; SUPEROXIDE; INFARCTION; GENERATION; OXYGEN C1 NIA, Cellular & Mol Biol Lab, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Cellular & Mol Biol Lab, Mol Dynam Sect, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 22 TC 15 Z9 16 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45711-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 428 BP 7 EP 13 PG 7 WC Medicine, Research & Experimental; Physiology; Peripheral Vascular Disease SC Research & Experimental Medicine; Physiology; Cardiovascular System & Cardiology GA BK38E UT WOS:000071952600002 PM 9500022 ER PT S AU Balagopalakrishna, C Nirmala, R Rifkind, JM Chatterjee, S AF Balagopalakrishna, C Nirmala, R Rifkind, JM Chatterjee, S BE Nemoto, EM LaManna, JC TI Modification of low density lipoproteins by erythrocytes and hemoglobin under hypoxic conditions SO OXYGEN TRANSPORT TO TISSUE XVIII SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the International-Society-on-Oxygen-Transport-to-Tissue - Oxygen Transport to Tissue XVIII CY AUG 23-27, 1995 CL PITTSBURGH, PA SP Int Soc Oxygen Transport Tissue ID SMOOTH-MUSCLE CELL; GROWTH; LDL AB Oxidation of low density lipoprotein (LDL) has been implicated in atherogenesis. It has also been suggested that modification of LDL in the presence of endothelial and smooth muscle cells is associated with the production of superoxide. Red cells and hemoglobin have been shown to be a source for enhanced superoxide production under hypoxic conditions. We now show that incubation of LDL with both hemoglobin and erythrocytes under hypoxic conditions produces the increased Relative Electrophoretic Mobility (REM) associated with LDL oxidation. With hypoxic hemoglobin, this reaction is over within 10 minutes, appreciably faster than other in vitro methods for LDL oxidation. The increased REM was found to be associated with partial deoxygenation of hemoglobin indicative of appreciable oxygen utilization and a more hypoxic state. At later times, the modified LDL was found to produce enhanced hemoglobin oxidation. The resultant modified LDL was shown to have elevated TEARS indicative of LDL oxidation. In addition, it was found to induce smooth muscle cell proliferation which is one of the biological factors thought to be associated with atherogenesis. The relatively rapid LDL modification detected with hypoxic erythrocytes and hemoglobin suggest that even under in vivo conditions with the antioxidants present in plasma, oxidation may still occur in the circulation with the associated vascular damage occurring as the blood containing elevated levels of oxidized LDL leave the pulmonary circulation. RP Balagopalakrishna, C (reprint author), NIA, CELLULAR & MOL BIOL LAB, NIH, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 14 TC 3 Z9 3 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45516-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 411 BP 337 EP 345 PG 9 WC Cell Biology; Medicine, Research & Experimental; Physiology SC Cell Biology; Research & Experimental Medicine; Physiology GA BJ31R UT WOS:A1997BJ31R00042 PM 9269446 ER PT B AU Long, LR Pillemer, SR Goh, GH Berman, LE Neve, L Thoma, GR Premkuman, A Ostchega, Y Lawrence, RC Altman, RD Lane, NE Scott, WW AF Long, LR Pillemer, SR Goh, GH Berman, LE Neve, L Thoma, GR Premkuman, A Ostchega, Y Lawrence, RC Altman, RD Lane, NE Scott, WW BE Horii, SC Blaine, GJ TI A digital atlas for spinal x-rays SO PACS DESIGN AND EVALUATION: ENGINEERING AND CLINICAL ISSUES - MEDICAL IMAGING 1997 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on PACS Design and Evaluation - Engineering and Clinical Issues, at the Medical Imaging 1997 Meeting CY FEB 25-28, 1997 CL NEWPORT BEACH, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, US FDA, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Informat Syst Consortium, Radiol Soc N Amer, Soc Comp Applicat Radiol DE atlas; digital; x-ray; osteoarthritis,; cervical spine; lumbar spine; Internet; World Wide Web; NHANES; NLM; NIAMS; NCHS AB At the National Library of Medicine (NLM) we are developing a digital atlas to serve as a reference tool for the interpretation of cervical and lumbar spine x-rays. The atlas contains representative images for four grades of severity for cervical/lumbar anterior osteophytes and disc space narrowing, and presence/absence for cervical subluxation and lumbar spondylolisthesis. A prototype version of the atlas has been built using images for which expert rheumatologist readers reached exact agreement in grading. The atlas functionality includes the ability to display cervical and lumbar anatomy, display of single images or multiple simultaneous images, image processing functions, and capability to add user-defined images to the atlas. Images are selected for display by the user specifying feature and grade (example: ''anterior osteophytes, grade 2''). Currently, the atlas runs on a Sun SPARC workstation under the Solaris operating system. The initial use of the atlas is to aid in reading a collection of 17,000 NHANES II digitized x-rays. The atlas may also be used as a general digital reference tool for the standardized interpretation of digital x-rays for osteoarthritis. We are investigating further development of the atlas to accommodate a wider set of Images, to operate on multiple platforms, and, to be accessible via the World Wide Web. RP Long, LR (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2446-3 J9 P SOC PHOTO-OPT INS PY 1997 VL 3035 BP 586 EP 594 DI 10.1117/12.274621 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BH98D UT WOS:A1997BH98D00073 ER PT J AU Adams, MM Herman, AA Notzon, FC AF Adams, MM Herman, AA Notzon, FC TI International symposium on maternally-linked pregnancy outcomes - Preface SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Editorial Material C1 NICHHD,NIH,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,OFF INT STAT,HYATTSVILLE,MD 20782. RP Adams, MM (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,DIV REPROD HLTH,WHO,ATLANTA,GA, USA. NR 0 TC 25 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 1997 VL 11 SU 1 BP 1 EP 1 PG 1 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA WC570 UT WOS:A1997WC57000001 ER PT J AU McCarthy, BJ Berendes, HW AF McCarthy, BJ Berendes, HW TI Pregnancy outcome investigation for the 21st century - Commentary SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Editorial Material C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,NIH,BETHESDA,MD 20892. RP McCarthy, BJ (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,DIV REPROD HLTH,WHO,ATLANTA,GA 30341, USA. NR 3 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 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 1997 VL 11 SU 1 BP 2 EP 4 PG 3 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA WC570 UT WOS:A1997WC57000002 PM 9018710 ER PT J AU Herman, AA McCarthy, BJ Bakewell, JM Ward, RH Mueller, BA Maconochie, NE Read, AW Zadka, P Skjaerven, R AF Herman, AA McCarthy, BJ Bakewell, JM Ward, RH Mueller, BA Maconochie, NE Read, AW Zadka, P Skjaerven, R TI Data linkage methods used in maternally-linked birth and infant death surveillance data sets from the United States (Georgia, Missouri, Utah and Washington State), Israel, Norway, Scotland and Western Australia SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Maternally Linked Pregnancy Outcomes CY SEP, 1995 CL ATLANTA, GA ID PREGNANCY AB In this paper we describe the methods used to link birth and infant mortality and morbidity surveillance data sets into sibships using deterministic or multistage probabilistic linkage methods. We describe nine linked data sets: four in the United States (Georgia, Missouri, Utah and Washington State), and four elsewhere (Scotland, Norway, Israel and Western Australia). Norway and Israel use deterministic methods to Link births and deaths into sibships. The deterministic linkage is usually dependent on the availability of national identification numbers. In both countries they assign these numbers at birth. Deterministic Linkage is usually highly successful, and the major problem is the validation of linkages. In the United States, Western Australia and UK linkage is multistage and probabilistic. This approach is usually dependent on the calculation linkage weights from sociodemographic variables. The success rates of probabilistic methods are above 80%. Maternally-linked perinatal data open new vistas for epidemiological research. Recurrence of poor perinatal outcomes is more appropriately studied using longitudinally-linked data sets. In addition, the emergence of risk factors and the recurrence of risk factors can be studied. C1 CTR DIS CONTROL & PREVENT, NATL CTR CHRON DIS PREVENT & HLTH PROMOT, DIV REPROD HLTH, WHO, ATLANTA, GA USA. MISSOURI DEPT HLTH, BUR HLTH DATA ANAL, JEFFERSON CITY, MO USA. UNIV UTAH, DEPT HUMAN GENET, SALT LAKE CITY, UT USA. UNIV WASHINGTON, DEPT EPIDEMIOL, SEATTLE, WA USA. UNIV OXFORD, ICRF, CANC EPIDEMIOL UNIT, OXFORD, ENGLAND. TVW TELETHON INST CHILD HLTH RES, PERTH, WA, AUSTRALIA. CENT BUR STAT, HLTH DIV, JERUSALEM, ISRAEL. UNIV BERGEN, MED INFORMAT & STAT SECT, BERGEN, NORWAY. RP Herman, AA (reprint author), NICHHD, EPIDEMIOL BRANCH,DIV EPIDEMIOL STAT & PREVENT RES, NIH,BLDG 6100, ROOM 7803, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [N01-HD-0-2915, N01-HD-0-2916]; Wellcome Trust NR 20 TC 106 Z9 107 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 1997 VL 11 SU 1 BP 5 EP 22 DI 10.1046/j.1365-3016.11.s1.11.x PG 18 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA WC570 UT WOS:A1997WC57000003 PM 9018711 ER PT J AU Krulewitch, CJ Herman, AA Yu, KF Johnson, YR AF Krulewitch, CJ Herman, AA Yu, KF Johnson, YR TI Does changing paternity contribute to the risk of intrauterine growth retardation? SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Maternally Linked Pregnancy Outcomes CY SEP, 1995 CL ATLANTA, GA ID CHRONIC VILLITIS; PRE-ECLAMPSIA; PREECLAMPSIA; PREGNANCIES; PLACENTAE; COMPLEX AB An immune reaction initiated by paternal antigens may be necessary for healthy placental development, pregnancy maintenance and infant growth. An inadequate immune response may result in intrauterine growth retardation (IUGR). We hypothesised that a change in paternity may interfere with the immune response and cause poor placentation with resultant IUGR. Ln this paper we examine the risk of IUGR associated with changes in paternity. We used the Utah Successive Pregnancies Data Set that contains information on women across their pregnancies. We restricted the analysis to 141 817 women with two or three pregnancies. Women who did not have an IUGR infant in the previous pregnancy were at a 20-30% greater risk of developing IUGR if they had changed partners. Women who had a previous IUGR infant were at no increased risk for IUGR after a change in paternity. These results may point to an immune mechanism or may be as a result of residual confounding of unmeasured risk factors for IUGR. Further studies with data that contain more sociodemographic and biological risk factors for IUGR are necessary to exclude residual confounding. C1 CTR DIS CONTROL & PREVENT,PREGNANCY & INFANT HLTH BRANCH,DIV REPROD HLTH,ATLANTA,GA. NICHHD,NIH,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. NR 23 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 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 1997 VL 11 SU 1 BP 41 EP 47 DI 10.1046/j.1365-3016.11.s1.7.x PG 7 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA WC570 UT WOS:A1997WC57000006 PM 9018714 ER PT J AU Herman, AA Yu, KF AF Herman, AA Yu, KF TI Adolescent age at first pregnancy and subsequent obesity SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Maternally Linked Pregnancy Outcomes CY SEP, 1995 CL ATLANTA, GA ID POSTPARTUM WEIGHT RETENTION; MATERNAL BODY-WEIGHT; RISK FACTOR; WOMEN AB Adolescent pregnancy has been associated with subsequent obesity. This paper examines the patterns of obesity for second and third pregnancies among women who had their first singleton pregnancy as teenagers. We used maternally-linked data from 1978 to 1990 among 43 160 Missouri resident women. Age, parity, interpregnancy interval and prior body mass index were significantly associated with subsequent obesity among adolescents. Race, marital status and smoking had significant interactions with age. Among older women, being African-American and never having married was associated with an increased probability of obesity, and smoking had a greater effect on obesity at higher maternal age. Race and marital status did not have significant effects on obesity among younger women, The most important predictor of obesity was prior body mass index. Body mass index before the first pregnancy had a greater effect on subsequent obesity if the intervening interpregnancy weight gains were large. Excessive weight gain during pregnancy presents the health care provider with a dilemma. An increase in birthweight associated with high prenatal weight gains may diminish the risk of infant mortality and morbidity in an index pregnancy, but subsequent obesity may increase perinatal mortality rates, the rates of obstetric problems and neural tube defects. C1 NICHHD,STAT BRANCH,DIV EPIDEMIOL STAT & PREVENT RES,NIH,BETHESDA,MD 20892. RP Herman, AA (reprint author), NICHHD,EPIDEMIOL BRANCH,DIV EPIDEMIOL STAT & PREVENT RES,NIH,BLDG 6100,ROOM 7803,BETHESDA,MD 20892, USA. NR 30 TC 31 Z9 31 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 1997 VL 11 SU 1 BP 130 EP 141 DI 10.1046/j.1365-3016.11.s1.5.x PG 12 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA WC570 UT WOS:A1997WC57000014 PM 9018722 ER PT J AU Cheever, AW Lewis, FA Wynn, TA AF Cheever, AW Lewis, FA Wynn, TA TI Schistosoma mansoni: Unisexual infections sensitize mice for granuloma formation around intravenously injected eggs SO PARASITOLOGY RESEARCH LA English DT Article ID IDENTIFICATION; RESPONSES; ANTIBODY; ANTIGENS AB Mice carrying unisexual infection with male or female Schistosoma mansoni for 9 weeks developed accelerated and augmented reactions to S. mansoni eggs injected intravenously. The size of circumoval granulomas observed in the lungs of unisexually infected mice did not differ significantly from the reactions seen in bisexually infected mice. Tissue eosinophilia in the granulomas was also augmented similarly over that in naive mice by unisexual or bisexual infection. The cross-reactivity between worm and egg antigens is relevant to the development of acute toxemic schistosomiasis mansoni and, perhaps, to the consideration of antigens to be used for vaccination against S. mansoni infection. C1 BIOMED RES INST,ROCKVILLE,MD 20852. RP Cheever, AW (reprint author), NIAID,PARASIT DIS LAB,NIH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 11 TC 22 Z9 23 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0044-3255 J9 PARASITOL RES JI Parasitol. Res. PD JAN PY 1997 VL 83 IS 1 BP 57 EP 59 PG 3 WC Parasitology SC Parasitology GA VW842 UT WOS:A1997VW84200012 PM 9000235 ER PT J AU Quakyi, EK Carter, PH Tsai, CM Marti, GE AF Quakyi, EK Carter, PH Tsai, CM Marti, GE TI Immunization with meningococcal membrane-bound lipooligosaccharide accelerates granulocyte recovery enhances lymphocyte proliferation in myelosuppressed mice SO PATHOBIOLOGY LA English DT Article DE septic shock; myelosuppression; granulocytes; lipooligosaccharide; meningococcus; cyclophosphamide; flow cytometry; interferon-gamma; interleukin-6; interleukin-1 beta; interleukin-3; white blood cell lysis ID COLONY-STIMULATING FACTOR; STEM-CELL FACTOR; MURINE HEMATOPOIETIC PROGENITORS; INTERFERON-GAMMA; BONE-MARROW; INTERLEUKIN-6; IL-6; CYCLOPHOSPHAMIDE; VACCINE; MECHANISMS AB Protective effects of detergent-treated outer membrane vesicles (D-OMVs) prepared from the parent group B M986 strain and the nonencapsulated M986-NCV mutant in myelosuppressed mice were investigated in models of experimental septic shock. The effects of D-OMVs on expansion of the myeloid compartment, on spleen cell proliferation to mitogen stimulation, and on cytokines induced during this period were investigated. On 3 consecutive days, mice were injected with 1 mu g/kg of lipooligosaccharide (LOS) or lipopolysaccharide, or 75 mu g/kg D-OMV followed by a single dose of cyclophosphamide (200 mg/kg) 24 h later, Eight weeks after the last injection, animals were challenged with a combination of galactosamine (400 mg/kg) and live Neisseria meningitidis. More than 90% of control mice died within 24 h when challenged with 10(5) CFU of bacteria. Mice immunized with LOS or D-OMV were rendered neutropenic but were protected against bacterial challenge of at least 10(7) CFU. At different time intervals, peripheral blood samples were obtained to characterize changes in circulating blood cells. The rise in absolute granulocyte numbers occurred 24 h earlier with peak cell counts about 3 times higher than those seen in the placebo groups, Peripheral blood cells from D-OMV-treated animals expressed about twofold more Gr-1 antigen (myeloid surface cell marker) than placebo-treated controls. The proliferative responses to both B and T cells were reduced in all treatment groups due to the effects of cyclophosphamide. D-OMV treatment afforded the greatest protection for mitogen-activated lymphocytes from the lethal effects of cyclophosphamide and also enhanced T and B cell proliferation. Low IL-1 beta levels and increases in serum IL-6 were detected in all treatment groups. In contrast, significant IFN-gamma and IL-3 levels were only detected in D-OMV-treated groups. These results indicate that D-OMVs, which have reduced toxicity, have prophylactic potential in inducing specific cytokines that accelerate granulocyte recovery following cytoreductive therapy by promoting both proliferation and maturation of myeloid precursors as well as augmenting the immune system. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELL & GENE THERAPIES,FLOW & IMAGE CYTOMETRY SECT,NIH,BETHESDA,MD 20892. NR 49 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD JAN-FEB PY 1997 VL 65 IS 1 BP 26 EP 38 DI 10.1159/000164100 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA XE702 UT WOS:A1997XE70200003 PM 9200187 ER PT J AU Shaffer, DN Mansmann, PT AF Shaffer, DN Mansmann, PT TI Leukotriene inhibition and advances in the treatment of asthma: A pharmacological review SO PEDIATRIC ASTHMA ALLERGY & IMMUNOLOGY LA English DT Review ID 5-LIPOXYGENASE AB The optimal treatment of asthma remains problematic when considered by healthcare providers, Despite increasing knowledge regarding the pathophysiology of asthma and the role of inflammatory mediators, prevalence as well as morbidity and mortality rates continue to rise, Since the introduction of inhaled beta-agonists and inhaled corticosteroids in the 1980s, little has changed in the pharmacological armamentarium of treatment options, Recently, attention has focused on the pharmacological manipulation of leukotrienes as treatment modalities, Two leukotriene modifiers introduced in 1996 herald the first new pharmacological class of antiasthma medicines in the United States in 25 years, With the significant morbidity and mortality of asthma as well as cost in healthcare dollars and time lost from work, attention to these agents and their role in the treatment of asthma is warranted. The objective of this article is to review the pharmacology and clinical applications of this new class of drugs focusing specifically on the two recently introduced agents, zafirlukast and zileuton, Historical perspectives in the treatment of asthma and potential, future uses of leukotriene modifiers is also addressed. C1 W Virginia Univ, Sch Med, Robert C Byrd Hlth Sci Ctr, Dept Med & Rheumatol, Morgantown, WV 26506 USA. RP Shaffer, DN (reprint author), NHLBI, NIH, Bldg 10,Room 8C103, Bethesda, MD 20892 USA. NR 18 TC 3 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0883-1874 J9 PEDIATR ASTHMA ALLER JI Pediatr. Asthma Allergy Immunol. PY 1997 VL 11 IS 4 BP 171 EP 179 DI 10.1089/pai.1997.11.171 PG 9 WC Allergy; Immunology; Pediatrics; Respiratory System SC Allergy; Immunology; Pediatrics; Respiratory System GA YZ957 UT WOS:000072312200002 ER PT J AU Freifeld, A Pizzo, P AF Freifeld, A Pizzo, P TI Use of fluoroquinolones for empirical management of febrile neutropenia in pediatric cancer patients SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE fluoroquinolones; febrile neutropenia; cancer; pediatric; empiric treatment ID INTRAVENOUS CIPROFLOXACIN; ANTIBIOTIC-THERAPY; RANDOMIZED TRIAL; IMMUNOCOMPROMISED PATIENTS; PREDICTION RULE; FEVER; CEFTAZIDIME; EPISODES; COMBINATION; MONOTHERAPY AB Background. Empiric antibiotic therapy has become a standard of care far the febrile neutropenic patient. Many clinical trials over the previous three decades have demonstrated that a variety of antibiotic combinations and more recently potent antibiotic monotherapies may preserve the patient through the critical time of fever and neutropenia. Recently attempts have been made to identify ''low risk'' patients who may not require traditional, intensive, hospitalized intravenous antimicrobial therapy. Therefore the need for new treatment alternatives for the febrile neutropenic pediatric cancer patient in particular revolves around the desire for less complex regimens, agents with minimal toxicity and expense and the option of an oral formulation for outpatient management. Objective. Fluoroquinolones, especially ciprofloxacin and ofloxacin, are examined in this paper as potential oral alternatives for managing the low risk neutropenic pediatric cancer patient population. Attention must be paid to their antibacterial spectra, however, and in some cases fluoroquinolones should be combined with a second agent for additional Gram-positive coverage. Results, Several studies, including one ongoing trial at the National. Cancer Institute, have shown the potential benefits of oral fluoroquinolone therapy among low risk febrile neutropenic patients, joint complaints in children after ciprofloxacin therapy in the National Cancer Institute trial thus far have been minimal, reversible and felt to be unrelated to ciprofloxacin treatment. Conclusion. The use of outpatient therapy, such as the fluoroquinolones, to manage febrile neutropenic episodes must be approached with caution and should be undertaken only in selected low risk patients. RP Freifeld, A (reprint author), NCI,INFECT DIS SECT,NIH,BETHESDA,MD 20892, USA. NR 29 TC 25 Z9 26 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 1997 VL 16 IS 1 BP 140 EP 146 DI 10.1097/00006454-199701000-00039 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA WC701 UT WOS:A1997WC70100035 PM 9002125 ER PT J AU Bendon, RW FayePetersen, O Pavlova, Z Qureshi, F Elder, N Das, A Hauth, J McNellis, D Mercer, B Miodovnik, M AF Bendon, RW FayePetersen, O Pavlova, Z Qureshi, F Elder, N Das, A Hauth, J McNellis, D Mercer, B Miodovnik, M TI Histologic features of chorioamnion membrane rupture: Development of methodology SO PEDIATRIC PATHOLOGY & LABORATORY MEDICINE LA English DT Article DE placenta; premature rupture of membranes; preterm labor ID PREMATURE RUPTURE; AGREEMENT; FLUID AB This study developed a set of histologic features that will allow subclassification of placentas with preterm premature rupture of membranes. Placentas were obtained from patients participating in a multi-institutional NICHD Maternal-Fetal Medicine Unit Network study of antimicrobial therapy after preterm premature rupture of membranes. The rupture site was sampled by inking the open sac margin and rolling a membrane strip in four quadrants from the ink to the placental margin. Independently, four pathologists used a provisional feature list to score the slides from 15 placentas. A concordance analysis was performed on those results. With those results, the slides were reviewed concurrently to discover the source of disagreements and to revise the feature list. The sampling method frequently demonstrated a rupture site with histology distinct front timi of the remainder of the membranes. After review of the preliminary scoring results, 29 features of membrane histology present in preterm premature rupture could be objectively described with agreement among four pathologists. The feature list allows both novel and commonly recognized histologic features of fetal membranes to be recorded with objectivity. This list, with the described sampling technique, is presented as a tool for clinical correlation in studies of membrane rupture, especially in preterm, premature rupture. C1 UNIV ALABAMA,BIRMINGHAM,AL. UNIV SO CALIF,MED CTR,LOS ANGELES,CA. WAYNE STATE UNIV,DETROIT,MI. UNIV CINCINNATI,CINCINNATI,OH. GEORGE WASHINGTON UNIV,WASHINGTON,DC. NICHHD,MFMU NETWORK,BETHESDA,MD. UNIV TENNESSEE,MEMPHIS,TN. RP Bendon, RW (reprint author), KOSAIR CHILDRENS HOSP,DEPT PATHOL,231 E CHESTNUT ST,LOUISVILLE,KY 40232, USA. FU NICHD NIH HHS [HD21414, HD21410, HD21434] NR 23 TC 20 Z9 20 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1077-1042 J9 PEDIATR PATHOL LAB M JI Pediatr. Pathol. Lab. Med. PD JAN-FEB PY 1997 VL 17 IS 1 BP 27 EP 42 DI 10.1080/107710497175001 PG 16 WC Pathology; Pediatrics SC Pathology; Pediatrics GA WF268 UT WOS:A1997WF26800003 PM 9050058 ER PT J AU Seibel, NL Walsh, TJ AF Seibel, NL Walsh, TJ TI Pulmonary aspergillosis in immunocompromised children SO PEDIATRIC PULMONOLOGY LA English DT Article; Proceedings Paper CT 2nd International Congress on Pediatric Pulmonology (CIPP II) CY JUN 02-05, 1996 CL NICE, FRANCE ID BRONCHOALVEOLAR LAVAGE; DIAGNOSIS C1 Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. NCI, Pediat Branch, Infect Dis Sect, Mycol Unit, Bethesda, MD 20892 USA. RP Seibel, NL (reprint author), Childrens Natl Med Ctr, Dept Hematol Oncol, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 9 TC 0 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 1997 SU 16 BP 61 EP 62 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA YR008 UT WOS:000071447800032 PM 9443201 ER PT J AU Berlin, CM McCarverMay, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Weller, EB Bennett, DR Mulinare, J Kaufman, P Krough, C Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ Blumer, JL Frader, JE Crain, LS Moseley, KL Nelson, RM Porter, IH Vizcarrondo, FE Bowes, WA Kazura, A Krug, EF Caniano, DA Dressser, R King, NMP AF Berlin, CM McCarverMay, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Weller, EB Bennett, DR Mulinare, J Kaufman, P Krough, C Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ Blumer, JL Frader, JE Crain, LS Moseley, KL Nelson, RM Porter, IH Vizcarrondo, FE Bowes, WA Kazura, A Krug, EF Caniano, DA Dressser, R King, NMP TI Considerations related to the use of recombinant human growth hormone in children SO PEDIATRICS LA English DT Article ID CONSTITUTIONAL SHORT STATURE; CREUTZFELDT-JAKOB DISEASE; CHRONIC-RENAL-FAILURE; DEFICIENT CHILDREN; TURNER SYNDROME; THERAPY; HYPOPITUITARISM; ADOLESCENTS; METABOLISM; SECRETION AB Since 1985 molecular biology techniques have made possible the synthetic synthesis of pure human growth hormone in potentially unlimited amounts. With this increased availability, its use in patients other than children with growth hormone deficiency has been associated with clinical and ethical questions. This statement presents an analysis of the current status of the use of human growth hormone in children. C1 AMER MED ASSOC,US PHARMACOPEIA,CHICAGO,IL. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. HLTH PROTECT BRANCH,OTTAWA,ON,CANADA. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD. AMER BOARD PEDIAT INC,CHAPEL HILL,NC. RI Moseley, Kathryn/A-8859-2009; Frader, Joel/A-8610-2010 NR 71 TC 39 Z9 40 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 JAN PY 1997 VL 99 IS 1 BP 122 EP 129 PG 8 WC Pediatrics SC Pediatrics GA WB350 UT WOS:A1997WB35000020 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R TI Recommended childhood immunization schedule - United States, January-December 1997 SO PEDIATRICS LA English DT Article C1 US FDA,ROCKVILLE,MD 20857. AMER THORAC SOC,NEW YORK,NY. NIAID,BETHESDA,MD. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. NR 1 TC 12 Z9 13 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 JAN PY 1997 VL 99 IS 1 BP 136 EP 138 PG 3 WC Pediatrics SC Pediatrics GA WB350 UT WOS:A1997WB35000023 ER PT J AU Viswanathan, M DeOliveira, AM Johren, O Saavedra, JM AF Viswanathan, M DeOliveira, AM Johren, O Saavedra, JM TI Increased endothelin ETA receptor expression in rat carotid arteries after balloon injury SO PEPTIDES LA English DT Article DE endothelin; endothelin receptor subtypes; growth; vascular smooth muscle ID SMOOTH-MUSCLE CELLS; INDUCED NEOINTIMA FORMATION; ANGIOTENSIN-II; DNA-SYNTHESIS; ANTAGONIST; PROLIFERATION; ANGIOPLASTY; ATHEROSCLEROSIS; BINDING; BQ-123 AB Endothelins are vasoactive peptides and are believed to act as vascular smooth muscle mitogens. Vascular injury results in medial smooth muscle migration and proliferation with the formation of a neointima. Using quantitative autoradiography, we examined the expression of endothelin receptor subtypes ETA and ETB in the rat carotid artery 2, 8, and 16 days after balloon- catheter injury. At two and eight days after balloon catheterization, ETA receptor expression was significantly increased in the media of the injured vessel when compared to that in the media of the intact vessel. The enhanced expression of receptors returned to normal levels by 16 days after the injury. Neointimal cells also expressed ETA receptors at a lower lever than that expressed by the injured media 8 days after injury, and continued to express ETA receptors 16 days after the injury. ETB receptors were not detectable in the media or the neointima at any time after the injury. Our results suggest that ETA receptors may have a significant role in injury induced vascular smooth muscle proliferation and neointima formation. Published by Elsevier Science Inc. RP Viswanathan, M (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,10 CTR DR MS 1514,BETHESDA,MD 20892, USA. RI Johren, Olaf/G-6967-2011 NR 42 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0196-9781 J9 PEPTIDES JI Peptides PY 1997 VL 18 IS 2 BP 247 EP 255 DI 10.1016/S0196-9781(96)00285-9 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA WX954 UT WOS:A1997WX95400011 PM 9149297 ER PT J AU Moody, TW Miller, MJ Martinez, A Unsworth, E Cuttitta, F AF Moody, TW Miller, MJ Martinez, A Unsworth, E Cuttitta, F TI Adrenomedullin binds with high affinity, elevates cyclic AMP, and stimulates c-fos mRNA in C6 glioma cells SO PEPTIDES LA English DT Article DE adrenomedullin; cGRP; receptors; cAMP; proliferation ID GENE-RELATED PEPTIDE; RAT ADRENOMEDULLIN; HUMAN TISSUE; CALCITONIN; RECEPTOR; EXPRESSION; GROWTH; SITES; IDENTIFICATION; NEUROBLASTOMA AB The effects of adrenomedul lin (ADM) on C6 glioma cells were investigated. [I-125]ADM bound with high affinity (K-d = 24 nM) to a single class of sites (B-max = 36,000/cell) in C6 cells. Specific [I-125]ADM binding was inhibited with high affinity by ADM (IC50 value of 10 nM) but not ADM(22-52) or pro-adrenomedullin N-terminal 20 peptide (PAMP). By RT-PCR, ADM receptors were detected in C6 cells. ADM elevated cAMP (ED50 value of 10 nM) whereas PAMP and ADM(22-52) did not. ADM stimulated transiently c-fos mRNA in a concentration-dependent manner. Monoclonal antibody G6, which neutralizes ADM, significantly inhibited C6 proliferation and decreased the ability of ADM to elevate c-fos mRNA. These data suggest that ADM is a regulatory peptide of C6 cells. (C) 1997 Elsevier Science Inc. RP Moody, TW (reprint author), NCI, MED BRANCH,DEPT CELL & CANC BIOL,DIV CLIN SCI, BLDG KWC,RM 300, 9610 MED CTR DR, ROCKVILLE, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 31 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PY 1997 VL 18 IS 8 BP 1111 EP 1115 DI 10.1016/S0196-9781(97)00179-4 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA YF797 UT WOS:A1997YF79700003 PM 9396050 ER PT J AU Wu, JY Henins, KA Gressens, P Gozes, I Fridkin, M Brenneman, DE Hill, JM AF Wu, JY Henins, KA Gressens, P Gozes, I Fridkin, M Brenneman, DE Hill, JM TI Neurobehavioral development of neonatal mice following blockade of VIP during the early embryonic period SO PEPTIDES LA English DT Article DE vasoactive intestinal peptide; neurobehavioral development; VIP antagonist; mouse embryos; developmental milestones; developmental retardation ID VASOACTIVE-INTESTINAL-PEPTIDE; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; INTRACELLULAR CALCIUM; FUNCTIONAL EXPRESSION; NEURONAL SURVIVAL; CEREBRAL-CORTEX; BINDING-SITES; SLEEP FACTOR; RECEPTORS AB Previous work has shown that blockade of VIP function in the early postimplantation embryo results in growth retardation and microcephaly. In the present work, the neurobehavioral development of neonatal mice was examined following treatment of dams with a VIP antagonist during this period. Inhibition of VIP functions during early embryogenesis impaired the performance of 5 of 10 developmental behaviors. These behaviors included developmental milestones (first appearance of ear twitch and eye opening) and complex motor behaviors (negative geotaxis, surface righting, and air righting). The retardation of neurobehavioral development produced by inhibition of VIP action indicates that this peptide is important to the progression of embryonic development. Published by Elsevier Science Inc. C1 NICHHD, LDN, SECT DEV & MOL PHARMACOL, NIH, BETHESDA, MD 20892 USA. HOP ROBERT DEBRE, SERV NEUROPEDIAT, F-75019 PARIS, FRANCE. TEL AVIV UNIV, SACKLER SCH MED, DEPT CLIN BIOCHEM, IL-69978 TEL AVIV, ISRAEL. WEIZMANN INST SCI, DEPT ORGAN CHEM, IL-76100 REHOVOT, ISRAEL. NR 45 TC 40 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PY 1997 VL 18 IS 8 BP 1131 EP 1137 DI 10.1016/S0196-9781(97)00146-0 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA YF797 UT WOS:A1997YF79700006 PM 9396053 ER PT B AU Schmidt, PJ Roca, CA Rubinow, DR AF Schmidt, PJ Roca, CA Rubinow, DR BE Lobo, RA TI Perimenopausal depression SO PERIMENOPAUSE SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT International Symposium on Perimenopause CY NOV 17-20, 1995 CL PALM BEACH GARDENS, FL SP Serono Symp USA Inc RP Schmidt, PJ (reprint author), NIMH,SECT BEHAV ENDOCRINOL,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 BN 0-387-94967-4 J9 SERONO SYMP PY 1997 BP 246 EP 254 PG 9 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA BJ84Q UT WOS:A1997BJ84Q00018 ER PT S AU LaMontagne, JR AF LaMontagne, JR BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI The United States research strategy on pertussis SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat AB Wide-scale use of whole-cell Vaccines has led to good control of pertussis disease in the United States; however, this control has been achieved at the cost of common and uncommon adverse events of known frequencies. Agencies of the U.S. Public Health Service actively stimulated the development of new pertussis Vaccines by directly supporting basic and applied research and increasing interactions with industry and with health authorities in other countries. This international cooperation resulted in a better understanding of the pathogenesis of pertussis and in the final development and clinical testing of several candidate acellular pertussis vaccines. RP LaMontagne, JR (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,NIH,3A18 SOLAR BLDG,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 25 EP 28 PG 4 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00003 PM 9272332 ER PT S AU Blackwelder, WC VanRaden, MJ Deloria, MA AF Blackwelder, WC VanRaden, MJ Deloria, MA BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI Estimation of pertussis vaccine efficacy in the presence of covariates in three randomized trials SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat DE acellular pertussis vaccines; efficacy; covariates; duration of protection AB We estimated efficacy of pertussis Vaccines in three randomized controlled trials with adjustment for several baseline covariates: presence of one or more other children in the household, sex of the study child, and geographical area. Adjusted and unadjusted efficacy estimates differed only trivially. We also assessed the association of efficacy with time since vaccination and background pertussis incidence. The acellular vaccines, except for the two-component vaccine in the Stockholm trial, appeared to maintain their efficacy during two years of follow-up. in contrast, efficacy of a whole-cell vaccine decreased significantly in both the Stockholm and Italian trials. The relationship between efficacy and background incidence was not consistent across studies and vaccines. RP Blackwelder, WC (reprint author), NIAID,SOLAR BLDG,ROOM 3A03,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 161 EP 166 PG 6 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00017 PM 9272346 ER PT S AU Schneerson, R Robbins, JB Taranger, J Lagerard, T Trollfors, B AF Schneerson, R Robbins, JB Taranger, J Lagerard, T Trollfors, B BE Brown, F Greco, D Mastrantonio, P Salmaso, S Wassilak, S TI Examination of similarities between diphtheria and pertussis and their toxoids provide insight into vaccine-induced protection to Bordetella pertussis SO PERTUSSIS VACCINE TRIALS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT International Symposium on Pertussis Vaccine Trials CY OCT 30, 1995-NOV 01, 1996 CL ROME, ITALY SP Ist Super Sanita, WHO, Childrens Vaccine Initiat, NiAID, Int Federat Pharm Manufacturers Assoc, European Commiss COST STD Initiat, European Vaccine Res, Int Assoc Biol Standardizat DE diphtheria toxoids; pertussis toxoids; vaccination ID WHOOPING-COUGH; TOXIN; EPIDEMIOLOGY; IMMUNITY; EFFICACY; GENE C1 NICHHD,NIH,BETHESDA,MD 20892. NR 34 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6481-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1997 VL 89 BP 321 EP 326 PG 6 WC Biology; Biotechnology & Applied Microbiology SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology GA BJ43T UT WOS:A1997BJ43T00037 PM 9272366 ER PT J AU He, XJ Tse, CM Donowitz, M Alper, SL Gabriel, SE Baum, BJ AF He, XJ Tse, CM Donowitz, M Alper, SL Gabriel, SE Baum, BJ TI Polarized distribution of key membrane transport proteins in the rat submandibular gland SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE confocal microscopy; immunofluorescence; membrane proteins; salivary secretion; salivary glands ID SALIVARY-GLANDS; FLUID SECRETION; ION-TRANSPORT; MOLECULAR-CLONING; WATER CHANNELS; ACINAR-CELLS; LOCALIZATION; DUCTS; IDENTIFICATION; EPITHELIUM AB Immunofluorescence labelling and confocal microscopy were employed to examine the polarized distribution of several membrane transport proteins believed to be essential for salivary secretion in the rat submandibular gland. The Na+/K+-ATPase, Na+/H+ exchanger isoform 1 (NHE1), and the secretory Na+/K+/2Cl(-) cotransporter isoform were all found in the basolateral membranes of acinar and intralobular duct cells. Anion exchanger isoform 2 (AE2) was found only in the basolateral membranes of acinar cells, while AE1 was absent from glandular epithelial cells. Aquaporin 5 was detected in the apical membranes of acinar cells, while the cystic fibrosis transmembrane conductance regulator was found only in apical membranes of intralobular duct cells. NHEs 2 and 3 were found in the apical membranes of both acinar and intralobular duct cells. Our results are generally consistent with the expected distribution of most transporters based on previous physiological and pharmacological experiments. However, the epical localization of NHEs 2 and 3, and the presence of the secretory isoform of the Na+/K+/2Cl(-) cotransporter in intralobular duct cells were not predicted. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GASTROENTEROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,DIV GASTROENTEROL,BALTIMORE,MD 21205. BETH ISRAEL HOSP,MOL MED UNIT,BOSTON,MA 02215. BETH ISRAEL HOSP,RENAL UNIT,BOSTON,MA 02215. UNIV N CAROLINA,CYST FIBROSIS RES & TREATMENT CTR,CHAPEL HILL,NC 27599. NR 43 TC 121 Z9 123 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JAN PY 1997 VL 433 IS 3 BP 260 EP 268 PG 9 WC Physiology SC Physiology GA WH693 UT WOS:A1997WH69300006 PM 9064641 ER PT J AU Gorlach, A Roesler, J Chanock, SJ Curnutte, JT AF Gorlach, A Roesler, J Chanock, SJ Curnutte, JT TI Identification of a pseudogene highly homologous to the NADPH oxidase component p47phox. SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Meeting Abstract C1 UNIV ZURICH IRCHEL, INST PHYSIOL, CH-8057 ZURICH, SWITZERLAND. SCRIPPS RES INST, LA JOLLA, CA 92037 USA. NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. TECH UNIV DRESDEN, KINDERKLIN, D-8027 DRESDEN, GERMANY. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PY 1997 VL 433 IS 6 SU S BP O92 EP O92 PG 1 WC Physiology SC Physiology GA WV421 UT WOS:A1997WV42100091 ER PT J AU Long, RM AF Long, RM TI What is the NIGMS doing to help smooth out the irregularities in funding for ongoing research programs that almost inevitably occur over time in today's fiscal climate? SO PHARMACEUTICAL RESEARCH LA English DT News Item RP Long, RM (reprint author), NIGMS,PHARMACOL & PHYSIOL SCI BRANCH,DIV PHARMACOL PHYSIOL & BIOL CHEM,NIH,BETHESDA,MD, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JAN PY 1997 VL 14 IS 1 BP 1 EP 1 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA WJ623 UT WOS:A1997WJ62300001 PM 9034213 ER PT J AU Witkin, JM Acri, JB Gleeson, S Barrett, EJ AF Witkin, JM Acri, JB Gleeson, S Barrett, EJ TI Blockade of behavioral effects of bretazenil by flumazenil and ZK 93,426 in pigeons SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE bretazenil; flumazenil; ZK 93,426; midazolam; punished behavior; drug discrimination ID BENZODIAZEPINE-RECEPTOR ANTAGONIST; DISCRIMINATIVE STIMULUS PROPERTIES; AMINOBUTYRIC ACID(A) RECEPTOR; GABA-A RECEPTORS; RO 15-1788; DRUG DISCRIMINATION; PARTIAL AGONISTS; PENTYLENETETRAZOLE-CUE; INTRINSIC EFFICACIES; DIAZEPAM AB Benzodiazepine receptor partial agonists manifest full efficacy in preclinical tests of anxiolytic drug action but do not fully reproduce the discriminative stimulus effects of benzodiazepine receptor full agonists in pigeons. The partial agonist, bretazenil, binds to both diazepam-sensitive and diazepam-insensitive GABA(A) receptors. Previous studies have suggested a role for each of these receptor populations in some behavioral effects of bretazenil in pigeons. A possible role for these receptor subtypes in the behavioral effects of bretazenil was further investigated through drug interaction studies with the benzodiazepine receptor antagonists, flumazenil and ZK 93,426. Whereas flumazenil binds with high affinity to both receptor isoforms, ZK 93,426 binds preferentially to diazepam-sensitive binding sites. Bretazenil markedly increased punished responding of pigeons without significantly affecting nonpunished responding. In pigeons discriminating the full benzodiazepine receptor agonist, midazolam, from saline, bretazenil produced only 60-75% maximal effect. Flumazenil and ZK 93,426 neither increased punished responding nor substituted for midazolam, but hose-dependently blocked the effects of bretazenil on punished responding. Flumazenil also dose-dependently blocked the effects of bretazenil in midazolam-discriminating pigeons, whereas ZK 93,426 only attenuated this effect. These results indicate that bretazenil's actions as a partial agonist at diazepam-sensitive benzodiazepine receptors mediate increases in unished responding and substitution for the discriminiative stimulus effects of midazolam in pigeons. The differences in the effects of flumazenil and ZK 93,426 on the discriminative stimulus effects of bretazenil suggest a potential contribution of diazepam-insensitive sites to this behavioral effect. Copyright (C) 1997 Elsevier Science Inc. C1 UNIFORMED SERV UNIV HLTH SCI, DEPT PSYCHIAT, BETHESDA, MD 20814 USA. RP Witkin, JM (reprint author), NIDA, ADDICT RES CTR, DRUG DEV GRP, NIH, POB 5180, BALTIMORE, MD 21224 USA. NR 56 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 1997 VL 56 IS 1 BP 1 EP 7 DI 10.1016/S0091-3057(96)00120-7 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA WA251 UT WOS:A1997WA25100001 PM 8981602 ER PT J AU Figg, WD Pluda, JM Lush, RM Saville, MW Wyvill, K Reed, E Yarchoan, R AF Figg, WD Pluda, JM Lush, RM Saville, MW Wyvill, K Reed, E Yarchoan, R TI The pharmacokinetics of TNP-470, a new angiogenesis inhibitor SO PHARMACOTHERAPY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; KAPOSIS-SARCOMA; TUMOR-GROWTH; AGM-1470; FUMAGILLIN; CELLS; SURAMIN; GENE AB Study Objective. To characterize the pharmacokinetic profile of TNP-470, a synthetic analog of fumagillin that is a potent inhibitor of angiogenesis and inhibits neovascularization in several solid tumor models. Design. A dose-escalation phase I clinical trial. Setting. The National Institutes of Health. Patients. Patients with human immunodeficiency virus-associated Kaposi's sarcoma. Interventions. The TNP-470 dosage was increased in 13 sequential cohorts using a modified Fibonacci escalation scheme (4.6, 9.3, 15.4, 23.2, and 43.1 mg/m(2)). The drug was administered as a 1-hour intravenous infusion. Serial blood samples were collected and assayed by reverse-phase highperformance liquid chromatography and the pharmacokinetics were characterized. Measurements and Main Results. There was a linear relationship between the dose of TNP-470 and both area under the curve to infinity (AUC([inf])) and time to maximum concentration (C-max). The C-max ranged between 6.6 ng/ml at the lowest dosage (4.6 mg/m(2)) and 597.1 ng/ml at the highest dosage (43.1 mg/m(2)). The agent was rapidly cleared from the circulation with a short terminal half-life (0.88 +/- 2.5 hr), which is consistent with preclinical data. Peak plasma concentrations of AGM-1883, an active metabolite, ranged between 0.4 and 158.1 ng/ml. Conclusion. Concentrations of TNP-470 that have in vitro activity were achievable in vivo. The drug was rapidly cleared from the circulation after a single 1-hour infusion. There was considerable interpatient variability in the clearance, but no evidence of saturable elimination. If more prolonged exposure is necessary for activity, administration of TNP-470 by continuous infusion may be suitable. C1 NCI,DEV CHEMOTHERAPY SECT,INVEST DRUG BRANCH,CANC TREATMENT EVALUAT PROGRAM,NIH,BETHESDA,MD 20892. NCI,RETROVIRAL DIS SECT,MED BRANCH,CLIN ONCOL PROGRAM,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. RP Figg, WD (reprint author), NCI,CLIN PHARMACOL BRANCH,CLIN PHARMACOKINET SECT,CLIN ONCOL PROGRAM,NIH,BLDG 10,ROOM 5A01,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 33 TC 51 Z9 53 U1 0 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JAN-FEB PY 1997 VL 17 IS 1 BP 91 EP 97 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WD766 UT WOS:A1997WD76600008 PM 9017768 ER PT J AU Spouge, JL AF Spouge, JL TI Single-particle survival in parallel gated trapping SO PHYSICAL REVIEW E LA English DT Article ID DYNAMIC TRAP AB Any chemical reaction A* + B --> C whose progress is modulated by another reaction of the form A* reversible arrow A is said to be gated. The gating reaction A* reversible arrow A represents a reversible fluctuation from a reactive state A* to an unreactive state A not reacting with B. Reversibly blocked chemical reactions, conformational fluctuations in proteins, and reactions occurring within biomembranes or involving biological molecules have all been studied recently in contexts related to gating. This article calculates certain trapping rates and mean survival times in the presence of a single gated trap. Unlike previous methods, the formalism in this paper is based directly on trapping rates and not on Green's functions. The trapping rate formalism leads quite naturally to explicit solutions for some recently developed (''parallel'') gating models, solutions that might be quite difficult to derive within a Green's-function formalism. These solutions give time-dependent rate coefficients for parallel gated chemical reactions. RP Spouge, JL (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 16 TC 7 Z9 7 U1 0 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD JAN PY 1997 VL 55 IS 1 BP 421 EP 425 DI 10.1103/PhysRevE.55.421 PN A PG 5 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA WD545 UT WOS:A1997WD54500053 ER PT S AU Sherman, A Smolen, P AF Sherman, A Smolen, P BE Soria, B TI Computer modeling of heterogeneous beta-cell populations SO PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE ISLETS OF LANGERHANS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 1st International Meeting of the Pancreatic-Islet-Study-Group of the European-Association-for-the-Study-of-Diabetes CY NOV 25-28, 1994 CL ALICANTE, SPAIN SP European Assoc Study Diabetes, Pancreat Islet Study Grp, Fundacion CAM, Generalitat Valenciana, Alicante City Council, Univ Alicante ID ELECTRICAL-ACTIVITY; PANCREATIC-ISLETS; MOUSE; OSCILLATIONS; GLUCOSE; LANGERHANS; CURRENTS; K+ C1 NIH, Math Res Branch, Bethesda, MD 20892 USA. RP Sherman, A (reprint author), NIH, Math Res Branch, Bldg 10, Bethesda, MD 20892 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45702-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 426 BP 275 EP 284 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Medicine, Research & Experimental; Pathology; Physiology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Research & Experimental Medicine; Pathology; Physiology GA BK61Q UT WOS:000072747900038 PM 9544285 ER PT B AU Bernard, M Iuvone, PM Cassone, VM Roseboom, PH Coon, SL Klein, DC AF Bernard, M Iuvone, PM Cassone, VM Roseboom, PH Coon, SL Klein, DC BE Webb, SM PuigDomingo, M Moller, M Pevet, P TI Chicken arylalkylamine N-acetyltransferase: Cloning and circadian regulation in the pineal gland SO PINEAL UPDATE: FROM MOLECULAR MECHANISMS TO CLINICAL IMPLICATIONS LA English DT Proceedings Paper CT 7th Colloquium of the European-Pineal-Society CY MAR 29-31, 1996 CL SITGES, SPAIN SP European Pineal Soc AB Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT) drives the circadian rhythm in melatonin production in the pineal gland. We have cloned cDNA encoding chicken AA-NAT and have used this to determine that AA-NAT mRNA levels in the pineal gland exhibit a strong day/night rhythm with a peak at night. This rhythm persists in constant darkness (DD) and constant lighting (LL), indicating that it is controlled by a circadian oscillator. Exposure to LL damps the AA-NAT activity rhythm, but does not decrease the amplitude of the rhythm in AA-NAT mRNA. Further evidence that activity and mRNA levels are not necessarily related comes from the observation that an unexpected pulse of light rapidly decreases enzyme activity, but not the levels of the AA-NAT transcript. In LL, the peak in both AA-NAT mRNA and AA-NAT activity was delayed by similar to 6 hr. These findings indicate that a clock controls the rhythm in AA-NAT mRNA and that independent mechanisms appear to control the translation of changes in mRNA into changes in enzyme activity. C1 NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 USA BN 0-915340-19-4 PY 1997 BP 29 EP 36 PG 4 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA BK42W UT WOS:000072152700003 ER PT B AU Baler, RD Klein, DC AF Baler, RD Klein, DC BE Webb, SM PuigDomingo, M Moller, M Pevet, P TI Circadian regulation of transcription factor Fra-2 in the rat pineal gland SO PINEAL UPDATE: FROM MOLECULAR MECHANISMS TO CLINICAL IMPLICATIONS LA English DT Proceedings Paper CT 7th Colloquium of the European-Pineal-Society CY MAR 29-31, 1996 CL SITGES, SPAIN SP European Pineal Soc AB Fra-2 is a member of the FOS family of transcription factors. We found that expression of this gene and its protein product is regulated on a circadian basis in the pineal gland and that regulation involves an adrenergic --> cyclic AMP mechanism. Fra-2 may be an integral component of transduction in this and other tissues. C1 NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 USA BN 0-915340-19-4 PY 1997 BP 37 EP 47 PG 3 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA BK42W UT WOS:000072152700004 ER PT S AU Vande Woude, GF Jeffers, M Cortner, J Alvord, G Tsarfaty, I Resau, J AF Vande Woude, GF Jeffers, M Cortner, J Alvord, G Tsarfaty, I Resau, J BE Bock, GR Goode, JA TI Met-HGF/SF: tumorigenesis, invasion and metastasis SO PLASMINOGEN-RELATED GROWTH FACTORS SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Plasminogen-Related Growth Factors CY APR 08-10, 1997 CL CIBA FDN, LONDON, ENGLAND HO CIBA FDN ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; BETA-CATENIN; HER-2/NEU AMPLIFICATION; PROTOONCOGENE PRODUCT; BREAST-CANCER; C127 CELLS; RECEPTOR; EXPRESSION; TRANSFORMATION AB Hepatocyte growth factor/scatter factor (HGF/SF) is synthesized by mesenchymal cells and is a paracrine effector of cells, predominantly epithelial, that express the Met tyrosine kinase-receptor. We have demonstrated that autocrine HGF/SF expression in mouse fibroblasts results in transformation and tumorigenesis. HGF/SF-treated cells expressing Met can respond in a variety of ways: mitogenically, by scattering (motility), and by forming branching tubules in gel matrices (branching morphogenesis). HGF/SF also induces in vitro invasiveness and is angiogenic ih in vivo assays. A human cell line and several mouse cell lines that we have constructed to express Met-HGF/SF in an autocrine fashion are tumorigenic, invasive and metastatic in athymic nude mice. Thus, the very complex process of invasion and metastasis can be mediated by a ligand-receptor signalling pathway, and the cell lines we have developed provide important model systems for identifying the signalling molecules that mediate these phenotypes: For example Met-HGF/SF signalling activates the urokinase plasminogen proteolysis network, thus coupling this signal transduction pathway to the proteases that mediate dissolution of the extracellular matrix. Branching morphogenesis, mediated by Met-HGF/SF signalling, is dependent on this process, as well as the formation of cell-cell junctions and interaction with the extracellular matrix. We have proposed a hypothesis for the role of Met and downstream signalling molecules in generating normal ducts and lumenal structures, as well as a model for how interruption of this signalling leads to abonormal malignant progression. Is Met involved in human cancer? Human sarcomas often inappropriately express Met, suggesting that it is an important oncogene in these cancers, and an increasing number of reports have implicated Met-HGF/SF signalling in a variety of human cancers. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Syst, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel. RP Vande Woude, GF (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. NR 40 TC 99 Z9 100 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND SN 0300-5208 BN 0-471-97456-0 J9 CIBA F SYMP PY 1997 VL 212 BP 119 EP 132 PG 14 WC Biochemistry & Molecular Biology; Oncology; Medicine, General & Internal SC Biochemistry & Molecular Biology; Oncology; General & Internal Medicine GA BM64R UT WOS:000079333200011 PM 9524767 ER PT S AU Leonard, EJ AF Leonard, EJ BE Bock, GR Goode, JA TI Biological aspects of macrophage-stimulating protein (MSP) and its receptor SO PLASMINOGEN-RELATED GROWTH FACTORS SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Plasminogen-Related Growth Factors CY APR 08-10, 1997 CL CIBA FDN, LONDON, ENGLAND HO CIBA FDN ID HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE; MOLECULAR-CLONING; GENE-PRODUCT; RON; STK; IDENTIFICATION; ACTIVATION; FAMILY; CHAIN AB Macrophage-stimulating protein (MSP; also known as HGF-like protein [HGF1]) is a 78 kDa plasma protein that is secreted by the liver into the circulation as single-chain, biologically inactive pro-MSP. The presence of conserved triple disulfide loops (kringles) places pro-MSP in a family of coagulation system serine protease zymogens that are activated by proteolytic cleavage. Although pro-MSP has lost enzymic activity, it has retained the activation mechanism, in that proteolytic cleavage at a single site yields biologically active disulfide-linked ap-chain heterodimeric MSP. The MSP receptor is a transmembrane protein tyrosine kinase. MSP causes phosphorylation of the receptor cytoplasmic domain, association of phosphatidylinositol (PI)-3 kinase with the receptor, and phosphorylation of receptor-bound PI-3 kinase. Inhibition of PI-3 kinase by wortmannin prevents MSP action on cells. MSP stimulates motility of murine resident peritoneal macrophages. However, it does not act on exudate macrophages or blood monocytes, since these earlier maturational stages of the lineage do not express the receptor. MSP also stimulates keratinocyte cell lines, causing either chemotactic responses or increased cell numbers in culture. We suggest that pro-MSP diffuses into local tissue sites, where proteolytic cleavage to MSP results in stimulation of keratinocytes and macrophages. It possibly plays a role in tissue injury or wound healing. C1 NCI, Immunol Lab, Frederick, MD 21702 USA. RP Leonard, EJ (reprint author), NCI, Immunol Lab, Bldg 560,Room 12-71, Frederick, MD 21702 USA. NR 29 TC 24 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND SN 0300-5208 BN 0-471-97456-0 J9 CIBA F SYMP PY 1997 VL 212 BP 183 EP 197 PG 15 WC Biochemistry & Molecular Biology; Oncology; Medicine, General & Internal SC Biochemistry & Molecular Biology; Oncology; General & Internal Medicine GA BM64R UT WOS:000079333200016 PM 9524771 ER PT S AU Rosen, EM Lamszus, K Laterra, J Polverini, PJ Rubin, JS Goldberg, ID AF Rosen, EM Lamszus, K Laterra, J Polverini, PJ Rubin, JS Goldberg, ID BE Bock, GR Goode, JA TI HGF/SF in angiogenesis SO PLASMINOGEN-RELATED GROWTH FACTORS SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Plasminogen-Related Growth Factors CY APR 08-10, 1997 CL CIBA FDN, LONDON, ENGLAND HO CIBA FDN ID HEPATOCYTE GROWTH-FACTOR; INVASIVE BREAST-CARCINOMA; C-MET RECEPTOR; SCATTER FACTOR; TUMOR ANGIOGENESIS; MOLECULAR-CLONING; EPITHELIAL-CELLS; ENDOTHELIAL-CELLS; SEQUENCE-ANALYSIS; FACTOR EXPRESSION AB Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchyme-derived cytokine that stimulates motility and invasiveness of epithelial and cancer cells. These responses are transduced through the c-met proto-oncogene product, a transmembrane tyrosine kinase that functions as the HGF/SF receptor. We have shown that HGF/SF is a potent angiogenic molecule and that its angiogenic activity is mediated primarily through direct actions on vascular endothelial cells. These include stimulation of cell migration, proliferation, protease production, invasion, and organization into capillary-like tubes. We further showed that HGF/SF is overexpressed in invasive human cancers, including breast cancer, relative to non-invasive cancers and benign conditions. In invasive breast cancers, the content of HGF/SF is strongly correlated with that of von Willebrand's factor, a marker of vascular endothelial cells. Furthermore, transfection of breast cancer and glioma cell lines with HGF/SF cDNA greatly enhanced the ability of these cells to grow as tumours in orthotopic sites in syngeneic or immunocompromized host animals. The increased growth rate of the HGF/SF-transfected cells was attributable, in part, to increased tumour angiogenesis. These findings suggest that HGF/SF may function as a tumour progression factor, in part by stimulating tumour cell invasiveness and in part by stimulating angiogenesis. C1 Long Isl Jewish Med Ctr, Dept Radiat Oncol, New Hyde Pk, NY 11040 USA. Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA. Kennedy Krieger Res Inst, Baltimore, MD USA. Sch Dent, Dept Oral Pathol, Ann Arbor, MI 48109 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Rosen, EM (reprint author), Long Isl Jewish Med Ctr, Dept Radiat Oncol, 270-05 76th Ave, New Hyde Pk, NY 11040 USA. FU NCI NIH HHS [CA-64869, CA-64416] NR 58 TC 90 Z9 90 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND SN 0300-5208 BN 0-471-97456-0 J9 CIBA F SYMP PY 1997 VL 212 BP 215 EP 229 PG 15 WC Biochemistry & Molecular Biology; Oncology; Medicine, General & Internal SC Biochemistry & Molecular Biology; Oncology; General & Internal Medicine GA BM64R UT WOS:000079333200018 PM 9524773 ER PT S AU Sherman, MR Williams, LD Saifer, MGP French, JA Kwak, LW Oppenheim, JJ AF Sherman, MR Williams, LD Saifer, MGP French, JA Kwak, LW Oppenheim, JJ BE Harris, JM Zalipsky, S TI Conjugation of high-molecular weight poly(ethylene glycol) to cytokines: Granulocyte-macrophage colony-stimulating factors as model substrates SO POLY(ETHYLENE GLYCOL): CHEMISTRY AND BIOLOGICAL APPLICATIONS SE ACS Symposium Series LA English DT Review CT Symposium on Poly(ethylene glycol) - Chemistry and Biological Applications, at the 213th National Meeting of the American-Chemical-Society CY APR 13-17, 1997 CL SAN FRANCISCO, CA SP Amer Chem Soc, Div Polym Chem ID FACTOR GM-CSF; MODIFIED SUPEROXIDE-DISMUTASE; WATER-SOLUBLE POLYMERS; TUMOR-NECROSIS-FACTOR; AMINO-ACID-SEQUENCE; POLYETHYLENE-GLYCOL; HORSERADISH-PEROXIDASE; GLOMERULAR-FILTRATION; RECOMBINANT INTERLEUKIN-2; CHEMICAL MODIFICATION AB The ability of the small receptor-binding protein, recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF), to increase the abundance of certain blood cell types in mice was enhanced markedly by covalent attachment of a single long strand of PEG (30-40 kDa). Potency was not increased further by coupling a second strand. Such conjugates can be synthesized efficiently by reaction of protein amino groups with PEG propionaldehydes in the presence of NaBH(3)CN or with PEG p-nitrophenyl carbonates. Both methods have been used to prepare recombinant human GM-CSF conjugates of predetermined composition, e.g. PEG(1)GM-CSF and PEG(2)GM-CSF, in high yield. These compounds, or analogous derivatives of other cytokines, purified by ion-exchange and size-exclusion chromatography, may be suitable candidates for pharmaceutical development. C1 Mt View Pharmaceut Inc, Menlo Pk, CA 94025 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Sherman, MR (reprint author), Mt View Pharmaceut Inc, 871-L Ind Pk, Menlo Pk, CA 94025 USA. NR 71 TC 22 Z9 22 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3537-6 J9 ACS SYM SER JI ACS Symp. Ser. PY 1997 VL 680 BP 155 EP 169 PG 15 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary; Polymer Science SC Chemistry; Pharmacology & Pharmacy; Polymer Science GA BK03M UT WOS:000070951700011 ER PT J AU Einolf, HJ Gross, MA Butch, ER Lin, JM Amin, S Yagi, H Jerina, DM Baird, WM AF Einolf, HJ Gross, MA Butch, ER Lin, JM Amin, S Yagi, H Jerina, DM Baird, WM TI Selective recognition of substituted chrysene-diol epoxide-2-DNA adducts by antiserum prepared against DNA adducts of benzo[C]-phenanthrene-diol epoxide-2 SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE immunodetection; benzo[c]phenanthrene-DNA adducts; substituted chrysene-DNA adducts ID ANTI-DIHYDRODIOL-EPOXIDES; SALMONELLA-TYPHIMURIUM; MOUSE SKIN; CHEMICAL CARCINOGENESIS; AROMATIC-HYDROCARBONS; MAMMALIAN-CELLS; NEWBORN MICE; REGION; MUTAGENICITY; BENZO(C)PHENANTHRENE AB Polyclonal antiserum prepared against DNA that was modified with racemic benzo[c]phenanthrene-3,4-diol-1,2-epoxide-2 (B[c]PhDE-2; benzylic hydroxyl and epoxide oxygen trans) was characterized for specificity of antigen recognition. Previous studies have demonstrated that the antisera stereoselectively recognized B[c]PhDE-2-DNA and failed to recognize DNA modified with racemic benzo [c]phenanthrene-3,4-diol-1,2-epoxide-1 (B[c]PhDE-1-DNA, benzylic hydroxyl and epoxide oxygen cis), benzo[a]pyrene-7,8-diol-9, 10-epoxide-2-DNA (B[a]PDE-2-DNA) and 7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1-DNA (DMBADE-1-DNA). DNA samples modified by diol-epoxide-2 diastereomers of several hydrocarbons were tested in competitive ELISA assays utilizing B[c]PhDE-2-DNA (270 fmol adducts per well). DNA modified with racemic diol-epoxide-2 of various substituted chrysenes (including chrysene, benzo[g]chrysene (B[g]C), 6-methylchrysene (6-MeC), and 5-methychrysene (5-MeC), gave 50% inhibition of antisera binding at significantly higher concentrations (5 to 7-fold) than the parent B[c]PhDE-2-DNA or 5,6-diMeCDE-DNA. DNA modified with 5, 7-dimethylchryseneDE-2 (5,7-diMeCDE-2) and dibenzo[a,l]pyreneDE-2 (DB[a,l] PDE-2) required 20 and > 100-fold greater levels of adducts to give 50% inhibition. Results with B[c]Ph, 5,6-diMeC, chrysene, 6-MeC and 5-MeC diol epoxide-2-DNA indicate that substitution of a methyl group in the vicinity of the bay-region of the PAH-molecule had limited effects on antigen recognition by this antiserum. However, the addition of a ring or methyl group remote from the diol epoxide moiety, as in DB[a,l] PDE-2-DNA or 5,7-diMeCDE-2-DNA greatly decreased antigen recognition. The ability of this antiserum to recognize DNA adducts of a particular class of polycyclic aromatic hydrocarbons will be useful for studies of their contribution to the DNA-binding that results from exposure to complex environmental mixtures. C1 PURDUE UNIV,DEPT MED CHEM & MOL PHARMACOL,W LAFAYETTE,IN 47907. AMER HLTH FDN,NAYLOR DANA INST DIS PREVENT,VALHALLA,NY 10595. NIDDK,NIH,BETHESDA,MD 20892. NR 37 TC 0 Z9 0 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1997 VL 12 IS 2 BP 125 EP 138 DI 10.1080/10406639708233831 PG 14 WC Chemistry, Organic SC Chemistry GA XY369 UT WOS:A1997XY36900002 ER PT S AU Dosemeci, M Rothman, N Yin, SN Li, GL Linet, M Wacholder, S Chow, WH Hayes, RB AF Dosemeci, M Rothman, N Yin, SN Li, GL Linet, M Wacholder, S Chow, WH Hayes, RB BE Bingham, E Rall, DP TI Validation of benzene exposure assessment SO PREVENTIVE STRATEGIES FOR LIVING IN A CHEMICAL WORLD: A SYMPOSIUM IN HONOR OF IRVING J. SELIKOFF SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Symposium on Preventive Strategies for Living in a Chemical World, Dedicated to the Memory of Irving J Selikoff CY NOV 02-05, 1995 CL WASHINGTON, D.C. SP Collegium Ramazzini ID OCCUPATIONAL EXPOSURE; VALIDITY; COHORT; CHINA; INFORMATION; AGREEMENT; CANCER C1 NCI, Occupat Epidemiol Branch, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Chinese Acad Prevent Med, Inst Occupat Med, Beijing 100050, Peoples R China. RP Dosemeci, M (reprint author), NCI, Occupat Epidemiol Branch, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, 6130 Execut Blvd,Room 418, Rockville, MD 20852 USA. NR 23 TC 5 Z9 5 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-074-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 837 BP 114 EP 121 DI 10.1111/j.1749-6632.1997.tb56868.x PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Multidisciplinary Sciences; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Science & Technology - Other Topics; Toxicology GA BK42P UT WOS:000072113300007 PM 9472334 ER PT S AU Cocco, P Blair, A Congia, P Saba, G Ecca, AR Palmas, C AF Cocco, P Blair, A Congia, P Saba, G Ecca, AR Palmas, C BE Bingham, E Rall, DP TI Long-term health effects of the occupational exposure to DDT - A preliminary report SO PREVENTIVE STRATEGIES FOR LIVING IN A CHEMICAL WORLD: A SYMPOSIUM IN HONOR OF IRVING J. SELIKOFF SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Symposium on Preventive Strategies for Living in a Chemical World, Dedicated to the Memory of Irving J Selikoff CY NOV 02-05, 1995 CL WASHINGTON, D.C. SP Collegium Ramazzini ID NON-HODGKINS-LYMPHOMA; ADIPOSE-TISSUE; BREAST-CANCER; ORGANOCHLORINE RESIDUES; MULTIPLE-MYELOMA; RISK; MORTALITY; PESTICIDES; COHORT; IOWA C1 Univ Cagliari, Ist Med Lavoro, Cagliari, Italy. NCI, Occupat Studies Sect, Environm Epidemiol Branch, Bethesda, MD 20892 USA. Univ Cagliari, Ist Parassitol, Cagliari, Italy. RP Cocco, P (reprint author), Univ Cagliari, Inst Occupat Med, Via San Giorgio 12, I-09126 Cagliari, Italy. EM coccop@pacs.unica.it NR 35 TC 27 Z9 27 U1 0 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-074-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 837 BP 246 EP 256 DI 10.1111/j.1749-6632.1997.tb56878.x PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Multidisciplinary Sciences; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Science & Technology - Other Topics; Toxicology GA BK42P UT WOS:000072113300017 PM 9472344 ER PT B AU Summers, RM Selbie, WS Popp, J Holland, SM Sneller, MC Shelhamer, JH AF Summers, RM Selbie, WS Popp, J Holland, SM Sneller, MC Shelhamer, JH BE Boom, H Robinson, C Rutten, W Neuman, M Wijkstra, H TI Implicit modeling and virtual endoscopy of pulmonic cavities SO PROCEEDINGS OF THE 18TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 18, PTS 1-5 SE PROCEEDINGS OF THE ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 18th Annual International Conference of IEEE Engineering-in-Medicine-amd-Biology-Society CY OCT 31-NOV 03, 1996 CL AMSTERDAM, NETHERLANDS SP IEEE Engn Med & Biol Soc AB Pulmonary cavities are a devastating consequence of severe pneumonia and other necrotizing pulmonary disorders. As part of a project to understand cavity formation and heating, we evaluated different techniques for determining the shape of the cavities. The pulmonary cavities were segmented from helical computed tomography scans of the thorax. We parameterized the shape of the cavities using two implicit functions, an ellipsoid and a superquadric. The original cavities and the parameterized models of the cavities were then visualized using a virtual endoscopy system. Both functions produced reasonable fits to the data. RMS errors were lower with the superquadric although the superquadric tended to deform inappropriately if a bronchial segment communicated with the cavity or if the top or bottom of the cavity was not capped. We found that fitting the cavity data to both ellipsoids and superquadrics provides straightforward estimation of the global shape. C1 NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-3812-X J9 P IEEE EMBS PY 1997 VL 18 BP 639 EP 640 PG 2 WC Engineering, Biomedical SC Engineering GA BK41A UT WOS:000072079000312 ER PT B AU Metter, EJ AF Metter, EJ BE Boom, H Robinson, C Rutten, W Neuman, M Wijkstra, H TI Prevention of physical frailty SO PROCEEDINGS OF THE 18TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 18, PTS 1-5 SE PROCEEDINGS OF THE ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 18th Annual International Conference of IEEE Engineering-in-Medicine-amd-Biology-Society CY OCT 31-NOV 03, 1996 CL AMSTERDAM, NETHERLANDS SP IEEE Engn Med & Biol Soc AB Aging is associated with continuous changes in strength and physical functioning. Different factors contribute to these changes at different ages. For discussion purposes, it, is useful to identify 4 adult stages that lay the ground work for disability: (1) Early adulthood where maximal performance is reached, (2) Late early adulthood where earliest changes begin with slowing of reactions, (3) Middle age with slow declines in strength and coordination, and (4) Older age with more dramatic and greater functional changes. Preventive strategies can be applied at each stage including exercise, diet, health habits, injury prevention, environmental and social adjustments. Interventions can focus on the person or their environment, and should consider the unique needs of each life stage, particularly middle aged and elderly. They should be acceptable to the average individual who is not health conscious, and should stimulate motivation toward safer and healthier lifestyles. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Metter, EJ (reprint author), NIA, Gerontol Res Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-3812-X J9 P IEEE EMBS PY 1997 VL 18 BP 2148 EP 2149 PG 2 WC Engineering, Biomedical SC Engineering GA BK41A UT WOS:000072079001036 ER PT S AU Kidder, LH Levin, IW Lewis, EN AF Kidder, LH Levin, IW Lewis, EN GP IEEE IEEE TI Infrared spectroscopic imaging using focal plane arrays: Applications to tissue analysis and histopathology SO PROCEEDINGS OF THE 19TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 19, PTS 1-6: MAGNIFICENT MILESTONES AND EMERGING OPPORTUNITIES IN MEDICAL ENGINEERING SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society CY OCT 30-NOV 02, 1997 CL CHICAGO, IL SP IEEE Engn Med & Biol Soc, Natl Inst Hlth DE infrared imaging; clinical diagnostic; pathology; FTIR spectroscopy; microscopy ID BRAIN-TISSUE; MICROSPECTROSCOPY; SILICONE; CANCERS AB Infrared imaging spectroscopy has been used to investigate several biological systems. The imaging instrument is comprised of IR sensitive array detectors coupled with a step-scan interferometer and microscope. Each pixel on the array simultaneously measures an IR spectrum in frequency ranges that depend only on the type of array employed. As image contrast is provided solely by spatial variations in a sample's intrinsic chemistry, this technique enables researchers and clinicians to visualize a sample directly in terms of its chemical heterogeneities. We illustrate the capability and versatility of this technique for readily and non-invasively visualizing chemical complexity and for providing statistical data on sample heterogeneity. FT-IR spectroscopic imaging provides the means to better understand the molecular composition and architecture of biological materials, as well the ability to probe the biochemistry of diseased tissue states. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Kidder, LH (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room B1-38, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-4262-3 J9 P ANN INT IEEE EMBS PY 1997 VL 19 BP 689 EP 692 PN 1-6 PG 4 WC Engineering, Biomedical SC Engineering GA BM91F UT WOS:000080103400197 ER PT J AU ChoChung, YS AF ChoChung, YS TI Antisense DNA toward type I protein kinase a produces sustained inhibition of tumor growth SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE cancer growth arrest; differentiation ID RI-ALPHA-SUBUNIT; MAMMARY EPITHELIAL-CELLS; CYCLIC-AMP ANALOGS; ADENOSINE 3'-5'-CYCLIC MONOPHOSPHATE; HL-60 LEUKEMIA-CELLS; AMINO-ACID SEQUENCE; REGULATORY SUBUNIT; GENE-EXPRESSION; MESSENGER-RNA; MOLECULAR-CLONING AB Expression of the RI(alpha) subunit of type I cyclic AMP-dependent protein kinase (PKA) is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. The sequence-specific inhibition of RI(alpha) gene expression by RI(alpha) antisense oligodeoxynucleotide results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin, A single-injection RI(alpha) antisense treatment in vivo also results in a reduction in RI(alpha) expression and inhibition of tumor growth. One injection was sufficient to inhibit tumor growth in mice for 2 weeks. The antisense DNA achieves this long-lasting effect by altering the balance between the production of PKA type I and a competitive molecule, PKA type II. Tumor cells behaved like untransformed cells by making less protein kinase type I. The RI(alpha) antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to restrain neoplastic growth in vivo. RP ChoChung, YS (reprint author), NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,NIH,BLDG 10,ROOM 5B05,BETHESDA,MD 20892, USA. NR 61 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JAN PY 1997 VL 109 IS 1 BP 23 EP 32 PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA WD146 UT WOS:A1997WD14600003 PM 9010913 ER PT B AU Shi, YB IshizuyaOka, A AF Shi, YB IshizuyaOka, A BE Shi, YB Shi, YF Xu, YH Scott, DW TI Activation of matrix metalloproteinase genes during thyroid hormone-induced apoptotic tissue remodeling SO PROGRAMMED CELL DEATH LA English DT Proceedings Paper CT 1996 International Symposium on Programmed Cell Death CY SEP 08-12, 1996 CL CHINESE ACAD SCI, SHANGHAI SCI CTR, SHANGHAI, PEOPLES R CHINA SP NICHHD, US, Amer Red Cross, Holland Lab, US, Natl Nat Sci Fdn China, Academia Sinica, Shanghai Inst Cell Biol, China, BASF Corp, US, Genetech Inc, US, Shanghai Huaxin High Biotechnol Inc, China, Amgen Ctr, US, Beckman, US, Boehringer Mannheim Corp, US, DNAX Res Inst Molec & Cell Biol, US, PharMingen, US, Promega Corp, US, Clontech Labs, US, Hoffmann La roche Inc, US, Life Technol Inc, US, New England Biolabs, US HO CHINESE ACAD SCI, SHANGHAI SCI CTR AB Programmed cell death or apoptosis is an essential process during amphibian metamorphosis, not only in the resorption of tadpole specific tissues but also in the remodeling of existing tissues and de novo development of adult ones. The control of metamorphosis by thyroid hormone has allowed the identification and characterization of a number of genes which are involved in this process. Among them are genes encoding matrix metalloproteinases (MMPs), which are capable of digesting various components of the extracellular matrix (ECM). Of particular interest is the MMP stromelysin-3. The gene is activated prior to larval cell death and its high levels of expression correlate with basal lamina (the ECM that separates epithelium and the mesenchyme) modification. These and other observations implicate that stromelysin-3 may participate in ECM remodeling, which in turn regulates cell fate during metamorphosis. In addition, our analyses of the expression of several other MMPs indicate multiple MMPs function, in a tissue-dependent manner, at various steps of organ transformation, some in the regulation of cell death, proliferation, and differentiation, while others in post-apoptotic ECM removal. RP Shi, YB (reprint author), NICHHD,MOL EMBRYOL LAB,BLDG 18T,RM 101,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45680-X PY 1997 BP 13 EP 26 PG 14 WC Cell Biology SC Cell Biology GA BJ94H UT WOS:A1997BJ94H00002 ER PT B AU Sarin, A Ebnet, K Zacharchuk, CM Henkart, PA AF Sarin, A Ebnet, K Zacharchuk, CM Henkart, PA BE Shi, YB Shi, YF Xu, YH Scott, DW TI Caspase inhibitors as molecular probes of cell death SO PROGRAMMED CELL DEATH LA English DT Proceedings Paper CT 1996 International Symposium on Programmed Cell Death CY SEP 08-12, 1996 CL CHINESE ACAD SCI, SHANGHAI SCI CTR, SHANGHAI, PEOPLES R CHINA SP NICHHD, US, Amer Red Cross, Holland Lab, US, Natl Nat Sci Fdn China, Academia Sinica, Shanghai Inst Cell Biol, China, BASF Corp, US, Genetech Inc, US, Shanghai Huaxin High Biotechnol Inc, China, Amgen Ctr, US, Beckman, US, Boehringer Mannheim Corp, US, DNAX Res Inst Molec & Cell Biol, US, PharMingen, US, Promega Corp, US, Clontech Labs, US, Hoffmann La roche Inc, US, Life Technol Inc, US, New England Biolabs, US HO CHINESE ACAD SCI, SHANGHAI SCI CTR RP Sarin, A (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45680-X PY 1997 BP 51 EP 62 PG 12 WC Cell Biology SC Cell Biology GA BJ94H UT WOS:A1997BJ94H00006 ER PT B AU Bortner, CD Hughes, FM Cidlowski, JA AF Bortner, CD Hughes, FM Cidlowski, JA BE Shi, YB Shi, YF Xu, YH Scott, DW TI Cell volume regulation, ions, and apoptosis SO PROGRAMMED CELL DEATH LA English DT Proceedings Paper CT 1996 International Symposium on Programmed Cell Death CY SEP 08-12, 1996 CL CHINESE ACAD SCI, SHANGHAI SCI CTR, SHANGHAI, PEOPLES R CHINA SP NICHHD, US, Amer Red Cross, Holland Lab, US, Natl Nat Sci Fdn China, Academia Sinica, Shanghai Inst Cell Biol, China, BASF Corp, US, Genetech Inc, US, Shanghai Huaxin High Biotechnol Inc, China, Amgen Ctr, US, Beckman, US, Boehringer Mannheim Corp, US, DNAX Res Inst Molec & Cell Biol, US, PharMingen, US, Promega Corp, US, Clontech Labs, US, Hoffmann La roche Inc, US, Life Technol Inc, US, New England Biolabs, US HO CHINESE ACAD SCI, SHANGHAI SCI CTR C1 NIEHS,LAB SIGNAL TRANSDUCT,NIH,RES TRIANGLE PK,NC 27709. RP Cidlowski, JA (reprint author), NIEHS,LAB SIGNAL TRANSDUCT,NIH,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45680-X PY 1997 BP 63 EP 70 PG 8 WC Cell Biology SC Cell Biology GA BJ94H UT WOS:A1997BJ94H00007 ER PT B AU Libutti, SK Bartlett, DL Alexander, HR AF Libutti, SK Bartlett, DL Alexander, HR BE Siewert, JR Roder, JD TI The treatment of peritoneal carcinomatosis using continuous hyperthermic peritoneal perfusion SO PROGRESS IN GASTRIC CANCER RESEARCH 1997: PROCEEDINGS OF THE 2ND INTERNATIONAL GASTRIC CANCER CONGRESS LA English DT Proceedings Paper CT 2nd International Gastric Cancer Congress CY APR 27-30, 1997 CL MUNICH, GERMANY SP Auto Suture Deutschland GmbH, Tonisvorst AB Peritoneal carcinomatosis resulting from gastrointestinal malignancy has a very poor prognosis and can present a very difficult management dilemma. Patients can develop very bulky intraabdominal disease resulting in symptoms from the mass effect of the tumor such as obstruction, abdominal pain and problems related to intractable ascites. Standard therapies such as surgical debulking are often ineffective in managing symptoms or impacting on the course of the disease. Continuous hyperthermic peritoneal perfusion (CHPP) as an adjunct to surgical debulking has shown some promise in ameliorating symptoms and altering the natural history of the disease. We describe the status of several ongoing clinical trials utilizing CHPP with a variety of chemotherapeutic agents for the management or prevention of peritoneal carcinomatosis. Technical aspects of the procedure and perfusion circuit will be highlighted. RP Libutti, SK (reprint author), NCI,SURG BRANCH,SURG METAB SECT,NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY BN 88-323-0427-9 PY 1997 BP 1371 EP 1377 PG 7 WC Oncology; Gastroenterology & Hepatology; Medicine, General & Internal; Pathology; Surgery SC Oncology; Gastroenterology & Hepatology; General & Internal Medicine; Pathology; Surgery GA BJ02Q UT WOS:A1997BJ02Q00260 ER PT J AU Young, HA Ghosh, P AF Young, HA Ghosh, P TI Molecular regulation of cytokine gene expression: Interferon-gamma as a model system SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL. 56 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review ID HUMAN T-CELLS; LARGE GRANULAR LYMPHOCYTES; TUMOR-BEARING MICE; NF-KAPPA-B; IFN-GAMMA; MESSENGER-RNA; TYROSINE PHOSPHORYLATION; STIMULATORY FACTOR; ACCESSORY CELLS; MOPC-315 TUMOR C1 NCI, Frederick Canc Res & Dev Ctr, Cellular & Mol Immunol Sect, Div Basic Sci, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Cellular & Mol Immunol Sect, Div Basic Sci, Frederick, MD 21702 USA. NR 82 TC 28 Z9 28 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 J9 PROG NUCLEIC ACID RE PY 1997 VL 56 BP 109 EP 127 DI 10.1016/S0079-6603(08)61004-1 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BK74H UT WOS:000073311000004 PM 9187053 ER PT S AU Chattoraj, DK Schneider, TD AF Chattoraj, DK Schneider, TD BE Moldave, K TI Replication control of plasmid P1 and its host chromosome: The common ground SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 57 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review ID MINI-F PLASMID; ESCHERICHIA-COLI CHROMOSOME; HEAT-SHOCK PROTEINS; COPY-NUMBER CONTROL; COMPLETE NUCLEOTIDE-SEQUENCE; CELL DIVISION CYCLE; REPE INITIATOR PROTEIN; REPEATED DNA-SEQUENCES; PARTITION PAR LOCUS; INCP-ALPHA PLASMIDS C1 NCI, FREDERICK CANC RES & DEV CTR, LAB MATH BIOL, FREDERICK, MD 21701 USA. RP Chattoraj, DK (reprint author), NCI, BIOCHEM LAB, NIH, BETHESDA, MD 20892 USA. OI Schneider, Thomas/0000-0002-9841-1531 NR 240 TC 28 Z9 28 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 BN 0-12-540057-8 J9 PROG NUCLEIC ACID RE JI Prog. Nucl. Res. Molec. Biol. PY 1997 VL 57 BP 145 EP 186 DI 10.1016/S0079-6603(08)60280-9 PG 42 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ03W UT WOS:A1997BJ03W00005 PM 9175433 ER PT J AU Angov, E McBride, JS Kaslow, DC Ballou, WR Diggs, CL Lyon, JA AF Angov, E McBride, JS Kaslow, DC Ballou, WR Diggs, CL Lyon, JA TI Structural analysis of refolded-recombinant Plasmodium falciparum MSP1 C-terminal fragment by using conformation-specific monoclonal antibodies. SO PROTEIN ENGINEERING LA English DT Meeting Abstract ID SURFACE C1 WRAIR,DEPT IMMUNOL,WASHINGTON,DC 20307. UNIV EDINBURGH,DIV BIOL SCI,EDINBURGH EH9 3JT,MIDLOTHIAN,SCOTLAND. US AGCY INT DEV,WASHINGTON,DC 20523. NIAID,BETHESDA,MD 20892. NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PY 1997 VL 10 SU S BP 21 EP 21 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XD832 UT WOS:A1997XD83200025 ER PT J AU Bychkova, VE Ptitsyn, OB AF Bychkova, VE Ptitsyn, OB TI Folding intermediates and genetic diseases SO PROTEIN ENGINEERING LA English DT Meeting Abstract ID TRANSMEMBRANE CONDUCTANCE REGULATOR; INTRACELLULAR-TRANSPORT; PROTEIN; MUTATIONS; CELLS C1 RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. NCI,LMMB,NIH,BETHESDA,MD 20892. NR 27 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PY 1997 VL 10 SU S BP 23 EP 23 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XD832 UT WOS:A1997XD83200029 ER PT J AU Ptitsyn, O Bychkova, V Dujsekina, A Rossi, GL Fantuzzi, A Uversky, V Tiktopulo, E Klenin, S AF Ptitsyn, O Bychkova, V Dujsekina, A Rossi, GL Fantuzzi, A Uversky, V Tiktopulo, E Klenin, S TI Modeling of the molten globule state of proteins near membranes SO PROTEIN ENGINEERING LA English DT Meeting Abstract C1 NCI,LMMB,NIH,BETHESDA,MD 20892. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 6 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PY 1997 VL 10 SU S BP 32 EP 32 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XD832 UT WOS:A1997XD83200048 ER PT J AU Tsai, CJ Nussinov, R AF Tsai, CJ Nussinov, R TI Hydrophobic folding units derived from dissimilar monomer structures and their interactions SO PROTEIN SCIENCE LA English DT Article DE compactness; domain cutting; folding unit; hydrophobic core; protein folding ID GLOBULAR-PROTEINS; COMPACT UNITS; DOMAINS; IDENTIFICATION; THERMODYNAMICS; ORGANIZATION; LOCATION; BARNASE AB We have designed an automated procedure to cut a protein into compact hydrophobic folding units. The hydrophobic units are large enough to contain tertiary non-local interactions, reflecting potential nucleation sites during protein folding. The quality of a hydrophobic folding unit is evaluated by four criteria. The first two correspond to visual characterization of a structural domain, namely, compactness and extent of isolation. We use the definition of Zehfus and Rose (Zehfus MH, Rose GD, 1986, Biochemistry 25:335-340) to calculate the compactness of a cut protein unit. The isolation of a unit is based on the solvent accessible surface area (ASA) originally buried in the interior and exposed to the solvent after cutting. The third quantity is the hydrophobicity, equivalent to the fraction of the buried non-polar ASA with respect to the total non-polar ASA. The last criterion in the evaluation of a folding unit is the number of segments it includes. To conform with the rationale of obtaining hydrophobic units, which may relate to early folding events, the hydrophobic interactions are implicitly and explicitly applied in their generation and assessment. We follow Helm and Sander (Helm L, Sander C, 1994, Proteins 19:256-268) to reduce the multiple cutting-point problem to a one-dimensional search for all reasonable trial cuts. However, as here we focus on the hydrophobic cores, the contact matrix used to obtain the first non-trivial eigenvector contains only hydrophobic contacts, rather than all, hydrophobic and hydrophilic, interactions. This dataset of hydrophobic folding units, derived from structurally dissimilar single chain monomers, is particularly useful far investigations of the mechanism of protein folding. For cases where there are kinetic data, the one or more hydrophobic folding units generated for a protein correlate with the two or with the three-state folding process observed. We carry out extensive amino acid sequence order independent structural comparisons to generate a structurally non-redundant set of hydrophobic folding units for fold recognition and for statistical purposes. C1 NCI,MATH BIOL LAB,FCRDC,SAIC,FREDERICK,MD 21702. TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. FU NCI NIH HHS [1-CO-74102] NR 44 TC 81 Z9 83 U1 0 U2 5 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 JAN PY 1997 VL 6 IS 1 BP 24 EP 42 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD201 UT WOS:A1997WD20100004 PM 9007974 ER PT J AU Tsai, CJ Lin, SL Wolfson, HJ Nussinov, R AF Tsai, CJ Lin, SL Wolfson, HJ Nussinov, R TI Studies of protein-protein interfaces: A statistical analysis of the hydrophobic effect SO PROTEIN SCIENCE LA English DT Article DE hydrophobic effect; protein cores; protein folding; protein-protein recognition; subunit interfaces ID SURFACE HYDROPHOBICITY; RECOGNITION; COMPLEMENTARITY; DOCKING; MOTIFS AB Data sets of 362 structurally nonredundant protein-protein interfaces and of 57 symmetry-related oligomeric interfaces have been used to explore whether the hydrophobic effect that guides protein folding is also the main driving force for protein-protein associations. The buried nonpolar surface area has been used to measure the hydrophobic effect. Our analysis indicates that, although the hydrophobic effect plays a dominant role in protein-protein binding, it is not as strong as that observed in the interior of protein monomers. Comparison of the interiors of the monomers with those of the interfaces reveals that, in general, the hydrophobic amino acids are more frequent in the interior of the monomers than in the interior of the protein-protein interfaces. On the other hand, a higher proportion of charged and polar residues are buried at the interfaces, suggesting that hydrogen bonds and ion pairs contribute more to the stability of protein binding than to that of protein folding. Moreover, comparison of the interior of the interfaces to protein surfaces indicates that the interfaces are poorer in polar/charged than the surfaces and are richer in hydrophobic residues. The interior of the interfaces appears to constitute a compromise between the stabilization contributed by the hydrophobic effect on the one hand and avoiding patches on the protein surfaces that are too hydrophobic on the other. Such patches would be unfavorable for the unassociated monomers in solution. We conclude that, although the types of interactions are similar between protein-protein interfaces and single-chain proteins overall, the contribution of the hydrophobic effect to protein-protein associations is not as strong as to protein folding. This implies that packing patterns and interatom, or interresidue, pairwise potential functions, derived from monomers, are not ideally suited to predicting and assessing ligand associations or design. These would perform adequately only in cases where the hydrophobic effect at the binding site is substantial. C1 NCI,MATH BIOL LAB,FCRF,SAIC,FREDERICK,MD 21702. TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 24 TC 279 Z9 284 U1 4 U2 18 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 JAN PY 1997 VL 6 IS 1 BP 53 EP 64 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD201 UT WOS:A1997WD20100006 PM 9007976 ER PT J AU Moult, J Hubbard, T Bryant, SH Fidelis, K Pedersen, JT AF Moult, J Hubbard, T Bryant, SH Fidelis, K Pedersen, JT TI Critical assessment of methods of protein structure prediction (CASP): Round II SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE protein structure prediction; community-wide experiment; GASP C1 Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. Natl Ctr Biotechnol Informat, Computat Branch, NIH, Bethesda, MD USA. Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA USA. RP Moult, J (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM jmoult@carb.nist.gov RI Hubbard, Tim/C-2567-2008 OI Hubbard, Tim/0000-0002-1767-9318 NR 9 TC 55 Z9 59 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PY 1997 SU 1 BP 2 EP 6 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YW306 UT WOS:000071920700002 ER PT J AU Marchler-Bauer, A Bryant, SH AF Marchler-Bauer, A Bryant, SH TI Measures of threading specificity and accuracy SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE fold recognition; protein threading ID PROTEIN-STRUCTURE PREDICTION; DOMAIN AB Threading predictions for CASP2 target proteins were compared to their true structures using a series of precisely defined measures of agreement, calculated in a fully automatic way, Fold recognition specificity was calculated as the proportion of a predictor's "bet" that was placed on previously known structures similar to the prediction target, as identified by a "jury" of well-tested structure-structure comparison methods, Values approaching 100% indicate that a prediction correctly identified the structural and/or evolutionary family to which a target belongs, Alignment specificity was calculated as the proportion of aligned residue pairs in the predicted target-to-known-structure alignment that also occur in the structure-structure alignments produced by the "jury" methods, Contact specificity was calculated as the proportion of nonlocal residue contacts in the molecular model implied by threading alignment, that also occur in the experimental structure. of the target, Alignment specificity and contact specificity measure the accuracy of a predicted 3-dimensional model, Values approaching 100% indicate that target residues have been assigned to the correct spatial locations and that the model is as accurate as possible for a threading prediction. (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 41 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 USA SN 0887-3585 J9 PROTEINS JI Proteins PY 1997 SU 1 BP 74 EP 82 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YW306 UT WOS:000071920700011 ER PT J AU Marchler-Bauer, A Levitt, M Bryant, SH AF Marchler-Bauer, A Levitt, M Bryant, SH TI A retrospective analysis of CASP2 threading predictions SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE fold recognition; protein threading ID PROTEIN-STRUCTURE PREDICTION; FOLD RECOGNITION AB Analysis of CASP2 protein threading results shows that the success rate of structure predictions varies widely among prediction targets, We set "critical" thresholds in fold recognition specificity and threading model accuracy at the points where "incorrect" CASP2 predictions just outnumber "correct" predictions. Using these thresholds we find that correct predictions were made for all of those targets and for only those targets where more than 50% of target residues may be superimposed on previously known structures, Three-fourths of these correct predictions were furthermore made for targets with greater than 12% residue identity in structural alignment, where characteristic sequence motifs are also present. Based on these observations we suggest that the sustained performance of threading methods is best characterized by counting the numbers of correct predictions for targets of increasing "difficulty" We suggest that target difficulty may be assigned, once the true structure of the target is known, according to the fraction of residues superimposable onto previously known structures and the fraction of identical residues in those structural alignments. (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. Stanford Univ Med, Dept Biol Struct, Beckman Labs Struct Biol, Stanford, CA USA. RP Bryant, SH (reprint author), Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; Levitt, Michael/E-4582-2012; OI Levitt, Michael/0000-0002-8414-7397; Marchler-Bauer, Aron/0000-0003-1516-0712 NR 19 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PY 1997 SU 1 BP 83 EP 91 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YW306 UT WOS:000071920700012 ER PT J AU Di Francesco, V Geetha, V Garnier, J Munson, PJ AF Di Francesco, V Geetha, V Garnier, J Munson, PJ TI Fold recognition using predicted secondary structure sequences and hidden Markov models of protein folds SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE protein structure prediction; hidden Markov models; fold recognition; secondary structure ID AMINO-ACID-SEQUENCE; EPIDERMOLYTIC TOXINS AB We present an analysis of the blind predictions submitted to the fold recognition category for the second meeting on the Critical Assessment of techniques for protein Structure Prediction. Our method achieves fold recognition from predicted secondary structure sequences using hidden Markov models (HMMs) of protein folds, HMMs are trained only with experimentally derived secondary structure sequences of proteins having similar fold, therefore protein structures are described by the models at a remarkably simplified level. We submitted predictions for five target sequences, of which four were later found to be suitable for threading. Our approach correctly predicted the fold for three of them, For a fourth sequence the fold could have been correctly predicted if a better model for its structure was available, We conclude that we have additional evidence that secondary structure information represents an important factor for achieving fold recognition. (C) 1998 Wiley-Liss, Inc. C1 NIH, Analyt Biostat Sect, Struct Biol Lab, Bethesda, MD USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Di Francesco, V (reprint author), Inst Genom Res, Rockville, MD 20850 USA. EM valedf@tigr.org NR 22 TC 17 Z9 19 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PY 1997 SU 1 BP 123 EP 128 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YW306 UT WOS:000071920700016 ER PT S AU Putnam, FW Trickett, PK AF Putnam, FW Trickett, PK BE Yehuda, R McFarlane, AC TI Psychobiological effects of sexual abuse - A longitudinal study SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Psychobiology of Posttraumatic Stress Disorder CY SEP 07-10, 1996 CL NEW YORK, NY SP New York Acad Sci ID POSTTRAUMATIC-STRESS-DISORDER; CHILDREN; FEMALES; IMPACT C1 UNIV SO CALIF, DEPT PSYCHOL, LOS ANGELES, CA 90089 USA. RP Putnam, FW (reprint author), NIMH, UDT, BEHAV ENDOCRINOL BRANCH, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 31 TC 70 Z9 71 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-079-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 821 BP 150 EP 159 DI 10.1111/j.1749-6632.1997.tb48276.x PG 10 WC Behavioral Sciences; Multidisciplinary Sciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Psychiatry GA BJ18D UT WOS:A1997BJ18D00013 PM 9238201 ER PT S AU Post, RM Weiss, SRB Smith, M Li, H McCann, U AF Post, RM Weiss, SRB Smith, M Li, H McCann, U BE Yehuda, R McFarlane, AC TI Kindling versus quenching - Implications for the evolution and treatment of posttraumatic stress disorder SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Psychobiology of Posttraumatic Stress Disorder CY SEP 07-10, 1996 CL NEW YORK, NY SP New York Acad Sci ID THYROTROPIN-RELEASING-HORMONE; RECURRENT AFFECTIVE-DISORDER; EXPRESSION; MECHANISMS; DEPRESSION; TRH; SENSITIZATION; NEUROBIOLOGY; STIMULATION; ACTIVATION RP Post, RM (reprint author), NIMH, BIOL PSYCHIAT BRANCH,NIH,BLDG 10,ROOM 3N212, 10 CTR DR MSC 1272, BETHESDA, MD 20892 USA. NR 50 TC 65 Z9 66 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-079-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 821 BP 285 EP 295 DI 10.1111/j.1749-6632.1997.tb48287.x PG 11 WC Behavioral Sciences; Multidisciplinary Sciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Psychiatry GA BJ18D UT WOS:A1997BJ18D00024 PM 9238212 ER PT S AU Hall, FS Huang, S Fong, G AF Hall, FS Huang, S Fong, G BE Yehuda, R McFarlane, AC TI Effects of isolation-rearing on acoustic startle and pre-pulse inhibition in Wistar and Fawn Hooded rats SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Psychobiology of Posttraumatic Stress Disorder CY SEP 07-10, 1996 CL NEW YORK, NY SP New York Acad Sci RP Hall, FS (reprint author), NIAAA, CLIN STUDIES LAB,DICBR,NIH,BLDG 10, ROOM 3C-207, BETHESDA, MD 20892 USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 5 TC 27 Z9 27 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-079-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 821 BP 542 EP 544 DI 10.1111/j.1749-6632.1997.tb48325.x PG 3 WC Behavioral Sciences; Multidisciplinary Sciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Psychiatry GA BJ18D UT WOS:A1997BJ18D00062 PM 9238248 ER PT J AU Oren, DA Giesen, HA Wehr, TA AF Oren, DA Giesen, HA Wehr, TA TI Restoration of detectable melatonin after entrainment to a 24-hour schedule in a 'free-running' man SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE hypernychthemeral; sleep; light; circadian rhythms; melatonin; testosterone ID SEASONAL AFFECTIVE-DISORDER; SLEEP PHASE SYNDROME; PINEAL-GLAND; SECRETION; LIGHT; HORMONE; RHYTHM; TESTOSTERONE; REPLACEMENT; ADAPTATION AB We evaluated a 37-year-old male with a non-24-h sleep-wake disorder. His environment gave him little exposure to bright light. Circadian profiles of temperature, melatonin, thyrotropin, cortisol and testosterone were obtained along with endocrine challenges of the thyroid, adrenal, growth hormone and gonadal axes. Multiple endocrine abnormalities were detected. Testosterone was low and nocturnal thyrotropin levels were erratic. Serum melatonin was undetectable throughout the day and night on multiple occasions, and responses to infusions of TRH, GnRH and GRF-44 were abnormal. Responses to CRH infusion were normal. The patient was successfully entrained to a 24-h schedule by daily exposure to 2500 lux light from 0700h to 0900h, avoidance of light (by wearing dark goggles) from 1800h to 2300h, and strict enforcement of a dark environment from 2300h to 0700h. After entrainment, a normal pattern of nocturnal melatonin secretion was found. GH response to GRF-44 also normalized, although abnormal responses to TRH and GnRH persisted. This case raises the possibility that a complex interaction of light exposure with the circadian system can reversibly suspend pineal gland secretion of melatonin indefinitely. It also suggests that circadian rhythm disorders be considered in the differential diagnosis of abnormal endocrine function. Published by Elsevier Science Ltd. C1 YALE UNIV,SCH MED,DVA,W HAVEN,CT 06516. NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. NR 43 TC 12 Z9 13 U1 1 U2 2 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 JAN PY 1997 VL 22 IS 1 BP 39 EP 52 DI 10.1016/S0306-4530(96)00038-8 PG 14 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA WR191 UT WOS:A1997WR19100004 PM 9141150 ER PT J AU Shoaib, M Schindler, CW Goldberg, SR AF Shoaib, M Schindler, CW Goldberg, SR TI Nicotine self-administration in rats: Strain and nicotine pre-exposure effects on acquisition SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; reinforcement; intravenous self-administration; strain differences; rat ID LOCOMOTOR-ACTIVITY; TASTE-AVERSION; COCAINE; BEHAVIOR; INJECTIONS; REINFORCEMENT; ADDICTION; SCHEDULE AB Nicotine has been shown to maintain intravenous self-administration behaviour in humans and laboratory animals. However, factors critical in the initiation of nicotine self administration are not well defined. In particular genetic differences and effects of pre-exposure to nicotine have not been examined. Male Sprague-Dawley or Long-Evans rats were surgically prepared with indwelling jugular catheters and 3 days later received chronic injections of nicotine (0.4 mg/kg SC) or vehicle (saline, 1 ml/kg) for 7 days in their home cage. The next day, 2-h daily test sessions were initiated, during which rats were given the opportunity to nose-poke for nicotine infusions (0.015, 0.03 or 0.06 mg/kg per infusion) under a one-response fixed-ratio (FR-1) schedule of reinforcement with a 20-s time out after each infusion. One hole was defined as active while pokes in the other hole were recorded but had no scheduled consequence. The response requirement was increased progressively to five (FR-5) over successive sessions. Both saline- and nicotine-pretreated Sprague-Dawley rats showed a preference for the active hole, while only the saline-pretreated Long-Evans rats acquired the self-administration as defined by significant differences between responding in the active versus the inactive holes. The Fisher (F344) and Lewis inbred strains also failed to acquire self-administration of nicotine under these conditions. With Sprague-Dawley and Long-Evans rats that acquired the self-administration, and showed stable levels of maintained responding for nicotine, substituting saline for the nicotine or pretreating with mecamylamine (2.0 mg/kg SC) extinguished the behaviour. When dose per infusion was varied, an inverted U-shaped dose-response curve was obtained. These results support previous reports that nicotine can serve as a reinforcer in rodents and demonstrate that environmental factors such as prior nicotine exposure or genetic factors such as rat strain can affect acquisition of nicotine self-administration. RP Shoaib, M (reprint author), NIDA,PRECLIN PHARMACOL LAB,ADDICT RES CTR,DIR,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 27 TC 183 Z9 184 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 1997 VL 129 IS 1 BP 35 EP 43 DI 10.1007/s002130050159 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WE139 UT WOS:A1997WE13900005 PM 9122361 ER PT J AU Gwirtsman, HE Blehar, MC McCullough, JP Kocsis, JH Prien, RF AF Gwirtsman, HE Blehar, MC McCullough, JP Kocsis, JH Prien, RF TI Standardized assessment of dysthymia: Report of a National Institute of Mental Health conference SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Editorial Material DE diagnosis; questionnaires; psychological interview; treatment outcome ID MAJOR DEPRESSION; SOCIOENVIRONMENTAL CHARACTERISTICS; DIAGNOSTIC INTERVIEW; SOCIAL ADJUSTMENT; ONSET DYSTHYMIA; GENERAL HEALTH; DISORDER; PERSONALITY; RELIABILITY; RATIONALE C1 NIMH,ROCKVILLE,MD 20857. VIRGINIA COMMONWEALTH UNIV,RICHMOND,VA. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY 10021. NR 48 TC 30 Z9 30 U1 3 U2 6 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 1 BP 3 EP 11 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA WU646 UT WOS:A1997WU64600002 PM 9133745 ER PT J AU Arnold, LE Hoagwood, K Jensen, PS Vitiello, B AF Arnold, LE Hoagwood, K Jensen, PS Vitiello, B TI Toward clinically relevant clinical trials SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE treatment; services; research; clinician; patient; algorithm ID METHYLPHENIDATE; DISORDER; CHILDREN AB This article grapples with two closely related tensions threatening the credibility and relevance of clinical trials to clinicians as well as patients and their families: (1) the tension between clinical flexibility and scientific standardization of protocol and (2) the tension between the need to ensure scientific integrity through a standard, pre-specified protocol and the need to increase compliance by involving patients and their families in goal setting and treatment planning. We propose four partial solutions: (1) relaxed exclusion criteria to maximize generalizability, using only those exclusion criteria essential to the treatment; (2) extensive use of clinical algorithms to incorporate clinical flexibility in a standardized way; (3) active involvement of therapists in decision-making, including cross-site clinical decision panels; and (4) active involvement of families through a goal-setting and treatment-planning session as the first step of treatment. Although we focus on clinical trials with children and adolescents, the principles and ideas may also apply to clinical trials with patients of any age. This article summarizes and elaborates on presentations made by three of the authors at workshops on psychiatric clinical trials in children and adolescents at the May 1996 New Clinical Drug Evaulation Unit (NCDEU) meeting, The focus was on enhancing the clinical relevance of clinical trials-making the results useful and credible to practitioners and patients and their families. C1 NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,DIV CLIN & TREATMENT RES,ROCKVILLE,MD 20857. OHIO STATE UNIV,COLUMBUS,OH 43210. NIMH,SERV RES BRANCH,ROCKVILLE,MD 20857. OI Jensen, Peter/0000-0003-2387-0650 NR 15 TC 6 Z9 6 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 1 BP 135 EP 142 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA WU646 UT WOS:A1997WU64600022 PM 9133765 ER PT J AU Schmidt, PJ Rubinow, DR AF Schmidt, PJ Rubinow, DR TI Neuroregulatory role of gonadal steroids in humans SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article ID HORMONE RECEPTORS; ACTIVATION RP Schmidt, PJ (reprint author), NIMH,BEHAV ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 12 TC 21 Z9 21 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 2 BP 219 EP 220 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XM243 UT WOS:A1997XM24300005 PM 9230633 ER PT J AU Schmidt, ME Goldstein, DS Schouten, JL Matochik, JA Kim, HG Potter, WZ AF Schmidt, ME Goldstein, DS Schouten, JL Matochik, JA Kim, HG Potter, WZ TI Acute alpha(2) blockade by idazoxan increases insulin and lowers plasma glucose during positron emission tomography SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE [F-18]-fluoro-deoxyglucose; alpha(2) adrenoceptor antagonist; norepinephrine; imidazoline ID ALPHA-2-ADRENOCEPTOR ANTAGONIST; HEALTHY-SUBJECTS; BINDING-SITES; BLOOD-FLOW; ADRENOCEPTOR; METABOLISM; RELEASE; SECRETION; CATECHOLAMINES; NOREPINEPHRINE AB The sympathetic nervous system can modulate glucose levels through a variety of mechanisms, including inhibition of insulin release by alpha(2)-adrenergic receptors. Such effects could potentially confound measurements of brain glucose metabolism during studies of the central actions of sympathomimetic drugs. Plasma glucose, insulin, and sympathetic responses to alpha, blockade were measured following infusion of idazoxan, a selective alpha, antagonist, or placebo, in 33 healthy volunteers (idazoxan: n=23, placebo: n=10). These measures were compared with estimates of global brain metabolism obtained from positron emission tomography (PET) scans before and after the infusion. Glucose revels fell and fractional levels of insulin rose after idazoxan, compared with placebo. Relative increases in insulin correlated with increases in epinephrine after active drug. The increases in insulin are consistent with the hypothesized role of alpha(2)-adrenoceptors in regulating insulin release. Estimates of global brain glucose metabolism did not appear to be influenced by the modest changes in plasma glucose. C1 NIH,CLIN PHARMACOL SECT,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NINCDS,CLIN NEUROCHEM SECT,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NIDA,BRAIN IMAGING SECT,NIH,BALTIMORE,MD. RP Schmidt, ME (reprint author), ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,893 DELAWARE ST,INDIANAPOLIS,IN 46285, USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 48 TC 5 Z9 5 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 2 BP 253 EP 259 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XM243 UT WOS:A1997XM24300011 PM 9230639 ER PT J AU Lebowitz, BD Pollock, BG Schneider, LS AF Lebowitz, BD Pollock, BG Schneider, LS TI Estrogen in geriatric psychopharmacology SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article ID OLDER WOMEN; REPLACEMENT THERAPY; ALZHEIMERS-DISEASE; RISK C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV SO CALIF,LOS ANGELES,CA 90089. RP Lebowitz, BD (reprint author), NIMH,MENTAL DISORDERS AGING RES BRANCH,DIV CLIN RES,5600 FISHERS LANE,ROOM 18-101,ROCKVILLE,MD 20857, USA. NR 23 TC 1 Z9 1 U1 4 U2 4 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 2 BP 287 EP 288 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XM243 UT WOS:A1997XM24300016 PM 9230644 ER PT J AU Rudorfer, MV Goldstein, H AF Rudorfer, MV Goldstein, H TI Research priorities in eating disorders SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Editorial Material C1 NIMH,EATING DISORDER PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 3 BP 317 EP 319 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XZ328 UT WOS:A1997XZ32800001 ER PT J AU Grilo, CM Devlin, MJ Cachelin, FM Yanovski, SZ AF Grilo, CM Devlin, MJ Cachelin, FM Yanovski, SZ TI Report of the National Institutes of Health (NIH) Workshop on the Development of Research Priorities in Eating Disorders SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Editorial Material DE eating disorders; anorexia nervosa; bulimia nervosa; research; workshops AB The National Institutes of Health (NIH) Workshop on the Development of Research Priorities in Eating Disorders was convened in New York on April 24 and 25, 1996. The goals of the workshop were (1) to identify important unanswered questions in the study and treatment of eating disorders, (2) to discuss potentially fruitful approaches to answering these questions through basic and clinical research, and (3) to assist the NIH and other funding agencies in assigning priorities for research on eating disorders. The program consisted of a series of brief presentations by moderators, each followed by facilitated discussion of the topic with members of the audience. Three reporters (CMG, MJD, FMC) took detailed notes of the proceedings, which have been incorporated into this article, A summary of this workshop is presented, along with recommendations for future research that were identified by workshop participants. C1 NIDDKD,DIV DIGEST DIS & NUTR,NIH,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK STATE PSYCHIAT INST,OFF MENTAL HLTH,NEW YORK,NY 10032. WESLEYAN UNIV,DEPT PSYCHOL,MIDDLETOWN,CT. NR 3 TC 28 Z9 28 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 3 BP 321 EP 333 PG 13 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XZ328 UT WOS:A1997XZ32800002 PM 9550875 ER PT J AU Kumra, S Herion, D Jacobsen, LK Briguglia, C Grothe, D AF Kumra, S Herion, D Jacobsen, LK Briguglia, C Grothe, D TI Risperidone-induced hepatotoxicity in pediatric patients SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 NIH,DEPT CHILD PSYCHIAT,BETHESDA,MD 20892. NIH,DEPT GASTROENTEROL,BETHESDA,MD 20892. NIH,DEPT CLIN CTR PHARM,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 3 BP 540 EP 540 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XZ328 UT WOS:A1997XZ32800088 ER PT J AU Kumra, S Jacobsen, LK Lenane, M Lee, PR Smith, AK Bedwell, J Malanga, CJ Rapoport, JL AF Kumra, S Jacobsen, LK Lenane, M Lee, PR Smith, AK Bedwell, J Malanga, CJ Rapoport, JL TI Childhood-onset schizophrenia: An open-label trial of olanzapine SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 3 BP 541 EP 541 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XZ328 UT WOS:A1997XZ32800089 ER PT J AU Malhotra, AK Goldman, D Buchanan, R Pickar, D Breier, A AF Malhotra, AK Goldman, D Buchanan, R Pickar, D Breier, A TI The antipsychotic efficacy of clozapine and NMDA receptor function: Evidence from clinical and molecular studies SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NIAAA,ROCKVILLE,MD 20852. MARYLAND PSYCHIAT RES CTR,CATONSVILLE,MD 21228. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 3 BP 551 EP 551 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XZ328 UT WOS:A1997XZ32800099 ER PT J AU Vitiello, B Goodkin, K Heaton, R Rochon, J Atkinson, H Wilkie, F Brown, S Feaster, D Goldschmidts, W Stover, E Koslow, S AF Vitiello, B Goodkin, K Heaton, R Rochon, J Atkinson, H Wilkie, F Brown, S Feaster, D Goldschmidts, W Stover, E Koslow, S TI Factors associated with HIV-related cognitive impairment SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Meeting Abstract C1 NIMH,NIH,ROCKVILLE,MD 20857. UNIV MIAMI,DEPT PSYCHIAT,MIAMI,FL 33152. UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,SAN DIEGO,CA 92103. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. RI Feaster, Daniel/I-6079-2013 NR 2 TC 0 Z9 0 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 3 BP 600 EP 600 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XZ328 UT WOS:A1997XZ32800148 ER PT J AU Hibbs, ED Clarke, G Hechtman, L Abikoff, HB Greenhill, LL Jensen, PS AF Hibbs, ED Clarke, G Hechtman, L Abikoff, HB Greenhill, LL Jensen, PS TI Manual development for the treatment of child and adolescent disorders SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the National-Center-for-Drug-Evaluation CY MAY 27-30, 1997 CL BOCA RATON, FLORIDA SP Natl Ctr Drug Eval Unit, NIMH DE manuals; treatment; child; adolescent; therapy ID COGNITIVE THERAPY; PSYCHOTHERAPY; ISSUES; CARE AB There has been a proliferation of treatment manuals in the past decade as part of an effort to operationalize treatment applications and standardize treatments across subjects, settings, and therapists. In this article we present the essential elements needed to develop manuals for the psychosocial and psychopharmacological treatments of child and adolescent disorders, using one modality or in multimodal treatment trials. We delineate how to integrate various treatment components for psychosocial and psychopharmacological manuals, as well as those for central conditions. We also examine the therapist variable as it concerns training and adherence to the structured or flexible scripted manuals. Finally, we discuss the advantages and disadvantages of manuals in terms of how they may affect outcome, recommending that treatments be both empirically grounded and clinically meaningful. C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Rockville, MD 20857 USA. Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. McGill Univ, Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. NYU, Med Ctr, New York, NY 10016 USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. RP Hibbs, ED (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Rm 100-09,5600 Fishers Lane, Rockville, MD 20857 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 33 TC 11 Z9 12 U1 0 U2 5 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1997 VL 33 IS 4 BP 619 EP 629 PG 11 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA YZ164 UT WOS:000072226700002 PM 9493471 ER PT J AU Sheffield, D Sheps, DS Light, KC Krantz, DS Stone, PH Raczynski, J Kaufmann, PG Forman, S AF Sheffield, D Sheps, DS Light, KC Krantz, DS Stone, PH Raczynski, J Kaufmann, PG Forman, S TI Triggers of myocardial ischemia during daily life: Results from the psychophysiological investigation of myocardial ischemia (pimi) study. SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC 27515. UNIFORMED SERV UNIV HLTH SCI,BRIGHAM & WOMENS HOSP,BOSTON,MA. UNIV ALABAMA,TUSCALOOSA,AL 35487. NHLBI,BETHESDA,MD. MARYLAND MED RES INST,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 1997 VL 59 IS 1 BP 92 EP 92 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA WF121 UT WOS:A1997WF12100080 ER PT J AU Sheps, D Krantz, D Knatterud, GL Burg, MM Blumenthal, JA Kaufmann, PG AF Sheps, D Krantz, D Knatterud, GL Burg, MM Blumenthal, JA Kaufmann, PG TI Psychological Stress-Induced Ischemia SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 MARYLAND MED RES INST,BALTIMORE,MD. VET ADM MED CTR,W HAVEN,CT 06516. DUKE UNIV,MED CTR,DURHAM,NC. NHLBI,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. UNIV N CAROLINA,CHAPEL HILL,NC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 1997 VL 59 IS 1 BP 108 EP 108 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA WF121 UT WOS:A1997WF12100147 ER PT J AU Schechter, AN AF Schechter, AN TI Sickle cell disease expenditures and outcomes SO PUBLIC HEALTH REPORTS LA English DT Editorial Material ID ANEMIA RP NIDDKD, BIOL CHEM LAB,NIH,BLDG 10,ROOM 9N307,10 CTR DR, MSC 1822, BETHESDA, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 9 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0033-3549 EI 1468-2877 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1997 VL 112 IS 1 BP 38 EP 39 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WD994 UT WOS:A1997WD99400023 PM 9018286 ER PT J AU Davis, H Moore, RM Gergen, PJ AF Davis, H Moore, RM Gergen, PJ TI Cost of hospitalizations associated with sickle cell disease in the United States SO PUBLIC HEALTH REPORTS LA English DT Article ID FREQUENCY AB Objective. This study estimated the number and cost of hospitalizations associated with sickle cell disease in the United Slates. Methods. To estimate the number of hospitalizations per year in the United States of people with sickle cell disease, the authors used data for the years 1989 through 1993 from national hospital discharge surveys conducted by the National Center for Health Statistics. The authors derived cost estimates using data from a 1992 national hospital discharge survey conducted by the Agency for Health Care Policy and Research and a 1992 survey of physicians conducted by the American Medical Association. Results. During the year 1989 through 1993, there were on average an estimated 75,000 hospitalizations per year of children and adults with sickle cell disease. The average direct cost per hospitalization (in 1996 dollars) was estimated at $6300, for a total direct cost of $475 million per year. In 66% of hospital discharge records, government programs were listed as the expected principal source of payment. Conclusions. The cost of hospitalizations associated with sickle cell disease is substantial, Because government programs pay most of this cost, further government-funded research to develop interventions that prevent complications of the disease has great potential for cost savings as well as for reducing the suffering of those afflicted with this painful genetic disorder. These national cost estimates contribute to an understanding of the impact of sickle cell disease and should be useful in establishing research priorities. C1 US DEPT HHS,OFF SECRETARY,OFF INT & REFUGE HLTH,WASHINGTON,DC 20201. NIAID,NIH,BETHESDA,MD. NR 6 TC 55 Z9 55 U1 1 U2 4 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1997 VL 112 IS 1 BP 40 EP 43 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WD994 UT WOS:A1997WD99400024 PM 9018287 ER PT J AU Davis, H Gergen, PJ Moore, RM AF Davis, H Gergen, PJ Moore, RM TI Geographic differences in mortality of young children with sickle cell disease in the United States SO PUBLIC HEALTH REPORTS LA English DT Article ID ANEMIA; SURVIVAL AB Objectives. Because geographic differences in health care have been found for many diseases, including those affecting children, there are probably geographic differences in the health care of young children with sickle. cell disease. Consequently, survival of young children with sickle cell disease might differ among geographic areas. This study's objective was to identify areas in the United States where young children with sickle cell disease are at especially high and low risk of dying. Methods. Using U.S. death certificate data From 1968 through 1992, the authors calculated the mortality rates of 1- through 4-year-old black children with sickle cell disease for states, counties, and cities. Deaths from trauma, congenital anomalies, and perinatal conditions were excluded. Results. From 1968 through 1980 and from 1981 through 1992, 1- through 4-year-old black children with sickle cell disease in Florida had a markedly higher risk of dying, and those in Pennsylvania had a markedly lower risk of dying, than the average 1- through 4-year-old black child with the disease in the United States, From 1981 through 1992, 1- through 4-year-old black children with sickle cell disease in Maryland had the lowest mortality rate in the nation, During the same time period, 1- through 4-year-old black children with sickle cell disease in five counties in Florida were at especially high risk while in Baltimore no young black children with the disease died, These geographic differences in mortality of black children with sickle cell disease greatly exceeded geographic differences in mortality of black children without the disease. Conclusions. Marked differences exist across the United States in mortality of young black children with sickle cell disease. To improve survival for children with the disease in high mortality areas, evaluations should be made of the accessibility and quality of medical care, and of parents' health care seeking behavior and compliance with antibiotic prophylaxis, in addition, efforts should be made to understand and duplicate the success of treatment programs in low mortality areas. C1 US DEPT HHS,OFF SECRETARY,OFF INT & REFUGEE HLTH,WASHINGTON,DC. NIAID,NIH,BETHESDA,MD 20892. NR 20 TC 24 Z9 24 U1 0 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1997 VL 112 IS 1 BP 52 EP 58 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WD994 UT WOS:A1997WD99400026 PM 9018289 ER PT J AU Wu, C Brechbiel, MW Gansow, OA Kobayashi, H Carrasquillo, J Pastan, I AF Wu, C Brechbiel, MW Gansow, OA Kobayashi, H Carrasquillo, J Pastan, I TI Stability of the four 2-(p-nitrobenzyl)-trans-CyDTPA Y-88 complexes SO RADIOCHIMICA ACTA LA English DT Article; Proceedings Paper CT Symposium on Radiochemistry and Radioimmunotherapy at the 212th National Meeting of the American-Chemical-Society CY AUG 25-29, 1996 CL ORLANDO, FLORIDA SP Amer Chem Soc, Div Nucl Chem & Technol DE yttrium; antibodies; radioimmunotherapy; chelates; stereochemistry ID PARTICLE-MEDIATED RADIOIMMUNOTHERAPY; MONOCLONAL-ANTIBODIES; BIODISTRIBUTION; LIGANDS; DTPA; B3 AB The unusual stereochemical influence on in vivo stability of the two C-Functionalized cyclohexyl diethylenetriamine-N,N,N',N ",N "-pentaacetic acid (CyDTPA) chelating agents, (CHX-A, CHX-B), recently reported warranted further investigation to determine why such differences in configuration produce such striking effects on the stability of the Yttrium complex. To this end, all four individual component stereoisomers of CHX-A and CHX-B were synthesized for a detailed investigation into their chelation chemistry. Results of transchelation measurements, serum stability studies, and in vivo femur deposition measurements with Y-88 indicate that the Y-88-CHX-A chelates are significantly more stable, in vitro and in vivo, than the Y-88-CHX-B complexes. Additionally, significant difference in vivo between the Y-88 complexes formed from the component enantiomeric ligands were observed. C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Nucl Med, CC, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 13 TC 6 Z9 6 U1 0 U2 0 PU R OLDENBOURG VERLAG PI MUNICH PA LEKTORAT M/N, K BERBER-NERLINGER, POSTFACH 80 13 60, D-81613 MUNICH, GERMANY SN 0033-8230 J9 RADIOCHIM ACTA JI Radiochim. Acta PY 1997 VL 79 IS 2 BP 123 EP 126 PG 4 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA YW901 UT WOS:000071986100012 ER PT J AU Wu, CC Brechbiel, MW Gansow, OA AF Wu, CC Brechbiel, MW Gansow, OA TI An improved generator for the production of Bi-213 from Ac-225 SO RADIOCHIMICA ACTA LA English DT Article; Proceedings Paper CT Symposium on Radiochemistry and Radioimmunotherapy at the 212th National Meeting of the American-Chemical-Society CY AUG 25-29, 1996 CL ORLANDO, FLORIDA SP Amer Chem Soc, Div Nucl Chem & Technol DE Ac-225; Bi-213; generator; radioimmunotherapy; actinide ID RADIOIMMUNOTHERAPY; RADIONUCLIDES; SEPARATION; RA-224 AB An improved generator was developed using a silica-based extraction chromatographic resin, Eichrom Silica Actinide Resin (Eichrom, Darien, IL), for the production of the alpha-emitting radionuclide Bi-213 and to minimize radiolysis of the Ac-225/Bi-213 generator. Ac-225 was adsorbed and evenly distributed on the top two-thirds of the generator resin. Bi-213 was eluted quantitatively with 1.0 M HCl. Simultaneous elution of the generator, subsequent dilution and re-adsorption of Bi-213 onto an MP-50 column to concentrate the activity was performed by assembling the columns in series. Breakthrough of Ac-225 from the generator was <0.05%, and no Ac-225 was found when Bi-213 was eluted from the second column. Bi-213 obtained can be easily used to radiolabel appropriate protein chelating agent conjugates. Hypothetically, resin damage by alpha-radiolysis should be obviated by employing such a silica-based resin and by broad distribution of the Ac-225 on the column. C1 NCI, Inorgan & Radioimmune Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, CC (reprint author), NCI, Inorgan & Radioimmune Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 14 TC 22 Z9 22 U1 3 U2 4 PU R OLDENBOURG VERLAG PI MUNICH PA LEKTORAT M/N, K BERBER-NERLINGER, POSTFACH 80 13 60, D-81613 MUNICH, GERMANY SN 0033-8230 J9 RADIOCHIM ACTA JI Radiochim. Acta PY 1997 VL 79 IS 2 BP 141 EP 144 PG 4 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA YW901 UT WOS:000071986100016 ER PT J AU Wolff, SD Balaban, RS AF Wolff, SD Balaban, RS TI Assessing contrast on MR images SO RADIOLOGY LA English DT Article DE magnetic resonance (MR), contrast enhancement; magnetic resonance (MR), pulse sequences; special reports ID FAST-SPIN-ECHO; 1.5 T; LIVER; ANGIOGRAPHY; SEQUENCE; LESIONS; NOISE AB Magnetic resonance imaging pulse sequences are frequently judged by their ability to facilitate discrimination between pathologic and normal tissue. Objective analysis is usually based on signal intensity measurements. However, the literature shows disagreement as to how this analysis should be performed. The ability to visually differentiate two objects on the basis of signal intensity depends on the contrast-to-noise ratio (CNR). This parameter, however, can be calculated only by measuring the intensity of photons reaching the eye from two distinct objects and, hence, is display dependent. The signal difference-to-noise ratio (SDNR) is a display-independent parameter that reflects the contrast-generating ability of a pulse sequence. When comparing two imaging sequences, the SDNR is proportional to the CNR, assuming the images being compared are displayed so that corresponding regions have the same intensity (ie, photon fluxes). Because the SDNR is display independent, it should be the preferred parameter for assessing the contrast-generating ability of a pulse sequence. The value and limitations of these parameters are discussed. RP Wolff, SD (reprint author), NHLBI,CARDIAC ENERGET LAB,NIH,BLDG 10,RM B1D161,10 CTR DR,MSC-1061,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 16 TC 64 Z9 65 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 JAN PY 1997 VL 202 IS 1 BP 25 EP 29 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WA401 UT WOS:A1997WA40100007 PM 8988186 ER PT J AU Bryan, RN Wells, SW Miller, TJ Elster, AD Jungreis, CA Poirier, VC Lind, BK Manolio, TA AF Bryan, RN Wells, SW Miller, TJ Elster, AD Jungreis, CA Poirier, VC Lind, BK Manolio, TA TI Infarctlike lesions in the brain: Prevalence and anatomic characteristics at MR imaging of the elderly - Data from the cardiovascular health study SO RADIOLOGY LA English DT Article DE brain, infarction; brain, MR ID LACUNAR INFARCTION; AGING BRAIN; OLDER ADULTS; RISK-FACTORS; STROKE; POPULATION; DISEASE; TOMOGRAPHY; REGISTRY; FEATURES AB PURPOSE: To determine the prevalence and anatomic characteristics of infarctlike lesions seen on cranial magnetic resonance (MR) images. MATERIALS AND METHODS: The study cohort consisted of 5,888 community-living individuals aged 65 years and older enrolled in a longitudinal, population-based study of cardiovascular disease. MR images were obtained from 3,658 participants and evaluated by trained readers. Lesion size, anatomic location, and signal intensity were recorded. Infarctlike lesion was defined as a nonmass, hyperintense region on spin-density- and T2- weighted images and, in cerebral white matter and brain stem, a hypointense region on n- weighted images. RESULTS: Infarctlike lesions were depicted on MR images of 1,323 (36%) participants. Eighty-five percent (1,128 participants) had lesions 3 mm or larger in maximum dimension, although 70.9% (1,320 of 1,861) of these lesions were 10 mn or less. Lesion prevalence increased with age, especially with lesions 3 mm or larger, which increased from 22.1% (86 of 389) in the 65-69-year age group to 42.9% (88 of 205) in the over-85-year age group (P < .0001). Lesion prevalence was slightly greater in men (497 of 1,527 [32.5%]) than in women (631 of 2,131 [29.6%]), but did not differ between blacks and nonblacks. The deep nuclei were the most commonly affected anatomic sites, with 78.2% (1,451 of 1,856) of lesions. Lesions that involved the cerebrum and posterior fossa accounted for 11.7% (218 of 1,856) and 10.1% (187 of 1,856) of lesions, respectively. CONCLUSION: If the lesions reported in this study indicate cerebrovascular disease, subclinical disease may be more prevalent than clinical disease, and the prevalence of disease may rise with age. Also, infarctlike lesions have a distinctive anatomic profile. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. PRESBYTERIAN UNIV HOSP,PITTSBURGH,PA 15213. UNIV CALIF DAVIS,SACRAMENTO,CA 95817. CARDIOVASC HLTH STUDY COORDINATING CTR,SEATTLE,WA. NHLBI,NIH,BETHESDA,MD 20892. RP Bryan, RN (reprint author), JOHNS HOPKINS MED INST,DIV NEURORADIOL,600 N WOLFE ST,BALTIMORE,MD 21287, USA. RI Bryan, R. Nick/P-1661-2014 FU NHLBI NIH HHS [N01-HC-15103] NR 34 TC 146 Z9 148 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1997 VL 202 IS 1 BP 47 EP 54 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WA401 UT WOS:A1997WA40100013 PM 8988191 ER PT J AU Termanini, B Gibril, F Doppman, JL Reynolds, JC Stewart, CA Sutliff, VE Venzon, DJ Jensen, RT AF Termanini, B Gibril, F Doppman, JL Reynolds, JC Stewart, CA Sutliff, VE Venzon, DJ Jensen, RT TI Distinguishing small hepatic hemangiomas from vascular liver metastases in gastrinoma: Use of a somatostatin-receptor scintigraphic agent SO RADIOLOGY LA English DT Article DE liver neoplasms; liver neoplasms, radionuclide studies; liver neoplasms, secondary; radionuclide imaging, comparative studies ID ZOLLINGER-ELLISON SYNDROME; PANCREATIC ENDOCRINE TUMORS; BLOOD-CELL SPECT; DYNAMIC BOLUS CT; CAVERNOUS HEMANGIOMA; LONG-TERM; NEUROENDOCRINE TUMORS; AGGRESSIVE RESECTION; MALIGNANT GASTRINOMA; COMPUTED-TOMOGRAPHY AB PURPOSE: To compare somatostatin-receptor scintigraphy and conventional imaging modalities in the differentiation of small hepatic hemangiomas from small liver metastases in Zollinger-Ellison syndrome. MATERIALS AND METHODS: Twenty-nine patients had hypervascular liver lesions smaller than 2 cm that could have been either metastases or hemangiomas. Fourteen patients had metastases, 14 had hemangiomas, and one had both. Scintigraphy was compared with computed tomography (CT), magnetic resonance (MR) imaging, and angiography for the correct identification of the lesions. RESULTS: The hemangiomas and liver metastases both had a mean size of 1.3 cm. In the patients with hepatic hemangiomas, scintigraphy showed no lesions. CT, angiography, or MR imaging showed a lesion in 40%-93%. With metastases present, any liver lesion was detected in 93% with scintigraphy versus 20%-60% with another modality. Scintigraphy depicted liver metastases in 93% of patients, which was higher than the sensitivities of other modalities. The accuracy (96%) and positive (100%) and negative (93%) predictive values of scintigraphy for detecting liver metastases were superior to those of other modalities. There were 45 liver metastases and 31 hemangiomas; a per lesion analysis gave results similar to the per patient analysis results. CONCLUSION: In Zollinger-Ellison syndrome, somatostatin-receptor scintigraphy provides an excellent diagnostic tool to differentiate small hepatic hemangiomas from small liver metastases. C1 NIDDK,NIH,WARREN GRANT MAGNUSON CLIN CTR,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,NIH,WARREN GRANT MAGNUSON CLIN CTR,BIOSTAT DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 57 TC 35 Z9 35 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 JAN PY 1997 VL 202 IS 1 BP 151 EP 158 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WA401 UT WOS:A1997WA40100027 PM 8988205 ER PT J AU Amado, FML Domingues, P SantanaMarques, MG FerrerCorreia, AJ Tomer, KB AF Amado, FML Domingues, P SantanaMarques, MG FerrerCorreia, AJ Tomer, KB TI Discrimination effects and sensitivity variations in matrix-assisted laser desorption/ionization SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article; Proceedings Paper CT 15th Annual Informal Meeting on Mass Spectrometry (IMMS) CY MAY 12-16, 1997 CL SMOLENICE, SLOVAKIA SP Italian Natl Council Res, Hungarian Acad Sci, Slovakian Acad Sci ID IONIZATION MASS-SPECTROMETRY; DESORPTION; ACID; PROTEINS; IONS AB In matrix-assisted laser desorption/ionization (MALDI) the analyte signal produced depends strongly on the analyte and on the sample preparation procedure. Comparing the results obtained with the dried-drop method with the results obtained,vith a homogeneous sample preparation procedure, discrimination effects, as web as sensitivity variations, are shown to be dependent on the molecular weight of the analysed compounds. The signal obtained in MALDI is shown to be dependent on the hydrophobicity and basicity of the analyte. With the dried-drop method, in particular, evidence of peripheral sample deposition of hydrophilic compounds is shown. These last effects are due to mass transfer caused by differences in surface activities during solvent evaporation, and are known as Marangoni effects. (C) 1997 by John Wiley & Sons, Ltd. C1 NIEHS,LAB MOL BIOPHYS,RES TRIANGLE PK,NC 27709. RP Amado, FML (reprint author), UNIV AVEIRO,DEPT CHEM,P-3800 AVEIRO,PORTUGAL. RI Tomer, Kenneth/E-8018-2013; Domingues, Pedro/E-5202-2010; Amado, Francisco/M-5337-2015 OI Domingues, Pedro/0000-0002-8060-7675; Amado, Francisco/0000-0001-8256-1749 NR 26 TC 72 Z9 72 U1 0 U2 10 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1997 VL 11 IS 12 BP 1347 EP 1352 DI 10.1002/(SICI)1097-0231(199708)11:12<1347::AID-RCM974>3.0.CO;2-8 PG 6 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA XR697 UT WOS:A1997XR69700020 ER PT B AU Brawley, OW Thompson, IM AF Brawley, OW Thompson, IM BE Schroder, FH TI Chemoprevention of prostate cancer and the prostate cancer prevention trial SO RECENT ADVANCES IN PROSTATE CANCER AND BPH LA English DT Proceedings Paper CT IV Congress on Progress and Controversies in Oncological Urology (PACIOU IV) CY APR, 1996 CL ROTTERDAM, NETHERLANDS RP Brawley, OW (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER, ENGLAND LA6 2LA BN 1-85070-784-7 PY 1997 BP 51 EP 59 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BH04Y UT WOS:A1997BH04Y00006 ER PT S AU Sekiya, F Morita, T AF Sekiya, F Morita, T BE Takada, A Collen, D Gaffney, PJ TI A new cascade theory of blood coagulation: Magnesium (II) is a crucial constituent of the blood coagulation cascade SO RECENT PROGRESS IN BLOOD COAGULATION AND FIBRINOLYSIS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT International Symposium on Clot Formation and Lysis, at the 74th Annual Meeting of the Japanese-Society-of-Physiology CY MAR 21-22, 1997 CL HAMAMATSU, JAPAN SP Japanese Soc Physiol C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Sekiya, F (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82602-5 J9 INT CONGR SER PY 1997 VL 1129 BP 3 EP 7 PG 5 WC Hematology; Physiology SC Hematology; Physiology GA BK22F UT WOS:000071570600001 ER PT S AU Klein, DC Coon, SL Roseboom, PH Weller, JL Bernard, M Gastel, JA Zatz, M Iuvone, PM Rodriguez, IR Begay, V Falcon, J Cahill, GM Cassone, VM Baler, R AF Klein, DC Coon, SL Roseboom, PH Weller, JL Bernard, M Gastel, JA Zatz, M Iuvone, PM Rodriguez, IR Begay, V Falcon, J Cahill, GM Cassone, VM Baler, R BE Conn, PM TI The melatonin rhythm-generating enzyme: Molecular regulation of serotonin N-acetyltransferase in the pineal gland SO RECENT PROGRESS IN HORMONE RESEARCH, PROCEEDINGS OF THE 1996 CONFERENCE, VOL 52 SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Article; Proceedings Paper CT 52nd Meeting of Recent Progress on Hormone Research CY 1996 CL STEVENSON, WASHINGTON SP Endocrine Soc, Merck & Co Inc, Glaxo Wellcome Inc, Eli Lilly & Co ID BETA-ADRENERGIC STIMULATION; PROTEIN KINASE-C; RAT PINEALOCYTES; CIRCADIAN-RHYTHMS; INDOLE METABOLISM; CHICKEN RETINA; KAINIC ACID; CELLS; EXPRESSION; LIGHT AB A remarkably constant feature of vertebrate physiology is a daily rhythm of melatonin in the circulation which serves as the hormonal signal of the daily light/dark cycle: melatonin levels are always elevated at night. The biochemical basis of this hormonal rhythm is one of the enzymes involved in melatonin synthesis in the pineal gland-the melatonin rhythm-generating enzyme-serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT, E.C. 2.3.1.87). In all vertebrates, enzyme activity is high at night. This reflects the influences of internal circadian clocks and of light. The dynamics of this enzyme an remarkable. The magnitude of the nocturnal increase in enzyme activity ranges from 7- to 150-fold on a species-to-species basis among vertebrates. In all cases the nocturnal levels of AA-NAT activity decrease very rapidly following exposure to light. A major advance in the study of the molecular basis of these changes was the cloning of cDNA encoding the enzyme. This has resulted in rapid progress in our understanding of the biology and structure of AA-NAT and how it is regulated. Several constant features of this enzyme have become apparent, including structural features, tissue distribution, and a close association of enzyme activity and protein. However, some remarkable differences among species in the molecular mechanisms involved in regulating the enzyme have been discovered. In sheep, AA-NAT mRNA levels show relatively little change over a 24-hour period and changes in AA-NAT activity are primarily regulated at the protein level. In the rat, AA-NAT is also regulated at a protein level; however, in addition, AA-NAT mRNA levels exhibit a 150-fold rhythm, which reflects cyclic AMP-dependent regulation of expression of the AA-NAT gene. In the chicken, cyclic AMP acts primarily at the protein level and a rhythm in AA-NAT mRNA is driven by a noncyclic AMP-dependent mechanism linked to the clock within the pineal gland. Finally, in the trout, AA-NAT mRNA levels shoe little change and activity is regulated by light acting directly on the pineal gland. The variety of mechanisms that have evolved among vertebrates to achieve the same goal-a rhythm in melatonin-underlines the important role melatonin plays as the hormonal signal of environmental lighting in vertebrates. C1 NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Sect Biochem Pharmacol, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. UFR Sci, Lab Neurobiol & Cellular Neuroendocrinol, Dept Neurosci, UMR CNRS 6558, F-86022 Poitiers, France. Univ Houston, Dept Biol, Houston, TX 77204 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Klein, DC (reprint author), NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RI FALCON, Jack/I-5302-2013 OI FALCON, Jack/0000-0002-7572-6581 FU NEI NIH HHS [EY-04864, R01 EY004864] NR 72 TC 396 Z9 408 U1 3 U2 26 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4410 USA SN 0079-9963 BN 1-879225-26-3 J9 RECENT PROG HORM RES PY 1997 VL 52 BP 307 EP 358 PG 52 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BK30S UT WOS:000071740900013 PM 9238858 ER PT J AU Kapp, OH Siemion, J Eckelman, WC Cohen, VI Reba, RC AF Kapp, OH Siemion, J Eckelman, WC Cohen, VI Reba, RC TI Molecular modeling of the interaction of diagnostic radiopharmaceuticals with receptor proteins - m2 antagonist binding to the muscarinic m2 subtype receptor SO RECEPTORS & SIGNAL TRANSDUCTION LA English DT Review DE muscarinic receptors; drug design; PET; SPECT; diagnostic radiopharmaceuticals; molecular modeling; G-protein-linked receptors; m2; antagonist ID SITE-DIRECTED MUTAGENESIS; BETA-ADRENERGIC-RECEPTOR; IN-VIVO SELECTIVITY; AMINO-ACID SUBSTITUTIONS; 3RD CYTOPLASMIC LOOP; COUPLED RECEPTORS; LIGAND-BINDING; ACETYLCHOLINE-RECEPTORS; 3-DIMENSIONAL MODELS; AUTORADIOGRAPHIC EVIDENCE AB Models of the m2 muscarinic receptor have been built and acetylcholine and an antagonist of the quinuclidinylbenzilate family docked to the putative active site. We have incorporated aspects of homology, site-directed mutagenesis studies and structure-activity studies of specific lead compounds in the construction of our receptor models with a primary focus on the structure of the binding sites. We have observed a deep pocket binding of 5-BrQNT, suggesting a plausible explanation for the observation that agonists and antagonists do not bind competitively. The results of these computational studies are interpreted within the context of the observed in vitro results. Our goal is to assist in the development of subtype receptor selective radiopharmaceuticals for use in PET and SPECT. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Univ Chicago, Enrico Fermi Inst, Chicago, IL 60637 USA. NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. NR 136 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1052-8040 J9 RECEPT SIGNAL TRANS JI Recept. Signal Transduct. PY 1997 VL 7 IS 3 BP 177 EP 201 PG 25 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YN149 UT WOS:000071138000005 PM 9440504 ER PT J AU Goyer, R Eknoyan, G DeBroe, ME Buckalew, VM Mutti, A Porter, GA Morin, JP AF Goyer, R Eknoyan, G DeBroe, ME Buckalew, VM Mutti, A Porter, GA Morin, JP TI Urinary biomarkers to detect significant effects of environmental and occupational exposure to nephrotoxins .2. Nephrotoxins of significant frequency and economic impact SO RENAL FAILURE LA English DT Article; Proceedings Paper CT Joint US/European Union Workshop on Urinary Biomarkers to Detect Significant Effects of Environmental and Occupational Exposure to Nephrotoxins CY SEP 15-17, 1995 CL ATLANTA, GA ID BALKAN ENDEMIC NEPHROPATHY; STAGE RENAL-FAILURE; ANALGESIC NEPHROPATHY; HYDROCARBON EXPOSURE; ORGANIC-SOLVENTS; OCHRATOXIN-A; CHRONIC GLOMERULONEPHRITIS; DIAGNOSTIC-CRITERIA; MODEL; RISK RP Goyer, R (reprint author), NIEHS, OFF SENIOR SCI ADVISOR DIRECTOR, MAIL DROP WC05, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Mutti, Antonio/C-1095-2011 OI Mutti, Antonio/0000-0003-2189-3808 NR 41 TC 1 Z9 1 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0886-022X J9 RENAL FAILURE JI Ren. Fail. PY 1997 VL 19 IS 4 BP 523 EP 534 DI 10.3109/08860229709048689 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA XR747 UT WOS:A1997XR74700003 PM 9276902 ER PT J AU Giurgiovich, AJ Anderson, LM Jones, AB Dove, LF Moskal, TJ Rice, JM Olivero, OA Poirier, MC AF Giurgiovich, AJ Anderson, LM Jones, AB Dove, LF Moskal, TJ Rice, JM Olivero, OA Poirier, MC TI Transplacental cisplatin exposure induces persistent fetal mitochondrial and genomic DNA damage in patas monkeys SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE fetal monkey; DNA adduct; cisplatin-DNA dissociation-enhanced lanthanide fluoroimmunoassay; genomic DNA; mitochondrial DNA ID EPITHELIAL OVARIAN-CARCINOMA; PREFERENTIAL BINDING; CHEMOTHERAPY; PREGNANCY; ADDUCTS; SAMPLES; TISSUES; TUMORS; RATS AB A previous attempt to model transplacental cisplatin exposure and genotoxicity employed several pregnant Erythrocebus patas monkeys; most of the animals were exposed near the end of gestation and cisplatin-DNA adduct analyses included only genomic DNA. Here, both genomic and mitochondrial DNA adduct formation have been determined in fetuses from two pregnant monkeys exposed at the end of the second trimester of gestation, Multiple fetal tissues were obtained after doses of 0.315 mg cisplatin/kg body weight (5.3 mg/m(2) total) on days 101 and 106 of gestation, Cesarean sections were performed 24 h after exposure and 27 d after exposure, Cisplatin genomic (g)-DNA adducts were observed in fetal adrenal, brain, heart, kidney, liver, skin, spleen, and thymus, When placentas from the two animals were divided into four concentric regions at increasing distances from the umbilical cord, and g-DNA was assayed, cisplatin DNA adduct levels were similar in all four regions, Mitochondrial (mt)-DNA adducts were higher than g-DNA adducts in maternal liver and fetal liver, brain and kidney, suggesting that the mitochondria may constitute a particular target for cisplatin genotoxicity. The study demonstrates significant fetal genotoxicity in g-DNA and mt-DNA of patas monkeys exposed to cisplatin in utero, suggesting that similarly exposed human fetuses may also sustain drug-induced DNA damage. (C) 1997 Elsevier Science Inc. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,FCRDC,FREDERICK,MD 21701. BIOQUAL INC,ROCKVILLE,MD. NR 22 TC 11 Z9 11 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 1997 VL 11 IS 1 BP 95 EP 100 DI 10.1016/S0890-6238(96)00201-8 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA WK538 UT WOS:A1997WK53800011 PM 9138639 ER PT J AU Clegg, ED Cook, JC Chapin, RE Foster, PMD Foster, GP AF Clegg, ED Cook, JC Chapin, RE Foster, PMD Foster, GP TI Leydig cell hyperplasia and adenoma formation: Mechanisms and relevance to humans SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Leydig cell hyperplasia; adenoma formation; humans ID ANDROGEN RECEPTOR ANTAGONIST; HUMAN CHORIONIC-GONADOTROPIN; LUTEINIZING-HORMONE LEVELS; CHRONIC TOXICITY; 5-ALPHA-REDUCTASE INHIBITOR; INHALATION TOXICITY; OXOLINIC ACID; GERM-CELL; MALE-RAT; AMMONIUM PERFLUOROOCTANOATE AB Leydig cell adenomas are observed frequently in studies evaluating the chronic toxicity of chemical agents in laboratory animals, Doubts have been raised about the relevance of such responses for human risk assessment, but the question of relevance has not been evaluated and presented in a comprehensive manner by a broad group of experts, This article reports the consensus conclusions from a workshop on rodent Leydig cell adenomas and human relevance. Five aspects of Leydig cell biology and toxicology were discussed: 1) control of Leydig cell proliferation; 2) mechanisms of toxicant-induced Leydig cell hyperplasia and tumorigenesis; 3) pathology of Leydig cell adenomas; 4) epidemiology of Leydig cell adenomas; and 5) risk assessment for Leydig cell tumorigens. Important research needs also were identified, Uncertainty exists about the true incidence of Leydig cell adenomas in men, although apparent incidence is rare and restricted primarily to white males, Also, surveillance databases for specific therapeutic agents as well as nicotine and lactose that have induced Leydig cell hyperplasia or adenoma in test species have detected no increased incidence in humans, Because uncertainties exist about the true incidence in humans, induction of Leydig cell adenomas in test species may be of concern under some conditions, Occurrence of Leydig cell hyperplasia alone in test species after lifetime exposure to a chemical does not constitute a cause for concern in a risk assessment for carcinogenic potential, but early occurrence may indicate a need for additional testing, Occurrence of Leydig cell adenomas in test species is of potential concern as both a carcinogenic and reproductive effect if the mode of induction and potential exposures cannot be ruled out as relevant for humans, The workgroup focused on seven hormonal modes of induction of which two, GnRH agonism and dopamine agonism, were considered not relevant to humans, Androgen receptor antagonism, 5 alpha-reductase inhibition, testosterone biosynthesis inhibition, aromatase inhibition, and estrogen agonism were considered to he relevant or potentially relevant, but quantitative differences may exist across species, with rodents being more sensitive, A margin of exposure (MOE; the ratio of the lowest exposure associated with toxicity to the human exposure level) approach should be used for compounds causing Leydig cell adenoma by a hormonal mode that is relevant to humans. For agents that are positive for mutagenicity, the decision regarding a MOE or linear extrapolation approach should be made on a case-by-case basis, In the absence of information about mode of induction, it is necessary to utilize default assumptions, including linear behavior below the observable range, All of the evidence should be weighed in the decision-making process. (C) 1997 Elsevier Science Inc. C1 DUPONT CO INC,HASKELL LAB TOXICOL & IND MED,CENT RES & DEV,NEWARK,DE 19714. NIEHS,RES TRIANGLE PK,NC 27709. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. PROCTER & GAMBLE CO,CINCINNATI,OH. RP Clegg, ED (reprint author), US EPA,NATL CTR ENVIRONM ASSESSMENT,8623,401 M ST SW,WASHINGTON,DC 20460, USA. OI Chapin, Robert/0000-0002-5997-1261 NR 170 TC 85 Z9 87 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 1997 VL 11 IS 1 BP 107 EP 121 DI 10.1016/S0890-6238(96)00203-1 PG 15 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA WK538 UT WOS:A1997WK53800013 PM 9138629 ER PT S AU Henderson, DK AF Henderson, DK BE Henderson, DK Levy, SB TI Confronting antimicrobial resistance - Historical perspectives SO RESISTANT ORGANISMS: GLOBAL IMPACT ON CONTINUUM OF CARE SE ROYAL SOCIETY OF MEDICINE INTERNATIONAL CONGRESS AND SYMPOSIUM SERIES LA English DT Proceedings Paper CT Conference on Resistant Organisms - Global Impact on Continuum of Care CY SEP 27, 1996 CL ROYAL SOC MED, LONDON, ENGLAND SP 3M Hlth Care & Regent Med HO ROYAL SOC MED RP Henderson, DK (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BLDG 10,ROOM 2C144,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0142-2367 BN 1-85315-313-3 J9 ROY SOC MED INT CONG PY 1997 VL 220 BP 1 EP 6 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BJ07F UT WOS:A1997BJ07F00001 ER PT S AU Lee, L AF Lee, L BE Henderson, DK Levy, SB TI Institutional care: Taking concepts into practice SO RESISTANT ORGANISMS: GLOBAL IMPACT ON CONTINUUM OF CARE SE ROYAL SOCIETY OF MEDICINE INTERNATIONAL CONGRESS AND SYMPOSIUM SERIES LA English DT Proceedings Paper CT Conference on Resistant Organisms - Global Impact on Continuum of Care CY SEP 27, 1996 CL ROYAL SOC MED, LONDON, ENGLAND SP 3M Hlth Care & Regent Med HO ROYAL SOC MED RP Lee, L (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BLDG 10,ROOM 2C144,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0142-2367 BN 1-85315-313-3 J9 ROY SOC MED INT CONG PY 1997 VL 220 BP 35 EP 41 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BJ07F UT WOS:A1997BJ07F00005 ER PT S AU Henderson, DK AF Henderson, DK BE Henderson, DK Levy, SB TI Implications for surgical practice SO RESISTANT ORGANISMS: GLOBAL IMPACT ON CONTINUUM OF CARE SE ROYAL SOCIETY OF MEDICINE INTERNATIONAL CONGRESS AND SYMPOSIUM SERIES LA English DT Proceedings Paper CT Conference on Resistant Organisms - Global Impact on Continuum of Care CY SEP 27, 1996 CL ROYAL SOC MED, LONDON, ENGLAND SP 3M Hlth Care & Regent Med HO ROYAL SOC MED RP Henderson, DK (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BLDG 10,ROOM 2C144,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0142-2367 BN 1-85315-313-3 J9 ROY SOC MED INT CONG PY 1997 VL 220 BP 43 EP 50 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BJ07F UT WOS:A1997BJ07F00006 ER PT B AU Berson, A AF Berson, A BE Thompson, DO Chimenti, DE TI Imaging structure and function in medicine and biology SO REVIEW OF PROGRESS IN QUANTITATIVE NONDESTRUCTIVE EVALUATION, VOLS 16A AND 16B SE REVIEW OF PROGRESS IN QUANTITATIVE NONDESTRUCTIVE EVALUATION LA English DT Proceedings Paper CT 23rd Symposium on Quantitative Nondestructive Evaluation CY JUL 28-AUG 02, 1996 CL BRUNSWICK, ME SP Iowa State Univ, Ctr NDE, Amer Soc Nondestruct Testing, US DOE, Ames Lab, FAA, NIST, Natl Sci Fdn, Ind Univ Cooperat Res Ctr Program RP Berson, A (reprint author), NHLBI,NIH,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45597-8 J9 REV PROG Q PY 1997 VL 16 BP 1 EP 8 PN A&B PG 8 WC Materials Science, Characterization & Testing SC Materials Science GA BJ03K UT WOS:A1997BJ03K00001 ER PT J AU Lu, B Figurov, A AF Lu, B Figurov, A TI Role of neurotrophins in synapse development and plasticity SO REVIEWS IN THE NEUROSCIENCES LA English DT Article DE neurotrophins; NGF; BDNF; NT-3; NT-4/5; trk receptor tyrosine kinases; neuromuscular junction; hippocampus; cortex; synapse; synaptogenesis; transmitter release; plasticity ID NERVE GROWTH-FACTOR; LONG-TERM POTENTIATION; DEVELOPING NEUROMUSCULAR SYNAPSES; CULTURED HIPPOCAMPAL-NEURONS; MESSENGER-RNA EXPRESSION; POSTNATAL RAT-BRAIN; VISUAL-CORTEX; TRANSMITTER RELEASE; CORTICAL-NEURONS; LIMBIC SEIZURES AB Neurotrophic factors are traditionally viewed as secretory proteins that regulate long-term survival and differentiation of neurons. The role of neurotrophic factors in the structural integrity of the nervous system makes them attractive candidates as therapeutic agents for neurodegenerative diseases, However, the fact that expression of many neurotrophic factors in the central nervous system is rapidly enhanced by neuronal activity suggests a new role for these factors in activity-dependent processes, such as synaptic development and plasticity. A series of recent studies has provided strong evidence for this novel function of neurotrophic factors, The neurotrophin family of proteins has been shown to acutely potentiate synaptic transmission at the neuromuscular junction and in the brain, These factors are also involved in the maturation of the neuromuscular synapses and in the development of synapses in the visual system. Gene targeting and experiments demonstrate that neurotrophic factor (BDNF) plays an important role in long-term potentiation (LTP), a cellular model for learning and memory. These findings have brought together two hotly pursued areas of neuroscience, namely, the function of neurotrophic factors and the mechanisms for synaptic plasticity. Continuous studies in this new field will help understand how synapses develop and function in the brain, and may have significant implications in treating learning disorders in both children and adults. C1 NICHHD,DEV NEUROBIOL LAB,UNIT SYNAPSE DEV & PLAST,NIH,BETHESDA,MD 20892. RI Lu, Bai/A-4018-2012 NR 78 TC 178 Z9 182 U1 0 U2 5 PU FREUND PUBLISHING HOUSE PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON, ENGLAND W1R 5FA SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PD JAN-MAR PY 1997 VL 8 IS 1 BP 1 EP 12 PG 12 WC Neurosciences SC Neurosciences & Neurology GA WZ054 UT WOS:A1997WZ05400001 PM 9402641 ER PT J AU Shore, D Hsiao, JK AF Shore, D Hsiao, JK TI At issue: Medication-free intervals and schizophrenia research - Editors' introduction SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material RP Shore, D (reprint author), NIMH,DIV CLIN & TREATMENT RES,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1997 VL 23 IS 1 BP 1 EP 1 PG 1 WC Psychiatry SC Psychiatry GA WJ706 UT WOS:A1997WJ70600001 ER PT J AU Wyatt, RJ AF Wyatt, RJ TI Research in schizophrenia and the discontinuation of antipsychotic medications SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material ID MAINTENANCE NEUROLEPTIC THERAPY; FOLLOW-UP; EARLY INTERVENTION; NATURAL COURSE; WITHDRAWAL; PREDICTORS; PSYCHOSIS; EPISODES; DURATION; ILLNESS AB This article, and the accompanying one by Dr. Carpenter, discuss the benefits and risks associated with taking patients with schizophrenia off medications for research purposes. This article reviews the concept that at least some forms of schizophrenia are progressive, Evidence for this view is provided by studies examining the impact of early intervention with antipsychotic medications on the long-term morbidity of schizophrenia, as well as the few studies examining the long-term risks of discontinuing antipsychotic medications in patients with schizophrenia. While there is evidence that early intervention improves the long-term course of the illness, it is not known whether withdrawal of antipsychotic medications increases long-term morbidity, This is an area where further information is needed for clinical practice and research. RP Wyatt, RJ (reprint author), NIMH,NEUROPSYCHIAT RES HOSP,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING,JR AVE,WASHINGTON,DC 20032, USA. NR 45 TC 27 Z9 27 U1 0 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1997 VL 23 IS 1 BP 3 EP 9 PG 7 WC Psychiatry SC Psychiatry GA WJ706 UT WOS:A1997WJ70600002 PM 9050108 ER PT J AU Weinberger, DR AF Weinberger, DR TI On localizing schizophrenic neuropathology SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material ID POSITRON EMISSION TOMOGRAPHY; MEDIODORSAL THALAMIC NUCLEUS; ABNORMALITIES; DISTURBANCES; LOBE AB Many brain regions and circuits have been implicated in the neuropathology of schizophrenia. Drs. Bogerts and Jones have reviewed the evidence that links the disorder to temporal limbic structures and to frontal-thalamic circuits, respectively. Each article is an important update on what we know about the relevance of these brain regions to schizophrenia, In addition, each article, in summarizing the accumulation of relevant research data, is a testament to the likelihood that these structures play a role in the disease. In light of their compelling arguments, this commentary emphasizes incompleteness in the data and inconsistencies in published findings. The principal weaknesses of the temporal limbic findings are that most have been reported in chronically ill patients and that the only qualitative finding of cytoarchitectural disorganization has not been replicated convincingly, Problems of replication also compromise the interpretation of neuropathological findings in prefrontal cortex and thalamus, Despite the loose ends, I agree with the conclusions of Drs, Bogerts and Jones that brain circuits involving thalamus, prefrontal, and temporolimbic cortices are involved in the basic biology of schizophrenia. RP Weinberger, DR (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NIH,WASHINGTON,DC 20032, USA. NR 22 TC 27 Z9 27 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1997 VL 23 IS 3 BP 537 EP 540 PG 4 WC Psychiatry SC Psychiatry GA XR438 UT WOS:A1997XR43800022 PM 9327520 ER PT J AU Moldin, SO Gottesman, II AF Moldin, SO Gottesman, II TI At issue: Genes, experience, and chance in schizophrenia - Positioning for the 21st century SO SCHIZOPHRENIA BULLETIN LA English DT Article ID BANTU-SPEAKING FAMILIES; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; CHROMOSOME 6P; VULNERABILITY LOCUS; POTENTIAL LINKAGE; COMPLEX TRAITS; NO EVIDENCE; FOLLOW-UP; DISEASE AB Genetic factors make important contributions to the etiologies of schizophrenia. The mode of familial inheritance remains unknown, but it is highly likely that multiple genes and idiosyncratic environmental factors are involved. Rapidly evolving genetic technologies have been applied in the genetic analysis of schizophrenia, and several genomic regions have been posited as harboring susceptibility genes. Currently, the strongest evidence implicates chromosomes 6 and 8, but these linkages are not yet confirmed. In this article we discuss genetic risk factors, gene-environment interaction, the feasibility of genetic testing, psychiatric genetic counseling, and the dangers of genetic discrimination as they apply to schizophrenia. We also address and correct specific misconceptions about the genetics of schizophrenia held by many in the scientific community and in the media, and discuss a blueprint for future genetic research and informed dissemination of findings to the public and to lawmakers. C1 GEORGETOWN UNIV,MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20057. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. RP Moldin, SO (reprint author), NIMH,DIV BASIC & CLIN NEUROSCI RES,NIH,PARKLAWN BLDG,RM 10C-26,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. RI G, I/D-8042-2011 NR 89 TC 91 Z9 92 U1 3 U2 7 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1997 VL 23 IS 4 BP 547 EP 561 PG 15 WC Psychiatry SC Psychiatry GA YE793 UT WOS:A1997YE79300001 PM 9365994 ER PT J AU Egan, ME Apud, J Wyatt, RJ AF Egan, ME Apud, J Wyatt, RJ TI Treatment of tardive dyskinesia SO SCHIZOPHRENIA BULLETIN LA English DT Review ID LONG-TERM TREATMENT; VITAMIN-E TREATMENT; DOUBLE-BLIND; SCHIZOPHRENIC-PATIENTS; PARKINSONS-DISEASE; MOVEMENT-DISORDERS; FOLLOW-UP; RAT-BRAIN; NEUROLEPTIC WITHDRAWAL; RISK-FACTORS AB Although the new generation of atypical antipsychotic agents could some day eliminate concerns about tardive dyskinesia (TD), this disorder remains a significant clinical problem for both patients and physicians. Fortunately, many, if not most, cases of TD are mild. For patients with mild to moderate TD, therapeutic efforts are primarily directed at minimizing neuroleptic exposure or, when possible, changing to atypical agents. Most cases of TD do not seem to progress, suggesting that the risk of remaining on typical neuroleptics is probably small. Patients with moderate to severe forms of TD present greater challenges. These patients frequently require medication to suppress their dyskinesias. A variety of suppressive agents have been tried with limited success. No treatment strategy has emerged that is clearly superior or even successful in most patients. Increasing doses of typical neuroleptics may be useful for short-term suppression; however, the long-term efficacy and risk of this strategy have not been studied carefully. Data on atypical neuroleptics are scant. Clozapine's short-term suppressive effects seem, at best, weak, but patients may improve with long-term treatment. Medications with relatively few side effects that may have suppressive efficacy for some patients include calcium channel blockers, adrenergic antagonists, and vitamin E. Gamma-amino-butyric acid agonists agents and dopamine depleters are frequently useful, but have troubling side effects of their own. A variety of other medications have been employed, but are not well studied. For patients with tardive dystonia, anticholinergic agents or botulinum toxin has been particularly effective. Efforts to understand the neurobiology of TD may shed light on this persistent clinical conundrum. RP Egan, ME (reprint author), ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,NEUROPSYCHIAT BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. NR 255 TC 106 Z9 106 U1 3 U2 5 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1997 VL 23 IS 4 BP 583 EP 609 PG 27 WC Psychiatry SC Psychiatry GA YE793 UT WOS:A1997YE79300004 PM 9365997 ER PT J AU Hyde, TM Weinberger, DR AF Hyde, TM Weinberger, DR TI Seizures and schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article ID TEMPORAL-LOBE EPILEPSY; 1ST UNPROVOKED SEIZURE; POSITRON-EMISSION TOMOGRAPHY; INDUCED WATER-INTOXICATION; FOLLOW-UP; PSYCHIATRIC MANIFESTATIONS; ANTIEPILEPTIC DRUGS; PSYCHOTROPIC-DRUGS; INVITRO TECHNIQUE; RELATIVE RISK AB Patients with epilepsy develop psychosis or schizophrenia at a rate exceeding that expected if the two disorders were independent. Similarly, patients with schizophrenia are more prone to seizures than the general population, This excess vulnerability may be conferred by the neuropathological substrate of schizophrenia itself or by the secondary effects of the illness, including exposure to psychotropic medications that lower the seizure threshold. Neuropathological investigations into the anatomic substrate of seizures in patients with psychosis or schizophrenia are consistent with the notion that there are neurodevelopmental abnormalities involving the mesial temporal lobe, Finally, clinical recommendations for the evaluation and pharmacological management of patients with schizophrenia who have one or more seizures are described. RP Hyde, TM (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 87 TC 53 Z9 53 U1 1 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1997 VL 23 IS 4 BP 611 EP 622 PG 12 WC Psychiatry SC Psychiatry GA YE793 UT WOS:A1997YE79300005 PM 9365998 ER PT B AU Bulte, JWM Brooks, RA AF Bulte, JWM Brooks, RA BE Hafeli, U Schutt, W Teller, J Zborowski, M TI Magnetic nanoparticles as contrast agents for MR imaging - An overview SO SCIENTIFIC AND CLINICAL APPLICATIONS OF MAGNETIC CARRIERS LA English DT Proceedings Paper CT International Conference on Scientific and Clinical Applications of Magnetic Carriers CY SEP 05-07, 1996 CL ROSTOCK, GERMANY AB Following a brief introduction to the basic concepts of relaxation and contrast enhancement in magnetic resonance imaging (MRI), this chapter presents an overview of the use of magnetic nanoparticles as contrast agents for MRI. It covers the basic principles of preparation and characterization, including variable-field relaxometry. II is shown how a detailed understanding of T1 and T2 relaxation by magnetic nanoparticles may aid further magnetopharmaceutical development. While this overview is far from complete because of the rapid recent developments in the field, an attempt is made to give an overview of current applications and future directions of magnetic nanoparticles as MR contrast agent. RP Bulte, JWM (reprint author), NIH,LAB DIAGNOST RADIOL RES,10 CTR DR MSC 1074,BETHESDA,MD 20892, USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 0 TC 37 Z9 40 U1 0 U2 3 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45687-7 PY 1997 BP 527 EP 543 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BJ32T UT WOS:A1997BJ32T00040 ER PT J AU Herman, B Iversen, L AF Herman, B Iversen, L TI Strategies for treatment of opiate abuse SO SEMINARS IN NEUROSCIENCE LA English DT Editorial Material C1 NIDA, Rockville, MD USA. Univ Oxford, Oxford OX1 3QT, England. RP Herman, B (reprint author), NIDA, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-5765 J9 SEMIN NEUROSCI JI Semin. Neurosci. PY 1997 VL 9 IS 3-4 BP 69 EP 69 DI 10.1006/smns.1997.0107 PG 1 WC Neurosciences SC Neurosciences & Neurology GA YP155 UT WOS:000071248200001 ER PT J AU Ernst, M London, ED AF Ernst, M London, ED TI Brain imaging studies of drug abuse: Therapeutic implications SO SEMINARS IN NEUROSCIENCE LA English DT Article DE brain imaging; human studies; positron emission tomography; substance abuse; single photon emission computed tomography ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; PRECIPITATED MORPHINE-WITHDRAWAL; OPIATE RECEPTOR-BINDING; COCAINE POLYDRUG USERS; GLUCOSE-METABOLISM; BUPRENORPHINE; SENSITIZATION; INHIBITION; DEPENDENCE C1 NIDA, Brain Imaging Ctr, Baltimore, MD 21224 USA. RP Ernst, M (reprint author), NIDA, Brain Imaging Ctr, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 65 TC 6 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-5765 J9 SEMIN NEUROSCI JI Semin. Neurosci. PY 1997 VL 9 IS 3-4 BP 120 EP 130 DI 10.1006/smns.1997.0112 PG 11 WC Neurosciences SC Neurosciences & Neurology GA YP155 UT WOS:000071248200006 ER PT J AU Herman, BH O'Brien, CP AF Herman, BH O'Brien, CP TI Clinical medications development for opiate addiction: Focus on nonopioids and opioid antagonists for the amelioration of opiate withdrawal symptoms and relapse prevention SO SEMINARS IN NEUROSCIENCE LA English DT Review ID NMDA RECEPTOR ANTAGONISTS; CCK-B RECEPTOR; OXIDE SYNTHASE INHIBITORS; DOUBLE-BLIND; ALCOHOL DEPENDENCE; MORPHINE-TOLERANCE; HEROIN-ADDICTS; ENKEPHALINASE INHIBITOR; NARCOTIC-ANTAGONISTS; GENERALIZED ANXIETY C1 NIDA, Clin Trials Branch, Medicat Dev Div, NIH, Rockville, MD 20857 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Herman, BH (reprint author), NIDA, Clin Trials Branch, Medicat Dev Div, NIH, 5600 Fishers Lane,Rm 11A55, Rockville, MD 20857 USA. NR 125 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-5765 J9 SEMIN NEUROSCI JI Semin. Neurosci. PY 1997 VL 9 IS 3-4 BP 158 EP 172 DI 10.1006/smns.1997.0115 PG 15 WC Neurosciences SC Neurosciences & Neurology GA YP155 UT WOS:000071248200009 ER PT J AU Cote, LR Azar, ST AF Cote, LR Azar, ST TI Child age, parent and child gender, and domain differences in parents' attributions and responses to children's outcomes SO SEX ROLES LA English DT Article; Proceedings Paper CT Annual Meeting of the Eastern-Psychological-Association CY APR 14-17, 1994 CL PROVIDENCE, RI SP E Psychol Assoc ID SOCIALIZATION; MOTHERS; PERCEPTIONS; ACHIEVEMENT; COMPETENCE; BEHAVIOR AB The influence of children's age, and parents' and children's gender on parents' attributions and emotional and behavioral responses to their children's successful and unsuccessful social and academic outcomes, was investigated. Seventy-six dual-parent families (mothers and fathers) of fifth (n = 28), eighth (n = 23), and eleventh grade (n = 25) children participated The results of this study suggest that from fifth grade on, at least, the ways parents explain the causes of and respond to their children's social behavior and academic outcomes involves a complex interaction of children's age, children's gender parents' gender, domain, and outcome. Results are discussed in terms of children's socialization. C1 CLARK UNIV,WORCESTER,MA 01610. RP Cote, LR (reprint author), NICHHD,CHILD & FAMILY RES LAB,BLDG 31,ROOM B2B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 15 Z9 15 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0360-0025 J9 SEX ROLES JI Sex Roles PD JAN PY 1997 VL 36 IS 1-2 BP 23 EP 50 DI 10.1007/BF02766237 PG 28 WC Psychology, Developmental; Psychology, Social; Women's Studies SC Psychology; Women's Studies GA WR788 UT WOS:A1997WR78800002 ER PT J AU Crowell, DH Brooks, LJ Colton, T Corwin, MJ Hoppenbrouwers, TT Hunt, CE Kapuniai, LE Lister, G Neuman, MR Peucker, M Ward, SLD WeeseMayer, DE Willinger, M Baird, M Hufford, D Keens, TG Martin, RJ Ramanathan, R Schafer, SC Silvestri, JM Tinsley, L AF Crowell, DH Brooks, LJ Colton, T Corwin, MJ Hoppenbrouwers, TT Hunt, CE Kapuniai, LE Lister, G Neuman, MR Peucker, M Ward, SLD WeeseMayer, DE Willinger, M Baird, M Hufford, D Keens, TG Martin, RJ Ramanathan, R Schafer, SC Silvestri, JM Tinsley, L TI Infant polysomnography: Reliability SO SLEEP LA English DT Article DE polysomnography; infant; reliability; scoring; SIDS ID PRETERM INFANTS; SLEEP; TERM; AGES AB Infant polysomnography (IPSG) is an increasingly important procedure for studying infants with sleep and breathing disorders. Since analyses of these IPSG data are subjective, an equally important issue is the reliability or strength of agreement among scorers (especially among experienced clinicians) of sleep parameters (SP) and sleep states (SS). One basic issue of this problem was examined by proposing and testing the hypothesis that infant SP and SS ratings can be reliably scored at substantial levels of agreement, that is, kappa (kappa) greater than or equal to 0.61. In light of the importance of IPSG reliability in the collaborative home infant monitoring evaluation (CHIME) study, a reliability training and evaluation process was developed and implemented. The bases for training on SP and SS scoring were CHIME criteria that were modifications and supplements to Anders, Emde, and Parmelee (10). The kappa statistic was adopted as the method for evaluating reliability between and among scorers. Scorers were three experienced investigators and four trainees. Inter- and intrarater reliabilities for SP codes and SSs were calculated for 408 randomly selected 30-second epochs of nocturnal IPSG recorded at five CHIME clinical sites from healthy full term (n = 5), preterm (n = 4), apnea of infancy (n = 2), and siblings of the sudden infant death syndrome (SIDS) (n = 4) enrolled subjects. Infant PSG data set 1 was scored by both experienced investigators and trained scorers and was used to asses initial inter-rater reliability. Infant PSG data set 2 was scored twice by the trained scorers and was used to reassess inter-rater reliability and to assess intrarater reliability. The kappa s for SS ranged from 0.45 to 0.58 for data set 1 and represented a moderate level of agreement. Therefore, rater disagreements were reviewed, and the scoring criteria were modified to clarify ambiguities. The kappa s and confidence intervals (CIs) computed for data set 2 yielded substantial inter-rater and intrarater agreements for the four trained scorers; for SS, the kappa = 0.68 and for SP the kappa s ranged from 0.62 to 0.76. Acceptance of the hypothesis supports the conclusion that the IPSG is a reliable source of clinical and research data when supported by significant kappa s and CIs. Reliability can be maximized with strictly detailed scoring guidelines and training. C1 RAINBOW BABIES & CHILDRENS HOSP,CLEVELAND,OH 44106. BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA. BOSTON UNIV,MED CTR,BOSTON,MA. LAC & USC MED CTR,WOMENS & CHILDRENS HOSP,LOS ANGELES,CA. MED COLL OHIO,TOLEDO,OH 43699. YALE UNIV,NEW HAVEN,CT 06520. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH CHILDRENS HOSP,CHICAGO,IL 60612. NICHD,CRMC,PREGNANCY & PERINATOL BRANCH,NIH,BETHESDA,MD 20892. TOLEDO HOSP,TOLEDO,OH. RP Crowell, DH (reprint author), UNIV HAWAII,KAPIOLANI MED CTR,1319 PUNAHOU ST,HONOLULU,HI 96826, USA. FU NICHD NIH HHS [2 U10 HD28971, HD29067, HD29071] NR 11 TC 38 Z9 39 U1 0 U2 1 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PY 1997 VL 20 IS 7 BP 553 EP 560 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XY817 UT WOS:A1997XY81700007 PM 9322271 ER PT J AU Quan, SF Howard, BV Iber, C Kiley, JP Nieto, FJ O'Connor, GT Rapoport, DM Redline, S Robbins, J Samet, JM Wahl, PW AF Quan, SF Howard, BV Iber, C Kiley, JP Nieto, FJ O'Connor, GT Rapoport, DM Redline, S Robbins, J Samet, JM Wahl, PW TI The sleep heart health study: Design, rationale, and methods SO SLEEP LA English DT Article DE sleep apnea; cardiovascular disease; epidemiology; risk factors ID AMBULATORY BLOOD-PRESSURE; APNEA; PREVALENCE; POPULATION; EXPERIENCE; MORTALITY; DISEASES AB The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke. C1 Univ Arizona, Coll Med, Resp Sci Ctr, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Dept Med, Tucson, AZ 85724 USA. Medlant Res Inst, Washington, DC USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NYU, Dept Med, New York, NY 10016 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Univ Calif Davis, Dept Med, Davis, CA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Quan, SF (reprint author), Univ Arizona, Coll Med, Resp Sci Ctr, 1501 N Campbell, Tucson, AZ 85724 USA. OI O'Connor, George/0000-0002-6476-3926 FU NHLBI NIH HHS [U01 HL053938, U01HL53938, U01HL53940, U01HL53941] NR 30 TC 342 Z9 349 U1 2 U2 8 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 USA SN 0161-8105 J9 SLEEP JI Sleep PY 1997 VL 20 IS 12 BP 1077 EP 1085 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YW402 UT WOS:000071931700002 PM 9493915 ER PT J AU Vissing, YM Diament, J AF Vissing, YM Diament, J TI Housing distress among high school students SO SOCIAL WORK LA English DT Article DE adolescents; homelessness; housing distress; school; youths ID HOMELESS AB The word ''homelessness'' is not a useful term to explain housing problems experienced by high school-aged youths. The term ''housing distress'' is preferable because it includes both teenagers who are homeless and those who are at risk of homelessness. Many teenagers feel that they have no place where they belong and seek alternative living arrangements for a variety of reasons. Housing distress is a problem for schools because students have difficulties achieving academic success when they have no consistent, safe place to live. To understand how much or how little housing distress is experienced by high school-aged youths, 3,676 high school-aged teenagers weve surveyed in nine communities along the seacoast of New Hampshire and southwestern Maine. Between 5 percent and 10 percent of the teenagers surveyed reported that they had been homeless sometime during the past year. Up to 20 percent of the high school students lived in arrangements that could be considered to be distressing and to put them at risk of becoming homeless. C1 SALEM STATE COLL,DURHAM,NH 03824. RP Vissing, YM (reprint author), NIMH,POB 547,DURHAM,NH 03824, USA. NR 39 TC 2 Z9 2 U1 0 U2 0 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 SN 0037-8046 J9 SOC WORK JI Soc. Work PD JAN PY 1997 VL 42 IS 1 BP 31 EP 41 PG 11 WC Social Work SC Social Work GA WC785 UT WOS:A1997WC78500005 PM 9009887 ER PT B AU Nussenblatt, R Gery, I Shiloach, J Ramaley, N Weiner, H Perry, C Caspi, R Ferris, F Foster, S Whitcup, S AF Nussenblatt, R Gery, I Shiloach, J Ramaley, N Weiner, H Perry, C Caspi, R Ferris, F Foster, S Whitcup, S BE Suveges, I Follmann, P TI The use of the oral administration of retinal antigens in the treatment of uveitis SO SOE '97 - XI CONGRESS OF THE EUROPEAN SOCIETY OF OPHTHALMOLOGY, VOLS 1 AND 2 LA English DT Proceedings Paper CT XI Congress of the European-Society-of-Ophthalmology (SOE 97) CY JUN 01-05, 1997 CL BUDAPEST, HUNGARY SP European Soc Ophthalmol AB The effect of the oral administration of retinal antigens to induce immunologic tolerance in patients with intermediate and posterior uveitis was evaluated. Patients received either Retinal S-antigen alone (n=10), Retinal S-antigen and a retinal mixture (n=10), retinal mixture alone (n=10), or placebo (n=15), given orally t.i.w. for eight weeks, then once a week for one year, and then monthly. An attempt was made to taper patients completely off their standard immunosuppressive therapy over an eight week period. Time to development of uveitis was not different between groups, but for the ability to totally discontinue immunosuppressive agents, there was a strong trend favoring the group receiving the purified S-antigen alone (p=0.08), white women in the S-antigen group fared even better when compared to the placebo group (p=0.01). No toxic effects attributable to any treatment were observed. RP Nussenblatt, R (reprint author), NEI,IMMUNOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY BN 88-323-0601-8 PY 1997 BP 669 EP 672 PG 4 WC Ophthalmology SC Ophthalmology GA BJ48B UT WOS:A1997BJ48B00122 ER PT B AU Chourpa, I Riou, JF Pommier, Y Manfait, M AF Chourpa, I Riou, JF Pommier, Y Manfait, M BE Carmona, P Navarro, R Hernanz, A TI SERS and fluorescence study of the molecular interactions of camptothecins with DNA and DNA topoisomerase I and in their ternary cleavable complexes. SO SPECTROSCOPY OF BIOLOGICAL MOLECULES: MODERN TRENDS LA English DT Proceedings Paper CT 1997 European Conference on Spectroscopy of Biological Molecules (ECSBM) CY 1997 CL MADRID, SPAIN SP Univ Nacl Educ Distancia, Consejo Super Invest Cient, Spanish Minist Educ, Complutense Univ Madrid, Univ S Pable CEU, Reg Community Madrid, Embassy France, Spain, British Council, Deutsch Forsch Gemeinsch, Caja Ahorros Madrid C1 UFR Pharm, Lab Spect Biomol, IFR 53, F-51096 Reims, France. Rhone Poulenc Rorer, F-94403 Vitry Sur Seine, France. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Chourpa, I (reprint author), UFR Pharm, Lab Spect Biomol, IFR 53, 51 Rue Cognacq Jay, F-51096 Reims, France. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4685-8 PY 1997 BP 361 EP 362 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Biophysics; Chemistry; Spectroscopy GA BK55N UT WOS:000072556800160 ER PT S AU Ludlow, CL Siren, K Zikria, M AF Ludlow, CL Siren, K Zikria, M BE Hulstijn, W Peters, HFM vanLieshout, PHH TI Speech production learning in adults with chronic developmental stuttering SO SPEECH PRODUCTION: MOTOR CONTROL, BRAIN RESEARCH AND FLUENCY DISORDERS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 3rd International Conference on Speech Motor Production and Fluency Disorders CY JUN 05-08, 1996 CL NIJMEGEN, NETHERLANDS SP Univ Hosp Nijmegen, Inst Otorhinolaryngol, Dept Voice & Speech Pathol, Nijmegen Inst Cognit & Informat, Univ Nijmegen, Interfac Res Unit Language & Speech, Univ Hosp Nijmegen, Inst Med Psychol, Univ Congress Off AB Speech learning for novel pseudowords was compared in adults who stutter and control subjects. Subjects performed 11 test recall trials which were interspersed with modeling practice trials for two novel pseudowords associated with meaningless idiographs. The number of phonemes correctly achieved on each of the 11 test trials were scored by the same listener. The adults who stuttered were impaired in their rate of learning as well as the overall accuracy of their word productions. The results suggest that the speech production learning is less efficient in those affected by chronic stuttering and may contribute to their less efficient and unstable speech production capabilities throughout adult life. C1 NIDCD, NIH, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NIDCD, NIH, 10 Ctr Dr MSC 1416,Room 5D38, Bethesda, MD 20892 USA. NR 0 TC 14 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82460-X J9 INT CONGR SER PY 1997 VL 1146 BP 221 EP 230 PG 10 WC Behavioral Sciences; Neurosciences; Psychology SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA BK04T UT WOS:000070984300019 ER PT S AU Braun, AR Varga, M Stager, S Schulz, G Selbie, S Maisog, JM Carson, RE Ludlow, CL AF Braun, AR Varga, M Stager, S Schulz, G Selbie, S Maisog, JM Carson, RE Ludlow, CL BE Hulstijn, W Peters, HFM vanLieshout, PHH TI A typical lateralization of hemispheric activity in developmental stuttering: An (H2O)-O-15 positron emission tomography study. SO SPEECH PRODUCTION: MOTOR CONTROL, BRAIN RESEARCH AND FLUENCY DISORDERS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 3rd International Conference on Speech Motor Production and Fluency Disorders CY JUN 05-08, 1996 CL NIJMEGEN, NETHERLANDS SP Univ Hosp Nijmegen, Inst Otorhinolaryngol, Dept Voice & Speech Pathol, Nijmegen Inst Cognit & Informat, Univ Nijmegen, Interfac Res Unit Language & Speech, Univ Hosp Nijmegen, Inst Med Psychol, Univ Congress Off AB Cerebral blood flow was measured with (H2O)-O-15 and positron emission tomography (PET) in order to assess dynamic brain function in adults who had stuttered since childhood. PET scans were performed during oral motor control tasks and speech tasks designed to evoke stuttering. Speech samples were acquired simultaneously and quantitatively compared with the PET images. Stuttering subjects differed markedly in the formulation and expression of language, failing to demonstrate left hemispheric lateralization typically observed in controls; instead, regional responses were either absent, bilateral, or lateralized to the right hemisphere. Covariance analyses indicated that activation of left hemispheric regions may be related to the production of stuttered speech, while activation of right hemispheric regions may represent compensatory processes associated with the production of fluent speech. C1 NIDCD, NIH, Bethesda, MD 20892 USA. RP Braun, AR (reprint author), NIDCD, NIH, 10 Ctr Dr MSC 1416,Room 5D38, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82460-X J9 INT CONGR SER PY 1997 VL 1146 BP 279 EP 292 PG 14 WC Behavioral Sciences; Neurosciences; Psychology SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA BK04T UT WOS:000070984300023 ER PT S AU Stager, S Calis, K Grothe, D Bloch, M Turcasso, N Ludlow, C Braun, A AF Stager, S Calis, K Grothe, D Bloch, M Turcasso, N Ludlow, C Braun, A BE Hulstijn, W Peters, HFM vanLieshout, PHH TI A double-blind trial of pimozide and paroxetine for stuttering SO SPEECH PRODUCTION: MOTOR CONTROL, BRAIN RESEARCH AND FLUENCY DISORDERS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 3rd International Conference on Speech Motor Production and Fluency Disorders CY JUN 05-08, 1996 CL NIJMEGEN, NETHERLANDS SP Univ Hosp Nijmegen, Inst Otorhinolaryngol, Dept Voice & Speech Pathol, Nijmegen Inst Cognit & Informat, Univ Nijmegen, Interfac Res Unit Language & Speech, Univ Hosp Nijmegen, Inst Med Psychol, Univ Congress Off AB A randomized double-blind, placebo-controlled crossover study was designed to examine the effects on fluency of a highly selective dopamine antagonist, pimozide, and a highly selective serotonin reuptake inhibitor, paroxetine, in adult persons who stutter. Eleven persons who stutter enrolled in this study but only a total of 6 individuals completed the pimozide phase, 6 the placebo phase, and 5 the paroxetine phase. This paper examined the following treatment outcome measures; self-perceptions of changes in fluency and factors to which they attributed these changes; comparison of self-ratings of fluency with objective measures of fluency; self-perceptions about changes in symptom severity, consistency of fluency, and measures of speech anxiety such as confidence in speaking, anxiety levels and satisfaction with speech; and reports from others noting fluency change. On pimozide, a positive clinical response was found for 4/6 individuals, and a negative clinical response for the other 2 individuals. Trends for significant differences between placebo and pimozide phases were found for percent of symptoms reported changed (p=0.03), percent of days where fluency change was attributed to medication (p=0.03); consistency of fluency (p=0.04); confidence in speaking (p=0.07), satisfaction with speech (p=0.08), anxiety while speaking (p=0.09) and level of fluency (p=0.1). Individuals randomized to the pimozide phase might have been more likely to report a change in fluency attributable to medication because they reported experiencing more side effects on pimozide than on paroxetine or placebo. No significant clinical response was found for paroxetine using any outcome measure, and significant side effects were experienced by 2 individuals while withdrawing from this medication. C1 NIDCD, NIH, Bethesda, MD 20892 USA. RP Stager, S (reprint author), NIDCD, NIH, 10 Ctr Dr,MSC 1416,Room 5D38, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82460-X J9 INT CONGR SER PY 1997 VL 1146 BP 371 EP 378 PG 8 WC Behavioral Sciences; Neurosciences; Psychology SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA BK04T UT WOS:000070984300031 ER PT J AU Farci, P Bukh, J Purcell, RH AF Farci, P Bukh, J Purcell, RH TI The quasispecies of hepatitis C virus and the host immune response SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review ID NON-B-HEPATITIS; ENVELOPE GLYCOPROTEIN GP70; POLYMERASE CHAIN-REACTION; MAJOR GENETIC GROUPS; 5' NONCODING REGION; NON-A; HYPERVARIABLE REGION; LIVER-DISEASE; SEQUENCE VARIATION; LONG-TERM C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,NIH,BETHESDA,MD 20892. RP Farci, P (reprint author), UNIV CAGLIARI,IST MED INTERNA,VIA SAN GIORGIO 12,I-09124 CAGLIARI,ITALY. NR 146 TC 53 Z9 56 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1997 VL 19 IS 1 BP 5 EP 26 DI 10.1007/BF00945022 PG 22 WC Immunology; Pathology SC Immunology; Pathology GA XL682 UT WOS:A1997XL68200002 PM 9266628 ER PT J AU Pantaleo, G Fauci, AS AF Pantaleo, G Fauci, AS TI Introduction: Recent advances in the pathogenesis of human immunodeficiency virus infection SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Editorial Material C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. RP Pantaleo, G (reprint author), CHU VAUDOIS,DIV INFECT DIS,DEPT MED,LAB AIDS IMMUNOPATHOGENESIS,CH-1011 LAUSANNE,SWITZERLAND. RI Pantaleo, Giuseppe/K-6163-2016 NR 0 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1997 VL 18 IS 3 BP 253 EP 256 DI 10.1007/BF00813496 PG 4 WC Immunology; Pathology SC Immunology; Pathology GA WN668 UT WOS:A1997WN66800001 PM 9089947 ER PT J AU Pantaleo, G Graziosi, C Fauci, AS AF Pantaleo, G Graziosi, C Fauci, AS TI Virologic and immunologic events in primary HIV infection SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FOLLICULAR DENDRITIC CELLS; LYMPHOID ORGANS; GENETIC-VARIATION; TYPE-1 INFECTION; IMMUNE-RESPONSE; AIDS; VIREMIA; PATHOGENESIS; PROGRESSION C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. RP Pantaleo, G (reprint author), CHU VAUDOIS,DIV INFECT DIS,DEPT INTERNAL MED,LAB AIDS IMMUNOPATHOGENESIS,CH-1011 LAUSANNE,SWITZERLAND. RI Pantaleo, Giuseppe/K-6163-2016 NR 47 TC 22 Z9 22 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1997 VL 18 IS 3 BP 257 EP 266 DI 10.1007/BF00813497 PG 10 WC Immunology; Pathology SC Immunology; Pathology GA WN668 UT WOS:A1997WN66800002 PM 9089948 ER PT J AU Cohen, OJ Pantaleo, G Lam, GK Fauci, AS AF Cohen, OJ Pantaleo, G Lam, GK Fauci, AS TI Studies on lymphoid tissue from HIV-infected individuals: Implications for the design of therapeutic strategies SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FOLLICULAR DENDRITIC CELLS; PLACEBO-CONTROLLED TRIAL; TYPE-1 INFECTION; CUBIC MILLIMETER; T-LYMPHOCYTES; NITRIC-OXIDE; LYMPHADENOPATHY SYNDROME; DOUBLE-BLIND; ZIDOVUDINE AB Lymphoid tissue is a major reservoir of human immunodeficiency virus (HIV) infection in vivo. In addition, the lymphoid microenvironment provides a replicative advantage to the virus in that it provides a milieu of activated target cells that allows for efficient virus spread. The process of mobilization and activation of immune competent cells directed against the virus paradoxically contributes to the propagation of virus replication. Disruption of the lymphoid microenvironment during the progression of HIV disease is a poorly understood process, which may be of considerable importance pathogenically. Studies of lymph node biopsy samples taken 8 weeks apart from individuals who did not undergo any change in their therapeutic regimen (i.e., patients who either remained untreated or remained on their ongoing nucleoside analogue reverse transcriptase inhibitor monotherapy regimen) revealed little change in histopathology or viral load over the 8-week period. These results with successive lymph node biopsy samples taken from different sites indicate that an isolated lymph node biopsy accurately reflects the pathologic process associated with HIV infection and that this process diffusely involves the lymphoid system. Treatment with reverse transcriptase inhibitor monotherapy of patients in relatively early stage HIV disease had no detectable impact on the viral load in lymphoid tissue, suggesting the need to investigate more potent antiretroviral regimens during this stage of disease. Among patients with moderately advanced HIV disease, switching to combination therapy from a monotherapy regimen resulted in decreased viral replication in lymph nodes; this effect was associated with decreases in plasma viremia. Despite the fact that measures of viral replication decreased significantly, the net frequency of HIV-infected cells in peripheral blood and lymph nodes remained unchanged. Potent antiretroviral drug combinations may be capable of profound and long-term downregulation of plasma viremia. It will be essential to monitor the status of viral trapping, viral burden, and viral replication within lymphoid tissue during treatment with such drugs to determine accurately their true potential for impact on these key features of HIV pathogenesis. RP Cohen, OJ (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,10 CTR DR MSC 1876,BLDG 10,ROOM 11B13,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 67 TC 31 Z9 31 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1997 VL 18 IS 3 BP 305 EP 322 DI 10.1007/BF00813500 PG 18 WC Immunology; Pathology SC Immunology; Pathology GA WN668 UT WOS:A1997WN66800005 PM 9089951 ER PT J AU Strober, W Kelsall, BL AF Strober, W Kelsall, BL TI Untitled - Introduction SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Editorial Material RP Strober, W (reprint author), NIAID,MUCOSAL IMMUN SECT,CLIN INVEST LAB,NIH,BLDG 10,ROOM 11N 238,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1997 VL 18 IS 4 BP 407 EP 408 DI 10.1007/BF00824049 PG 2 WC Immunology; Pathology SC Immunology; Pathology GA WW201 UT WOS:A1997WW20100001 ER PT J AU Kelsall, BL Strober, W AF Kelsall, BL Strober, W TI Dendritic cells of the gastrointestinal tract SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID LANGERHANS CELLS; PEYERS-PATCHES; EPITHELIAL-CELLS; SMALL-INTESTINE; MONOCLONAL-ANTIBODY; LYMPHOID-CELLS; LAMINA PROPRIA; MOUSE SPLEEN; T-CELLS; ANTIGEN RP Kelsall, BL (reprint author), NIAID, MUCOSAL IMMUN SECT,CLIN INVEST LAB,NIH,BLDG 10, ROOM 11N238, 9000 ROCKVILLE PIKE, BETHESDA, MD 20814 USA. NR 56 TC 22 Z9 22 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1997 VL 18 IS 4 BP 409 EP 420 DI 10.1007/BF00824050 PG 12 WC Immunology; Pathology SC Immunology; Pathology GA WW201 UT WOS:A1997WW20100002 PM 9144862 ER PT J AU Orlic, D Girard, LJ Anderson, SM Do, BKQ Seidel, NE Jordan, CT Bodine, DM AF Orlic, D Girard, LJ Anderson, SM Do, BKQ Seidel, NE Jordan, CT Bodine, DM TI Transduction efficiency of cell lines and hematopoietic stem cells correlates with retrovirus receptor mRNA levels SO STEM CELLS LA English DT Article; Proceedings Paper CT Symposium on Hematopoietic Stem Cells CY 1996 CL HOHENZOLLERN CASTLE, MOUNT ZOLLERN, GERMANY SP AMGEN HO HOHENZOLLERN CASTLE DE retrovirus; gene transfer; stem cells; bone marrow; cytokines; receptors ID APE LEUKEMIA-VIRUS; MESSENGER-RNA; C-KIT; GENE; PURIFICATION; MOUSE AB The low transduction efficiency of hematopoietic stem cells (HSC) using amphotropic retroviruses continues to plague gene therapy protocols. This low transduction efficiency may be related to a low level of amphotropic retrovirus binding to target cell receptors. We have assayed murine and human cell lines as well as primary bone marrow HSC populations for mRNA encoding retrovirus receptors. Total cellular RNA was amplified by reverse transcriptase-polymerase chain reaction and the level of ecotropic and amphotropic receptor mRNA was compared to the level of beta 2-microglobulin mRNA in the same cell populations. Cell lines that are easily transduced by ecotropic and amphotropic retroviruses have high levels of receptor mRNA. In studies using murine HSC-enriched populations obtained from bone marrow, we observed a high correlation between transduction efficiency and the level of ecotropic and amphotropic receptor mRNA. We predict from these findings that purification of monkey and human HSC populations with high levels of amphotropic receptor mRNA will enable us to obtain improved efficiency of gene transfer. C1 SOMATIX THERAPY CORP, ALAMEDA, CA USA. NATL HUMAN GENOME RES INST, LAB GENE TRANSFER, NIH, BETHESDA, MD USA. NR 12 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 23 EP 28 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100008 PM 9368321 ER PT J AU Spangrude, GJ Orlic, D Griffin, JD Moore, MAS AF Spangrude, GJ Orlic, D Griffin, JD Moore, MAS TI Transduction efficiency of cell lines and hematopoietic stem cells correlates with retrovirus receptor mRNA levels - Discussion SO STEM CELLS LA English DT Editorial Material C1 NIH, LAB GENE TRANSFER, NCHGR, BETHESDA, MD 20892 USA. DANA FARBER CANC INST, DIV HEMATOL MALIGNANCIES, BOSTON, MA 02115 USA. SLOAN KETTERING INST CANC RES, NEW YORK, NY 10021 USA. RP UNIV UTAH, SALT LAKE CITY, UT 84132 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 28 EP 29 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100009 ER PT J AU Muszynski, KW Ruscetti, FW Gooya, JM Linnekin, DM Keller, JR AF Muszynski, KW Ruscetti, FW Gooya, JM Linnekin, DM Keller, JR TI Raf-1 protein is required for growth factor-induced proliferation of primitive hematopoietic progenitors stimulated with synergistic combinations of cytokines SO STEM CELLS LA English DT Article DE Raf-1; synergy; hematopoiesis; stem cells ID STEM-CELL FACTOR; BONE-MARROW; FACTOR-I; ACTIVATION; KINASE; PHOSPHORYLATION; DIFFERENTIATION; LINE; INTERLEUKIN-3 AB Raf-l is a serine/threonine kinase that has been identified as a component of growth factor-activated signal transduction pathways, and is required for growth factor-induced proliferation of leukemic cell lines and colony formation of hematopoietic progenitors stimulated,vith single colony-stimulating factors, which promote the growth of committed hematopoietic progenitor cells, However, it is known that the most primitive progenitors in the bone marrow require stimulation with multiple cytokines to promote cell growth, We have determined that c-raf antisense oligonucleotides inhibit the growth of murine lineage-negative progenitors stimulated with two-, three- and four-factor combinations of growth factors, including GM-CSF + interleukin (IL)-1, IL-3 + steel factor (SLF), IL-3 + IL-11 + SLF and IL-3 + IL-II + SLF + G-CSF, In addition, c-raf antisense oligonucleotides inhibit the synergistic response of the MO7e human progenitor cell line induced to proliferate with IL-3 + SLF (99%) or GM-CSF + SLF (99%), In contrast, c-paf antisense oligonucleotides only partially inhibited day 14 colony formation of CD34(+) human progenitors stimulated with IL-3 + SLF (50%) or GM-CSF + SLF (55%) but completely inhibited day 7 colony formation, However, pulsing CD34(+) cells with additional oligonucleotides on day 7 of the colony assay further inhibited day 14 colony formation (70%-80%), Furthermore, a comparison of the effect of c-raf antisense oligonucleotides on the synergistic response of normal human fetal liver cells in [H-3]thymidine incorporation assays and colony assays showed strong inhibition in short-term proliferation assays and partial inhibition in 14-day colony assays, Taken together, these results demonstrate that partial inhibition of colony formation of primitive human progenitors stimulated with multiple growth factors is a result of the length (14 days) of the human colony assay and does not represent a differential requirement of primitive progenitors for Raf-l, Thus Raf-l is required for the proliferation and differentiation of primitive hematopoietic progenitor cells stimulated with synergistic combinations of cytokines. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-56000] NR 36 TC 7 Z9 7 U1 0 U2 1 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 IS 1 BP 63 EP 72 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA WE088 UT WOS:A1997WE08800009 PM 9007224 ER PT J AU Sharkis Zanjani Dunbar Quesenberry TorokStorb AF Sharkis Zanjani Dunbar Quesenberry TorokStorb TI Transplantation of hematopoietic stem cells in utero - Discussion SO STEM CELLS LA English DT Editorial Material C1 VET ADM MED CTR, RENO, NV 89520 USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. NHLBI, HEMATOL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV MASSACHUSETTS, MED CTR, CTR CANC, WORCESTER, MA 01605 USA. RP JOHNS HOPKINS UNIV, CTR ONCOL, ROOM 2-127, 600 N WOLFE ST, BALTIMORE, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 93 EP 93 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100023 ER PT J AU Licht, T Herrmann, F Gottesman, MM Pastan, I AF Licht, T Herrmann, F Gottesman, MM Pastan, I TI In vivo drug-selectable genes: A new concept in gene therapy SO STEM CELLS LA English DT Review DE chemotherapy; hematopoietic stem cells; multidrug resistance; myelosuppression; P-glycoprotein; dihydrofolate reductase; transgenic animals; retroviral vectors ID MULTIDRUG-RESISTANCE GENE; HEMATOPOIETIC STEM-CELLS; DIHYDROFOLATE-REDUCTASE GENE; GLUTATHIONE-S-TRANSFERASE; BONE-MARROW CELLS; ADENOSINE-DEAMINASE GENE; ACUTE MYELOID-LEUKEMIA; LONG-TERM PROTECTION; HUMAN MDR1 GENE; TRANSGENIC MICE AB Chemoresistance genes, initially considered to be a major impediment to the successful treatment of cancer, may become useful tools for gene therapy of cancer and of genetically determined disorders, Various target cells are rendered resistant to anticancer drugs by transfer of chemoresistance genes encoding P-glycoprotein, the multidrug resistance-associated protein-transporter, dihydrofolate reductase, glutathione-S-transferase, O-6-alkylguanine DNA alkyltransferase, or aldehyde reductase. These genes can be used for selection in vivo because of the pharmacology and pharmacokinetics of their substrates, In contrast, several other selectable marker genes conferring resistance to substrates Like neomycin or hygromycin can only be utilized in tissue culture. Possible applications for chemoresistance genes include protection of bone marrow and other organs from adverse effects caused by the toxicity of chemotherapy. Strategies have also been developed to introduce and overexpress nonselectable genes in target cells by cotransduction with chemoresistance genes, Thereby expression of both transgenes can be increased following selection with drugs, Moreover, treatment with chemotherapeutic agents should restore transgene expression when or if expression levels decrease after several weeks or months, This approach may improve the efficacy of somatic gene therapy of hematopoietic disorders which is hampered by low or unstable gene expression in progenitor cells, In this article we review preclinical studies in tissue culture and animal models, and ongoing clinical trials on transfer of chemoresistance genes to hematopoietic precursor cells of cancer patients. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,NIH,BETHESDA,MD. UNIV ULM,DEPT INTERNAL MED 3,D-7900 ULM,GERMANY. NR 85 TC 32 Z9 32 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 IS 2 BP 104 EP 111 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA WQ814 UT WOS:A1997WQ81400003 PM 9090786 ER PT J AU Dunbar, CE Tisdale, J Yu, JM Soma, T Zujewski, J Bodine, D Sellers, S Cowan, K Donahue, R Emmons, R AF Dunbar, CE Tisdale, J Yu, JM Soma, T Zujewski, J Bodine, D Sellers, S Cowan, K Donahue, R Emmons, R TI Transduction of hematopoietic stem cells in humans and in nonhuman primates SO STEM CELLS LA English DT Article; Proceedings Paper CT Symposium on Hematopoietic Stem Cells CY 1996 CL HOHENZOLLERN CASTLE, MOUNT ZOLLERN, GERMANY SP AMGEN HO HOHENZOLLERN CASTLE DE hematopoiesis; retrovirus; gene therapy; gene transfer; stem cell; transforming grow factor-beta; stem cell factor; autologous transplantation ID COLONY-STIMULATING FACTOR; CULTURE-INITIATING CELLS; BONE-MARROW; PERIPHERAL-BLOOD; PROGENITOR CELLS; EX-VIVO; EXPANSION; GENE; ENGRAFTMENT; INFUSION AB Primitive hematopoietic progenitor and stem cells have been pursued as highly desirable targets for genetic therapy, Retroviral vectors have been used for the majority of preclinical and clinical studies directed at these cells; however, both preclinical and early clinical studies indicate that the gene transfer efficiency of the current generation of vectors using known transduction conditions into primate and human repopulating stem cells is too low to be of clinical utility in most situations. In this presentation I will summarize the status of our completed and ongoing clinical genetic marking trials, and describe our efforts in the laboratory and use of primate transplantation models to improve on these results. RP NHLBI, HEMATOL BRANCH,HEMATOPOIESIS SECT,NCHGR,NIH, BLDG 10,ROOM 7C103, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 15 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 135 EP 139 PG 5 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100032 PM 9368333 ER PT J AU Spangrude Dunbar Hoffman Moore AF Spangrude Dunbar Hoffman Moore TI Transduction of hematopoietic stem cells in humans and in nonhuman primates - Discussion SO STEM CELLS LA English DT Editorial Material C1 NHLBI, HEMATOL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV ILLINOIS, COLL MED, HEMATOL ONCOL SECT, CHICAGO, IL 60607 USA. SLOAN KETTERING INST CANC RES, NEW YORK, NY 10021 USA. RP UNIV UTAH, SALT LAKE CITY, UT 84132 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 139 EP 140 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100033 ER PT J AU Zanjani Kolb Dunbar Rammensee TorokStorb AF Zanjani Kolb Dunbar Rammensee TorokStorb TI Hematopoietic transplantation: State of the art - Discussion SO STEM CELLS LA English DT Editorial Material C1 UNIV MUNICH, KLINIKUM GROSSHADERN, MED KLIN 3, D-81377 MUNICH, GERMANY. NHLBI, HEMATOL BRANCH, NIH, BETHESDA, MD 20892 USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. RP VET ADM MED CTR, 1000 LOCUST ST, RENO, NV 89520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 158 EP 158 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100036 ER PT J AU Hoffman Brugger Dunbar AF Hoffman Brugger Dunbar TI Purging of peripheral blood progenitor cell autografts and treatment of minimal residual disease - Discussion SO STEM CELLS LA English DT Editorial Material C1 UNIV TUBINGEN, D-72076 TUBINGEN, GERMANY. NHLBI, HEMATOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP UNIV ILLINOIS, COLL MED,HEMATOL ONCOL SECT,ROOM 3150, MOL BIOL RES BLDG, 900 S ASHLAND AVE, CHICAGO, IL 60607 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 165 EP 165 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100038 ER PT J AU Barrett, AJ AF Barrett, AJ TI Mechanisms of the graft-versus-leukemia reaction SO STEM CELLS LA English DT Review DE graft-versus-leukemia; graft-versus-host disease; bone marrow transplantation; leukemia; immunogenicity; T cells ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; CYTOTOXIC LYMPHOCYTES-T; TUMOR NECROSIS FACTOR; HOST DISEASE; CELL CLONES; HEMATOLOGIC RELAPSE; SCID MICE AB It is now clear that the graft-versus-leukemia (GVL) effect which accompanies allogeneic bone marrow transplantation for hematological malignancies is a powerful therapeutic weapon which, if harnessed, could improve our ability to treat refractory malignant disorders. Advances in the understanding of the alloimmune response now provide a clearer picture of the mechanisms involved in the GVL reaction: the CD4(+) T cell plays a central role in the orchestration of leukemia cell killing. The immunogenicity of the leukemia is also a major factor determining the effectiveness of the GVL response. The characterization of antigens restricted to leukemia and hematopoietic tissues should make it eventually possible to produce specific and powerful antileukemic alloresponses in donor lymphocytes by adoptive immunotherapy or by vaccines. RP Barrett, AJ (reprint author), NHLBI,BMT UNIT,HEMATOL BRANCH,NIH,BLDG 10,ROOM 7C 103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 106 TC 67 Z9 71 U1 0 U2 2 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 IS 4 BP 248 EP 258 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA XM463 UT WOS:A1997XM46300001 PM 9253108 ER PT J AU Sharkis, SJ Moore, MAS Lansdorp, PM Eaves, C TorokStorb, B Broxmeyer, HE Adamson, JW Spangrude, GJ Griffin, JD Papayannopoulou, T Ogawa, M Orlic, D Kanz, L AF Sharkis, SJ Moore, MAS Lansdorp, PM Eaves, C TorokStorb, B Broxmeyer, HE Adamson, JW Spangrude, GJ Griffin, JD Papayannopoulou, T Ogawa, M Orlic, D Kanz, L TI Stem cell proliferation: Ex vivo and in vivo observations - Discussion SO STEM CELLS LA English DT Editorial Material C1 SLOAN KETTERING INST CANC RES, NEW YORK, NY 10021 USA. TERRY FOX LAB, VANCOUVER, BC V5Z 1L3, CANADA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. INDIANA UNIV, SCH MED, WALTHER ONCOL CTR, DEPT IMMUNOL & MICROBIOL, INDIANAPOLIS, IN 46202 USA. NEW YORK BLOOD CTR, NEW YORK, NY 10021 USA. UNIV UTAH, SALT LAKE CITY, UT USA. DANA FARBER CANC INST, DIV HEMATOL MALIGNANCIES, BOSTON, MA 02115 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. VET ADM MED CTR, CHARLESTON, SC 29401 USA. NIH, NCHGR, LAB GENE TRANSFER, BETHESDA, MD 20892 USA. UNIV TUBINGEN, DEPT HEMATOL, D-72076 TUBINGEN, GERMANY. RP JOHNS HOPKINS UNIV, CTR ONCOL, 600 N WOLFE ST, BALTIMORE, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 248 EP 251 PG 4 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100057 ER PT J AU Nienhuis, A Moore, MAS Dick, JE Stamatoyannopoulos, G Lemischka, IR TorokStorb, B Spangrude, GJ Papayannopoulou, T Flugel, RM Orlic, D Broxmeyer, HE Quesenberry, PJ Sharkis, SJ Lansdorp, PM AF Nienhuis, A Moore, MAS Dick, JE Stamatoyannopoulos, G Lemischka, IR TorokStorb, B Spangrude, GJ Papayannopoulou, T Flugel, RM Orlic, D Broxmeyer, HE Quesenberry, PJ Sharkis, SJ Lansdorp, PM TI What are the current limitations for HSC transduction? How can we overcome them? Discussion SO STEM CELLS LA English DT Editorial Material C1 SLOAN KETTERING INST CANC RES, NEW YORK, NY 10021 USA. UNIV TORONTO, HOSP SICK CHILDREN, RES INST, DEPT GENET, TORONTO, ON M5G 1X8, CANADA. UNIV WASHINGTON, DIV MED GENET, SEATTLE, WA 98195 USA. PRINCETON UNIV, DEPT MOL BIOL, PRINCETON, NJ 08544 USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. UNIV UTAH, SALT LAKE CITY, UT 84132 USA. DFKZ, INF 242, FORSCH SCHEWERPUNKT ANGEW TUMORVIROL, ABT RETROVIRALE GENEXPRESSION, D-69009 HEIDELBERG, GERMANY. NIH, NCHGR, LAB GENE TRANSFER, BETHESDA, MD 20892 USA. INDIANA UNIV, SCH MED, WALTHER ONCOL CTR, DEPT IMMUNOL & MICROBIOL, INDIANAPOLIS, IN 46202 USA. UNIV MASSACHUSETTS, MED CTR, CTR CANC, WORCESTER, MA 01605 USA. TERRY FOX LAB, VANCOUVER, BC V5Z 1L3, CANADA. JOHNS HOPKINS UNIV, CTR ONCOL, BALTIMORE, MD 21287 USA. RP ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, DIV EXPT HEMATOL, 332 N LAUDERDALE ST, MEMPHIS, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 255 EP 263 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100058 PM 9368349 ER PT J AU Orlic, D Sharkis, SJ AF Orlic, D Sharkis, SJ TI The elusive stem cell: How close are we? SO STEM CELLS LA English DT Editorial Material C1 JOHNS HOPKINS UNIV, CTR ONCOL, BALTIMORE, MD 21287 USA. RP NIH, LAB GENE TRANSFER,NCHGR,BLDG 49,ROOM 3A14, 49 CONVENT DR, MSC 4442, BETHESDA, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 1997 VL 15 SU 2 BP 283 EP 284 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA YF081 UT WOS:A1997YF08100061 ER PT J AU Dufau, ML Miyagawa, Y Takada, S Khanum, A Miyagawa, H Buczko, E AF Dufau, ML Miyagawa, Y Takada, S Khanum, A Miyagawa, H Buczko, E TI Regulation of androgen synthesis: The late steroidogenic pathway SO STEROIDS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Molecular Steroidogenesis CY JUN 08-11, 1996 CL OFFICE CONTINUING MED EDUC, SAN FRANCISCO, CA SP UCSF Dept Pediat HO OFFICE CONTINUING MED EDUC DE 17 beta-HSD; P450 17 alpha-hydroxylase; CYP17; P450c17; testosterone ID SITE-DIRECTED MUTAGENESIS; 17-ALPHA-HYDROXYLASE/17,20 LYASE; TRANSCRIPTIONAL REGULATION; CYTOCHROME P-45017-ALPHA; RAT P45017-ALPHA; ACTIVE-SITE; GENE; CYP17; EXPRESSION; SEQUENCE AB Studies of the regulation of androgen synthesis in steroidogenic cells have focused on both transcriptional and post-translational regulation of the proteins that catalyze these reactions: the P450c17 that catalyzed the production of DHEA or androstenedione in consecutive hydroxylase and lyase activities, and the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) that catalyzes the conversion of androstenedione to testosterone. Our studies of the regulation of the CYP17 lyase activity at the molecular level have utilized species-and tissue-specific differences to identify target regulatory sequences. Adenovirus infection of rat CYP17 promoter/luciferase reporter gene constructs in primary cultures of rat adrenal and rat Leydig cells revealed a rat-specific domain between-1 and -108bp that cause inhibition of both basal and cAMP-induced CYP17 transcription in the adrenal, but not the Leydig cell. In contrast, similar promoter constructs from other species exhibited substantial cAMP-induced transcriptional activity in the rat adrenal. Mutagenesis of the conserved region of the rat and human proteins reveals significant differences in the amino acid domains required for hydroxylase and lyase activities within and between the two species, consistent with their differential regulation of lyase activity. The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) reaction requires a viable glucose transporter system for optimal activity, and a high-energy phosphate was discovered to be the requisite product of glucose metabolism in 17 beta-HSD activation. These studies have provided insight into potential mechanisms of control of androgen synthesis in the late steroidogenic pathway, at the transcriptional and post-translational levels. (C) 1997 by Elsevier Science Inc. RP Dufau, ML (reprint author), NICHHD,NIH,ENDOCRINOL & REPROD RES BRANCH,SECT MOL ENDOCRINOL,BETHESDA,MD 20892, USA. NR 23 TC 12 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0039-128X J9 STEROIDS JI Steroids PD JAN PY 1997 VL 62 IS 1 BP 128 EP 132 DI 10.1016/S0039-128X(96)00171-7 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA WF577 UT WOS:A1997WF57700021 PM 9029727 ER PT B AU Long, LR Ostchega, Y Goh, GH Thoma, GR AF Long, LR Ostchega, Y Goh, GH Thoma, GR BE Sethi, IK Jain, RC TI Distributed data collection for a database of radiological image interpretations SO STORAGE AND RETRIEVAL FOR IMAGE AND VIDEO DATABASES V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Storage and Retrieval for Image and Video Databases V CY FEB 13-14, 1997 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, Soc Photo Opt Instrumentat Engineers DE radiographs; digital xray; client/server; National Library of Medicine; DBMS; Internet DBMS AB The National Library of Medicine, in collaboration with the National Center for Health Statistics and the National Institute for Arthritis and Musculoskeletal and Skin Diseases, has built a system for collecting radiological interpretations for a large set of x-ray images acquired as part of the data gathered in the second National Health and Nutrition Examination Survey. This system is capable of delivering across the Internet 5- and 10-megabyte x-ray images to Sun workstations equipped with X Window based 2048x2560 image displays, for the purpose of having these images interpreted for the degree of presence of particular osteoarthritic conditions in the cervical and lumbar spines. The collected interpretations can then be stored in a database at the National Library of Medicine, under control of the Illustra DBMS. This system is a client/server database application which integrates (1) distributed server processing of client requests, (2) a customized image transmission method for faster Internet data delivery, (3) distributed client workstations with high resolution displays, image processing functions and an on-line digital atlas, and (4) relational database management of the collected data. RP Long, LR (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2433-1 J9 P SOC PHOTO-OPT INS PY 1997 VL 3022 BP 228 EP 237 DI 10.1117/12.263412 PG 2 WC Computer Science, Information Systems; Computer Science, Software Engineering; Optics SC Computer Science; Optics GA BH07C UT WOS:A1997BH07C00021 ER PT S AU Long, LR Pillemer, SR Lawrence, RC Goh, GH Neve, L Thoma, GR AF Long, LR Pillemer, SR Lawrence, RC Goh, GH Neve, L Thoma, GR BE Sethi, IK Jain, RC TI WebMIRS: Web-based Medical Information Retrieval System SO STORAGE AND RETRIEVAL FOR IMAGE AND VIDEO DATABASES VI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Storage and Retrieval for Image and Video Databases VI Conference CY JAN 28-30, 1998 CL SAN JOSE, CA SP Soc Photo Opt Instrumentat Engineers, Soc Imaging Sci & Technol DE World Wide Web; biomedical; informatics; Internet; database; spine; digital image; morphometry; x-ray image; image query by content; NHANES; NLM AB At the Lister Hill National Center for Biomedical Communications, a research and development division of the National Library of Medicine (NLM), we are developing a prototype multimedia database system to provide World Wide Web access to biomedical databases. WebMIRS (Web-based Medical Information Retrieval System) will allow access to databases containing text and images and will allow database query by standard SQL, by image content, or by a combination of the two. The system is being developed in the form of Java applets, which will communicate with the Informix DBMS on an NLM Sun workstation running the Solaris operating system. The system architecture will allow access from any hardware platform, which supports a Java-enabled Web browser, such as Netscape or Internet Explorer. Initial databases will include data from two national health surveys conducted by the National Center for Health Statistics (NCHS), and will include x-ray images from those surveys. In addition to describing in-house research in database access systems, this paper describes ongoing work toward querying by image content. Image content search capability will include capability to search for x-ray images similar to an input image with respect to vertebral morphometry used to characterize features such as fractures and disc space narrowing. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Long, LR (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-2752-7 J9 P SOC PHOTO-OPT INS PY 1997 VL 3312 BP 392 EP 403 DI 10.1117/12.298448 PG 12 WC Computer Science, Information Systems; Engineering, Electrical & Electronic; Optics SC Computer Science; Engineering; Optics GA BK26B UT WOS:000071633300035 ER PT S AU Garvey, MA Swedo, SE AF Garvey, MA Swedo, SE BE Horaud, T Bouvet, A Leclercq, R deMontclos, H Sicard, M TI Sydenham's chorea - Clinical and therapeutic update SO STREPTOCOCCI AND THE HOST SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT XIII Lancefield International Symposium on Streptococci and Streptococcal Diseases CY SEP 16-20, 1996 CL INST PASTEUR, PARIS, FRANCE SP Inst Pasteur, Abbott Labs, Assoc Enseignement Odontol & Stomatol, bioMerieux, Bristol Meyers Squibb Co, CNRS, Federat European Microbiol Soc, Fdn Marcel Merieux, GenProbe, Grp Danone, Inst Sci Roussel, Int Lancefield Soc, Int Sci Fdn, Pasteur Merieux MSD, Pharmacia & Upjohn, Rhone Poulenc Rorer, Rhone Poulene Rorer, Ctr Rech Vitry Alfortville, France, Rhone Poulenc Rorer Bellon, France, Rhone Poulenc Rorer Specia, France, Sanofi Diagnost Pasteur, France, SmithKline Beecham Labs Pharm, France, Wyeth Ayerst, Lederle Int, US, Yamanouchi Pharm, Japan HO INST PASTEUR ID SYMPTOMS RP Garvey, MA (reprint author), NIMH, CHILD PSYCHIAT BRANCH, BEHAV PEDIAT SECT, NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 17 TC 28 Z9 28 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45603-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 418 BP 115 EP 120 PG 6 WC Infectious Diseases; Medicine, Research & Experimental; Microbiology SC Infectious Diseases; Research & Experimental Medicine; Microbiology GA BJ94C UT WOS:A1997BJ94C00028 PM 9331612 ER PT S AU Andersen, RN Lunsford, RD Kolenbrander, PE AF Andersen, RN Lunsford, RD Kolenbrander, PE BE Horaud, T Bouvet, A Leclercq, R deMontclos, H Sicard, M TI Determination of the transcript size and start site of the putative sca operon of Streptococcus gordonii ATCC 51656 (formerly strain PK488) SO STREPTOCOCCI AND THE HOST SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT XIII Lancefield International Symposium on Streptococci and Streptococcal Diseases CY SEP 16-20, 1996 CL INST PASTEUR, PARIS, FRANCE SP Inst Pasteur, Abbott Labs, Assoc Enseignement Odontol & Stomatol, bioMerieux, Bristol Meyers Squibb Co, CNRS, Federat European Microbiol Soc, Fdn Marcel Merieux, GenProbe, Grp Danone, Inst Sci Roussel, Int Lancefield Soc, Int Sci Fdn, Pasteur Merieux MSD, Pharmacia & Upjohn, Rhone Poulenc Rorer, Rhone Poulene Rorer, Ctr Rech Vitry Alfortville, France, Rhone Poulenc Rorer Bellon, France, Rhone Poulenc Rorer Specia, France, Sanofi Diagnost Pasteur, France, SmithKline Beecham Labs Pharm, France, Wyeth Ayerst, Lederle Int, US, Yamanouchi Pharm, Japan HO INST PASTEUR ID ACTINOMYCES-NAESLUNDII PK606; NUCLEOTIDE-SEQUENCE; ORAL STREPTOCOCCI; COAGGREGATION; CLONING; ADHESIN; GENE RP Andersen, RN (reprint author), NIDR, NIH, BLDG 30, ROOM 310, 30 CONVENT DR MSC 4350, BETHESDA, MD 20892 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45603-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 418 BP 657 EP 660 PG 4 WC Infectious Diseases; Medicine, Research & Experimental; Microbiology SC Infectious Diseases; Research & Experimental Medicine; Microbiology GA BJ94C UT WOS:A1997BJ94C00153 PM 9331737 ER PT S AU Whittaker, CJ Kolenbrander, PE AF Whittaker, CJ Kolenbrander, PE BE Horaud, T Bouvet, A Leclercq, R deMontclos, H Sicard, M TI Identification and further characterization of a locus coding for a hypothetical 33.6-kDa protein involved in intrageneric coaggregation of oral streptococci SO STREPTOCOCCI AND THE HOST SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT XIII Lancefield International Symposium on Streptococci and Streptococcal Diseases CY SEP 16-20, 1996 CL INST PASTEUR, PARIS, FRANCE SP Inst Pasteur, Abbott Labs, Assoc Enseignement Odontol & Stomatol, bioMerieux, Bristol Meyers Squibb Co, CNRS, Federat European Microbiol Soc, Fdn Marcel Merieux, GenProbe, Grp Danone, Inst Sci Roussel, Int Lancefield Soc, Int Sci Fdn, Pasteur Merieux MSD, Pharmacia & Upjohn, Rhone Poulenc Rorer, Rhone Poulene Rorer, Ctr Rech Vitry Alfortville, France, Rhone Poulenc Rorer Bellon, France, Rhone Poulenc Rorer Specia, France, Sanofi Diagnost Pasteur, France, SmithKline Beecham Labs Pharm, France, Wyeth Ayerst, Lederle Int, US, Yamanouchi Pharm, Japan HO INST PASTEUR ID CHALLIS RP Whittaker, CJ (reprint author), NIDR, NIH, BLDG 30, ROOM 312, 30 CONVENT DR MSC 4350, BETHESDA, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45603-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 418 BP 695 EP 698 PG 4 WC Infectious Diseases; Medicine, Research & Experimental; Microbiology SC Infectious Diseases; Research & Experimental Medicine; Microbiology GA BJ94C UT WOS:A1997BJ94C00162 PM 9331746 ER PT S AU Mittleman, BB AF Mittleman, BB BE Horaud, T Bouvet, A Leclercq, R deMontclos, H Sicard, M TI Cytokine networks in Sydenham's chorea and pandas SO STREPTOCOCCI AND THE HOST SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT XIII Lancefield International Symposium on Streptococci and Streptococcal Diseases CY SEP 16-20, 1996 CL INST PASTEUR, PARIS, FRANCE SP Inst Pasteur, Abbott Labs, Assoc Enseignement Odontol & Stomatol, bioMerieux, Bristol Meyers Squibb Co, CNRS, Federat European Microbiol Soc, Fdn Marcel Merieux, GenProbe, Grp Danone, Inst Sci Roussel, Int Lancefield Soc, Int Sci Fdn, Pasteur Merieux MSD, Pharmacia & Upjohn, Rhone Poulenc Rorer, Rhone Poulene Rorer, Ctr Rech Vitry Alfortville, France, Rhone Poulenc Rorer Bellon, France, Rhone Poulenc Rorer Specia, France, Sanofi Diagnost Pasteur, France, SmithKline Beecham Labs Pharm, France, Wyeth Ayerst, Lederle Int, US, Yamanouchi Pharm, Japan HO INST PASTEUR ID DYSFUNCTION; CELLS RP Mittleman, BB (reprint author), NIMH, CHILD PSYCHIAT BRANCH, BEHAV PEDIAT SECT, BLDG 10, ROOM 4N312, BETHESDA, MD 20892 USA. NR 11 TC 10 Z9 10 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45603-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 418 BP 933 EP 935 PG 3 WC Infectious Diseases; Medicine, Research & Experimental; Microbiology SC Infectious Diseases; Research & Experimental Medicine; Microbiology GA BJ94C UT WOS:A1997BJ94C00219 PM 9331803 ER PT J AU Becker, KJ McCarron, RM Hallenbeck, JM AF Becker, KJ McCarron, RM Hallenbeck, JM TI Oral tolerance to myelin basic protein decreases stroke size SO STROKE LA English DT Meeting Abstract C1 NIH,STROKE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1997 VL 28 IS 1 BP 72 EP 72 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA WB814 UT WOS:A1997WB81400123 ER PT J AU Bhardwaj, A Kirsch, JR Koehler, RC London, ED Traystman, RJ AF Bhardwaj, A Kirsch, JR Koehler, RC London, ED Traystman, RJ TI The sigma ligand (+)-pentazocine attenuates N-methyl-D-aspartate enhanced striatal nitric oxide production in vivo SO STROKE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIDA,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1997 VL 28 IS 1 BP 125 EP 125 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA WB814 UT WOS:A1997WB81400176 ER PT J AU Yasuma, Y McCarron, RM Strasser, A Spatz, M AF Yasuma, Y McCarron, RM Strasser, A Spatz, M TI The role of ET receptors in postischemic cerebral hypoperfusion SO STROKE LA English DT Meeting Abstract C1 NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1997 VL 28 IS 1 BP 135 EP 135 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA WB814 UT WOS:A1997WB81400186 ER PT J AU Leshner, AI AF Leshner, AI TI Comments on ''Perspective on the integration of substance user needs assessment and treatment planning,'' by William E. Ford SO SUBSTANCE USE & MISUSE LA English DT Editorial Material ID SERVICES; ABUSE RP Leshner, AI (reprint author), NATL INST DRUG ABUSE,5600 FISHERS LANE,ROOM 10-05,ROCKVILLE,MD 20857, USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1997 VL 32 IS 3 BP 351 EP 357 DI 10.3109/10826089709055855 PG 7 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA WK835 UT WOS:A1997WK83500008 ER PT J AU Gordis, E AF Gordis, E TI Comments on ''Perspective on the integration of substance user needs assessment and treatment planning,'' by William E. Ford SO SUBSTANCE USE & MISUSE LA English DT Editorial Material RP Gordis, E (reprint author), NIAAA,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1997 VL 32 IS 3 BP 359 EP 360 DI 10.3109/10826089709055856 PG 2 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA WK835 UT WOS:A1997WK83500009 ER PT J AU Leshner, AI AF Leshner, AI TI Understanding and preventing drug abuse SO SUBSTANCE USE & MISUSE LA English DT Editorial Material DE drug use; policy; etiology; prevention; treatment; psychopathology; behavior problems AB The National Institute on Drug Abuse (NIDA) is the lead Federal agency responsible for monitoring the nature and extent of drug abuse in the United States. NIDA engages in research on the etiology of drug use and supports state-of-the-art research to develop prevention and treatment methods. NIDA's etiology research has played a crucial role not only in helping to understand the origins and development of substance abuse, psychopathologies, and other mental health and behavioral problems, but also has contributed significantly to effective prevention and treatment. RP Leshner, AI (reprint author), NIDA,5600 FISHERS LANE,PARKLAWN BLDG,ROOM 10-05,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 1997 VL 32 IS 12-13 BP 1619 EP 1624 DI 10.3109/10826089709035554 PG 6 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA YF362 UT WOS:A1997YF36200001 ER PT J AU Liu, QY Vautrin, J Schaffner, AE Ma, W Barker, JL AF Liu, QY Vautrin, J Schaffner, AE Ma, W Barker, JL TI GABA induces GABAergic MSCs in cultured embryonic rat thalamic neurons SO SYNAPSE LA English DT Article DE GABA(A) receptors; thalamus; neurotransmission; neuronal development; synapse ID CA3 HIPPOCAMPAL-NEURONS; EARLY POSTNATAL LIFE; DORSAL HORN NEURONS; SPINAL-CORD; EXCITATORY TRANSMITTER; GRANULE CELLS; VISUAL-CORTEX; CURRENTS; GLYCINE; DEPOLARIZATION AB Application of 0.1-10 mu M GABA in the vicinity of cultured embryonic rat thalamic neurons recorded with patch pipettes in the presence of 2 mu M TTX induced or increased the frequency of miniature synaptic currents (MSCs) that reversed polarity at the Cl- equilibrium potential. These MSCs were blocked by the GABA(A) receptor antagonist bicuculline and exhibited exponential decay kinetics that closely paralleled those estimated from fluctuation analysis of Cl- channels activated pharmacologically by applying 1-10 mu M GABA to the same cells. We conclude that the MSCs are mediated by GABA. Application of the GABA(A) receptor agonist muscimol activated Cl- current but failed to induce GABAergic MSCs while submicromolar concentrations of GABA evoked GABAergic MSCs but did not activate Cl- channels. The GABA(B) receptor agonist (-)baclofen did not mimic GABA in inducing MSCs. Induction of GABAergic MSCs by GABA required extracellular Ca2+. Verapamil and Co2+, which block voltage-dependent calcium channels, completely blocked GABA-induced MSCs independent of their effects on the direct activation of a Cl- current response. The results indicate that GABA can trigger GABAergic Cl--dependent MSCs in a Ca-o(2+)-dependent manner. The mechanism may involve a novel receptor and/or signal transduction pathway. (C) 1997 Wiley-Liss, Inc.* RP Liu, QY (reprint author), NINCDS,NEUROPHYSIOL LAB,NIH,BLDG 36,RM 2C02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 5 Z9 5 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD JAN PY 1997 VL 25 IS 1 BP 15 EP 23 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VZ866 UT WOS:A1997VZ86600002 PM 8987143 ER PT B AU Chertova, E Kane, BP Coren, LV Johnson, DG Sowder, RC Nower, P CasasFinet, JR Arthur, LO Henderson, LE AF Chertova, E Kane, BP Coren, LV Johnson, DG Sowder, RC Nower, P CasasFinet, JR Arthur, LO Henderson, LE BE Marshak, DR TI Reaction of HIV-1 NC p7 zinc fingers with electrophilic reagents SO TECHNIQUES IN PROTEIN CHEMISTRY VIII SE TECHNIQUES IN PROTEIN CHEMISTRY (ACADEMIC PRESS INC) LA English DT Proceedings Paper CT 10th Symposium of the Protein-Society CY AUG 03-07, 1996 CL SAN JOSE, CA SP Protein Soc, Aviv Instruments Inc, Beckman Instruments Inc, BioMolecular Technol Inc, BIOSYM Molec Simulat, Bristol Myers Squibb, Finnigan MAT, Fisons Instruments, Hewlett Packard Co, IntelliGenetics Inc, JASCO Inc, Kirin Brewery Co Ltd, Michrom BioResources Inc, Molec Simulat Inc, Perkin Elmer Corp, Appl Biosyst Div, PerSept Biosyst Inc, Pharm Biotech Inc, Rainin Instrument Co Inc, Schering Plough Res Inst, Shimadzu Sci Instruments Inc, Supelco Inc, VYDAC, Waters Corp, Wyatt Technol Corp, ZymoGenetics RP Chertova, E (reprint author), NCI,SAIC,FCRDC,FREDERICK,MD 21702, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 BN 0-12-473557-6 J9 TECH PROT CHEM PY 1997 VL 8 BP 231 EP 244 DI 10.1016/S1080-8914(97)80025-7 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BJ32Y UT WOS:A1997BJ32Y00022 ER PT B AU Alexandratos, J Bujacz, G Jaskolski, M Wlodawer, A Merkel, G Katz, RA Skalka, AM AF Alexandratos, J Bujacz, G Jaskolski, M Wlodawer, A Merkel, G Katz, RA Skalka, AM BE Marshak, DR TI Crystal structure of avian sarcoma virus integrase with bound essential cations SO TECHNIQUES IN PROTEIN CHEMISTRY VIII SE TECHNIQUES IN PROTEIN CHEMISTRY (ACADEMIC PRESS INC) LA English DT Proceedings Paper CT 10th Symposium of the Protein-Society CY AUG 03-07, 1996 CL SAN JOSE, CA SP Protein Soc, Aviv Instruments Inc, Beckman Instruments Inc, BioMolecular Technol Inc, BIOSYM Molec Simulat, Bristol Myers Squibb, Finnigan MAT, Fisons Instruments, Hewlett Packard Co, IntelliGenetics Inc, JASCO Inc, Kirin Brewery Co Ltd, Michrom BioResources Inc, Molec Simulat Inc, Perkin Elmer Corp, Appl Biosyst Div, PerSept Biosyst Inc, Pharm Biotech Inc, Rainin Instrument Co Inc, Schering Plough Res Inst, Shimadzu Sci Instruments Inc, Supelco Inc, VYDAC, Waters Corp, Wyatt Technol Corp, ZymoGenetics RP Alexandratos, J (reprint author), NCI,MACROMOL STRUCT LAB,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 BN 0-12-473557-6 J9 TECH PROT CHEM PY 1997 VL 8 BP 417 EP 425 DI 10.1016/S1080-8914(97)80042-7 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BJ32Y UT WOS:A1997BJ32Y00039 ER PT B AU SchalkHihi, C Lubkowski, J Zdanov, A Wlodawer, A Gustchina, A Laco, GS Elder, JH AF SchalkHihi, C Lubkowski, J Zdanov, A Wlodawer, A Gustchina, A Laco, GS Elder, JH BE Marshak, DR TI Structure of the D30N active site mutant of FIV proteinase complexed with a statine-based inhibitor SO TECHNIQUES IN PROTEIN CHEMISTRY VIII SE TECHNIQUES IN PROTEIN CHEMISTRY (ACADEMIC PRESS INC) LA English DT Proceedings Paper CT 10th Symposium of the Protein-Society CY AUG 03-07, 1996 CL SAN JOSE, CA SP Protein Soc, Aviv Instruments Inc, Beckman Instruments Inc, BioMolecular Technol Inc, BIOSYM Molec Simulat, Bristol Myers Squibb, Finnigan MAT, Fisons Instruments, Hewlett Packard Co, IntelliGenetics Inc, JASCO Inc, Kirin Brewery Co Ltd, Michrom BioResources Inc, Molec Simulat Inc, Perkin Elmer Corp, Appl Biosyst Div, PerSept Biosyst Inc, Pharm Biotech Inc, Rainin Instrument Co Inc, Schering Plough Res Inst, Shimadzu Sci Instruments Inc, Supelco Inc, VYDAC, Waters Corp, Wyatt Technol Corp, ZymoGenetics RP SchalkHihi, C (reprint author), NCI,MACROMOL STRUCT LAB,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 BN 0-12-473557-6 J9 TECH PROT CHEM PY 1997 VL 8 BP 643 EP 654 DI 10.1016/S1080-8914(97)80064-6 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BJ32Y UT WOS:A1997BJ32Y00061 ER PT B AU Geetha, V Munson, PJ AF Geetha, V Munson, PJ BE Marshak, DR TI Analysis of linkers of regular secondary structures in proteins SO TECHNIQUES IN PROTEIN CHEMISTRY VIII SE TECHNIQUES IN PROTEIN CHEMISTRY (ACADEMIC PRESS INC) LA English DT Proceedings Paper CT 10th Symposium of the Protein-Society CY AUG 03-07, 1996 CL SAN JOSE, CA SP Protein Soc, Aviv Instruments Inc, Beckman Instruments Inc, BioMolecular Technol Inc, BIOSYM Molec Simulat, Bristol Myers Squibb, Finnigan MAT, Fisons Instruments, Hewlett Packard Co, IntelliGenetics Inc, JASCO Inc, Kirin Brewery Co Ltd, Michrom BioResources Inc, Molec Simulat Inc, Perkin Elmer Corp, Appl Biosyst Div, PerSept Biosyst Inc, Pharm Biotech Inc, Rainin Instrument Co Inc, Schering Plough Res Inst, Shimadzu Sci Instruments Inc, Supelco Inc, VYDAC, Waters Corp, Wyatt Technol Corp, ZymoGenetics RP Geetha, V (reprint author), NIH,ANALYT BIOSTAT SECT,STRUCT BIOL LAB,DCRT,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 BN 0-12-473557-6 J9 TECH PROT CHEM PY 1997 VL 8 BP 667 EP 677 DI 10.1016/S1080-8914(97)80066-X PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BJ32Y UT WOS:A1997BJ32Y00063 ER PT B AU Thompson, PA AF Thompson, PA BE Marshak, DR TI Laser temperature jump for the study of early events in protein folding SO TECHNIQUES IN PROTEIN CHEMISTRY VIII SE TECHNIQUES IN PROTEIN CHEMISTRY (ACADEMIC PRESS INC) LA English DT Proceedings Paper CT 10th Symposium of the Protein-Society CY AUG 03-07, 1996 CL SAN JOSE, CA SP Protein Soc, Aviv Instruments Inc, Beckman Instruments Inc, BioMolecular Technol Inc, BIOSYM Molec Simulat, Bristol Myers Squibb, Finnigan MAT, Fisons Instruments, Hewlett Packard Co, IntelliGenetics Inc, JASCO Inc, Kirin Brewery Co Ltd, Michrom BioResources Inc, Molec Simulat Inc, Perkin Elmer Corp, Appl Biosyst Div, PerSept Biosyst Inc, Pharm Biotech Inc, Rainin Instrument Co Inc, Schering Plough Res Inst, Shimadzu Sci Instruments Inc, Supelco Inc, VYDAC, Waters Corp, Wyatt Technol Corp, ZymoGenetics RP Thompson, PA (reprint author), NIDDK,PHYS CHEM LAB,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 BN 0-12-473557-6 J9 TECH PROT CHEM PY 1997 VL 8 BP 735 EP 743 DI 10.1016/S1080-8914(97)80072-5 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BJ32Y UT WOS:A1997BJ32Y00069 ER PT B AU Sergeev, YV Hejtmancik, JF AF Sergeev, YV Hejtmancik, JF BE Marshak, DR TI A method for determining domain binding sites in proteins with swapped domains: implications for beta A3- and beta B2-crystallins SO TECHNIQUES IN PROTEIN CHEMISTRY VIII SE TECHNIQUES IN PROTEIN CHEMISTRY (ACADEMIC PRESS INC) LA English DT Proceedings Paper CT 10th Symposium of the Protein-Society CY AUG 03-07, 1996 CL SAN JOSE, CA SP Protein Soc, Aviv Instruments Inc, Beckman Instruments Inc, BioMolecular Technol Inc, BIOSYM Molec Simulat, Bristol Myers Squibb, Finnigan MAT, Fisons Instruments, Hewlett Packard Co, IntelliGenetics Inc, JASCO Inc, Kirin Brewery Co Ltd, Michrom BioResources Inc, Molec Simulat Inc, Perkin Elmer Corp, Appl Biosyst Div, PerSept Biosyst Inc, Pharm Biotech Inc, Rainin Instrument Co Inc, Schering Plough Res Inst, Shimadzu Sci Instruments Inc, Supelco Inc, VYDAC, Waters Corp, Wyatt Technol Corp, ZymoGenetics RP Sergeev, YV (reprint author), NEI,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 BN 0-12-473557-6 J9 TECH PROT CHEM PY 1997 VL 8 BP 817 EP 826 DI 10.1016/S1080-8914(97)80079-8 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology GA BJ32Y UT WOS:A1997BJ32Y00076 ER PT B AU Altschul, SE AF Altschul, SE BE Suhai, S TI Evaluating the statistical significance of multiple distinct local alignments SO THEORETICAL AND COMPUTATIONAL METHODS IN GENOME RESEARCH LA English DT Proceedings Paper CT International Symposium on Theoretical and Computational Genome Research CY MAR 24-27, 1996 CL HEIDELBERG, GERMANY SP Commiss European Communities AB A comparison of two sequences may uncover multiple regions of local similarity. While the significance of each local alignment may be evaluated independently, sometimes a combined assessment is appropriate. This paper discusses a variety of statistical and algorithmic issues that such an assessment presents. RP Altschul, SE (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NATL INST HLTH,BETHESDA,MD 20894, USA. NR 0 TC 44 Z9 45 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45503-X PY 1997 BP 1 EP 14 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Genetics & Heredity SC Biochemistry & Molecular Biology; Biophysics; Biotechnology & Applied Microbiology; Computer Science; Genetics & Heredity GA BJ19F UT WOS:A1997BJ19F00001 ER PT S AU Talan, M AF Talan, M BE Blatteis, CM TI Age-related changes in thermoregulation of mice SO THERMOREGULATION: TENTH INTERNATIONAL SYMPOSIUM ON THE PHARMACOLOGY OF THERMOREGULATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th International Symposium on Thermoregulation CY AUG 17-22, 1996 CL MEMPHIS, TENNESSEE SP New York Acad Sci, Mini Mitter Co Inc, Data Sci Int, Augustine Med Inc, Int Sci Fdn, Int Union Physiol Sci, IUPS Commiss Thermal Physiol, Univ Tennessee, Memphis, Dept Physiol & Biophys ID BROWN ADIPOSE-TISSUE; SYMPATHETIC NERVOUS ACTIVITY; UNCOUPLING PROTEIN; C57BL/6J MICE; GDP BINDING; COLD STRESS; OLD RATS; THERMOGENESIS; EXPRESSION C1 NIA, Gerontol Res Ctr, Behav Sci Lab, Baltimore, MD 21224 USA. RP Talan, M (reprint author), NIA, Gerontol Res Ctr, Behav Sci Lab, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 21 TC 4 Z9 4 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-088-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 813 BP 95 EP 100 DI 10.1111/j.1749-6632.1997.tb51678.x PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BM49A UT WOS:000078895700014 PM 9100868 ER PT J AU Merryman, P Tannenbaum, SH Gralnick, HR Yu, K Arnold, WS Alexander, HR Fraker, D Horne, MK AF Merryman, P Tannenbaum, SH Gralnick, HR Yu, K Arnold, WS Alexander, HR Fraker, D Horne, MK TI Fibrinolytic and coagulant responses to regional limb perfusions of tumor necrosis factor, interferon-gamma, and/or melphalan SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR; ENDOTHELIAL-CELLS; CARDIOPULMONARY BYPASS; VASCULAR ENDOTHELIUM; CYTOKINE ACTIVATION; FACTOR INFUSIONS; CARDIAC-SURGERY; PLASMA; PAI-1; DEGRADATION AB Regional limb perfusion with antineoplastic agents stresses the local vasculature in a variety of ways. However, by monitoring the perfusates from limbs treated with melphalan alone or with melphalan plus tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma), we were able to distinguish the effect of the cytokines on the observed coagulant and fibrinolytic responses. We collected samples of effluent from a series of lower extremities that were perfused with the cytokines and/or melphalan as treatment for localized melanoma. Both regimens produced statistically significant evidence of coagulant and fibrinolytic activation. However, limbs receiving cytokines in addition to the melphalan responded with a sharper rise in tissue plasminogen activator (tPA) and plasmin (plasmin-antiplasmin complexes [PAP]) than limbs treated with melphalan alone. Evidence of thrombin formation (prothrombin fragment 1+2 [F1+2], thrombin-antithrombin complexes [TAT]) was also greater when the cytokines were included, although the response was delayed and less consistent than the fibrinolytic activation. C1 NCI,HEMATOL SECT,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 29 TC 6 Z9 6 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 JAN PY 1997 VL 77 IS 1 BP 53 EP 56 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA WE554 UT WOS:A1997WE55400010 PM 9031449 ER PT J AU Waalkes, MP Rehm, S Devor, DE AF Waalkes, MP Rehm, S Devor, DE TI The effects of continuous testosterone exposure on spontaneous and cadmium-induced tumors in the male Fischer (F344/NCr) rat: Loss of testicular response SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-of-Toxicology CY MAR 10-14, 1996 CL ANAHEIM, CA SP Soc Toxicol ID LEYDIG-CELL TUMORIGENESIS; MECHANISM; CHLORIDE; INVITRO; SYSTEM; CANCER AB In the rodent testes, cadmium induces severe necrosis followed by chronic degeneration. Cadmium is also an effective testicular tumorigen, and a single dose produces a high incidence of Leydig cell tumors. The mechanism of tumor formation is unknown, but pituitary feedback, i.e., increased luteinizing hormone (LH) production due to low circulating androgen, has been implicated in causation of proliferative lesions within degenerate, hypofunctioning testes. Thus, the effects of androgen replacement on the testicular toxicity of cadmium in Fischer (F344/NCr) rats was studied. Groups (n = 50) of 10-week-old rats either received testosterone implants that approximate normal circulating levels in castrated rats or were left untreated. After 2 weeks of stabilization, rats were given either 20 mu mol CdCl2/kg, sc, weekly for the next 5 weeks (total dose 100 mu mol/kg) or saline for a total of four treatment groups (control, testosterone alone, testosterone + cadmium, or cadmium alone). Portions of each group were killed either 10 weeks after initiation of cadmium exposure (n = 10), for assessment of endocrine function, or over the next 2 years (n = 40), for assessment of testicular neoplastic lesions. At 10 weeks, cadmium reduced circulating testosterone in nonimplanted rats by nearly 80% and induced a marked weight loss of the testes (>70%) and sex accessory glands (reflected in a 50% reduction in prostate mass). Testosterone implantation restored circulating testosterone levels in cadmium-treated rats and prevented Cd-induced weight loss of the sex accessory glands but not of the testes. Over 2 years, cadmium alone induced a >84% incidence of Leydig cell neoplasia and a >97% incidence of chronic degeneration, both significant increases over control rates (60 and 0%, respectively). Testosterone implantation abolished both cadmium-induced and spontaneously occurring Leydig cell tumors but had no effect on cadmium-induced chronic testicular degeneration. Thus cadmium-induced hypofunction of the testes, and subsequent loss of circulating testesterone, appears to be a critical aspect in cadmium induction of tumors in the rat testes. (C) 1997 Academic Press. RP Waalkes, MP (reprint author), NCI,INORGAN CARCINOGENESIS SECT,COMPARAT CARCINOGENESIS LAB,DIV BASIC SCI,FREDERICK,MD 21702, USA. NR 36 TC 37 Z9 43 U1 1 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 JAN PY 1997 VL 142 IS 1 BP 40 EP 46 DI 10.1006/taap.1996.8005 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WD570 UT WOS:A1997WD57000005 PM 9007032 ER PT J AU Valentine, WM Amarnath, V Graham, DG Morgan, DL Sills, RC AF Valentine, WM Amarnath, V Graham, DG Morgan, DL Sills, RC TI CS2-mediated cross-linking of erythrocyte spectrin and neurofilament protein: Dose response and temporal relationship to the formation of axonal swellings SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-of-Toxicology CY MAR 10-14, 1996 CL ANAHEIM, CA SP Soc Toxicol ID CARBON-DISULFIDE NEUROTOXICITY; 2,5-HEXANEDIONE INTOXICATION; 3,4-DIMETHYL SUBSTITUTION; PYRROLE FORMATION; NERVOUS-SYSTEM; EXPOSURE; TRANSPORT; NEUROPATHY; RATS; DEGENERATION AB Using model proteins, a mechanism for CS2-mediated covalent cross-linking of proteins has been demonstrated previously, The biologic importance of CS2-promoted protein cross-linking is apparent as a possible dosimeter of CS2 exposure and as a potential mechanism to account for the identical neuropathies produced by 2,5-hexanedione and CS2. The present investigation examines the utility of erythrocyte spectrin cross-linking as a biomarker of effect for inhalation exposure to CS2 and examines the ability of CS2 to cross-link neurofilament proteins, a potential neurotoxic target. Rats were exposed to CS2 via inhalation at control, 50-, 500-, and 800-ppm levels for 2, 4, 8, and 13 weeks and spectrin dimer formation was quantified using denaturing gel electrophoresis and densitometry. Neurofilament preparations were also obtained from spinal cords and examined for cross-linking using Western blotting methods, The results obtained for protein crosslinking were compared to morphologic changes in the cervical and lumbar spinal cord using light and electron microscopy. The spectrin dimer exhibited a cumulative dose response and was detectable at both the 50-ppm level employed that did not produce axonal swellings and prior to the development of axonal swellings for the 500- and 800-ppm levels used. Neurofilament protein cross-linking involved all three subunits and the temporal relationship of cross-linking was consistent with a contributing role in the development of axonal swellings. These results establish the sensitivity of spectrin cross-linking for evaluating inhalation exposures and extend the similarities observed for 2,5-hexanedione and CS2 in both clinical settings and in vitro models to their effects exerted on neurofilaments in the axon. (C) 1997 Academic Press. C1 NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP Valentine, WM (reprint author), VANDERBILT UNIV,MED CTR,DEPT PATHOL,NASHVILLE,TN 37232, USA. FU NIEHS NIH HHS [ES02611, ES06387] NR 50 TC 24 Z9 24 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN PY 1997 VL 142 IS 1 BP 95 EP 105 DI 10.1006/taap.1996.8028 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WD570 UT WOS:A1997WD57000011 PM 9007038 ER PT J AU Shimada, H Hochadel, JF Waalkes, MP AF Shimada, H Hochadel, JF Waalkes, MP TI Progesterone pretreatment enhances cellular sensitivity to cadmium despite a marked activation of the metallothionein gene SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID PRIMARY HEPATOCYTE CULTURES; BINDING PROTEIN; CYTO-TOXICITY; HEPATIC METALLOTHIONEIN; INDUCED HEPATOTOXICITY; RE-EXAMINATION; LIVER-CELLS; RAT-LIVER; GLUTATHIONE; RESISTANCE AB Previously, we found that in vivo pretreatment with progesterone markedly increased cadmium lethality in rats, apparently by enhancing cadmium-induced hepatonecrosis. Therefore, the present study was designed to investigate this phenomenon at the molecular level in an in vitro system. TRL-1215 rat liver cells were exposed to various concentrations of progesterone (0, 1, 10, and 100 mu M) for 24 hr and subsequently exposed to cadmium (0, 1, 5, 10, and 50 mu M; as CdCl2) for an additional 24 hr. Although the levels of progesterone used were essentially nontoxic, progesterone pretreatment resulted in a concentration-dependent increase in sensitivity to cadmium as assessed by loss of mitochondrial enzyme activity (tetrazolium-based dye assay) and loss of cytosolic enzyme activity (glutamic oxaloacetic transaminase). The effects of progesterone treatment on intracellular levels of metallothionein (MT), an inducible metal-binding protein generally associated with cadmium tolerance, were also measured. Progesterone (100 mu M) alone increased MT levels 2.4-fold, while cadmium (10 mu M) alone resulted in a 7-fold increase over control. Progesterone pretreatment followed by cadmium exposure caused a marked, 16-fold induction in MT synthesis, a level of activity that has been associated with acquired tolerance to cadmium. In addition, progesterone pretreatment clearly induced transcription of the MT gene as evidenced by enhanced cadmium-induced accumulation of cellular MT mRNA. Progesterone pretreatment had no effect on the level of glutathione, a cellular thiol thought to be important in detoxication of cadmium prior to MT gene activation and MT protein accumulation, or on cellular accumulation of cadmium during the initial 3 hr of exposure to the metal. The proportion of total cellular cadmium bound to MT in cells pretreated with progesterone was greater than that in the cells treated with cadmium alone, indicating an enhanced sequestration of the metal by MT after pretreatment. These results indicate that progesterone, at nontoxic levels, markedly exacerbates cadmium toxicity at the cellular level in liver cells. This is in accord with the observed progesterone-induced enhancement of the hepatotoxic effects of cadmium in vivo. The observed facilitation of cytotoxicity is not based in altered toxicokinetics of cadmium and occurs despite a pronounced activation of the MT gene resulting in an enhanced sequestration of cadmium by MT. The mechanism by which progesterone enhances cadmium toxicity deserves further study. (C) 1997 Academic Press C1 NCI,INORGAN CARCINOGENESIS SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 58 TC 18 Z9 18 U1 1 U2 2 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 JAN PY 1997 VL 142 IS 1 BP 178 EP 185 DI 10.1006/taap.1996.8008 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WD570 UT WOS:A1997WD57000020 PM 9007047 ER PT J AU Kanitz, MH Li, EI Schulte, PA Anderson, NL AF Kanitz, MH Li, EI Schulte, PA Anderson, NL TI Investigation of ornithine decarboxylase activity and two-dimensional electrophoretic protein profile following exposure of T24 bladder carcinoma cells to tumor promoter and carcinogen SO TOXICOLOGY METHODS LA English DT Article DE biomarker; bladder carcinogenesis; occupational exposure; ODC; 2D PAGE ID GENE-EXPRESSION; URINARY-BLADDER; CANCER; RAT; INHIBITION; ADENOMAS; SMOKING; GROWTH; MUCOSA; MICE AB To develop appropriate screening tools for biomarkers of effects of exposure to occupational chemical insult. Changes were investigated in T24 human bladder carcinoma cell ornithine decarboxylase activity and protein profiles by quantitative two-dimensional polyacrylamide gel electrophoresis (2D PAGE), biochemical events potentially altered by an established human bladder carcinogen and tumor promoter. A unique chromatographic approach was used to demonstrate that in vitro exposure of T24 cells for 6 h to varying concentrations of the carcinogen 4-aminobiphenyl elevates enzyme activity 5.3- to 5.9-fold. As a second method to identify potential biomarkers of exposure, two-dimensional gel electrophoresis was used to compare the protein pattern of vehicle control-treated T24 to 4-aminobiphenyl or tumor promoter (12-o-tetradecanoylphorbol-13-acetate)-treated cells. Changes in abundance and modification of proteins are determined using the Kepler software package to analyze and compare gels across treatment groups. With this technology, protein markers are identified by significant alterations in spot density (mean ratio of Coomassie Blue intensity; p <.001, Student's t test) following T24 treatment with the carcinogen or the tumor promoter. Fifteen protein spots from a detectable pool of 542 demonstrate two-fold or greater changes in intensity. The results illustrate the potential of automated two-dimensional gel analysis for classifying different gel patterns, an approach that can be applied to patterns whose differences are obscured by the minor changes in spot intensity that arise between separate cell cultures. In addition to the ornithine decarboxylase assay, 2D PAGE offers much promise to evaluate potential biomarkers for occupational and environmental carcinogens. These results will be used to further develop NIOSH efforts in the molecular epidemiology of occupational bladder carcinogenesis. C1 LARGE SCALE BIOL CORP,ROCKVILLE,MD. NCI,BETHESDA,MD 20892. RP Kanitz, MH (reprint author), NIOSH,TAFT LABS,MS-C-23,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1051-7235 J9 TOXICOL METHOD JI Toxicol. Method. PD JAN-MAR PY 1997 VL 7 IS 1 BP 27 EP 41 PG 15 WC Toxicology SC Toxicology GA XC193 UT WOS:A1997XC19300004 ER PT J AU Klein, HG Dodd, RY Ness, PM Fratantoni, JA Nemo, GJ AF Klein, HG Dodd, RY Ness, PM Fratantoni, JA Nemo, GJ TI Current status of microbial contamination of blood components: Summary of a conference SO TRANSFUSION LA English DT Editorial Material ID RNA GENE PROBE; BACTERIAL-CONTAMINATION; YERSINIA-ENTEROCOLITICA; RED-CELLS; TRANSFUSION; IDENTIFICATION; PLATELETS; SURVEILLANCE; SEPTICEMIA; SEPSIS C1 AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892. NHLBI,DIV BLOOD DIS & RESOURCES,TRANSFUS MED SCI RES GRP,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,BLOOD BANK,BALTIMORE,MD 21287. RP Klein, HG (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C711,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 58 Z9 64 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 1997 VL 37 IS 1 BP 95 EP 101 DI 10.1046/j.1537-2995.1997.37197176958.x PG 7 WC Hematology SC Hematology GA WF548 UT WOS:A1997WF54800018 PM 9024497 ER PT J AU Blajchman, MA Klein, HG AF Blajchman, MA Klein, HG TI Looking back in anger: Retrospection in the face of a paradigm shift SO TRANSFUSION MEDICINE REVIEWS LA English DT Editorial Material ID TRANSFUSION; SYSTEM; SAFETY C1 MCMASTER UNIV,DEPT MED,HAMILTON,ON L8N 3Z5,CANADA. CANADIAN RED CROSS SOC,BLOOD SERV,HAMILTON,ON,CANADA. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP Blajchman, MA (reprint author), MCMASTER UNIV,DEPT PATHOL,1200 MAIN ST W,ROOM HSC 2N34,HAMILTON,ON L8N 3Z5,CANADA. NR 19 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 1997 VL 11 IS 1 BP 1 EP 5 DI 10.1016/S0887-7963(97)80004-1 PG 5 WC Hematology SC Hematology GA WF980 UT WOS:A1997WF98000001 PM 9031485 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - False positives from the yeast two-hybrid system SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID PROTEIN RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 9 TC 23 Z9 23 U1 0 U2 9 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 JAN PY 1997 VL 22 IS 1 BP 33 EP 34 DI 10.1016/S0968-0004(96)30047-9 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE017 UT WOS:A1997WE01700010 PM 9020590 ER PT J AU Hengen, PN AF Hengen, PN TI Internet newsgroups SO TRENDS IN CELL BIOLOGY LA English DT Article ID REAGENTS RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,FREDERICK,MD 21702, USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JAN PY 1997 VL 7 IS 1 BP 34 EP 35 DI 10.1016/S0962-8924(97)60045-8 PG 2 WC Cell Biology SC Cell Biology GA WE013 UT WOS:A1997WE01300008 ER PT J AU Clerici, M Clivio, A Shearer, GM AF Clerici, M Clivio, A Shearer, GM TI Resistance to HIV infection: The genes are only part of the solution SO TRENDS IN MICROBIOLOGY LA English DT Editorial Material ID RESPONSES; VIRUS C1 UNIV MILAN,HL SACCO,PADIGL LITA,DIPARTIMENTO BIOL & GENET SCI MED,I-20157 MILAN,ITALY. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Clerici, M (reprint author), UNIV MILAN,HL SACCO,PADIGL LITA,CATTEDRA IMMUNOL,VIA GB GRASSI 74,I-20157 MILAN,ITALY. OI CLIVIO, ALBERTO/0000-0002-1423-046X NR 15 TC 6 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JAN PY 1997 VL 5 IS 1 BP 2 EP 4 DI 10.1016/S0966-842X(97)81762-3 PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA WE728 UT WOS:A1997WE72800003 PM 9025227 ER PT J AU Vanham, G Toossi, Z Hirsch, CS Wallis, RS Schwander, SK Rich, EA Ellner, JJ AF Vanham, G Toossi, Z Hirsch, CS Wallis, RS Schwander, SK Rich, EA Ellner, JJ TI Examining a paradox in the pathogenesis of human pulmonary tuberculosis: immune activation and suppression/anergy SO TUBERCLE AND LUNG DISEASE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; CD4+ T-CELLS; INTERFERON-GAMMA PRODUCTION; HIV-INFECTED INDIVIDUALS; ANTIGEN-PRESENTING CELL; MYCOBACTERIUM-TUBERCULOSIS; IFN-GAMMA; CYTOKINE PRODUCTION AB Protective immunity against Mycobacterium tuberculosis (MTB) in animal models is based on cell-mediated immunity (CMI), involving bi-directional interactions between T cells and cells of the monocyte/macrophage (MO/MA) lineage. Key factors include MO-derived interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha as well as T cell derived IL-2 and interferon (IFN)-gamma. These cytokines appear particularly crucial in the induction of MA-mediated elimination of mycobacteria. Several lines of evidence indicate that similar mechanisms are operating in humans. During active pulmonary tuberculosis (PTB), signs of both immune depression and immune activation are concomitantly present. Decreased tuberculin skin test reactivity in vivo and deficient IFN-gamma production by MTB-stimulated mononuclear cells in vitro are observed. On the other hand, the serum levels of several cytokines, including TNF, and other inflammatory mediators are increased and circulating MO and T cell show phenotypic and functional evidence of in vivo activation. In this review, we will discuss the evidence for three models, which could explain this apparent paradox: 1. Stimulation of the T cell-suppressive function from MO/MA; 2. Intrinsic T cell refractoriness, possibly associated with tendency to apoptosis (programmed cell death), and 3. Compartmentalization and redistribution of immune responses to the site of disease. The opportunistic behavior of MTB during human immunodeficiency virus (HIV) infection can be explained by suppression of type-1 responses at the level of antigen-presenting cells, CD4 T cells and effector macrophages. The ominous prognostic significance of intercurrent PTB during HIV infection seems primarily due to prolonged activation of HIV replication in macrophages. Supportive immune therapy during PTB could aim at correcting the type-1 deficiency either by IFN-gamma inducers (e.g. IL-12, IL-18) or by neutralizing the suppressive cytokines transforming growth factor beta (TGF-P) and IL-10. Alternatively, inflammatory over-activity could be reduced by neutralizing TNF. Finally, anti-apoptotic therapies (e.g. IL-15) might be considered. C1 Inst Trop Med, Dept Microbiol, Immunol Lab, B-2000 Antwerp, Belgium. Case Western Reserve Univ Hosp, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. Case Western Reserve Univ Hosp, Dept Med, Div Pulm & Crit Care Med, Cleveland, OH 44106 USA. NIH, TB Res Unit, Bethesda, MD 20892 USA. RP Vanham, G (reprint author), Inst Trop Med, Dept Microbiol, Immunol Lab, Nat Str 155, B-2000 Antwerp, Belgium. EM gvanham@itg.be RI Wallis, Robert/A-8018-2009 OI Wallis, Robert/0000-0001-6152-5183 NR 201 TC 52 Z9 56 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0962-8479 J9 TUBERCLE LUNG DIS JI Tubercle Lung Dis. PY 1997 VL 78 IS 3-4 BP 145 EP 158 DI 10.1016/S0962-8479(97)90021-6 PG 14 WC Respiratory System SC Respiratory System GA ZT128 UT WOS:000074051300001 PM 9713647 ER PT J AU Jacobs, GG Johnson, JL Boom, WH Wallis, RS Whalen, CC Ginsberg, AM AF Jacobs, GG Johnson, JL Boom, WH Wallis, RS Whalen, CC Ginsberg, AM TI Tuberculosis vaccines: how close to human testing? SO TUBERCLE AND LUNG DISEASE LA English DT Editorial Material C1 NIAID, Div Microbiol & Infect Dis, Resp Dis Branch, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Div Infect Dis, Cleveland, OH 44106 USA. RP Jacobs, GG (reprint author), NIAID, Div Microbiol & Infect Dis, Resp Dis Branch, NIH, Solor Bldg,Rm 3A41,6003 Execut Blvd,MSC 7630, Bethesda, MD 20892 USA. RI Wallis, Robert/A-8018-2009 OI Wallis, Robert/0000-0001-6152-5183 NR 0 TC 10 Z9 10 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0962-8479 J9 TUBERCLE LUNG DIS JI Tubercle Lung Dis. PY 1997 VL 78 IS 3-4 BP 159 EP 169 DI 10.1016/S0962-8479(97)90022-8 PG 11 WC Respiratory System SC Respiratory System GA ZT128 UT WOS:000074051300002 PM 9713648 ER PT J AU Riley, WA Evans, GW Sharrett, AR Burke, GL Barnes, RW AF Riley, WA Evans, GW Sharrett, AR Burke, GL Barnes, RW TI Variation of common carotid artery elasticity with intimal-medial thickness: The ARIC study SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE arterial elasticity; distensibility; compliance; stiffness; intimal-medial thickness; elastic modulus; ultrasonic imaging; echo-tracking ID B-MODE ULTRASOUND; ATHEROSCLEROTIC LESIONS; AORTIC COMPLIANCE; WALL; DISTENSIBILITY; HYPERTENSION; PROGRESSION; STIFFNESS; MODULUS; RATIO AB Atherosclerosis Risk in Communities (ARIC) study is a prospective investigation of the etiology and natural history of atherosclerosis and cardiovascular disease in four U.S. communities. The purpose of this work is to investigate the relationship between common carotid artery elasticity and intimal-medial thickness (IMT) in the four race-gender groups represented in the ARIC cohort. Noninvasive ultrasonic methods were used to measure IMT and the [systolic minus diastolic] diameter change (DC) of the left common carotid artery in 10,920 black and white, men and women between the ages of 45 and 64 y. The relationship between DC and IMT and IMT(2) was examined after adjustment of DC for age, height, diastolic diameter, diastolic blood pressure and linear and quadratic terms for pulse pressure. This adjusted value of DC was used as an index of elasticity of the common carotid artery in the ARIC cohort with larger values of adjusted DC implying a more elastic vessel. The general behavior of adjusted DC with increasing IMT was observed to be qualitatively similar in all four race-gender groups. Adjusted DC remained nearly constant or increased slightly for values of IMT between approximately 0.4 and 0.8 mm, up to approximately the 90th percentile of IMT, and then decreased above the 90th percentile of IMT. Common carotid artery elasticity, defined as adjusted DC, varies with increasing IMT in the ARIC cohort in a manner consistent with results from previous studies in animals and human subjects addressing the variation of several elasticity indices with atherosclerotic involvement and risk factor exposure in the aorta, and brachial and radial arteries. Our results suggest that thicker common carotid artery walls in middle-aged U.S. populations are no stiffer than thinner walls, except for the thickest 10% of arteries. Since the distal common carotid artery frequently contains atheromatous plaques in this population, the lack of change in stiffness, indeed, the reduction in stiffness per unit thickness, may reflect the various stages of early common carotid atherosclerosis most often found in this population. These are characterized more by destruction of arterial wall structural elements than by changes such as widespread or circumferential sclerosis, which would strengthen and stiffen the artery. (C) 1997 World Federation for Ultrasound in Medicine & Biology. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27157. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,NIH,BETHESDA,MD 20892. RP Riley, WA (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROL,300 S HAWTHORNE RD,WINSTON SALEM,NC 27157, USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 27 TC 77 Z9 81 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PY 1997 VL 23 IS 2 BP 157 EP 164 DI 10.1016/S0301-5629(96)00211-6 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA WT394 UT WOS:A1997WT39400001 PM 9140173 ER PT J AU Wagner, JR Kleiner, DE Walther, MM Linehan, WM AF Wagner, JR Kleiner, DE Walther, MM Linehan, WM TI Perirenal myelolipoma SO UROLOGY LA English DT Article ID RETROPERITONEAL AB Extra-adrenal myelolipomas are rare, benign tumors composed of hematopoietic and adipose elements. Although these tumors can cause local symptoms or hemorrhage, they are generally asymptomatic. However, when discovered intraoperatively, they pose a diagnostic dilemma to the urologic surgeon. We present a case of perirenal extra-adrenal myelolipoma discovered intraoperatively in a patient with von Hippel-Lindau disease undergoing partial nephrectomy. C1 NEI,UROL ONCOL SECT,SURG BRANCH,NIH,BETHESDA,MD 20892. OI Kleiner, David/0000-0003-3442-4453 NR 10 TC 12 Z9 13 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JAN PY 1997 VL 49 IS 1 BP 128 EP 130 DI 10.1016/S0090-4295(97)00368-3 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA WC217 UT WOS:A1997WC21700033 PM 9000202 ER PT S AU Nieman, L AF Nieman, L BE Bulletti, C deZiegler, D Guller, S Levitz, M TI Antiprogestin action on the endometrium SO UTERUS: ENDOMETRIUM AND MYOMETRIUM SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Conference on the Uterus - Endometrium and Myometrium CY OCT 14-16, 1996 CL NYU MED CTR, NEW YORK, NY SP Matria Hlth Care Inc, Schering AG, Takeda Italia Farmaceutici S p A, Upjohn Co, Wyeth Ayerst Int Inc, Wyeth Ayerst Labs, Wyeth S p A HO NYU MED CTR ID MENSTRUAL-CYCLE; LUTEAL-PHASE; MIFEPRISTONE RU-486; FOLLICULAR PHASE; NORMAL WOMEN; LONG-TERM; RU486; PROGESTERONE; INHIBITION; MATURATION AB A variety of synthetic steroidal compounds, including onapristone, lilopristone and mifepristone (RU 486), interact with the progesterone receptor and show antagonist properties in vivo.(1) Given the importance of progesterone to normal endometrial differentiation, one would predict that these agents have important endometrial effects during the luteal phase by blocking progesterone action. However, clinical studies have revealed a more complex spectrum of action. These competitive inhibitors of progesterone effects on transcription may have mixed agonist-antagonist properties related to the hormonal milieu and, like agonist compounds, the dose-response relationships seen with antiprogestins are tissue dependent. Thus, in addition to direct antagonism of progesterone action on the endometrium, antiprogestins may also alter endometrial function indirectly, by reducing gonadal steroid production. Evidence is also accumulating that some antiprogestins may interfere with estrogen action on the endometrium. This paper reviews endometrial effects of the best-studied antiprogestin, RU 486, in women and other primates. Emphasis is placed on morphologic and functional changes in the endometrium, as well as the ability to interrupt pregnancy or induce menstrual bleeding. RU 486 is an orally active 19-norsteroid with glucocorticoid, androgen, and progesterone antagonist properties and little, if any, agonist activity; it does not react with the mineralocorticoid or estrogen receptor.(1,2). After oral administration to men or women, RU 486 has a prolonged half-life of about 20 hours, probably because of extensive binding to plasma proteins.(3) Although antiglucocorticoid effects are seen at single doses of > 5 mg/kg, antiprogestational activity is seen at smaller doses, in part allowing for exploitation of antiprogestin properties without clinical compromise of glucocorticoid status.(2) RP Nieman, L (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 28 TC 1 Z9 1 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-105-7; 1-57331-104-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 828 BP 103 EP 107 DI 10.1111/j.1749-6632.1997.tb48527.x PG 5 WC Multidisciplinary Sciences; Obstetrics & Gynecology; Reproductive Biology SC Science & Technology - Other Topics; Obstetrics & Gynecology; Reproductive Biology GA BJ68F UT WOS:A1997BJ68F00009 PM 9329827 ER PT S AU Garrity, RR Nara, PL Lin, G Johnson, S AF Garrity, RR Nara, PL Lin, G Johnson, S BE Brown, F Burton, D Doherty, P Mekalanos, J Norrby, E TI Genetic vaccination with naked HIV-1 RNA results in low-titer anti-gp120 response SO VACCINES 97 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES SE VACCINES (COLD SPRING HARBOR LABORATORY PRESS) LA English DT Proceedings Paper CT 14th Annual Meeting on Modern Approaches to the Control of Infectious Diseases CY SEP 09-13, 1996 CL COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY SP Pharmacia LKB Biotechnol, Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Merck Pharm Co, Forest Labs Inc, Genentech Inc, Hoechst Marion Roussel Inc, Hoffman La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Merck Genome Res InstOncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Research Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharm Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC, Amer Cyanamid Co, Kirin Brewery, Monsanto Co, Pioneer Hi Bred Int Inc, Westvaco Corp HO COLD SPRING HARBOR LAB RP Garrity, RR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRUS BIOL SECT,LTCB,FREDERICK,MD 21701, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 SN 0899-4056 BN 0-87969-516-1 J9 VACCINES PY 1997 BP 151 EP 156 PG 6 WC Infectious Diseases; Medicine, Research & Experimental; Microbiology; Virology SC Infectious Diseases; Research & Experimental Medicine; Microbiology; Virology GA BH99A UT WOS:A1997BH99A00026 ER PT S AU Hirsch, VM AdgerJohnson, D Campbell, B Goldstein, S Brown, C Elkins, WR Montefiori, DC AF Hirsch, VM AdgerJohnson, D Campbell, B Goldstein, S Brown, C Elkins, WR Montefiori, DC BE Brown, F Burton, D Doherty, P Mekalanos, J Norrby, E TI A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3 SO VACCINES 97 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES SE VACCINES (COLD SPRING HARBOR LABORATORY PRESS) LA English DT Proceedings Paper CT 14th Annual Meeting on Modern Approaches to the Control of Infectious Diseases CY SEP 09-13, 1996 CL COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY SP Pharmacia LKB Biotechnol, Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Merck Pharm Co, Forest Labs Inc, Genentech Inc, Hoechst Marion Roussel Inc, Hoffman La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Merck Genome Res InstOncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Research Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharm Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC, Amer Cyanamid Co, Kirin Brewery, Monsanto Co, Pioneer Hi Bred Int Inc, Westvaco Corp HO COLD SPRING HARBOR LAB RP Hirsch, VM (reprint author), NIAID,IMMUNOL VIRUSES SECT,LID,NIH,TWINBROOK 2 FACIL,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 SN 0899-4056 BN 0-87969-516-1 J9 VACCINES PY 1997 BP 285 EP 289 PG 5 WC Infectious Diseases; Medicine, Research & Experimental; Microbiology; Virology SC Infectious Diseases; Research & Experimental Medicine; Microbiology; Virology GA BH99A UT WOS:A1997BH99A00048 ER PT S AU Glamann, J Parren, P Ditzel, H Arnold, C Kent, KA Montefiori, D Burton, D Hirsch, VM AF Glamann, J Parren, P Ditzel, H Arnold, C Kent, KA Montefiori, D Burton, D Hirsch, VM BE Brown, F Burton, D Doherty, P Mekalanos, J Norrby, E TI Characterization of SIV envelope-specific fabs obtained by combinatorial antibody cloning from a long-term, nonprogressor macaque SO VACCINES 97 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES SE VACCINES (COLD SPRING HARBOR LABORATORY PRESS) LA English DT Proceedings Paper CT 14th Annual Meeting on Modern Approaches to the Control of Infectious Diseases CY SEP 09-13, 1996 CL COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY SP Pharmacia LKB Biotechnol, Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Merck Pharm Co, Forest Labs Inc, Genentech Inc, Hoechst Marion Roussel Inc, Hoffman La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Merck Genome Res InstOncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Research Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharm Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC, Amer Cyanamid Co, Kirin Brewery, Monsanto Co, Pioneer Hi Bred Int Inc, Westvaco Corp HO COLD SPRING HARBOR LAB RP Glamann, J (reprint author), NIAID,LID,NIH,TWINBROOK 2 FACIL,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 SN 0899-4056 BN 0-87969-516-1 J9 VACCINES PY 1997 BP 299 EP 303 PG 5 WC Infectious Diseases; Medicine, Research & Experimental; Microbiology; Virology SC Infectious Diseases; Research & Experimental Medicine; Microbiology; Virology GA BH99A UT WOS:A1997BH99A00050 ER PT S AU Nara, PL VanCott, TC Birx, DL AF Nara, PL VanCott, TC Birx, DL BE Brown, F Burton, D Doherty, P Mekalanos, J Norrby, E TI Evidence for a primary IgG response to the oligomeric form of gp160 during primary HIV-1 infection in both chimpanzees and humans SO VACCINES 97 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES SE VACCINES (COLD SPRING HARBOR LABORATORY PRESS) LA English DT Proceedings Paper CT 14th Annual Meeting on Modern Approaches to the Control of Infectious Diseases CY SEP 09-13, 1996 CL COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY SP Pharmacia LKB Biotechnol, Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Merck Pharm Co, Forest Labs Inc, Genentech Inc, Hoechst Marion Roussel Inc, Hoffman La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Merck Genome Res InstOncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Research Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharm Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC, Amer Cyanamid Co, Kirin Brewery, Monsanto Co, Pioneer Hi Bred Int Inc, Westvaco Corp HO COLD SPRING HARBOR LAB RP Nara, PL (reprint author), NCI,FREDERICK CANC RES FACIL,VIRUS BIOL SECT,FREDERICK,MD 21701, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 SN 0899-4056 BN 0-87969-516-1 J9 VACCINES PY 1997 BP 331 EP 337 PG 7 WC Infectious Diseases; Medicine, Research & Experimental; Microbiology; Virology SC Infectious Diseases; Research & Experimental Medicine; Microbiology; Virology GA BH99A UT WOS:A1997BH99A00055 ER PT J AU Haynes, JS Halbur, PG Sirinarumitr, T Paul, PS Meng, XJ Huffman, EL AF Haynes, JS Halbur, PG Sirinarumitr, T Paul, PS Meng, XJ Huffman, EL TI Temporal and morphologic characterization of the distribution of porcine reproductive and respiratory syndrome virus (PRRSV) by in situ hybridization in pigs infected with isolates of PRRSV that differ in virulence SO VETERINARY PATHOLOGY LA English DT Article DE in situ hybridization; interdigitating dendritic cells; lymphoid tissue; macrophages; porcine reproductive and respiratory syndrome virus; swine ID SWINE INFERTILITY; LELYSTAD VIRUS; ATCC VR-2332; ANTIGEN AB Three groups of 5-week-old cesarian-derived, colostrum-deprived pigs were inoculated intranasally with either a high-virulence isolate (VR2385) or a low-virulence isolate (VR2431) of porcine reproductive and respiratory syndrome virus (PRRSV) or with uninfected cell culture and media. Formalin-fixed, paraffin-embedded tissues from pigs euthanatized at 10, 21, and 28 days post-inoculation were examined by in situ hybridization for PRRSV nucleic acid using a digoxigenin-labeled antisense RNA probe approximately 1,000 nucleotides in length. Alveolar macrophages were positive in the lungs of 9/9, 2/2, and 0/2 VR2385-inoculated pigs and 7/9, 1/2, and 2/3 VR2431-inoculated pigs at 10, 21, and 28 days post-inoculation, respectively. More positive cells were detected in lungs from VR2385-inoculated pigs compared to VR2431-inoculated pigs at 10 and 21 days post-inoculation. Positive cells within lymph nodes were tingible body macrophages in germinal centers and macrophages or interdigitating dendritic cells within the paracortical areas. VR2385 was detected in the tracheobronchial lymph node (TBLN) and mediastinal lymph node (MLN) of 7/9 and 9/9 pigs at 10 days post-inoculation, but was only detected in the TBLN of 1/2 and 0/2 pigs and in the MLN of 0/2 and 1/2 pigs at 21 and 28 days post-inoculation, respectively. In contrast, VR2431 was detected in the TBLN and MLN of 5/9 and 2/9 pigs at 10 days post-inoculation and in the TBLN of 0/2 and 1/3 pigs and in the MLN of 0/2 and 0/3 pigs at 21 and 28 days post-inoculation, respectively. There were more positive cells in TBLN and MLN in pigs inoculated with VR2385 at 10 days post-inoculation. Macrophages located at the epithelial-lymphoid interface of tonsilar crypts and within the paracortical areas were positive in tonsils of 9/9, 2/2, and 1/2 VR2385-inoculated pigs and 7/9, 1/2, and 1/3 VR2431-inoculated pigs at 10, 21, and 28 days post-inoculation, respectively. Positive cells in the thymic medulla were multinucleate and were only detected at 10 days post-inoculation in 2/9 VR2385-inoculated pigs and 4/9 VR2431-inoculated pigs. Positive cells within the spleen were few, spindle-shaped, located within smooth muscle trabecula, and only present at 10 days post-inoculation in 3/9 VR2385-inoculated pigs. We conclude that the tissue tropism and distribution of positive cells within tissues is similar for VR2385 and VR2431. However, tissues from more pigs and more cells within tissues were positive in pigs inoculated with VR2385 than VR2431 at 10 and 21 days post-inoculation. These findings indicate that the more virulent isolate VR2385 may replicate better in vivo than the less virulent isolate VR2431. This supports the hypothesis that an increased ability to replicate in vivo contributes to increased virulence of PRRSV. C1 IOWA STATE UNIV,COLL VET MED,VET MED RES INST,AMES,IA 50011. IOWA STATE UNIV,COLL VET MED,VET DIAGNOST LAB,AMES,IA 50011. NIAID,NIH,BETHESDA,MD 20892. RP Haynes, JS (reprint author), IOWA STATE UNIV,COLL VET MED,DEPT VET PATHOL,2718 VET MED BLDG,AMES,IA 50011, USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 12 TC 41 Z9 43 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD JAN PY 1997 VL 34 IS 1 BP 39 EP 43 PG 5 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA WC748 UT WOS:A1997WC74800006 PM 9150544 ER PT J AU King, AD Green, KY AF King, AD Green, KY TI Sequence analysis of the gene encoding the capsid protein of the snow mountain human calicivirus SO VIRUS GENES LA English DT Article DE SMV capsid; sequence analysis; calicivirus; gastroenteritis ID ROUND-STRUCTURED VIRUSES; MOLECULAR CHARACTERIZATION; DIVERSITY AB Snow Mountain virus (SMV) is the reference strain for serotype 3 as determined by immune electron microscopy of the human caliciviruses that are associated with epidemic gastroenteritis. In order to establish the genetic relationship of its capsid protein with those from other human caliciviriuses, the sequence of the open reading frame 2 (ORF2) encoding the SMV capsid protein was determined. The SMV ORF2 sequence was 1626 nucleotides in length and the deduced protein of 542 amino acids had a calculated molecular weight of 59.2 kD. The SMV capsid sequence showed approximately 48 and 77% amino acid sequence identity with the capsid proteins of the Norwalk (serotype 1) and Hawaii (serotype 2) human calicivirus reference strains, respectively, a finding consistent with its serotypic distinctiveness. Furthermore, the predicted amino acid sequence of the SMV capsid was found to share highest sequence identity (98%) with the Melksham human calicivirus in database searches. C1 NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. NR 8 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PY 1997 VL 15 IS 1 BP 5 EP 7 DI 10.1023/A:1007953126436 PG 3 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA YB480 UT WOS:A1997YB48000001 PM 9354262 ER PT J AU Tami, C Kaplan, G Piccone, ME Palma, EL AF Tami, C Kaplan, G Piccone, ME Palma, EL TI Nucleotide sequence of the P1 region of foot-and-mouth disease virus strain O1 Caseros SO VIRUS GENES LA English DT Article DE picornavirus; foot-and-mouth disease virus; O1 Caseros P1 nucleotide sequence ID AMINO-ACID SUBSTITUTIONS; ANTIGENIC SITES; CAPSID PROTEINS; PROTECTION; IDENTIFICATION; NEUTRALIZATION; HETEROGENEITY; RESPONSES; VARIANTS; SURFACE AB It has been shown that variation of antigenic site I in VP1 of foot-and-mouth disease virus (FMDV) plays an important role in the antigenic diversification of this virus. However, the O1 Campos strain is able to efficiently cross-protect cattle against the O1 Caseros strain, despite having a different sequence in the site I. In this paper we report and compare the P1 coding region for the capsid proteins of FMDV O1 Caseros and O1 Campos. The deduced amino acid sequence showed a total of 31 amino acid differences. Eight of them are located in surface-exposed loops that have been implicated in antigenic sites. This study should help to identify additional sites to be considered in the development of a new generation of FMDV vaccines. C1 NIH,FDA GBER OVRR DVPP,BETHESDA,MD 20892. INTA,CICV,INST BIOTECHNOL,MORON,BUENOS AIRES,ARGENTINA. NR 30 TC 4 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PY 1997 VL 14 IS 3 BP 255 EP 259 PG 5 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA XW592 UT WOS:A1997XW59200012 PM 9311571 ER PT J AU Levine, M Rumsey, S Wang, YH AF Levine, M Rumsey, S Wang, YH TI Principles involved in formulating recommendations for vitamin C intake: A paradigm for water-soluble vitamins SO VITAMINS AND COENZYMES, PT I SE METHODS IN ENZYMOLOGY LA English DT Review ID ASCORBIC-ACID TRANSPORT; HUMAN-NEUTROPHILS; ACCUMULATION; ABSORPTION; DEPLETION; EXCRETION RP Levine, M (reprint author), NIDDKD,MOL & CLIN NUTR SECT,NIH,BETHESDA,MD 20892, USA. NR 44 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 279 BP 43 EP 54 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ25G UT WOS:A1997BJ25G00006 PM 9211256 ER PT S AU Fitzhugh, AL Akee, RK AF Fitzhugh, AL Akee, RK BE McCormick, DB Suttie, JW Wagner, C TI Chemical synthesis of (6S)-5-formyl-5,6,7,8-tetrahydropteroylpoly-gamma-L-glutamates SO VITAMINS AND COENZYMES, PT K SE Methods in Enzymology LA English DT Review RP Fitzhugh, AL (reprint author), NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, FREDERICK, MD 21702 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182182-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 281 BP 88 EP 96 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ41A UT WOS:A1997BJ41A00011 PM 9250971 ER PT S AU Milstien, S AF Milstien, S BE McCormick, DB Suttie, JW Wagner, C TI Interconversion of 6- and 7-substituted tetrahydropterins via enzyme-generated 4a-hydroxytetrahydropterin intermediates SO VITAMINS AND COENZYMES, PT K SE Methods in Enzymology LA English DT Review ID 4A-CARBINOLAMINE DEHYDRATASE; PHENYLALANINE HYDROXYLATION; PTERINS; COFACTOR RP Milstien, S (reprint author), NIMH, LAB CELL & MOL REGULAT, NIH, BETHESDA, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182182-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 281 BP 116 EP 123 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ41A UT WOS:A1997BJ41A00014 PM 9250974 ER PT S AU Levine, M Rumsey, SC Wang, YH Park, J Kwon, O Amano, N AF Levine, M Rumsey, SC Wang, YH Park, J Kwon, O Amano, N BE McCormick, DB Suttie, JW Wagner, C TI In situ kinetics: An approach to recommended intake of vitamin C SO VITAMINS AND COENZYMES, PT K SE Methods in Enzymology LA English DT Review ID ASCORBIC-ACID TRANSPORT; LOW-DENSITY-LIPOPROTEIN; CHROMAFFIN GRANULES; HUMAN-NEUTROPHILS; NOREPINEPHRINE BIOSYNTHESIS; INSITU KINETICS; PLASMA-CONCENTRATIONS; ELECTRON-TRANSFER; BETA-CAROTENE; ELDERLY MEN RP Levine, M (reprint author), NIDDKD, MOL & CLIN NUTR SECT, NIH, BETHESDA, MD 20892 USA. NR 89 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182182-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 281 BP 425 EP 437 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ41A UT WOS:A1997BJ41A00046 PM 9251006 ER PT S AU Ferrari, N Vidali, G Pfeffer, U AF Ferrari, N Vidali, G Pfeffer, U BE McCormick, DB Suttie, JW Wagner, C TI Use of quantitative polymerase chain reaction to study retinoid receptor expression SO VITAMINS AND COENZYMES, PT L SE Methods in Enzymology LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; REVERSE TRANSCRIPTION; RT-PCR; ENZYMATIC AMPLIFICATION; DNA-POLYMERASE; RNA; ALPHA; BETA; DIAGNOSIS RP Ferrari, N (reprint author), NATL CANC INST, ADV BIOTECHNOL CTR, MOL BIOL LAB, I-16132 GENOA, ITALY. RI Pfeffer, Ulrich/J-7064-2016 OI Pfeffer, Ulrich/0000-0003-0872-4671 NR 20 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182183-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 282 BP 48 EP 64 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ75E UT WOS:A1997BJ75E00005 PM 9330276 ER PT S AU Wojnowski, L Zimmer, A AF Wojnowski, L Zimmer, A BE McCormick, DB Suttie, JW Wagner, C TI Use of transgenic mice to study activation of retinoic acid-responsive promoters SO VITAMINS AND COENZYMES, PT L SE Methods in Enzymology LA English DT Review ID BETA-GALACTOSIDASE; LACZ GENE; RECEPTORS; ELEMENT; IDENTIFICATION; EXPRESSION; SEQUENCE; CELLS RP Wojnowski, L (reprint author), NIMH, GENET SECT, NIH, BETHESDA, MD 20892 USA. RI Zimmer, Andreas/B-8357-2009 NR 20 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182183-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 282 BP 77 EP 85 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ75E UT WOS:A1997BJ75E00007 PM 9330278 ER PT J AU Snow, JB AF Snow, JB TI Research on hearing and balance - Current and future developments SO VOLTA REVIEW LA English DT Article ID MULTICHANNEL COCHLEAR IMPLANTS; SERUM ANTIBODIES; MENIERES-DISEASE; CHILDREN; GENE; EXPRESSION; MUTATION; DEAFNESS; CELLS; AIDS AB A multitude of disease genes causing hearing impairment have been located in the human genome, as have genes responsible for the normal development of the ear. Sensory cells of the inner ear have been demonstrated to regenerate in fish, birds, and even mammals. Substantial progress has been made in the development of vaccines to prevent otitis media. Hearing aids are now programmable, and cochlear implants continue to be improved with new sound processing strategies. Great progress has occurred in rehabilitation of individuals with balance disorders through the use of physical therapy. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NR 21 TC 0 Z9 0 U1 1 U2 1 PU ALEXANDER GRAHAM BELL ASSOC FOR THE DEAF PI WASHINGTON PA 3417 VOLTA PLACE NW, WASHINGTON, DC 20007 USA SN 0042-8639 J9 VOLTA REV JI Volta Rev. PY 1997 VL 99 IS 5 BP 29 EP 42 PG 14 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 331FF UT WOS:000088006100003 ER PT B AU Brigger, P Unser, M AF Brigger, P Unser, M BE Aldroubi, A Laine, AF Unser, MA TI General discrete centered image pyramids SO WAVELET APPLICATIONS IN SIGNAL AND IMAGE PROCESSING V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Wavelet Applications in Signal and Image Processing V CY JUL 30-AUG 01, 1997 CL SAN DIEGO, CA SP Soc Photo Opt Instrumentat Engineers DE splines; multi-resolution decomposition; image pyramids; least squares pyramids; centered pyramids AB We present an improved type of image pyramid based on general approximation functions. The type of pyramid proposed maintains the good properties of symmetry and consistent boundary conditions of the Haar pyramid. Moreover, it is not restricted to a piece-wise constant image model, but allows the use of any generating sequence. The centered topology guarantees a clearly defined up-projection of labels and may be employed in applications for contour detection, object recognition and segmentation. We start by introducing the general discrete framework for the design of least squares pyramids using the standard filtering and decimation tools based on arbitrary basis functions. Our design criterion is to minimize the l(2) norm of the approximation error. We then define the centered pyramid and give explicit filter coefficients for odd and even spline approximation functions. Finally, we compare the centered pyramid to the ordinary one and highlight some applications. RP Brigger, P (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NCRR,BLDG 13,ROOM 3N17,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2591-5 J9 P SOC PHOTO-OPT INS PY 1997 VL 3169 BP 212 EP 223 DI 10.1117/12.279688 PG 12 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BJ98C UT WOS:A1997BJ98C00020 ER PT B AU Thevenaz, P Unser, M AF Thevenaz, P Unser, M BE Aldroubi, A Laine, AF Unser, MA TI Spline pyramids for inter-modal image registration using mutual information SO WAVELET APPLICATIONS IN SIGNAL AND IMAGE PROCESSING V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Wavelet Applications in Signal and Image Processing V CY JUL 30-AUG 01, 1997 CL SAN DIEGO, CA SP Soc Photo Opt Instrumentat Engineers DE multiresolution; B-spline; Parzen window; Marquardt-Levenberg AB We propose a new optimizer for multiresolution image registration. It is adapted to a criterion known as mutual information and is well suited to inter-modality. Our iteration strategy is inspired by the Marquardt-Levenberg algorithm, even though the underlying problem is not least-squares. We develop a framework based on a continuous polynomial spline representation of images. Together with the use of Parzen histogram estimates, it allows for closed-form expressions of the gradient and Hessian of the criterion. Tremendous simplifications result from the choice of Parzen windows satisfying the partition of unity, also based on B-splines. We use this framework to compute an image pyramid and to set our optimizer in a multiresolution context. We perform several experiments and show that it is particularly well adapted to a coarse-to-fine optimization strategy. We compare our approach to the popular Powell algorithm and conclude that our proposed optimizer is faster, at no cost in robustness or precision. RP Thevenaz, P (reprint author), NIH,BEIP,NATL CTR RES RESOURCES,BETHESDA,MD 20892, USA. NR 0 TC 29 Z9 29 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2591-5 J9 P SOC PHOTO-OPT INS PY 1997 VL 3169 BP 236 EP 247 DI 10.1117/12.292794 PG 12 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BJ98C UT WOS:A1997BJ98C00022 ER PT B AU Unser, M AF Unser, M BE Aldroubi, A Laine, AF Unser, MA TI Ten good reasons for using spline wavelets SO WAVELET APPLICATIONS IN SIGNAL AND IMAGE PROCESSING V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Wavelet Applications in Signal and Image Processing V CY JUL 30-AUG 01, 1997 CL SAN DIEGO, CA SP Soc Photo Opt Instrumentat Engineers DE splines; wavelet basis; biorthogonal wavelets; regularity; smoothness; time-frequency localization; approximation properties AB The purpose of this note is to highlight some of the unique properties of spline wavelets. These wavelets can be classified in four categories: othogonal (Battle-Lemarie), semi-orthogonal (e.g., B-spline), shift-orthogonal, and biorthogonal (Cohen-Daubechies-Feauveau). Unlike most other wavelet bases, splines have explicit formulae in both the time and frequency domain, which greatly facilitates their manipulation. They allow for a progressive transition between the two extreme cases of a multiresolution: Haar's piecewise constant representation (spline of degree zero) versus Shannon's bandlimited model (which corresponds to a spline of infinite order). Spline wavelets are extremely regular and usually symmetric or anti-symmetric. They can be designed to have compact support and to achieve optimal time-frequency localization (B-spline wavelets). The underlying scaling functions are the B-splines, which are the shortest and most regular scaling functions of order L. Finally, splines have the best approximation properties among all known wavelets of a given order L. In other words, they are the best for approximating smooth functions. RP Unser, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N17,BETHESDA,MD 20892, USA. NR 0 TC 46 Z9 47 U1 0 U2 3 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2591-5 J9 P SOC PHOTO-OPT INS PY 1997 VL 3169 BP 422 EP 431 DI 10.1117/12.292801 PG 10 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BJ98C UT WOS:A1997BJ98C00039 ER PT B AU Aldroubi, A AF Aldroubi, A BE DAttellis, CE FernandezBerdaguer, EM TI Oblique multiwavelet bases SO WAVELET THEORY AND HARMONIC ANALYSIS IN APPLIED SCIENCES SE APPLIED AND NUMERICAL HARMONIC ANALYSIS LA English DT Proceedings Paper CT 1st Latin-American Conference on Mathematics in Industry and Medicine CY NOV 27-DEC 01, 1995 CL BUENOS AIRES, ARGENTINA RP Aldroubi, A (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER BOSTON PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139-2333 BN 0-8176-3953-5 J9 APPL NUM HARM ANAL PY 1997 BP 73 EP 91 PG 19 WC Mathematics, Applied SC Mathematics GA BJ84R UT WOS:A1997BJ84R00004 ER PT J AU Gerlach, KK Marino, C Weed, DL Hoffman-Goetz, L AF Gerlach, KK Marino, C Weed, DL Hoffman-Goetz, L TI Lack of colon cancer coverage in seven women's magazines SO WOMEN & HEALTH LA English DT Article ID COLORECTAL-CANCER; STATISTICS; RISK; MACRONUTRIENTS; SMOKING; HAZARDS; MEDIA; FIBER AB Women's magazines are an important source of health information. To evaluate the relevancy of articles in these publications to known disease risks, seven women's magazines were reviewed to assess their coverage of colon cancer, the third leading cause of cancer mortality in U.S. women. Specifically, the amount of coverage devoted to colon cancer as well as the presentation of issues in the prevention, risks, treatment, diagnosis and genetics of colon cancer were recorded. Twenty articles were published on colon cancer in these magazines during the years 1987-1995. Compared to five other cancers that also affect women, colon cancer was the focus of the fewest articles in the seven magazines analyzed. C1 NCI, Prevent Oncol Branch, Bethesda, MD 20892 USA. NCI, Canc Prevent & Control Fellowship Program, Bethesda, MD 20892 USA. RP Weed, DL (reprint author), Execut Plaza S,Suite T-41,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 44 TC 23 Z9 23 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 1997 VL 26 IS 2 BP 57 EP 68 PG 12 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA YU463 UT WOS:000071720400004 PM 9472955 ER PT B AU Korach, KS Taki, M Kimbro, KS AF Korach, KS Taki, M Kimbro, KS BE Paoletti, R Crosignani, PG Kenemans, P Samsioe, G Soma, MR Jackson, AS TI Rie effects of estrogen receptor gene disruption on bone SO WOMEN'S HEALTH AND MENOPAUSE: RISK REDUCTION STRATEGIES SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT 2nd International Symposium on Womens Health in Menopause - Risk Reduction Strategies CY DEC 05-08, 1996 CL FLORENCE, ITALY RP Korach, KS (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4697-1 J9 MED SCI SYMP SER PY 1997 VL 11 BP 69 EP 73 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BJ79C UT WOS:A1997BJ79C00010 ER PT J AU Leipe, DD Tong, SM Goggin, CL Slemenda, SB Pieniazek, NJ Sogin, ML AF Leipe, DD Tong, SM Goggin, CL Slemenda, SB Pieniazek, NJ Sogin, ML TI 16S-like rDNA sequences from Developayella elegans, Labyrinthuloides haliotidis, and Proteromonas lacertae confirm that the stramenopiles are a primarily heterotrophic group SO EUROPEAN JOURNAL OF PROTISTOLOGY LA English DT Article DE chromophytes; evolution; proteromonads; phylogeny; stramenopiles ID RIBOSOMAL-RNA SEQUENCES; PHYLOGENETIC ANALYSIS; FLAGELLAR APPARATUS; ALGAE; CLASSIFICATION; ULTRASTRUCTURE; REGIONS; TREES AB A phylogenetic analysis of the S-16-like ribosomal RNA coding regions from Labyrinthuloides haliotidis, Developayella elegans, Proteromonas lacertae and other organisms corroborates morphological evidence that proteromonads and other eukaryotes with tripartite tubular hairs form a monophyletic group of organisms, the stramenopiles. Within the stramenopiles, the heterotrophic groups (proteromonads, Labyrinthulida, bicosoecids, Developayella and oomycetes) diverge before the radiation of the ''heterokont algae'', the autotrophic stramenopiles. The stramenopiles were initially ''protozoan'' but their ecological success is largely attributable to the late symbiotic acquisition of chloroplasts. The stramenopiles and other taxa with chlorophyll a+c containing chloroplasts (cryptomonads, dinoflagellates, and haptophytes) do not share a common autotrophic ancestor. These photosynthetic assemblages acquired their plastids independently. C1 MARINE BIOL LAB, CTR MOL EVOLUT, WOODS HOLE, MA 02543 USA. NATL LIB MED, NIH, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. UNIV SOUTHAMPTON, DEPT BIOL, SOUTHAMPTON SO16 7PX, HANTS, ENGLAND. UNIV PRINCE EDWARD ISL, ATLANTIC VET COLL, CHARLOTTETOWN, PE C1A 4P3, CANADA. CTR DIS CONTROL & PREVENT MS F13, ATLANTA, GA 30341 USA. NR 55 TC 76 Z9 78 U1 1 U2 6 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0932-4739 EI 1618-0429 J9 EUR J PROTISTOL JI Eur. J. Protistol. PD DEC 31 PY 1996 VL 32 IS 4 BP 449 EP 458 PG 10 WC Microbiology SC Microbiology GA WG561 UT WOS:A1996WG56100004 ER PT J AU Park, YM Yoo, YD Paik, SY Kim, BS Tabor, E AF Park, YM Yoo, YD Paik, SY Kim, BS Tabor, E TI Mutation of tumor suppressor gene p53 in hepatocellular carcinomas from Korea SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE reverse transcription polymerase chain reaction; polymerase chain reaction single strand conformation polymorphism; p53; tumor suppressor gene; hepatocellular carcinoma ID CHINA; HETEROGENEITY; ABERRATIONS; EXPRESSION; OCCUR AB Mutation of the p53 gene in hepatocellular carcinoma has been recognized as one of the most important genetic alterations to occur during hepatocarcinogenesis. This study was performed to analyze the frequency and nature of p53 mutations in advanced hepatocellular carcinomas from Korea. Tissue samples were obtained by laparoscopic biopsy from 35 patients; adjacent nontumorous liver tissue was also obtained from 24 of them. Mutations of the p53 gene were identified in 11/35 (31%) of hepatocellular carcinomas, These included 7 missense mutations and 4 deletion mutations. Only one mutation was detected at codon 249, a ''hot spot'' at which mutations have been found frequently in hepatocellular carcinomas from some geographic areas; however, this was an A-to-T transversion at the first nucleotide, thus differing from commonly reported G-to-T transversion at the third nucleotide of codon 249 in hepatocellular carcinomas, Patients whose serum alkaline phosphatase levels were higher than the mean Value were more likely to have p53 mutations, compared to patients whose alkaline phosphatase levels were lower than the mean value [55% (6/11) vs. 21% (5/24)] (p<0.05). Thus, p53 mutations are found in many hepatocellular carcinomas in Korea. However, mutations commonly thought to be due to aflatoxin B-1 (G-to-T transversion at codon 249) were not found, suggesting that aflatoxin-B-1 does not play an important role in the etiology of hepatocellular carcinoma in Korea. C1 NCI,NIH,BETHESDA,MD 20892. CATHOLIC UNIV,SCH MED,KANGNAM ST MARYS HOSP,DEPT INTERNAL MED,SEOUL,SOUTH KOREA. KOREAN CANC CTR HOSP,LAB EXPT THERAPEUT,SEOUL,SOUTH KOREA. CATHOLIC UNIV,SCH MED,DEPT MICROBIOL,SEOUL,SOUTH KOREA. US FDA,BETHESDA,MD 20014. NR 26 TC 6 Z9 6 U1 1 U2 2 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD DEC 31 PY 1996 VL 28 IS 4 BP 173 EP 179 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA WC363 UT WOS:A1996WC36300004 ER PT J AU Lin, YJ Bovetto, S Carver, JM Giordano, T AF Lin, YJ Bovetto, S Carver, JM Giordano, T TI Cloning of the cDNA for the human NMDA receptor NR2C subunit and its expression in the central nervous system and periphery SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NMDA receptors; NR2C; distribution; cloning, in situ; human ID D-ASPARTATE RECEPTORS; LONG-TERM POTENTIATION; GLUTAMATE-RECEPTOR; MOLECULAR-CLONING; PHARMACOLOGICAL CHARACTERIZATION; SYNAPTIC PLASTICITY; EPSILON-4 SUBUNIT; MESSENGER-RNAS; CLONED CDNAS; CHANNEL AB Several overlapping cDNA clones containing 3995 nucleotides of the human 2C NMDA receptor subunit (NR2C) were isolated from human hippocampal and cerebellar cDNA libraries. The nucleic acid sequence of the overlapping cDNA clones displays 85% identity to that of rat NR2C. The predicted protein sequence is 1233 amino acids long and has 88% identity to the amino acid sequence of the rat NR2C. Northern blot analysis has demonstrated a wide distribution pattern of the NR2C transcript in the brain. While the predominant expression is in the cerebellum, as observed in the rat, readily detectable levels are present in the hippocampus, amygdala, caudate nucleus, corpus callosum, subthalamic nuclei and thalamus. NR2C was also detected in the heart, skeletal muscle and pancreas. Distribution of the mouse NR2C NMDA receptor subunit homologue was investigated in mouse brain by in situ hybridization histochemistry using exonic genomic probes. Expression of the transcript was principally in the cerebellum, but is also detected in the hippocampus, dentate gyrus, thalamic and subthalamic nuclei, vestibular nuclei and olfactory bulb. These results demonstrate a widespread expression pattern of the NR2C gene, both in the CNS and in the periphery. C1 SYMPHONY PHARMACEUT INC,DEPT MOL BIOL,MALVERN,PA 19355. NIDDK,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 41 TC 28 Z9 29 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 31 PY 1996 VL 43 IS 1-2 BP 57 EP 64 DI 10.1016/S0169-328X(96)00146-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA WD744 UT WOS:A1996WD74400007 ER PT J AU Soh, Y Jeong, KS AF Soh, Y Jeong, KS TI In vitro phosphorylation of purified transketolase by protein kinase C SO MOLECULES AND CELLS LA English DT Article ID WERNICKE-KORSAKOFF-SYNDROME; PURIFICATION; ABNORMALITY; ALCOHOLICS; ENZYME AB Catalytically active transketolase was purified from rat liver cytosolic fi action by more than 120-fold to near homogeneity by successive column chromatography using DEAE-Sephacel, hydroxylapatite and Mono P matrices. The purified transketolase was rapidly phosphorylated by protein kinase C (PKC) while it was minimally phosphorylated by cAMP-dependent protein kinase and casein kinase II. Phosphoamino acid analysis of the P-32-labeled enzyme revealed that only threonine residue was phosphorylated by PKC. The phosphorylated enzyme became less active (about 40%) than the non-phosphorylated counterpart. Our data suggest that transketolase can be phosphorylated by PKC, which could represent a new type of regulatory mechanism for transketolase. C1 KIST,KOREA RES INST BIOSCI & BIOTECHNOL,TAEJON 305606,SOUTH KOREA. RP Soh, Y (reprint author), NIAAA,NEUROGENET LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU KOREAN SOC MOLECULAR BIOLOGY PI SEOUL PA KOREA SCI TECHNOLOGY CENTER, ROOM 815, 635-4 YEOGSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD DEC 31 PY 1996 VL 6 IS 6 BP 692 EP 696 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WA011 UT WOS:A1996WA01100010 ER PT J AU Tonk, V Schultz, RA Christian, SL Kubota, T Ledbetter, DH Wilson, GN AF Tonk, V Schultz, RA Christian, SL Kubota, T Ledbetter, DH Wilson, GN TI Robertsonian (15q;15q) translocation in a child with Angelman syndrome: Evidence of uniparental disomy SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE chromosome 15 translocations; Robertsonian translocation 15q15q; Angelman syndrome; Prader-Willi syndrome; paternal uniparental disomy AB A balanced Robertsonian translocation 45,XY,t(15q15q) was detected in a patient with mental retardation, microcephaly, and hypertonia. Deletion of the 15q11q13 region was unlikely based on fluorescence in situ hybridization studies that revealed hybridization of appropriate DNA probes to both arms of the Robertsonian chromosome. Inheritance of alleles from 13 highly polymorphic DNA markers on chromosome 15 showed paternal uniparental isodisomy. The clinical, cytogenetic, and molecular results are consistent with a diagnosis of Angelman syndrome. (C) 1996 Wiley-Liss, Inc. C1 UNIV TEXAS,SW MED CTR,DEPT PEDIAT,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,MCDERMOTT CTR HUMAN GENET & DEV,DALLAS,TX 75235. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 8 TC 13 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 30 PY 1996 VL 66 IS 4 BP 426 EP 428 DI 10.1002/(SICI)1096-8628(19961230)66:4<426::AID-AJMG7>3.0.CO;2-I PG 3 WC Genetics & Heredity SC Genetics & Heredity GA WA357 UT WOS:A1996WA35700007 PM 8989460 ER PT J AU Wyszynski, DF Lewanda, AF Beaty, TH AF Wyszynski, DF Lewanda, AF Beaty, TH TI Phenotypic discordance in a family with monozygotic twins and non-syndromic cleft lip and palate SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID GROWTH-FACTOR-ALPHA; MATERNAL CIGARETTE-SMOKING; AUTOSOMAL MAJOR LOCUS; ORAL CLEFTS; CONGENITAL-MALFORMATIONS; OROFACIAL CLEFTS; FOLIC-ACID; LINKAGE; PREGNANCY; GENE C1 NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT MED GENET,WASHINGTON,DC 20010. JOHNS HOPKINS UNIV HOSP,DEPT PEDIAT,BALTIMORE,MD 21287. RP Wyszynski, DF (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NIDCR NIH HHS [D01-DE10293] NR 40 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 30 PY 1996 VL 66 IS 4 BP 468 EP 470 DI 10.1002/(SICI)1096-8628(19961230)66:4<468::AID-AJMG17>3.0.CO;2-S PG 3 WC Genetics & Heredity SC Genetics & Heredity GA WA357 UT WOS:A1996WA35700017 PM 8989470 ER PT J AU Chen, N Chrambach, A AF Chen, N Chrambach, A TI Improved resolution in the gel electrophoresis of proteins by a periodically interrupted electric field SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE protein; resolution; periodically interrupted electric field; field strength; gel electrophoresis ID AGAROSE GELS; DNA; SEPARATION; PARTICLES AB The capability of the commercial gel electrophoresis apparatus with intermittent scanning of fluorescence (HPGE-1000, LabIntelligence) to provide time-dependent zone dispersion allows one to quantitate resolution. Using a model protein separation, that between phycoerythrin and fluorescein-labeled conalbumin, resolution was compared between separations conducted at a constant field strength of 80 V/cm and one conducted in 10-s pulses of the same field strength, interrupted periodically by 120 s in the absence of an electric field. Resolution was improved by a factor of two in the discontinuous application of the electric field compared to that obtained in its continuous application. Similarly, the intermittent application of 80 V/cm for 10 s, followed by 120-s pauses, gave rise to twice the resolution obtained from a continuous application of 7 V/cm. C1 NICHHD,MACROMOL ANAL SECT,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. NR 21 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD DEC 30 PY 1996 VL 33 IS 3 BP 163 EP 170 DI 10.1016/S0165-022X(96)00021-8 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WE643 UT WOS:A1996WE64300002 PM 9029260 ER PT J AU Wenner, P Tsau, Y Cohen, LB ODonovan, MJ Dan, Y AF Wenner, P Tsau, Y Cohen, LB ODonovan, MJ Dan, Y TI Voltage-sensitive dye recording using retrogradely transported dye in the chicken spinal cord: Staining and signal characteristics SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE voltage-sensitive dye; optical recording; embryonic chick spinal cord; multi-site recording; retrograde staining; dye vs electrode recording ID SALAMANDER OLFACTORY-BULB; CENTRAL NERVOUS-SYSTEM; GILL-WITHDRAWAL REFLEX; NEURONS; EMBRYO; MOTONEURONS; ORGANIZATION; ORIGIN; FURA-2; SLICE AB We describe a novel method for retrogradely labeling specific neuronal populations using voltage-sensitive dyes. Styryl dyes were injected into the Ventral roots of the isolated embryonic chick spinal cord. After waiting several hours, the dye labeled motoneurons and autonomic preganglionic neurons. Neuronal cell bodies, dendrites and axons were labeled; we presume that the dye traveled either by retrograde transport or by diffusion within the membrane of the axon to which the dyes were initially applied. Using either a photodiode array or a photomultiplier, fluorescence changes could be recorded from motoneurons following antidromic or synaptic activation. Several characteristics of the fluorescence changes were measured indicating that the signals did indeed reflect changes in the motoneuron membrane potential. The best labeling and optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12-ANEPEQ. In the great majority of cases these dyes responded with an increase in fluorescence of 1-3% (Delta F/F) in response to synaptic or antidromic depolarization of the motoneurons. We anticipate that these techniques should be useful in the mapping of activity patterns and connectivity in neural networks within a defined population of neurons. C1 YALE UNIV,SCH MED,DEPT PHYSIOL,NEW HAVEN,CT 06510. RP Wenner, P (reprint author), NIH,LAB NEURAL CONTROL,NINDS,BETHESDA,MD 20892, USA. OI Wenner, Peter/0000-0002-7072-2194 FU NIGMS NIH HHS [GM35063]; NINDS NIH HHS [NS08437] NR 28 TC 22 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD DEC 28 PY 1996 VL 70 IS 2 BP 111 EP 120 DI 10.1016/S0165-0270(96)00108-2 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WC979 UT WOS:A1996WC97900001 PM 9007750 ER PT J AU Tsau, Y Wenner, P ODonovan, MJ Cohen, LB Loew, LM Wuskell, JP AF Tsau, Y Wenner, P ODonovan, MJ Cohen, LB Loew, LM Wuskell, JP TI Dye screening and signal-to-noise ratio for retrogradely transported voltage-sensitive dyes SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE voltage-sensitive dye; optical recording; embryonic chick spinal cord; multi-site recording; retrograde staining; styryl dye; dye synthesis; hydrophobic vs hydrophilic dye ID CHARGE-SHIFT PROBES; SALAMANDER OLFACTORY-BULB; CENTRAL NERVOUS-SYSTEM; MEMBRANE; FLUORESCENCE; NEURONS; AXONS AB Using a novel method for retrogradely labeling specific neuronal populations, we tested different styryl dyes in attempt to find dyes whose staining would be specific, rapid, and lead to large activity dependent signals. The dyes were injected into the ventral roots of the isolated chick spinal cord from embryos at days E9-E12. The voltage-sensitive dye signals were recorded from synaptically activated motoneurons using a 464 element photodiode array. The best labeling and optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12-ANEPEQ. Over the 24 h period we examined, these dyes bound specifically to the cells with axons in the ventral roots. The dyes responded with an increase in fluorescence of 1-3% (Delta F/F) in response to synaptic depolarization of the motoneurons. The signal-to-noise ratio obtained in a single trial from a detector that received light from a 14 X 14 mu m(2) area of the motoneuron population was about 10:1. Nonetheless, signals on neighboring diodes were similar, suggesting that we were not detecting the activity of individual neurons. Retrograde labeling and optical recording with voltage-sensitive dyes provides a means for monitoring the activity of identified neurons in situations where microelectrode recordings are not feasible. C1 YALE UNIV, SCH MED, DEPT PHYSIOL, NEW HAVEN, CT 06510 USA. NIH, NEURAL CONTROL LAB, NINDS, BETHESDA, MD 20892 USA. UNIV CONNECTICUT, CTR HLTH, DEPT PHYSIOL, FARMINGTON, CT 06032 USA. MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. OI Loew, Leslie/0000-0002-1851-4646; Wenner, Peter/0000-0002-7072-2194 FU NIGMS NIH HHS [GM35063]; NINDS NIH HHS [NS08437] NR 18 TC 33 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD DEC 28 PY 1996 VL 70 IS 2 BP 121 EP 129 DI 10.1016/S0165-0270(96)00109-4 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WC979 UT WOS:A1996WC97900002 PM 9007751 ER PT J AU Mizzen, CA Yang, XJ Kokubo, T Brownell, JE Bannister, AJ OwenHughes, T Workman, J Wang, L Berger, SL Kouzarides, T Nakatani, Y Allis, CD AF Mizzen, CA Yang, XJ Kokubo, T Brownell, JE Bannister, AJ OwenHughes, T Workman, J Wang, L Berger, SL Kouzarides, T Nakatani, Y Allis, CD TI The TAF(II)250 subunit of TFIID has histone acetyltransferase activity SO CELL LA English DT Article ID RNA-POLYMERASE-II; TATA-BOX-BINDING; TRANSCRIPTION FACTOR; NUCLEOSOMAL DNA; FACILITATED BINDING; ACETYLATION; CHROMATIN; GENE; ACTIVATION; INITIATION AB The transcription initiation factor TFIID is a multimeric protein complex composed of TATA box-binding protein (TBP) and many TBP-associated factors (TAF(II)s). TAF(II)s are important cofactors that mediate activated transcription by providing interaction sites for distinct activators. Here, we present evidence that human TAF(II)250 and its homologs in Drosophila and yeast have histone acetyltransferase (HAT) activity in vitro. HAT activity maps to the central, most conserved portion of dTAF(II)230 and yTAF(II)130. The HAT activity of dTAF(II)230 resembles that of yeast and human GCN5 in that it is specific for histones H3 and H4 in vitro. Our findings suggest that targeted histone acetylation at specific promoters by TAF(II)250 may be involved in mechanisms by which TFIID gains access to transcriptionally repressed chromatin. C1 UNIV ROCHESTER, DEPT BIOL, ROCHESTER, NY 14627 USA. NICHHD, LAB MOL GROWTH REGULAT, NIH, BETHESDA, MD 20892 USA. UNIV CAMBRIDGE, WELLCOME CRC INST, CAMBRIDGE CB2 1QR, ENGLAND. PENN STATE UNIV, DEPT BIOCHEM & MOL BIOL, UNIVERSITY PK, PA 16802 USA. WISTAR INST ANAT & BIOL, PHILADELPHIA, PA 19104 USA. NARA INST SCI & TECHNOL, NARA 63001, JAPAN. OI Owen-Hughes, Tom/0000-0002-0618-8185 FU NIGMS NIH HHS [NIH-GM53512]; Wellcome Trust NR 70 TC 578 Z9 585 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 27 PY 1996 VL 87 IS 7 BP 1261 EP 1270 DI 10.1016/S0092-8674(00)81821-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WA541 UT WOS:A1996WA54100014 PM 8980232 ER PT J AU Rice, PA Yang, SW Mizuuchi, K NAsh, HA AF Rice, PA Yang, SW Mizuuchi, K NAsh, HA TI Crystal structure of an IHF-DNA complex: A protein-induced DNA u-turn SO CELL LA English DT Article ID INTEGRATION HOST FACTOR; ESCHERICHIA-COLI; BINDING PROTEINS; ADENINE TRACT; MINOR-GROOVE; HU PROTEIN; SITES; LATTICE; MUTANTS; RECOMBINATION AB Integration host factor (IHF) is a small heterodimeric protein that specifically binds to DNA and functions as an architectural factor in many cellular processes in prokaryotes. Here, we report the crystal structure of IHF complexed with 35 bp of DNA. The DNA is wrapped around the protein and bent by >160 degrees, thus reversing the direction of the helix axis within a very short distance. Much of the bending occurs at two large kinks where the base stacking is interrupted by intercalation of a proline residue. IHF contacts the DNA exclusively via the phosphodiester backbone and the minor groove and relies heavily on indirect readout to recognize its binding sequence. One such readout involves a six-base A tract, providing evidence for the importance of a narrow minor groove. C1 NIMH,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RP Rice, PA (reprint author), NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 66 TC 558 Z9 566 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 27 PY 1996 VL 87 IS 7 BP 1295 EP 1306 DI 10.1016/S0092-8674(00)81824-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WA541 UT WOS:A1996WA54100017 PM 8980235 ER PT J AU Puzianowska-Kuznicka, M Wong, JM Kanamori, A Shi, YB AF Puzianowska-Kuznicka, M Wong, JM Kanamori, A Shi, YB TI Functional characterization of a mutant thyroid hormone receptor in Xenopus laevis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOIC ACID RECEPTORS; TRANSCRIPTIONAL ACTIVATION; AMPHIBIAN METAMORPHOSIS; RESPONSE ELEMENTS; ONCOGENE PRODUCT; GENE-EXPRESSION; DIRECT REPEATS; X RECEPTORS; BETA; REPRESSION AB Thyroid hormone plays a causative role during frog metamorphosis, and its effect is mediated by thyroid hormone receptors (TRs), To investigate the function of Xenopus TRs, we have recently developed a thyroid hormone dependent in vivo transcription system by introducing TRs and RXRs (9-cis-retinoic acid receptors) into Xenopus oocytes. Interestingly, using this system, we have found that the TR alpha B cloned previously is defective in transcriptional activation compared with TR alpha A, In vitro DNA binding experiments show that TR alpha B . RXR heterodimers have drastically reduced affinity for a thyroid hormone response element, Site-directed mutagenesis shows that two of the seven amino acid residues that differ between TR alpha A and TR alpha B are responsible for the defect in TR alpha B function. These two residues affect the DNA binding by both TR . RXR heterodimers and TR homodimers, In contrast, heterodimer formation with RXRs is not affected as demonstrated by coimmunoprecipitation and dominant-transcriptional inhibition experiments, By cDNA and genomic DNA sequence analysis, we have demonstrated that the residues, which affect TR alpha B function when mutated, are identical between the wild type TR alpha B and TR alpha A, Thus, our experiments have discovered the first amphibian TR mutant, The DNA binding and transcription activation functions of the mutant are discussed in relation to the recently published TR crystal structure. C1 NICHHD, MOL EMBRYOL LAB, NIH, BETHESDA, MD 20892 USA. NATL RES INST AQUACULTURE, TAMAKI, MIE 51904, JAPAN. NR 42 TC 9 Z9 9 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 1996 VL 271 IS 52 BP 33394 EP 33403 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA713 UT WOS:A1996WA71300035 PM 8969201 ER PT J AU Pelton, JG Torchia, DA Remington, SJ Murphy, KP Meadow, ND Roseman, S AF Pelton, JG Torchia, DA Remington, SJ Murphy, KP Meadow, ND Roseman, S TI Structures of active site histidine mutants of IIIGlc, a major signal-transducing protein in Escherichia coli - Effects on the mechanism of regulation and phosphoryl transfer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; BACTERIAL PHOSPHOTRANSFERASE SYSTEM; 3-DIMENSIONAL NMR-SPECTROSCOPY; HYDROGEN-BONDING INTERACTIONS; ALPHA-LYTIC PROTEASE; PHOSPHOCARRIER PROTEIN; BACILLUS-SUBTILIS; GLUCOSE PERMEASE; IIA-DOMAIN; SUGAR-TRANSPORT AB IIIGlc (also called IIA(Glc)), a major signal-transducing protein in Escherichia coli, is also a phosphorylcarrier in glucose uptake, The crystal and NMR structures of IIIGlc show that His(90), the phosphoryl acceptor, adjoins His(75) in the active site, Glutamine was substituted for His-, giving (IIIGlc)-I-H75Q and (IIIGlc)-I-H90Q, respectively (Presper, K. A., Wong, C.-Y., Liu, L., Meadow, N. D., and Roseman, S. (1989) Proc, Natl. Acad. Sci. U.S.A. 86, 4052-4055), but the mutants showed unexpected properties, (IIIGlc)-I-H90Q loses regulatory functions of IIIGlc, and the phosphoryltransfer rates between Hpr/(IIIGlc)-I-H75Q are 200-fold less than HPr/IIIGlc (Meadow, N. D., and Roseman, S. (1996) J. Biol. Chem. 271, 33440-33445), X-ray crystallography, differential scanning calorimetry, and NMR have now been used to determine the structures of the mutants (phospho-(IIIGlc)-I-H75Q was studied by NMR), The three methods gave completely consistent results. Except for the His to Gin substitutions, the only significant structural changes were in a few hydrogen bonds, (IIIGlc)-I-H90Q contains two structured water molecules (to Gln(90)), which could explain its inability to regulate glycerol kinase. Phospho-IIIGlc contains a chymotrypsin like, hydrogen bond network (Thr(73)-His(75) -O(-)phosphoryl), whereas phospho-(IIIGlc)-I-H75Q contains only one bond (Gln(75)-O--phosphoryl), Hydrogen bonds play an essential role in a proposed mechanism for the phosphoryltransfer reaction. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,MCCOLLUM PRATT INST,BALTIMORE,MD 21218. NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. UNIV OREGON,DEPT PHYS,EUGENE,OR 97403. UNIV IOWA,DEPT BIOCHEM,IOWA CITY,IA 52242. FU NIGMS NIH HHS [GM38759, GM42618] NR 63 TC 15 Z9 15 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 DEC 27 PY 1996 VL 271 IS 52 BP 33446 EP 33456 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA713 UT WOS:A1996WA71300042 PM 8969208 ER PT J AU Simpson, PB Russell, JT AF Simpson, PB Russell, JT TI Mitochondria support inositol 1,4,5-trisphosphate-mediated Ca2+ waves in cultured oligodendrocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTRACELLULAR CALCIUM-CONCENTRATION; ENDOPLASMIC-RETICULUM; PHOSPHOINOSITIDE HYDROLYSIS; RAT OLIGODENDROCYTES; ASTROCYTES; CELLS; RECEPTORS; NEURONS; AGONIST; LOCALIZATION AB We have examined the spatial and temporal nature of Ca2+ signals activated via the phosphoinositide pathway in oligodendrocytes and the cellular specializations underlying oligodendrocyte Ca2+ response characteristics. Cultured cortical oligodendrocytes were incubated with fluo 3 or fura 2, and digital video fluorescence microscopy was used to study the effect of methacholine on [Ca2+](i). Single peaks, oscillations, and steady-state plateau [Ca2+](i) elevations were evoked by increasing agonist concentration. The peaks and oscillations were found to be Ca2+ wave fronts, which propagate via distinct amplification regions in the cell where the kinetics of Ca2+ release (amplitude and rate of rise of response) are elevated. Staining with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolecarbocyanine iodide (JC-1) and 3,3'-dihexyloxacarbocyanine iodide revealed that mitochondria are found in groups of three or more in oligodendrocyte processes and that the groups are distributed with considerable distance separating them. Cross-correlation analysis showed a high degree of correlation between sites where mitochondria are present and peaks in the amplitude and rate of rise of the Ca2+ response. Intramitochondrial Ca2+ concentration, measured using rhod 2, increased upon treatment with methacholine. Methacholine also evoked a rapid change in mitochondrial membrane potential as measured by the J-aggregate fluorescence of JC-1. Pretreatment with the mitochondrial inhibitors carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (1 mu M, 2 min) or antimycin (2 mu g/ml, 2 min) altered the methacholine-evoked Ca2+ response in most cells studied, responses being either markedly potentiated or inhibited. The results of this study demonstrate that stimulation of phosphoinositide-coupled muscarinic acetylcholinoceptors activates propagating Ca2+ wave fronts in oligodendrocytes and that the characteristics of these waves are dependent on mitochondrial location and function. C1 NICHHD,LCMN,NIH,BETHESDA,MD 20892. NR 46 TC 127 Z9 129 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 DEC 27 PY 1996 VL 271 IS 52 BP 33493 EP 33501 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA713 UT WOS:A1996WA71300047 PM 8969213 ER PT J AU Sax, CM Salamon, C Kays, WT Guo, J Yu, FSX Cuthbertson, RA Piatigorsky, J AF Sax, CM Salamon, C Kays, WT Guo, J Yu, FSX Cuthbertson, RA Piatigorsky, J TI Transketolase is a major protein in the mouse cornea SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WERNICKE-KORSAKOFF SYNDROME; ADENYLATE-CYCLASE ACTIVITY; LENS CRYSTALLINS; ALDEHYDE DEHYDROGENASE; GLUTATHIONE-PEROXIDASE; SUPEROXIDE-DISMUTASE; HUMAN-ERYTHROCYTES; EYE; EPITHELIUM; EXPRESSION AB Earlier experiments in this laboratory identified a highly expressed 65-68-kDa protein in both mouse and human corneas (Cuthbertson, R. A., Tomarev, S. I., and Piatigorsky J. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4004-4008). Here, we demonstrate that this protein is transketolase (TKT; EC 2.2.1.1), an enzyme in the nonoxidative branch of the pentose-phosphate pathway, based on peptide and cDNA isolation and sequence analysis of mouse cornea protein and RNA samples, respectively. While expressed at low levels in a number of tissues, the 2.1-kilobase TKT mRNA was expressed at a 50-fold higher level in the adult mouse cornea. The area of most abundant expression was localized to the cornea epithelial cell layer by in situ hybridization. Western blot analysis confirmed TKT protein abundance in the cornea and indicated that TKT may comprise as much as 10% of the total soluble protein of the adult mouse cornea. Soluble cornea extracts exhibited a correspondingly high level of TKT enzymatic activity. TKT expression increased progressively through cornea maturation, as shown by Northern blot, in situ hybridization, Western blot, and enzymatic analyses. TKT mRNA and protein were expressed at low levels in the cornea prior to eye opening, while markedly increased levels were observed after eye opening. Taken together, these observations suggest that TKT may be a cornea enzyme-crystallin, and suggest that the crystallin paradigm and concept of gene sharing, once thought to be restricted to the lens, apply to other transparent ocular tissues. C1 HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA 02114. RP Sax, CM (reprint author), NEI,MOL & DEV BIOL LAB,NIH,MSC 2730,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY10869] NR 71 TC 61 Z9 63 U1 0 U2 3 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 DEC 27 PY 1996 VL 271 IS 52 BP 33568 EP 33574 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA713 UT WOS:A1996WA71300057 PM 8969223 ER PT J AU Zhang, SY Coso, OA Lee, CH Gutkind, JS Simonds, WF AF Zhang, SY Coso, OA Lee, CH Gutkind, JS Simonds, WF TI Selective activation of effector pathways by brain-specific G protein beta(5) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; GAMMA-SUBUNITS; PHOSPHOLIPASE-C; SIGNALING PATHWAY; KINASE ACTIVATION; ADENYLYL CYCLASE; ALPHA-SUBUNIT; BINDING; STIMULATION; EXPRESSION AB While multiple G protein beta and gamma subunit isoforms have been identified, the implications of this potential diversity of beta gamma heterodimers for signaling through beta gamma-regulated effector pathways remains unclear. Furthermore the molecular mechanism(s) by which the beta gamma complex modulates diverse mammalian effector molecules is unknown. Effector signaling by the structurally distinct brain-specific beta(5) subunit was assessed by transient cotransfection with gamma(2) in COS cells and compared with beta(1). Transfection of either beta(1) or beta(5) with gamma(2) stimulated the activity of cotransfected phospholipase C-beta(2) (PLC-beta(2)), as previously reported, In contrast, cotransfection of beta(1) but not beta(5) with gamma(2) stimulated the mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) pathways even though the expression of beta(5) in COS cells was evident by immunoblotting. The G protein beta(5) expressed in transfected COS cells was properly folded as its pattern of stable C-terminal proteolytic fragments was identical to that of native brain beta(5). The inability of beta(5) to activate the MAPK and JNK pathways was not overcome by cotransfection with three additional G gamma isoforms. These results suggest it is the G beta subunit which determines the pattern of downstream signaling by the beta gamma complex and imply that the structural features of the beta gamma complex mediating effector regulation may differ among effectors. C1 NIDDK,METAB RES BRANCH,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,MOL SIGNALLING UNIT,NIH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 54 TC 74 Z9 74 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 DEC 27 PY 1996 VL 271 IS 52 BP 33575 EP 33579 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA713 UT WOS:A1996WA71300058 PM 8969224 ER PT J AU Rixe, O Ortuzar, W Alvarez, M Parker, R Reed, E Paull, K Fojo, T AF Rixe, O Ortuzar, W Alvarez, M Parker, R Reed, E Paull, K Fojo, T TI Oxaliplatin, tetraplatin, cisplatin, and carboplatin: Spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's Anticancer Drug Screen panel SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE platinum; oxaliplatin; cisplatin; platinum resistance; drug screen; drug discovery ID OVARIAN-CARCINOMA XENOGRAFTS; ANTITUMOR-ACTIVITY; GLUTATHIONE DEPLETION; CROSS-RESISTANCE; PLATINUM ANALOGS; AMPHOTERICIN-B; CYTO-TOXICITY; PHASE-I; ACCUMULATION; CYTOTOXICITY AB The present study was designed to explore the activity of platinum compounds in cisplatin-resistant cell lines, the unselected cell lines of the National Cancer Institute's Anticancer Drug Screen, and the potential for use in combination. The activities of four platinum compounds in cisplatin-resistant KB and A2780 cells were investigated. The cells were highly resistant to cisplatin and cross-resistant to carboplatin, but less than one tenth as resistant to oxaliplatin and tetraplatin. Cellular accumulation of all platinum compounds was decreased in both resistant cell lines. When the activities of cisplatin and oxaliplatin were evaluated in the National Cancer Institute's Anticancer Drug Screen, marked differences were observed. Evaluation of the activity profile using the COMPARE program revealed a different pattern for both agents: the cisplatin activity profile was similar to those of other diamine platinum compounds, alkylating agents including melphalan, and camptothecin analogs, whereas the activity profile of oxaliplatin resembled those of other ''dach'' (diaminocyclohexane) platinum compounds and of acridine derivatives. The sensitivity profiles are influenced by the target(s)/mechanism(s) of action and the mechanism(s) of resistance of a drug. The dissimilarity in profiles suggests that these two platinum compounds have a different target(s)/mechanism(s) of action, a different mechanism(s) of resistance, or most likely both. Studies evaluating combinations of cisplatin/oxaliplatin suggest that the activities of these two agents are at least additive and possibly synergistic. Oxaliplatin has a different spectrum of activity and low cross resistance to cisplatin and should be valuable in cisplatin refractory patients or in combination with cisplatin. Copyright (C) 1996 Elsevier Science Inc. C1 NCI, NIH, DIV CLIN SCI, MED BRANCH, BETHESDA, MD 20892 USA. HOP LA PITIE SALPETRIERE, MED ONCOL SERV, F-75651 PARIS, FRANCE. NCI, NIH, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. NR 48 TC 431 Z9 449 U1 6 U2 58 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 24 PY 1996 VL 52 IS 12 BP 1855 EP 1865 DI 10.1016/S0006-2952(97)81490-6 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VV550 UT WOS:A1996VV55000007 PM 8951344 ER PT J AU Levine, RL Mosoni, L Berlett, BS Stadtman, ER AF Levine, RL Mosoni, L Berlett, BS Stadtman, ER TI Methionine residues as endogenous antioxidants in proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN ALPHA-1-PROTEINASE INHIBITOR; COLI GLUTAMINE-SYNTHETASE; METAL-CATALYZED OXIDATION; ESCHERICHIA-COLI; SULFOXIDE FORMATION; INACTIVATION; DISSOCIATION; PROTEOLYSIS; PROTEASE; ACID AB Cysteine and methionine are the two sulfur-containing residues normally found in proteins, Cysteine residues function in the catalytic cycle of many enzymes, and they can form disulfide bonds that contribute to protein structure. In contrast, the specific functions of methionine residues are not known. We propose that methionine residues constitute an important antioxidant defense mechanism, A variety of oxidants react readily with methionine to farm methionine sulfoxide, and surface exposed methionine residues create an extremely high concentration of reactant, available as an efficient oxidant scavenger, Reduction back Po methionine by methionine sulfoxide reductases would allow the antioxidant system to function catalytically. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coli was studied as an in vitro model system, Eight of the 16 methionine residues could he oxidized with little effect on catalytic activity of the enzyme, The oxidizable methionine residues were found to be relatively surface exposed, whereas the intact residues were generally buried within the core of the protein. Furthermore, the susceptible residues were physically arranged in an array that guarded the entrance to the active site. RP Levine, RL (reprint author), NHLBI, BIOCHEM LAB, NIH, 3 CTR DR, MSC 0320, BETHESDA, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 28 TC 628 Z9 646 U1 2 U2 56 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 DEC 24 PY 1996 VL 93 IS 26 BP 15036 EP 15040 DI 10.1073/pnas.93.26.15036 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400010 PM 8986759 ER PT J AU Guimaraes, MJ Peterson, D Vicari, A Cocks, BG Copeland, NG Gilbert, DJ Jenkins, NA Ferrick, DA Kastelein, RA Bazan, JF Zlotnik, A AF Guimaraes, MJ Peterson, D Vicari, A Cocks, BG Copeland, NG Gilbert, DJ Jenkins, NA Ferrick, DA Kastelein, RA Bazan, JF Zlotnik, A TI Identification of a novel selD homolog from Eukaryotes, Bacteria, and Archaea: Is there an autoregulatory mechanism in selenocysteine metabolism? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID 3' UNTRANSLATED REGION; SELENOPROTEIN SYNTHESIS; SECONDARY STRUCTURE; SELENIUM DONOR; MESSENGER-RNA; GENE-PRODUCT; SEQUENCES; ENZYMES; CELLS; MOUSE AB Escherichia coli selenophosphate synthetase (SPS, the selD gene product) catalyzes the production of monoselenophosphate, the selenium donor compound required for synthesis of selenocysteine (Sec) and seleno-tRNAs. We report the molecular cloning of human kind mouse homologs of the selD gene, designated Sps2, which contains an in-frame TGA codon at a site corresponding to the enzyme's putative active site, These sequences allow the identification of selD gene homologs in the genomes of the bacterium Haemophilus influenzae and the archaeon Methanococcus jannaschii, which had been previously misinterpreted due to their in-frame TGA codon. Sps2 mRNA levels are elevated in organs previously implicated in the synthesis of selenoproteins and in active sites of blood cell development. In addition, we show that Sps2 mRNA is up-regulated upon activation of T lymphocytes and have mapped the Sps2 gene to mouse chromosome 7. Using the mouse gene isolated from the hematopoietic cell line FDCPmixA4, we devised a construct for protein expression that results in the insertion of a FLAG Lag sequence at the N terminus of the SPS2 protein, This strategy allowed us to document: the readthrough of the in-frame TGA codon and the incorporation of Se-75 into SPS2. These results suggest the existence of an autoregulatory mechanism involving the incorporation of Sec into SPS2 that might be relevant to blood cell biology. This mechanism is likely to have been present in ancient life forms and conserved in a variety of living organisms from all domains of life. C1 DNAX RES INST MOL & CELLULAR BIOL INC, DEPT MOL BIOL, PALO ALTO, CA 94304 USA. DNAX RES INST MOL & CELLULAR BIOL INC, DEPT IMMUNOL, PALO ALTO, CA 94304 USA. NCI, ADV BIOSCI LABS, BASIC RES PROGRAM, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. LAWRENCE LIVERMORE NATL LAB, SCH VET MED, DEPT PATHOL MICROBIOL & IMMUNOL, DAVIS, CA 95616 USA. RI Bazan, J. Fernando/B-4562-2010; Zlotnik, Albert/C-3791-2011 NR 42 TC 154 Z9 161 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 1996 VL 93 IS 26 BP 15086 EP 15091 DI 10.1073/pnas.93.26.15086 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400019 PM 8986768 ER PT J AU DeVries, L Elenko, E Hubler, L Jones, TLZ Farquhar, MG AF DeVries, L Elenko, E Hubler, L Jones, TLZ Farquhar, MG TI GAIP is membrane-anchored by palmitoylation and interacts with the activated (GTP-bound) form of G alpha(i) subunits SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G protein; regulator of G-protein signaling; GTPase-activating protein; cysteine string ID CYSTEINE-STRING PROTEIN; NIH 3T3 CELLS; ENDOPLASMIC-RETICULUM; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; ADENYLYL CYCLASE; ESCHERICHIA-COLI; BETA-COP; GS-ALPHA; MUTATIONS AB GAIP (G Alpha Interacting Protein) is a member of the recently described RGS (Regulators of G-protein Signaling) family that was isolated by interaction cloning with the heterotrimeric G-protein G alpha(i3) and was recently shown to be a GTPase-activating protein (GAP). In AtT-20 cells stably expressing GAIP, we found that GAIP is membrane-anchored and faces the cytoplasm, because it was not released by sodium carbonate treatment but was digested by proteinase K, When Cos cells were transiently transfected with GAIP and metabolically labeled with [S-35]methionine, two pools of GAIP-a soluble and a membrane-anchored pool-were found, Since the N terminus of GAIP contains a cysteine string motif and cysteine string proteins are heavily palmitoylated, we investigated the possibility that membrane-anchored GAIP might be palmitoylated, We found that after labeling with [H-3] palmitic acid, the membrane-anchored pool but not the soluble pool was palmitoylated, In the yeast two-hybrid system, GAIP was found to interact specifically with members of the G alpha(i) subfamily, G alpha(i1), G alpha(i2), G alpha(i3), G alpha(z), and G alpha(o), but not with members of other G alpha subfamilies, G alpha(s), G alpha(q), and G alpha(12/13). The C terminus of G alpha(i3) is important for binding because a 10-aa C-terminal truncation and a point mutant of G alpha(i3) showed significantly diminished interaction, GAIP interacted preferentially with the activated (GTP) form of G alpha(i3), which is in keeping with its GAP activity, We conclude that GAIP is a membrane-anchored GAP with a cysteine string motif, This motif, present in cysteine string proteins found on synaptic vesicles, pancreatic zymogen granules, and chromaffin granules, suggests GAIP's possible involvement in membrane trafficking. C1 UNIV CALIF SAN DIEGO,DIV CELLULAR & MOL MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT PATHOL,LA JOLLA,CA 92093. NIDDK,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA58689, F32 CA066289]; NIDDK NIH HHS [R01 DK017780, DK17780]; NIGMS NIH HHS [GM07752, T32 GM007752] NR 56 TC 140 Z9 141 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 DEC 24 PY 1996 VL 93 IS 26 BP 15203 EP 15208 DI 10.1073/pnas.93.26.15203 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400040 PM 8986788 ER PT J AU Reiser, J Harmison, G KluepfelStahl, S Brady, RO Karlson, S Schubert, M AF Reiser, J Harmison, G KluepfelStahl, S Brady, RO Karlson, S Schubert, M TI Transduction of nondividing cells using pseudotyped defective high-titer HIV type 1 particles SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene therapy; quiescent cells; human skin fibroblasts; CD34(+) cells; cell cycle ID HUMAN-IMMUNODEFICIENCY-VIRUS; VESICULAR STOMATITIS-VIRUS; EFFICIENT GENE-TRANSFER; NUCLEAR-LOCALIZATION; MURINE RETROVIRUSES; HUMAN-LYMPHOCYTES; AIDS VIRUS; INFECTION; VECTORS; EXPRESSION AB The use of Moloney marine leukemia virus (Mo-MLV)-based vectors to deliver therapeutic genes into target cells is limited by their inability to transduce nondividing cells. To test the capacity of HIV-based vectors to deliver genes into nondividing cells, we have generated replication-defective HIV type 1 (HIV-1) reporter vectors carrying neomycin phosphotransferase or mouse heat stable antigen, replacing the HIV-1 sequences encoding gp160. These vectors also harbor inactive vpr, vpu, and nef coding regions, Pseudotyped HIV-1 particles carrying either the ecotropic or the amphotropic Mo-MLV envelope proteins or the vesicular stomatitis virus G protein were released after single or double transfections of either human 293T or monkey COS-7 cells with titers of up to 10(7) colony-forming units per milliliter, A simple ultrafiltration procedure resulted in an additional 10- to 20-fold concentration of the pseudotyped particles. These vectors along with Mo-MLV-based vectors were used to transduce primary human skin fibroblasts and human peripheral blood CD34(+) cells. The HIV-1 vector system was significantly more efficient than its Mo-MLV-based counterpart in transducing human skin fibroblasts arrested al the G(0)/G(1) stage of the cell. cycle by density-dependent inhibition of growth. Human CD34(+) cells were transduced efficiently using HIV-1 pseudotype particles without prior stimulation with cytokines. C1 NATL INST NEUROL DISORDERS & STROKE,LAB MOL MED & NEUROSCI,MOL & VIRAL GENET SECT,NIH,BETHESDA,MD 20892. RP Reiser, J (reprint author), NATL INST NEUROL DISORDERS & STROKE,DEV & METAB NEUROL BRANCH,MOL & MED GENET SECT,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 56 TC 256 Z9 263 U1 0 U2 4 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 DEC 24 PY 1996 VL 93 IS 26 BP 15266 EP 15271 DI 10.1073/pnas.93.26.15266 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400051 PM 8986799 ER PT J AU Moriuchi, H Moriuchi, M Combadiere, C Murphy, PM Fauci, AS AF Moriuchi, H Moriuchi, M Combadiere, C Murphy, PM Fauci, AS TI CD8(+) T-cell-derived soluble factor(s), but not beta-chemokines RANTES, MIP-1 alpha, an MIP-1 beta, suppress HIV-1 replication in monocyte/macrophages SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONONUCLEAR PHAGOCYTES; U1 CELLS; MACROPHAGES; EXPRESSION; INFECTION; TYPE-1; INTERLEUKIN-6; LYMPHOCYTES; MONOCYTES AB It has been demonstrated that CD8(+) T cells produce a soluble factor(s) that suppresses human immunodeficiency virus (HIV) replication in CD4(+) T cells. The role of soluble factors in the suppression of HIV replication in monocyte/macrophages (M/M) has not been fully delineated. To investigate whether a CD8(+) T-cell-derived soluble factor(s) can also suppress HIV infection in the M/M system, primary macrophages were infected with the macrophage tropic HIV-1 strain Ba-L. CD8(+) T-cell-depleted peripheral blood mononuclear cells were also infected with HIV-1 IIIB or Ba-L. HIV expression from the chronically infected macrophage cell line U1 was also determined in the presence of CD8(+) T-cell supernatants or beta-chemokines. We demonstrate that: (i) CD8(+) T-cell supernatants did, but beta-chemokines did not, suppress HIV replication in the M/M system; (ii) antibodies to regulated on activation normal T-cell expressed and Secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta did not, whereas antibodies to interleukin 10, interleukin 13, interferon alpha, or interferon gamma modestly reduced anti-HIV activity of the CD8(+) T-cell supernatants; and (iii) the CD8(+) T-cell supernatants did, but beta-chemokines did not, suppress HIV-1 IIIB replication in peripheral blood mononuclear cells as well as HIV expression in U1 cells. These results suggest that HIV-suppressor activity of CD8(+) T cells is a multifactorial phenomenon, and that RANTES, MIP-1 alpha, and MIP-1 beta do not account for the entire scope of CD8(+) T-cell-derived HIV-suppressor factors. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. RP Moriuchi, H (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 6A-11,10 CTR DR,MSC-1576,BETHESDA,MD 20892, USA. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 32 TC 141 Z9 142 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 DEC 24 PY 1996 VL 93 IS 26 BP 15341 EP 15345 DI 10.1073/pnas.93.26.15341 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400065 PM 8986813 ER PT J AU Farci, P Shimoda, A Wong, D Cabezon, T DeGioannis, D Strazzera, A Shimizu, Y Shapiro, M Alter, HJ Purcell, RH AF Farci, P Shimoda, A Wong, D Cabezon, T DeGioannis, D Strazzera, A Shimizu, Y Shapiro, M Alter, HJ Purcell, RH TI Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NON-B HEPATITIS; HUMORAL IMMUNE-RESPONSE; NON-A; GLYCOPROTEIN GP70; GENETIC DRIFT; ANTIBODY; E2/NS1; GENOME; NEUTRALIZATION; PREVALENCE AB The identification of the neutralization domains of hepatitis C virus (HCV) is essential for the development of an effective vaccine. sere, we show that the hypervariable region 1 (HVR1) of the envelope 2 (E2) protein is a critical neutralization domain of HCV. Neutralization of HCV in vitro was attempted with a rabbit hyperimmune serum raised against a homologous synthetic peptide derived from the HVR1 of the E2 protein, and the residual infectivity was evaluated by inoculation of HCV-seronegative chimpanzees. The source of HCV was plasma obtained from a patient (H) during the acute phase of posttransfusion non-A, non-B hepatitis, which hall been titered for infectivity in chimpanzees. The anti-HVR1 antiserum induced protection against homologous HCV infection in chimpanzees, but not against the emergence of neutralization escape mutants that were found to be already present in the complex viral quasispecies of the inoculum. The finding that HVR1 can elicit protective immunity opens new perspectives for the development of effective preventive strategies. However, the identification of the most variable region of HCV as a critical neutralization domain poses a major challenge for the development of a broadly reactive vaccine against HCV. C1 SMITHKLINE BEECHAM BIOL,B-1330 RIXENSART,BELGIUM. UNIV CAGLIARI,IST MED INTERNA,I-09124 CAGLIARI,ITALY. UNIV TOKYO,DEPT BACTERIOL,TOKYO 113,JAPAN. BIOEQUAL INC,ROCKVILLE,MD 20852. NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP Farci, P (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,NIH,BLDG 7,ROOM 200,7 CTR DR,MSC 0740,BETHESDA,MD 20892, USA. RI Cheng, Yushao/E-6256-2011 NR 37 TC 436 Z9 459 U1 0 U2 5 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 DEC 24 PY 1996 VL 93 IS 26 BP 15394 EP 15399 DI 10.1073/pnas.93.26.15394 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC204 UT WOS:A1996WC20400074 PM 8986822 ER PT J AU Steiner, H Gerfen, CR AF Steiner, H Gerfen, CR TI Dynorphin regulates D1 dopamine receptor-mediated responses in the striatum: Relative contributions of pre- and postsynaptic mechanisms in dorsal and ventral striatum demonstrated by altered immediate-early gene induction SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE c-fos; zif 268; kappa receptor; opioid; gene expression ID KAPPA-OPIOID RECEPTOR; IN-SITU HYBRIDIZATION; RAT NUCLEUS-ACCUMBENS; FACTOR MESSENGER-RNAS; C-FOS EXPRESSION; STRIATONIGRAL DYNORPHIN; DIFFERENTIALLY ALTERS; INSITU HYBRIDIZATION; SUBSTANTIA-NIGRA; OPIATE AGONISTS AB Dynorphin, an endogenous kappa opioid receptor ligand, acts in the striatum to regulate the response of striatonigral neurons to D1 dopamine receptor stimulation. We investigated the relative contributions of both presynaptic kappa receptors on dopamine terminals and postsynaptic kappa receptors on striatal neurons by analyzing opioid regulation of D1 effects in the absence of presynaptic kappa receptors, after B-hydroxydopamine depletion of striatal dopamine. D1-receptor-mediated immediate-early gene induction was measured by using in situ hybridization histochemistry. First, repeated treatment with the Dm-receptor agonist SKF-38393 (2 mg/kg/day, 3-14 days) was used to increase dynorphin levels in rats with dopamine depletions. In the nucleus accumbens, increased dynorphin expression was accompanied by reduced induction of the immediate-early genes c-fos and zif 268 by SKF-38393. In contrast, in dorsal/lateral aspects of the dopamine-depleted striatum, this Dm response was sustained despite a large increase in dynorphin expression, These results are consistent with a requirement of dopamine terminals (presynaptic kappa receptors) for the inhibitory action of dynorphin in the dorsal/lateral striatum, but not in the ventral striatum. Second, the kappa receptor agonist spiradoline (1-10 mg/kg) reduced c-fos and zif 268 induction by SKF-38393 (2.5 mg/kg) preferentially in ventral parts of the dopamine-depleted striatum, which contain higher levels of kappa receptor mRNA and binding. These results also indicate that postsynaptic kappa receptors contribute to the inhibition of the D1 response at least in the ventral striatum. Together, these results indicate that dynorphin in the striatum functions to regulate dopamine input to striatonigral neurons, acting at both pre- and postsynaptic sites, and that the relative contributions of these mechanisms differ between dorsal and ventral striatal regions. (C) 1996 Wiley-Liss, Inc. C1 NIMH,LNP,BETHESDA,MD 20892. NR 73 TC 60 Z9 61 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 DEC 23 PY 1996 VL 376 IS 4 BP 530 EP 541 DI 10.1002/(SICI)1096-9861(19961223)376:4<530::AID-CNE3>3.0.CO;2-2 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VZ433 UT WOS:A1996VZ43300003 PM 8978468 ER PT J AU Dunn, SE Cullen, JM AF Dunn, SE Cullen, JM TI Woodchuck p-glycoprotein found in virus-induced hepatocellular carcinomas binds anticancer drugs SO CANCER LETTERS LA English DT Article DE multidrug resistance; viral carcinogenesis; liver; animal model; p-glycoprotein ID MULTIDRUG RESISTANCE; CANCER; DNA AB Virally-induced hepatocellular carcinomas (HCC) are intrinsically resistant to cancer chemotherapy partly due to increased expression of p-glycoprotein (pgp). In this study, we determined that pgp expressed in woodchuck HCC had binding properties were similar to the drug resistant human pgp. Pgp drug binding properties were characterized by photoaffinity labeling with the calcium channel blocker [H-3]azidopine (AZD). AZD bound pgp in HCC but not in non-tumor liver samples, and binding was confirmed by competition with Adriamycin (IC50 = 10 mu M) and actinomycin D (IC50 = 1 mu M). In summary, WHV-induced HCC overexpress a pgp which binds anticancer drugs suggesting a common pathway for drug resistance. C1 N CAROLINA STATE UNIV,COLL VET MED,DEPT MICROBIOL PATHOL & PARASITOL,RALEIGH,NC 27606. RP Dunn, SE (reprint author), NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. NR 11 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 20 PY 1996 VL 110 IS 1-2 BP 177 EP 180 DI 10.1016/S0304-3835(96)04488-6 PG 4 WC Oncology SC Oncology GA WD796 UT WOS:A1996WD79600025 PM 9018098 ER PT J AU Page, JE Pataki, J Harvey, RG Dipple, A AF Page, JE Pataki, J Harvey, RG Dipple, A TI Mutational specificity of the syn 1,2-dihydrodiol 3,4-epoxide of 5-methylchrysene SO CANCER LETTERS LA English DT Article DE mutational spectra; dihydrodiol epoxide; 5-methylchrysene ID SHUTTLE VECTOR; NEWBORN MICE; TUMORIGENICITY; MUTAGENESIS; DIHYDRODIOL; EPOXIDES AB The mutational specificity of the syn dihydrodiol epoxide of 5-methylchrysene in the supF gene of the pSP189 vector was examined. Transversion mutations at GC pairs predominated with G --> T and G --> C changes accounting for 42 and 21% of total base change mutations. The types of mutations found reflect the previously determined chemical preference of this reactive species for reaction with deoxyguanosine residues in DNA. C1 NCI, ABL BASIC RES PROGRAM, CHEM CARCINOGENESIS LAB, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. UNIV CHICAGO, BEN MAY INST, CHICAGO, IL 60637 USA. NR 18 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 20 PY 1996 VL 110 IS 1-2 BP 249 EP 252 DI 10.1016/S0304-3835(96)04506-5 PG 4 WC Oncology SC Oncology GA WD796 UT WOS:A1996WD79600036 PM 9018109 ER PT J AU George, A Bannon, L Sabsay, B Dillon, JW Malone, J Veis, A Jenkins, NA Gilbert, DJ Copeland, NG AF George, A Bannon, L Sabsay, B Dillon, JW Malone, J Veis, A Jenkins, NA Gilbert, DJ Copeland, NG TI The carboxyl-terminal domain of phosphophoryn contains unique extended triplet amino acid repeat sequences forming ordered carboxyl-phosphate interaction ridges that may be essential in the biomineralization process SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE DENTIN PHOSPHOPHORYN; RAT INCISOR DENTIN; IMPERFECTA TYPE-II; PHOSPHOPROTEIN; LOCALIZATION; PROTEINS; LOCUS; GENE; ORGANIZATION; INDUCTION AB Phosphophoryns (PPs), a family of Asp and Ser(P)-rich dentin proteins, are considered to be archetypal regulators of several aspects of extracellular matrix (ECM) biomineralization. We have cloned a rat incisor PP gene, Dmp2, from our odontoblast cDNA library and localized it to mouse chromosome 5q21 within 2 centimorgans of Dmp1, another tooth-specific ECM protein. The carboxyl-terminal region of Dmp2 protein (60 residue % Ser, 31 residue % Asp) is divided into two domains, one with unique repetitive blocks of [DSS](n,3 less than or equal to 14), the other with [SD](m = 2,3). Conformational analysis shows the phosphorylated form of the [DS*S*](n) repeats to have a unique structure with well defined ridges of phosphates and carboxyls available for counter ion binding. The [S*D](m) domains have different phosphate and carboxylate interaction edges and thus different calcium ion and apatite surface binding properties. These two domains and the colocalization of Dmp1 and Dmp2 genes at a position equivalent to the dentinogenesis imperfecta type II location on human 4q21 all suggest that the PPs are indeed involved in some aspect of ECM mineralization. C1 NORTHWESTERN UNIV,CHICAGO,IL 60611. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,NIH,FREDERICK,MD 21702. OI GEORGE, ANNE/0000-0002-9008-7642 FU NIDCR NIH HHS [DE 01374, DE 07201] NR 32 TC 149 Z9 151 U1 0 U2 9 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 DEC 20 PY 1996 VL 271 IS 51 BP 32869 EP 32873 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ373 UT WOS:A1996VZ37300061 PM 8955126 ER PT J AU Lee, KP Carlson, LM Woodcock, JB Ramachandra, N Schultz, TL Davis, TA Lowe, JB Thompson, CB Larsen, RD AF Lee, KP Carlson, LM Woodcock, JB Ramachandra, N Schultz, TL Davis, TA Lowe, JB Thompson, CB Larsen, RD TI Molecular cloning and characterization of CFT1, a developmentally regulated avian alpha(1,3)-fucosyltransferase gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIALYL-LEWIS-X; HUMAN ALPHA(1,3)FUCOSYLTRANSFERASE GENE; ELAM-1-DEPENDENT CELL-ADHESION; CARBOHYDRATE ANTIGEN; FUCOSYL-TRANSFERASE; EMBRYONIC ANTIGEN; ALPHA(1,3)-FUCOSYL-TRANSFERASE GENE; DIFFERENTIAL EXPRESSION; DETERMINES EXPRESSION; MONOCLONAL-ANTIBODY AB Although coordinate expression of carbohydrate epitopes during development is well described, mechanisms which regulate this expression remain largely unknown. In this study we demonstrate that developing chicken B cells express the Lewis(x) terminal oligosaccharide structure in a stage-specific manner. To examine regulation of this expression, we have cloned and expressed the chicken alpha(1,3)-fucosyltransferase gene involved in Lewis(x) biosynthesis, naming it chicken fucosyltransferase 1 (CFT1), CFT1 is characterized by a single long open reading frame of 356 amino acids encoding a type II transmembrane glycoprotein. The domain structure and predicted amino acid sequence are highly conserved between CFT1 and mammalian Fuc-TIV genes (52.8% and 46.3% identity to mouse and human respectively). In vitro CFT1 fucosyltransferase activity utilizes LacNAc > 3'sialyl-LacNAc accepters with almost no utilization of other neutral type II (lactose, 2-fucosyllactose), or type I (lacto-N-biose I) accepters, CFT1-transfected cells make cell surface Lewis(x) (COS-7) and Lewis(x) + VIM-2 structures (Chinese hamster ovary). CFT1 gene expression is tissue-specific and includes embryonic thymus and bursa. Furthermore, expression of the CFT1 gene and cell surface Lewis(x) structures are closely linked during B cell development. These findings reveal the evolutionary conservation between nonmammalian and mammalian alpha(1,3)-fucosyltransferase genes and demonstrate a role for fucosyltransferase gene regulation in the developmental expression of oligosaccharide structures. C1 UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. NIAID,NIH,BETHESDA,MD 20892. GLYCOMED INC,ALAMEDA,CA 94501. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MOL GENET & CELL BIOL,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MED,GWENN KNAPP CTR LUPUS & IMMUNOL RES,CHICAGO,IL 60637. RP Lee, KP (reprint author), USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,RM 228,BLDG 18,8901 WISCONSIN AVE,BETHESDA,MD 20889, USA. NR 61 TC 26 Z9 26 U1 1 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 DEC 20 PY 1996 VL 271 IS 51 BP 32960 EP 32967 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ373 UT WOS:A1996VZ37300074 PM 8955139 ER PT J AU Das, K Ding, JP Hsiou, Y Clark, AD Moereels, H Koymans, L Andries, K Pauwels, R Janssen, PAJ Boyer, PL Clark, P Smith, RH Smith, MBK Michejda, CJ Hughes, SH Arnold, E AF Das, K Ding, JP Hsiou, Y Clark, AD Moereels, H Koymans, L Andries, K Pauwels, R Janssen, PAJ Boyer, PL Clark, P Smith, RH Smith, MBK Michejda, CJ Hughes, SH Arnold, E TI Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE antiviral inhibitors; reverse transcriptase; drug resistance; protein structure; drug design ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; NONNUCLEOSIDE INHIBITORS; MACROMOLECULAR STRUCTURES; ANGSTROM RESOLUTION; MUTATIONS; MECHANISM; THERAPY; POTENT; DERIVATIVES AB Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is an important target for chemotherapeutic agents used in the treatment of AIDS; the TIBO compounds are potent non-nucleoside inhibitors of HIV-1 RT (NNRTls). Crystal structures of HIV-1 RT complexed with 8-Cl TIBO (R86183, IC50 = 4.6 nM) and 9-Cl TIBO (R82913, IC50 = 33 nM) have been determined at 3.0 Angstrom resolution. Mutant HIV-1 RT, containing Cys in place of Tyr at position 181 (Tyr181Cys), is highly resistant to many NNRTIs and HIV-1 variants containing this mutation have been selected in both cell culture and clinical trials. We also report the crystal structure of Tyr181Cys HIV-1 RT in complex with 8-Cl TIBO (IC50 = 130 nM) determined at 3.2 Angstrom resolution. Averaging of the electron density maps computed for different HIV-1 RT/NNRTI complexes and from diffraction datasets obtained using a synchrotron source from frozen (-165 degrees C) and cooled (-10 degrees C) crystals of the same complex was employed to improve the quality of electron density maps and to reduce model bias. The overall locations and conformations of the bound inhibitors in the complexes containing wild-type HIV-1 RT and the two TIBO inhibitors are very similar, as are the overall shapes and volumes of the non-nucleoside inhibitor-binding pocket (NNIBP). The major differences between the two wild-type HIV-1 RT/TIBO complexes occur in the vicinity of the TIBO chlorine substituents and involve the polypeptide segments around the beta 5-beta 6 connecting loop (residues 95 to 105) and the beta 13-beta 14 hairpin (residues 235 and 236). In all known structures of HIV-1 RT/NNRTI complexes, including these two, the position of the beta 12-beta 13 hairpin or the ''primer grip'' is significantly displaced relative to the position in the structure of HIV-1 RT complexed with a double-stranded DNA and in unliganded HIV-1 RT structures. Since the primer grip helps to position the template-primer, this displacement suggests that binding of NNRTIs would affect the relative positions of the primer terminus and the polymerase active site. This could explain biochemical data showing that NNRTI binding to HIV-1 RT reduces efficiency of the chemical step of DNA polymerization, but does not prevent binding of either dNTPs or DNA. When the structure of the Tyr181Cys mutant HIV-1 RT in complex with 8-Cl TIBO is compared with the corresponding structure containing wild-type HIV-1 RT, the overall conformations of Tyr181Cys and wild-type HIV-1 RT and of the 8-Cl TIBO inhibitors are very similar. Some positional changes in the polypeptide backbone of the beta 6-beta 10-beta 9 sheet containing residue 181 are observed when the Tyr181Cys and wild-type complexes are compared, particularly near residue Val179 of beta 9. In the p51 subunit, the Cys181 side-chain is oriented in a similar direction to the Tyr181 side-chain in the wild-type complex. However, the electron density corresponding to the sulfur of the Cys181 side-chain in the p66 subunit is very weak, indicating that the thiol group is disordered, presumably because there is no significant interaction with either 8-Cl TIBO or nearby amino acid residues. III the mutant complex, there are slight rearrangements of the side-chains of other amino acid residues in the NNIBP and of the flexible dimethylallyl group of 8-Cl TIBO; these conformational changes could potentially compensate for the interactions that were lost when the relatively large tyrosine at position 181 was replaced by a less bulky cysteine residue. In the corresponding wild-type complex, Tyr181 in the p66 subunit has significant interactions with the bound inhibitor and the position of the Tyr181 side-chain is well defined in both subunits. Apparently the Tyr181-->Cys mutation eliminates favorable contacts of the aromatic ring of the tyrosine and the bound inhibitor, reducing the stability of NNRTI binding. This is consistent with the observation that the Tyr181Cys mutant HIV-1 RT is more resistant to NNRTIs that have extensive interactions with the Tyr181 side-chain. This interpretation is supported by a recent biochemical study which found that an NNRTI dissociates from its complex with Tyr181Cys HIV-1 RT faster than it does from a complex with wild-type HIV-1 RT. (C) 1996 Academic Press Limited C1 RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. JANSSEN RES FDN,CTR MOL DESIGN,B-2350 VOSELAAR,BELGIUM. JANSSEN RES FDN,B-2340 BEERSE,BELGIUM. TIBOTEC,INST ANTIVIRAL RES,B-2650 EDEGEM,BELGIUM. NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. FU NIAID NIH HHS [AI 27690, AI 36144] NR 61 TC 183 Z9 188 U1 1 U2 3 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 DEC 20 PY 1996 VL 264 IS 5 BP 1085 EP 1100 DI 10.1006/jmbi.1996.0698 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ951 UT WOS:A1996VZ95100018 PM 9000632 ER PT J AU Generoso, WM Sega, GA Lockhart, AM Hughes, LA Cain, KT Cacheiro, NLA Shelby, MD AF Generoso, WM Sega, GA Lockhart, AM Hughes, LA Cain, KT Cacheiro, NLA Shelby, MD TI Dominant lethal mutations, heritable translocations, and unscheduled DNA synthesis induced in male mouse germ cells by glycidamide, a metabolite of acrylamide SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE dominant lethal rest; heritable translocation test; UDS ID HEMOGLOBIN ADDUCT FORMATION; MALE-MICE; LOCUS MUTATIONS; INDUCTION; METHANESULFONATE; PROTAMINE; EXPOSURE; GENOTOXICITY; MUTAGENICITY; ETHYLATION AB The hypothesis that acrylamide induces dominant lethal mutations and heritable translocations in male mice, not through direct adduction, but by conversion to the reactive epoxide, glycidamide, was investigated. Three studies, namely, induction of dominant lethal mutations, heritable translocations, and unscheduled DNA synthesis in spermatids, which were conducted earlier in this laboratory for acrylamide, were also performed for glycidamide to determine its mutagenic properties and to compare responses. Results of these studies are consistent with the proposal that in vivo conversion to glycidamide is responsible for the mutagenicity of acrylamide in male mice. C1 OAK RIDGE NATL LAB,DIV CHEM & ANALYT SCI,OAK RIDGE,TN 37831. COMP SCI CORP,RES TRIANGLE PK,NC 27709. NIEHS,RES TRIANGLE PK,NC 27709. RP Generoso, WM (reprint author), OAK RIDGE NATL LAB,DIV BIOL,POB 2009,OAK RIDGE,TN 37831, USA. FU NIEHS NIH HHS [YIO-ES-20085] NR 29 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD DEC 20 PY 1996 VL 371 IS 3-4 BP 175 EP 183 DI 10.1016/S0165-1218(96)90106-8 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA WC890 UT WOS:A1996WC89000004 PM 9008719 ER PT J AU TitenkoHolland, N Levine, AJ Smith, MT Quintana, PJE Boeniger, M Hayes, R Suruda, A Schulte, P AF TitenkoHolland, N Levine, AJ Smith, MT Quintana, PJE Boeniger, M Hayes, R Suruda, A Schulte, P TI Quantification of epithelial cell micronuclei by fluorescence in situ hybridization (FISH) in mortuary science students exposed to formaldehyde SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE exfoliated cell; mortuary science student; micronuclei; FISH; formaldehyde ID EXFOLIATED HUMAN-CELLS; OCCUPATIONAL EXPOSURE; GASEOUS FORMALDEHYDE; LYMPHOCYTES; WORKERS; CANCER; CHROMOSOME; DAMAGE AB A micronucleus assay employing fluorescence in situ hybridization (FISH) with a centromeric probe was used on specimens of exfoliated buccal and nasal cells collected from mortuary science students exposed to embalming fluid containing formaldehyde. FISH labeling allowed micronuclei (MN) containing a whole chromosome (centromere-positive, MN(+)) to be differentiated from those containing only chromosomal fragments (centromere-negative, MN(-)). Each student was sampled before and after the 90 day embalming class. We determined if an increase in MN frequency could be attributed to formaldehyde exposure and was specific to either MN(+) or MN(-). In buccal cells, total MN frequency was significantly increased from 0.6/1000 to 2/1000 (p = 0.007) following the course, whereas in nasal cells it was not (2 and 2.5/1000, respectively, p = 0.2). Cells with multiple MN were present only in samples taken after exposure to embalming fluid. Although the baseline frequency was higher for MN(+) in both buccal (0.4/1000 for MN(+) and 0.1/1000 for MN(-)) and nasal cells (1.2/1000 for MN(+) and 0.5/1000 for MN(-)), the increase in MN frequency was greater for MN(-), (9-fold, p = 0.005 for buccal cells; 2-fold, p = 0.03 for nasal cells) than for MN(+) (> 2-fold, p = 0.08 for buccal cells; no change, p = 0.31 for nasal cells) in both tissues, Thus, the primary mechanism of micronucleus formation appeared to be chromosome breakage, This finding is consistent with known clastogenic properties of formaldehyde, the component of embalming fluid most likely responsible for micronucleus induction. C1 NIOSH,CINCINNATI,OH 45226. NCI,ROCKVILLE,MD 20892. RP TitenkoHolland, N (reprint author), UNIV CALIF BERKELEY,DIV ENVIRONM HLTH SCI,SCH PUBL HLTH,217 WARREN HALL,BERKELEY,CA 94720, USA. FU NIEHS NIH HHS [P30 ES01896, P42-ES04705] NR 34 TC 63 Z9 67 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD DEC 20 PY 1996 VL 371 IS 3-4 BP 237 EP 248 DI 10.1016/S0165-1218(96)90112-3 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA WC890 UT WOS:A1996WC89000010 PM 9008725 ER PT J AU Liechty, MC Crosby, H Murthy, A Davis, LM Caspary, WJ Hozier, JC AF Liechty, MC Crosby, H Murthy, A Davis, LM Caspary, WJ Hozier, JC TI Identification of a heteromorphic microsatellite within the thymidine kinase gene in L5178Y mouse lymphoma cells SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE L5178Y mouse lymphoma cell; Tk1; microsatellite; loss of heterozygosity; polymorphic probe ID TK-/ MUTANTS; TRIFLUOROTHYMIDINE-RESISTANT; ASSAY SYSTEM; CYTOGENETIC ANALYSIS; CHROMOSOME ANALYSIS; MAMMALIAN-CELLS; IN-SITU; MUTATIONS; LOCUS; POLYMORPHISMS AB The objective of this work is to identify a heteromorphism within the thymidine kinase (Tk1) gene which can be used to assay for allele loss by means of PCR. Intron F of mouse Tk1 contains two (CA), microsatellite sequences separated by 107 bp of non-repetitive sequence. We tested this region for heteromorphism in L5178Y mouse lymphoma cells. A PCR primer pair designated Agl1 yielded products of 396 and 194 bp from L5178Y tk(+/-) genomic DNA. The 194-bp product resulted from a secondary binding site between the two (CA), repeats for the forward Agl1 primer and was not produced from tk(-/-) mutants that had lost the functional Tk1(b) allele. Agl2 primers produced two PCR products of 523 and similar to 440 bp and Agl3 primers produced products of 579 and similar to 500 bp. In both these cases, the difference in product size was approximately equal, indicating that Intron F is similar to 80 bp shorter in the non-functional Tk1(a) allele than in Tk1(b). This heteromorphism forms the basis for an assay for allele loss by means of PCR. Agl1 and Agl3 primers yielded additional products of 91 and 274 bp, respectively, consistent with sizes expected from the mouse Tk1 pseudogenes (Tk1-ps), Our conclusions drawn from an analysis of 122 mutants for Tk1(b) loss using Agl2 primers agreed with previous analysis of the NcoI heteromorphism. Thus, a simple PCR-based analysis can identify Tk1(b) loss in the L5178Y mouse lymphoma cells. C1 NIH,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. RP Liechty, MC (reprint author), APPL GENET LABS INC,1335 GATEWAY DR,SUITE 2001,MELBOURNE,FL 32901, USA. NR 24 TC 12 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD DEC 20 PY 1996 VL 371 IS 3-4 BP 265 EP 271 DI 10.1016/S0165-1218(96)90115-9 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA WC890 UT WOS:A1996WC89000013 PM 9008728 ER PT J AU Rothman, RB Ayestas, M Baumann, MH AF Rothman, RB Ayestas, M Baumann, MH TI Phentermine pretreatment antagonizes the cocaine-induced rise in mesolimbic dopamine SO NEUROREPORT LA English DT Article DE cocaine; fenfluramine; in vivo microdialysis; phentermine; treatment agents ID SUICIDAL-BEHAVIOR; WEIGHT CONTROL; SEROTONIN; RATS; MICRODIALYSIS; WITHDRAWAL; DRUGS AB COADMINISTRATION Of phentermine and fenfluramine has been used to treat cocaine dependence. Patients who relapse while receiving this treatment report diminished subjective effects of cocaine. Due to the importance of mesolimbic dopamine (DA) in mediating cocaine reinforcement, we hypothesized that phentermine might attenuate the effects of cocaine on DA transmission. We examined this proposal directly using in vivo microdialysis methods in the nucleus accumbens of awake rats. Rats were pretreated with saline or phentermine (1 mg kg(-1), i.v.) and then challenged with cocaine (3 mg kg(-1), i.v.). Phentermine alone caused a modest increase in DA, and phentermine pretreatment substantially reduced the cocaine-induced rise in extracellular DA. Phentermine did not alter the stimulatory effect of cocaine on 5-HT. Our findings suggest that phentermine may antagonize the subjective effects of cocaine in humans via a DA mechanism. RP Rothman, RB (reprint author), NIDA,CLIN PSYCHOPHARMACOL SECT,DIR,NIH,5500 NATHAN SHOCK DR,BALTIMORE,MD 21224, USA. NR 24 TC 14 Z9 14 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 DEC 20 PY 1996 VL 8 IS 1 BP 7 EP 9 DI 10.1097/00001756-199612200-00002 PG 3 WC Neurosciences SC Neurosciences & Neurology GA WX339 UT WOS:A1996WX33900003 PM 9051742 ER PT J AU Hokari, M Wu, HQ Schwarcz, R Smith, QR AF Hokari, M Wu, HQ Schwarcz, R Smith, QR TI Facilitated brain uptake of 4-chlorokynurenine and conversion to 7-chlorokynurenic acid SO NEUROREPORT LA English DT Article DE blood-brain barrier; 4-chlorokynurenine; excitotoxicity; glycine; kynurenic acid; neurodegenerative disorders; NMDA; transport ID NMDA RECEPTOR; GLYCINE SITE; TRANSPORT; ANTAGONISTS; BARRIER; KYNURENINE; RAT AB 7-CHLOROKYNURENIC acid (7-Cl-KYNA) and 5,7-dichlorokynurenic acid (5,7-Cl-2-KYNA) are of therapeutic interest as potent glycine/N-methyl-D-aspartate (NMDA) receptor antagonists, but are excluded from brain by the blood-brain barrier. We examined whether these compounds could be delivered to brain through their respective precursors, L-4-chlorokynurenine (4-Cl-KYN) and L-4,6-dichlorokynurenine (4,6-Cl-2-KYN), which are amino acids. 4-Cl-KYN was shown to be rapidly shuttled into the brain by the large neutral amino acid transporter of the blood-brain barrier (K-m = 105 +/- 14 mu M, V-max = 16.9 +/- 2.3 nmol min(-1) g(-1)) and to be converted intracerebrally to 7-Cl-KYNA. 4,6-Cl-2-KYN also expressed affinity for the transporter, but four-fold less than that of 4-Cl-KYN. In summary, the results show that because of their facilitated uptake 4-Cl-KYN and 4,6-Cl2KYN might be useful prodrugs for brain delivery of glycine-NMDA receptor antagonists. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. FU NINDS NIH HHS [NS 28236, NS 16102] NR 14 TC 37 Z9 40 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 20 PY 1996 VL 8 IS 1 BP 15 EP 18 DI 10.1097/00001756-199612200-00004 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WX339 UT WOS:A1996WX33900005 PM 9051744 ER PT J AU Chang, MCJ Grange, E Rabin, O Bell, JM Allen, DD Rapaport, SI AF Chang, MCJ Grange, E Rabin, O Bell, JM Allen, DD Rapaport, SI TI Lithium decreases turnover of arachidonate in several brain phospholipids SO NEUROSCIENCE LETTERS LA English DT Article DE lithium; arachidonate; palmitate; fatty acids; phospholipids; phospholipase A(2); acyl-CoA; brain; rat; in vivo incorporation; turnover; signal transduction ID CEREBRAL-CORTEX; ACID RELEASE; CELLS; RAT; HIPPOCAMPUS; RECEPTORS; GTP AB In vivo rates of incorporation and turnover of palmitate and arachidonate in brain phospholipids were measured in awake rats treated chronically with lithium, following intravenous infusion of radiolabeled palmitate and arachidonate, respectively. Chronic lithium, at a brain level considered to be therapeutic in humans, decreased turnover of arachidonate within brain phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine by up to 80% (P < 0.001). In contrast, lithium had a minimal effect on turnover of palmitate, causing only a 26% reduction in turnover in phosphatidylcholine (P < 0.01). These results suggest that a major therapeutic effect of lithium is to reduce turnover specifically of arachidonate, possibly by inhibiting phospholipase A(2) involved in signal transduction. The effect may be secondary to the known action of lithium on the phosphoinositide cycle, by inhibiting the activity of inositol monophosphatase. (C) 1996 Elsevier Science Ireland Ltd. RP Chang, MCJ (reprint author), NIA, NEUROSCI LAB, NIH, 10 CTR DR, MSC 1582, BETHESDA, MD 20892 USA. NR 20 TC 127 Z9 127 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 20 PY 1996 VL 220 IS 3 BP 171 EP 174 DI 10.1016/S0304-3940(96)13264-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA WB596 UT WOS:A1996WB59600007 PM 8994220 ER PT J AU Constantino, JN Murphy, DL AF Constantino, JN Murphy, DL TI Monoamine metabolites in 'leftover' newborn human cerebrospinal fluid - A potential resource for biobehavioral research SO PSYCHIATRY RESEARCH LA English DT Article DE 5-hydroxyindoleacetic acid; homovanillic acid; 3-methoxy-4-hydroxyphenylglycol; temperament; infancy; circadian rhythm; twin studies ID DISRUPTIVE BEHAVIOR DISORDERS; MACARTHUR LONGITUDINAL TWIN; RHESUS-MONKEYS; 5-HYDROXYINDOLEACETIC ACID; AMINE METABOLITES; HOMOVANILLIC-ACID; SEROTONIN; CHILDREN; CSF; AGGRESSION AB Although variations in monoamine neurotransmission have been implicated in a Variety of psychopathologic outcomes in man, little is known about how monoamines influence or are affected by developmental processes early in childhood. In this study, assays for 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were obtained from 'leftover' cerebrospinal fluid (CSF) of 119 human newborns. The levels of these monoamine metabolites were in keeping with pre-existing 'normative' data from two small previously published studies. The levels were largely unaffected by variations in the infants' physiologic condition at the time of lumbar puncture, and exhibited evidence for circadian rhythms. Among 32 infants (8 neurologically normal, 24 neurologically compromised) for whom more than one CSF sample was obtained during the first year of life, the correlations between baseline and follow-up measurements for 5-HIAA and HVA were on the order of 0.75. Correlations between twins (four sets) were significantly higher than those between unrelated individuals for 5-HIAA and HVA. At 9-month follow-up, neurologically normal infants in the lower extreme 15% of the distribution for 5-HIAA exhibited a trend toward lower scores for sociability on the Colorado Childhood Temperament Inventory (maternal report) than their counterparts at the upper extreme of the 5-HIAA distribution. Leftover CSF is a readily available resource for measurements of monoamine metabolites (and possibly other CSF constituents) in population-based samples of human newborns. Copyright (C) 1996 Elsevier Science Ireland Ltd. C1 UNIV WASHINGTON,SCH MED,DEPT PEDIAT,ST LOUIS,MO. NIMH,CLIN SCI LAB,CTR CLIN,NIH,BETHESDA,MD 20892. RP Constantino, JN (reprint author), WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,4940 CHILDRENS PL,ST LOUIS,MO 63110, USA. NR 46 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 20 PY 1996 VL 65 IS 3 BP 129 EP 142 DI 10.1016/S0165-1781(96)02976-9 PG 14 WC Psychiatry SC Psychiatry GA WF290 UT WOS:A1996WF29000001 PM 9029662 ER PT J AU McFarland, HF AF McFarland, HF TI Complexities in the treatment of autoimmune disease SO SCIENCE LA English DT Editorial Material ID GAMMA-INTERFERON; ENCEPHALOMYELITIS; RESPONSES; PROTEIN RP McFarland, HF (reprint author), NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 53 Z9 54 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 20 PY 1996 VL 274 IS 5295 BP 2037 EP 2038 DI 10.1126/science.274.5295.2037 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY974 UT WOS:A1996VY97400033 PM 8984662 ER PT J AU Cortez, D Stoica, G Pierce, JH Pendergast, AM AF Cortez, D Stoica, G Pierce, JH Pendergast, AM TI The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent signaling pathway SO ONCOGENE LA English DT Article DE BCR-ABL; apoptosis; Ras; tyrosine phosphorylation ID HEMATOPOIETIC-CELLS; PC12 CELLS; TRANSFORMATION; DEATH; ONCOGENE; PROLIFERATION; PROTEIN AB BCR-ABL is a deregulated tyrosine kinase that is expressed in Philadelphia chromosome (Ph(1)) positive human leukemias, When expressed in hematopoietic cells, BCR-ABL causes cytokine independent proliferation, induces tumorigenic growth and prevents apoptosis in response to cytokine deprivation or DNA damage, One mechanism by which BCR-ABL signals in cells is by activating the small guanine nucleotide binding protein Ras, BCR-ABL-transformed cells have constitutively high levels of active, GTP-bound Ras, Here we use 32D cells that inducibly express a dominant negative Ras protein to define the Ras requirements in BCR-ABL-transformed cells, Dominant negative Ras inhibits BCR-ABL-mediated Ras activation, and induces cell death by an apoptotic mechanism, Therefore, BCR-ABL inhibits apoptosis through activation of a Ras-dependent signaling pathway. C1 DUKE UNIV,MED CTR,DEPT MOL CANC BIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. GEORGETOWN UNIV,SCH MED,DEPT BIOCHEM,WASHINGTON,DC 20007. NIH,CELL & MOL BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA61033] NR 23 TC 122 Z9 126 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 19 PY 1996 VL 13 IS 12 BP 2589 EP 2594 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VZ654 UT WOS:A1996VZ65400008 PM 9000132 ER PT J AU Tayebi, N Stern, H Dymarskaia, I Herman, J Sidransky, E AF Tayebi, N Stern, H Dymarskaia, I Herman, J Sidransky, E TI 55-base pair deletion in certain patients with Gaucher disease complicates screening for common Gaucher alleles SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Gaucher disease; glucocerebrosidase; pseudogene; deletion; genotyping ID GLUCOCEREBROSIDASE GENE; MUTATIONS; PCR AB Mutations in the glucocerebrosidase gene which result in Gaucher disease can originate from the highly homologous glucocerebrosidase pseudogene, A 55-bp deletion in exon 9, which corresponds to a 55-bp segment absent from the pseudogene, has been identified in patients with Gaucher disease, We have developed a simple polymerase chain reaction (PCR)-based method to detect this 55-bp deletion, and have found this mutation in 3 of 75 DNA samples (4%) collected from patients with Gaucher disease. Commonly used PCR-based screening methods for specific Gaucher mutations frequently make use of primers either within or surrounding the 55-bp gap to selectively distinguish the glucocerebrosidase gene from the pseudogene. However, if the 55-bp deletion in exon 9 occurs, primers will either fail to produce an amplification product or will produce a shortened product which will be falsely attributed to the pseudogene. This could lead to inaccurate genotyping and genetic counseling for some Gaucher patients and their families, We therefore recommend that laboratories using PCR-based screening techniques involving primers in this region initially determine whether this 55-bp sequence is present. (C) 1996 Wiley-Liss, Inc. C1 NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. CHILDRENS NATL MED CTR,DEPT LAB MED & MED GENET,WASHINGTON,DC 20010. NR 20 TC 27 Z9 27 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 18 PY 1996 VL 66 IS 3 BP 316 EP 319 DI 10.1002/(SICI)1096-8628(19961218)66:3<316::AID-AJMG15>3.0.CO;2-P PG 4 WC Genetics & Heredity SC Genetics & Heredity GA WA048 UT WOS:A1996WA04800015 PM 8985494 ER PT J AU Henningfield, JE Hariharan, M Kozlowski, LT AF Henningfield, JE Hariharan, M Kozlowski, LT TI Nicotine content and health risks of cigars SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CIGARETTES; SMOKERS C1 UNIV MICHIGAN,SCH MED,DEPT PSYCHIAT,ANN ARBOR,MI. PENN STATE UNIV,COLL HLTH & HUMAN DEV,DEPT BIOBEHAV HLTH,UNIVERSITY PK,PA 16802. RP Henningfield, JE (reprint author), NATL INST DRUG ABUSE,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224, USA. NR 12 TC 21 Z9 21 U1 1 U2 3 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 DEC 18 PY 1996 VL 276 IS 23 BP 1857 EP 1858 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VX522 UT WOS:A1996VX52200002 PM 8967995 ER PT J AU Tucker, KL Mahnken, B Wilson, PWF Jacques, P Selhub, J AF Tucker, KL Mahnken, B Wilson, PWF Jacques, P Selhub, J TI Folic acid fortification of the food supply - Potential benefits and risks for the elderly population SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COBALAMIN DEFICIENCY; PERNICIOUS-ANEMIA; PLASMA HOMOCYSTEINE; FOLATE; HYPERHOMOCYSTEINEMIA; VITAMIN-B12; QUESTIONNAIRE; MACROCYTOSIS; PREVALENCE; DIAGNOSIS AB Objective.-To estimate the potential benefits and risks of food folic acid fortification for an elderly population, Benefits are expected through the improvement of folate and homocysteine status, but there is also a risk of masking or precipitating clinical manifestations related to vitamin B-12 deficiency with increasing exposure to folic acid. Design.-Cross-sectional analysis, with projected change at various levels of folic acid fortification. Setting.-Participants in the Framingham Heart Study original cohort. Participants.-A total of 747 subjects aged 67 to 96 years who both completed usable food frequency questionnaires and had blood concentrations of B vitamins and homocysteine measured. Main Outcome Measures.-Projected blood folate and homocysteine concentrations and combined high folate intake and low plasma vitamin B-12 concentration. Results.-Percentages of this elderly population with folate intake below 400 mu g/d are projected to drop from 66% at baseline to 49% with 140 mu g of folate per 100 g of cereal-grain product, to 32% with 280 mu g, to 26% with 350 mu g, and to 11% with 700 mu g. Percentages with elevated homocysteine concentrations (>14 mu mol/L) are projected to drop from 26% at baseline to 21% with 140 mu g of folate per 100 g, to 17% with 280 mu g, to 16% with 350 mu g, and to 12% with 700 mu g. Without fortification, the prevalence of combined high folate intake (>1000 mu g/d) and low plasma vitamin B-12 concentration (<185 pmol/L [<250 pg/mL]) was 0.1%. This is projected to increase to 0.4% with folate fortification levels of 140 to 350 mu g/100 g and to 3.4% with 700 mu g. Conclusion.-The evidence suggests that, at the level of 140 mu g/100 g of cereal-grain product mandated by the Food and Drug Administration, the benefits of folate fortification, through projected decreases in homocysteine level and heart disease risk, greatly outweigh the expected risks, However, quantification of the actual risks associated with vitamin B-12 deficiency remains elusive. Before higher levels of folio acid fortification are implemented, further research is needed to better understand the clinical course of various forms of Vitamin B-12 deficiency, to measure the potential effect of high folate intake on this course, and to identify cost-effective approaches to the identification and treatment of all forms of vitamin B-12 deficiency. C1 NHLBI,FRAMINGHAM MASS HEART STUDY,BETHESDA,MD 20892. RP Tucker, KL (reprint author), TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,711 WASHINGTON ST,BOSTON,MA 02111, USA. RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X FU NHLBI NIH HHS [N01-HC-38038] NR 48 TC 137 Z9 139 U1 1 U2 8 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 DEC 18 PY 1996 VL 276 IS 23 BP 1879 EP 1885 DI 10.1001/jama.276.23.1879 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VX522 UT WOS:A1996VX52200035 PM 8968013 ER PT J AU Curb, JD Pressel, SL Cutler, JA Savage, PJ Applegate, WB Black, H Camel, G Davis, BR Frost, PH Gonzalez, N Guthrie, G Oberman, A Rutan, GH Stamler, J AF Curb, JD Pressel, SL Cutler, JA Savage, PJ Applegate, WB Black, H Camel, G Davis, BR Frost, PH Gonzalez, N Guthrie, G Oberman, A Rutan, GH Stamler, J TI Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EUROPEAN WORKING PARTY; HIGH BLOOD-PRESSURE; MORTALITY; MORBIDITY; THERAPY; TRIAL AB Objective.-To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients. Design.-Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP). Setting.-Multiple clinical and support centers in the United States. Participants.-A total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], greater than or equal to 160 mm Hg; diastolic BP, <90 mm Hg) al baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (greater than or equal to 140 mg/dL), or any combination of these characteristics. Intervention.-The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patient's private physician for persistently high BP. Main Outcome Measures.-The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality. Results.-The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group, Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. Conclusion.-Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic cider patients with ISH. C1 UNIV HAWAII,JOHN A BURNS SCH MED,HONOLULU,HI 96822. UNIV TEXAS,SCH PUBL HLTH,HOUSTON,TX. NHLBI,BETHESDA,MD 20892. UNIV TENNESSEE,MEMPHIS,TN 38163. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV KENTUCKY,LEXINGTON,KY. UNIV ALABAMA,BIRMINGHAM,AL. VET AFFAIRS MED CTR,MEMPHIS,TN. NORTHWESTERN UNIV,CHICAGO,IL 60611. SYSTOL HYPERTENS ELDERLY PROGRAM COORDINATING CTR,HOUSTON,TX 77030. NR 20 TC 588 Z9 604 U1 3 U2 13 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 DEC 18 PY 1996 VL 276 IS 23 BP 1886 EP 1892 DI 10.1001/jama.276.23.1886 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VX522 UT WOS:A1996VX52200036 PM 8968014 ER PT J AU Yanovski, SZ Dietz, WH Goodwin, NJ Hill, JO PiSunyer, FX Rolls, B Stern, J Weinsier, RL Wilson, GT Wing, RR Hoofnagle, JH Everhart, JE Hubbard, VS AF Yanovski, SZ Dietz, WH Goodwin, NJ Hill, JO PiSunyer, FX Rolls, B Stern, J Weinsier, RL Wilson, GT Wing, RR Hoofnagle, JH Everhart, JE Hubbard, VS TI Long-term pharmacotherapy in the management of obesity SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID FENFLURAMINE PLUS PHENTERMINE; CARDIOVASCULAR RISK-FACTORS; DOUBLE-BLIND TRIAL; WEIGHT CONTROL; CALORIC RESTRICTION; BODY-WEIGHT; FOLLOW-UP; DEXFENFLURAMINE TREATMENT; PULMONARY-HYPERTENSION; BEHAVIOR-MODIFICATION AB Objectives.-To examine the rationale for long-term use of medications in the management of obesity, to provide an overview of published scientific information on their safety and efficacy, and to provide guidance to patients and practitioners regarding risks and benefits of treatment. Data Sources.-Original reports and reviews obtained through electronic database searches on anorexiant drugs supplemented by a manual search of bibliographies. Study Selection.-English-language articles that discussed the role of medications in the treatment of human obesity, and studies that evaluated their safety and efficacy for a minimum of 24 weeks. Data Extraction.-Studies were reviewed by experts in the fields of nutrition, obesity, and eating disorders to evaluate study design and the validity of authors' conclusions. Data Synthesis.-The long-term use of medications in the management of obesity is consistent with the current consensus that obesity responds poorly to short-term interventions. Net weight loss attributable to medication is modest, ranging from 2 to 10 kg, but patients taking active drug are more likely to lose 10% or more of initial body weight. Weight loss tends to reach a plateau by 6 months. Weight remains below baseline throughout treatment, although some studies show partial weight regain despite continued drug therapy. Most adverse effects are mild and self-limited, but rare serious outcomes have been reported. Conclusions.-Pharmacotherapy for obesity, when combined with appropriate behavioral approaches to change diet and physical activity, helps some obese patients lose weight and maintain weight loss for at least 1 year. There is little justification for the short-term use of anorexiant medications, but few studies have evaluated their safety and efficacy for more than 1 year. Until more data are available, pharmacotherapy cannot be recommended for routine use in obese individuals, although it may be helpful in carefully selected patients. C1 TUFTS UNIV,SCH MED,BOSTON,MA 02111. HLTH WATCH INFORMAT & PROMOT SERV,NEW YORK,NY. UNIV COLORADO,DENVER,CO 80202. COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP CTR,NEW YORK,NY. PENN STATE UNIV,STATE COLL,PA 16804. UNIV CALIF DAVIS,DAVIS,CA 95616. UNIV ALABAMA,BIRMINGHAM,AL. RUTGERS STATE UNIV,PISCATAWAY,NJ. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. NIDDK,DIV DIGEST DIS & NUTR,NIH,BETHESDA,MD. NR 114 TC 163 Z9 163 U1 0 U2 2 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 DEC 18 PY 1996 VL 276 IS 23 BP 1907 EP 1915 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VX522 UT WOS:A1996VX52200040 ER PT J AU LiWang, AC Bax, A AF LiWang, AC Bax, A TI Equilibrium protium/deuterium fractionation of backbone amides in U-C-13/N-15 labeled human ubiquitin by triple resonance NMR SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEINS; SPECTRA; C-13 C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NR 17 TC 42 Z9 42 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 18 PY 1996 VL 118 IS 50 BP 12864 EP 12865 DI 10.1021/ja9630553 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VY900 UT WOS:A1996VY90000060 ER PT J AU Karp, JE Smith, MA AF Karp, JE Smith, MA TI Modifying risks of secondary leukemias: Is drug scheduling important? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; CELL LUNG-CANCER; DNA-TOPOISOMERASE-II; HPRT GENE; CHROMOSOME TRANSLOCATIONS; MALIGNANT TRANSFORMATION; RANDOMIZED TRIAL; ETOPOSIDE; EPIPODOPHYLLOTOXINS; RECOMBINASE C1 NCI,CLIN TRIALS EVALUAT PROGRAM,DIV CANC TREATMENT DIAG & CTR,BETHESDA,MD 20892. RP Karp, JE (reprint author), UNIV MARYLAND,CTR CANC,22 S GREENE ST,RM S9D15,BALTIMORE,MD 21201, USA. NR 36 TC 7 Z9 7 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 DEC 18 PY 1996 VL 88 IS 24 BP 1787 EP 1789 DI 10.1093/jnci/88.24.1787 PG 3 WC Oncology SC Oncology GA VY199 UT WOS:A1996VY19900001 PM 8961963 ER PT J AU Burke, TR Ye, B Yan, XJ Wang, SM Jia, ZC Chen, L Zhang, ZY Barford, D AF Burke, TR Ye, B Yan, XJ Wang, SM Jia, ZC Chen, L Zhang, ZY Barford, D TI Small molecule interactions with protein-tyrosine phosphatase PTP1B and their use in inhibitor design SO BIOCHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; O-PHOSPHOTYROSINE; NONHYDROLYZABLE MIMETICS; N-BOC; POTENT; DERIVATIVES; ANALOGS; 1B; PHENYLALANINE; INACTIVATION AB We have previously shown that a small peptide bearing the hydrolytically stable phosphotyrosyl (pTyr) mimetic, (difluorophosphonomethyl)phenylalanine (F(2)Pmp), is an extremely potent inhibitor of PTP1B, with an IC50 value of 100 nM [Burke, T. R., Kole, H. K., & Roller, P. P. (1994) Biochem. Biophys. Res. Commun. 204, 129-134]. We further demonstrated that removal of the peptide portion and incorporation of the difluorophosphonomethyl moiety onto a naphthalene ring system, but not a phenyl ring system, resulted in good inhibitory potency [Kole, H. K., Smyth, M. S., Russ, P. L., & Burke, T. R., Jr. (1995) Biochem. J. 311, 1025-1031]. In order to understand the structural basis for this inhibition, and to aid in the design of further analogs, we solved the X-ray structure of [1,1-difluoro-1-(2-naphthalenyl)-methyl]phosphonic acid (6) complexed within the catalytic site of PTP1B, solved to 2.3 Angstrom resolution. In addition to showing the manner in which the phosphonate group is held within the catalytic site, the X-ray structure also revealed extensive hydrophobic interactions with the naphthalene ring system, beyond that possible with an analog bearing a single phenyl ring. It is further evident that, of the two fluorine atoms, the pro-R alpha-fluorine interacts with the enzyme to a significantly greater degree than the pro-S alpha-fluorine, forming a hydrogen bond to Phe 182. On the basis of a computer-assisted molecular modeling analysis, it was determined that addition of a hydroxyl to the naphthyl 4-position, giving [1,1-difluoro-1-[2-(4-hydroxynaphthalenyl)] methyl]phosphonic acid (8), could potentially replace a water molecule situated in the PTP1B . 6 complex, thereby allowing new hydrogen-bonding interactions with Lys 120 and Tyr 46. Compound 8 was therefore prepared and found to exhibit a doubling of affinity (K-i = 94 mu M) relative to parent unsubstituted 6 (K-i = 179 mu M), supporting, in principle, the development of high-affinity ligands based on molecular modeling analysis of the enzyme-bound parent. C1 UNIV OXFORD,MOL BIOPHYS LAB,OXFORD OX1 3QU,ENGLAND. ALBERT EINSTEIN COLL MED,DEPT MOL PHARMACOL,BRONX,NY 10461. RP Burke, TR (reprint author), NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [5P60 DK20541]; Wellcome Trust NR 45 TC 118 Z9 120 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 17 PY 1996 VL 35 IS 50 BP 15989 EP 15996 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY897 UT WOS:A1996VY89700004 PM 8973169 ER PT J AU Arai, T Jones, CR Rapoport, SI Weiss, SRB AF Arai, T Jones, CR Rapoport, SI Weiss, SRB TI Evidence for membrane remodeling in ipsilateral thalamus and amygdala following left amygdala-kindled seizures in awake rats SO BRAIN RESEARCH LA English DT Article DE kindling; amygdala; thalamus; fatty acid; palmitate; lipid; deoxyglucose; brain; plasticity; seizure; phospholipid; phosphatidylcholine; activation ID CEREBRAL PALMITATE INCORPORATION; RADIOLABELED FATTY-ACIDS; GLUCOSE-UTILIZATION; UNANESTHETIZED RATS; BRAIN INCORPORATION; PLASMA PALMITATE; DENTATE GYRUS; MESSENGER-RNA; PHOSPHOLIPIDS; NEUROPLASTICITIES AB We examined regional cerebral metabolic rates for glucose (rCMR(glc)) and brain incorporation coefficients (k*) of each of three intravenously infused fatty acid radiotracers, [9,10-H-3]palmitate ([H-3]PAM), [1-C-14]arachidonate ([C-14]AA) and [1-C-14]docosahexaenoate ([C-14]DHA), in awake rats fully kindled by once-daily electrical stimulation of the left amygdala. Compared with sham-stimulated animals, rCMR(glc) was increased bilaterally during a seizure, particularly in midbrain-brain stem regions, thalamus and basolateral nucleus of the amygdala. At 24 h and 2 weeks after a seizure, there was no significant change in k* for either [C-14]AA or [C-14]DHA in any brain region, whereas k* for [H-3]PAM at 24 h was increased significantly (by 32-53%) ipsilateral to stimulation in regions of the amygdala and thalamus. Contralateral regions showed no significant change. Two weeks after a seizure, k* for [3H]PAM was increased in the ipsilateral lateral dorsal nucleus of the thalamus. These results argue for membrane remodeling involving phosphatidylcholine in the ipsilateral amygdala and thalamus at the completed phase of amygdala kindling. Remodeling may continue for up to 2 weeks after a seizure during the completed phase. C1 NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. TOKYO MED & DENT UNIV,SCH MED,DEPT NEUROSURG,BUNKYO KU,TOKYO 113,JAPAN. NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 59 TC 5 Z9 5 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 DEC 16 PY 1996 VL 743 IS 1-2 BP 131 EP 140 DI 10.1016/S0006-8993(96)00854-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA WC373 UT WOS:A1996WC37300018 PM 9017240 ER PT J AU Pullia, D DAmato, FR Mele, A Oliverio, A Zocchi, A Pavone, F AF Pullia, D DAmato, FR Mele, A Oliverio, A Zocchi, A Pavone, F TI Time-related effects of stress on cholinergic sensitivity SO BRAIN RESEARCH LA English DT Article DE restraint; oxotremorine; locomotor activity; acetylcholine; muscarinic receptor; prefrontal cortex; DBA/2 mice ID ACUTE RESTRAINT STRESS; IMMOBILIZATION STRESS; LIFE EVENTS; OXOTREMORINE; RATS; RECEPTORS; SUPERSENSITIVITY; HIPPOCAMPUS; TOLERANCE; RESPONSES AB The effect of the administration of the muscarinic cholinergic agonist oxotremorine on locomotor activity was investigated in DBA/2 mice subjected to chronic restraint stress of different durations (120 min daily for 10, 14 or 18 days). Oxotremorine induced a depressant effect on locomotion, which was reduced after 10 and 14 days of restraint, but not after a 18-day restraint stress. Acetylcholine (ACh) content was significantly reduced in prefrontal cortex after 10 and 14 days of stress but returned to control values after 18 days of restraint. No changes in ACh content were observed in nucleus accumbens and striatum. These results are discussed in terms of possible changes in muscarinic receptor sensitivity. C1 CNR,IST PSICOBIOL & PSICOFARMACOL,I-00198 ROME,ITALY. UNIV ROMA LA SAPIENZA,DIPARTIMENTO GENET & BIOL MOL,ROME,ITALY. NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. OI Pavone, Flaminia/0000-0001-5189-2748; D'Amato, Francesca/0000-0002-4577-4574 NR 25 TC 11 Z9 12 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 DEC 16 PY 1996 VL 743 IS 1-2 BP 333 EP 336 DI 10.1016/S0006-8993(96)00799-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WC373 UT WOS:A1996WC37300042 PM 9017264 ER PT J AU Bezrukov, SM Vodyanoy, I Brutyan, RA Kasianowicz, JJ AF Bezrukov, SM Vodyanoy, I Brutyan, RA Kasianowicz, JJ TI Dynamics and free energy of polymers partitioning into a nanoscale pore SO MACROMOLECULES LA English DT Article ID PROBING ALAMETHICIN CHANNELS; WATER-SOLUBLE POLYMERS; SINGLE-ION CHANNEL; ALPHA-TOXIN; STAPHYLOCOCCUS-AUREUS; VOLUME CHANGES; PATCH-CLAMP; MEMBRANES; PROTEIN; DIFFUSION AB Membrane-bound proteinaceous nanoscale pores allow us to simultaneously observe the thermodynamic and kinetic properties of differently sized polymers within their confines. We determine the dynamic partitioning of poly(ethylene glycol) (PEG) into the pore formed by Staphylococcus aureus alpha-toxin and evaluate the free energy of polymer confinement by measuring polymer-induced changes to the pore's ionic conductance. The free energy deduced from the partition coefficient has a sharper dependence on polymer length (or weight) than scaling theory predicts. Moreover, the polymer-induced conductance fluctuations show a striking nonmonotonic dependence on the polymer molecular weight. The movement of polymer inside the pore is characterized by a diffusion coefficient that is orders of magnitude smaller than that for polymer in the bulk aqueous solution, which suggests that PEG has an attractive interaction with the pore. Using an ad-hoc approach,we show that a simple molecular weight-dependent modification of the polymer's diffusion coefficient accounts for these results, but only qualitatively. Given that PEG associates with hydrophobic regions in proteins, we also conclude that, contrary to the conventional view of ion channels, the aqueous cavity of the alpha-toxin pore's interior is, to some extent, hydrophobic. C1 ST PETERSBURG NUCL PHYS INST,GATCHINA 188350,RUSSIA. ONR EUROPE,LONDON NW1 5TH,ENGLAND. INST BIOTECHNOL,YEREVAN 375056,ARMENIA. NIST,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. RP Bezrukov, SM (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 44 TC 184 Z9 186 U1 2 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD DEC 16 PY 1996 VL 29 IS 26 BP 8517 EP 8522 DI 10.1021/ma960841j PG 6 WC Polymer Science SC Polymer Science GA VY915 UT WOS:A1996VY91500034 ER PT J AU Oopik, AJ Dorogy, M Devereux, RB Yeh, JL Okin, PM Lee, ET Cowan, L Fabsitz, RR Howard, BV Welty, TK AF Oopik, AJ Dorogy, M Devereux, RB Yeh, JL Okin, PM Lee, ET Cowan, L Fabsitz, RR Howard, BV Welty, TK TI Major electrocardiographic abnormalities among American Indians aged 45 to 74 years (The Strong Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; PIMA-INDIANS; DIABETES-MELLITUS; HIGH PREVALENCE; ROCHESTER; MINNESOTA; CRITERIA; HEALTH AB As part of the Strong Heart Study assessment of prevalent cardiovascular disease in middle-aged to elderly American Indians, the prevalence of major Minnesota code electrocardiographic (ECG) abnormalities was assessed in 4,531 participants aged 45 to 74 years (59% women) in selected tribal communities in Arizona, South and North Dakota, and Oklahoma. The overall prevalence of major ECG abnormalities was lowest in Arizona participants, (e.g., definite ECG myocardial infarction in 0.3% vs 1.8% in the other centers), although nearly two thirds of them had diabetes. One or more major ECG abnormality occurred in progressively more women (10.4% to 21.2%) and men (13.3% to 32%) (both p <0.0001) from 45- to 54- to 55- to 64- and 65- to 74-year age groups, with the latter prevalence rates exceeding those in predominately white age peers in the Cardiovascular Health Study. Diabetes in women, but not in men, and hypertension in both genders showed positive associations with prevalence rates of major ECG abnormalities compatible with coronary artery disease or hypertensive cardiac hypertrophy. Hypercholesterolemia was not associated with ECG abnormalities except for definite myocardial infarction in women. In conclusion, major ECG abnormalities are common in middle-aged to elderly American Indians, consistent with recent documentation of higher cardiovascular mortality in this population than in similar-aged U.S. whites. (C) 1996 by Excerpta Medica, Inc. C1 INDIAN HLTH SERV,ABERDEEN AREA,DENVER,CO. FITZSIMONS ARMY MED CTR,DENVER,CO. CORNELL UNIV,MED CTR,NEW YORK HOSP,DEPT MED,NEW YORK,NY 10021. UNIV OKLAHOMA,CTR EPIDEMIOL RES,OKLAHOMA CITY,OK. NHLBI,BETHESDA,MD 20892. MEDLANT RES INST,WASHINGTON,DC. FU NHLBI NIH HHS [U01-HL41652, U01-HL41642, U01-HL41654] NR 28 TC 19 Z9 19 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 1996 VL 78 IS 12 BP 1400 EP 1405 DI 10.1016/S0002-9149(96)00642-X PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VX770 UT WOS:A1996VX77000013 PM 8970414 ER PT J AU Mathew, J Davidson, S Narra, L Hafeez, T Garg, R AF Mathew, J Davidson, S Narra, L Hafeez, T Garg, R TI Etiology and characteristics of congestive heart failure in blacks SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VENTRICULAR DYSFUNCTION SOLVD; RISK AB In this study of 301 black patients with congestive heart failure (CHF), systemic hypertension is the most common cause of CHF and is the primary etiology of CHF in 61%. Left ventricular hypertrophy is highly prevalent and is seen in 63% of the patients who had an echocardiogram. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,BETHESDA,MD 20892. RP Mathew, J (reprint author), COOK CTY HOSP,DIV ADULT CARDIOL,DEPT MED,1835 W HARRISON ST,CHICAGO,IL 60612, USA. NR 13 TC 24 Z9 24 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 1996 VL 78 IS 12 BP 1447 EP & DI 10.1016/S0002-9149(96)00635-2 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VX770 UT WOS:A1996VX77000025 PM 8970426 ER PT J AU Koley, AP Buters, JTM Robinson, RC Markowitz, A Friedman, FK AF Koley, AP Buters, JTM Robinson, RC Markowitz, A Friedman, FK TI Interaction of polycyclic aromatic hydrocarbons with human cytochrome P450 1A1: A CO flash photolysis study SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cytochrome P450; protein conformation; polycyclic aromatic hydrocarbons; resorufins; kinetics ID YEAST SACCHAROMYCES-CEREVISIAE; MICROSOMAL CYTOCHROME-P-450; ENDOPLASMIC-RETICULUM; BINDING-KINETICS; EXPRESSION; BENZOPYRENE; PURIFICATION; METABOLISM; ACTIVATION; OXIDATION AB The kinetics of CO binding to human cytochrome P450 1A1 was used to probe the interaction of polycyclic aromatic hydrocarbons (PAHs) with the membrane-bound P450 expressed in baculovirus-infected SF9 insect cells. Biexponential kinetics was observed, indicating that P450 1A1 is composed of at least two kinetically distinguishable species. To define the substrate specificity of the individual species, we evaluated the effect of a series of PAHs of varying sizes and shapes on the CO binding kinetics of P450 1A1. The overall rate of CO binding was increased in the presence of the tricyclic PAHs phenanthrene and anthracene and the tetracyclic PAHs pyrene and 1,2-benzanthracene, but was decreased by the pentacyclic PAHs benzo[a]pyrene and 1,2:3,4-dibenzanthracene. A kinetic difference method was applied to kinetically define the individual P450 1A1 species. Two species differing in their PAH specificities were identified: a slowly reacting species sensitive to the smaller PAHs, and a rapidly reacting species responsive to larger PAHs. Upon PAH binding, CO binding to these species was accelerated and decelerated, respectively. The results furthermore suggest that the two species are interconvertable. In addition to PAHs, the interactions of P450 1A1 with 7-ethoxy- and 7-pentoxyresorufin were likewise examined for their effect on the CO binding kinetics. These compounds interacted with and decreased the rate of the rapidly and slowly reacting P450 1A1 species, respectively. The markedly variable effects of these PAHs and resorufins on the CO binding kinetics indicate differential modes of interaction with the two target P450 1A1 species, resulting in differential modulation of their conformations. These results demonstrate that multiple P450 1A1 species with distinct conformations and substrate recognition profiles coexist in a biological membrane and are resolvable using a rapid kinetic technique. (C) 1996 Academic Press, Inc. C1 NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Buters, Jeroen/G-5070-2011; Friedman, Fred/D-4208-2016 NR 32 TC 6 Z9 6 U1 1 U2 2 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 DEC 15 PY 1996 VL 336 IS 2 BP 261 EP 267 DI 10.1006/abbi.1996.0556 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WA819 UT WOS:A1996WA81900008 PM 8954573 ER PT J AU Murphy, DL Aulakh, C MazzolaPomietto, P Briggs, NC AF Murphy, DL Aulakh, C MazzolaPomietto, P Briggs, NC TI Neuroendocrine responses to serotonergic agonists as indices of the functional status of central serotonin neurotransmission in humans: A preliminary comparative analysis of neuroendocrine endpoints versus other endpoint measures SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 3rd IUPHAR Satellite Meeting on Serotonin CY JUL 30-AUG 03, 1994 CL CHICAGO, IL DE cortisol; prolactin; serotonin; serotonin receptor; temperature; anxiety; m-chlorophenylpiperazine ID OBSESSIVE-COMPULSIVE DISORDER; TERM LITHIUM TREATMENT; META-CHLOROPHENYLPIPERAZINE; PANIC DISORDER; M-CPP; RECEPTOR HYPERSENSITIVITY; CLOMIPRAMINE TREATMENT; HEALTHY-SUBJECTS; FOOD-INTAKE; HUMAN-BRAIN AB The status of central serotonergic neurotransmission and of specific serotonin (5-HT) receptor subtype sensitivity has been inferred from neuroendocrine and other endpoint responses to serotonergic agents given to humans. The question of whether changes in neuroendocrine responsivity to the 5-HT2C partial agonist, meta-chlorophenylpiperazine (m-CPP), are accompanied by similar changes in other endpoints (temperature, behavior) is addressed in this brief review of published studies. These studies were selected based on the following criteria: (1) neuroendocrine (cortisol, prolactin increases) and at least one other endpoint (behavior and/or temperature increases) were measured in the same populations, and (2) statistically significant changes were observed after m-CPP in the healthy volunteer control or pre-long-term-treatment subjects. Parenthetically, in the 13 of 14 studies that reported both prolactin and cortisol responses, the results were congruent for the two neuroendocrine measures in 12 of the 13 (92%). However, neuroendocrine versus behavioral results were in agreement in fewer (7 of the 13) studies (54%). Neuroendocrine vs. temperature results were non-concordant in all 4 of the studies which included temperature measurements. These generally disparate findings suggest that these different endpoints may reflect brain serotonin neuroanatomic and receptor subsystem complexity and/or m-CPP's complex pharmacological properties. Thus, these neuroendocrine response measures cannot at this time be considered a general index of the other response measures, nor necessarily an index of the functional status of central serotonergic neurotransmission until this is established by more direct experimental investigations. RP Murphy, DL (reprint author), NIMH, CLIN SCI LAB, BLDG 10, RM 3D41, 10 CTR DR MSC 1264, BETHESDA, MD 20892 USA. NR 51 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD DEC 15 PY 1996 VL 73 IS 1-2 BP 209 EP 214 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA TP015 UT WOS:A1995TP01500038 PM 8788504 ER PT J AU Bonson, KR Murphy, DL AF Bonson, KR Murphy, DL TI Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 3rd IUPHAR Satellite Meeting on Serotonin CY JUL 30-AUG 03, 1994 CL CHICAGO, IL DE lithium; lysergic acid diethylamide; monoamine oxidase; tricyclic antidepressant; chronic drug administration ID LYSERGIC-ACID DIETHYLAMIDE; DOPAMINE-RECEPTORS; RAT-BRAIN; CHRONIC IMIPRAMINE; SUPER-SENSITIVITY; AGONISTS; BINDING; 5-HT; HALLUCINOGENS; HYPOTHESIS AB This study sought to investigate possible interactions between antidepressant agents and lysergic acid diethylamide (LSD) in humans through the use of retrospective questionnaires. Ten subjects were identified who used LSD during chronic (3 weeks or longer) periods of antidepressant administration. These subjects were asked to describe the phenomenological effects of self-administered hallucinogens prior to and during antidepressant treatment; a structured, standardized questionnaire was used to evaluate LSD experiences. Chronic tricyclic antidepressant administration was associated with subjective increases in physical, hallucinatory and psychological responses to LSD. Similarly, subjects receiving lithium chronically also reported increases in their responses to LSD. In contrast, subjects who had been chronically taking an monoamine oxidase (MAO) inhibitor reported subjective decreases in the effects of LSD. This is similar to a previous report by our group of a decreased response to LSD in individuals who were chronically taking serotonin-selective antidepressants. These altered responses to LSD most likely involve differential changes in central serotonin and dopamine receptor systems and are consistent with other recent data suggesting that the clinical efficacy of different classes of antidepressants may not necessarily rely on a common mechanism of action in the brain. RP Bonson, KR (reprint author), NIMH, CLIN SCI LAB, BLDG 10, ROOM 3D41, 10 CTR DR MSC 1264, BETHESDA, MD 20892 USA. NR 41 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD DEC 15 PY 1996 VL 73 IS 1-2 BP 229 EP 233 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA TP015 UT WOS:A1995TP01500042 PM 8788508 ER PT J AU Yakel, JL AF Yakel, JL TI Desensitization of 5-HT3 receptors expressed in Xenopus oocytes: Dependence on voltage and primary structure SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 3rd IUPHAR Satellite Meeting on Serotonin CY JUL 30-AUG 03, 1994 CL CHICAGO, IL DE serotonin; ligand-gated ion channel; mutagenesis ID CHANNEL AB The wild-type and a mutant 5-HT3 receptor were expressed in Xenopus oocytes to further explore how the rate of onset of desensitization of the 5-HT3 receptor was dependent on membrane voltage and primary structure of the channel. The rapid application of serotonin (5-HT; 50 mu M) in a Ca2+-containing (1.8 mM) bathing solution elicited inward currents that decayed rapidly and with a biphasic time course in most cases. For oocytes expressing the wild-type 5-HT3 receptor and held at a potential of -90 mV, the value of the fast time constant of decay (tau(fast)) was 0.79+/-0.3 s (n=7), while tau(slow) was 16+/-3 s; the area of the decay phase contributed by tau(fast) (i.e., A(fast)) was 50+/-4% and A(slow) was 38+/-5%, with a remainder (i.e., non-desensitizing component) of 12%. The kinetics of the decay phase were strongly voltage-dependent. At a holding potential of -30 mV, the desensitization decay phase was now monophasic, with a time constant of 14.0+/-3.1 s (n=4). Mutating the leucine at position 286 of the wild-type 5-HT3 receptor to threonine (i.e., mutant L286T) resulted in desensitization kinetics that were biphasic at all membrane potentials tested and with a rate of decay that was not voltage dependent. Therefore, desensitization is a multifaceted and complex process, whose rate of onset depends in part to membrane voltage and primary structure of the ion channel. RP Yakel, JL (reprint author), NIEHS, CELLULAR & MOLEC PHARMACOL LAB, POB 12233, 104 T W ALEXANDER DR, RES TRIANGLE PK, NC 27709 USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD DEC 15 PY 1996 VL 73 IS 1-2 BP 269 EP 272 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA TP015 UT WOS:A1995TP01500050 PM 8788516 ER PT J AU Burnet, PWJ Mefford, IN Smith, CC Gold, PW Sternberg, EM AF Burnet, PWJ Mefford, IN Smith, CC Gold, PW Sternberg, EM TI Hippocampal 5-HT1A receptor binding site densities, 5-HT1A receptor messenger ribonucleic acid abundance and serotonin levels parallel the activity of the hypothalamo-pituitary-adrenal axis in rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 3rd IUPHAR Satellite Meeting on Serotonin CY JUL 30-AUG 03, 1994 CL CHICAGO, IL DE adrenalectomy; 5-HT metabolism; 5-HT1A receptor density; 5-HT1A receptor mRNA; rat strain differences; hippocampus; frontal cortex ID LEWIS RATS; ARTHRITIS; CLONING; HORMONE; BRAIN AB We have previously demonstrated that susceptibility of the Lewis rat to inflammatory disease, compared to the relatively resistant Fischer F344 rat, is related to a hyporesponsive hypothalamopituitary adrenal axis to inflammatory and other stress mediators. Since 5-HT and the 5HT(1A) receptor are important stimulators of this axis, we have investigated the levels of 5-HT1A receptor binding sites and encoding mRNA, 5-HT and 5-hydroxyindole acetic acid in various brain regions of Lewis, Harlan Sprague Dawley and Fischer F344 rats. Lewis rats expressed significantly less hippocampal and frontal cortical 5-HT1A receptor binding sites and mRNA than Harlan Sprague-Dawley and Fischer F344 rats. Adrenalectomy increased the number of 5HT(1A) receptor binding sites and mRNA expression in the hippocampus of all three strains. The levels of hippocampal 5-HT in Fischer F344 rats were significantly greater than levels detected in the same regions for the other two strains. Hypothalamic 5-HT and 5-hydroxyindole acetic acid levels in Harlan Sprague-Dawley rats were higher than the same area from the other two strains. Adrenalectomy increased the levels of 5-hydroxyindole acetic acid in the hypothalamus of all three strains. We conclude that hippocampal 5-HT1A receptor densities and 5-HT levels in the rat parallel the activity and responsiveness of the hypthalamopituitary-adrenal axis. We have published these data in an earlier report. C1 RADCLIFFE INFIRM, NHS TRUST, DEPT NEUROPATHOL, OXFORD OX2 6HE, ENGLAND. NIMH, CLIN NEUROENDOCRINOL BRANCH, UNIT NEUROENDOCRINE IMMUNOL & BEHAV, BETHESDA, MD 20892 USA. NIMH, EXPTL THERAPEUT BRANCH, UNIT NEUROPHARMACOL, BETHESDA, MD 20892 USA. RP Burnet, PWJ (reprint author), UNIV OXFORD, RADCLIFFE INFIRM, NHS TRUST, DEPT CLIN NEUROL, OXFORD OX2 6HE, ENGLAND. NR 12 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD DEC 15 PY 1996 VL 73 IS 1-2 BP 365 EP 368 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA TP015 UT WOS:A1995TP01500067 PM 8788533 ER PT J AU Knable, MB Hyde, TM Murray, AM Herman, MM Kleinman, JE AF Knable, MB Hyde, TM Murray, AM Herman, MM Kleinman, JE TI A postmortem study of frontal cortical dopamine D1 receptors in schizophrenics, psychiatric controls, and normal controls SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; prefrontal cortex; cingulate cortex; dopamine; D1 receptors; [H-3]-SCH 23390 ID PRIMATE CEREBRAL-CORTEX; CHRONIC NEUROLEPTIC TREATMENT; PREFRONTAL CORTEX; CINGULATE CORTEX; RAT STRIATUM; HALOPERIDOL; SYSTEM; BRAIN; D-1; ABNORMALITIES AB We tested the hypothesis that aberrant dopaminergic innervation in frontal and cingulate cortices of schizophrenic patients might be revealed by examining dopamine DI receptor density in these brain regions, A quantitative autoradiographic assay with [H-3]-SCH 23390 was performed with samples from schizophrenic patients, normal controls, neuroleptic-treated controls, and suicides, There was a significant elevation in specific binding of [H-3]-SCH 23390 in the intermediate layer of the prefrontal cortex from neuroleptic-treated controls (p = .05). Elevated [H-3]-SCH 23390 binding in several layers from prefrontal and cingulate cortex was observed in schizophrenic subjects, although these results did not reach statistical significance, When data from subjects who had received neuroleptics (schizophrenics and neuroleptic controls) were compared to subjects who had not received neuroleptics (normal controls and suicides), there was a significant elevation in receptor density in both the prefrontal (p = .05) and cingulate cortices (p = .03), These data suggest that elevated [H-3]-SCH 23390 binding in human prefrontal and cingulate cortices may occur with chronic neuroleptic treatment, although increased receptor density that may exist as a feature of psychotic illnesses cannot be excluded. RP Knable, MB (reprint author), NIMH, INTRAMURAL RES PROGRAM, CLIN BRAIN DISORDERS BRANCH, 2700 MARTIN LUTHER KING JR AVE, WASHINGTON, DC 20032 USA. NR 43 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1996 VL 40 IS 12 BP 1191 EP 1199 DI 10.1016/S0006-3223(96)00116-3 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VW938 UT WOS:A1996VW93800001 PM 8959283 ER PT J AU Jacobsen, LK Hommer, DW Hong, WL Castellanos, FX Frazier, JA Giedd, JN Rapoport, JL AF Jacobsen, LK Hommer, DW Hong, WL Castellanos, FX Frazier, JA Giedd, JN Rapoport, JL TI Blink rate in childhood-onset schizophrenia: Comparison with normal and attention-deficit hyperactivity disorder controls SO BIOLOGICAL PSYCHIATRY LA English DT Article DE blink rate; schizophrenia; children; ADHD; eye tracking ID SACCADIC EYE-MOVEMENTS; MONKEY SUPERIOR COLLICULUS; GABA-RELATED SUBSTANCES; NIGRA PARS RETICULATA; SMOOTH-PURSUIT; NEUROLEPTIC TREATMENT; TRACKING DYSFUNCTION; CHILDREN; RECEPTORS; DOPAMINE AB Several lines of evidence have implicated central dopaminergic pathways in the modulation of blink rate. In the present study, blink rare during smooth pursuit was examined in 17 children with childhood-onset schizophrenia, on and off of clozapine, and compared to that of age-matched normal children and unmedicated children with attention-deficit hyperactivity disorder (ADHD). As has been observed in adolescent and adult schizophrenics, blink rate was significantly higher in schizophrenic children relative to normal and ADHD controls, Within the schizophrenic group, blink rate did not significantly change with the introduction of clozapine and was not related to clinical variables, Blink rate was positively correlated with deterioration in smooth pursuit in normal subjects. (C) 1996 Society of Biological Psychiatry C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. ZENECA PHARMACEUT,CNS CLIN RES,WILMINGTON,DE. RP Jacobsen, LK (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,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 55 TC 21 Z9 21 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1996 VL 40 IS 12 BP 1222 EP 1229 DI 10.1016/0006-3223(95)00625-7 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VW938 UT WOS:A1996VW93800005 PM 8959287 ER PT J AU Ozaki, N Rosenthal, NE Pesonen, U Lappalainen, J FeldmanNaim, S Schwartz, PJ Turner, EH Goldman, D AF Ozaki, N Rosenthal, NE Pesonen, U Lappalainen, J FeldmanNaim, S Schwartz, PJ Turner, EH Goldman, D TI Two naturally occurring amino acid substitutions of the 5-HT2A receptor: Similar prevalence in patients with seasonal affective disorder and controls SO BIOLOGICAL PSYCHIATRY LA English DT Article DE seasonal affective disorder; 5-HT2A; receptor; gene; polymorphism; polymerase chain reaction; sequence ID INCREASED SEROTONIN2; POINT MUTATIONS; GENE HTR2; BINDING; POLYMORPHISM; RESPONSES AB We screened the 5-HT2A receptor gene coding region in 50 patients with seasonal affective disorder (SAD) using a single strand conformational polymorphism analysis and estimated the frequencies of two synonymous and two non-synonymous substitutions we detected in 70 Centre d'Etude du Polymorphism Humain (CEPH) population controls and 62 normal controls, Both of the amino acid substitutions: Ala(447)-Val(447) and His(452)-Tyr(452), were located within the cytoplasmic, C-terminal tail of the receptor, Rarer allele frequencies in CEPH were 0.7% and 9.3% for Val(447) and Tyr(452), respectively. Allele frequencies of all four polymorphisms, including the two amino acid substitutions, were not significantly different in SAD patients as compared to CEPH and normal controls, Lack of association of Val(447) and Tyr(452) to SAD is consistent with observations showing normal 5-HT2A receptor Ca2+ response in platelets with this disorder, however, the two 5-HT2A amino acid substitutions may lead to differences in behavioral phenotypes. (C) 1996 Society of Biological Psychiatry C1 NIAAA,NEUROGENET LAB,BETHESDA,MD. RP Ozaki, N (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008; Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Turner, Erick/0000-0002-3522-3357; Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 27 TC 63 Z9 64 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1996 VL 40 IS 12 BP 1267 EP 1272 DI 10.1016/0006-3223(95)00649-4 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VW938 UT WOS:A1996VW93800009 PM 8959291 ER PT J AU Adinoff, B Kiser, JMC Martin, PR Linnoila, M AF Adinoff, B Kiser, JMC Martin, PR Linnoila, M TI Response of dehydroepiandrosterone to corticotropin-releasing hormone stimulation in alcohol-dependent subjects SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcoholism; corticotropin; hypothalamic-hypophyseal system; steroids ID PLASMA DEHYDROEPIANDROSTERONE; SULFATE; INSULIN; MEN C1 UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX 75230. MED UNIV S CAROLINA,DEPT BIOMETRY & EPIDEMIOL,CHARLESTON,SC 29425. VANDERBUILT SCH MED,DEPT PSYCHIAT,NASHVILLE,TN. NIAAA,BETHESDA,MD. RP Adinoff, B (reprint author), VET ADM MED CTR,4500 S LANCASTER,DALLAS,TX 75216, USA. RI Martin, Peter/A-7738-2008 NR 15 TC 7 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1996 VL 40 IS 12 BP 1305 EP 1307 DI 10.1016/S0006-3223(96)00381-2 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VW938 UT WOS:A1996VW93800016 PM 8959298 ER PT J AU Cumming, RC Liu, JM Youssoufian, H Buchwald, M AF Cumming, RC Liu, JM Youssoufian, H Buchwald, M TI Suppression of apoptosis in hematopoietic factor-dependent progenitor cell lines by expression of the FAC gene SO BLOOD LA English DT Article ID ABNORMAL LYMPHOKINE PRODUCTION; DISEASE FANCONI-ANEMIA; GROUP-C; BCL-2 ONCOPROTEIN; STROMAL CELLS; PLASMA-CELLS; IN-VITRO; DEATH; GROWTH; SURVIVAL AB Fanconi anemia (FA) is a genetically heterogeneous, inherited blood disorder characterized by bone marrow failure, congenital malformations, and a predisposition to leukemias. Because FA cells are hypersensitive to DNA cross-linking agents and have chromosomal instability, FA has been viewed as a disorder of DNA repair, However, the exact cellular defect in FA cells has not been identified. Sequence analysis of the gene defective in group C patients (FAC) has shown no significant homologies to other known genes. The FAC protein has been localized to the cytoplasm, indicating that FAC may either play an indirect role in DMA repair or is involved in a different cellular pathway. Recent evidence has indicated that FA cells may be predisposed to apoptosis, especially after treatment with DNA cross-linking agents. The demonstration that genes can suppress apoptosis has been accomplished by overexpression of such genes in growth factor-dependent cell lines that die by apoptosis after factor withdrawal. Using retroviral-mediated gene transfer, we present evidence that expression of FAC in the hematopoietic factor-dependent progenitor cell lines 32D and MO7e can suppress apoptosis induced by growth factor withdrawal. Flow cytometry and morphologic analysis of propidium iodide stained cells showed significantly lower levels of apoptosis in FAC-retroviral transduced cells after growth factor deprivation. Expression of FAC in both cell lines promoted increased viability rather than proliferation, which is consistent with other apoptosis-inhibiting genes such as Bcl-2. These findings imply that FAC may act as a mediator of an apoptotic pathway initiated by growth factor withdrawal. Furthermore, the congenital malformations and hematologic abnormalities characterizing FA may be related to an increased predisposition of FA progenitor cells to undergo apoptosis, particularly in the absence of extracellular signals. (C) 1996 by The American Society of Hematology. C1 HOSP SICK CHILDREN,RES INST,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. UNIV TORONTO,DEPT MOL & MED GENET,TORONTO,ON,CANADA. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. RI Cumming, Robert/G-2185-2010 FU NHLBI NIH HHS [HL52138] NR 56 TC 70 Z9 70 U1 0 U2 1 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 DEC 15 PY 1996 VL 88 IS 12 BP 4558 EP 4567 PG 10 WC Hematology SC Hematology GA VZ305 UT WOS:A1996VZ30500017 PM 8977247 ER PT J AU Bridges, KR Barabino, GD Brugnara, C Cho, MR Christoph, GW Dover, G Ewenstein, BM Golan, DE Guttmann, CRG Hofrichter, J Mulkern, RV Zhang, B Eaton, WA AF Bridges, KR Barabino, GD Brugnara, C Cho, MR Christoph, GW Dover, G Ewenstein, BM Golan, DE Guttmann, CRG Hofrichter, J Mulkern, RV Zhang, B Eaton, WA TI A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy SO BLOOD LA English DT Article ID VASCULAR ENDOTHELIAL-CELLS; HEMOGLOBIN-F PRODUCTION; GLOBIN GENE-CLUSTER; RED-BLOOD-CELLS; S GELATION; DELAY TIME; ANEMIA; DISEASE; POLYMERIZATION; KINETICS AB During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, H-1-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement. This is a US government work. There are no restrictions on its use. C1 BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA. CHILDRENS HOSP,DEPT LAB MED,BOSTON,MA. CHILDRENS HOSP,DEPT RADIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOL PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA. NORTHEASTERN UNIV,DEPT CHEM ENGN,BOSTON,MA 02115. JOHNS HOPKINS UNIV HOSP,PEDIAT HEMATOL DIV,BALTIMORE,MD 21205. NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RP Bridges, KR (reprint author), BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,DEPT MED,221 LONGWOOD AVE,LMRC 620,BOSTON,MA 02115, USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NHLBI NIH HHS [HL15157, HL28028, HL32854] NR 48 TC 115 Z9 117 U1 0 U2 6 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 DEC 15 PY 1996 VL 88 IS 12 BP 4701 EP 4710 PG 10 WC Hematology SC Hematology GA VZ305 UT WOS:A1996VZ30500034 PM 8977264 ER PT J AU Hakim, F Childs, R Balow, J Cowan, K Zujewski, J Gress, R AF Hakim, F Childs, R Balow, J Cowan, K Zujewski, J Gress, R TI Development of paroxysmal nocturnal hemoglobinuria after chemotherapy SO BLOOD LA English DT Letter ID APLASTIC-ANEMIA; PATHOGENETIC LINK RP Hakim, F (reprint author), NIDDK,NCI,BETHESDA,MD 20892, USA. NR 7 TC 4 Z9 4 U1 0 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 DEC 15 PY 1996 VL 88 IS 12 BP 4725 EP 4726 PG 2 WC Hematology SC Hematology GA VZ305 UT WOS:A1996VZ30500037 PM 8977267 ER PT J AU Henson, DE AF Henson, DE TI 25th Anniversary of the Signing of the National Cancer Act, December 23, 1971 - Introduction SO CANCER LA English DT Editorial Material RP Henson, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EPN BLDG,ROOM 305,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1996 VL 78 IS 12 BP 2582 EP 2583 PG 2 WC Oncology SC Oncology GA VW714 UT WOS:A1996VW71400019 PM 8952567 ER PT J AU Tisevich, DA AF Tisevich, DA TI Legislative history of the National Cancer Institute and the National Cancer Program SO CANCER LA English DT Article; Proceedings Paper CT 25th Anniversary Meeting of the Signing of the National Cancer Act CY JUN 10, 1996 CL WASHINGTON, DC SP Amer Canc Soc RP Tisevich, DA (reprint author), NCI,OFF LEGISLAT & CONGRESS ACTIV,BLDG 311,ROOM A11A21,31 CTR DR MSC 2590,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1996 VL 78 IS 12 BP 2620 EP 2621 DI 10.1002/(SICI)1097-0142(19961215)78:12<2620::AID-CNCR34>3.0.CO;2-W PG 2 WC Oncology SC Oncology GA VW714 UT WOS:A1996VW71400032 PM 8952578 ER PT J AU Kohn, KW AF Kohn, KW TI Beyond DNA cross-linking: History and prospects of DNA-targeted cancer treatment - Fifteenth Bruce F. Cain memorial award lecture SO CANCER RESEARCH LA English DT Article ID MOUSE LEUKEMIA-L1210 CELLS; TOPOISOMERASE-II CLEAVAGE; P53 TUMOR-SUPPRESSOR; DIFFERENTIAL CYTO-TOXICITY; L-PHENYLALANINE MUSTARD; CARCINOMA HT-29 CELLS; SIMIAN VIRUS-40 DNA; HAMSTER OVARY CELLS; C-MYC PROTOONCOGENE; DOUBLE-STRAND BREAK AB The origin of cancer chemotherapy can be traced to the wartime discovery of the lymphotoxic action of nitrogen mustards, These and other bifunctional agents were later found to produce various types of DNA cross-links, and some of these agents continue to be mainstays of current therapy, The cellular pharmacology of these drugs was studied extensively during the 1970s and 1980s by means of DNA filter elution methodology. In the course of these investigations, DNA topoisomerases were discovered to be targets of anthracyclines and several other classes of anticancer drugs, DNA cross-linkers and topoisomerase blockers have generally similar cytotoxic mechanisms, which depend on DNA damage detection, DNA repair, cell cycle arrest, and cell death by apoptosis, The molecular control of these processes, involving oncogenes and tumor suppressor genes, is being revealed by current research, Cancer cells often have defects within these control systems, and these defects may confer selective sensitivity to appropriately designed drug therapy. Panels of human tumor cell lines may serve to link the molecular defects with specific drug sensitivities, Such correlations could guide the selection of drugs for therapy based on molecular diagnosis of individual tumors. RP Kohn, KW (reprint author), NCI,MOL PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892, USA. NR 206 TC 78 Z9 79 U1 1 U2 2 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 DEC 15 PY 1996 VL 56 IS 24 BP 5533 EP 5546 PG 14 WC Oncology SC Oncology GA VX880 UT WOS:A1996VX88000002 PM 8971150 ER PT J AU Karp, JE Chiarodo, A Brawley, O Kelloff, GJ AF Karp, JE Chiarodo, A Brawley, O Kelloff, GJ TI Prostate cancer prevention: Investigational approaches and opportunities SO CANCER RESEARCH LA English DT Review ID ANDROGEN-RECEPTOR GENE; ENDOTHELIAL GROWTH-FACTOR; IN-SITU HYBRIDIZATION; E-CADHERIN EXPRESSION; INTRAEPITHELIAL NEOPLASIA; UNITED-STATES; BREAST-CANCER; INTEGRIN ALPHA(V)BETA(3); NUCLEOTIDE EXCHANGE; TUMOR ANGIOGENESIS C1 NCI,CHEMPREVENT BRANCH,DIV CANC PREVENT & CONTROL,NIH,ROCKVILLE,MD 20852. NCI,ORGAN SYST PROGRAM,DIV CANC TREATMENT DIAG & CTR,NIH,ROCKVILLE,MD 20852. NCI,COMMUNITY ONCOL BRANCH,DIV CANC PREVENT & CONTROL,NIH,ROCKVILLE,MD 20852. NR 120 TC 38 Z9 38 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 DEC 15 PY 1996 VL 56 IS 24 BP 5547 EP 5556 PG 10 WC Oncology SC Oncology GA VX880 UT WOS:A1996VX88000003 PM 8971151 ER PT J AU Puri, RK Hoon, DS Leland, P Snoy, P Rand, RW Pastan, I Kreitman, RJ AF Puri, RK Hoon, DS Leland, P Snoy, P Rand, RW Pastan, I Kreitman, RJ TI Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma SO CANCER RESEARCH LA English DT Article ID RENAL-CELL-CARCINOMA; TUMOR-NECROSIS-FACTOR; RECEPTOR GAMMA-CHAIN; CHIMERIC PROTEIN; IL-4 RECEPTORS; HUMAN-MELANOMA; EXPRESSION; GROWTH; INHIBITION; INTERFERON AB Effective treatment is lacking for malignant glioblastoma/astrocytoma. We have identified interleukin-4 receptors (IL-4R) on human malignant astrocytoma. We demonstrate that 16 of 21 surgical samples of high-grade astrocytoma and glioblastoma but not normal brain tissues expressed IL-4R as assessed by reverse transcriptase PCR. We further demonstrate that human malignant astrocytoma cell lines express high-affinity IL-4R. Using a chimeric protein composed of circularly permuted IL-4 and a truncated form of Pseudomonas exotoxin A, we observed that this toxin (IL4(38-37)-PE38KDEL) is highly cytotoxic to IL-4R-bearing glioblastoma cells. Compared with a previously reported IL4-PE chimeric protein (IL-PE4E), IL4(38-37)-PE38KDEL bound with higher affinity and was 3-30-fold more cytotoxic to glioblastoma cell lines, Upon intrathecal administration in monkeys, high cerebrospinal fluid IL4(38-37)-PE38KDEL levels mere achieved using 2- and 6-mu g/kg doses without any central nervous system or other abnormalities. IL4(38-37)-PE38KDEL levels were not detectable in the serum of any monkey studied. When IL4(38-37)-PE38KDEL was injected into the right frontal cortex of rats, localized necrosis was observed at 1000-ng/ml doses but not at less than or equal to 100-ng/ml doses. We conclude that by localized administration, nontoxic levels of IL4(38-37)-PE38KDEL can be achieved, which may have significant cytotoxic activity against malignant astrocytoma. C1 NIH,LAB MOL TUMOR BIOL,DIV VET SERV,CTR BIOL EVALUAT & RES,FOOD & DRUG ADM,BETHESDA,MD 20892. ST JOHNS HOSP,JOHN WAYNE CANC INST,DIV MOL & CELLULAR IMMUNOL & NEUROONCOL,SANTA MONICA,CA 90404. NCI,MOL BIOL LAB,DIV CANC BIOL DIAGNOSIS & CTR,NIH,BETHESDA,MD 20892. RP Puri, RK (reprint author), NIH,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,FOOD & DRUG ADM,BETHESDA,MD 20892, USA. OI Hoon, Dave/0000-0003-1915-3683 NR 32 TC 91 Z9 95 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 DEC 15 PY 1996 VL 56 IS 24 BP 5631 EP 5637 PG 7 WC Oncology SC Oncology GA VX880 UT WOS:A1996VX88000020 PM 8971168 ER PT J AU Siders, WM Halloran, PJ Fenton, RG AF Siders, WM Halloran, PJ Fenton, RG TI Transcriptional targeting of recombinant adenoviruses to human and murine melanoma cells SO CANCER RESEARCH LA English DT Article ID THYMIDINE KINASE GENE; MOUSE TYROSINASE GENE; LUNG-CANCER CELLS; TRANSGENIC MICE; CARCINOEMBRYONIC ANTIGEN; HEPATOCELLULAR-CARCINOMA; MICROPHTHALMIA GENE; RETROVIRAL VECTORS; ENHANCER-PROMOTER; HUMAN-BREAST AB One potential avenue for future cancer therapy involves the specific targeting of effector genes to cancer cells throughout the body, including distant metastatic sites. As a first step toward this goal, we tested the ability of the transcriptional regulatory elements of the human and mouse tyrosinase genes to promote high levels of pigment cell-specific transcription. A construct consisting of 209 hp of the human tyrosinase promoter linked to two enhancer elements was demonstrated to drive high-level, melanoma-specific expression of a beta-galactosidase (beta-gal) reporter gene in transient transfection assays, In studies of the murine tyrosinase promoter region, constructs containing up to 2500 bp of the 5' regulatory region were found to have very low transcriptional activity in murine melanoma cells, However, as with the human system, addition of two tandem repeats of an upstream enhancer element resulted in high levels of lineage-specific transcriptional activation, The murine tyrosinase promoter-enhancer expression cassette was introduced into the E1 region of a recombinant adenovirus to generate the virus AdmTyr-beta gal. This virus grows to high titer and maintains transcriptional specificity for pigment cell lineages, Strikingly, AdmTyF-beta gal is extremely active in human melanoma cells, in some cases exceeding the transcriptional activity of a cytomegalovirus promoter-driven recombinant beta-gal virus. Tissue specificity of gene expression is maintained, with very low levels observed in tumors and primary human cells derived from other lineages. These data provide evidence that it is possible to target human melanoma cells with great efficiency and specificity using high-titer recombinant adenovirus vectors. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CLIN SCI,FREDERICK,MD 21702. RI Halloran, Philip/J-1390-2012 OI Halloran, Philip/0000-0003-1371-1947 FU NCI NIH HHS [N01-CO-74102] NR 47 TC 67 Z9 71 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 DEC 15 PY 1996 VL 56 IS 24 BP 5638 EP 5646 PG 9 WC Oncology SC Oncology GA VX880 UT WOS:A1996VX88000021 PM 8971169 ER PT J AU Reeves, ME Royal, RE Lam, JS Rosenberg, SA Hwu, P AF Reeves, ME Royal, RE Lam, JS Rosenberg, SA Hwu, P TI Retroviral transduction of human dendritic cells with a tumor-associated antigen gene SO CANCER RESEARCH LA English DT Article ID INFILTRATING LYMPHOCYTES; STEM-CELLS; TNF-ALPHA; VIRUS; IDENTIFICATION; PEPTIDES AB Dendritic cells (DCs) are potent antigen-presenting cells that can activate quiescent T lymphocytes. When pulsed with tumor-associated antigen (TAA) peptide or protein, murine DCs can provide antitumor immunity. me reasoned that DCs retrovirally transduced with TAA genes might have important advantages over peptide- or protein-pulsed DCs, including long-term TAA presentation in pipe, and presentation of important but undefined epitopes. Therefore, we attempted to retrovirally transduce human DCs with a melanoma TAA gene (MART-1) and determine whether these transduced DCs could raise a specific antitumor response from quiescent autologous T lymphocytes. After retroviral transduction, human CD34(+) cells were differentiated into DCs in vitro using granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, and stem cell factor, This method consistently yielded a population of DCs as analyzed by morphology phenotype, and MLR. Flow cytometric analysis revealed that 22-28% of cells expressing the DC phenotype also expressed a transduced marker gene. When DCs were transduced with the gene encoding MART-1, they stimulated much higher levels of cytokine release by MART-1-specific tumor-infiltrating lymphocytes than control DCs transduced with an irrelevant gene. In vitro stimulation using MART-1-transduced DCs but not control-transduced DCs raised specific antitumor CTLs from autologous quiescent T cells. These results provide evidence that human DCs can be retrovirally transduced with a TAA gene and that these transduced cells can raise a specific antitumor immune response in vitro, Transduced DCs may be useful for in vivo immunization against TAA. C1 NCI, SURG BRANCH, NIH, BETHESDA, MD 20892 USA. NR 28 TC 195 Z9 199 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1996 VL 56 IS 24 BP 5672 EP 5677 PG 6 WC Oncology SC Oncology GA VX880 UT WOS:A1996VX88000026 PM 8971174 ER PT J AU Thompson, JS Reese, KJ DeBaun, MR Perlman, EJ Feinberg, AP AF Thompson, JS Reese, KJ DeBaun, MR Perlman, EJ Feinberg, AP TI Reduced expression of the cyclin-dependent kinase inhibitor gene p57(KIP2) in Wilms' tumor SO CANCER RESEARCH LA English DT Article ID WIEDEMANN-BECKWITH SYNDROME; HUMAN CANCER; CHROMOSOME-11; H19; RELAXATION; ANGELMAN; LOCUS AB We have previously shown that the p57(KIP2) gene, which encodes a cyclin-dependent kinase inhibitor, undergoes genomic imprinting and lies within a 700-kb domain of imprinted genes on 11p15, including IGF2 and H19, Loss of heterozygosity and loss of imprinting (LOI) of this region are frequently observed in Wilms' tumor (WT) and other embryonal malignancies, Although LOI of p57(KIP2) was observed in some WTs (similar to 10%), allele-specific expression was preserved in most tumors examined, Because our initial studies were inconclusive concerning the absolute expression level of p57(KIP2) in WT, we developed a sensitive and quantitative RNase protection assay to determine if changes in p57(KIP2) expression play a role in WT. Expression of p57(KIP2) was found to he virtually absent in 21 of 21 WTs compared to matched normal kidney from the same patients, as well as compared to fetal kidney. We also examined p57(KIP2) expression in the normal kidney and tongue of patients with Beckwith-Wiedemann syndrome (BWS), which predisposes to WT and also involves LOI of IGF2 and H19, Although p57(KIP2) was undetectable in BWS tongue, similar results were also observed in postnatal non-BWS tongue samples. Most primary skin fibroblast cultures of BWS cell lines exhibited normal imprinting of p57(KIP2). However, one BWS patient did show LOI of p57(KIP2) in skin fibroblasts, Thus, p57(KIP2) is part of a domain of genes on 11p15 that show altered expression and, in some cases, altered imprinting in WT and BWS. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA65145] NR 28 TC 67 Z9 68 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 DEC 15 PY 1996 VL 56 IS 24 BP 5723 EP 5727 PG 5 WC Oncology SC Oncology GA VX880 UT WOS:A1996VX88000034 PM 8971182 ER PT J AU Wang, J Hargrove, ME Ting, CC AF Wang, J Hargrove, ME Ting, CC TI IL-2 and IL-4 mediate through two distinct kinase pathways for the activation of alpha CD3-induced activated killer cells SO CELLULAR IMMUNOLOGY LA English DT Article ID STIMULATORY FACTOR-I; PROTEIN-TYROSINE KINASE; LYMPHOCYTE-T PRECURSORS; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY; ANTIGEN RECEPTOR; MYELOID CELLS; JANUS KINASE; INTERLEUKIN-2; PHOSPHORYLATION AB The present study has examined the role of IL-2 and IL-4 in the regulation of different kinase pathways for the generation of alpha CD3-induced activated killer cells, CD3-AK, It has previously been shown that the IL-2 promoted CD3-AK cell response is mediated through a PKC (protein kinase C)-dependent pathway, which is susceptible to PKC inhibitors and resistant to inhibitors of PTK (protein tyrosine kinase), and that IL-4 synergized with IL-2 to induce CD3-AK cells, However, the IL-4-promoted CDS-AK cell response was PKC-independent as assessed by its resistance to PKC inhibitors, These findings suggest a dichotomy in the pathways leading to CD3-AK cell generation, To further determine whether IL-4 mediated a different kinase pathway to activate the T cells, we studied its effect on protein tyrosine phosphorylation, IL-4 up-regulated protein tyrosine phosphorylation in CD3-AK cells in a dose-dependent fashion, and resulted in increased levels of a number of phosphorylated proteins, Of particular note was the increase of tyrosine phosphorylated p56(lck) and p59(fyn) in CD3-AK cells, The changes in global protein tyrosine phosphorylation were correlated with the up-regulation by IL-4 of CD3-AK cell cytolytic activity, and the production of granzyme A, alpha IL-4 specifically blocked all the effects which were induced by IL-4. The PTK inhibitor genistein inhibited the IL-4-augmented cytolytic activity of CD3-AK cells as well as the IL-4-induced augmentation of protein tyrosine phosphorylation to the basal level of CD3-AK cells cultured in IL-2 alone, Consistent with a dichotomy in pathways for IL-2- and IL-4-mediated CD3-AK generation, genistein had no effect on the generation of CDS-AK cells cultured in IL-2 alone, Thus while PKC is primarily involved in the generation of IL-2-promoted CD3-AK cells, PTK appears to be required for the regulation of IL-4-promoted CD3-AK response. (C) 1996 Academic Press, Inc. C1 NCI,DIV BASIC SCI,LAB IMMUNE CELL BIOL,NIH,BETHESDA,MD 20892. NR 43 TC 7 Z9 7 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 1996 VL 174 IS 2 BP 138 EP 146 DI 10.1006/cimm.1996.0303 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VZ377 UT WOS:A1996VZ37700004 PM 8954613 ER PT J AU Secord, EA Rizzo, LV Barroso, EWS Umetsu, DT Thorbecke, GJ DeKruyff, RH AF Secord, EA Rizzo, LV Barroso, EWS Umetsu, DT Thorbecke, GJ DeKruyff, RH TI Reconstitution of germinal center formation in nude mice with Th1 and Th2 clones SO CELLULAR IMMUNOLOGY LA English DT Article ID CENTER B-CELLS; INDUCER T-CELLS; LEU 7+ CELLS; IMMUNE-RESPONSES; FUNCTIONAL-HETEROGENEITY; LYMPHOID FOLLICLES; ANTIBODY-RESPONSES; CD40 LIGAND; IN-VIVO; MEMORY AB We investigated the ability of hemocyanin (KLH)-specific cloned CD4(+) T cells expressing defined cytokine profiles to support germinal center (GC) formation in syngeneic athymic recipients in response to hapten-KLH challenge. Th1 clones producing IL-2 and IFN-gamma did not by themselves increase GC production above background, while Th2 cells producing IL-4 and IL-5 did. However, the combination of Th1 and Th2 cytokines was more effective than Th2 cytokines alone, suggesting a synergistic effect in this aspect of their help for B cells. In contrast to GC formation, antibody production could be induced with Th1 or Th2 clones given separately (Th1 clones inducing IgG2a, and Th2 clones inducing IgG1 and IgE). These results indicate that the T cell requirements for GC production are different from those for isotype switching and Ig secretion. It is postulated that the synergy between Th1 and Th2 cells in the induction of GC formation reflects the synergy between Th1 and Th2 cytokines, such as IFN-gamma and IL-5, in promotion of GC cell proliferation. (C) 1996 Academic Press, Inc. C1 NYU,SCH MED,KAPLAN CANC CTR,NEW YORK,NY 10016. NEI,IMMUNOL LAB,SECT IMMUNOREGULAT,BETHESDA,MD 20892. STANFORD UNIV,DEPT PEDIAT,PALO ALTO,CA 94305. RP Secord, EA (reprint author), NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10016, USA. RI Rizzo, Luiz Vicente/B-4458-2009 FU NIA NIH HHS [AG-04980] NR 62 TC 13 Z9 13 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 1996 VL 174 IS 2 BP 173 EP 179 DI 10.1006/cimm.1996.0307 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VZ377 UT WOS:A1996VZ37700008 PM 8954617 ER PT J AU Schott, ME Wells, DT Schlom, J Abrams, SI AF Schott, ME Wells, DT Schlom, J Abrams, SI TI Comparison of linear and branched peptide forms (MAPs) in the induction of T helper responses to point-mutated ras immunogens SO CELLULAR IMMUNOLOGY LA English DT Article ID DEFINED SYNTHETIC VACCINE; MULTIPLE-ANTIGEN PEPTIDES; CELL RECOGNITION; B-EPITOPE; DESIGN; LYMPHOCYTES; ANTIBODIES; PROTECTION; SYSTEM; HIV-1 AB The utility of multiple antigenic peptides (MAPs) for the induction of antibody and cellular immune responses in animal models has been demonstrated for a variety of peptide epitopes involved in human disease, However, little is known about immune responses to MAPs constructed with antigenic tumor epitopes, nor has peptide specificity in branched forms been addressed, A potentially important advantage of the MAP system over linear peptide immunogens for clinical applications is elimination of the need for a protein carrier with its associated toxicity and immunogenicity. Here, we examined cellular immune responses following in vivo administration of MAPs incorporating a 13-mer T helper epitope from point-mutated ras p21 (ras V12) and compared the potency of the responses to that of the linear peptide. The Gly --> Val mutation in position 12, which is associated with a range of human carcinomas, represents a useful system for evaluating the specificity of the immune response, In initial studies with the point-mutated Linear peptide epitope, optimal in vitro proliferation responses were obtained following sc administration of the peptide in a squalane-containing adjuvant formulation, Comparative immunization studies using point-mutated MAPs bearing two, four, or eight branches were administered either in saline or in adjuvant. These studies showed that adjuvant was required for the induction of cellular immune responses using both linear and all three forms of branched peptides, Moreover, there was no apparent advantage of using any of the MAPs vs linear peptide when equivalent mass amounts were administered, i.e., the intensity of the immune response was no greater using any of the branched structures compared to the linear form. Specificity of the in vivo responses for both the linear and the MAP immunogens was demonstrated by the higher stimulation indices observed in vitro in the presence of the mutant ras V12 vs the normal ras G12 linear peptide, No apparent cellular immune response to the MAP core structure itself was observed. However, a nonspecific response to the two-branched MAP2G12 structure was observed in some assays, the nature of which is unknown at this time, This work represents the first reported investigation of a cellular immune response using MAP immunogens incorporating a tumor-specific peptide epitope and demonstrates that linear peptides are as efficient as three different MAP structures in the generation of specific T cell responses. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 30 TC 12 Z9 13 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 1996 VL 174 IS 2 BP 199 EP 209 DI 10.1006/cimm.1996.0310 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VZ377 UT WOS:A1996VZ37700011 PM 8954620 ER PT J AU Fukushima, PI Phuong, KTN OGrady, P StetlerStevenson, M AF Fukushima, PI Phuong, KTN OGrady, P StetlerStevenson, M TI Flow cytometric analysis of kappa and lambda light chain expression in evaluation of specimens for B-cell neoplasia SO CYTOMETRY LA English DT Article DE light chain restriction; monoclonal B-cell detection; flow cytometry ID NON-HODGKINS LYMPHOMA; IMMUNOGLOBULIN LIGHT; PERIPHERAL-BLOOD; CLONAL EXCESS; ANTIBODIES; MYELOMA AB Analysis of light chain expression is one of the most important determinations in flow cytometric immunophenotyping of patient specimens. Numerous technical factors, such as antibody choice and cytophilic antibody artifact, impact a laboratory's ability to perform this test. There have been conflicting reports concerning the efficacy of polyclonal versus monoclonal antibodies, as well as methods of circumventing cytophilic antibodies, indicating that a consensus has not been reached on optimal methods for light chain determination. The authors have investigated methods for light chain analysis in 104 normal donors and 366 patient specimens, comparing different anti-light chain antibodies as well as strategies for analysis of specimens with low numbers of monoclonal B cells, admired polyclonal B cells, or cytophilic antibodies. The patient specimens were either part of the initial diagnostic evaluation of patients with suspected lymphoma, or were performed for staging or assessment of treatment of patients with known B-cell neoplasia. No monoclonality was detected in control specimens, and there was no significant difference in staining with monoclonal verses polyclonal anti-light chain antibodies. In addition, cytophilic antibody did not obscure results in normal controls. Monoclonality was detected in 106 patient specimens, with 89 showing gross involvement with a predominant monoclonal B-cell process. However, in 43% of the grossly monoclonal specimens, there was failure to detect monoclonality with at least one light chain antibody set, with 8% of these cases showing failure with two anti-light chain sets. This indicates the importance of antibody choice in light chain analysis. Cytophilic antibody artifact in monoclonal specimens was easily overcome by appropriate antibody combinations, obviating the need for cytophilic antibody-shedding by incubation at 37 degrees C in fetal calf serum. In 27 patient specimens with low numbers of B cells or admired polyclonal B cells, a clonal search based on FSC and CD19 or CD20 expression was performed. In 17 of the 27 cases (63%), a small monoclonal population was detected among admired polyclonal B cells. The authors conclude that multiple strategies are necessary in flow cytometric analysis for B-cell monoclonality. (C) 1996 Wiley-Liss, Inc.* C1 NCI,FLOW CYTOMETRY UNIT,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 18 TC 46 Z9 48 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 0196-4763 J9 CYTOMETRY JI Cytometry PD DEC 15 PY 1996 VL 26 IS 4 BP 243 EP 252 DI 10.1002/(SICI)1097-0320(19961215)26:4<243::AID-CYTO2>3.0.CO;2-D PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WB910 UT WOS:A1996WB91000002 PM 8979022 ER PT J AU Mardiney, M Brown, MR Fleisher, TA AF Mardiney, M Brown, MR Fleisher, TA TI Measurement of T-cell CD69 expression: A rapid and efficient means to assess mitogen- or antigen-induced proliferative capacity in normals SO CYTOMETRY LA English DT Article DE CD69; H-3-thymidine; lymphocyte; mitogen; antigen ID ACTIVATION ANTIGEN; LEU-23; INDUCTION; EA-1 AB We have analyzed the expression of the activation antigen CD69 on normal human T cells by flow cytometry following stimulation with mitogens and recall antigen. These data were compared to parallel studies assessing the proliferative response using the H-3-thymidine (H-3-TdR) incorporation assay. Three different mitogens (PHA, ConA, and CD2/CD2R) induced maximal expression of CD69 at 24 h, which remained stable throughout the 72 h culture period. The mitogen-stimulated cells initiated DNA synthesis as determined by the H-3-TdR assay (72 h) while nonstimulated cells failed to upregulate CD69 or incorporate H-3-TdR. We next compared T cell CD69 expression (n = 12) following stimulation with either CD2/CD2R (5 mu g/ml) or the recall antigen, tetanus toroid (1:1500). Cell proliferation was determined by the 3H-TdR assay at 72 h (CD2/CD2R) or 120 h (tetanus toxoid). Evaluation of CD69 expression at 6 h predicted CD2/CD2R but not tetanus responder status as defined by H-3-TdR incorporation. However, when 4 known tetanus responders (H-3-TdR) were evaluated over time, it was found that at 48 h the fluorescence intensity (of CD69) on tetanus-stimulated CD3(+) cells increased markedly compared with nonstimulated cells (range of increase 43-850%). One individual whose cells failed to respond to tetanus toroid (H-3-TdR and CD69) did respond normally to CD2/CD2R. These observations suggest that flow cytometric evaluation of T cell CD69 expression following mitogen (6 h) or antigen (48 h) stimulation may provide an accurate screen of T-cell responsiveness in normals. (C) 1996 Wiley-Liss, Inc.* C1 NIH,SERV IMMUNOL,BETHESDA,MD 20892. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 17 TC 75 Z9 85 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD DEC 15 PY 1996 VL 26 IS 4 BP 305 EP 310 DI 10.1002/(SICI)1097-0320(19961215)26:4<305::AID-CYTO11>3.0.CO;2-V PG 6 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WB910 UT WOS:A1996WB91000011 PM 8979031 ER PT J AU Wolfsberg, TG White, JM AF Wolfsberg, TG White, JM TI ADAMs in fertilization and development SO DEVELOPMENTAL BIOLOGY LA English DT Review ID SPERM-EGG FUSION; MDC PROTEIN FAMILY; DISINTEGRIN-LIKE; METALLOPROTEASE DOMAIN; TRANSMEMBRANE PROTEIN; PLATELET-AGGREGATION; MEMBRANE-PROTEINS; ALPHA-SUBUNIT; VENOM; CELL C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT CELL BIOL,CHARLOTTESVILLE,VA 22908. RP Wolfsberg, TG (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. FU NIGMS NIH HHS [GM48739] NR 63 TC 202 Z9 212 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 1996 VL 180 IS 2 BP 389 EP 401 DI 10.1006/dbio.1996.0313 PG 13 WC Developmental Biology SC Developmental Biology GA WA846 UT WOS:A1996WA84600002 PM 8954712 ER PT J AU Wray, S Fueshko, SM Kusano, K Gainer, H AF Wray, S Fueshko, SM Kusano, K Gainer, H TI GABAergic neurons in the embryonic olfactory pit/vomeronasal organ: Maintenance of functional GABAergic synapses in olfactory explants SO DEVELOPMENTAL BIOLOGY LA English DT Article ID HORMONE-RELEASING HORMONE; GAMMA-AMINOBUTYRIC-ACID; GLUTAMATE DECARBOXYLASES; GENE-EXPRESSION; NERVOUS-SYSTEM; MOUSE; GABA; CELLS; CULTURES; SIGNALS AB In previous work, we showed a robust gamma-aminobutyric acid (GABAergic) synaptic input onto embryonic luteinizing hormone-releasing hormone (LHRH) neurons maintained in olfactory explants. In this study, we identify GABAergic neurons in olfactory pit (OF) of embryonic mice in vivo and study, using patch-pipet whole-cell current and voltage clamp techniques, synaptic interactions of these neurons in explant cultures. In vivo, glutamate decarboxylase (GAD, the enzyme which synthesizes GABA) mRNA was first detected in nasal regions on Embryonic Day (E) 11.5. From E12.5 to E13.5, robust GAD expression was localized to cells primarily in the ventral aspect of the OF. GAD mRNA was not detected over dorsally located cells in olfactory sensory or respiratory epithelium. In addition, GAD mRNA was not observed in cells along olfactory axons. GAD mRNA was dramatically reduced in the OP/vomeronasal organ by E16.5. Using antibodies against both GABA and GAD, immunopositive axonal-like tracts were detected in the nasal septum on E12.5. GABAergic staining decreased by E13.5. To examine synaptic interactions of these GABAergic cells, embryonic olfactory explants were generated and maintained in serum-free media. As explants spread, neuron-like cells migrated into the periphery, sometimes forming ganglion-like clusters. Cells were recorded, marked intracellularly with Lucifer Yellow and postfixation, immunocytochemically examined. forty-six cells, typically multipolar, were GABAergic, had resting potentials around -50 mV, and exhibited spontaneous action potentials which were generated by spontaneous depolarizing GABAergic (GABA(A)) synaptic activity. OP neurons depolarized in response to GABA by increasing Cl- conductance. The biophysical properties of OF-derived GABAergic neurons were distinct from those reported for olfactory receptor neurons but similar to embryonic LHRH neurons. However, unlike LHRH neurons, GABAergic neurons did not migrate large distances in olfactory explants or appear to leave the olfactory pit in vivo. (C) 1996 Academic Press, Inc. RP Wray, S (reprint author), NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892, USA. OI wray, susan/0000-0001-7670-3915 NR 33 TC 54 Z9 54 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 1996 VL 180 IS 2 BP 631 EP 645 DI 10.1006/dbio.1996.0334 PG 15 WC Developmental Biology SC Developmental Biology GA WA846 UT WOS:A1996WA84600023 PM 8954733 ER PT J AU Johe, KK Hazel, TG Muller, T DugichDjordjevic, MM McKay, RDG AF Johe, KK Hazel, TG Muller, T DugichDjordjevic, MM McKay, RDG TI Single factors direct the differentiation of stem cells from the fetal and adult central nervous system SO GENES & DEVELOPMENT LA English DT Article DE stem cells; neurons; glia ID RAT CEREBRAL-CORTEX; REGION-SPECIFIC DIFFERENTIATION; FOREBRAIN SUBVENTRICULAR ZONE; CLONALLY RELATED CELLS; GROWTH-FACTOR; PRECURSOR CELL; DEVELOPMENTAL EXPRESSION; FUNCTIONAL-PROPERTIES; HIPPOCAMPAL-NEURONS; COMMON PROGENITOR AB Identifying the signals that regulate stem cell differentiation is fundamental to understanding cellular diversity in the brain. In this paper we identify factors that act in an instructive fashion to direct the differentiation of multipotential stem cells derived from the embryonic central nervous system (CNS). CNS stem cell clones differentiate to multiple fates: neurons, astrocytes, and oligodendrocytes. The differentiation of cells in a clone is influenced by extracellular signals: Platelet-derived growth factor (PDGF-AA, -AB, and -BB) supports neuronal differentiation. In contrast, ciliary neurotrophic factor and thyroid hormone T3 act instructively on stem cells to generate clones of astrocytes and oligodendrocytes, respectively. Adult stem cells had remarkably similar responses to these growth factors. These results support a simple model in which transient exposure to extrinsic factors acting through known pathways initiates fate decisions by multipotential CNS stem cells. C1 NINCDS,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 58 TC 892 Z9 959 U1 3 U2 33 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 1996 VL 10 IS 24 BP 3129 EP 3140 DI 10.1101/gad.10.24.3129 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA WA909 UT WOS:A1996WA90900006 PM 8985182 ER PT J AU Miura, Y Miyake, K Yamashita, Y Shimazu, R Copeland, NG Gilbert, DJ Jenkins, NA Inazawa, J Abe, T Kimoto, M AF Miura, Y Miyake, K Yamashita, Y Shimazu, R Copeland, NG Gilbert, DJ Jenkins, NA Inazawa, J Abe, T Kimoto, M TI Molecular cloning of a human RP105 homologue and chromosomal localization of the mouse and human RP105 genes (Ly64 and LY64) SO GENOMICS LA English DT Article ID LEUCINE-RICH REPEATS; B-CELL ACTIVATION; TRANSMEMBRANE PROTEIN; LINKAGE MAP; DROSOPHILA; POLARITY; DOMAINS; TOLL AB RP105 is a mouse B cell surface molecule that transmits a growth-promoting signal and is implicated in the life/death decision of B cells. RP105 has tandem repeats of a leucine-rich motif in the extracellular domain that is expected to be involved in protein-protein interactions. In the present study, a cDNA clone encoding the human homologue of RP105 was isolated. The amino acid sequence of human RP105 is highly homologous to that of mouse RP105 with 74% identity, and the leucine-rich repeats are well conserved. The expression of the human RP105 transcript was detected in some B cell lines, a histiocytic leukemia cell line, and peripheral blood leukocytes. We also determined the chromosomal locations of the mouse RP105 gene (Ly64 locus) and the human RP105 gene (LY64 locus). Interspecific mouse backcross analysis was used to map the Ly64 locus at the distal region of chromosome 13. The human LY64 locus was localized to 5q12 by fluorescence in situ hybridization, confirming the syntenic relationship between these regions of the mouse and human chromosomes. (C) 1996 Academic Press, Inc. C1 SAGA MED SCH,DEPT IMMUNOL,SAGA 849,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. KYOTO PREFECTURAL UNIV MED,DEPT HYG,KYOTO 602,JAPAN. NR 24 TC 32 Z9 33 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 0888-7543 J9 GENOMICS JI Genomics PD DEC 15 PY 1996 VL 38 IS 3 BP 299 EP 304 DI 10.1006/geno.1996.0632 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WB429 UT WOS:A1996WB42900008 PM 8975706 ER PT J AU Takai, S Kozak, CA Kitamura, K Takeda, A AF Takai, S Kozak, CA Kitamura, K Takeda, A TI Assignment of the CD45-AP gene to the centromeric end of mouse chromosome 19 and human chromosome 11q13.1-q13.3 SO GENOMICS LA English DT Article ID INSITU HYBRIDIZATION; PROTEIN; RECEPTOR; LOCALIZATION; ANTIGEN AB CD45-AP is a recently identified phosphorylated protein that specifically associates with the leukocyte-specific transmembrane glycoprotein CD45. The gene for CD45-AP, Ptprcap (protein tyrosine phosphatase, receptor type c polypeptide associated protein), was mapped in mouse by typing the progeny of two multilocus crosses using the mouse CD45-AP cDNA as a Southern hybridization probe, The CD45-AP gene mapped to the centromeric region of Chr 19 proximal to the genes Fth, Cd5, and Pcna-rs. The gene for the human CD45-AP homologue, PTPRCAP, was localized to chromosome band 11q13.1-q13.3 by fluorescence in situ hybridization using human genomic CD45-AP DNA as a hybridization probe, The genetic mapping of the Ptprcap/PTPRCAP genes extends the previously defined synteny conservation of various genes that have been assigned to these regions of the mouse and the human chromosomes. (C) 1996 Academic Press, Inc. C1 BROWN UNIV,ROGER WILLIAMS MED CTR,DEPT PATHOL,PROVIDENCE,RI 02908. INT MED CTR JAPAN,DEPT GENET,RES INST,TOKYO 162,JAPAN. NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 48188] NR 23 TC 3 Z9 3 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 0888-7543 J9 GENOMICS JI Genomics PD DEC 15 PY 1996 VL 38 IS 3 BP 429 EP 431 DI 10.1006/geno.1996.0648 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WB429 UT WOS:A1996WB42900024 PM 8975722 ER PT J AU Farzadegan, H Henrard, DR Kleeberger, CA Schrager, L Kirby, AJ Saah, AJ Rinaldo, CR OGorman, M Detels, R Taylor, E Phair, JP Margolick, JB AF Farzadegan, H Henrard, DR Kleeberger, CA Schrager, L Kirby, AJ Saah, AJ Rinaldo, CR OGorman, M Detels, R Taylor, E Phair, JP Margolick, JB TI Virologic and serologic markers of rapid progression to AIDS after HIV-1 seroconversion SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; seroconversion; anti-gag immune response; progression; viral load ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; TYPE-1 INFECTION; HOMOSEXUAL MEN; ANTIBODY; ANTIGEN; PLASMA; BLOOD; P24; RESPONSES AB The association between early virologic and immunologic events after human immunodeficiency virus type 1 (HIV-1) infection and progression of HIV-1 infection to acquired immunodeficiency syndrome (AIDS) was studied among 59 homosexual men with documented time of seroconversion. Epidemiologic factors, such as number of lifetime sexual partners, history of sexually transmitted diseases, and other factors, also were studied. AII 17 seroconverters in the cohort who developed AIDS within 3 years (rapid progressors = RPs) were compared with 42 men without AIDS for at least 6 years seroconversion (nonrapid progressors = non-RPs). Plasma levels of HIV-1 RNA, p24 antigen, antibodies to HIV-1 structural genes, beta-2 microglobulin, neopterin, and interferon-alpha were measured at four time points: (a) the last seronegative visit, (b) the first seropositive visit, (c) the visit closest to AIDS (or the corresponding visit for the non-RPs) and (d) 6 years after seroconversion (for non-RPs). Up to seroconversion, the RPs had a significantly higher number of lifetime sexual partners than non-RPs (503 versus 171, respectively). At the first seropositive visit, RPs had significantly higher concentrations of plasma HIV-1 RNA (p < 0.01) and prevalence of p24 antigenemia (p < 0.001) and significantly lower levels of antibodies to the HIV-1 gag proteins p17 and p24 (p < 0.01-0.001) compared with non-RPs. These differences increased during follow-up visits. Antibodies to p66 and gp120 were significantly different only at the visit closest to AIDS (p < 0.001), as were beta-2 microglobulin and interferon alpha. These findings suggest that early virologic-immunologic events after HIV-1 infection may determine the rate of progression to AIDS. Anti-gag immune response may prevent rapid progression of HIV-1 disease and should be considered for future vaccine studies. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD. NIH,BETHESDA,MD 20892. ABBOTT LABS,N CHICAGO,IL 60064. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA. UNIV PITTSBURGH,DEPT MICROBIOL,PITTSBURGH,PA. NORTHWESTERN UNIV,SCH MED,DEPT PEDIAT,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,DEPT EPIDEMIOL,LOS ANGELES,CA. NORTHWESTERN UNIV,SCH MED,COMPREHENS AIDS CTR,CHICAGO,IL. FU NIAID NIH HHS [U01-AI-35041, U01-AI-35039, U01-AI-35040] NR 55 TC 32 Z9 32 U1 1 U2 2 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 DEC 15 PY 1996 VL 13 IS 5 BP 448 EP 455 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VY574 UT WOS:A1996VY57400008 PM 8970472 ER PT J AU Kotake, S Schumacher, HR Wilder, RL AF Kotake, S Schumacher, HR Wilder, RL TI A simple nested RT-PCR method for quantitation of the relative amounts of multiple cytokine mRNAs in small tissue samples SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE reverse transcriptase-polymerase chain reaction; synovium; cytokine; mRNA; quantitation; needle biopsy ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; THEORETICAL CONSIDERATIONS; MONONUCLEAR-CELLS; VIRUS; EXPRESSION; RESPONSES; PRIMERS; GENE AB It is difficult to quantitate cytokine mRNA profiles in small human tissue specimens obtained by a needle biopsy, even using standard RT-PCR methods, because the amount of mRNA in the specimens is very small. To address this problem, we developed highly sensitive, quantitative, nested RT-PCR techniques to evaluate the expression of multiple cytokine mRNAs in synovial specimens obtained by needle biopsy. To reduce effects of variation of initial RNA concentrations, cDNA from each target RNA sample was normalized, using a simplified competitive PCR method, to the levels of beta-actin cDNA. The first and the second (nested) PCR were performed in the same tube to prevent contamination. The number of PCR-product bands, evident on polyacrylamide gel electrophoresis, was used to quantitate the relative amounts of target cDNA. Using our methods, it was possible to evaluate, in a single synovial tissue specimen obtained by needle biopsy, the relative amounts of mRNAs for 10 cytokines (TNF-alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12 p40, IL-13, IL-15, IFN-gamma) and CD3 delta chain. Our methods are particularly valuable if there are multiple target mRNAs, numerous samples, or if the amounts of mRNAs are limited. The methods are applicable to a wide variety of tissues and target mRNAs. C1 NIAMSD,ARB,NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. NR 25 TC 39 Z9 39 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 DEC 15 PY 1996 VL 199 IS 2 BP 193 EP 203 DI 10.1016/S0022-1759(96)00184-6 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA VZ015 UT WOS:A1996VZ01500011 PM 8982362 ER PT J AU Kanno, T Siebenlist, U AF Kanno, T Siebenlist, U TI Activation of nuclear factor-kappa B via T cell receptor requires a Raf kinase and Ca2+ influx - Functional synergy between Raf and calcineurin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE; CYCLOSPORINE-A; ANTIGEN RECEPTOR; LYMPHOCYTE-ACTIVATION; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; I TAX; CALCIUM; ALPHA; PHOSPHORYLATION AB Signals transduced via the TCR activate the transcription factor nuclear factor-kappa B (NF-kappa B), which, in turn, is critical to the transcriptional induction of many genes important for the proliferation and expression of a differentiated phenotype. Treatment of T cells with the protein kinase C activator PMA in combination with Ca2+ ionophores mimics this process, and the two agents are often substituted for TCR stimulation, bypassing the TCR. Here we identify intracellular signaling components involved in activation of NF-kappa B following TCR stimulation. TCR signaling was triggered by treating Jurkat T cells with PHA or anti-CD3 Abs, and NF-kappa B activation was monitored by electrophoretic mobility shift assays and/or by kappa B-dependent reporter assays. Contrary to the idea that protein kinase C is involved in TCR-mediated activation of NF-kappa B, high doses of staurosporine did not interfere with activation of NF-kappa B by PHA, while the same dose of staurosporine completely blocked activation by PMA. PHA-induced kappa B-dependent reporter activity was, however, effectively blocked by a dominant negative form of Raf-l, suggesting a critical role for a Raf kinase. The TCR-mediated activation of NF-kappa B was also dependent on a Ca2+ influx, because the Ca2+ channel blocker, SK&F 96365, as well as other agents that prevented the Ca2+ influx, inhibited NF-kappa B activation. Cotransfection of a constitutively active form of calcineurin largely substituted for the Ca2+ requirement and reversed the blockade by SK&F 96365. Consistent with these observations, coexpression of constitutively active forms of Raf-l and calcineurin synergistically induced kappa B-dependent reporter activity, suggesting a physiologically relevant functional interaction between the kinase and the phosphatase. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. KYOTO UNIV,INST VIRUS RES,DEPT VIRAL ONCOL,KYOTO 606,JAPAN. NR 48 TC 73 Z9 74 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1996 VL 157 IS 12 BP 5277 EP 5283 PG 7 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600009 PM 8955173 ER PT J AU Garboczi, DN Utz, U Ghosh, P Seth, A Kim, J VanTienhoven, EAE Biddison, WE Wiley, DC AF Garboczi, DN Utz, U Ghosh, P Seth, A Kim, J VanTienhoven, EAE Biddison, WE Wiley, DC TI Assembly, specific binding, and crystallization of a human TCR-alpha beta with an antigenic tax peptide from human T lymphotropic virus type 1 and the class I MHC molecule HLA-A2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL RECEPTOR FRAGMENTS; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; EXPRESSION; CHAIN; SECRETION; HETERODIMERS; PROTEINS; RECOGNITION AB T lymphocytes use TCR-alpha beta to bind and to recognize complexes of antigenic peptides bound to MHC proteins located at the surface of APCs, We have assembled and crystallized this intercellular complex of TCR/peptide/MHC from soluble human TCR-alpha beta and soluble peptide/HLA-A2 complexes. The soluble TCR-alpha beta binds specifically to its in vivo ligand, the complex of HLA-AZ, and a peptide from the Tax protein of human T lymphotropic virus type 1. The soluble TCR also binds in vitro to an altered peptide ligand, which appears to be a partial agonist in T cell assays as determined by its ability to elicit different cytolytic and lymphokine secretion responses, Heterodimerization and the antigenic specificity of the TCR do not require its interchain disulfide bond, transmembrane segments, or glycosylations, Crystals of the TCR/peptide/HLA-A2 complex diffract x-rays, providing the means to study in atomic detail the mechanism of Ag-specific cell-cell recognition between T cells and target cells. C1 HARVARD UNIV,DEPT MOL & CELLULAR BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. CLIN RES INST MONTREAL,IMMUNOL LAB,MONTREAL,PQ H2W 1R7,CANADA. NINCDS,MOL IMMUNOL SECT,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. CHILDRENS HOSP,HOWARD HUGHES MED INST,MOL MED LAB,BOSTON,MA 02115. FU NICHD NIH HHS [HD-17461] NR 48 TC 121 Z9 124 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 DEC 15 PY 1996 VL 157 IS 12 BP 5403 EP 5410 PG 8 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600024 PM 8955188 ER PT J AU Gray, JX Haino, M Roth, MJ Maguire, JE Jensen, PN Yarme, A StetlerStevenson, MA Siebenlist, U Kelly, K AF Gray, JX Haino, M Roth, MJ Maguire, JE Jensen, PN Yarme, A StetlerStevenson, MA Siebenlist, U Kelly, K TI CD97 is a processed, seven-transmembrane, heterodimeric receptor associated with inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EGF-LIKE DOMAIN; TYROSINE PHOSPHATASE; G-PROTEINS; LYMPHOCYTE INTERACTIONS; EXTRACELLULAR DOMAIN; ADHESION MOLECULE; CALCIUM-BINDING; MARFAN-SYNDROME; CELL-ADHESION; ACTIVATION AB CD97 is a receptor that spans the membrane seven times, a defining feature of C protein-coupled receptors, CD97 is predominantly expressed in leukocytes, but the function and accurate protein structure of this receptor have not been described, We show here that CD97 has the novel property among C protein-coupled receptors characterized to date of being processed intracellularly in either the endoplasmic reticulum or early Golgi from a proprotein into a noncovalently associated two-subunit structure that becomes expressed on the cell surface and is composed of a large extracellular protein (CD97 alpha) and a seven-membrane spanning protein (CD97 beta), CD97 beta is part of an evolutionarily conserved subfamily of four proteins, including two Caenorhabditis elegans proteins of as yet unknown function, which is distinct from but most closely related to the glucagon receptor family, CD97 alpha exists in three alternatively spliced isoforms that contain between three and five epidermal growth factor (EGF)-like repeats that are related to the calcium binding EGF-like repeats in the microfibril protein fibrillin, Leukocytes strongly positive for CD97 are concentrated at sites of inflammation relative to CD97 expression in normal lymphoid tissues, Soluble CD97 alpha was found in body fluids from inflamed tissues, suggesting that a functional consequence of the CD97 heterodimeric structure is the stable existence of CD97 alpha in a cellfree form, CD97 appears to be a multifunctional protein that may play a signal transduction role associated with the establishment or development of an inflammatory process. C1 NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NIAID, IMMUNOREGULAT LAB, NIH, BETHESDA, MD 20892 USA. NR 40 TC 127 Z9 131 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1996 VL 157 IS 12 BP 5438 EP 5447 PG 10 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600028 PM 8955192 ER PT J AU Kim, PKM Dutra, AS Chandrasekharappa, SC Puck, JM AF Kim, PKM Dutra, AS Chandrasekharappa, SC Puck, JM TI Genomic structure and mapping of human FADD, an intracellular mediator of lymphocyte apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOPROLIFERATIVE SYNDROME; BREAST-CANCER; DEATH DOMAIN; CYCLIN D1; FAS; GENE; AMPLIFICATION; PROTEINS; REGION; INTERACTS AB Fas-associated death domain protein (FADD)/MORT1 is a 23-kDa cytoplasmic protein containing a C-terminal death domain that interacts with the intracellular death domain of the Fas transmembrane receptor. Cross-linking of Fas mediates apoptosis in a variety of cells, primarily peripheral T lymphocytes, for which this pathway plays a major role in mature lymphocyte homeostasis, We report the characterization of the human FADD gene, which spans approximately 3.6 kb and contains two exons (286 and 341 bp) separated by a 2.0-kb intron, FADD was mapped to chromosome 11q13.3 by the independent techniques of PCR screening of somatic cell hybrid mapping panels and fluorescence in situ hybridization, In addition FADD was shown by fluorescence in situ hybridization to be amplified along with other 11q13.3 genes previously studied in the breast cancer cell line MDA-MB-134-VI, raising the possibility that overexpression of mutant FADD could contribute to poor prognosis and increased invasiveness of tumors, Its known role in apoptosis has made FADD a candidate susceptibility gene for autoimmune lymphoproliferative syndrome, Now that it has been colocalized in 11q13.3 with IDDM4, a diabetes susceptibility locus, alterations in FADD should also be considered as potential contributors to insulin-dependent familial diabetes. Elucidation of the map position and gene structure of FADD will make possible linkage and mutation analysis to study the role of this gene in human diseases. C1 NIH,NATL CTR HUMAN GENOME RES,IMMUNOL GENET SECT,LAB GENE TRANSFER,BETHESDA,MD 20892. NR 42 TC 30 Z9 33 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 DEC 15 PY 1996 VL 157 IS 12 BP 5461 EP 5466 PG 6 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600031 PM 8955195 ER PT J AU GarciaZepeda, EA Combadiere, C Rothenberg, ME Sarafi, MN Lavigne, F Hamid, Q Murphy, PM Luster, AD AF GarciaZepeda, EA Combadiere, C Rothenberg, ME Sarafi, MN Lavigne, F Hamid, Q Murphy, PM Luster, AD TI Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTIONAL EXPRESSION; CHEMOTACTIC PROTEIN-1; MOLECULAR-CLONING; ENDOTHELIAL-CELLS; MESSENGER-RNA; T-CELLS; GENE-EXPRESSION; CYTOKINE; RANTES; MCP-2 AB The chemokines are a large family of cytokines that regulate the complex and precise recruitment of immune cells into inflammatory foci. To fully appreciate their role in the pathogenesis of human diseases, the entire spectrum of chemokines, their receptors, their cellular targets, and mechanisms of regulation need to be delineated. Using eotaxin as a probe, we isolated a cDNA for a novel human beta (or CC) chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-4. Purified recombinant MCP-4 protein was a potent chemoattractant for monocytes and eosinophils and stimulated histamine release from basophils. MCP-4 induced a calcium flux in HEK-293 cells transfected with the monocyte selective MCP-1 receptor (CCR-2B) and the eosinophil selective eotaxin receptor (CCR-3), but not in the more widely expressed CCR-1 or CCR-5. This novel chemokine is expressed in TNF-alpha and IL-1 activated epithelial and endothelial cells in vitro, and in the epithelial mucosa of patients with both Th2-type allergic and Th1-type nonallergic sinusitis. Furthermore, both IFN-gamma and IL-4, products of Th1 and Th2 cells, respectively, synergized with TNF-alpha and IL-1 in inducing MCP-4 mRNA accumulation, These properties of MCP-4 offer a molecular explanation for the observed accumulation of monocytes, eosinophils and basophils in both Th1- and Th2-type immune responses. C1 MASSACHUSETTS GEN HOSP E,INFECT DIS UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. NIAID,HOST DEF LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MCGILL UNIV,MEAKINS CHRISTIE LABS,DEPT PATHOL & MED,MONTREAL,PQ H3A 2T5,CANADA. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 FU NCI NIH HHS [R01 CA69212-01] NR 66 TC 215 Z9 218 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1996 VL 157 IS 12 BP 5613 EP 5626 PG 14 WC Immunology SC Immunology GA VX026 UT WOS:A1996VX02600050 PM 8955214 ER PT J AU Weiss, GH Calabrese, PP AF Weiss, GH Calabrese, PP TI Occupation times of a CTRW on a lattice with anomalous sites SO PHYSICA A LA English DT Article AB We develop formalism allowing us to derive results for the probability density of the occupation time of a set of sites on a lattice of a CTRW in which the pausing-time density on the set can differ from those on the remaining lattice sites. The problem is suggested by transillumination techniques used in optical imaging. Details are given for the case of a single site on the lattice and an anomalous pausing-time density. It is shown that if the random walk is transient (i.e., in three or more dimensions when the variance of a single jump is finite) the asymptotic density for the occupation time at the special point is a negative exponential. In one dimension the random walk is recurrent. Here it is shown that the occupation time scales as t(1/2). These results extend to finite numbers of anomalous points. RP Weiss, GH (reprint author), NATL INST HLTH,BETHESDA,MD 20892, USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD DEC 15 PY 1996 VL 234 IS 1-2 BP 443 EP 454 DI 10.1016/S0378-4371(96)00362-7 PG 12 WC Physics, Multidisciplinary SC Physics GA WA080 UT WOS:A1996WA08000027 ER PT J AU Pinals, DA Malhotra, AK Missar, CD Pickar, D Breier, A AF Pinals, DA Malhotra, AK Missar, CD Pickar, D Breier, A TI Lack of gender differences in neuroleptic response in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE gender; schizophrenia; neuroleptic treatment; sex differences ID SEX; VARIABLES; AFTERCARE; ILLNESS; ONSET; DRUG; AGE AB Objective: The authors sought to determine if there were gender differences in neuroleptic response in male and female patients with schizophrenia who were matched for clinical and demographic variables and participated in a double-blind trial of traditional antipsychotic drugs. Methods: 24 males (m) and 20 females (f) with schizophrenia or schizoaffective disorder who did not differ in clinical characteristics (age of onset, course of illness, prior hospitalizations, premorbid functioning) participated in an extended drug-free period followed by a neuroleptic trial under double-blind, placebo-controlled conditions. Results: Males and females showed significant improvement in total, positive and negative BPRS symptoms during neuroleptic treatment. However, there were no significant differences in treatment response between sexes. No sex differences were found in baseline drug-free symptomatology, neuroleptic dose or dosage by weight. Conclusions: There were no significant sex differences in neuroleptic treatment response in male and female patients well-matched for clinical, treatment and demographic characteristics. Methodological issues which distinguish this study from prior studies reporting gender differences in neuroleptic response are examined. C1 NIMH,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 27 TC 28 Z9 28 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 1996 VL 22 IS 3 BP 215 EP 222 DI 10.1016/S0920-9964(96)00067-9 PG 8 WC Psychiatry SC Psychiatry GA WA779 UT WOS:A1996WA77900004 PM 9000318 ER PT J AU Peell, GD Green, JP Elkashef, AM Khandelwal, JK Linnoila, M Wyatt, RJ Lawson, WB Jaeger, AC Kaufmann, CA Kirch, DG AF Peell, GD Green, JP Elkashef, AM Khandelwal, JK Linnoila, M Wyatt, RJ Lawson, WB Jaeger, AC Kaufmann, CA Kirch, DG TI The relationship between urine excretion and biogenic amines and their metabolites in cerebrospinal fluid of schizophrenic patients (vol 19, pg 171, 1996) SO SCHIZOPHRENIA RESEARCH LA English DT Correction, Addition ID HISTAMINE METABOLITES; BRAIN C1 ST ELIZABETH HOSP,NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NIAAA,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD 20205. RP Peell, GD (reprint author), CUNY MT SINAI SCH MED,DEPT PHARMACOL,BOX 1215,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 1996 VL 22 IS 3 BP 267 EP 267 DI 10.1016/S0920-9964(96)00073-4 PG 1 WC Psychiatry SC Psychiatry GA WA779 UT WOS:A1996WA77900011 ER PT J AU Peat, TS Frank, EG McDonald, JP Levine, AS Woodgate, R Hendrickson, WA AF Peat, TS Frank, EG McDonald, JP Levine, AS Woodgate, R Hendrickson, WA TI The UmuD' protein filament and its potential role in damage induced mutagenesis SO STRUCTURE LA English DT Article DE filament structure; mutagenesis; self-cleavage reaction; SOS response; X-ray crystallography ID RECA-MEDIATED CLEAVAGE; DNA POLYMERASE-III; ESCHERICHIA-COLI; SOS MUTAGENESIS; ANOMALOUS DIFFRACTION; STRUCTURAL BASIS; REPAIR; REPRESSOR; MUTATIONS; DEFICIENT AB Background: Damage induced 'SOS mutagenesis' may occur transiently as part of the global SOS response to DNA damage in bacteria, A key participant in this process is the UmuD protein, which is produced in an inactive form but converted to the active form, UmuD', by a RecA-mediated self-cleavage reaction. UmuD', together with UmuC and activated RecA (RecA*), enables the DNA polymerase III holoenzyme to replicate across chemical and UV induced lesions. The efficiency of this reaction depends on several intricate protein-protein interactions. Results: Recent X-ray crystallographic analysis shows that in addition to forming molecular dimers, the N- and C-terminal tails of UmuD' extend from a globular beta structure to associate and produce crystallized filaments. We have investigated this phenomenon and find that these filaments appear to relate to biological activity. Higher order oligomers are found in solution with UmuD', but not with UmuD nor with a mutant of UmuD' lacking the extended N terminus. Deletion of the N terminus of UmuD' does not affect its ability to form molecular dimers but does severely compromise its ability to interact with a RecA-DNA filament and to participate in mutagenesis. Mutations in the C terminus of UmuD' result in both gain and loss of function for mutagenesis. Conclusions: The activation of UmuD to UmuD' appears to cause a large conformational change in the protein which allows it to form oligomers in solution at physiologically relevant concentrations. Properties of these oligomers are consistent with the filament structures seen in crystals of UmuD'. C1 COLUMBIA UNIV,DEPT BIOCHEM & MOL BIOPHYS,NEW YORK,NY 10032. NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,BETHESDA,MD 20892. COLUMBIA UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10032. RI Peat, Thomas/F-9817-2010 OI Peat, Thomas/0000-0002-6488-0831 NR 56 TC 32 Z9 32 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD DEC 15 PY 1996 VL 4 IS 12 BP 1401 EP 1412 DI 10.1016/S0969-2126(96)00148-7 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VY739 UT WOS:A1996VY73900004 PM 8994967 ER PT J AU Kocher, JP Prevost, M Wodak, SJ Lee, B AF Kocher, JP Prevost, M Wodak, SJ Lee, B TI Properties of the protein matrix revealed by the free energy of cavity formation SO STRUCTURE LA English DT Article DE folding; hydrophobic interactions; sidechain packing; stability ID PANCREATIC TRYPSIN-INHIBITOR; GLOBULAR-PROTEINS; BACTERIOPHAGE-T4 LYSOZYME; HYDROSTATIC-PRESSURE; POTENTIAL FUNCTIONS; INTERNAL CAVITIES; MOLECULAR LIQUIDS; PACKING DEFECTS; BURIED WATERS; STABILITY AB Background: The classical picture of the hydrophobic stabilization of proteins invokes a resemblance between the protein interior and nonpolar solvents, but the extent to which this is the case has often been questioned. The protein interior is believed to be at least as tightly packed as organic crystals, and was shown to have very low compressibility. There is also evidence that these properties are not uniform throughout the protein, and conflicting views exist on the nature of sidechain packing and on its influence on the properties of the protein. Results: In order to probe the physical properties of the protein, the free energy associated with the formation of empty cavities has been evaluated for two proteins: barnase and T4 lysozyme. To this end, the likelihood of encountering such cavities was computed from room temperature molecular dynamics trajectories of these proteins in water. The free energy was evaluated in each protein taken as a whole and in submolecular regions. The computed free energies yielded information on the manner in which empty space is distributed in the system, while the latter undergoes thermal motion, a property hitherto not analyzed in heterogeneous media such as proteins. Our results showed that the free energy of cavity formation is higher in proteins than in both water and hexane, providing direct evidence that the native protein medium differs in fundamental ways from the two liquids. Furthermore, although the packing density was found to be higher in nonpolar regions of the protein than in polar ones, the free energy cost of forming atomic size cavities is significantly lower in nonpolar regions, implying that these regions contain larger chunks of empty space, thereby increasing the likelihood of containing atomic size packing defects. These larger empty spaces occur preferentially where buried hydrophobic sidechains belonging to secondary structures meet one another. These particular locations also appear to be more compressible than other parts of the core or surface of the protein. Conclusions: The cavity free energy calculations described here provide a much more detailed physical picture of the protein matrix than volume and packing calculations. According to this picture, the packing of hydrophobic sidechains is tight in the interior of the protein, but far from uniform. In particular, the packing is tighter in regions where the backbone forms less regular hydrogen-bonding interactions than at interfaces between secondary structure elements, where such interactions are fully developed. This may have important implications on the role of sidechain packing in protein folding and stability. C1 FREE UNIV BRUSSELS,UNITE CONFORMAT MACROMOL BIOL,B-1050 BRUSSELS,BELGIUM. NCI,MOL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 75 TC 52 Z9 52 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD DEC 15 PY 1996 VL 4 IS 12 BP 1517 EP 1529 DI 10.1016/S0969-2126(96)00157-8 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VY739 UT WOS:A1996VY73900013 PM 8994976 ER PT J AU Tsai, WP Conley, SR Kung, HF Garrity, RR Nara, PL AF Tsai, WP Conley, SR Kung, HF Garrity, RR Nara, PL TI Preliminary in vitro growth cycle and transmission studies of HIV-1 in an autologous primary cell assay of blood-derived macrophages and peripheral blood mononuclear cells SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INFECTION; NEUTRALIZING ANTIBODY; QUANTITATIVE-ANALYSIS; SOLUBLE CD4; TROPISM; PLASMA; PROTEINS; GLYCOPROTEINS; PATHOGENESIS AB Recent interest focused on the dynamics of HIV-1 replication in primary monocytes/macrophages and T-lymphocytes of the immune system, as well as the standardization of virological and immunological in vitro assays with primary isolates, provided the impetus for these studies. These types of studies have never been performed as they would occur in vivo, i.e., where the envelope of the virus and cell membranes of the two cell types of the same host origin. Therefore, the biological and physicochemical properties of an uncloned, primary dual-tropic isolate HIV-1(ADA) during the initial lag, log, and stationary phases of viral replication were studied in an autologous donor cell assay in peripheral blood mononuclear cells (PBMC) and blood monocyte-derived macrophages (MDM). Similar total numbers (10(9) virus particles/ml) were produced by both cell types during the stationary period. On a per cell per day basis, during peak stationary periods, 0.92 x 10(3) virions/day for MDMs and 5.31 x 10(3) virions/day for PBMCs were produced. Interestingly, virus replicating from MDMs during the log-growth phase demonstrated the greatest infectious fraction which was 3 logs greater than virus replicating in PBMCs. Despite constant virus particle production in MDMs, the infectious fraction was found to fall 3 to 4 lags over a In-day period. Due to an infectious fraction less than 1 (0.053 infectious unit/cell/24 hr), virus spread in PBMCs during the rapid log phase could only have occurred by cell-to-cell contact, whereas in MDMs with an infectious fraction of about one infectious particle (similar to 1/cell/24 hr), cell-free transmission could account for the observed results. Most of the MDMs (> 90%) became productively infected, whereas only 5-10% of the total PBMCs were found replicating virus. The period of peak stationary virus production (i.e., stationary phase) was at minimum 4 to 5 times longer in MDMs than PBMCs. Whereas the majority of p24, RT, and gp120 found to be associated with MDM-derived virions, no increased dissociation of these components was observed in PBMC-derived virions. The virion-associated gp120 was 3 to 4 times more stable on both PBMC- and MDM-derived virus (> 96 hr) and present at 10-25 times the concentration per virion than that observed for a T-cell-line-adapted laboratory strain of HIV-1 replicating in T-cell lines. These in vitro results suggest that important differences exist between MDMs and PBMCs with regard to the viral dynamics of infection and replication which should provide for a qualitative and quantitative basis to estimate virus replication on a per-cell basis for other known cellular targets of HIV-1. Studying the multiple biophysicochemical characteristics and viral replication dynamics as described herein provides an autologous in vitro model of additional quantifiable parameters for analysis and understanding of virus/host factor(s) and/or antivirals which influence them. (C) 1996 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,OFF DIRECTORS,DIRECTORS LAB,VIRUS BIOL SECT,FREDERICK,MD 21702. SCI APPLICAT INT CORP,FREDERICK,MD 21702. RP Tsai, WP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,DIV BASIC SCI,POB B,BLDG 560,ROOM 12-15,FREDERICK,MD 21702, USA. NR 44 TC 30 Z9 30 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 0042-6822 J9 VIROLOGY JI Virology PD DEC 15 PY 1996 VL 226 IS 2 BP 205 EP 216 DI 10.1006/viro.1996.0648 PG 12 WC Virology SC Virology GA VZ463 UT WOS:A1996VZ46300008 PM 8955040 ER PT J AU Portis, JL Fujisawa, R McAtee, FJ AF Portis, JL Fujisawa, R McAtee, FJ TI The glycosylated gag protein of MuLV is a determinant of neuroinvasiveness: Analysis of second site revertants of a mutant MuLV lacking expression of this protein SO VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; POLYPROTEIN PRECURSORS; INCUBATION PERIOD; RETROVIRUS; SEQUENCE; DISEASE; TRANSLATION; INTERFERENCE; REPLICATION; CELLS AB Neuroinvasiveness is a property of all neurovirulent murine retroviruses, although the factors which facilitate infection of the CNS are not understood. We previously showed that mutant MuLV which lack expression of an accessory protein, glycosylated gag, had lost neurovirulence, indicating that this protein may be involved in promoting CNS infection, The mutations were located in the ''Kozak'' consensus sequence of the initiation codon for this protein. Here it is shown that shortly after inoculation of mice with one of these mutant viruses, revertants emerged which had regained expression or glycosylated gag and had also regained the neuroinvasiveness and neurovirulence exhibited by the wild-type virus. The phenotypic revertants retained the mutations in the ''Kozak'' consensus sequence but exhibited a G --> A mutation 12 codons downstream from the mutated start site, creating a new initiation codon and a glycosylated gag protein, which was truncated at its N-terminus. Using antibodies specific for glycosylated gag it is shown that the frequency of splenic infectious centers expressing revertant virus increased progressively during the 2 months following inoculation of mutant virus until greater than or equal to 50% of the virus-producing cells in the spleen expressed revertant virus; In contrast although phenotypic revertants were detectable at low frequency after cell-free passage in vitro in M. dunni fibroblasts, there was no evidence for selection. These results indicate that glycosylated gag facilitates virus spread within the spleen and to extra-splenic sites, such as the CNS, and suggest that the protein may function through its interaction with the host. (C) 1996 Academic Press, Inc. RP Portis, JL (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 34 TC 16 Z9 16 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 DEC 15 PY 1996 VL 226 IS 2 BP 384 EP 392 DI 10.1006/viro.1996.0666 PG 9 WC Virology SC Virology GA VZ463 UT WOS:A1996VZ46300026 PM 8955058 ER PT J AU Gvakharia, BO Koonin, EK Mathews, CK AF Gvakharia, BO Koonin, EK Mathews, CK TI Vaccinia virus G4L gene encodes a second glutaredoxin SO VIROLOGY LA English DT Article ID RIBONUCLEOTIDE REDUCTASE; THIOLTRANSFERASE GLUTAREDOXIN; THIOREDOXIN; PROTEIN; SEQUENCE; ENZYME; ACID AB Vaccinia virus (VV) was previously shown to encode a functional glutaredoxin, the product of the o21 gene, which is synthesized late in infection, after the onset of DNA replication. Here we report that an open reading frame in the VV genome designated as g41 encodes a protein that has sequence similarity to glutaredoxins and possesses thioltransferase and dehydroascorbate reductase activities. G4L protein in infected cells can be detected as early as 4 hr after infection and is constitutively expressed up to 24 hr postinfection. A protein homologous to G4L and retaining the predicted glutaredoxin active center is encoded by the recently sequenced Molluscum Contagiosum virus (MCV), whereas O2L protein is not conserved, suggesting that the glutaredoxin activity of G4L may be involved in replication of ail poxviruses. (C) 1996 Academic Press, Inc. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP Gvakharia, BO (reprint author), OREGON STATE UNIV,DEPT BIOCHEM & BIOPHYS,2011 AGR & LIFE SCI BLDG,CORVALLIS,OR 97331, USA. FU NIGMS NIH HHS [GM 37508] NR 25 TC 23 Z9 24 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 DEC 15 PY 1996 VL 226 IS 2 BP 408 EP 411 DI 10.1006/viro.1996.0669 PG 4 WC Virology SC Virology GA VZ463 UT WOS:A1996VZ46300029 PM 8955061 ER PT J AU Auvinen, A AF Auvinen, A TI Long cancer risk from indoor radon SO LANCET LA English DT Letter RP Auvinen, A (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. OI Auvinen, Anssi/0000-0003-1125-4818 NR 2 TC 1 Z9 1 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 DEC 14 PY 1996 VL 348 IS 9042 BP 1662 EP 1663 DI 10.1016/S0140-6736(05)65732-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VX876 UT WOS:A1996VX87600058 PM 8962013 ER PT J AU Bozzi, F Bertuzzi, S Strina, D Giannetto, C Vezzoni, P Villa, A AF Bozzi, F Bertuzzi, S Strina, D Giannetto, C Vezzoni, P Villa, A TI The exon-intron structure of human LHX1 gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEINS; MOTIF; HOMEODOMAIN; ELEGANS; DOMAIN AB We have determined the genomic structure of the human LHX1 gene, a member of the LIM/homeobox (Lhx) gene family. The transcript is assembled from five exons, which are separated by introns ranging in size from 93 nt to 2.3 kb. The two LIM domains are entirely contained in the first and second exons, respectively, while the homeodomain is split into exons three and four. This structure closely parallels the organization of other mouse and human Lhx genes whose genomic Structure is known. An exception is the mouse and human isl1 genes, whose homeodomain does not contain introns. An intron at the same position also occurs in the Xlim1 gene as well as in other homeobox genes, such as evx1 and evx2, suggesting that this intron insertion represents an ancestral event, from which homeobox genes of different families originated. In this context, evolution of the Lhx gene family probably involved the shuffling of this intron-containing homeobox in the proximity of a LIM-only gene, while Islet genes were formed either by the shuffling of an intronless homeobox to the same LIM domain or, alternatively, by intron loss during their evolution. (C) 1996 Academic Press. Inc. C1 NIHHD,NIH,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RP Bozzi, F (reprint author), CNR,IST TECNOL BIOMED AVANZATE,VIA AMPERE 56,I-20131 MILAN,ITALY. OI Villa, Anna/0000-0003-4428-9013 NR 12 TC 8 Z9 8 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 13 PY 1996 VL 229 IS 2 BP 494 EP 497 DI 10.1006/bbrc.1996.1832 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VZ799 UT WOS:A1996VZ79900022 PM 8954926 ER PT J AU Mitton, KP Kamiya, T Tumminia, SJ Russell, P AF Mitton, KP Kamiya, T Tumminia, SJ Russell, P TI Cysteine protease activated by expression of HIV-1 protease in transgenic mice - MIP26 (aquaporin-0) cleavage and cataract formation in vivo and ex vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL CHANNEL PROTEIN; LENS MEMBRANE; CALMODULIN; SEQUENCE; PERMEABILITY; LIPOSOMES; COMPLEX; FAMILY; AIDS AB Transgenic mice, homozygous for HIV-1 protease expression in the eye lens, display degradation of some lens crystallins and cytoskeletal proteins prior to cataract formation on postnatal days 23-25, Alterations to the internal lens hydration state also occur; therefore, the status of the aquaporin protein MIP26 was examined over postnatal days 16-25 to determine if it was altered during cataractogenesis. The MTP was identical in transgenic and control lenses until day 21. By postnatal day 25 (frank cataract), in the lenses obtained from transgenic animals, the 26-kDa band was absent and there was a concurrent increase in the proportion of MIP23, Immunoblotting demonstrated cleavage at the C terminus, Lenses were also maintained in an organ culture system to demonstrate that the cataractogenic process is inherent to the isolated lens and to determine the contribution of cysteine protease action, Organ culture experiments revealed a similar progression to nuclear cataract formation as seen in vivo. Two-dimensional gel analysis of the soluble lens crystallin fraction of organ cultured lenses revealed the same cleavage pattern as occurs in vivo, Organ culture of transgenic lenses with E64, a cysteine protease inhibitor, dramatically delayed cataractogenesis and prevented proteolytic cleavage of both MIP26 and crystallins, HIV-1 protease, while the trigger of cataract formation, does not appear to be the protease responsible for cleavage of MIP or lens crystallins. These results suggest that activation of endogenous cysteine protease activity is involved in the cleavage of these proteins and occurs downstream of HIV-1 protease action. C1 KYOWA HAKKO KOGYO CO LTD,TOKYO 194,JAPAN. RP Mitton, KP (reprint author), NEI,LAB MECHANISM OCULAR DIS,NIH,BLDG 6,RM 228,BETHESDA,MD 20892, USA. NR 35 TC 13 Z9 13 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 DEC 13 PY 1996 VL 271 IS 50 BP 31803 EP 31806 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY340 UT WOS:A1996VY34000011 PM 8943220 ER PT J AU Kosugi, S Mori, T Shenker, A AF Kosugi, S Mori, T Shenker, A TI The role of Asp(578) in maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LUTEINIZING-HORMONE RECEPTOR; LIMITED PRECOCIOUS PUBERTY; PROTEIN-COUPLED RECEPTOR; ACTIVATING POINT MUTATION; 2ND TRANSMEMBRANE DOMAIN; CHORIOGONADOTROPIN RECEPTOR; CONSTITUTIVE ACTIVATION; SIGNAL-TRANSDUCTION; BINDING; GENE AB A constitutively activating mutation encoding Asp(578)-->Gly in transmembrane helix 6 of the lutropin/choriogonadotropin receptor (LHR) is the most common cause of gonadotropin-independent, male-limited precocious puberty. This mutant LHR produces a 4.5-fold increase in basal cAMP when expressed in COS-7 cells. To better understand the normal role of Asp(578) in the LHR we studied the effect of seven other amino acid substitutions at this position. No agonist binding or response was detected with the Asp(578)-->Pro mutant. Agonist binding affinity was unaffected by the other substitutions and estimated receptor concentrations ranged from 11 to 184% of wild type. Substitution of Asp(578) with Asn, a similarly sized, uncharged residue, did not produce agonist-independent activation. In contrast, replacement with Glu, Ser, or Leu caused 4.9-5.6-fold stimulation of basal cAMP. Substitution with Tyr (8.5-fold) or Phe (7.5-fold) had a greater activating effect. Only the Tyr, Phe, and Leu mutants showed constitutive activation of the inositol phosphate pathway. Our data suggest that it is the ability of the Asp(578) side chain to serve as a properly positioned hydrogen bond acceptor, rather than its negative charge, that is important for stabilizing the inactive state of the LHR. A bulky aromatic side chain at position 578 may further destabilize the inactive receptor conformation. C1 KYOTO UNIV HOSP,SCH MED,DEPT LAB MED,SAKYO KU,KYOTO 60601,JAPAN. NIDDK,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. CHILDRENS MEM HOSP,CHICAGO,IL 60614. NORTHWESTERN UNIV,SCH MED,DEPT PEDIAT,DIV ENDOCRINOL,CHICAGO,IL 60614. NR 34 TC 75 Z9 75 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 DEC 13 PY 1996 VL 271 IS 50 BP 31813 EP 31817 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY340 UT WOS:A1996VY34000013 PM 8943222 ER PT J AU Wartmann, M Cella, N Hofer, P Groner, B Liu, XW Hennighausen, L Hynes, NE AF Wartmann, M Cella, N Hofer, P Groner, B Liu, XW Hennighausen, L Hynes, NE TI Lactogenic hormone activation of Stat5 and transcription of the beta-casein gene in mammary epithelial cells is independent of p42 ERK2 mitogen-activated protein kinase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; DNA-BINDING; MAP KINASE; SERINE PHOSPHORYLATION; DEPENDENT ACTIVATION; PROLACTIN RECEPTOR; NUCLEAR FACTOR; FACTOR APRF; EXPRESSION; TYROSINE AB HC11 mammary epithelial cells have been used to characterize molecular events involved in the regulation of milk protein gene expression, Treatment of HC11 cells with the lactogenic hormones prolactin, insulin, and glucocorticoids results in transcription of the beta-casein gene, Prolactin induces a signaling event which involves tyrosine phosphorylation of the mammary gland factor, Stat5, a member of the family of signal transducers and activators of transcription (Stat). Here we show that HC11 cells express two Stat5 proteins, Stat5a and Stat5b. Phosphopeptide and phosphoamino acid analysis of Stat5a and Stat5b immunoprecipitated from phosphate-labeled HC11 cells revealed that both proteins were constitutively phosphorylated on serine, Lactogenic hormone treatment resulted in the appearance of a tyrosine-phosphorylated peptide in both Stat5 proteins, Consistent with this observation, a Western blot analysis of Stat5a and Stat5b showed that lactogenic hormones induced a rapid, transient increase in phosphotyrosine which paralleled the binding of Stat5 to its cognate recognition sequence in the beta-casein gene promoter, Lactogenic hormone treatment of the HC11 cells also led to a rapid activation of the mitogen activated protein (MAP) kinase pathway, We examined the role of this pathway in beta-casein transcription using a specific MAP kinase kinase inhibitor, PD98059, Concentrations of PD98059 which completely abrogated lactogen-induced MAP kinase activation did not affect the phosphorylation state of Stat5, its DNA binding activity, or transcriptional activation of a beta-casein reporter construct, This indicates that the MAP kinase pathway does not contribute to lactogenic hormone induction of the beta-casein gene. C1 FRIEDRICH MIESCHER INST,CH-4002 BASEL,SWITZERLAND. INST EXPT CANC RES,TUMOR BIOL CTR,D-79106 FREIBURG,GERMANY. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. RI Cella, Nathalie/A-3542-2012 OI Cella, Nathalie/0000-0001-6060-1076 NR 55 TC 99 Z9 99 U1 0 U2 3 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 DEC 13 PY 1996 VL 271 IS 50 BP 31863 EP 31868 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY340 UT WOS:A1996VY34000020 PM 8943229 ER PT J AU Fuhrer, C Hall, ZW AF Fuhrer, C Hall, ZW TI Functional interaction of Src family kinases with the acetylcholine receptor in C2 myotubes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASES; TORPEDO ELECTRIC ORGAN; SIGNAL-TRANSDUCTION; DELTA-SUBUNIT; GROWTH-FACTOR; GENE-PRODUCT; MUSCLE-CELLS; PHOSPHORYLATION; AGRIN; DYSTROPHIN AB Tyrosine phosphorylation of the beta subunit of the acetylcholine receptor (AChR) has been postulated to play a role in AChR clustering during development of the neuromuscular junction. me have investigated the mechanism of this phosphorylation in mammalian C2 myotubes and report that the tyrosine kinase Src binds and phosphorylates glutathione S-transferase fusion proteins containing the N-terminal half of the cytoplasmic loop of the beta subunit. No binding occurs to the related kinases Fyn or Yes or to the corresponding regions from the gamma and delta subunits. Furthermore, AChRs affinity-isolated from C2 myotubes using alpha-bungarotoxin-Sepharose mere specifically associated with Src and Fyn and had tyrosine-phosphorylated beta subunits. We suggest that AChRs are initially phosphorylated by Src and subsequently bind Fyn in a phosphotyrosine-dependent manner. These interactions are likely to play an important role in construction of the specialized postsynaptic membrane during synaptogenesis. C1 UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. NIMH,SECT SYNAPT MECHANISMS,CELL BIOL LAB,BETHESDA,MD 20892. NR 55 TC 74 Z9 74 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 DEC 13 PY 1996 VL 271 IS 50 BP 32474 EP 32481 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY340 UT WOS:A1996VY34000105 PM 8943314 ER PT J AU Radko, SP Chrambach, A AF Radko, SP Chrambach, A TI Electrophoresis in polymer solutions: Mechanisms of molecular sieving SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID CONVEX FERGUSON PLOTS; GEL-ELECTROPHORESIS; UNCROSSLINKED POLYACRYLAMIDE; DNA; MACROMOLECULES; SCATTERING; MOBILITY; MODEL AB Passsage of rigid, ''spherical'' proteins in the range of 2-5 nm radius, R (40-500 kDa molecular weight), through semidilute solutions of a representative polymer, polyethylene glycol in the molecular weight range of (0.6-8) x 10(6), gives rise to a size dependent retardation (''molecular sieving'') analogous to that in a porous network composed of random planes. The average distance between those planes being equal to the screening length, xi, the retardation can be described by log(mu/mu(0)) = -(ARc(0.75)) where A is a constant dependent on solvent and type of monomer and c is the polymer concentration. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOL ANAL SECT,NIH,BETHESDA,MD 20892. NR 25 TC 18 Z9 18 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD DEC 12 PY 1996 VL 100 IS 50 BP 19461 EP 19465 DI 10.1021/jp9612339 PG 5 WC Chemistry, Physical SC Chemistry GA VX875 UT WOS:A1996VX87500040 ER PT J AU Fauci, AS AF Fauci, AS TI Host factors and the pathogenesis of HIV-induced disease SO NATURE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; TYPE-1 INFECTION; IMMUNE-RESPONSE; FACTOR-ALPHA; PERIPHERAL-BLOOD; HOMOSEXUAL MEN; CELL-LINE; IN-VIVO AB The level of human immunodeficiency virus (HIV) replication in patients reflects a balance between stimulatory and inhibitory host factors (particularly endogenous cytokines). New information concerning the cellular co-receptors for HIV and the cellular tropism of different strains of virus will advance our understanding of HIV-induced pathogenesis and suggests new therapeutic and preventive strategies. RP Fauci, AS (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 113 TC 692 Z9 707 U1 0 U2 19 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 12 PY 1996 VL 384 IS 6609 BP 529 EP 534 DI 10.1038/384529a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VX769 UT WOS:A1996VX76900048 PM 8955267 ER PT J AU Flake, AW Roncarolo, MG Puck, JM AlmeidaPorada, G Evans, MI Johnson, MP Abella, EM Harrison, DD Zanjani, ED AF Flake, AW Roncarolo, MG Puck, JM AlmeidaPorada, G Evans, MI Johnson, MP Abella, EM Harrison, DD Zanjani, ED TI Treatment of X-linked severe combined immunodeficiency by in utero transplantation of paternal bone marrow SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; CHROMOSOME INACTIVATION; INUTERO TRANSPLANTATION; CD34(+) CELLS; LYMPHOCYTES-T; SHEEP; ENGRAFTMENT; CARRIERS; ONTOGENY; LINKAGE C1 WAYNE STATE UNIV,DEPT PEDIAT SURG,DETROIT,MI. WAYNE STATE UNIV,DEPT OBSTET & GYNECOL,CTR MOL MED & GENET,DETROIT,MI. WAYNE STATE UNIV,DEPT PEDIAT,DETROIT,MI 48202. DNAX RES INST MOL & CELLULAR BIOL INC,DEPT HUMAN IMMUNOL,PALO ALTO,CA 94304. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV NEVADA,VET AFFAIRS MED CTR,DEPT MED,RENO,NV 89557. OI RONCAROLO, Maria Grazia/0000-0002-2193-9186 FU NHLBI NIH HHS [HL 52954, HL48378, HL49042-04]; Telethon [TGT06S01] NR 42 TC 221 Z9 228 U1 0 U2 3 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 DEC 12 PY 1996 VL 335 IS 24 BP 1806 EP 1810 DI 10.1056/NEJM199612123352404 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VW683 UT WOS:A1996VW68300004 PM 8943162 ER PT J AU Lockshin, MD AF Lockshin, MD TI Venous thromboembolism during pregnancy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Lockshin, MD (reprint author), NIH,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 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 DEC 12 PY 1996 VL 335 IS 24 BP 1847 EP 1847 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VW683 UT WOS:A1996VW68300026 PM 8965900 ER PT J AU Praseuth, D Grigoriev, M Guieysse, AL Pritchard, LL HarelBellan, A Nielsen, PE Helene, C AF Praseuth, D Grigoriev, M Guieysse, AL Pritchard, LL HarelBellan, A Nielsen, PE Helene, C TI Peptide nucleic acids directed to the promoter of the alpha-chain of the interleukin-2 receptor SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE peptide nucleic acid; interleukin 2 receptor; triple-helix; anti-gene strategy; strand invasion; transcription regulation ID THYMINE-SUBSTITUTED POLYAMIDE; STRAND-DISPLACEMENT; GENE-EXPRESSION; DUPLEX DNA; PNA; SEQUENCE; BINDING; INHIBITION; ACTIVATION; BACKBONE AB Two 10-mer oligopyrimidine peptide nucleic acids (PNAs) were designed to interfere with IL-2R alpha. promoter expression by binding to the regulatory sequences overlapping SRF and NF-kappa B transcription factor sites. Specific complexes were formed on each target sequence, and clearly involved(1) Hoogsteen hydrogen bonds as shown by experiments in which the purine strand of a single or double-stranded target was substituted with 7-deazadeoxyguanosine, (2) P-loop formation on double-helical DNA as evidenced by susceptibility to a single-strand-specific nuclease, When formed on a single-stranded DNA target, these highly stable complexes were responsible for efficient physical blockage of T7 DNA polymerase elongation on the template DNA containing the target oligopurine sequence, On a double-stranded target, these complexes only formed at low ionic strength and were slowly dissociated at physiological ionic strength (pH 6.5) with a t(1/2) of 6.5-7 h. The salt-dependent instability of preformed complexes on a plasmid target was probably the critical factor responsible for their lack of significant sequence-specific effect on IL-2R alpha promoter activity inside living cells. C1 INST GUSTAVE ROUSSY, LAB BIOL TUMEURS HUMAINES, CNRS URA 1156, F-94805 VILLEJUIF, FRANCE. NIKDD, GENET & BIOCHEM BRANCH, NIH, BETHESDA, MD 20892 USA. INSERM U267 IMMUNOGENET ALLOGREFFES, F-94807 VILLEJUIF, FRANCE. UNIV COPENHAGEN, PANUM INST, DEPT MED BIOCHEM & GENET, CTR BIOMOL RECOGNIT, DK-2200 COPENHAGEN N, DENMARK. RP Praseuth, D (reprint author), MUSEUM NATL HIST NAT, BIOPHYS LAB, INSERM U201, CNRS URA 481, 43 RUE CUVIER, F-75231 PARIS 05, FRANCE. RI Harel-Bellan, Annick/M-9795-2015; OI Harel-Bellan, Annick/0000-0002-2339-153X NR 29 TC 27 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD DEC 11 PY 1996 VL 1309 IS 3 BP 226 EP 238 DI 10.1016/S0167-4781(96)00146-7 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VX952 UT WOS:A1996VX95200012 PM 8982260 ER PT J AU Kafadar, K Prorok, PC AF Kafadar, K Prorok, PC TI Computer simulation of randomized cancer screening trials to compare methods of estimating lead time and benefit time SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE bivariate gamma density; catch-up point; disease progression model; incidence rate; test sensitivity; sojourn time; survival time ID DEPENDENT STOCHASTIC-MODEL; DISEASE STATE; LENGTH BIAS; LUNG AB Screening studies provide information on lead time of the screening test (time by which diagnosis is advanced) and benefit (defined either as a reduction in overall mortality, or as the time by which survival has been extended by virtue of the screen), particularly when these studies are randomized trials. Several methods have been proposed to estimate average lead rime and average benefit time for the population which is offered screening. When applied to data from actual screening trials, the performance of these methods is uncertain, since the true averages are unknown. A simulated randomized screening trial offers flexibility in choosing the parameters of an actual trial, including distributions of preclinical and clinical disease, test sensitivity, actual benefit time, and correlation between any two of these parameters. By adjusting these parameters, we gain information on their joint effects on proposed estimators. This paper demonstrates this method of evaluation for estimators of average lead time and average benefit time and proposes avenues for generalizing these types of investigations. C1 UNIV COLORADO,DEPT MATH,DENVER,CO 80217. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NR 30 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD DEC 11 PY 1996 VL 23 IS 2 BP 263 EP 291 DI 10.1016/S0167-9473(96)00029-1 PG 29 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA VZ700 UT WOS:A1996VZ70000006 ER PT J AU Nonnenmacher, B Kjaer, SK Svare, EI Scott, JD Hubbert, NL vandenBrule, AJC Kirnbauer, R Walboomers, JMM Lowy, DR Schiller, JT AF Nonnenmacher, B Kjaer, SK Svare, EI Scott, JD Hubbert, NL vandenBrule, AJC Kirnbauer, R Walboomers, JMM Lowy, DR Schiller, JT TI Seroreactivity to HPV16 virus-like particles as a marker for cervical cancer risk in high-risk populations SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; POLYMERASE CHAIN-REACTION; HERPES-SIMPLEX VIRUS; GREENLAND; DENMARK; SCRAPES; ANTIBODIES; GENOTYPES; INFECTION; NEOPLASIA AB Sexually transmitted genital human papillomavirus (HPV) infection, most often HPV 16, is considered the major etiologic determinant of cervical cancer. However, some studies have found relatively low prevalences of genital tract HPV DNA in some geographical areas, such as Greenland, that have high rates of cervical cancer. We sought to evaluate HPV 16 infection in high-risk cohorts using a serologic assay that assesses prior exposure as well as current infection and to compare the results with those obtained using a sensitive PCR-based HPV DNA assay. An ELISA based on HPV 16 virus-like particles was used to detect IgG serum antibodies in women attending sexually transmitted disease (STD) clinics in Nuuk, Greenland and Copenhagen, Denmark. Using a preassigned cut-off, 56% of Greenlandic and 41% of Danish women were seropositive (p=0.02). In Greenlandic women, there was a non-significant increase in seropositivity with age, and odds ratios for seropositivity were similar far women with more than 5 lifetime sex partners. Seropositivity in the Danish women, however, increased linearly with increases in these 2 factors, which are likely correlates of lifetime exposure to genital HPVs. In contrast, any genital HPV DNA (HPV16 specifically) was detected in 24% and 36% of Greenlandic and Danish women, respectively and was most frequently detected in women below 20. The finding that HPV DNA prevalences, unlike seroprevalences, tended to decrease with increased lifetime risk of infection, provides an explanation for the lack of correlation between HPV DNA prevalences and cervical cancer risk in previous studies of high-risk populations. (C) 1996 Wiley-Liss, Inc. C1 NIH,CELLULAR ONCOL LAB,BETHESDA,MD 20892. DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. FREE UNIV AMSTERDAM HOSP,DEPT PATHOL,AMSTERDAM,NETHERLANDS. NR 21 TC 33 Z9 34 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 11 PY 1996 VL 68 IS 6 BP 704 EP 709 DI 10.1002/(SICI)1097-0215(19961211)68:6<704::AID-IJC3>3.0.CO;2-7 PG 6 WC Oncology SC Oncology GA WB320 UT WOS:A1996WB32000003 PM 8980170 ER PT J AU Biggar, RJ Rosenberg, PS Cote, T AF Biggar, RJ Rosenberg, PS Cote, T TI Kaposi's sarcoma and non-Hodgkin's lymphoma following the diagnosis of aids SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HOMOSEXUAL MEN; DNA-SEQUENCES; RISK; CANCER; INFECTION AB We linked records of 83,434 AIDS cases reported to AIDS registries through 1990 to cancer registry records during times when overlap in registration existed. Of 8,496 Kaposi's-sarcoma (KS) cases meeting enrollment criteria, 1,045 occurred semesters 2 through 4 (6 through 23 months) after another AIDS-defining illness. KS risk in this period after AIDS declined steadily over the 1980s. Adjusting for age, gender, ethnic origin and calendar time period, we found the relative risk (RR) of KS to be 106,000 for homo/bisexual men with AIDS and 13,000 for other men with AIDS, Risk was highest for homo/bisexual men between 30 and 39 years old and among 20- to 29-year-old non-homo/bisexual men. The RR in black men was approximately half that reported in white men among home-bisexual men and others. Between the second and fourth semester after AIDS, the ratio of RR of KS to that of non-AIDS-related cancers increased 1.5-fold. In a similar analysis, there were 335 non-Hodgkin's lymphoma (NHL) cases in semesters 2 through 4 after AIDS. The overall risk was elevated 283-fold in homo/bisexual men and the RR ratio increased 1.8-fold between semester 2 and 4 after AIDS. In summary, the risk of KS following another AIDS-defining illness is strikingly high, more in white men than in black men, and the risks of KS and, especially, NHL appear to increase with time from AIDS. (C) 1996 Wiley-Liss, Inc. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NR 18 TC 80 Z9 81 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 11 PY 1996 VL 68 IS 6 BP 754 EP 758 PG 5 WC Oncology SC Oncology GA WB320 UT WOS:A1996WB32000012 PM 8980179 ER PT J AU Nelson, KB AF Nelson, KB TI Magnesium sulfate and risk of cerebral palsy in very low-birth-weight infants SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PREVENTION; BRAIN RP Nelson, KB (reprint author), NIH,NEUROEPIDEMIOL BRANCH,7550 WISCONSIN AVE,ROOM 714 FB,BETHESDA,MD 20892, USA. NR 17 TC 14 Z9 15 U1 0 U2 0 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 DEC 11 PY 1996 VL 276 IS 22 BP 1843 EP 1844 DI 10.1001/jama.276.22.1843 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VV997 UT WOS:A1996VV99700037 PM 8946908 ER PT J AU Wang, YX Freedberg, DI Wingfield, PT Stahl, SJ Kaufman, JD Kiso, Y Bhat, TN Erickson, JW Torchia, DA AF Wang, YX Freedberg, DI Wingfield, PT Stahl, SJ Kaufman, JD Kiso, Y Bhat, TN Erickson, JW Torchia, DA TI Bound water molecules at the interface between the HIV-1 protease and a potent inhibitor, KNI-272, determined by NMR SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SPECTROSCOPY; HYDRATION AB KNI-272 is a peptidomimetic transition state analog inhibitor, having very high specificity and binding affinity for the HIV-1 protease. In order to understand the interactions that enhance drug binding to the protease, we recorded 2D water/NOESY and water/ROESY spectra to identify water molecules that bind tightly to the protease/KNI-272 complex. Well-ordered water molecules are observed at the protease/inhibitor interface in the crystal structure of the complex that have short interproton distances to the Ile50/150, Ala28/128, and Asp29/129 amide protons. The cross peaks between these protein protons and water protons, observed in water/NOESY and water/ROESY spectra, provide strong evidence that these water molecules are present in the solution structure of the complex. Analysis of measured NOE and ROE cross relaxation rates indicates that, in solution, these water molecules have long residence times, at least 1 ns and possibly greater than 7 ns. The presence of long-lived hydration water molecules at the protein/inhibitor interface suggests that interactions involving these water molecules contribute to the potency of the inhibitor. Hence, consideration of the potential role of hydration water molecules in stabilizing protein/inhibitor structures could contribute to improved drug design and to a better understanding of the mechanisms of drug resistance. C1 NIDR,STRUCT MOL BIOL UNIT,NIH,BETHESDA,MD 20892. NIAMSD,PROT EXPRESS LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,STRUCT BIOCHEM PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. KYOTO PHARMACEUT UNIV,YAMASHIMA KU,KYOTO 607,JAPAN. NR 21 TC 47 Z9 48 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 11 PY 1996 VL 118 IS 49 BP 12287 EP 12290 DI 10.1021/ja962612i PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA VX654 UT WOS:A1996VX65400005 ER PT J AU Esteban, EN Sherman, MP Poiesz, BL Marshak, RR Waters, DJ Ferrer, JF AF Esteban, EN Sherman, MP Poiesz, BL Marshak, RR Waters, DJ Ferrer, JF TI Transmission of human T cell leukemia virus type I to sheep: Antibody profile and detection of viral DNA sequences SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; POLYMERASE CHAIN-REACTION; HTLV-I; GENE AMPLIFICATION; INFECTION; RABBITS; LYMPHOCYTES; RETROVIRUS; MYELOPATHY; LYMPHOMA AB Lambs were inoculated intraperitoneally with either 1.8 x 10(7) live peripheral blood cells from an HTLV-I-infected person (five lambs) or with 8 x 10(7) live cells from the HTLV-I-producing cell lines MT-2 (four lambs) or C10 MJ (five lambs), Four control lambs were inoculated with minimal essential medium supplemented with fetal calf serum, The animals were monitored during a period of 24 months, Beginning at 5 to 12 months after inoculation, four of the five lambs inoculated with the fresh HTLV-I-infected peripheral blood cells began to develop detectable levels of antibodies to a recombinant HTLV-I gp21(env) antigen, as determined by an enzyme-linked immunoassay (ELISA). The anti-gp21 antibodies persisted for the remaining observation period, These antibodies were not detected in the sera from the other sheep, Absorption and blocking experiments demonstrated the specificity of the gp21 reactivity, This reactivity was also confirmed by Western blot (WB). With the exception of the serum of an MT-2-inoculated sheep that formed a weak band with p19 by WB, none of the sera of the four gp21-positive sheep or of the other experimental sheep reacted with other structural or regulatory HTLV-I proteins, as determined by ELISA, WB, and radioimmunoassay, PCR analyses demonstrated the presence of the HTLV-I provirus in peripheral blood leukocytes of the four sheep showing antibodies to gp21(env), The remaining sheep were negative, PCR analyses failed to detect BLV sequences in any of the experimental sheep, None of the sheep showed clinical abnormalities during the observation period, The potential value of the sheep model for studying atypical virus-host interactions in infected people is discussed. C1 UNIV PENN, NEW BOLTON CTR, KENNETT SQ, PA 19348 USA. SUNY HLTH SCI CTR, DEPT MED, SYRACUSE, NY 13210 USA. FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. FU NHLBI NIH HHS [HB 67021]; NIAID NIH HHS [AI 27658] NR 47 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC 10 PY 1996 VL 12 IS 18 BP 1717 EP 1724 DI 10.1089/aid.1996.12.1717 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VY708 UT WOS:A1996VY70800010 PM 8959249 ER PT J AU Shou, M Gonzalez, FJ Gelboin, HV AF Shou, M Gonzalez, FJ Gelboin, HV TI Stereoselective epoxidation and hydration at the K-region of polycyclic aromatic hydrocarbons by cDNA-expressed cytochromes P450 1A1, 1A2, and epoxide hydrolase SO BIOCHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CHIRAL STATIONARY PHASES; LIVER MICROSOMAL-ENZYMES; 5,6-EPOXIDE ENANTIOMERS; DIRECT SEPARATION; DIOL ENANTIOMERS; VACCINIA VIRUS; ARENE OXIDES; METABOLISM; BENZOPYRENE AB Stereoselective epoxidation by cytochrome P450s (P450s) and regioselective hydration by epoxide hydrolase determine the carcinogenic potency of some polycyclic aromatic hydrocarbons (PAHs). In this report, cDNA-expressed human and mouse P450s 1A1 and 1A2 and epoxide hydrolase were used to characterize the stereoselective epoxidation and regioselective hydration at the K-region of benz[a]anthracene (BA), 7,12-dimethylbenz[a]anthracene (DMBA), chrysene (CR), benzo[a]pyrene (B[a]P), dibenz[a,h]anthrancene (DB[a,h]A), and benzo[c]phenanthrene (B[c]Ph) by direct chiral stationary-phase HPLC (CSP-HPLC) analyses. Our results indicated that all P450 isoforms preferentially produced major K-region S,R-epoxides of BA (95-98%), DMBA (94-97%), B[a]P (91-96%), DB[a,h]A (94-98%), and B[c]Ph (87-92%), and major R,S-epoxide of CR (74-85%) in the presence of 3,3,3-trichloropropylene 1,2-oxide (TCPO), an inhibitor of epoxide hydrolase, suggesting that P450 enzymes exhibited the high stereoselectivity toward one of two stereoheterotopic faces of K-region double bond of the PAHs. Epoxide hydrolase either expressed from recombinant vaccinia virus or contained in human hepatoma G2 cells (HepG2) hydrated the C-O bond of epoxy-ring at the S-carbon of major metabolically-formed K-region epoxide enantiomers of BA, CR, DMBA, B[a]P, and DB[a,h]A to yield 80-98% dihydrodiols enriched in R,R-form and that at the R-carbon of B[c]Ph epoxide to yield 77-92% dihydrodiol enriched in S,S-form, suggesting that epoxide hydrolase was highly regioselective. The various enantiomeric components of dihydrodiol products in the metabolism of PAHs were apparently due to the combined effect of stereoselectivity of the P450s and regioselectivity of epoxide hydrolase. Our results provide a clear understanding of how these enzymes catalyze overall stereoselective metabolism at the K-region of the PAHs. RP Shou, M (reprint author), NCI,MOL CARCINOGENESIS LAB,NATL INST HLTH,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. NR 43 TC 64 Z9 65 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 10 PY 1996 VL 35 IS 49 BP 15807 EP 15813 DI 10.1021/bi962042z PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VX510 UT WOS:A1996VX51000023 PM 8961944 ER PT J AU Eurenius, KP Chatfield, DC Brooks, BR Hodoscek, M AF Eurenius, KP Chatfield, DC Brooks, BR Hodoscek, M TI Enzyme mechanisms with hybrid quantum and molecular mechanical potentials .1. Theoretical considerations SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY LA English DT Article ID FREE-ENERGY PERTURBATION; HYDROGEN-BONDED SYSTEMS; PROTON TRANSFERS; AQUEOUS-SOLUTION; DYNAMICS SIMULATIONS; TRANSITION-STATES; PHOSPHOLIPASE-A2; PHASE; ETHER; WATER AB The application of hybrid quantum mechanical and molecular mechanical (QM/MM) potentials to the study of chemical reactions in enzymes is outlined. The discussion is general and addresses the difficulties encountered in an enzyme QM/MM study. First, general criteria for determining whether a particular enzyme is an appropriate candidate for a QM/MM approach are outlined. Methods for obtaining starting structures are detailed. The importance of choosing appropriate levels of ab initio or semiempirical theory is emphasized. Approaches for interfacing the QM and MM regions are briefly discussed, with greater detail given to describing our CHARMM-GAMESS interface. Techniques for partitioning the system into QM and MM regions are explored. Link atom placement, as distant from reacting atoms as possible within the confines of computational efficiency, is examined in some detail. Methods for determining reaction paths are also discussed. (C) 1996 John Wiley & Sons, Inc. C1 NATL INST HLTH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. NATL INST CHEM,LJUBLJANA 61115,SLOVENIA. NR 48 TC 161 Z9 161 U1 2 U2 10 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7608 J9 INT J QUANTUM CHEM JI Int. J. Quantum Chem. PD DEC 10 PY 1996 VL 60 IS 6 BP 1189 EP 1200 DI 10.1002/(SICI)1097-461X(1996)60:6<1189::AID-QUA7>3.0.CO;2-W PG 12 WC Chemistry, Physical; Mathematics, Interdisciplinary Applications; Physics, Atomic, Molecular & Chemical SC Chemistry; Mathematics; Physics GA VU308 UT WOS:A1996VU30800008 ER PT J AU Frenking, G Dapprich, S Kohler, KF Koch, W Collins, JR AF Frenking, G Dapprich, S Kohler, KF Koch, W Collins, JR TI Structure and bonding of the remarkable donor-acceptor complexes XBeO (X=NH3, NMe(3), CO, N-2, C2H2, C2H4, H-2, H2CO, O-2) SO MOLECULAR PHYSICS LA English DT Article ID MOLECULAR-ORBITAL METHODS; VALENCE BASIS-SETS; INFRARED-SPECTRA; THEORETICAL PREDICTIONS; 2ND-ROW ELEMENTS; GROUND-STATE; SOLID ARGON; CHEMISTRY; HELIUM; BEO AB Quantum mechanical calculations at the MP4/6-311G(2df,2pd)//MP2/6-31G(d,p) level of theory are reported for the compounds XBeO with X = NH3 NMe(3), CO, N-2, C2H2, C2H4, H-2, H2CO and O-2. The calculations show that BeO is a very strong Lewis acid. The X-BeO bond strength is between D-e = 69.5 kcal mol(-1) for Me(3)NBeO and D-e = 11.2 kcal mol(-1) for pi-bonded N2BeO. The calculated bond strength for the yet unknown donor-acceptor complex Me(3)NBeO is significantly higher than the strongest experimentally known main-group donor-acceptor complex Me(3)NAlCl(3) (D-o = 47.5 kcal mol(-1)). Even the weak donor H-2 is bonded with D-e = 18.5 kcal mol(-1). The compounds O2BeO and its isomer berylliumozonide BeO3 should not be considered as donor-acceptor complexes. The results of the CDA method show that the donor-acceptor interactions in terms of orbital mixing are mainly described by the mixing of occupied orbitals of X with vacant orbitals of BeO, while the mixing of occupied orbitals of BeO with vacant orbitals of X is negligible. The topological analysis of the electronic charge distribution and the NBO partitioning scheme demonstrate that the X-BeO bonds have little or no covalent character; the bonds are caused by electrostatic attraction. The charge concentration at the donor atoms in the stronger bonded compounds is significantly deformed towards the beryllium atom. C1 TECH UNIV BERLIN, INST ORGAN CHEM, D-10623 BERLIN, GERMANY. NCI, FREDERICK, MD 21702 USA. RP UNIV MARBURG, FACHBEREICH CHEM, HANS MEERWEIN STR, D-35032 MARBURG, GERMANY. NR 43 TC 30 Z9 30 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0026-8976 EI 1362-3028 J9 MOL PHYS JI Mol. Phys. PD DEC 10 PY 1996 VL 89 IS 5 BP 1245 EP 1263 PG 19 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA VZ714 UT WOS:A1996VZ71400003 ER PT J AU Hill, TL AF Hill, TL TI Adsorption from a one-dimensional lattice gas and the Brunauer-Emmett-Teller equation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Ising model; reference system; Gibbs excess adsorption; Gibbs integral AB An exact treatment of adsorption from a one-dimensional lattice gas is used to eliminate and correct a well-known inconsistency in the Brunauer-Emmett-Teller (B.E.T.) equation-namely Gibbs excess adsorption is not taken into account and the Gibbs integral diverges at the transition point, However, neither model should be considered realistic for experimental adsorption systems. RP Hill, TL (reprint author), NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 9 TC 16 Z9 16 U1 1 U2 4 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 DEC 10 PY 1996 VL 93 IS 25 BP 14328 EP 14332 DI 10.1073/pnas.93.25.14328 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800027 PM 8962050 ER PT J AU Sweitzer, TD Hanover, JA AF Sweitzer, TD Hanover, JA TI Calmodulin activates nuclear protein import: A link between signal transduction and nuclear transport SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PERMEABILIZED MAMMALIAN-CELLS; ENDOPLASMIC-RETICULUM; PORE COMPLEX; LOCALIZATION SIGNALS; BINDING-PROTEINS; IN-VITRO; CALCIUM; IDENTIFICATION; SUBSTRATE; INTERACTS AB In addition to the well-characterized GTP-dependent nuclear transport observed in permeabilized cells. we detected a mode of nuclear transport that was GTP-independent at elevated cytoplasmic calcium concentrations. Nuclear transport under these conditions was blocked by calmodulin inhibitors, Recombinant calmodulin restored ATP-dependent nuclear transport in the absence of cytosol. Calmodulin-dependent transport was inhibited by wheat germ agglutinin consistent with transport proceeding through nuclear pores, We propose that release of intracellular calcium stores upon cell activation inhibits GTP-dependent nuclear transport: the elevated cytosolic calcium then acts through calmodulin to stimulate the novel GTP-independent mode of import. C1 NIDDKD,CELL BIOCHEM & BIOL LAB,NIH,BETHESDA,MD 20892. NR 50 TC 69 Z9 69 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 DEC 10 PY 1996 VL 93 IS 25 BP 14574 EP 14579 DI 10.1073/pnas.93.25.14574 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800071 PM 8962094 ER PT J AU Iiri, T Backlund, PS Jones, TLZ Wedegaertner, PB Bourne, HR AF Iiri, T Backlund, PS Jones, TLZ Wedegaertner, PB Bourne, HR TI Reciprocal regulation of G(s alpha) by palmitate and the beta gamma subunit SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE trimeric G proteins; lipid modification; membrane localization; protein-protein interaction ID PROTEIN ALPHA-SUBUNIT; GTP-BINDING PROTEIN; LIPID MODIFICATIONS; MEMBRANE ATTACHMENT; SF9 CELLS; PALMITOYLATION; MYRISTOYLATION; ACTIVATION; EXPRESSION; PURIFICATION AB Hormonal activation of G(s), the stimulatory regulator of adenylyl cyclase, promotes dissociation of alpha(s) from G beta gamma, accelerates removal of covalently attached palmitate from the G alpha subunit, and triggers release of a fraction of alpha(s) from the plasma membrane into the cytosol. To elucidate relations among these three events, we assessed biochemical effects in vitro of attached palmitate on recombinant alpha(s) prepared from Sf9 cells. In comparison to the unpalmitoylated protein (obtained from cytosol of Sf9 cells, treated with a palmitoyl esterase, or expressed as a mutant protein lacking the site for palmitoylation), palmitoylated alpha(s) (from Sf9 membranes, 50% palmitoylated) was more hydrophobic, as indicated by partitioning into TX-114, and bound beta gamma with 5-fold higher affinity. beta gamma protected GDP-bound alpha(s), but not alpha(s) . GTP[gamma S], from depalmitoylation by a recombinant esterase. We conclude that beta gamma binding and palmitoylation reciprocally potentiate each other in promoting membrane attachment of at, and that dissociation of alpha(s) . GTP from beta gamma is likely to mediate receptor-induced alpha(s) depalmitoylation and translocation of the protein to cytosol in intact cells. C1 UNIV CALIF SAN FRANCISCO,DEPT CELLULAR & MOL PHARMACOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. NIMH,LAB GEN & COMPARAT BIOCHEM,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT BIOCHEM & MOL PHARMACOL,PHILADELPHIA,PA 19107. NR 37 TC 89 Z9 90 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 DEC 10 PY 1996 VL 93 IS 25 BP 14592 EP 14597 DI 10.1073/pnas.93.25.14592 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800074 PM 8962097 ER PT J AU Gueguen, M Long, EO AF Gueguen, M Long, EO TI Presentation of a cytosolic antigen by major histocompatibility complex class II molecules requires a long-lived form of the antigen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antigen processing; HLA-DR; N-end rule; protein degradation; ubiquitin ID NATURALLY PROCESSED PEPTIDES; RESTRICTED T-CELLS; HLA-DR MOLECULES; HEN EGG LYSOZYME; ENHANCED DEGRADATION; RHEUMATOID-ARTHRITIS; VACCINIA VIRUS; INFECTED CELLS; LYMPHOCYTES-T; MHC AB Class I and class II molecules of the major histocompatibility complex present peptides to T cells, Class I molecules bind peptides that hare been generated in the cytosol by proteasomes and delivered into the endoplasmic reticulum by the transporter associated with antigen presentation, In contrast, class II molecules are very efficient in the presentation of antigens that have been internalized and processed in endosomal lysosomal compartments, In addition, class II molecules can present some cytosolic antigens by a TAP-independent pathway. To test whether this endogenous class II presentation pathway was linked to proteasome-mediated degradation of antigen in the cytosol, the N-end rule was utilized to produce two forms of the influenza virus matrix protein with different in vivo half-lives (10 min vs. 5 h) when expressed in human B cells, Whereas class I molecules presented both the short- and the long-lived matrix proteins, class II molecules presented exclusively the long-lived form of antigen, Thus, rapid degradation of matrix protein in the cytosol precluded its presentation by class II molecules, These data suggest that the turnover of long-lived cytosolic proteins, some of which is mediated by delivery into endosomal/lysosomal compartments, provides a mechanism for immune surveillance by CD4(+) T cells. C1 NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 47 TC 46 Z9 46 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 DEC 10 PY 1996 VL 93 IS 25 BP 14692 EP 14697 DI 10.1073/pnas.93.25.14692 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800093 PM 8962116 ER PT J AU Grossman, Z Singer, A AF Grossman, Z Singer, A TI Tuning of activation thresholds explains flexibility in the selection and development of T cells in the thymus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSITIVE SELECTION; RECEPTOR LIGAND; DIFFERENTIATION; PROLIFERATION; SPECIFICITY; THYMOCYTES; LYMPHOCYTE; TOLERANCE; ANERGY; INVIVO AB Immature CD4(+)CD8(+) thymocytes expressing T-cell antigen receptors (TCR) are selected by TCR-mediated recognition of peptides associated with major histocompatibility complex molecules on thymic stromal cells. Selection ensures reactivity of the mature cells to foreign antigens and tolerance to self Although much has been learned about tbe factors that determine whether a thymocyte with a given specificity will be positively or negatively selected, selection as an aspect of the developmental process as a whole is less well-understood. Here we invoke a model in which thymocytes tune their response characteristics individually and dynamically in the course of development, Cellular development and selection are driven by receptor-mediated metabolic perturbations. Perturbation is a measure of the net intracellular change induced by external stimulation, It results from the integration of several signals and countersignals over time and therefore depends on the environment and the maturation stage of the cell. Individual cell adaptation limits the range of perturbations. Such adaptation renders thymocytes less sensitive to the level of stimulation per se, but responsive to environmental changes in that level, This formulation begins to explain the mechanisms that link developmental and selection events to each other. C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. RP Grossman, Z (reprint author), TEL AVIV UNIV,SACKLER FAC MED,DEPT PHYSIOL & PHARMACOL,IL-69978 TEL AVIV,ISRAEL. RI Grossman, Zvi/A-9643-2008 NR 26 TC 99 Z9 99 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 DEC 10 PY 1996 VL 93 IS 25 BP 14747 EP 14752 DI 10.1073/pnas.93.25.14747 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800103 PM 8962126 ER PT J AU Lorimer, IAJ KepplerHafkemeyer, A Beers, RA Pegram, CN Bigner, DD Pastan, I AF Lorimer, IAJ KepplerHafkemeyer, A Beers, RA Pegram, CN Bigner, DD Pastan, I TI Recombinant immunotoxins specific for a mutant epidermal growth factor receptor: Targeting with a single chain antibody variable domain isolated by phage display SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE EGFRvIII; glioblastoma; cancer therapy; Pseudomonas exotoxin A ID HUMAN-BRAIN-TUMORS; PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY; LUNG CARCINOMAS; EXPRESSION; FV; GLIOBLASTOMA; PROTEINS; GENE AB EGFRvIII is a mutant epidermal growth factor receptor found in glioblastoma, and in carcinoma of the breast, ovary, and lung, The mutant receptor has a deletion in its extracellular domain that results in the formation of a new, tumor-specific extracellular sequence, Mice were immunized with a synthetic peptide corresponding to this sequence and purified EGFRvIII, A single chain antibody variable domain (scFv) phage display library of 8 x 10(6) members was made from the spleen of one immunized mouse. A scFv specific for EGFRvIII was isolated from this library by panning with successively decreasing amounts of synthetic peptide, This was used to make an immunotoxin by fusing the scFv DNA sequence to sequences coding for domains II and III of Pseudomonas exotoxin A. Purified immunotoxin had a K-d of 22 nM for peptide and a K-d of 11 nM for cell-surface EGFRvIII. The immunotoxin was very cytotoxic to cells expressing EGFRvIII, with an IC50 of 1 ng/ml (16 pM) on mouse fibroblasts transfected with EGFRvIII and an IC50 of 7-10 ng/ml (110-160 pM) on transfected glioblastoma cells, There was no cytotoxic activity at 1000 ng/ml on the untransfected parent glioblastoma cell line, The immunotoxin was completely stable upon incubation at 37 degrees C for 24 h in human serum, The combination of good affinity, cytotoxicity and stability make this immunotoxin a candidate for further preclinical evaluation. C1 NCI,DIV BASIC SCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. NR 30 TC 107 Z9 109 U1 0 U2 4 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 DEC 10 PY 1996 VL 93 IS 25 BP 14815 EP 14820 DI 10.1073/pnas.93.25.14815 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VY448 UT WOS:A1996VY44800115 PM 8962138 ER PT J AU Miller, M Lubkowski, J Rao, JKM Danishefsky, AT Omichinski, JG Sakaguchi, K Sakamoto, H Appella, E Gronenborn, AM Clore, GM AF Miller, M Lubkowski, J Rao, JKM Danishefsky, AT Omichinski, JG Sakaguchi, K Sakamoto, H Appella, E Gronenborn, AM Clore, GM TI The oligomerization domain of p53: Crystal structure of the trigonal form SO FEBS LETTERS LA English DT Article DE p53; tumor suppressor; tetramerization domain; X-ray crystallography; NMR; joint refinement ID PROTEIN-STRUCTURE DETERMINATION; TUMOR-SUPPRESSOR; TRANSCRIPTIONAL ACTIVATION; TETRAMERIZATION DOMAIN; DIRECT REFINEMENT; DNA-BINDING; X-RAY; NMR; SEQUENCE; APOPTOSIS AB The structure of the oligomerization domain of the p53 tumor suppressor protein was determined in the trigonal crystal form, using a refined NMR structure as a model. A synthetic peptide comprising residues 319-360 of human p53 crystallized in the space group P3(1)21. There is one biologically relevant tetrameric domain in the crystallographic asymmetric unit. The structure was refined jointly,vith NMR data, only the third such case (the previous examples being IL-1 beta (Shaanan, B., Gronenborn, A.M., Cohen, G.H., Gilliland, G.L., Veerapandian, B., Davies, D.R. and Clore, G.M. (1992) Science 257, 961-964 [1]) and BPTI (Schiffer, C., Huber, R., Wuthrich, K. and Van Gunsteren, W.F. (1994) J. Mol. Biol. 241, 588-599 [2])), to 2.5 Angstrom resolution with an R factor of 0.207. The distribution of tumor-derived mutations in the oligomerization region together with structural and biological data suggest a strategy for the design of antitumor therapeutics. C1 UNIV MARYLAND,DEPT MED RES & TECHNOL,BALTIMORE,MD 21201. NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RP Miller, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOL STRUCT LAB,FREDERICK,MD 21702, USA. RI Clore, G. Marius/A-3511-2008; Sakamoto, Hiroshi/A-3181-2011; Miller, Maria/I-1636-2013 OI Clore, G. Marius/0000-0003-3809-1027; Miller, Maria/0000-0003-0252-5348 NR 29 TC 30 Z9 30 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 9 PY 1996 VL 399 IS 1-2 BP 166 EP 170 DI 10.1016/S0014-5793(96)01231-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VY759 UT WOS:A1996VY75900037 PM 8980144 ER PT J AU Finegold, AA Shatwell, KP Segal, AW Klausner, RD Dancis, A AF Finegold, AA Shatwell, KP Segal, AW Klausner, RD Dancis, A TI Intramembrane bis-heme motif for transmembrane electron transport conserved in a yeast iron reductase and the human NADPH oxidase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; SACCHAROMYCES-CEREVISIAE; CYTOCHROME-B; FERRIC REDUCTASE; GENE; PHAGOCYTES; LOCATION; PROTEIN; SYSTEM AB A plasma membrane iron reductase, required for cellular iron acquisition by Saccharomyces cerevisiae, and the human phagocytic NADPH oxidase, implicated in cellular defense, contain low potential plasma membrane b cytochromes that share elements of structure and function, Four critical histidine residues in the FRE1 protein of the iron reductase were identified by site-directed mutagenesis, Individual mutation of each histidine to alanine eliminated the entire heme spectrum without affecting expression of the apoprotein, documenting the specificity of the requirement for the histidine residues, These critical residues are predicted to coordinate a bis-heme structure between transmembrane domains of the FRE1 protein. The histidine residues are conserved in the related gp91(phox) protein of the NADPH oxidase of human granulocytes, predicting the sites of heme coordination in that protein complex, Similarly spaced histidine residues have also been implicated in heme binding by organelle b cytochromes with little overall sequence similarity to the plasma membrane b cytochromes. This bis-heme motif may play a role in transmembrane electron transport by distinct families of polytopic b cytochromes. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. UNIV LONDON UNIV COLL,SCH MED,DEPT MED,LONDON WC1E 6JJ,ENGLAND. OI Segal, Anthony/0000-0001-7602-9043 FU Wellcome Trust NR 27 TC 128 Z9 135 U1 0 U2 6 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 DEC 6 PY 1996 VL 271 IS 49 BP 31021 EP 31024 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600004 PM 8940093 ER PT J AU Vito, P Wolozin, B Ganjei, JK Iwasaki, K Lacana, E DAdamio, L AF Vito, P Wolozin, B Ganjei, JK Iwasaki, K Lacana, E DAdamio, L TI Requirement of the familial Alzheimer's disease gene PS2 for apoptosis - Opposing effect of ALG-3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL HYBRIDOMAS; DNA FRAGMENTATION; CLONAL ELIMINATION; MISSENSE MUTATIONS; SELF-TOLERANCE; ENTEROTOXIN-B; IN-SITU; DEATH; ACTIVATION; ANTIGEN AB ALG-3, a truncated mouse homologue of the chromosome I familial Alzheimer's disease gene PS2, rescues T hybridoma 3DO cells from T-cell receptor-induced apoptosis by inhibiting Fas ligand induction and Fas signaling, Here we show that ALG-3 transfected 3DO cells express a COOH-terminal PS2 polypeptide, Overexpression of PS2 in ALG-3 transfected 3DO cells reconstitutes sensitivity to receptor-induced cell death, suggesting that the artificial PS2 polypeptide functions as a dominant negative mutant of PS2, ALG-3 and antisense PS2 protect PC12 cells from glutamate-induced apoptosis but not from death induced by hydrogen peroxide or the free radical MPP(+). Thus, the PS2 gene is required for some forms of cell death in diverse cell types, and its function is opposed by ALG-3. C1 NIAID,T CELL MOL BIOL UNIT,CELLULAR & MOL IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIMH,UNIV ALZHEIMER BIOL,CLIN SCI LAB,BETHESDA,MD 20892. NR 32 TC 121 Z9 122 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 DEC 6 PY 1996 VL 271 IS 49 BP 31025 EP 31028 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600005 PM 8940094 ER PT J AU Kusk, P John, S Fragoso, G Michelotti, J Hager, GL AF Kusk, P John, S Fragoso, G Michelotti, J Hager, GL TI Characterization of an NF-1/CTF family member as a functional activator of the mouse mammary tumor virus long terminal repeat 5' enhancer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR FACTOR-I; TGGCA-BINDING PROTEIN; TRANSGENIC MICE; DNA-REPLICATION; GLUCOCORTICOID REGULATION; TRANSCRIPTION FACTOR; PROVIRAL ACTIVATION; RESPONSIVE ELEMENT; ONCOGENE INT-1; ADENOVIRUS DNA AB The long terminal repeat of the mouse mammary tumor virus restricts virus expression primarily to the mammary epithelium. The extreme 5' end of the long terminal repeat contains an enhancer that has been associated with tissue-specific expression of the virus. A total of six functional cis-acting elements have been identified in the enhancer. Although proteins binding to these elements have been reported, only one has been identified; this factor, mp5, is identical or closely related to the transcription factor AP-2 (Mellentin-Michelotti, J., John, S., Pennie, W. D., Williams, T., and Hager, G. L. (1994) J. Biol. Chem. 269, 31983-31990). The other factors are hitherto unidentified and poorly described. We report here the characterization of another of the six elements, previously referred to as the F3 site (Mink, S., Hartig, E., Jennewein, P., Doppler, W., and Cato, A. C. (1992) Mol. Cell Biol, 12, 4906-4918), We show that the F3 binding activity and AP-2 act synergistically to enhance mouse mammary tumor virus-directed transcription, but only in the presence of glucocorticoid hormone, The F3 element has an NF-l-like half-site, but the activity recognizing this element has binding characteristics distinct from the NF-1/CTF family as well as the rest of the CCAAT-binding proteins. We conclude that the F3 activity represents a new member of the NF-1/CTF family. C1 NCI,LAB RECEPTOR BIOL & GENE EXPRESS,BETHESDA,MD 20892. NR 47 TC 18 Z9 18 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 DEC 6 PY 1996 VL 271 IS 49 BP 31269 EP 31276 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600042 PM 8940131 ER PT J AU Kole, HK Liotta, AS Kole, S Roth, J MontroseRafizadeh, C Bernier, M AF Kole, HK Liotta, AS Kole, S Roth, J MontroseRafizadeh, C Bernier, M TI A synthetic peptide derived from a COOH-terminal domain of the insulin receptor specifically enhances insulin receptor signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; SRC HOMOLOGY-2 DOMAINS; GROWTH-FACTOR RECEPTOR; HAMSTER OVARY CELLS; BETA-SUBUNIT DOMAIN; FACTOR-I RECEPTORS; PHOSPHATIDYLINOSITOL 3'-KINASE; C-TERMINUS; SUBSTRATE PHOSPHORYLATION; AUTOPHOSPHORYLATION SITES AB The role of the insulin receptor COOH-terminal domain in the regulation of insulin signal transduction was explored with a variety of synthetic peptides, One of the peptides, termed peptide HC, whose structure corresponds to residues 1293-1307 of the insulin proreceptor sequence, enhanced insulin-stimulated autophosphorylation of the insulin receptor in cell-free systems and in semipermeabilized Chinese hamster ovary (CHO) cells that had been transfected with an expression plasmid encoding the human insulin receptor (CHO/HIRc) at concentrations where there was no detectable effect on basal autophosphorylation levels or on receptor de phosphorylation, A lipophilic analogue of peptide HC, stearyl peptide HC, added to intact CHO/HIRc cells enhanced significantly insulin-stimulated insulin receptor autophosphorylation while having no effect on ligand-stimulated receptor phosphorylation in CHO cells overexpressing either the IGF-1 receptor or epidermal growth factor receptor, Addition of stearyl peptide HC to CHO/HIRc cells resulted in a 2.4 +/- 0.3-fold increase in the amount of insulin stimulated phosphatidylinositol 3-kinase detected in anti-IRS-1 immunoprecipitates and a 2.1 +/- 0.6-fold increase in the levels of tyrosine phosphorylation of mitogen-activated protein kinase in response to insulin, Finally, a derivative of peptide HC coupled to a biotin moiety was prepared and showed to bind with the beta-subunit of the wild-type insulin receptor and a truncated receptor that lacks 43 amino acids from its carboxyl terminus, However, there was little binding, if any, of the peptide with the IGF-1 receptors or the epidermal growth factor receptors, Taken together, our data demonstrate that a pentadecapeptide related to the carboxyl terminus of the insulin receptor binds to the insulin receptor beta-subunit and that this interaction may contribute to the increased receptor's intrinsic activity and signal transduction. C1 NIA,GERONTOL RES CTR,DIABET SECT,LAB CLIN PHYSIOL,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21224. OI Bernier, Michel/0000-0002-5948-368X NR 52 TC 15 Z9 15 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 DEC 6 PY 1996 VL 271 IS 49 BP 31619 EP 31626 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600092 PM 8940181 ER PT J AU DavisSmyth, T Duncan, RC Zheng, T Michelotti, G Levens, D AF DavisSmyth, T Duncan, RC Zheng, T Michelotti, G Levens, D TI The far upstream element-binding proteins comprise an ancient family of single-strand DNA-binding transactivators SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RICH ACTIVATION MOTIF; TRANSCRIPTION FACTOR; RNA-BINDING; C-MYC; FOS PROTEINS; NUCLEIC-ACID; KH DOMAIN; REPLICATION; EXPRESSION; PROMOTER AB The cloning and expression of two new human cDNAs encoding proteins highly related to the far upstream element-binding protein (FBP) are described, FBP, FBP2, and FBP3 comprise a family of single-strand DNA-binding proteins that possess all of the general features of more conventional transcription factors. The FBPs each bind sequence specifically to only one strand of the far upstream element (FUSE; originally identified upstream of c-myc), and each possesses potent activation domains when fused to the GAL4 DNA-binding domain and assayed by transient transfection. Typical of transcription factors, the proteins are most highly related in their central, DNA-binding domains, but extensive homology is also shared within the tyrosine-rich, carboxyl-terminal activation domains. Comparison with Gen Bank sequences revealed a fourth FBP family member encoded by Caenorhabditis elegans chromosome III, illustrating the high degree of homology in this evolutionarily ancient and conserved family. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Levens, David/C-9216-2009; Duncan, Robert/I-8168-2015 OI Levens, David/0000-0002-7616-922X; Duncan, Robert/0000-0001-8409-2501 NR 41 TC 98 Z9 101 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 DEC 6 PY 1996 VL 271 IS 49 BP 31679 EP 31687 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VW686 UT WOS:A1996VW68600100 PM 8940189 ER PT J AU Lee, J Lewin, NE Acs, P Blumberg, PM Marquez, VE AF Lee, J Lewin, NE Acs, P Blumberg, PM Marquez, VE TI Conformationally constrained analogues of diacylglycerol .13. Protein kinase C ligands based on templates derived from 2,3-dideoxy-L-erythro(threo)-hexono-1,4-lactone and 2-deoxyapiolactone SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACTIVATION; SPECIFICITY; RECEPTOR; LACTONES; BINDING; FAMILY AB In the present investigation, the last two possible modes of generating conformationally semirigid diacylglycerol (DAG) analogues embedded into five-membered ring lactones as templates III and IV are investigated. The first two templates studied in previous investigations corresponded to 2-deoxyribonolactone (template I) and 4,4-disubstituted gamma-butyrolactone (template II), with the latter producing potent protein kinase C (PK-C) ligands with low nanomolar binding affinities. The templates reported in this work correspond to 2,3-dideoxy-L-erythro- or -threo-hexono-1,4-lactone (template III) and 2-deoxyapiolactone (template IV). Compounds constructed with the dideoxy-L-erythro- or -threo-hexono-1,4-lactone template were synthesized stereospecifically from tri-O-acetyl-L-glucal and L-galactono-1,4-lactone, respectively. Compounds constructed with the 2-deoxyapiolactone template were synthesized stereoselectively from di-O-isopropylidene-alpha-D-apiose. Inhibition of the binding of [H-3]phorbol-12,13-dibutyrate to PK-C alpha showed that only the threo-isomer, 5-O-tetradecanoyl-2,3-dideoxy-L-threo-hexono-1,4-lactone (2) was a good PK-C ligand (K-i = 1 mu M). The rest of the ligands had poorer affinities with K-i values between 10 and 28 mu M. With these results, the order of importance of five-membered ring lactones as competent templates for the construction of semirigid DAG surrogates with effective PK-C binding affinity can be established as II much greater than I similar to III > IV. C1 NIH,NATL CANC INST,MED CHEM LAB,DIV BASIC SCI,BETHESDA,MD 20892. NIH,NATL CANC INST,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,BETHESDA,MD 20892. NR 23 TC 11 Z9 11 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 6 PY 1996 VL 39 IS 25 BP 4912 EP 4919 DI 10.1021/jm960525v PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VX863 UT WOS:A1996VX86300007 PM 8960550 ER PT J AU Houlihan, WJ Boja, JW Parrino, VA Kopajtic, TA Kuhar, MJ AF Houlihan, WJ Boja, JW Parrino, VA Kopajtic, TA Kuhar, MJ TI Halogenated mazindol analogs as potential inhibitors of the cocaine binding site at the dopamine transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NONHUMAN-PRIMATES; GROWTH-HORMONE; RHESUS-MONKEYS; RAT-BRAIN; ABUSE; AMPHETAMINE; SEROTONIN; POTENCIES; STRIATUM; BEHAVIOR AB A series of halogenated (F, Cl, Br, I), pyrimido and diazepino homologs of mazindol were prepared and evaluated for their ability to displace [H-3]WIN 35,428 binding and to inhibit uptake of [H-3]dopamine (DA) in rat striatal tissue. All of the compounds except for the 2'-chloro (6) and 2'-bromo (16) analogs of mazindol displaced [H-3]WIN 35,428 binding and inhibited [H-3]DA uptake more effectively than (R)-cocaine. Structure-activity studies indicated that best inhibition of [H-3]WIN 35,428 binding occurred in the imidazo series with compounds containing one or two Cl or Br atoms in the 3'- or 4'-position of the free phenyl group. Replacement of the imidazo ring by a pyrimido or diazepino ring enhanced binding inhibition. The most potent inhibitors of [H-3]WIN 35,428 binding and [H-3]DA uptake were 6-(3'-chlorophenyl)-2,3,4,6-tetrahydropyrimido[2,1-a]isoindol-6-ol (23; IC50 1.0 nM; 8x mazindol) and 7-(3',4'-dichlorophenyl)-2,3,4,5-tetrahydro-7H-diazepino[2,1-a]isoindol-7-ol (28; IC50 0.26 nM; 32x mazindol), respectively. No significant differences was found between binding and uptake inhibition. Mazindol and the pyrimido and diazepino homologs 24 and 27 showed a selectivity for the DA uptake over the serotonin (5-HT) uptake site of 5-, 250-, and 465-fold, respectively, and displayed weak or no affinity for a variety of neurotransmitter receptor sites. C1 SANDOZ INC,RES INST,E HANOVER,NJ 07936. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP Houlihan, WJ (reprint author), DREW UNIV,CHARLES A DANA RES INST,HALL SCI,ROOM 331,MADISON,NJ 07940, USA. FU NIDA NIH HHS [5RO3DA 08516-02] NR 76 TC 26 Z9 26 U1 4 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 6 PY 1996 VL 39 IS 25 BP 4935 EP 4941 DI 10.1021/jm960288w PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VX863 UT WOS:A1996VX86300010 PM 8960553 ER PT J AU Kaphalia, BS Ghanayem, BI Ansari, GAS AF Kaphalia, BS Ghanayem, BI Ansari, GAS TI Nonoxidative metabolism of 2-butoxyethanol via fatty acid conjugation in Fischer 344 rats SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID GLYCOL MONOBUTYL ETHER; BUTOXYACETIC ACID; MAJOR METABOLITE; INHALATION; TOXICITY; 2-CHLOROETHANOL; SOLVENTS; HUMANS AB Nonoxidative metabolism of ethylene glycol monobutyl ether (2-butoxyethanol or BE) via fatty acid conjugation was studied in the liver of Fischer 344 male rats following a single oral administration of 500 mg/kg body weight [ethyl-1,2-C-14]BE (70 mu Ci/kg). Animals were killed 2 h after the treatment, hepatic lipids extracted, and the neutral lipids were separated using solid-phase extraction. The neutral lipid fraction was subjected to preparative thin-layer chromatography, and the esters corresponding to the relative flow of authentic fatty acid 2-butoxyethyl esters were recovered and analyzed by reversed-phase high-performance liquid chromatography (HPLC) using methanol-water (37:3, v/v) as solvent. Approximately 85% of the C-14 label present in the ester fraction was coeluted at retention times corresponding to the different fatty acid 2-butoxyethyl ester standards. The radioactive fractions were analyzed by electron impact mass spectrometry. Molecular ion peaks and fragmentation patterns similar to that of 16:0, 18:0, 18:1, 18:2, and 20:4 fatty acid 2-butoxyethyl ester standards were detected in the corresponding radioactive HPLC fractions. Fatty acid ethyl ester synthase (FAEES), purified from the rat liver microsomal fraction, was also found to catalyze the formation of 18:1 fatty acid 2-butoxyethyl ester. These studies demonstrate that BE is metabolized nonoxidatively via conjugation with long-chain fatty acids, and the formation of these esters appears to be catalyzed by the enzyme(s) involved in fatty acid conjugation of xenobiotic alcohols. However, the biological significance of BE conjugation with fatty acids remains to be investigated. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. RP Kaphalia, BS (reprint author), UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77555, USA. FU NIEHS NIH HHS [ES 04815] NR 30 TC 9 Z9 10 U1 1 U2 5 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD DEC 6 PY 1996 VL 49 IS 5 BP 463 EP 479 DI 10.1080/009841096160691 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VX941 UT WOS:A1996VX94100002 PM 8968408 ER PT J AU Eaton, WA Henry, ER Hofrichter, J AF Eaton, WA Henry, ER Hofrichter, J TI Nanosecond crystallographic snapshots of protein structural changes SO SCIENCE LA English DT Editorial Material ID CARBON-MONOXIDE; HEME-PROTEINS; CONFORMATIONAL-CHANGES; MOLECULAR-DYNAMICS; SINGLE-CRYSTALS; LIGAND-BINDING; HEMOGLOBIN; MYOGLOBIN; SPECTROSCOPY; REACTIVITY RP Eaton, WA (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 5,BETHESDA,MD 20892, USA. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 31 TC 10 Z9 10 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 6 PY 1996 VL 274 IS 5293 BP 1631 EP 1632 DI 10.1126/science.274.5293.1631 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VW712 UT WOS:A1996VW71200038 PM 8984630 ER PT J AU Wolozin, B Iwasaki, K Vito, P Ganjei, JK Lacana, E Sunderland, T Zhao, BY Kusiak, JW Wasco, V DAdamio, L AF Wolozin, B Iwasaki, K Vito, P Ganjei, JK Lacana, E Sunderland, T Zhao, BY Kusiak, JW Wasco, V DAdamio, L TI Participation of Presenilin 2 in apoptosis: Enhanced basal activity conferred by an Alzheimer mutation SO SCIENCE LA English DT Article ID AMYLOID PRECURSOR PROTEIN; PROGRAMMED CELL-DEATH; MISSENSE MUTATIONS; ENDOTHELIAL-CELLS; DISEASE; GENE; ACTIVATION AB Overexpression of the familial Alzheimer's disease gene Presenilin 2 (PS2) in nerve growth factor-differentiated PC12 cells increased apoptosis induced by trophic factor withdrawal or beta-amyloid. Transfection of antisense PS2 conferred protection against apoptosis induced by trophic withdrawal in nerve growth factor-differentiated or amyloid precursor protein-expressing PC12 cells, The apoptotic cell death induced by PS2 protein was sensitive to pertussis toxin, suggesting that heterotrimeric GTP-binding proteins are involved, A PS2 mutation associated with familial Alzheimer's disease was found to generate a molecule with enhanced basal apoptotic activity, This gain of function might accelerate the process of neurodegeneration that occurs in Alzheimer's disease, leading to the earlier age of onset characteristic a familial Alzheimer's disease. C1 NIMH,UNIT ALZHEIMER BIOL,CLIN SCI LAB,BETHESDA,MD 20892. NIAID,T CELL MOL BIOL UNIT,CELLULAR & MOL IMMUNOL LAB,BETHESDA,MD 20892. NIA,MOL NEUROBIOL UNIT,BALTIMORE,MD 21224. NINCDS,CELLULAR NEUROBIOL BRANCH,GERONTOL RES CTR,BALTIMORE,MD 21224. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP E,DEPT NEUROL,GENET & AGING UNIT,CHARLESTOWN,MA 02139. NIH,T CELL MOL BIOL UNIT,CELLULAR & MOL IMMUNOL LAB,BETHESDA,MD 20892. NR 28 TC 389 Z9 394 U1 2 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 6 PY 1996 VL 274 IS 5293 BP 1710 EP 1713 DI 10.1126/science.274.5293.1710 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VW712 UT WOS:A1996VW71200060 PM 8939861 ER PT J AU Schneider, TD Mastronarde, DN AF Schneider, TD Mastronarde, DN TI Fast multiple alignment of ungapped DNA sequences using information theory and a relaxation method SO DISCRETE APPLIED MATHEMATICS LA English DT Article ID BINDING-SITES; MOLECULAR MACHINES; PROTEIN; LOGOS AB An information theory based multiple alignment (''Malign'') method was used to align the DNA binding sequences of the OxyR and Fis proteins, whose sequence conservation is so spread out that it is difficult to identify the sites. In the algorithm described here, the information content of the sequences is used as a unique global criterion for the quality of the alignment. The algorithm uses look-up tables to avoid recalculating computationally expensive functions such as the logarithm. Because there are no arbitrary constants and because the results are reported in absolute units (bits), the best alignment can be chosen without ambiguity. Starting from randomly selected alignments, a hill-climbing algorithm can track through the immense space of s(n) combinations where s is the number of sequences and n is the number of positions possible for each sequence. Instead of producing a single alignment, the algorithm is fast enough that one can afford to use many start points and to classify the solutions. Good convergence is indicated by the presence of a single well-populated solution class having higher information content than other classes. The existence of several distinct classes for the Fis protein indicates that those binding sites have self-similar features. C1 UNIV COLORADO,DEPT MOL CELLULAR & DEV BIOL,BOULDER,CO 80309. RP Schneider, TD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,POB B,FREDERICK,MD 21702, USA. OI Schneider, Thomas/0000-0002-9841-1531 FU Intramural NIH HHS [Z01 BC008396-20]; NIGMS NIH HHS [R01 GM028755] NR 23 TC 27 Z9 28 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-218X J9 DISCRETE APPL MATH JI Discret Appl. Math. PD DEC 5 PY 1996 VL 71 IS 1-3 BP 259 EP 268 DI 10.1016/S0166-218X(96)00068-6 PG 10 WC Mathematics, Applied SC Mathematics GA VX698 UT WOS:A1996VX69800016 PM 19953199 ER PT J AU VonLubitz, DKJE Lin, RCS Paul, IA Beenhakker, M Boyd, M Bischofberger, N Jacobson, KA AF VonLubitz, DKJE Lin, RCS Paul, IA Beenhakker, M Boyd, M Bischofberger, N Jacobson, KA TI Postischemic administration of adenosine amine congener (ADAC): Analysis of recovery in gerbils SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ischemia, treatment; adenosine; memory; MAP2 (microtubule-associated protein 2); (gerbil) ID MICROTUBULE-ASSOCIATED PROTEIN-2; CEREBRAL-ISCHEMIA; FOREBRAIN ISCHEMIA; BRAIN; RAT; TEMPERATURE; DEGRADATION; RECEPTORS; AGONIST; INJURY AB Although adenosine receptor-based treatment of cerebral ischemia and other neurodegenerative disorders has been frequently advocated, cardiovascular side effects and an uncertain therapeutic time window of such treatment have constituted major obstacles to clinical implementation. Therefore, we have investigated the neuroprotective effects of the adenosine A, receptor agonist adenosine amine congener (ADAC) injected after either 5 or 10 min ischemia at 100 mu g/kg. When the drug was administered at either 6 or 12 h following 5 min forebrain ischemia, all animals were still alive on the 14th day after the occlusion. In both ADAC treated groups neuronal survival was approximately 85% vs. 50% in controls. Administration of a single dose of ADAC at times 15 min to 12 h after 10 min ischemia resulted in a significant improvement of survival in animals injected either at 15 or 30 min, or at 1, 2, or 3 h after the insult. In all 10 min ischemia groups, administration of ADAC resulted in a significant protection of neuronal morphology and preservation of microtubule associated protein 2 (MAP-2). However, postischemic Morris' water maze tests revealed full preservation of spatial memory and learning ability in animals injected at 6 h. On the other hand, the performance of gerbils treated at 12 h postischemia was indistinguishable from that of the controls. Administration of ADAC at 100 mu g/kg in non-ischemic animals did not result in bradycardia, hypotension, or hypothermia. The data indicate that when ADAC is used postischemically, the most optimal level of protection is obtained when drugs are given at 30 min to 6 h after the insult. Although the mechanisms involved in neuroprotective effects of adenosine A(1) receptor agonists require further studies, the present results demonstrate the feasibility of their clinical applications. C1 MED COLL PENN & HAHNEMANN UNIV, DEPT ANAT & NEUROBIOL, PHILADELPHIA, PA 19102 USA. UNIV MISSISSIPPI, DEPT PSYCHIAT & HUMAN BEHAV, JACKSON, MS 39216 USA. GILEAD SCI INC, FOSTER CITY, CA 94404 USA. RP VonLubitz, DKJE (reprint author), NIDDK, MOL RECOGNIT SECT, NIH, BLDG 8, ROOM 1A15, 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 44 TC 37 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 5 PY 1996 VL 316 IS 2-3 BP 171 EP 179 DI 10.1016/S0014-2999(96)00667-X PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VZ903 UT WOS:A1996VZ90300007 PM 8982684 ER PT J AU Bonifacino, JS AF Bonifacino, JS TI Reversal of fortune for nascent proteins SO NATURE LA English DT Editorial Material ID PROTEASOME; CFTR RP Bonifacino, JS (reprint author), NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892, USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 13 TC 39 Z9 39 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 5 PY 1996 VL 384 IS 6608 BP 405 EP 406 DI 10.1038/384405a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VW687 UT WOS:A1996VW68700029 PM 8945460 ER PT J AU Kost, RG Straus, SE AF Kost, RG Straus, SE TI Treatment of postherpetic neuralgia - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Kost, RG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 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 DEC 5 PY 1996 VL 335 IS 23 BP 1769 EP 1769 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VW795 UT WOS:A1996VW79500023 ER PT J AU Todd, MC Xiang, RH Garcia, DK Kerbacher, KE Moore, SL Hensel, CH Liu, P Siciliano, MJ Kok, K vandenBerg, A Veldhuis, P Buys, CHCM Killary, AM Naylor, SL AF Todd, MC Xiang, RH Garcia, DK Kerbacher, KE Moore, SL Hensel, CH Liu, P Siciliano, MJ Kok, K vandenBerg, A Veldhuis, P Buys, CHCM Killary, AM Naylor, SL TI An 80 Kb P1 clone from chromosome 3p21.3 suppresses tumor growth in vivo SO ONCOGENE LA English DT Article DE tumor suppressor gene; small cell lung cancer; human chromosome 3; positional cloning; homozygous deletion ID CELL LUNG-CANCER; POLYMERASE CHAIN-REACTION; SHORT ARM; HOMOZYGOUS DELETION; DNA-SEQUENCE; ALLELIC LOSS; OVARIAN-CANCER; CARCINOMA; LINE; GENE AB High frequencies of allelic loss on the short arm of chromosome 3 in small cell lung cancer (SCLC) and a number of other tumors suggest the existence of a tumor suppressor gene(s) within the deleted regions. Two small cell lung cancer lines, NCI H740 and GLC20, have been described which have homozygous deletions in the region 3p21.3. The deleted region overlaps with a 2 Mb fragment of human DNA present in the interspecies hybrid HA(3)BB9F, that suppresses tumor formation by mouse A9 fibrosarcoma cells. Human sequences from this cell hybrid were isolated using inter Alu PCR. From this starting point, a P1 contig was developed for the region of 450 Kb that is common to the homozygous deletions seen in the SCLC lines NCI H740 and GLC20 and is also present in HA(3)BB9F, the suppressed A9 hybrid. Individual P1 clones were assayed for their ability to suppress the tumorigenicity of the mouse fibrosarcoma cell line A9 as assayed by injection of transfected A9 cells into athymic nude mice. The introduction of one of the P1 clones into A9 cells resulted in suppression of tumor growth whereas two other P1 clones from the contig failed to suppress tumor formation in athymic nude mice. These data functionally delimit a tumor suppressor locus to a region of 80 kb within a P1 clone at 3p21.3. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. MD ANDERSON CANC INST,DEPT MOL GENET,HOUSTON,TX 77030. MD ANDERSON CANC INST,DEPT LAB MED,HOUSTON,TX 77030. UNIV GRONINGEN,DEPT MED GENET,GRONINGEN,NETHERLANDS. RI Liu, Paul/A-7976-2012; van den Berg, Anke/H-1718-2011; todd, martin/I-4143-2015 OI Liu, Paul/0000-0002-6779-025X; FU NCI NIH HHS [CA54174, CA56626]; PHS HHS [H600470] NR 56 TC 49 Z9 50 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 5 PY 1996 VL 13 IS 11 BP 2387 EP 2396 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VX108 UT WOS:A1996VX10800011 PM 8957080 ER PT J AU Wong, ML Khatri, P Licinio, J Esposito, A Gold, PW AF Wong, ML Khatri, P Licinio, J Esposito, A Gold, PW TI Identification of hypothalamic transcripts upregulated by antidepressants SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; MESSENGER-RNA; THERAPEUTIC IMPLICATIONS; TYROSINE-HYDROXYLASE; RAT-BRAIN; DEPRESSION; DISPLAY AB Identification of quantitative changes in gene expression that occur in the brain after antidepressant treatment can yield novel molecular markers that may be useful in the diagnosis and treatment of major depression. Using a modification of the differential display polymerase chain reaction, we describe the isolation of two transcripts that are differentially expressed in the brain after an 8-week course of antidepressant administration, compared to saline-treated control animals. (C) 1996 Academic Press, Inc. RP Wong, ML (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 9 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 4 PY 1996 VL 229 IS 1 BP 275 EP 279 DI 10.1006/bbrc.1996.1792 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VX982 UT WOS:A1996VX98200046 PM 8954118 ER PT J AU Quinn, TC Gaydos, C Shepherd, M Bobo, L Hook, EW Viscidi, R Rompalo, A AF Quinn, TC Gaydos, C Shepherd, M Bobo, L Hook, EW Viscidi, R Rompalo, A TI Epidemiologic and microbiologic correlates of Chlamydia trachomatis infection in sexual partnerships SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POLYMERASE CHAIN-REACTION; PELVIC INFLAMMATORY DISEASE; FIRST-VOID URINE; REACTION ASSAY; MONOCLONAL-ANTIBODIES; NEISSERIA-GONORRHOEAE; ENZYME-IMMUNOASSAY; ASYMPTOMATIC MEN; DIAGNOSIS; WOMEN AB Objectives.-To determine the frequency of Chlamydia trachomatis genital infection within sexual partnerships using highly sensitive polymerase chain reaction (PCR) amplification and to identify the variables that might modify transmission. Design.-Cross-sectional study of sexual partnerships comparing in vitro culture and PCR amplification for C trachomatis. Setting.-Two outpatient sexually transmitted disease clinics. Participants.-Four hundred ninety-four people in sexual partnerships attending sexually transmitted disease clinics. Main Outcome Measure.-Genital infection with C trachomatis. Methods.-DNA sequencing was performed to examine specific genotypes within and between partnerships. Cross-sectional analysis was performed to determine characteristics associated with concordance or discordance of infection with partnerships. Results.-Cultures were positive for C trachomatis in 8.5% of males and 12.9% of females (P=.03), Using PCR, more infections were identified both in males (14.2%) and in females (15.8%), and the difference in infection rates analyzed by sex was no longer significant. In 20.4% of 494 couples, at least 1 partner had PCR results positive for C trachomatis, with a concordant infection rate of 10.7%, significantly higher than the 5.5% concordant infection rate demonstrable by culture (P<.01). Male-female and female-male transmission frequencies were equal (68%). The nucleotide sequences of the major outer membrane protein gene products were identical and unique for each of 15 culture-negative, PCR-positive concordant partnerships. In concordant infections, factors associated with infection in female partners were age less than 20 years, more than 1 partner in the past 6 months, and cervical ectopy greater than 25%. Conclusions.-Using PCR, the frequency of chlamydia transmission by infected males and females was nearly identical. The high rate of concordant infection, high frequency of infection among asymptomatic individuals, and high frequency of transmission regardless of sex underscore the importance of routine screening for chlamydia in both males and females, along with provision of treatment to all sexual partners of chlamydia-infected individuals. C1 NIAID, NIH, BETHESDA, MD 20892 USA. BALTIMORE CITY DEPT HLTH, BALTIMORE, MD USA. RP Quinn, TC (reprint author), JOHNS HOPKINS UNIV, DIV INFECT DIS, DEPT MED, ROSS 1159, 720 RUTLAND AVE, BALTIMORE, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010 FU NIAID NIH HHS [5R01 AI27727-03, 5R01 AI29508-02] NR 41 TC 146 Z9 147 U1 0 U2 4 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 DEC 4 PY 1996 VL 276 IS 21 BP 1737 EP 1742 DI 10.1001/jama.276.21.1737 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VV566 UT WOS:A1996VV56600031 PM 8940322 ER PT J AU Weed, DL Kramer, BS AF Weed, DL Kramer, BS TI Induced abortion, bias, and breast cancer: Why epidemiology hasn't reached its limit SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RISK; WOMEN C1 GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057. RP Weed, DL (reprint author), NCI,PREVENT ONCOL BRANCH,DIV CANC PREVENT & CONTROL,NIH,EXECUT PLAZA S,RM T-41,BETHESDA,MD 20892, USA. NR 29 TC 17 Z9 17 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 DEC 4 PY 1996 VL 88 IS 23 BP 1698 EP 1700 DI 10.1093/jnci/88.23.1698 PG 3 WC Oncology SC Oncology GA VV998 UT WOS:A1996VV99800001 PM 8943995 ER PT J AU Lee, JH Miele, ME Hicks, DJ Phillips, KK Trent, JM Weissman, BE Welch, DR AF Lee, JH Miele, ME Hicks, DJ Phillips, KK Trent, JM Weissman, BE Welch, DR TI KiSS-1, a novel human malignant melanoma metastasis-suppressor gene SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SH3 DOMAINS; DIFFERENTIAL DISPLAY; SIGNAL-TRANSDUCTION; CANCER METASTASIS; SUBTRACTIVE HYBRIDIZATION; MESSENGER-RNAS; CELL-LINES; CHROMOSOME-6; TUMORIGENICITY; PROTEINS AB Background: Microcell-mediated transfer of chromosome 6 into human C8161 and MelJuSo melanoma cells suppresses their ability to metastasize by at least 95% without affecting their tumorigenicity. This observation demonstrates that the ability to metastasize is a phenotype distinct from tumor formation and suggests that tumorigenic cells acquire metastatic capability only after accumulating additional genetic defects. These results also imply that mutations of genes on chromosome 6 are among those late genetic changes responsible for metastatic potential. They further suggest that a melanoma metastasis-suppressor gene(s) is encoded on chromosome 6 or is regulated by genes on chromosome 6. Purpose: Our objective was to identify the gene(s) responsible for the suppression of metastasis in chromosome 6/melanoma cell hybrids. Methods: A modified subtractive hybridization technique was used to compare the expression of messenger RNAs (mRNAs), via an analysis of complementary DNAs (cDNAs), in metastatic cells (C8161 or MelJuSo) and nonmetastatic hybrid clones (neo6/C8161 or neo6/MelJuSo). Results: A novel cDNA, designated KiSS-1, was isolated from malignant melanoma cells that had been suppressed for metastatic potential by the introduction of human chromosome 6. Northern blot analyses comparing mRNAs from a panel of human melanoma cells revealed that KiSS-1 mRNA expression occurred only in nonmetastatic melanoma cells. Expression of this mRNA in normal heart, brain, liver, lung, and skeletal muscle was undetectable by northern blot analysis. Weak expression was found in the kidney and pancreas, but the highest expression was observed in the placenta. The KiSS-1 cDNA encodes a predominantly hydrophilic, 164 amino acid protein with a polyproline-rich domain indicative of an SH3 ligand (binds to the homology 3 domain of the oncoprotein Src) and a putative protein-kinase C-alpha phosphorylation site. Transfection of a full-length KiSS-1 cDNA into C8161 melanoma cells suppressed metastasis in an expression-dependent manner. Conclusions: These data strongly suggest that KiSS-1 expression may suppress the metastatic potential of malignant melanoma cells, implications: KiSS-1 may be a useful marker for distinguishing metastatic melanomas from nonmetastatic melanomas. C1 PENN STATE UNIV,COLL MED,DEPT EXPT PATHOL C7810,JAKE GITTLEN CANC RES INST,HERSHEY,PA 17033. UNIV N CAROLINA,DEPT PATHOL,LINEBERGER CANC CTR,CHAPEL HILL,NC. NIH,NATL CTR HUMAN GENOME RES,DIV INTRAMURAL RES,BETHESDA,MD 20892. RI Welch, Danny/B-7310-2009 OI Welch, Danny/0000-0002-1951-4947 FU NCI NIH HHS [CA44470, CA62168] NR 45 TC 503 Z9 585 U1 3 U2 18 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 DEC 4 PY 1996 VL 88 IS 23 BP 1731 EP 1737 DI 10.1093/jnci/88.23.1731 PG 7 WC Oncology SC Oncology GA VV998 UT WOS:A1996VV99800013 PM 8944003 ER PT J AU Shopland, DR Hartman, AM Gibson, JT Mueller, MD Kessler, LG Lynn, WR AF Shopland, DR Hartman, AM Gibson, JT Mueller, MD Kessler, LG Lynn, WR TI Cigarette smoking among US adults by state and region: Estimates from the current population survey SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID UNITED-STATES; PREVALENCE; CANCER AB Background: Cigarette smoking is responsible for at least one third of all cancer deaths annually in the United States. Few sources exist in the peer-reviewed literature documenting state and regional differences in smoking behavior, despite the fact that cancer prevention and control efforts are increasingly being implemented below the national level. Purpose: Our goals were to determine smoking prevalence rates among men and women, by region, and for each of the 50 states and the District of Columbia from census survey data collected in 1992 and 1993 and to compare these rates with rates determined in 1985. Methods: Every month, the U.S. Bureau of the Census collects labor force statistics on more than 100 000 individuals on its Current Population Survey (CPS). For the September 1992, January 1993, and May 1993 CPS, the National Cancer Institute sponsored a 40-item Tobacco Use Supplement. The definition of a current smoker changed slightly between 1985 and 1992-1993. For the 1985 CPS, individuals were considered current smokers if they had smoked 100 cigarettes in their lifetime and were smoking at the time of interview; for the 1992-1993 CPS, current smokers included anyone who had smoked 100 cigarettes and was currently smoking every day or just an some days. We calculated current smoking rates (every day and some days combined) based on more than a quarter million adults (n = 266 988) interviewed in 1992-1993. Results: Substantial geographic variation exists in rates of current cigarette use among adults within the United States. In general, adults in the southern United States have higher rates of smoking and adults in the western states have lower rates of smoking than adults in the rest of the country, although differences in smoking behavior between men and women and among various racial and ethnic populations strongly influence these patterns. Only two states, Kentucky and West Virginia, exhibited adult smoking rates (men and women combined) of 30% or higher in 1992-1993; in contrast, in 1985, such rates were reported from 20 states. The only states in which the prevalence was below 20% in 1992-1993 were Utah (17.1%) and California (19.5%). Rates approaching 20% were reported from New Jersey (20.7%), Massachusetts (21.5%), and Nebraska, New York, and Hawaii (22.0% each) in 1992-1993. Rhode Island experienced the greatest relative decline in smoking prevalence from 1985 to 1992-1993, with a calculated relative change of -30.7% (based on a change in rate from 33.5% to 23.2%), followed by Delaware (-25.9%), the of Columbia and New Jersey (-23.9% each), Connecticut (-23.2%), California (-22.9%), Alaska (-22.8%), Georgia (-22.6%), Massachusetts (-22.1%), and New York (-22.0%). Conclusions: Smoking rates are not uniform in the United States but vary considerably from state to state, even within the same region of the country. The CPS is the only mechanism currently capable of simultaneously monitoring smoking trends nationally, regionally, and on a state-by-state basis. C1 IMS INC,SILVER SPRING,MD. ROW SCI INC,ROCKVILLE,MD. RP Shopland, DR (reprint author), NCI,DIV CANC PREVENT & CONTROL,NIH,EXECUT PLAZA N,RM 241,BETHESDA,MD 20892, USA. NR 21 TC 71 Z9 72 U1 1 U2 3 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 DEC 4 PY 1996 VL 88 IS 23 BP 1748 EP 1758 DI 10.1093/jnci/88.23.1748 PG 11 WC Oncology SC Oncology GA VV998 UT WOS:A1996VV99800015 PM 8944005 ER PT J AU Calvert, RJ Buzard, GS Anisimov, VN Rice, JM AF Calvert, RJ Buzard, GS Anisimov, VN Rice, JM TI K-ras codon 12 and 61 point mutations in bromodeoxyuridine- and N-nitrosomethylurea-induced rat renal mesenchymal tumors SO CANCER LETTERS LA English DT Article DE K-ras; bromodeoxyuridine; N-nitrosomethylurea; renal mesenchymal tumors; polymerase chain reaction ID MAMMARY-GLANDS; ONCOGENES; ACTIVATION; CELLS; GENE; CARCINOGENESIS; MUTAGENESIS; METHYLUREA AB The mutagenic thymidine analog bromodeoxyuridine (BrdUrd) may incorrectly incorporate opposite deoxyguanine in DNA, then pair with deoxyadenosine during subsequent replication. It appears to preferentially target the 3'-G of 5'-NGGN-3' sequences in mammalian cells in culture to induce G --> A transitions. Ras genes should therefore be vulnerable to activation by mutation at glycine codons 12 (GGT) and/or 13 (GGC) by misincorporation of BrdUrd. There is limited evidence that BrdUrd may be carcinogenic or co-carcinogenic in rats: three renal mesenchymal tumors, a tumor known to be associated with activating mutations in the c-K-ras-2 oncogene, were reported in 87 rats treated with BrdUrd alone, while N-nitrosomethylurea (NMU) alone or MMU + BrdUrd resulted in incidences of 12/52 and 26/76, respectively, against a zero incidence in untreated rats. We analyzed renal mesenchymal tumors from rats treated with BrdUrd for mutations in K-ras exons 1 and 2 and compared the prevalence and spectrum of mutations with those found in comparable tumors induced with NMU. DNAs from 22 paraffin-embedded renal mesenchymal tumors from rats treated 12-15 months earlier with BrdUrd (three specimens) or NMU (11 specimens) or both agents sequentially (eight specimens) were amplified by PCR. The base sequence of codons 12-13 and 59-63 of K-ras was determined by the dideoxynucleotide method. Sequencing results were confirmed by allele-specific oligonucleotide hybridization. Two of three tumors that appeared in rats given BrdUrd alone contained both a codon 12 GGT --> GAT transition and a codon 61 CAA --> CTA transversion. One tumor induced by NMU alone also showed a codon 12 GGT --> GAT mutation, while only wild type sequence could be demonstrated in the codon 12-13 region in the remaining ten such tumors. Three NMU-induced tumors also showed codon 61 CAA --> CTA mutations, while the remaining tumors had wild type sequence. While the GGT --> GAT transitions identified in tumors from BrdUrd-treated rats are consistent with BrdUrd mutagenesis by misincorporation, the co-occurrence of CAA --> CTA transversions, the overall low prevalence of mutations, and the lack of any difference in mutation spectrum between tumors induced by NMU and those that occurred in BrdUrd-treated rats suggests that in both groups the mutations that did occur did not result from a direct effect of either agent. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NN PETROV ONCOL RES INST,ST PETERSBURG,RUSSIA. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Calvert, RJ (reprint author), US FDA,OFF SPECIAL NUTRIT,MOD-1,HFS-452,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 22 TC 4 Z9 4 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 3 PY 1996 VL 109 IS 1-2 BP 1 EP 7 DI 10.1016/S0304-3835(96)04350-9 PG 7 WC Oncology SC Oncology GA VZ698 UT WOS:A1996VZ69800001 PM 9020896 ER PT J AU Cysyk, RL Chisena, CA Hyman, R Monks, A AF Cysyk, RL Chisena, CA Hyman, R Monks, A TI Tiazofurin enhances the anabolism and toxicity of 5-fluorouracil SO CANCER LETTERS LA English DT Article DE tiazofurin; 5-fluorouracil; 5-phosphoribosyl-1-pyrophosphate (PRPP); pyrimidines ID 2-BETA-D-RIBOFURANOSYLTHIAZOLE-4-CARBOXAMIDE NSC 286193; CULTURED L1210 CELLS; N-(PHOSPHONACETYL)-L-ASPARTIC ACID; MECHANISM; MURINE; LEUKEMIA; CONVERSION; CARCINOMA; ACIVICIN AB Tiazofurin, a clinically active anticancer agent, is undergoing additional clinical testing in combination with other agents. We found that tiazofurin is an effective biochemical modulator of 5-fluorouracil anabolism. Pretreatment of cultured L1210 cells with tiazofurin at concentrations of 1-100 mu M results in an increase in the rate of conversion of 5-fluorouracil to phosphorylated metabolites. Concentrations of tiazofurin effective in increasing 5-fluorouracil anabolism cause a corresponding increase in the 5-phosphoribosyl-1-pyrophosphate pool. Studies in mice show that tiazofurin increases the lethal toxicity of 5-fluorouracil and increases the antitumor effectiveness of low doses of 5-fluorouracil; however, the combination is not more effective than an optimal dose of 5-fluorouracil given alone. These results indicate that caution should be exercised in the concurrent use of tiazofurin with other drugs, particularly 5-fluorouracil, that require 5-phosphoribosyl-1-pyrophosphate for activation or that are affected by a decrease in pyrimidine nucleotide synthesis. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD. RP Cysyk, RL (reprint author), NCI,DIV BASIC SCI,MED CHEM LAB,BLDG 37,ROOM 5E18,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 22 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 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 3 PY 1996 VL 109 IS 1-2 BP 49 EP 55 DI 10.1016/S0304-3835(96)04416-3 PG 7 WC Oncology SC Oncology GA VZ698 UT WOS:A1996VZ69800007 PM 9020902 ER PT J AU Yu, FL Cahill, JM Lipinski, LJ Dipple, A AF Yu, FL Cahill, JM Lipinski, LJ Dipple, A TI Effect of aflatoxin B-1-8,9-epoxide-DNA adducts on transcription of a supF gene fragment SO CANCER LETTERS LA English DT Article DE transcription; aflatoxin; carcinogen ID RNA-POLYMERASE; DNA; BINDING; RAT; ELONGATION; CYTOSINE; INVITRO; GUANINE; LESIONS; ADENINE AB A linearized template, obtained from the vector pGEM-3Zf(+) containing a supF gene fragment, was treated with aflatoxin B-1-8,9-epoxide (AFB(1) epoxide) and transcription in vitro was then studied. The template functions of both strands of the supF gene were similarly inhibited as shown by transcription with both T7 and SP6 RNA polymerases. This inhibition was dose-dependent and affected the elongation step more extensively than the initiation step. Gel electrophoretic analysis of RNA formed by T7 RNA polymerase indicated that template treated with different AFB1 epoxide doses yielded the same three major truncated RNA fragments. Sequence analysis showed that these major sites of RNA truncation occurred in the vicinity of adjacent guanine residues in the template. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV ILLINOIS,COLL MED,DEPT BIOMED SCI,ROCKFORD,IL 61107. FU NCI NIH HHS [NC-CO-46000] NR 28 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 3 PY 1996 VL 109 IS 1-2 BP 77 EP 83 DI 10.1016/S0304-3835(96)04423-0 PG 7 WC Oncology SC Oncology GA VZ698 UT WOS:A1996VZ69800010 PM 9020905 ER PT J AU Lazutka, JR Neel, JV Major, EO Dedonyte, V Mierauskine, J Slapsyte, G Kesminiene, A AF Lazutka, JR Neel, JV Major, EO Dedonyte, V Mierauskine, J Slapsyte, G Kesminiene, A TI High titers of antibodies to two human polyomaviruses, JCV and BKV, correlate with increased frequency of chromosomal damage in human lymphocytes SO CANCER LETTERS LA English DT Article DE chromosome aberrations; rogue cells; JC virus; BK virus; p53 ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CHERNOBYL ACCIDENT; HUMAN BRAIN; VIRUS; ABERRATIONS; CELLS; PATHOGENESIS; PERSISTENCE; ONCOGENESIS; FIBROBLASTS AB Associations of antibody titers to the JC and BK human polyoma viruses and the frequency of chromosome aberrations (CA) in human peripheral blood lymphocytes were studied. Study group consisted of 33 workers occupationally exposed to low doses of ionizing radiation and 11 control persons. There were no statistically significant differences in the JC and BK virus titer values between two groups of donors. It was found that JC and BK virus titers explained approximately 6% of total inter-individual variation in CA frequency. Such factors as alcohol abuse, age and, in this special group, exposure to ionizing radiation explained an additional 53% of the total variation in CA frequency. In six clean-up workers and one control, rogue cells (cells with multiple chromosome-type aberrations) were found. The incidence of rogue cells correlated significantly with JC and BK virus titers as well as a history of recent acute respiratory disease. C1 UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. NINCDS,MOL MED & VIROL SECT,LAB MOL MED & NEUROSCI,NIH,BETHESDA,MD 20892. LITHUANIAN CHERNOBYL MED CTR,LT-2001 VILNIUS,LITHUANIA. RP Lazutka, JR (reprint author), VILNIUS STATE UNIV,DEPT BOT & GENET,21 CIURLIONIS ST,LT-2009 VILNIUS,LITHUANIA. NR 28 TC 30 Z9 32 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 3 PY 1996 VL 109 IS 1-2 BP 177 EP 183 DI 10.1016/S0304-3835(96)04448-5 PG 7 WC Oncology SC Oncology GA VZ698 UT WOS:A1996VZ69800023 PM 9020918 ER PT J AU Kubota, T Sutcliffe, JS Aradhya, S GillessenKaesbach, G Christian, SL Horsthemke, B Beaudet, AL Ledbetter, DH AF Kubota, T Sutcliffe, JS Aradhya, S GillessenKaesbach, G Christian, SL Horsthemke, B Beaudet, AL Ledbetter, DH TI Validation studies of SNRPN methylation as a diagnostic test for Prader-Willi syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Prader-Willi syndrome; DNA methylation; SNRPN; genomic imprinting ID DNA METHYLATION; ANGELMAN SYNDROMES; MOLECULAR DIAGNOSIS; REGION; 15Q11-Q13; IMPRINT; DEFINE; PARENT AB Prader-Willi syndrome (PWS) is caused by absence of a paternal contribution of the chromosome region 15q11-q13, resulting from paternal deletions, maternal uniparental disomy, or rare imprinting mutations. Laboratory diagnosis is currently performed using fluorescence in situ hybridization (FISH), DNA polymorphism (microsatellite) analysis, or DNA methylation analysis at locus PW71 (D15S63). We examined another parent-of-origin-specific DNA methylation assay at exon ex of the small nuclear ribonucleoprotein-associated polypeptide N gene (SNRPN) in patients referred with clinical suspicion of PWS or Angelman syndrome (AS). These included 30 PWS and 17 AS patients with known deletion or uniparental disomy status, and a larger cohort of patients (n = 512) suspected of PWS who had been analyzed previously for their methylation status at the PW71 locus. Results of SNRPN methylation were consistent with known deletion or uniparental disomy (UPD) status as determined by other molecular methods in all 47 cases of PWS and AS. In the larger cohort of possible PWS patients, SNRPN results were consistent with clinical diagnosis by examination and with PW71 methylation results in all cases. These data provide support for the use of SNRPN methylation as a diagnostic method. Because methylation analysis can detect all three major classes of genetic defects associated with PWS (deletion, UPD, or imprinting mutations), methylation analysis with either PW71 or SNRPN is an efficient primary screening test to rule out a diagnosis of PWS. Only patients with an abnormal methylation result require further diagnostic investigation by FISH or DNA polymorphism analysis to distinguish among the three classes for accurate genetic counseling and recurrence-risk assessment. (C) 1996 Wiley-Liss, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. UNIV ESSEN GESAMTHSCH KLINIKUM,INST HUMAN GENET,D-4300 ESSEN,GERMANY. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,HOWARD HUGHES MED INST,HOUSTON,TX 77030. RI Sutcliffe, James/C-1348-2012 OI Sutcliffe, James/0000-0001-5200-6007 NR 19 TC 61 Z9 63 U1 2 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 2 PY 1996 VL 66 IS 1 BP 77 EP 80 DI 10.1002/(SICI)1096-8628(19961202)66:1<77::AID-AJMG18>3.0.CO;2-N PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VV306 UT WOS:A1996VV30600018 PM 8957518 ER PT J AU Kustova, Y Sei, Y Goping, G Basile, AS AF Kustova, Y Sei, Y Goping, G Basile, AS TI Gliosis in the LP-BM5 murine leukemia virus-infected mouse: An animal model of retrovirus-induced dementia SO BRAIN RESEARCH LA English DT Article DE astrocyte; microglia; mouse; LP-BM5 virus; dementia; AIDS ID CENTRAL-NERVOUS-SYSTEM; HUMAN-IMMUNODEFICIENCY-VIRUS; QUINOLINIC ACID; BRAIN; MICROGLIA; MACROPHAGES; ASTROCYTES; DISEASE; AIDS; CYTOKINES AB Mice infected with the LP-BM5 murine leukemia virus (MuLV) mixture develop severe immunosuppression, neurotransmitter abnormalities and cognitive impairments in the absence of significant viral or macrophage invasion of the CNS. The time-course of the changes in glial activation have been characterized in an effort to understand the cellular basis of the neurobehavioral abnormalities observed in these mice. Glial activation was determined by measuring the relative changes in F4/80 protein and GFAP immunoreactivity using immunoblots. Augmented F4/80 expression preceded that of GFAP, with global elevations of 4-6-fold at 3 weeks, sustained for up to 12 weeks after inoculation. GFAP immunoreactivity increased 2-fold only in the cerebral cortex and striatum 5 weeks postinfection, declining to control levels by 12 weeks. Immunohistochemistry revealed significant increases in microglial size and staining intensity in the cortex, corpus callosum and striatum, with the development of a unique population of highly ramified, intensely stained microglia and microglial nodules in the corpus callosum and striatum. No evidence of ameboid microglia was found. Astrocyte size and degree of ramification was increased in the hippocampus, cortex, striatum and corpus callosum. Thus, microgliosis is an early event in LP-BM5 infection, preceding astrocytosis, neurotransmitter loss, and development of cognitive deficits. Activated microglia may secrete neurotoxins leading to the neurochemical alterations and cognitive deficits observed in these mice. Because gliosis and microglial nodule formation are hallmarks of HIV-1 encephalopathy, LP-BM5 MuLV-infected C57/B16 mice may afford insights into the mechanisms contributing to the early stages of this syndrome. C1 NIDDK,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NIDDK,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892. NR 45 TC 16 Z9 16 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 DEC 2 PY 1996 VL 742 IS 1-2 BP 271 EP 282 DI 10.1016/S0006-8993(96)01014-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA WC372 UT WOS:A1996WC37200032 PM 9117405 ER PT J AU Bujacz, G Alexandratos, J ZhouLiu, Q ClementMella, C Wlodawer, A AF Bujacz, G Alexandratos, J ZhouLiu, Q ClementMella, C Wlodawer, A TI The catalytic domain of human immunodeficiency virus integrase: Ordered active site in the F185H mutant SO FEBS LETTERS LA English DT Article DE integrase; active site; disorder; metal binding ID DNA-BINDING; RETROVIRAL INTEGRATION; HIV-1 INTEGRASE; PROTEIN; IDENTIFICATION AB We solved the structure and traced the complete active site of the catalytic domain of the human immunodeficiency virus type 1 integrase (HIV-1 IN) with the F185H mutation, The only previously available crystal structure, the F185K mutant of this domain, lacks one of the catalytically important residues, E152, located in a stretch of 12 disordered residues [Dyda et al, (1994) Science 266, 1981-1986], It is clear, however, that the active site of HIV-1 IN observed in either structure cannot correspond to that of the functional enzyme, since the cluster of three conserved carboxylic acids does not create a proper metal-binding site. The conformation of the loop was compared with two different conformations found in the catalytic domain of the related avian sarcoma virus integrase [Bujacz et al. (1995) J. Mol. Biol. 253, 333-346]. Flexibility of the active site region of integrases may be required in order for the enzyme to assume a functional conformation in the presence of substrate and/or cofactors. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOL STRUCT LAB,FREDERICK,MD 21702. TECH UNIV LODZ,FAC FOOD CHEM & BIOTECHNOL,PL-90924 LODZ,POLAND. RHONE POULENC RORER SA,SERV BIOCHIM,F-94403 VITRY SUR SEINE,FRANCE. NR 16 TC 99 Z9 101 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 2 PY 1996 VL 398 IS 2-3 BP 175 EP 178 DI 10.1016/S0014-5793(96)01236-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VX781 UT WOS:A1996VX78100010 PM 8977101 ER PT J AU Watts, JD Brabb, T Bures, EJ Wange, RL Samelson, LE Aebersold, R AF Watts, JD Brabb, T Bures, EJ Wange, RL Samelson, LE Aebersold, R TI Identification and characterization of a substrate specific for the T cell protein tyrosine kinase ZAP-70 SO FEBS LETTERS LA English DT Article DE tyrosine kinase; T cell; band 3 protein; ZAP-70; Lck; Itk ID SEVERE COMBINED IMMUNODEFICIENCY; HUMAN ERYTHROCYTE BAND-3; IONIZATION MASS-SPECTROMETRY; TANDEM SH2 DOMAINS; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; ZETA-CHAIN; PHOSPHORYLATION; LYMPHOCYTE; ACTIVATION AB ZAP-70 is a protein tyrosine kinase (PTK) that plays a critical role in T cell activation, To study the role of ZAP-70 catalytic activity in this process, a substrate capable of distinguishing between the activities of ZAP-70 and other PTKs would be useful, especially since it has recently been shown that ZAP-70 interacts with another T cell PTK, Lck, We have thus identified a site of phosphorylation on the cytoplasmic fragment of the erythrocyte band 3 protein that is recognized by ZAP-70, but not Lck, A synthetic peptide based on this site has been demonstrated to be a good in vitro substrate for ZAP-70 and a poor substrate for the T cell PTKs Lck and Itk. This peptide molecule should thus prove useful to many investigators working in the field of T cell activation. C1 NICHHD,NIH,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP Watts, JD (reprint author), UNIV WASHINGTON,DEPT MOL BIOTECHNOL,BOX 357730,SEATTLE,WA 98195, USA. FU NCRR NIH HHS [RR07019] NR 38 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 2 PY 1996 VL 398 IS 2-3 BP 217 EP 222 DI 10.1016/S0014-5793(96)01241-0 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VX781 UT WOS:A1996VX78100019 PM 8977110 ER PT J AU Kessel, M Wu, WF Gottesman, S Kocsis, E Steven, AC Maurizi, MR AF Kessel, M Wu, WF Gottesman, S Kocsis, E Steven, AC Maurizi, MR TI Six-fold rotational symmetry of ClpQ, the E-coli homolog of the 20S proteasome, and its ATP-dependent activator, ClpY SO FEBS LETTERS LA English DT Article DE Clp protease; HslU/HsiV; ATP-dependent protease; proteasome; rotational symmetry; image analysis ID ESCHERICHIA-COLI; ELECTRON-MICROSCOPY; THERMOPLASMA-ACIDOPHILUM; CRYSTAL-STRUCTURE; PROTEIN; SEQUENCE; ORGANIZATION; RESOLUTION; BACTERIAL; SUBSTRATE AB ClpQ (HslV) is a homolog of the beta-subunits of the 20S proteasome. In E. coli, it is expressed from an operon that also encodes ClpY (HsIU), an ATPase homologous to the protease chaperone, ClpX. ClpQ (subunit M(r) 19 000) and ClpY (subunit M(r) 49 000) were purified separately as oligomeric proteins with molecular weights of similar to 220 000 and similar to 350 000, respectively, estimated by gel filtration. Mixtures of ClpY and ClpQ displayed ATP-dependent proteolytic activity against casein, and a complex of the two proteins was isolated by gel filtration in the presence of ATP. Image processing of negatively stained electron micrographs revealed strong six-fold rotational symmetry for both ClpY and ClpQ, suggesting that the subunits of both proteins are arranged in hexagonal rings. The molecular weight of ClpQ combined with its symmetry is consistent with a double hexameric ring, whereas the data on ClpY suggest only one such ring. The symmetry mismatch previously observed between hexameric ClpA and heptameric ClpP in the related ClpAP protease is apparently not reproduced in the symmetry-matched ClpYQ system. C1 NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. NCI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NCI,NIH,MOL BIOL LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MEMBRANE & ULTRASTRUCT RES,IL-91010 JERUSALEM,ISRAEL. OI WU, WHI-FIN/0000-0002-9526-6287 NR 32 TC 89 Z9 91 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 2 PY 1996 VL 398 IS 2-3 BP 274 EP 278 DI 10.1016/S0014-5793(96)01261-6 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VX781 UT WOS:A1996VX78100031 PM 8977122 ER PT J AU Gronenborn, AM Frank, MK Clore, GM AF Gronenborn, AM Frank, MK Clore, GM TI Core mutants of the immunoglobulin binding domain of streptococcal protein G: Stability and structural integrity SO FEBS LETTERS LA English DT Article DE protein G; B1 domain; core mutant; library; protein design; structure; stability ID AMINO-ACIDS; HYDROPHOBIC CORE; NMR-SPECTROSCOPY; FOLDED PROTEINS; PACKING; DESIGN; LIBRARIES; HAIRPIN AB A library of core mutants of the GB1 domain of streptococcal protein G was created, and the structure and stability of selected members was assessed by H-1-N-15 heteronuclear correlation NMR spectroscopy and fluorescence. All mutants comprised changes in beta-sheet residues, with sidechains at positions 5 (Leu), 7 (Leu), 52 (Phe) and 54 (Val) forming the beta-sheet side of the sheet-helix core interface. A solvent exposed position Ile-6 was chosen as a control. Randomization of bases at codon positions 1 and 3 with thymine at position 2 introduces five possible hydrophobic amino acids, namely Leu, Val, Ile, Phe, and Met. The distribution of encoded amino acids at all five positions is approximately as expected theoretically and indicates that no major bias was introduced towards particular residues. The overall structural integrity of several mutants, as assessed by NMR, ranges from very close to wild type to fully unfolded. Interestingly, the stability of the mutants is not strictly correlated with the number of changes or residue volume. C1 UNIV MARYLAND,INST PHYS SCI & TECHNOL,CHEM PHYS GRAD PROGRAM,COLLEGE PK,MD 20742. RP Gronenborn, AM (reprint author), NIDDK,NIH,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 32 TC 21 Z9 21 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 2 PY 1996 VL 398 IS 2-3 BP 312 EP 316 DI 10.1016/S0014-5793(96)01262-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VX781 UT WOS:A1996VX78100038 PM 8977129 ER PT J AU VanBockstaele, EJ Colago, EEO Moriwaki, A Uhl, GR AF VanBockstaele, EJ Colago, EEO Moriwaki, A Uhl, GR TI Mu-opioid receptor is located on the plasma membrane of dendrites that receive asymmetric synapses from axon terminals containing leucine-enkephalin in the rat nucleus locus coeruleus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE norepinephrine; drug abuse; enkephalin; opiates; morphine ID OPIATE WITHDRAWAL; ADENYLATE-CYCLASE; IMMUNOREACTIVE TERMINALS; CATECHOLAMINE AFFERENTS; CHRONIC MORPHINE; BRAIN; NEURONS; CERULEUS; ULTRASTRUCTURE; LOCALIZATION AB We have recently shown, by using immunoelectron microscopy, that the mu-opioid receptor (mu OR) is prominently distributed within noradrenergic perikarya and dendrites of the nucleus locus coeruleus (LC), many of which receive excitatory-type (i.e., asymmetric) synaptic contacts from unlabeled axon terminals. To characterize further the neurotransmitter present in these afferent terminals, we examined in the present study the ultrastructural localization of an antipeptide sequence unique to the mu OR in sections that were also dually labeled for the opioid peptide leucine-enkephalin (L-ENK). Immunogold-silver labeling for mu OR was localized to extrasynaptic portions of the plasma membranes of perikarya and dendrites. The mu OR-labeled dendrites were usually postsynaptic to axon terminals containing heterogeneous types of synaptic vesicles and forming asymmetric synaptic specializations characteristic of excitatory-type synapses. The majority of these were immunolabeled for the endogenous opioid peptide L-ENK. Some mu OR-labeled dendrites received synaptic contacts from unlabeled axon terminals in fields containing L-ENK immunoreactivity. In such cases, the mu OR-labeled dendrites were in proximity to L-ENK axon terminals that contained intense peroxidase labeling within large dense core vesicles along the perimeter of the axoplasm. These results indicate that L-ENK may be released by exocytosis from the dense core vesicles and diffuse within the extracellular space to reach mu OR sites on the postsynaptic dendrite or dendrites of other neighboring neurons. The present study also reveals that unlabeled terminals apposed to mu OR-labeled dendrites may contain other opioid peptides, such as methionine-enkephalin. These data demonstrate several sites where endogenous opioid peptides may interact with mu OR receptive sites in the LC and may provide an anatomical substrate for the LC's involvement in mechanisms of opiate dependence and withdrawal. (C) 1996 Wiley-Liss, Inc. C1 CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,NEW YORK,NY 10021. NIDA,ADDICT RES CTR,DIV INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. FU NIDA NIH HHS [R29 DA09082]; PHS HHS [18974] NR 48 TC 29 Z9 30 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 DEC 2 PY 1996 VL 376 IS 1 BP 65 EP 74 DI 10.1002/(SICI)1096-9861(19961202)376:1<65::AID-CNE4>3.0.CO;2-M PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VU885 UT WOS:A1996VU88500004 PM 8946284 ER PT J AU Hof, PR Ungerleider, LG Webster, MJ Gattass, R Adams, MM Sailstad, CA Morrison, JH AF Hof, PR Ungerleider, LG Webster, MJ Gattass, R Adams, MM Sailstad, CA Morrison, JH TI Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE corticocortical projections; cytoskeleton; feedforward and feedback projections; occipitoparietal and occipitotemporal pathways; primate visual system ID SUPERIOR TEMPORAL SULCUS; ALZHEIMERS-DISEASE; PYRAMIDAL NEURONS; RHESUS-MONKEY; CORTICAL CONNECTIONS; QUANTITATIVE-ANALYSIS; MONOCLONAL-ANTIBODY; EXTRASTRIATE CORTEX; AREA V2; TOPOGRAPHIC ORGANIZATION AB Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). Tn contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and V1 in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons. (C) 1996 Wiley-Liss, Inc. C1 CUNY MT SINAI SCH MED,LABS NEUROBIOL AGING,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT OPHTHALMOL,NEW YORK,NY 10029. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NIMH,CTR NEUROSCI,STANLEY FDN RES PROGRAM,WASHINGTON,DC 20032. FED UNIV RIO DE JANEIRO,INST BIOFIS CARLOS CHAGAS FILHO,DEPT NEUROBIOL,BR-21941900 RIO JANEIRO,BRAZIL. RP Hof, PR (reprint author), CUNY MT SINAI SCH MED,FISHBERG RES CTR NEUROBIOL,BOX 1065,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. RI Morrison, John/F-9229-2012 FU NIA NIH HHS [AG06647]; NIMH NIH HHS [MH DA52154] NR 94 TC 83 Z9 83 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 DEC 2 PY 1996 VL 376 IS 1 BP 112 EP 127 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VU885 UT WOS:A1996VU88500007 PM 8946287 ER PT J AU Taffe, BG Larminat, F Laval, J Croteau, DL Anson, RM Bohr, VA AF Taffe, BG Larminat, F Laval, J Croteau, DL Anson, RM Bohr, VA TI Gene-specific nuclear and mitochondrial repair of formamidopyrimidine DNA glycosylase-sensitive sites in Chinese hamster ovary cells SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE oxidative DNA damage; DNA repair; mitochondrial DNA; gene-specific repair; 8-oxodeoxyguanosine; 8-hydroxydeoxyguanosine; DNA adduct; Chinese hamster ovary (CHO) ID DIHYDROFOLATE-REDUCTASE GENE; OXIDATIVE DAMAGE; ESCHERICHIA-COLI; PYRIMIDINE DIMERS; ACRIDINE-ORANGE; FREE SYSTEMS; DHFR GENE; 8-HYDROXYGUANINE; AGENTS; CANCER AB This study examines the capacity of a mammalian cell to repair, at the gene level, DNA base lesions generated by photoactivation of acridine orange. Chinese hamster ovary fibroblasts were exposed to acridine orange and visible light, and gene-specific DNA repair was measured in the dihydrofolate reductase (DHFR) gene and in the mitochondrial genome. DNA lesions were recognized by Escherichia coli formamidopyrimidine-DNA glycosylase (FPG) which removes predominantly 8-oxodG and the corresponding formamidopyrimidine ring opened bases, and subsequently cleaves the DNA at the resulting apurinic site, FPG-recognized DNA lesions increased linearly with increasing photo-activation of AO, while cell survival was not affected by light alone and was negligibly affected by preincubation with AO in the dark. The frequency of induction of FPG-sensitive DNA damage by photoactivation of AO was similar in the transcribed and non-transcribed nuclear DNA as well as in the mitochondrial DNA. FPG-sensitive sites in the DHFR gene were repaired quickly, with 84% of adducts repaired within 4 h. The lesion frequency, kinetics and percent of repair of non-transcribed genomic DNA did not differ significantly from repair in the active DHFR gene up to 1 h postexposure. At late time points, transcribed DNA was repaired faster than the non-transcribed DNA. Mitochondrial DNA was efficiently repaired, at a rate similar to that in the active nuclear DNA. C1 CNRS,LAB PHARMACOL & TOXICOL FONDAMENTALES,TOULOUSE,FRANCE. INST GUSTAVE ROUSSY,VILLEJUIF,FRANCE. NIA,GENET MOL LAB,NIH,BALTIMORE,MD. WAYNE STATE UNIV,DETROIT,MI 48202. NR 50 TC 61 Z9 62 U1 0 U2 1 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 DEC 2 PY 1996 VL 364 IS 3 BP 183 EP 192 DI 10.1016/S0921-8777(96)00031-6 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VW254 UT WOS:A1996VW25400005 PM 8960130 ER PT J AU Wakayama, I Nerurkar, VR Strong, MJ Garruto, RM AF Wakayama, I Nerurkar, VR Strong, MJ Garruto, RM TI Comparative study of chronic aluminum-induced neurofilamentous aggregates with intracytoplasmic inclusions of amyotrophic lateral sclerosis SO ACTA NEUROPATHOLOGICA LA English DT Article DE immunocytochemistry; Bunina body; spheroid; neurofilament; animal model ID MOTOR-NEURON DISEASE; ANTERIOR HORN CELLS; SPINAL MUSCULAR-ATROPHY; BODY-LIKE INCLUSIONS; NEUROFIBRILLARY CHANGES; HYALINE INCLUSIONS; PARKINSONISM-DEMENTIA; ANIMAL-MODEL; PATHOGENESIS; UBIQUITIN AB Amyotrophic lateral sclerosis (ALS) is characterized neuropathologically by chromatolysis, Bunina bodies, hyaline inclusions, skein-like inclusions and axonal spheroids, Aluminum, a known neurotoxin, is the cause of dialysis encephalopathy and is considered to be a causative agent in high incidence foci of ALS in the western Pacific. We have developed an experimental model of motor neuron degeneration in New Zealand white rabbits using chronic low-dose intracisternal administration of aluminum and compared the clinical and neuropathological changes to those of human ALS. Aluminum-inoculated rabbits developed progressive hyperreflexia, hypertonia, limb splaying, gait impairment, muscle wasting, hindlimb paralysis and impaired tonic immobility responses without overt encephalopathic features over a 14-month period. Examination of spinal cords from these animals demonstrated the frequent occurrence and progressive development of anterior horn cell lesions that included small, round, argentophilic perikaryal inclusions similar to hyaline inclusions seen in human ALS. Other inclusions were more condensed and eosinophilic, while still others had neurofibrillary tangle-like morphologies. Axonal spheroids and neuritic thickenings were also prominent and were identical to those seen in human ALS, We believe that the similar and progressive development of neuropathological changes observed in the chronic aluminum-intoxication model, compared to hu man ALS, warrants further study to aid in understanding the cellular and molecular mechanisms of human motor neuron disease. C1 NINCDS,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. KANSAI COLL ORIENTAL MED,RES CTR NEUROL DIS,KUMATORI,OSAKA,JAPAN. NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892. JOHN P ROBARTS RES INST,NEURODEGENERAT DIS RES GRP,LONDON,ON N6A 5A5,CANADA. RI Strong, Michael/H-9689-2012 NR 68 TC 31 Z9 32 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD DEC PY 1996 VL 92 IS 6 BP 545 EP 554 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VW431 UT WOS:A1996VW43100002 PM 8960311 ER PT J AU Dawson, D AF Dawson, D TI Gender differences in the risk of alcohol dependence: United States, 1992 SO ADDICTION LA English DT Article ID PROBLEM DRINKING; INTOXICATION; ADOLESCENCE; CONSUMPTION; PREVALENCE; STABILITY; WOMEN; MEN AB Data from a representative sample of US adults revealed that 24% of male life-time drinkers and 15% of female life-time drinkers met the DSM-IV criteria for life-time alcohol dependence, i.e. dependence during the year preceding interview or in any 12-month period prior to that year. The median interval from first drink to onset of dependence was 3.6 years for men and 3.0 years for women. After using survival techniques to adjust for potential gender differences in the exposure to risk of developing alcohol dependence, the cumulative conditional probability of having experienced onset of dependence was 35.1% for men and 24.6% for women. The conditional probability of onset of dependence was equal for men and women in the first year after initiation of drinking, about 30% higher for men in the period 1-4 years after the first drink, and about 45% higher for men thereafter. After using proportional hazard; models to adjust for the effects of age cohort, race and ethnicity, family history of alcoholism and age at first drink, these period-specific risk ratios remained virtually unchanged. Including a measure of average daily ethanol intake during periods of heaviest consumption rendered most of the gender differences statistically insignificant, revealing a slight excess risk of female dependence within the first year after initiation of drinking among the heaviest drinkers and leaving an excess male risk of dependence mostly among individuals with average daily intakes of less than one ounce of ethanol. The results suggest that different frequencies of binge drinking might help to account for these remaining gender differences and that men's and women's relative risk of developing alcohol dependence may vary as a function of life cycle stage, with men's excess risk greatest in the college/young adult years. C1 NIAAA,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD 20852. NR 36 TC 33 Z9 33 U1 0 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1996 VL 91 IS 12 BP 1831 EP 1842 DI 10.1111/j.1360-0443.1996.tb03812.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WB702 UT WOS:A1996WB70200014 PM 8997764 ER PT J AU Allen, J Loman, C Miller, WR AF Allen, J Loman, C Miller, WR TI Perspectives on precipitants of relapse SO ADDICTION LA English DT Editorial Material C1 UNIV NEW MEXICO,DEPT PSYCHOL,ALBUQUERQUE,NM 87131. RP Allen, J (reprint author), NIAAA,NIH,SUITE 500,6000 EXECUT BLVD,WILLCO BLDG,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1996 VL 91 SU S BP S3 EP S4 DI 10.1111/j.1360-0443.1996.tb02322.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WC567 UT WOS:A1996WC56700001 ER PT J AU Longabaugh, R Rubin, A Stout, RL Zywiak, WH Lowman, C AF Longabaugh, R Rubin, A Stout, RL Zywiak, WH Lowman, C TI The reliability of Marlatt's taxonomy for classifying relapses SO ADDICTION LA English DT Article ID MALE ALCOHOLICS; CUE REACTIVITY; SITUATIONS; DRINKING; EXPOSURE AB Marlatt's focus on the relapse situation has had a major impact upon research and clinical practice in treating addictions. One component of his work was the development of a taxonomy for classifying precipitants of relapse. This taxonomy has been incorporated into the nomenclature of clinicians and clinical researchers as part of an explanatory framework for understanding relapses. Despite the taxonomy's influence it has never been examined for the reliability of its use across research studies. The present study compared the reliability of independent classifications of 149 relapse episodes by trained raters at three research laboratories. Despite considerable across-laboratory training, reliability was found to be inconsistent for research purposes. It is concluded that comparability of results based on Marlatt's relapse taxonomy across independent studies must be subject to question, and assumptions necessary for the aggregation of a Knowledge base are not supported. Recommendations are offered for improving the reliability of the taxonomy and the methods used to collect taxonomy data. More generally, questions regarding the value of the specific relapse categories, as well as the overall taxonomy, are raised. C1 RES INST ADDICT,BUFFALO,NY 14203. NIAAA,ROCKVILLE,MD 20852. RP Longabaugh, R (reprint author), BROWN UNIV,CTR ALCOHOL & ADDICT STUDIES,SCH MED,BOX G,PROVIDENCE,RI 02912, USA. FU ADAMHA HHS [ADM 281-91-0011] NR 28 TC 20 Z9 20 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1996 VL 91 SU S BP S73 EP S88 DI 10.1111/j.1360-0443.1996.tb02328.x PG 16 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WC567 UT WOS:A1996WC56700007 PM 8997782 ER PT J AU Lowman, C Allen, J Stout, RL Connors, GJ Longabaugh, R Maisto, SA Miller, WR Rubin, A Waldron, D Westerberg, VS Zywiak, WH AF Lowman, C Allen, J Stout, RL Connors, GJ Longabaugh, R Maisto, SA Miller, WR Rubin, A Waldron, D Westerberg, VS Zywiak, WH TI Replication and extension of Marlatt's taxonomy of relapse precipitants: Overview of procedures and results SO ADDICTION LA English DT Article ID COPING BEHAVIORS; ALCOHOLICS AB The Relapse Replication and Extension Project (RREP) was a multisite study to replicate and extend Marlatt's taxonomy of relapse precipitants. In addition to replicating Marlatt's original taxonomic system, three independent research teams utilized prospective designs to identify additional predictors of relapse and developed and evaluated two alternative systems for assessing high risk relapse situations. This overview describes the replication methodology, summarizes seven RREP studies completed by the three research groups, and discusses five cross-cutting conclusions emerging from the studies. These conclusions are: (1) reliability of Marlatt's taxonomic system was variable both within and across the three research sites; (2) Marlatt's taxonomic system showed little predictive validity in analyses that used pretreatment relapse data to predict post-treatment relapse, but there are important unresolved issues; (3) an alternative taxonomy provided little more predictive validity than the original taxonomy even though it measured more dimensions of relapse situations and provided greater analytic flexibility; (4) the Reasons for Drinking Questionnaire appeared to be a successful psychometric transformation of Marlatt's taxonomy, one which did demonstrate predictive validity; and (5) Marlatt's taxonomy was based on a time-intensive model of relapse prediction whereas RREP prospective analyses represented time-extensive models of relapse prediction. Coping responses are noted to be effective predictors of relapse under both models. C1 BROWN UNIV,CTR ALCOHOL & ADDICT STUDIES,PROVIDENCE,RI 02912. RP Lowman, C (reprint author), NIAAA,NIH,WILCO BLDG,SUITE 505,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. FU ADAMHA HHS [ADM 281-91 0006, ADM 281-91 0007, ADM 281-91-0011] NR 51 TC 56 Z9 57 U1 0 U2 9 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1996 VL 91 SU S BP S51 EP S71 DI 10.1111/j.1360-0443.1996.tb02327.x PG 21 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WC567 UT WOS:A1996WC56700006 PM 8997781 ER PT J AU Lauermann, V Peden, K Boeke, JD AF Lauermann, V Peden, K Boeke, JD TI Alternative tRNA primers for HIV SO AIDS LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSFER-RNA; NUCLEOTIDE-SEQUENCE; RHESUS-MONKEYS; BINDING-SITE; AIDS VIRUS; RETROTRANSPOSITION; DEFECT; TY1 C1 US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. RP Lauermann, V (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS BASIC RES PROGRAM,FREDERICK,MD 21702, USA. 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 0269-9370 J9 AIDS JI Aids PD DEC PY 1996 VL 10 IS 14 BP 1738 EP 1740 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VY172 UT WOS:A1996VY17200021 PM 8970697 ER PT J AU Yanovski, JA Yanovski, SZ Filmer, KM Hubbard, VS Avila, N Lewis, B Reynolds, JC Flood, M AF Yanovski, JA Yanovski, SZ Filmer, KM Hubbard, VS Avila, N Lewis, B Reynolds, JC Flood, M TI Differences in body composition of black and white girls SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE visceral adipose tissue; race; blacks; whites; magnetic resonance imaging; dual-energy X-ray absorptiometry; anthropometry; bioelectrical impedance analysis ID MASS INDEX; BIOELECTRIC IMPEDANCE; CHILDREN; FAT; OBESITY; WOMEN; HEALTH; ALDOSTERONE; GREATER; ADULTS AB Adults have racial differences in body composition that may modulate risks resulting from obesity. Although black and white children have been shown previously to have differences in bone mineral density and subcutaneous body fat, differences in visceral adipose tissue have not been evaluated. We studied 20 black and 20 white normal-weight girls aged 7-10 y, who were matched for weight, body mass index (BMI), bone age, chronological age, Tanner breast stage, and socioeconomic status. Each underwent anthropometric measurements, bioelectrical impedance analysis, dual-energy X-ray absorptiometry (DXA), and abdominal magnetic resonance imaging (MRI) for determination of total (TAT), visceral (VAT), and subcutaneous (SAT) adipose tissue. Serum lipids and fasting and 2-h oral-glucose-tolerance test (OGTT) glucose and insulin concentrations were also measured. There were no differences between groups in absolute waist circumference or waist-to-hip ratio, but waist-to-thigh ratio was smaller in black than in white girls. Black girls had greater bone mineral density and less TAT, VAT, and SAT than whites. VAT was not significantly correlated with any measure of insulin, or with serum lipids. However, both basal and 2-h OGTT serum insulin were significantly correlated with SAT as assessed by MRI in black girls (r(2) = 0.46 for basal insulin, P = 0.001; r(2) = 0.31 for 2-h insulin, P = 0.01) but not in white girls (r(2) < 0.05, for basal and 2-h insulin, NS). We conclude that there are significant racial differences in body composition and differences in the strength of association between abdominal adipose tissue depots and insulin sensitivity in black and white girls. C1 NIDDK, DIV DIGEST DIS & NUTR, NIH, BETHESDA, MD USA. RP Yanovski, JA (reprint author), NICHHD, WARREN GRANT MAGNUSON CLIN CTR, DEV ENDOCRINOL BRANCH,NIH,MSC 1862,BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 39 TC 105 Z9 106 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1996 VL 64 IS 6 BP 833 EP 839 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VU814 UT WOS:A1996VU81400001 PM 8942404 ER PT J AU Dorgan, JF Judd, JT Longcope, C Brown, C Schatzkin, A Clevidence, BA Campbell, WS Nair, PP Franz, C Kahle, L Taylor, PR AF Dorgan, JF Judd, JT Longcope, C Brown, C Schatzkin, A Clevidence, BA Campbell, WS Nair, PP Franz, C Kahle, L Taylor, PR TI Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: A controlled feeding study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet; dietary fats; dietary fiber; estrogen; androgens ID HORMONE-BINDING GLOBULIN; PROSTATE-CANCER RISK; SERUM SEX-HORMONES; FREE TESTOSTERONE; ADULT MEN; WOMEN; VEGETARIAN; INTERRELATIONSHIPS; CONSUMPTION; ESTRADIOL AB We conducted a controlled feeding study to evaluate the effects of fat and fiber consumption on plasma and urine sex hormones in men. The study had a crossover design and included 43 healthy men aged 19-56 y. Men were initially randomly assigned to either a low-fat, high-fiber or high-fat, low-fiber diet for 10 wk and after a 2-wk washout period crossed over to the other diet. The energy content of diets was varied to maintain constant body weight but averaged approximate to 13.3 MJ (3170 kcal)/d on both diets. The low-fat diet provided 18.8% of energy from fat with a ratio of polyunsaturated to saturated fat (P:S) of 1.3, whereas the high-fat diet provided 41.0% of energy from fat with a P:S of 0.6. Total dietary fiber consumption from the low- and high-fat diets averaged 4.6 and 2.0 g . MJ(-1) . d(-1), respectively. Mean plasma concentrations of total and sex-hormone-binding-globulin (SHBG)-bound testosterone were 13% and 15% higher, respectively, on the high-fat, low-fiber diet and the difference from the low-fat, high-fiber diet was significant for the SHBG-bound fraction (P = 0.04). Men's daily urinary excretion of testosterone also was 13% higher with the high-fat, low-fiber diet than with the low-fat, high-fiber diet (P = 0.01). Conversely, their urinary excretion of estradiol and estrone and their 2-hydroxy metabolites were 12-28% lower with the high-fat, low-fiber diet (P less than or equal to 0.01). Results of this study suggest that diet may alter endogenous sex hormone metabolism in men. C1 ARS,DIET & HUMAN PERFORMANCE LAB,USDA,BELTSVILLE,MD. UNIV MASSACHUSETTS,SCH MED,DEPT OBSTET & GYNECOL,WORCESTER,MA. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Dorgan, JF (reprint author), NCI,DIV CANC PREVENT & CONTROL,CPSA,EXECUT PLAZA N,ROOM 211,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 45 TC 110 Z9 113 U1 0 U2 7 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1996 VL 64 IS 6 BP 850 EP 855 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VU814 UT WOS:A1996VU81400004 PM 8942407 ER PT J AU Witte, JS Longnecker, MP Bird, CL Lee, ER Frankl, HD Haile, RW AF Witte, JS Longnecker, MP Bird, CL Lee, ER Frankl, HD Haile, RW TI Relation of vegetable, fruit, and grain consumption to colorectal adenomatous polyps SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; cereals; colonic neoplasms; diet; fruit; garlic; vegetables ID COLON-CANCER; ANTIOXIDANT VITAMINS; DIETARY; EPIDEMIOLOGY; FOOD; RISK; PREVENTION; QUESTIONNAIRE; RECURRENCE; HEALTH AB Previous studies suggest that colorectal cancer risk decreases with higher intake of vegetables, fruits, and grains. Few studies, however, have examined these factors in relation to occurrence of colorectal polyps. The authors used case-control data from 488 matched pairs to evaluate associations of vegetables, fruits, and grains with polyps. Subjects were southern Californians aged 50-74 years who had a sigmoidoscopy in 1991-1993. Diet in the year before sigmoidoscopy was measured with a food frequency questionnaire. Frequent consumption of vegetables, fruits, and grains was associated with decreased polyp prevalence. Specifically, the adjusted odds ratio comparing the highest with the lowest quintile of intake for vegetables was 0.47 (95% confidence interval (CI) 0.29-0.76), for fruits was 0.65 (95% CI 0.40-1.05), and for grains was 0.55 (95% CI 0.33-0.91). The authors also found inverse associations for high carotenoid vegetables, cruciferae, high vitamin C fruits, garlic, and tofu (or soybeans). After further adjusting for potentially anticarcinogenic constituents of these foods, high carotenoid vegetables, cruciferous vegetables, garlic, and tofu (or soybeans) remained inversely associated with polyps. These findings support the hypothesis that high intake of vegetables, fruits, or grains decreases the risk of polyps and suggest that any protective effects might reflect unmeasured constituents in these foods. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC. UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. KAISER PERMANENTE MED CTR,DIV GASTROENTEROL BELLFLOWER,LOS ANGELES,CA 90034. KAISER PERMANENTE MED CTR,DIV GASTROENTEROL SUNSET,LOS ANGELES,CA 90034. RP Witte, JS (reprint author), CASE WESTERN RESERVE UNIV,SCH MED,METROHLTH MED CTR,DEPT EPIDEMIOL & BIOSTAT,2500 METROHLTH DR,CLEVELAND,OH 44109, USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA 09142, CA 51923] NR 37 TC 118 Z9 119 U1 0 U2 6 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1996 VL 144 IS 11 BP 1015 EP 1025 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VV535 UT WOS:A1996VV53500002 PM 8942431 ER PT J AU Klebanoff, MA Clemens, JD Read, JS AF Klebanoff, MA Clemens, JD Read, JS TI Maternal smoking during pregnancy and childhood cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carcinogens; cohort studies; neoplasms; pregnancy; smoking ID PARENTS SMOKING; RISK; EXPOSURE AB The association between maternal smoking during pregnancy and childhood cancer was investigated using prospectively collected data from 54,795 liveborn children in the Collaborative Perinatal Project (1959-1966). Cases of cancer had a histologic diagnosis and/or a compatible clinical course. There were 51 children with cancer, for a cumulative incidence of cancer of 1.1 per 1,000 by 96 months of age. Maternal smoking was determined al each prenatal visit; 52% of mothers reported smoking at one or more visits. By age 8 years, cancer had occurred in 1.4 per 1,000 children whose mothers did not smoke during pregnancy, compared with 0.9 per 1,000 children whose mothers smoked (p = 0.15 by log rank test); the hazard ratio was 0.67 (95% confidence interval (CI) 0.38-1.17). There was no dose-response effect of smoking compared with nonsmokers (hazard ratio for one to 10 cigarettes/day = 0.45, more than 10 cigarettes/day = 0.83). The hazard ratio for leukemia among children whose mothers smoked was 0.82 (95% CI 0.31-2.11); the hazard ratio for cancers other than leukemia was 0.60 (95% CI 0.30-1.20). Adjustment did not change the hazard ratio substantially. Although the relatively small number of cases precluded extensive study of individual types of cancer, the authors conclude that maternal smoking during pregnancy is not associated with an increased risk of childhood cancer in this cohort. RP Klebanoff, MA (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,NIH,6100 BLDG,ROOM 7B03,BETHESDA,MD 20892, USA. NR 22 TC 39 Z9 40 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1996 VL 144 IS 11 BP 1028 EP 1033 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VV535 UT WOS:A1996VV53500004 PM 8942433 ER PT J AU Szklo, M Cerhan, J DiezRoux, AV Chambless, L Cooper, L Folsom, AR Fried, LP Knopman, D Nieto, FJ AF Szklo, M Cerhan, J DiezRoux, AV Chambless, L Cooper, L Folsom, AR Fried, LP Knopman, D Nieto, FJ TI Estrogen replacement therapy and cognitive functioning in the atherosclerosis risk in communities (ARIC) study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cognition; cognition disorders; estrogen replacement therapy; menopause; women's health ID DENDRITIC SPINE DENSITY; RAT PREOPTIC AREA; ALZHEIMERS-DISEASE; BASAL FOREBRAIN; OLDER PERSONS; FEMALE RATS; WOMEN; POPULATION; RECEPTORS; MORTALITY AB The association of estrogen replacement therapy (ERT) with cognitive functioning was assessed in 6,110 women aged 48-67 years participating in the Atherosclerosis Risk in Communities (ARIC) study, a multicenter longitudinal investigation. ERI was evaluated in relation to results of three cognitive tests (the Delayed Word Recall (DWR) Test, the Digit Symbol Subtest of the Wechsler Adult Intelligence Scale-Revised (DSS/WAIS-R), and the Word Fluency (WF) Test) using data from the first follow-up visit of the cohort (1990-1992). No consistent associations were seen between ERT and either the DWR test or the DSS/WAIS-R after adjusting for age, education, and additional covariates previously found to be associated with cognitive function scores. Among surgically menopausal women aged 48-57 years, adjusted mean WF scores were slightly greater in ERT current users (mean WF 35.9) than in never users (mean WF 33.5) (p < 0.02); and within current users, adjusted WF scores increased with duration of ERT use. However, the finding that ERT was associated with a slightly higher level of performance on only one of three measures offers little support for the hypothesis that ERT has a major protective effect on cognitive function in women less than 68 years of age. The generalizability of these findings to older women who are more likely to experience cognitive decline and who may be using ERT for longer periods of time is limited by the relatively young age of the cohort. C1 UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC. NHLBI,NIH,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. JOHNS HOPKINS MED INST,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD 21205. UNIV MINNESOTA,DEPT NEUROL,MINNEAPOLIS,MN 55455. RP Szklo, M (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,605 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 46 TC 60 Z9 61 U1 1 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1996 VL 144 IS 11 BP 1048 EP 1057 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VV535 UT WOS:A1996VV53500007 PM 8942436 ER PT J AU Ioannidis, JPA Cappelleri, JC Schmid, CH Lau, J AF Ioannidis, JPA Cappelleri, JC Schmid, CH Lau, J TI Impact of epidemic and individual heterogeneity on the population distribution of disease progression rates - An example from patient populations in trials of human immunodeficiency virus infection SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE HIV; latency; models; statistical; randomized controlled trials; study design; survival ID PLACEBO-CONTROLLED TRIAL; PNEUMOCYSTIS-CARINII PNEUMONIA; DEFERRED ZIDOVUDINE THERAPY; AIDS-RELATED COMPLEX; CUBIC MILLIMETER; HIV-1 INFECTION; UNITED-STATES; DOUBLE-BLIND; CLINICAL-TRIALS; NATURAL-HISTORY AB Patients at the same stage of a chronic disease may have had different rates of disease progression. The authors developed a mathematical modeling approach that allows reconstructing and comparing populations in terms of the disease progression rates of their participants when the disease onset and progression rates are unknown for individual patients. Human immunodeficiency virus 1 infection was used as an example. Both published and hypothetical models were used to describe the human immunodeficiency virus 1 epidemic (epidemic heterogeneity) and incubation and survival functions for different disease stages (individual heterogeneity). Reconstructions of populations with late disease (e.g., acquired immunodeficiency syndrome patients) show a marked predominance of rapid progressors, unless the incidence of new infections has been decreasing for a long time. Rapid progressors would also predominate in populations of acute seroconverters, unless diagnosis is based on repeated serologic screening rather than symptoms. Populations of patients who have not progressed beyond an early stage of the disease (e.g., patients with CD4 cell counts >500/mu l) tend to overrepresent slow progressors, especially if the epidemic has been decreasing for a long time. With this approach, one can assess whether the target population of a clinical trial is comparable with other patient populations at different places and times. Epidemic and individual diversity may even affect trial results if patients with different progression rates experience different benefits from a treatment. By modeling the targeted populations in trials of early versus deferred antiretroviral treatment, the authors observed larger treatment benefits in trials in which rapid progressors probably predominated, compared with trials of slow progressors. C1 TUFTS UNIV NEW ENGLAND MED CTR,DIV CLIN CARE RES,BOSTON,MA. TUFTS UNIV NEW ENGLAND MED CTR,BIOSTAT RES CTR,BOSTON,MA. TUFTS UNIV,SCH MED,BOSTON,MA 02111. RP Ioannidis, JPA (reprint author), NIAID,NIH,HIV RES BRANCH,THERAPEUT RES PROGRAM,SOLAR BLDG,ROOM 2C15,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Ioannidis, John/G-9836-2011; OI Schmid, Christopher/0000-0002-0855-5313 FU AHRQ HHS [R01 HS 07782]; NIAID NIH HHS [T32 AI07389] NR 50 TC 25 Z9 25 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1996 VL 144 IS 11 BP 1074 EP 1085 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VV535 UT WOS:A1996VV53500011 PM 8942440 ER PT J AU Martinez, RA Mulsant, BH Meyers, BS Lebowitz, BD AF Martinez, RA Mulsant, BH Meyers, BS Lebowitz, BD TI Delusional and psychotic depression in late life - Clinical research needs SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID ELECTROCONVULSIVE-THERAPY; FOLLOW-UP; MEDICATION RESISTANCE; AFFECTIVE-DISORDERS; MAJOR DEPRESSION; OLD-AGE; SUICIDE; UNIPOLAR; MELANCHOLIA; LEUKOENCEPHALOPATHY AB Psychotic depression in younger patients has been associated with an increased rate of suicide, refractoriness to somatic treatment, and overall poor prognosis. However, the public health and scientific significance of this disorder in older patients has received limited attention in the past two decades; the topic was excluded from the 1991 NIH Consensus Development Conference on the Diagnosis and Treatment of Depression in Late Life. To address this obvious need in the field, a special work-group of recognized experts met in a special NIMH workshop to review and discuss clinical issues and key research questions. This is a report of that workshop's proceedings. C1 NIMH,MENTAL DISORDERS AGING RES BRANCH,ROCKVILLE,MD 20857. NR 59 TC 13 Z9 13 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD WIN PY 1996 VL 4 IS 1 BP 77 EP 84 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA TL531 UT WOS:A1996TL53100009 ER PT J AU Williams, S Linardic, C Wilson, O Comp, P Gralnick, HR AF Williams, S Linardic, C Wilson, O Comp, P Gralnick, HR TI Acquired hypoprothrombinemia: Effects of Danazol(R) treatment SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE hypoprothrombinemia; lupus anticoagulant; discoid lupus erythematosus; Danazol(R); factor II; factor IX; factor X; protein C; protein S ID SYSTEMIC LUPUS-ERYTHEMATOSUS; PROTHROMBIN; ANTICOAGULANT; ANTIBODIES; MECHANISM; ASSAY AB The lupus anticoagulant may be accompanied by an acquired factor II deficiency and bleeding. We report on a patient with a lupus anticoagulant and factor II (FII) deficiency responsive to Danazol(R). Acquired hypoprothrombinemia (FII) with the lupus anticoagulant (LA) may be accompanied by a hemorrhagic diathesis. A 64-year-old male with discoid lupus erythematosis bled after an intestinal polypectomy. His FII level was 18%, and his FII antigen level was 20%. Danazol(R) (D) (600 mg per day) administration was associated with a rise in FII activity and antigen to 50% within 10 days. The patient underwent abdominal surgery. We studied the effect(s) of D on the FII level and on other coagulation factors in this patient. The patient's plasma FII antigen had a single precipitin are compared to the two peaks of normal plasma on counterimmunoelectrophoresis with Ca++. The samples pre- and during D therapy had the same positively charged are as normal samples, although they were quantitatively different. Neuraminidase treatment demonstrated a decrease in the positively charged migration of normal and the patient's FII antigen. Affinity chromatography of normal and patient plasma on a Sepharose protein A column revealed FII antigen present in the patient's bound fraction. The relative percentages of bound FII before and during D treatment were similar. During D therapy, levels of FIX and X rose 50-100%, and protein C rose 20-25%, while free protein S did not change. D is an effective therapy for acquired FII deficiency associated with LA. D does not affect the binding of Ig to FII, but D raises FII levels by increasing synthesis of the FII protein. (C) 1996 Wiley-Liss, Inc. C1 NIH,DEPT CLIN HEMATOL,BETHESDA,MD 20892. UNIV OKLAHOMA,OKLAHOMA CITY,OK. NR 12 TC 11 Z9 11 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 1996 VL 53 IS 4 BP 272 EP 276 DI 10.1002/(SICI)1096-8652(199612)53:4<272::AID-AJH14>3.0.CO;2-E PG 5 WC Hematology SC Hematology GA VV478 UT WOS:A1996VV47800014 PM 8948670 ER PT J AU Zheng, CJ Byers, B AF Zheng, CJ Byers, B TI Implications of the oocyte-selection hypothesis: A response SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID MATERNAL-AGE; MITOTIC ERRORS; TRISOMY-21 C1 UNIV WASHINGTON,DEPT GENET,SEATTLE,WA 98195. RP Zheng, CJ (reprint author), NIDCD,EPIDEMIOL STAT & DATA SYST BRANCH,NIH,6120 EXECUT BLVD EPS 432,BETHESDA,MD 20892, USA. NR 10 TC 3 Z9 3 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1996 VL 59 IS 6 BP 1397 EP 1398 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA VV315 UT WOS:A1996VV31500029 ER PT J AU Sparks, SM AF Sparks, SM TI Use of the Internet for infection control and epidemiology SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article AB Infection control professionals are taking advantage of the Internet for the rapid transmission and distribution of information that includes sounds, still and motion images, and text to their peers, colleagues, patients, and the public. This article provides some background information on the Internet and examples of some electronic resources and offers suggestions of additional applications of the Internet for infection control and epidemiology. RP Sparks, SM (reprint author), NATL LIB MED,DIV EXTRAMURAL PROGRAMS,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD DEC PY 1996 VL 24 IS 6 BP 435 EP 439 DI 10.1016/S0196-6553(96)90037-1 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA VY556 UT WOS:A1996VY55600004 PM 8974169 ER PT J AU Buckalew, VM Berg, RL Wang, SR Porush, JG Rauch, S Schulman, G AF Buckalew, VM Berg, RL Wang, SR Porush, JG Rauch, S Schulman, G TI Prevalence of hypertension in 1,795 subjects with chronic renal disease: The modification of diet in renal disease study baseline cohort SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hypertension; chronic renal disease; risk factors ID POLYCYSTIC KIDNEY-DISEASE; BLOOD-PRESSURE; CHRONIC GLOMERULONEPHRITIS; WEIGHT-LOSS; BODY-MASS; FAILURE; SENSITIVITY; SODIUM; INSUFFICIENCY; PROGRESSION AB The Modification of Diet in Renal Disease Study was a multicenter trial of the effect of protein restriction and strict blood pressure control on the progression rate of chronic renal failure of multiple causes. At the first baseline visit, 1,795 screened patients with renal disease had blood pressure measured, antihypertensive medications recorded, glomerular filtration rate (GFR) determined by I-125-iothalamate clearance, a nutritional assessment, and a 24-hour urine collection to determine sodium and potassium levels, A total of 1,494 patients in this cohort were classified as hypertensive (83%) and the remainder (301 patients) as nonhypertensive. Ninety-one percent of the hypertensive subjects were on treatment, 54% being controlled to a blood pressure of less than or equal to 140/90 mm Hg, To better understand the factors that contribute to the development of hypertension in chronic renal disease, some determinants of the prevalence of hypertension in this cohort were investigated, Compared with normotensive subjects, hypertensive patients were older (51.2 +/- 12.7 years v 46.6 +/- 13.1 years [mean +/- SD]), had a higher body mass index (BMI; 27.5 +/- 4.7 kg/m(2) v 25.4 +/- 4.2 kg/m(2)), and had a lower GFR (37.8 +/- 19.6 ml/min/1.73 m(2) v 50.1 +/- 25 mL/min/1.73 m(2)). All these differences were significant (P < 0.01). The prevalence of hypertension was significantly higher for men than for women (86% v 80%; P = 0.001), and for blacks than for whites (93% v 81%; P < 0.001). The prevalence of hypertension was higher in subjects with glomerular disease than in those with tubulointerstitial disease (85% v 62.6%; P < 0.001), The prevalence of hypertension varied inversely with GFR (from 66% at a GFR of 83 mL/min/1.73 m(2) to 95% at a GFR of 12 ml/min/1.73 m(2)). The prevalence of hypertension varied directly with BMI (from 70% with a BMI at the 10th percentile to 94% with a BMI at the 97th percentile), This relationship was independent of GFR. Multiple logistic regression analysis showed five predictors in decreasing order of significance as determined by chi-square values: GFR, 83.2; BMI, 36.7; black race, 19.9; increasing age, 14.5 (all P < 0.001); and male gender, 5.1 (P = 0.024). Salt intake was not a determinant of blood pressure status, These results confirm previous reports indicating that hypertension in renal disease is determined by the level of renal function, For the first time, three factors known to predict blood pressure levels in populations with normal renal function were also shown to be determinants of blood pressure in renal disease: BMI, black race, and age, In addition, the data suggest that hypertension is inadequately treated in more than half of patients with chronic renal disease in the United States. (C) 1996 by the National Kidney Foundation, Inc. C1 NIDDK,NIH,BETHESDA,MD. NR 44 TC 139 Z9 141 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 1996 VL 28 IS 6 BP 811 EP 821 DI 10.1016/S0272-6386(96)90380-7 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA VX333 UT WOS:A1996VX33300004 PM 8957032 ER PT J AU Goldenberg, RL DuBard, MB Cliver, SP Nelson, KG Blankson, K Ramey, SL Herman, A AF Goldenberg, RL DuBard, MB Cliver, SP Nelson, KG Blankson, K Ramey, SL Herman, A TI Pregnancy outcome and intelligence at age five years SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preterm birth; growth restriction; intelligence ID LOW-BIRTH-WEIGHT; FETAL GROWTH-RETARDATION; MENTAL-RETARDATION; GESTATIONAL-AGE; INFANTS; CHILDREN; TERM; METAANALYSIS; PREVALENCE; PRETERM AB OBJECTIVE: Our purpose was to determine the influence of being small for gestational age at term and being preterm <34 weeks on cognitive functioning at age 5 years. STUDY DESIGN: Five hundred forty-six children of black low-income mothers, nearly all at risk for being small for gestational age, followed up prenatally with early ultrasonographic gestational age dating, were classified as either term appropriate for gestational age, term small for gestational age, or preterm at <34 weeks. At a mean of 5.5 +/- 0.5 years, a Wechsler Preschool and Primary Scale of Intelligence-Revised intelligence quotient test was administered. An intelligence quotient <70 was used to define mental retardation. Univariate and multivariate analyses adjusted for maternal age, smoking, education and language skills, home environment, and child gender and preschool attendance were performed. RESULTS: Term small-for-gestational-age and preterm infants at <34 weeks had 4 and 6 point intelligence quotient reductions compared with term appropriate-for-gestational-age infants. In the regression analyses these differences in intelligence quotient remained significant after confounders were adjusted. High maternal receptive language level (8 points), a positive home environment (5 points), and attendance at preschool (5 points) were each significantly associated with an increase in intelligence quotient. CONCLUSION: Both term small-for-gestational-age infants and those born at <34 weeks had a significantly lower mean intelligence quotient, and small-for-gestational-age infants had an increased risk of mental retardation at age 5 years. Higher maternal language skills, a positive home environment, and attendance at preschool each were associated with an increase in the mean intelligence quotient of 5 to 7 points. C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PEDIAT,BIRMINGHAM,AL 35294. NICHHD,NIH,BETHESDA,MD 20892. RP Goldenberg, RL (reprint author), UNIV ALABAMA,CTR OBSTET RES,BIRMINGHAM,AL 35294, USA. FU BHP HRSA HHS [DHHS-282-92-0055]; NICHD NIH HHS [N01-HD-42811]; PHS HHS [PRP-90-11] NR 25 TC 56 Z9 56 U1 4 U2 6 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 DEC PY 1996 VL 175 IS 6 BP 1511 EP 1515 DI 10.1016/S0002-9378(96)70099-6 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WA641 UT WOS:A1996WA64100029 PM 8987934 ER PT J AU Alexander, M Salgaller, ML Celis, E Sette, A Barnes, WA Rosenberg, SA Steller, MA AF Alexander, M Salgaller, ML Celis, E Sette, A Barnes, WA Rosenberg, SA Steller, MA TI Generation of tumor-specific cytolytic T lymphocytes from peripheral blood of cervical cancer patients by in vitro stimulation with a synthetic human papillomavirus type 16 E7 epitope SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE human papillomavirus; vaccine; peptide epitopes; cervical cancer; cytolytic T lymphocytes ID CARCINOMA CELL-LINES; INFILTRATING LYMPHOCYTES; CTL EPITOPES; IN-VIVO; HLA-A; IDENTIFICATION; SEQUENCES; PEPTIDES; E6; EXPRESSION AB OBJECTIVE: Approximately 90% of squamous carcinomas of the cervix harbor the human papillomavirus and type 16 has been detected in nearly 50% of cases. Recent studies in mice have shown that the human papillomavirus type 16 E7 oncoprotein contains peptide epitopes that are processed and presented in association with a major histocompatibility antigen for recognition by cytolytic T lymphocytes. We investigated whether an epitope from human papillomavirus type 16 E7 could be used to generate specific human cytolytic T lymphocytes in patients with cervical carcinoma. STUDY DESIGN: After radiation therapy, three patients with antigen HLA-A2 and with locally advanced cervical cancer underwent leukapheresis, Epitope-specific cytolytic T lymphocytes were generated from the peripheral blood mononuclear cells by in vitro stimulation with autologous peripheral blood mononuclear cells pulsed with a human papillomavirus type 16 E7, HLA-A2-restricted, synthetic peptide, E7(11-20) (YMLDLQPETT). RESULTS: In two patients cytolytic T lymphocytes were capable of E7(11-20)-specific, HLA-A2-restricted cytolysis of the peptide-pulsed, HLA-matched, T2 target cell line. Cytolytic T lymphocytes from one of these patients also demonstrated specific cytolysis against the HLA-A2(+), HPV-16(+) CaSki cervical cancer cell line but did not lyse either HLA-A2(+), HPV-16(-) MS-751 cells or HLA-A2(-), HPV-16(-) HT-3 cells. CONCLUSIONS: These experiments demonstrate that novel cytolytic T lymphocytes that recognize a human papillomavirus type 16 E7 epitope can be generated by using the peripheral blood mononuclear cells from irradiated patients with cervical cancer. In addition, because CaSki cells were specifically lysed by the cytolytic T lymphocytes, these data indicate that the peptide E7(11-20) is endogenously processed and presented on the cell surface of the CaSki cells. The demonstration of epitope-specific lysis of cytolytic T lymphocytes of HPV-16(+) cervical cancer cells supports further efforts to develop human papillomavirus peptide-based vaccines or antigen-specific adoptive immunotherapy for the prevention and treatment of cervical carcinoma. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DIV GYNECOL ONCOL,WASHINGTON,DC 20007. CYTEL CORP,SAN DIEGO,CA 92121. NR 25 TC 65 Z9 68 U1 0 U2 6 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 DEC PY 1996 VL 175 IS 6 BP 1586 EP 1593 DI 10.1016/S0002-9378(96)70110-2 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WA641 UT WOS:A1996WA64100040 PM 8987945 ER PT J AU Han, DP Vine, AK Blodi, BA Elner, SG Johnson, MW Jessup, LM Khanderia, S Pierson, CL Willis, J McIver, F Stanley, S Sneed, SR Capone, A Aaberg, TM Lim, JI Sternberg, P Coffman, DS Moore, CN Gardner, SK Nolte, FS Fremstad, A Gibbs, D Gilman, J Swords, R Aguilar, HE Meredith, TA Lakhanpal, V Christian, FD Hood, MA Schwalbe, RS Billings, EE Buie, W Mallonee, JJ Millar, MA Verbeek, S Campochiaro, PA Palardy, CB Reynolds, L Dick, JD Cain, D DAmico, DJ Frederick, AR Morley, MG Pesavento, RD Puliafito, CA Topping, TM Finn, SM Raymond, LA Baker, AS Paton, B Evans, C Napoli, J Kiernan, C Makris, K McInnes, T Reidy, WT White, R Garfinkel, RA Pilkerton, AR Frantz, RA Abernathy, GB Barbaccia, JG Ensey, HR Ormes, CA Park, CH Caplan, J Russel, K Toma, R Packo, KH deBustros, S Flood, TP Glazer, L DeAlba, M Evanich, E Montwill, MA Rothman, JJ Ruderman, G Beard, M Landau, W Shen, MH Gordon, M Graff, S Kwiatkowski, K Pappas, L Bryant, D Doherty, D Morini, F Arredondo, L Garretson, BR Gerena, C Hunt, M Kinnaird, SM Neri, T Rice, TA Novak, MA Rwe, PS Jamieson, S Newberry, D Rech, GR Dul, MJ Kinser, L Strozewski, K ClarkRath, S DeLisio, M Dempsey, DL Kukula, D PinterSmith, A Rowe, PS SmithBrewer, S Ludwig, T Chambers, RB Davidorf, FH Taylor, CS Hale, KN Buesching, WJ Chaudhuri, C Cover, NJ Shortlidge, GR Keating, MJ Savage, SJ Andrzejewska, P Cornetet, S Milliron, JD Richmond, R Schneider, L Weisenberger, D Cantrill, HL Ramsay, RC Brallier, AB Johnson, TP Rossing, EE Knauth, KA Monahan, MM Oestreich, NW Clark, KF Glennen, AM Yarian, DL Green, SN Leff, SR Masciulli, L Lucido, MM Ludwig, EJ Marano, CL Peters, L Joho, K Volkert, DC Andersen, F Coffey, D Schlosser, A Honeywell, A Mames, RN Driebe, WT Stern, GA Francis, A Zam, ZS Cooper, R Gaskins, D Shamis, DJ Willingham, M Barker, K Rosa, H Friedman, SM Gardner, TW Blankenship, GW Coyle, CJ Bero, CJ Halas, C Schick, S Walker, J Cunningham, D Lambert, HM Clogston, PS Frady, PM Gardner, SN Osato, MS Carr, L Shigley, J Lopez, PF Chong, LP Frambach, DA Cisneros, L Padilla, M Yee, EM Nakamura, T Walonker, AF Morales, R Nichols, T Huete, ME Liggett, PE Ober, RR QuillenThomas, B Williams, M Barr, CC Bloom, SM Greene, PJ Whittington, GK Martin, ME Watson, G JenkinsCurry, B Gilkey, LA Huelsman, S Burton, TC Mieler, WF Pulido, JS Reeser, FH Newman, JL Werner, KA Pisarzewicz, PJ Reinerio, NA Walloch, MLK Wilmer, Z Laabs, J Picchiottino, R Phillips, J Wipplinger, W Abrams, GW Jurkiewicz, DT Leet, ML Mandel, P Metzger, K Suchla, L Zarling, D Balles, MW Ryan, EH Knobloch, WH Cook, SM Luke, DG Ferrieri, P Schiminsky, NM Genia, A Philiph, DA Stinson, EK Wright, LM McMichael, WC Mielke, SJ Ponwith, LJ Pavan, PR Pautler, SE Coats, ML Kirk, NM Millard, SM Castellano, FC Edwards, CR Marquardt, A McCormack, AJ McCormick, MT Renshaw, B Restuccia, A Campbell, M Christopher, N Garrett, LS Halkias, DG Hothersall, K MIckler, K Minnick, TS Burr, C Saxon, W Arcacha, MA Carlton, S Edison, SK Mallis, MJ Sayers, TL Sudds, TW Tiberia, RJ Wolabaugh, S Bradford, RH Parke, DW Wolf, TC Shofner, JM Tobey, LE Jensen, HG Sanchez, D Shofner, J Burris, R Drake, KK Grissom, KR Rowsey, JJ Wilkinson, CP Brown, GC Benson, WE Federman, JL Lucier, AC Maguire, JI Sarin, LK Shakin, EP Sivalingam, A Tasman, W Vander, JF Ward, N Weisbecker, CA Agnew, CL Lambert, R Tomer, T Carlson, K Franchine, G Serfass, MS Doft, BH Bergren, RL Lobes, LA Olsen, KR Rinkoff, JS Metz, DJ Leonard, MN Karenchak, LM Kowalski, RP Wellman, LA Wilcox, LA Campbell, AF Steinberg, DR Vagstad, GL Flook, KA Good, MM Keenen, BJ Mellinger, KA Margherio, RR Cox, MS Murphy, PL Trese, MT Werner, JC Williams, GA Manatrey, PE Prote, JL Lucarotti, R Martin, S Band, J Bostic, G Cumming, K Mitchell, B Regan, VS Bridges, C Cox, S Houston, G Johnson, J Streasik, P Wood, B Blumenkranz, MS Cayo, L Kaye, V Valenzuela, CL Orgel, IK Poliner, LS Tornambe, PE Cannon, SV Nielsen, JL Carlson, A Chan, P Drake, L Grim, M Peterson, C Borg, LA Gillyatt, J Beyer, C Hammer, ME Grizzard, WS Shannon, TL Traynom, JR Collado, MJ McManus, DW Sweeney, DE Adams, DH Watson, TT Antworth, MV Araos, JG Greenwald, MA Habib, M Myers, SK Ockers, KM Thibodeau, JA Watkins, B Nelsen, PT Rosenthal, JG Mintz, FV Biedenbach, M Leonardy, NJ Lawniczak, SM Bork, C Hageage, G Hunter, EB Marshall, MJ Roman, P Hill, R HOfbauer, T Lemanowicz, J Cupples, HP Guzman, GI Brodeur, RJ Yee, D Delaha, EC Geyer, SL Slovis, S Shields, WJ Lauber, S Michelitsch, K Barza, M Kassoff, A Watling, S Wilson, LA Buehler, JC McVay, J Kelsey, SF Wisniewski, SR Podobinski, GK Sillett, RL Groer, S Avery, B Belle, SH Boles, J Henry, L Shema, SJ TitusErnstoff, L Davis, M Magli, YL Hubbard, L Thomas, S Everett, DF Mowery, R Davis, K Azen, S Covey, P McCuen, B Packer, A Robbin, J AF Han, DP Vine, AK Blodi, BA Elner, SG Johnson, MW Jessup, LM Khanderia, S Pierson, CL Willis, J McIver, F Stanley, S Sneed, SR Capone, A Aaberg, TM Lim, JI Sternberg, P Coffman, DS Moore, CN Gardner, SK Nolte, FS Fremstad, A Gibbs, D Gilman, J Swords, R Aguilar, HE Meredith, TA Lakhanpal, V Christian, FD Hood, MA Schwalbe, RS Billings, EE Buie, W Mallonee, JJ Millar, MA Verbeek, S Campochiaro, PA Palardy, CB Reynolds, L Dick, JD Cain, D DAmico, DJ Frederick, AR Morley, MG Pesavento, RD Puliafito, CA Topping, TM Finn, SM Raymond, LA Baker, AS Paton, B Evans, C Napoli, J Kiernan, C Makris, K McInnes, T Reidy, WT White, R Garfinkel, RA Pilkerton, AR Frantz, RA Abernathy, GB Barbaccia, JG Ensey, HR Ormes, CA Park, CH Caplan, J Russel, K Toma, R Packo, KH deBustros, S Flood, TP Glazer, L DeAlba, M Evanich, E Montwill, MA Rothman, JJ Ruderman, G Beard, M Landau, W Shen, MH Gordon, M Graff, S Kwiatkowski, K Pappas, L Bryant, D Doherty, D Morini, F Arredondo, L Garretson, BR Gerena, C Hunt, M Kinnaird, SM Neri, T Rice, TA Novak, MA Rwe, PS Jamieson, S Newberry, D Rech, GR Dul, MJ Kinser, L Strozewski, K ClarkRath, S DeLisio, M Dempsey, DL Kukula, D PinterSmith, A Rowe, PS SmithBrewer, S Ludwig, T Chambers, RB Davidorf, FH Taylor, CS Hale, KN Buesching, WJ Chaudhuri, C Cover, NJ Shortlidge, GR Keating, MJ Savage, SJ Andrzejewska, P Cornetet, S Milliron, JD Richmond, R Schneider, L Weisenberger, D Cantrill, HL Ramsay, RC Brallier, AB Johnson, TP Rossing, EE Knauth, KA Monahan, MM Oestreich, NW Clark, KF Glennen, AM Yarian, DL Green, SN Leff, SR Masciulli, L Lucido, MM Ludwig, EJ Marano, CL Peters, L Joho, K Volkert, DC Andersen, F Coffey, D Schlosser, A Honeywell, A Mames, RN Driebe, WT Stern, GA Francis, A Zam, ZS Cooper, R Gaskins, D Shamis, DJ Willingham, M Barker, K Rosa, H Friedman, SM Gardner, TW Blankenship, GW Coyle, CJ Bero, CJ Halas, C Schick, S Walker, J Cunningham, D Lambert, HM Clogston, PS Frady, PM Gardner, SN Osato, MS Carr, L Shigley, J Lopez, PF Chong, LP Frambach, DA Cisneros, L Padilla, M Yee, EM Nakamura, T Walonker, AF Morales, R Nichols, T Huete, ME Liggett, PE Ober, RR QuillenThomas, B Williams, M Barr, CC Bloom, SM Greene, PJ Whittington, GK Martin, ME Watson, G JenkinsCurry, B Gilkey, LA Huelsman, S Burton, TC Mieler, WF Pulido, JS Reeser, FH Newman, JL Werner, KA Pisarzewicz, PJ Reinerio, NA Walloch, MLK Wilmer, Z Laabs, J Picchiottino, R Phillips, J Wipplinger, W Abrams, GW Jurkiewicz, DT Leet, ML Mandel, P Metzger, K Suchla, L Zarling, D Balles, MW Ryan, EH Knobloch, WH Cook, SM Luke, DG Ferrieri, P Schiminsky, NM Genia, A Philiph, DA Stinson, EK Wright, LM McMichael, WC Mielke, SJ Ponwith, LJ Pavan, PR Pautler, SE Coats, ML Kirk, NM Millard, SM Castellano, FC Edwards, CR Marquardt, A McCormack, AJ McCormick, MT Renshaw, B Restuccia, A Campbell, M Christopher, N Garrett, LS Halkias, DG Hothersall, K MIckler, K Minnick, TS Burr, C Saxon, W Arcacha, MA Carlton, S Edison, SK Mallis, MJ Sayers, TL Sudds, TW Tiberia, RJ Wolabaugh, S Bradford, RH Parke, DW Wolf, TC Shofner, JM Tobey, LE Jensen, HG Sanchez, D Shofner, J Burris, R Drake, KK Grissom, KR Rowsey, JJ Wilkinson, CP Brown, GC Benson, WE Federman, JL Lucier, AC Maguire, JI Sarin, LK Shakin, EP Sivalingam, A Tasman, W Vander, JF Ward, N Weisbecker, CA Agnew, CL Lambert, R Tomer, T Carlson, K Franchine, G Serfass, MS Doft, BH Bergren, RL Lobes, LA Olsen, KR Rinkoff, JS Metz, DJ Leonard, MN Karenchak, LM Kowalski, RP Wellman, LA Wilcox, LA Campbell, AF Steinberg, DR Vagstad, GL Flook, KA Good, MM Keenen, BJ Mellinger, KA Margherio, RR Cox, MS Murphy, PL Trese, MT Werner, JC Williams, GA Manatrey, PE Prote, JL Lucarotti, R Martin, S Band, J Bostic, G Cumming, K Mitchell, B Regan, VS Bridges, C Cox, S Houston, G Johnson, J Streasik, P Wood, B Blumenkranz, MS Cayo, L Kaye, V Valenzuela, CL Orgel, IK Poliner, LS Tornambe, PE Cannon, SV Nielsen, JL Carlson, A Chan, P Drake, L Grim, M Peterson, C Borg, LA Gillyatt, J Beyer, C Hammer, ME Grizzard, WS Shannon, TL Traynom, JR Collado, MJ McManus, DW Sweeney, DE Adams, DH Watson, TT Antworth, MV Araos, JG Greenwald, MA Habib, M Myers, SK Ockers, KM Thibodeau, JA Watkins, B Nelsen, PT Rosenthal, JG Mintz, FV Biedenbach, M Leonardy, NJ Lawniczak, SM Bork, C Hageage, G Hunter, EB Marshall, MJ Roman, P Hill, R HOfbauer, T Lemanowicz, J Cupples, HP Guzman, GI Brodeur, RJ Yee, D Delaha, EC Geyer, SL Slovis, S Shields, WJ Lauber, S Michelitsch, K Barza, M Kassoff, A Watling, S Wilson, LA Buehler, JC McVay, J Kelsey, SF Wisniewski, SR Podobinski, GK Sillett, RL Groer, S Avery, B Belle, SH Boles, J Henry, L Shema, SJ TitusErnstoff, L Davis, M Magli, YL Hubbard, L Thomas, S Everett, DF Mowery, R Davis, K Azen, S Covey, P McCuen, B Packer, A Robbin, J TI Microbiologic factors and visual outcome in the endophthalmitis vitrectomy study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID STAPHYLOCOCCUS-EPIDERMIDIS ENDOPHTHALMITIS; COAGULASE-NEGATIVE STAPHYLOCOCCI; INFECTIOUS ENDOPHTHALMITIS; MANAGEMENT; SPECTRUM AB PURPOSE: To evaluate the relationship between microbiologic factors, effect of treatment, and visual outcome in the Endophthalmitis Vitrectomy Study. METHODS: Four hundred twenty patients were enrolled in the Endophthalmitis Vitrectomy Study between February 1990 and January 1994. Of these, 394 completed 9 to 12 months of follow-up. Patients presented with features of bacterial endophthalmitis within 6 weeks of cataract extraction or secondary intraocular lens implantation. The relations between visual outcome and the identity of infecting species, gram stain results, antibiotic susceptibilities, and presence of vitrectomy cassette growth were examined. RESULTS: Rates of achieving final visual acuity of 20/100 or better for the more common isolates were as follows: gram-positive, coagulase-negative micrococci, 84%; Staphylococcus aureus, 50%; streptococci, 30%; enterococci, 14%; and gram-negative organisms, 56%. A positive gram stain or infection with species other than gram-positive, coagulase-negative micrococci were significantly associated with poorer visual outcome (P <.001 for species group comparisons). However, presenting visual acuity was more powerful than microbiologic factors in predicting visual outcome and favorable response to vitrectomy. Bacterial growth from the vitrectomy cassette specimen had prognostic significance equivalent to growth from other intraocular sources. CONCLUSIONS: Visual prognosis was strongly associated with the type of infecting organism and gram stain positivity. However, visual acuity at initial presentation appeared to be more useful than microbiologic factors in predicting visual outcome and judging the value of immediate vitrectomy in acute bacterial endophthalmitis after cataract surgery. C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. EMORY EYE CTR,ATLANTA,GA. UNIV MARYLAND,EYE ASSOCIATES,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,BALTIMORE,MD. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RETINA GRP WASHINGTON,CHEVY CHASE,MD. RUSH UNIV,INGALLS HOSP,CHICAGO,IL 60612. RETINA ASSOCIATES CLEVELAND INC,CLEVELAND,OH. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV MINNESOTA,EDINA,MN. RETINA VITREOUS CTR PA,EDISON,NJ. UNIV FLORIDA,GAINESVILLE,FL. PENN STATE UNIV,HERSHEY,PA 17033. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV SO CALIF,LOS ANGELES,CA. UNIV LOUISVILLE,KENTUCKY LIONS EYE RES INST,LOUISVILLE,KY 40292. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV S FLORIDA,TAMPA,FL. DEAN A MCGEE EYE INST,OKLAHOMA CITY,OK. THOMAS JEFFERSON UNIV,WILLS EYE HOSP,PHILADELPHIA,PA 19107. RETINA VITREOUS CONSULTANTS,PITTSBURGH,PA. ASSOCIATED RETINAL CONSULTANTS,ROYAL OAK,MI. RETINA CONSULTANTS,SAN DIEGO,CA. UNIV S FLORIDA,TAMPA,FL. RETINA CONSULTANTS NE OHIO,TOLEDO,OH. RETINA VITREOUS ASSOCIATES INC,TOLEDO,OH. GEORGETOWN UNIV,WASHINGTON,DC. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV WISCONSIN,MADISON,WI. NEI,PROGRAM OFF,BETHESDA,MD 20892. WASHINGTON UNIV,SAFETY & DATA MONITORING COMM,ST LOUIS,MO. UNIV SO CALIF,SAFETY & DATA MONITORING COMM,LOS ANGELES,CA 90089. CARNEGIE MELLON UNIV,SAFETY & DATA MONITORING COMM,PITTSBURGH,PA 15213. DUKE UNIV,CTR EYE,SAFETY & DATA MONITORING COMM,DURHAM,NC. UNIV ILLINOIS,SAFETY & DATA MONITORING COMM,CHICAGO,IL 60680. NIH,SAFETY & DATA MONITORING COMM,BETHESDA,MD 20892. UNIV PITTSBURGH,SAFETY & DATA MONITORING COMM,PITTSBURGH,PA. UNIV WISCONSIN,SAFETY & DATA MONITORING COMM,MADISON,WI 53706. RI Rice, Treva/D-1385-2009 NR 23 TC 119 Z9 125 U1 0 U2 9 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 DEC PY 1996 VL 122 IS 6 BP 830 EP 846 PG 17 WC Ophthalmology SC Ophthalmology GA VW758 UT WOS:A1996VW75800009 ER PT J AU Kupfer, C AF Kupfer, C TI The expanded role of randomized clinical trials SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material RP Kupfer, C (reprint author), NEI,NIH,BLDG 31,ROOM 6A03,31 CTR DR,MSC 2510,BETHESDA,MD 20892, USA. NR 0 TC 10 Z9 10 U1 0 U2 1 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 DEC PY 1996 VL 122 IS 6 BP 883 EP 885 PG 3 WC Ophthalmology SC Ophthalmology GA VW758 UT WOS:A1996VW75800015 PM 8956644 ER PT J AU Whitcup, SM Iwata, F Podgor, MJ Valle, D Sran, PK KaiserKupfer, MI AF Whitcup, SM Iwata, F Podgor, MJ Valle, D Sran, PK KaiserKupfer, MI TI Association of thyroid disease with retinitis pigmentosa and gyrate atrophy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To compare the prevalence of thyroid disease in patients with retinitis pigmentosa, in patients with gyrate atrophy of the choroid and retina, and in patients with no history of ocular disease. METHOD: Forty four patients with retinitis pig mentosa, 34 patients with gyrate atrophy, and 30 normal control patients with no ocular disease were evaluated in a case control study for the presence of thyroid disease. RESULTS: Thyroid disease was diagnosed in six of 44 patients with retinitis pigmentosa and seven of 34 patients with gyrate atrophy but in only one of 30 control patients. Compared with control patients, the odds ratio for the occurrence of thyroid disease was 6.2 for patients with retinitis pigmentosa and 12.7 for patients with gyrate atrophy. CONCLUSION: These data suggest an increased occurrence of thyroid disease in patients with retinitis pigmentosa and gyrate atrophy. C1 JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,GENET LAB,BALTIMORE,MD 21218. RP Whitcup, SM (reprint author), NEI,NIH,10 CTR DR,BLDG 10,RM 10N 202,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 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 DEC PY 1996 VL 122 IS 6 BP 903 EP 905 PG 3 WC Ophthalmology SC Ophthalmology GA VW758 UT WOS:A1996VW75800026 PM 8956655 ER PT J AU Lubensky, IA Gnarra, JR Bertheau, P Walther, MM Linehan, WM Zhuang, ZP AF Lubensky, IA Gnarra, JR Bertheau, P Walther, MM Linehan, WM Zhuang, ZP TI Allelic deletions of the VHL gene detected in multiple microscopic clear cell renal lesions in von Hippel Lindau disease patients SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; CARCINOMA; CHROMOSOME-3; PATHOLOGY; MUTATIONS; SURGERY; REGION AB Patients with von Hippel-Lindau (VHL) disease develop a spectrum of bilateral clear-cell renal lesions including cysts and renal cell carcinomas (RCCs). VHL gene deletions have been previously reported in VHL-associated macroscopic RCC. Although histological analysis suggests that microscopic cystic lesions in the VHL patients may represent precursors of the RCC, there is at present no direct molecular evidence of their relationship. To investigate the relationship between cystic lesions and RCC, 26 microdissected archival renal lesions from two VHL disease patients were studied for loss of heterozygosity at the VHL gene locus using polymerase chain reaction single-strand conformation polymorphism analysis. The renal lesions included 2 benign cysts, 5 atypical cysts, 5 microscopic RCCs in situ, 5 cysts lined by a single layer of cells, in which RCCs in situ were developing, and 2 microscopic and 7 macroscopic RCCs. Except for a single benign cyst, 25 of 26 renal lesions showed nonrandom allelic loss of the VHL gene. In either of the 2 patients, the same VHL allele was deleted in all of the lesions tested, indicating loss of the wild-type allele and retention of the inherited, mutated VHL allele. The results suggest that all clear-cell lesions in the VHL kidney represent neoplasms and that the loss of the VHL gene occurs early in their development. Atypical and benign cysts most likely represent the initial phenotype in malignant transformation to the RCC. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. HOP ST LOUIS,ANAT PATHOL LAB,PARIS,FRANCE. NR 21 TC 150 Z9 155 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 DEC PY 1996 VL 149 IS 6 BP 2089 EP 2094 PG 6 WC Pathology SC Pathology GA VW787 UT WOS:A1996VW78700027 PM 8952541 ER PT J AU Wang, W Merrill, MJ Borchardt, RT AF Wang, W Merrill, MJ Borchardt, RT TI Vascular endothelial growth factor affects permeability of brain microvessel endothelial cells in vitro SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE vascular permeability factor; blood-brain barrier; brain tumor ID TYROSINE KINASE; TUMOR ANGIOGENESIS; BINDING-SITES; HUMAN GLIOMAS; MODEL SYSTEM; RAT-TISSUES; BARRIER; EXPRESSION; RECEPTOR; VEGF AB Vascular endothelial growth factor (VEGF), which stimulates endothelial cell growth and induces hyperpermeability of the microvasculature, plays an important role in normal and tumor-vasculature development and tumor edema generation. In this study, we investigated the effect of VEGF on the permeability of cultured bovine brain microvessel endothelial cells (BMECs), an in vitro blood-brain barrier (BBB) model. We found that addition of purified VEGF to both the apical and basolateral sides of the BMEC monolayers increased the permeability of the monolayer to [C-14]sucrose (similar to 3-fold). A more significant increase in permeability was observed when VEGF was applied to the basolateral side of the monolayer (3-fold) than to the apical side (1.5-fold). The permeability-increasing activity of VEGF on the BMEC monolayers is both dose and time dependent. The VEGF-induced permeability increase in BMECs requires a long incubation time with VEGF, and the effect is durable. These results suggest that this cell culture system may be useful for exploring the role of VEGF in regulating the permeability of the BBB, for studying the mechanism of the permeability-increasing effect of VEGF on the endothelial cells, and for evaluating the strategies to regulate the activity of VEGF. C1 UNIV KANSAS, DEPT PHARMACEUT CHEM, SIMONS RES LABS, LAWRENCE, KS 66047 USA. NINCDS, SURG NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 39 TC 95 Z9 97 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 1996 VL 271 IS 6 BP C1973 EP C1980 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WA681 UT WOS:A1996WA68100023 ER PT J AU Shamburek, RD Zech, LA Cooper, PS Vandenbroek, JM Schwartz, CC AF Shamburek, RD Zech, LA Cooper, PS Vandenbroek, JM Schwartz, CC TI Disappearance of two major phosphatidylcholines from plasma is predominantly via LCAT and hepatic lipase SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE cholesteryl ester; lecithin-cholesterol acyltransferase; bile acid; compartmental model; lysophosphatidylcholine ID LECITHIN-CHOLESTEROL ACYLTRANSFERASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; HIGH-DENSITY LIPOPROTEIN; BILIARY PHOSPHATIDYLCHOLINES; RAT-LIVER; ESTERS; SPECIFICITY; METABOLISM; ACID; DEFICIENCY AB Metabolism of 1-stearoyl-2-arachidonyl-phosphatidylcholine (SAPC), a major phosphatidylcholine (PC) species in rat plasma, was compared with 1-palmitoyl-2-linoleoyl-PC (PLPC) metabolism. High-density lipoproteins containing SAPC and PLPC tracers labeled in the sn-2 fatty acid with H-3 and C-14 isotopes, respectively, were administered. The rats were depleted of endogenous bile acids and infused via the ileum with individual bile acids that ranged widely in hydrophobicity. The half-lives for SAPC and PLPC in plasma were 48 and 57 min, respectively. Most of the H-3 activity that disappeared from plasma at 1 h was found in the liver in 1-palmitoyl-2-arachidonyl-PC, SAPC, and 1-oleoyl-2-arachidonyl-PC, indicating phospholipase A(1) hydrolysis of plasma SAPC forming 2-arachidonyl-lysophosphatidylcholine, which was reacylated in the liver. Plasma PLPC also underwent phospholipase A(1) hydrolysis, as reported previously. The fraction of H-3 dose that accumulated in plasma cholesteryl arachidonate was two- to threefold higher than the fraction of C-14 dose in cholesteryl linoleate. Multicompartmental models for SAPC and PLPC were developed that included lysophosphatidylcholines and cholesteryl esters. Bile acids did not influence plasma PC metabolism. Lecithin-cholesterol acyltransferase and phospholipase A(1) (hepatic lipase) hydrolysis accounted for greater than or equal to 90% of the SAPC and PLPC that disappeared from plasma; SAPC and PLPC are comparable as substrates for hepatic lipase, but SAPC is preferred by lecithin-cholesterol acyltransferase. C1 VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT MED, DIV GASTROENTEROL, RICHMOND, VA 23298 USA. NHLBI, NIH, BETHESDA, MD 20892 USA. NR 30 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 1996 VL 271 IS 6 BP E1073 EP E1082 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA WA522 UT WOS:A1996WA52200018 ER PT J AU Bonner, JC Badgett, A Lindroos, PM Coin, PG AF Bonner, JC Badgett, A Lindroos, PM Coin, PG TI Basic fibroblast growth factor induces expression of the PDGF receptor-alpha on human bronchial smooth muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE smooth muscle cell hyperplasia; asthma; platelet-derived growth factor; receptor upregulation; inflammatory cytokines ID CHAIN MESSENGER-RNA; ALVEOLAR MACROPHAGES; SIGNAL TRANSDUCTION; UP-REGULATION; IN-VITRO; ASTHMA; BETA; PROLIFERATION; GENE; FIBROSIS AB Bronchial smooth muscle cell (SMC) hyperplasia is a key feature in the pathology of asthma. Platelet-derived growth factor (PDGF) isoforms are SMC mitogens. We investigated the effect of basic fibroblast growth factor (bFGF), transforming growth factor-beta 1 (TGF-beta 1), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) on the PDGF receptor system on human bronchial SMC from three different donors. bFGF induced gene expression of the PDGF alpha-receptor (PDGF-R alpha) approximately threefold without altering the PDGF beta-receptor (PDGF-R beta). IL-1 beta and TNF-alpha did not affect the PDGF receptor system. TGF-beta 1 downregulated PDGF-R alpha mRNA similar to 60% without changing PDGF-R beta mRNA levels. Receptor assays showed that bFGF increased the [I-125]PDGF-AA binding site approximately twofold, whereas TGF-beta 1 reduced [I-125]PDGF-AA binding similar to 60%. TGF-beta 1, but not latent TGF-beta 1, counteracted the bFGF-induced increase in [I-125]PDGF-AA binding. PDGF-AA-stimulated tyrosine phosphorylation on the PDGF-R alpha was enhanced after treatment with bFGF. bFGF pretreatment enhanced the mitogenic response of SMC to PDGF-AA and PDGF-AB. These findings suggest that upregulation of the PDGF-R alpha by bFGF could contribute to SMC hyperplasia during chronic airway inflammation in asthma. C1 VET AFFAIRS MED CTR, DURHAM, NC 27705 USA. RP Bonner, JC (reprint author), NIEHS, PULM PATHOBIOL LAB, AIRWAY INFLAMMAT SECT, MAILDROP D2-02, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 35 TC 40 Z9 41 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD DEC PY 1996 VL 271 IS 6 BP L880 EP L888 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA VZ650 UT WOS:A1996VZ65000002 PM 8997257 ER PT J AU Guzman, K Gray, TE Yoon, JH Nettesheim, P AF Guzman, K Gray, TE Yoon, JH Nettesheim, P TI Quantitation of mucin RNA by PCR reveals induction of both MUC2 and MUC5AC mRNA levels by retinoids SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE reverse transcriptase polymerase chain reaction; vitamin A; retinoic acid; retinol; tracheobronchial ID POLYMERASE CHAIN-REACTION; EPITHELIAL-CELLS; MESSENGER-RNA; VITAMIN-A; GENE-EXPRESSION; IN-VITRO; AMPLIFICATION; TITRATION; CLONING; CDNA AB The polydispersity of most human secretory mucin messages has made them difficult to detect specifically and quantitatively, impeding the evaluation of the relative expression of the various mucin genes and their role in normal and pathological conditions. For this reason, we developed competitive reverse transcriptase-polymerase chain reaction (PCR) methods to measure the airway mucins MUC2 and MUC5AC. Oligonucleotide pairs were designed that specifically detect MUC2 and MUC5AC, as demonstrated by the size and sequence of the PCR product and the expected tissue distribution. The mucin oligonucleotide primers were used to synthesize internal competitive standards, called MIMIC. Using this assay, the relative expression of these messages was analyzed in retinoid-replete or -deprived cultures of normal human tracheobronchial epithelial (NHTBE) cells. Retinoid deficiency induces squamous metaplasia in vivo and in vitro. Consistent with these observations and in contrast to a previous report, retinoid-deprived cultures produced at least an order of magnitude less MUC2 and MUC5AC message than retinoid-replete cultures. In summary, this paper describes methodology that can be applied to the specific and quantitative measurement of mucin messages and demonstrates that, in NHTBE cells, the level of MUC2 and MUC5AC mRNA is increased by retinoids. RP Guzman, K (reprint author), NIEHS, PULM PATHOBIOL LAB, POB 12233, LPP, MD D2-03, RES TRIANGLE PK, NC 27709 USA. RI Yoon, Joo-Heon/E-5781-2016 NR 24 TC 49 Z9 50 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD DEC PY 1996 VL 271 IS 6 BP L1023 EP L1028 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA VZ650 UT WOS:A1996VZ65000019 ER PT J AU Klein, SL Taymans, SE DeVries, AC Nelson, RJ AF Klein, SL Taymans, SE DeVries, AC Nelson, RJ TI Cellular immunity is not compromised by high serum corticosterone concentrations in prairie voles SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE arvicoline rodent; house mouse; adrenal; spleen; immunology ID HORMONE-BINDING GLOBULIN; GLUCOCORTICOID RECEPTOR; LYMPHOCYTE-PROLIFERATION; CORTISOL; RESISTANCE; INHIBITION; INTERLEUKIN-1; DISEASE; MOUSE; RATS AB Glucocorticoids compromise immune function in glucocorticoid-sensitive species (e.g., mice), but these immunosuppressive effects may be reduced in glucocorticoid-resistant species. Prairie voles (Microtus ochrogaster) have been characterized as glucocorticoid-resistant to their high circulating levels of corticosterone. Because glucocorticoid-sensitive species display suppressed lymphocyte proliferation in response to elevated blood glucocorticoid levels, proliferative values were hypothesized to be reduced in house mice (Mus musculus) compared with prairie voles. Prairie voles exhibited significantly higher splenocyte proliferative responses to the T cell mitogen, Concanavalin A, despite having higher basal total and free serum corticosterone levels than mice. Neither total nor free serum corticosterone correlated with proliferative responses from either species. These data provide further evidence for glucocorticoid resistance in prairie voles and suggest that the interactions between the hypothalamic-pituitary-adrenal axis and the immune system in prairie voles may differ from those in mice or other glucocorticoid-sensitive species. Therefore, prairie voles may serve as a valuable animal model for the syndrome of glucocorticoid resistance in humans and the role of glucocorticoids in conditions characterized by a hyperactive immune system. C1 JOHNS HOPKINS UNIV, DEPT POPULAT DYNAM, BALTIMORE, MD 21218 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Klein, SL (reprint author), JOHNS HOPKINS UNIV, DEPT PSYCHOL, BEHAV NEUROENDOCRINOL GRP, BALTIMORE, MD 21218 USA. NR 41 TC 14 Z9 14 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 1996 VL 271 IS 6 BP R1608 EP R1613 PG 6 WC Physiology SC Physiology GA WB876 UT WOS:A1996WB87600020 ER PT J AU Stonestreet, BS Patlak, CS Pettigrew, KD Reilly, CB Cserr, HF AF Stonestreet, BS Patlak, CS Pettigrew, KD Reilly, CB Cserr, HF TI Ontogeny of blood-brain barrier function in ovine fetuses, lambs, and adults SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE brain; blood-brain barrier permeability; sheep; alpha-aminoisobutyric acid ID ALPHA-AMINOISOBUTYRIC-ACID; CARDIOPULMONARY-RESUSCITATION; TRANSPORT; RAT; ELECTROLYTES; PERMEABILITY; CAPILLARIES; INTEGRITY; CORTEX; GROWTH AB The ontogeny of regional blood-brain barrier function was quantified with the rate constant for influx (K-i) across the blood-brain barrier with the small molecular weight synthetic, inert hydrophilic amino acid alpha-aminoisobutyric acid (AIB) in chronically instrumented early (87 days of gestation, 60% of gestation) and late (137 days of gestation, 90% of gestation) gestation fetal, newborn (3 days of age), older (24 days of age), and adult (3 years of age) sheep. The K-i was significantly (P < 0.05) lower int he brain regions of the adult sheep and in most brain regions of newborn and older lambs compared with fetuses at 60 and 90% of gestation. The K-i exhibited regional brain heterogeneity (P < 0.05) in the five groups. The patterns of regional heterogeneity were accentuated (P < 0.05) in the younger groups. We conclude that ontogenic decreases in blood-brain barrier permeability are observed in ovine fetuses from 60% of gestation of maturity in the adult. C1 BROWN UNIV, SCH MED, DEPT PEDIAT, PROVIDENCE, RI 02905 USA. SUNY STONY BROOK, DEPT SURG, STONY BROOK, NY 11794 USA. NIMH, DIV EPIDEMIOL & SERV RES, BETHESDA, MD 20892 USA. RP Stonestreet, BS (reprint author), BROWN UNIV, WOMEN & INFANTS HOSP,SCH MED,DEPT PEDIAT, SECT PHYSIOL, 101 DUDLEY ST, PROVIDENCE, RI 02905 USA. NR 35 TC 71 Z9 71 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 1996 VL 271 IS 6 BP R1594 EP R1601 PG 8 WC Physiology SC Physiology GA WB876 UT WOS:A1996WB87600018 ER PT J AU Masereeuw, R Russel, FGM Miller, DS AF Masereeuw, R Russel, FGM Miller, DS TI Multiple pathways of organic anion secretion in renal proximal tubule revealed by confocal microscopy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE fluorescein; killifish; methotrexate; sodium-independent transport; sulforhodamine 101; image analysis ID FLUORESCEIN TRANSPORT; CANALICULAR MEMBRANE; MULTIDRUG-RESISTANCE; METHOTREXATE; INHIBITION; CELLS; MECHANISMS; INVITRO; MONKEY; RAT AB Previous studies with p-aminohippurate (PAH) and fluorescein (FL) have shown that cellular uptake and tubular secretion of organic anions is driven by indirect coupling to sodium. Here we used killifish proximal tubules and laser-scanning confocal microscopy to study the transport of a larger organic anion, fluorescein-methotrexate (FL-MTX, mol mass 923 Da). When tubules were incubated in medium containing 2 mu M FL-MTX, dye accumulated in both cells and tubular lumens. At steady state, luminal fluorescence was 4-5 times higher than cellular fluorescence. Ouabain (0.1 mM) did not affect cellular or luminal fluorescence, and replacement of medium sodium by N-methylglucamine had only a modest effect; preincubation with glutarate had no effect. KCN did not affect cellular uptake but abolished secretion into the lumen. Uptake and secretion of FL-MTX were inhibited by micromolar concentrations of other organic anions (MTX, folate, probenecid, bromocresol green, bromosulfophthalein), but 1 mM PAH had a relatively small effect. FL-MTX secretion into the lumen was inhibited by leukotriene C-4, cyclosporine A, and verapamil, none of which affected FL transport. Thus a substantial component of FL-MTX secretion is Na independent and ouabain insensitive. Both the basolateral and luminal steps in the Na-independent pathway differ from those usually associated with FL and PAH secretion. C1 NIEHS, PHARMACOL & CHEM LAB, NIH, INTRACELLULAR REGULAT SECT, RES TRIANGLE PK, NC 27709 USA. UNIV NIJMEGEN, FAC MED SCI, DEPT PHARMACOL, NL-6500 HB NIJMEGEN, NETHERLANDS. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014 OI Russel, Frans/0000-0002-7959-2314; NR 29 TC 59 Z9 59 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD DEC PY 1996 VL 271 IS 6 BP F1173 EP F1182 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA WA678 UT WOS:A1996WA67800009 ER PT J AU Bertolino, A Nawroz, S Mattay, VS Barnett, AS Duyn, JH Moonen, CTW Frank, JA Tedeschi, G Weinberger, DR AF Bertolino, A Nawroz, S Mattay, VS Barnett, AS Duyn, JH Moonen, CTW Frank, JA Tedeschi, G Weinberger, DR TI Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; HUMAN BRAIN; IN-VIVO; CORTEX; ABNORMALITIES; HIPPOCAMPUS; METABOLITES; CHOLINE AB Objective: Several single-voxel proton magnetic resonance spectroscopy (H-1-MAS) studies of patients with schizophrenia have found evidence of reductions of N-acetyl-aspartate (NAA) concentrations in the temporal lobes. Multislice proton magnetic resonance spectroscopy imaging (H-1-MRSI) permits simultaneous acquisition and mapping of NAA, choline-containing compounds (CHO), and creatine/phosphocreatine (CRE) signal intensities from multiple whole brain slices consisting of 1.4-ml single-volume elements. We have used H-1-MRSI to assess the regional specificity of previously reported changes of metabolite signal intensities in schizophrenia. Hippocampal volume was also measured to test the relationship between H-1-MRSI findings and tissue volume in this region. Method: Ratios of areas under the metabolite peaks of she proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions in 10 inpatients with schizophrenia. Results: Patients showed significant reductions of NAA/CRE and NAA/CHO bilaterally in the hippocampal region and in the dorsolateral prefrontal cortex. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios in the hippocampal region and its volume. Conclusions: NAA-relative signal intensity reductions in schizophrenia appear to be remarkably localized, involving primarily she hippocampal region and the dorsolateral prefrontal cortex, two regions implicated prominently in the pathophysiology of this disorder. C1 NIMH, ST ELIZABETHS HOSP,CTR NEUROSCI, INTRAMURAL RES PROGRAMS,CLIN BRAIN DISORDERS BRAN, WASHINGTON, DC 20032 USA. NINCDS, NEUROIMAGING BRANCH, BETHESDA, MD 20892 USA. NIH, LAB DIAGNOST RADIOL RES, BETHESDA, MD 20892 USA. NIH, OFF DIRECTOR, BETHESDA, MD 20892 USA. NIH, IN VIVO NMR CTR, BETHESDA, MD 20892 USA. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016; Bertolino, Alessandro/O-6352-2016 OI Moonen, Chrit/0000-0001-5593-3121; Bertolino, Alessandro/0000-0002-1251-1380 NR 55 TC 222 Z9 224 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 1996 VL 153 IS 12 BP 1554 EP 1563 PG 10 WC Psychiatry SC Psychiatry GA VV491 UT WOS:A1996VV49100009 PM 8942451 ER PT J AU Pickar, D Su, TP Weinberger, DR Coppola, R Malhotra, AK Knable, MB Lee, KS Gorey, J Bartko, JJ Breier, A Hsiao, J AF Pickar, D Su, TP Weinberger, DR Coppola, R Malhotra, AK Knable, MB Lee, KS Gorey, J Bartko, JJ Breier, A Hsiao, J TI Individual variation in D-2 dopamine receptor occupancy in clozapine-treated patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; FREE SCHIZOPHRENIC-PATIENTS; PLASMA HOMOVANILLIC-ACID; I-123 IBZM; CLINICAL-RESPONSE; ATYPICAL NEUROLEPTICS; ANTIPSYCHOTIC-DRUGS; IMAGING AGENT; BASAL GANGLIA; HUMAN-BRAIN AB Objective: The objectives of this study were 1) to pursue the question of clozapine's striatal D-2 occupancy in relation to its clinical effectiveness; 2) to investigate the relation between schizophrenic symptoms, clozapine blood levels, and estimated D-2 occupancy during clinically stable and unstable conditions; and 3) to eh amine long-term stability in D-2 occupancy. Method: Specific binding of the D-2 radioligand [I-123]benzamide [I-123]IBZM) was studied with single photon emission computed tomography in 13 patients with schizophrenia when they were clinically stable during chronic clozapine treatment, after clozapine dose reduction of greater than or equal to 50%, and in a subgroup (N=7) after restabilization on clozapine regimens. Clozapine's estimated D-2 occupancy was based on comparison with values from drug-free normal subjects. Results: A wide range of estimated D-2 occupancies (18% to greater than or equal to 80%) were associated with sustained, favorable response to clozapine without correlation with residual symptoms. Clonzapine blood levels were negatively related to [(123)]IBZM specific binding. Acute dose reduction was associated with predicted worsening in positive and negative symptoms and increases in [I-123]IBZM specific binding. Independent of clozapine blood level, patients with more symptoms showed lower [I-123]IBZM specific binding, consistent with competition of endogenous dopamine for D-2 binding sites in patients with greater symptoms. Restabilization on clozapine regimens produced D-2 Occupancies closely correlated with baseline values. Conclusions: There was no evidence for a critical degree of D-2 occupancy required to sustain clozapine's therapeutic effects across subjects. Simple linear regression was the best-fit model for clozapine's D-2 occupancy. Longitudinal follow-up suggests stability over time of D-2 occupancy in relation to dose and clinical response within individual patients. C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP Pickar, D (reprint author), NIMH,EXPT THERAPEUT BRANCH,BLDG 10,RM 4N212,BETHESDA,MD 20892, USA. NR 55 TC 51 Z9 52 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 DEC PY 1996 VL 153 IS 12 BP 1571 EP 1578 PG 8 WC Psychiatry SC Psychiatry GA VV491 UT WOS:A1996VV49100011 PM 8942453 ER PT J AU Turino, GM Barker, AF Brantly, ML Cohen, AB Connelly, RP Crystal, RG Eden, E Schluchter, MD Stoller, JK AF Turino, GM Barker, AF Brantly, ML Cohen, AB Connelly, RP Crystal, RG Eden, E Schluchter, MD Stoller, JK TI Clinical features of individuals with PI(*)SL phenotype of alpha(1)-antitrypsin deficiency SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID BRITISH-THORACIC-ASSOCIATION; PI-TYPE-SZ; ALPHA1-ANTITRYPSIN AB This report describes the clinical characteristics of a group of 59 individuals with the PI*SZ phenotype and alpha(1)-antitrypsin (alpha(1)-AT) deficiency, identified during recruitment of a registry for subjects with severe alpha(1)-antitrypsin deficiency, Currently, 1,129 individuals with levels of alpha(1)-AT of 11 mu M or below have been enrolled in this registry. individuals with the SZ phenotype whose alpha(1)-AT levels are at or below 11 mu M will be followed in the registry; those whose levels exceeded 11 mu M had baseline studies and are included in this report. Baseline pulmonary function tests included spirometry before and after an inhaled bronchodilator, diffusing capacity for carbon monoxide (DL(CO)), and chest roentgenograms. Among nonsmokers, subjects with the 52 phenotype demonstrated airflow obstruction less frequently than those with with the-ZZ phenotype. Among ex- and current smokers, the frequency and severity: of airflow obstruction was similar between Sf and 22 subjects. individuals with the 52 phenotype reported respiratory symptoms less frequently than did ZZ subjects. Overall, airflow obstruction was less common and milder among PI*SZ than PI*ZZ subjects. Cigarette smoking correlated more strongly with airflow obstruction among PI*SZ than PI*ZZ subjects. These observations indicate that in smokers, the PI*SZ phenotype confers a significant risk of the development of chronic obstructive pulmonary disease (COPD). Of itself, except in rare instances in nonsmoking individuals, the PI*SZ phenotype may confer little or no added risk of developing COPD. C1 OREGON HLTH SCI UNIV,DEPT PULM & CRIT CARE MED,PORTLAND,OR 97201. NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. UNIV TEXAS,CTR HLTH,DEPT MED,TYLER,TX 75710. CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT PULM & CRIT CARE MED,CLEVELAND,OH 44195. CORNELL UNIV,NEW YORK HOSP,MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY. RP Turino, GM (reprint author), COLUMBIA UNIV COLL PHYS & SURG,ST LUKES ROOSEVELT HOSP CTR,DEPT MED,1000 10TH AVE,NEW YORK,NY 10019, USA. FU NHLBI NIH HHS [N01-HR-86036] NR 15 TC 93 Z9 100 U1 0 U2 2 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 DEC PY 1996 VL 154 IS 6 BP 1718 EP 1725 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VY202 UT WOS:A1996VY20200023 PM 8970361 ER PT J AU Paakko, P Kirby, M duBois, RM Gillissen, A Ferrans, VJ Crystal, RG AF Paakko, P Kirby, M duBois, RM Gillissen, A Ferrans, VJ Crystal, RG TI Activated neutrophilis secrete stored alpha(1)-antitrypsin SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ALPHA-1-ANTITRYPSIN GENE; HUMAN-MONOCYTES; ELASTASE GENE; EXPRESSION; MYELOPEROXIDASE; IMMUNOGOLD; INHIBITOR; CELLS AB Neutrophil elastase (NE), a potent serine protease, is stored in primary granules of neutrophils and released following neutrophil activation. Alpha-1-antitrypsin (alpha(1)-AT), the major inhibitor of NE, is synthesized by mature neutrophils. In the context of the maintenance of tissue homeostasis, we hypothesized that neutrophils may be able to store alpha(1)-AT, thus having it available for release concordantly with NE. Immunofluorescence and quantitative flow-cytometric studies of neutrophils and monocytes labeled with fluorescein-conjugated alpha(1)-AT-anti body demonstrated larger amounts of cytoplasmic alpha(1)-AT in neutrophils than in monocytes. [S-35]methionine-labeling and anti-alpha(1)-AT immunoprecipitation analysis showed that although both neutrophils and monocytes synthesize alpha(1)-AT, the proportion of newly synthesized intracellular alpha(1)-AT was much higher in neutrophils than in monocytes. Flowcytometric analysis showed that in the presence of surface stimulation with cytochalasin B followed by formyl-methionyleucyIphenylalanine (fMLP), mean intracellular alpha(1)-AT was decreased in stimulated neutrophils compared with that in resting cells, suggesting that the stored alpha(1)-AT was rapidly released following surface triggering. Evaluation of surface-stimulated neutrophils by [S-35]methionine labeling and anti-alpha(1)-AT immunoprecipitation demonstrated increased secretion of alpha(1)-AT compared with that of resting neutrophils, with some of the secreted alpha(1)-AT capable of forming complexes with NE. Thus, neutrophils respond to surface stimulation not only by secreting NE but also by secreting its inhibitor, alpha(1)-AT, suggesting that these cells have an inherent mechanism for damping the local effects of NE, their most powerful proteolytic enzyme. C1 NHLBI,PATHOL SECT,BETHESDA,MD 20892. NHLBI,PULM BRANCH,BETHESDA,MD 20892. UNIV OULU,DEPT PATHOL,OULU,FINLAND. NR 32 TC 36 Z9 36 U1 0 U2 1 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 DEC PY 1996 VL 154 IS 6 BP 1829 EP 1833 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VY202 UT WOS:A1996VY20200039 PM 8970377 ER PT J AU Weinmann, GG Hyatt, R AF Weinmann, GG Hyatt, R TI Evaluation and research in lung volume reduction surgery SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; EMPHYSEMA; SMOKERS; PRESSURE C1 MAYO CLIN,DEPT MED,ROCHESTER,MN. RP Weinmann, GG (reprint author), NHLBI,DIV LUNG DIS,NIH,MSC7952,BETHESDA,MD 20892, USA. NR 21 TC 34 Z9 35 U1 0 U2 0 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 DEC PY 1996 VL 154 IS 6 BP 1913 EP 1918 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VY202 UT WOS:A1996VY20200048 PM 8970386 ER PT J AU Simeonova, PP Luster, MI AF Simeonova, PP Luster, MI TI Asbestos induction of nuclear transcription factors and interleukin 8 gene regulation SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; IDIOPATHIC PULMONARY FIBROSIS; TRACHEAL EPITHELIAL-CELLS; BRONCHOALVEOLAR LAVAGE; CROCIDOLITE ASBESTOS; ALVEOLAR MACROPHAGES; INFLAMMATORY CYTOKINES; RAT LUNG; EXPRESSION; ACTIVATION AB Proinflammatory cytokines and chemotactic peptides are strongly implicated as mediators of the pathophysiologic responses of asbestosis and other chronic inflammatory lung diseases. Recent studies in our laboratory have demonstrated that asbestos fibers stimulate lung epithelial cells to produce interleukin-8 (IL-8), the major neutrophil chemoattractant in the lung. The mechanisms by which asbestos regulates IL-8 expression were studied using the pulmonary type II-like epithelial cell line A549. Membrane permeable hydroxyl scavengers inhibited asbestos induced IL-8 expression. Using A549 cells transfected with the -546 IL-8 construct linked to a chloramphenicol acetyl transferase reporter gene, we have shown that these antioxidants directly inhibited asbestos-stimulated IL-8 promoter-dependent transcription. Asbestos fibers as well as reactive oxygen species generating systems hypoxanthine-xanthine oxidase and hydrogen peroxide stimulated DNA binding activity to the regulatory elements in the IL-8 promoter, binding sites of nuclear factor (NF)-kappa B- and NF-IL-6-like transcription factors. Asbestos-inducible DNA binding activity was partially inhibited by tetramethylthiourea, a hydroxyl radical scavenger. IL-8 secretion was also suppressed by staurosporine, an inhibitor of protein kinase C, and by inhibitors of tyrosine kinase such as herbimycin A and genistein. The suppression paralleled the effect of these inhibitors on asbestos-induced DNA binding to the NF-kappa B- and NF-IL-6-like binding sites of the IL-8 promoter. Taken together, the results suggest that asbestos-induced redox changes and phosphorylation events, mediated by staurosporine-sensitive and tyrosine kinase(s), activate nuclear proteins which recognize the NF-kappa B/NF-IL-6 binding sites of the IL-8 promoter and contribute to the regulation of IL-8 gene expression. C1 NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. RP Simeonova, PP (reprint author), NIOSH,HELD,TOXICOL & MOL BIOL BRANCH,1095 WILLOWDALE RD,MORGANTOWN,WV 26505, USA. NR 42 TC 73 Z9 76 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 1996 VL 15 IS 6 BP 787 EP 795 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA VY402 UT WOS:A1996VY40200013 PM 8969274 ER PT J AU Chow, CK McCarthy, JS Neafie, R Cooper, RI Limpuangthip, T Limpuangthip, P Nutman, TB AF Chow, CK McCarthy, JS Neafie, R Cooper, RI Limpuangthip, T Limpuangthip, P Nutman, TB TI Mammography of lymphatic filariasis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. WASHINGTON ADVENTIST HOSP,DEPT RADIOL,TAKOMA PK,MD 20812. WASHINGTON ADVENTIST HOSP,DEPT SURG,TAKOMA PK,MD 20812. WASHINGTON ADVENTIST HOSP,DEPT INTERNAL MED,INFECT DIS BRANCH,TAKOMA PK,MD 20812. RP Chow, CK (reprint author), NIH,DEPT DIAGNOST RADIOL,WARREN G MAGNUSON CLIN CTR,BLDG 10,RM 1C-660,10 CTR DR MSC 1182,BETHESDA,MD 20892, USA. NR 6 TC 6 Z9 6 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 DEC PY 1996 VL 167 IS 6 BP 1425 EP 1426 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VW769 UT WOS:A1996VW76900015 PM 8956571 ER PT J AU Kingma, DW Shad, A Tsokos, M Fest, T Otsuki, T Frekko, K Werner, E Werner, A Magrath, I Raffeld, M Jaffe, ES AF Kingma, DW Shad, A Tsokos, M Fest, T Otsuki, T Frekko, K Werner, E Werner, A Magrath, I Raffeld, M Jaffe, ES TI Epstein-Barr virus (EBV)-associated smooth-muscle tumor arising in a post-transplant patient treated successfully for two PT-EBV-associated large-cell lymphomas - Case report SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article ID LATENT MEMBRANE-PROTEIN; LYMPHOPROLIFERATIVE DISORDERS; HODGKINS-DISEASE; KAPOSIS-SARCOMA; DNA-SEQUENCES; NASOPHARYNGEAL CARCINOMA; AIDS; GENE; IDENTIFICATION; EXPRESSION AB The association of Epstein-Barr virus (EBV) with smooth-muscle tumors was recently reported in the setting of acquired immunodeficiency syndrome (AIDS) and post-transplantation. We report a case of an EBV-associated smooth-muscle tumor arising in a post-transplant (PT) patient who previously was treated successfully for two EBV-associated PT large-cell lymphomas. A 4-year-old girl required cardiac transplantation for dilated cardiomyopathy when she was aged 23 months. Her PT regimen included cyclosporine, azothiaprine, and diltiazem. At 16 months PT, she presented with anemia, guaiac-positive stools, and an abdominal mass diagnosed as diffuse large-cell lymphoma of B-cell phenotype. Immunosuppressive therapy was reduced, and interferon and i.v. immunoglobulin were initiated. She rapidly developed signs of rejection, and a cardiac biopsy was performed, revealing grade IIIB rejection. Subsequently, immunosuppressive therapy increased. At 23 months PT, a biopsy was done of a large pelvic mass that was diagnosed as immunoblastic large-cell lymphoma After treatment with chemotherapy and retinoic acid, the size of the mass markedly decreased. Follow-up computed tomography scan revealed multiple liver nodules. A needle biopsy of the liver showed a smooth-muscle tumor of indeterminate grade. Both the lymphomas and the smooth-muscle tumor contained EBV within >95% of tumor cells by Epstein-Barr (EBER1) in situ hybridization, were of strain type A by Epstein-Barr nuclear antigen-2 (EBNA-2) polymerase chain reaction (PCR) and contained an identical 30 base-pair deletion (amino acids 346-355) of the latent membrane protein (LMP)-1 oncogene by PCR analysis. Notably, the initial large-cell lymphoma and the subsequent immunoblastic lymphoma each contained a unique p53 mutation, suggesting that they were distinct. These data suggest that the same virus contributed to the pathogenesis of both the malignant lymphomas and the smooth-muscle tumor. C1 NCI,LYMPHOMA BIOL SECT,PEDIAT BRANCH,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. EASTERN VIRGINIA MED SCH,CHILDRENS HOSP KINGS DAUGHTERS,NORFOLK,VA 23501. RP Kingma, DW (reprint author), NCI,HEMATOPATHOL SECT,PATHOL LAB,DIV CANC BIOL DIAG & CTR,NIH,BLDG 10,ROOM 2N110,BETHESDA,MD 20892, USA. NR 33 TC 47 Z9 48 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 1996 VL 20 IS 12 BP 1511 EP 1519 DI 10.1097/00000478-199612000-00011 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA VV544 UT WOS:A1996VV54400011 PM 8944045 ER PT J AU Contoreggi, C Cheskin, LJ Lange, WR AF Contoreggi, C Cheskin, LJ Lange, WR TI Acute hepatitis after clozapine administration SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID HEPATOTOXICITY; GLUTATHIONE; ALCOHOLICS AB The authors present a case report of a cocaine abuser who developed acute hepatitis and an extrapyramidal reaction after administration of clozapine, a novel dopamine antagonist. Previous clinical experience with clozapine is reviewed. Both clozapine and cocaine undergo hepatic metabolism, increasing the potential for hepatotoxicity in selected patients. The authors also review hepatic metabolism of biogenic amines, their central nervous system effects, and the pharmacologic effects of clozapine and other abused substances on bioamine metabolism. Substance abusers' high susceptibility to hepatotoxicity highlights the need for careful monitoring for this form of liver dysfunction when administering clozapine. RP Contoreggi, C (reprint author), NIDA,NIH,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 29 TC 16 Z9 16 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 1996 VL 5 IS 1 BP 5 EP 11 PG 7 WC Substance Abuse SC Substance Abuse GA TV374 UT WOS:A1996TV37400001 ER PT J AU ElHachimi, KH Cervenakova, L Brown, P Goldfarb, LG Rubenstein, R Gajdusek, DC Foncin, JF AF ElHachimi, KH Cervenakova, L Brown, P Goldfarb, LG Rubenstein, R Gajdusek, DC Foncin, JF TI Mixed features of Alzheimer disease and Creutzfeldt-Jakob disease in a family with a presenilin 1 mutation in chromosome 14 SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Article; Proceedings Paper CT World-Federation-of-Neurology-Research-Group-on-Dementia Meeting CY APR 18-19, 1995 CL MARRAKECH, MOROCCO SP World Federat Neurol Res Grp Dementia DE presenilin; Alzheimer disease; Creutzfeldt-Jakob disease; AD3 gene; PRNP gene; amyloid; prion ID STRAUSSLER-SCHEINKER DISEASE; AMYLOID PRECURSOR PROTEIN; PAIRED HELICAL FILAMENTS; NEUROFIBRILLARY TANGLES; MISSENSE MUTATIONS; PLAQUES; GENE; INDIANA; DEMENTIA; COEXISTENCE AB Alzheimer disease and Creutzfeldt-Jakob disease are both characterized by the onset in late-middle age of progressive dementia with a fatal outcome, and a degenerative neuropathology with neuronal loss and amyloid deposition. Whereas early studies underlined clinico-pathologic and genetic similarities between the two diseases, the more recent discovery of pathogenic mutations in genes on different chromosomes producing chemically distinct amyloids has emphasized their differences. We here describe a family with clinico-pathologic features of both diseases, including substantial cerebral deposition of both beta A4 and PrP amyloid proteins, in which the pathogenesis is linked to a mutation in codon 163 of the presenilin 1 (S182, AD3) gene on chromosome 14. C1 NINCDS,CNS STUDIES LAB,NIH,BETHESDA,MD 20892. NINCDS,LAB MOL & CELLULAR NEUROBIOL 3,NIH,BETHESDA,MD 20892. EPHE,LAB NEUROHISTOL,F-75006 PARIS,FRANCE. HOP LA PITIE SALPETRIERE,U106 INSERM,PARIS,FRANCE. INST BASIC RES DEV DISABIL,STATEN ISL,NY. NR 63 TC 17 Z9 17 U1 1 U2 1 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE, ENGLAND LA6 2LA SN 1350-6129 J9 AMYLOID JI Amyloid-Int. J. Exp. Clin. Investig. PD DEC PY 1996 VL 3 IS 4 BP 223 EP 233 DI 10.3109/13506129609014369 PG 11 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA VZ041 UT WOS:A1996VZ04100001 ER PT J AU Chan, KC Muschik, CM Issaq, HJ Garvey, KJ Generlette, PL AF Chan, KC Muschik, CM Issaq, HJ Garvey, KJ Generlette, PL TI High-speed screening of polymerase chain reaction products by capillary electrophoresis SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID DNA FRAGMENTS; LIQUID-CHROMATOGRAPHY; ZONE ELECTROPHORESIS; OLIGONUCLEOTIDES; SEPARATION; MUTATION AB In an effort to develop capillary electrophoresis (CE) for high-throughput polymerase chain reaction (PCR) molecular diagnostics, a method was developed to rapidly screen small PCR products of similar molecular weights. The assay of interest required the separation of two PCR products (375 and 400 bp) in an assay of TGF-beta(1) knockout mice to determine the genotype of neonates. Using a commercially available CE instrument, the two PCR products were separated in 12 min with a replaceable gel buffer, a 20-cm effective length DB-17 capillary, and 185 V/cm field strength. With the coinjection of a 20-bp ladder, the sizes of the PCR products were determined hom the electropherogram without using a calibration plot and curve-fitting program. Faster separation was obtained using the combination of a short effective length capillary and high field strength. The two PCR products were separated in 82 s with a 7-cm effective length capillary and 556 V/cm. A 60% buffer further reduced the separation time in about a minute. This high-speed separation, with minimum postrun data processing, is highly desirable for the high-throughput screening of PCR products using a single-capillary CE system. (C) 1996 Academic Press, Inc. C1 NCI, RECOMBINANT DNA LAB, SAIC FREDERICK, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. RP Chan, KC (reprint author), NCI, CHEM SYNTH & ANAL LAB, SAIC FREDERICK, FREDERICK CANC RES & DEV CTR, POB B, FREDERICK, MD 21702 USA. NR 25 TC 22 Z9 22 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 1 PY 1996 VL 243 IS 1 BP 133 EP 139 DI 10.1006/abio.1996.0491 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VX622 UT WOS:A1996VX62200017 PM 8954535 ER PT J AU Berlin, W Sauer, B AF Berlin, W Sauer, B TI In situ color detection of alpha-L-arabinofuranosidase, a ''no-background'' reporter gene, with 5-bromo-3-indolyl-alpha-L-arabinofuranoside SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID SEQUENCE AB We describe the synthesis and use of 5-bromo-3-indolyl-alpha-L-arabinofuranoside (5-BI-ara) for the detection of alpha-L-arabinofuranosidase in bacterial colonies. Since the product of 5-BI-ara hydrolysis is an intensely colored indigo precipitate, it is a useful substrate for in situ detection of alpha-L-arabinofuranosidase activity. Here we show that colonies of an Escherichia coli strain expressing a recombinant alpha-L-arabinofuranosidase gene from Streptomyces lividans are readily identified by visual inspection on bacterial plates containing 5-BI-ara. Use of 5-BI-ara should facilitate the detection of endogenous alpha-L-arabinofuranosidase activity in a variety of microorganisms. In addition, since alpha-L-arabinofuranosidase activity is not commonly found in a large number of bacteria, yeast, and animal cells, 5-BI-ara will be useful in exploring the use of genes coding for alpha-L-arabinofuranosidase as gene expression reporters in heterologous systems. (C) 1996 Academic Press, Inc. C1 NIDDKD,NIH,BETHESDA,MD 20892. NR 11 TC 10 Z9 10 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 1 PY 1996 VL 243 IS 1 BP 171 EP 175 DI 10.1006/abio.1996.0497 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VX622 UT WOS:A1996VX62200023 PM 8954541 ER PT J AU Stover, ES Goldschmidts, WL Grau, LE Mitnick, L Pequegnat, W Rausch, DM Vitiello, B AF Stover, ES Goldschmidts, WL Grau, LE Mitnick, L Pequegnat, W Rausch, DM Vitiello, B TI Perspectives from the National Institute of Mental Health: Preventing or living with AIDS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID HIV SEROPREVALENCE; CONDOM-USE; INTERVENTION; PREVALENCE; REDUCTION; INFECTION AB This article provides a succinct overview of the history and current and future research priorities of the office on AIDS at the National Institute of Mental Health (NIMH). Throughout its history and currently, the Office on AIDS has encouraged and supported research on primary prevention of human immunodeficiency virus (HIV) transmission, effects of HIV disease on the central nervous system, and coping with the sequelae of infection. Future directions for the NIMH include the dissemination of research findings to the community, investigation of mechanisms for involving and retaining participants in large-scale vaccine trials, and continued attention to the prevention of HIV transmission through behavior change. C1 NIMH,OFF AIDS,ROCKVILLE,MD 20857. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SOC BEHAVIORAL MEDICINE PI ROCKVILLE PA 103 S ADAMS ST, ROCKVILLE, MD 20850 SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD WIN PY 1996 VL 18 IS 1 BP 58 EP 60 DI 10.1007/BF02903940 PG 3 WC Psychology, Multidisciplinary SC Psychology GA UY096 UT WOS:A1996UY09600008 PM 24203644 ER PT J AU Masur, H Shelhamer, JH AF Masur, H Shelhamer, JH TI Outpatient management of HIV-related pneumonia - In response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID IMMUNODEFICIENCY-VIRUS INFECTION; PNEUMOCYSTIS-CARINII PNEUMONIA; TUBERCULOSIS RP Masur, H (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 1 PY 1996 VL 125 IS 11 BP 938 EP 939 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VV541 UT WOS:A1996VV54100017 ER PT J AU Grassi, G Marini, JC AF Grassi, G Marini, JC TI Ribozymes: Structure, function and potential therapy for dominant genetic disorders SO ANNALS OF MEDICINE LA English DT Review DE genetic diseases; mRNA suppression; ribozymes ID FIBROBLAST GROWTH-FACTOR; HEPATITIS-DELTA-VIRUS; SELF-CLEAVAGE REACTION; OSTEOGENESIS IMPERFECTA; HAMMERHEAD RIBOZYMES; CROUZON-SYNDROME; MARFAN-SYNDROME; RNA ENZYME; MEDIATED CLEAVAGE; MESSENGER-RNA AB Some dominant genetic disorders, viral processes and neoplastic disorders base their pathogenicity on the production of protein or proteins that negatively affect cellular metabolism or environment. Thus, the inhibition of the synthesis of those proteins should prevent the biological damage. A promising approach to decreasing the level of the abnormal protein(s) is represented by specific interference with gene expression at the level of mRNA. The specific suppression of the expression of an mRNA can be achieved by using ribozymes. Ribozymes are RNA molecules able to break and form covalent bonds within a nucleic acid molecule. These molecules, with even greater potential advantages than antisense oligodeoxynucleotides, are able to bind specifically and cleave an mRNA substrate. There are advantages to using ribozymes instead of antisense oligodeoxynucleotides. Ribozymes can inactivate the target RNA without relying on the host cell's machinery and they have the capacity to cleave more than one copy of the target RNA by dissociating from the cleavage products and binding to another target molecule. Most of the studies performed to date have described the use of ribozymes as therapeutic agents for viral and cancer diseases. However, some dominant genetic disorders may also benefit from this approach. This is the case for some connective tissue disorders such as osteogenesis imperfecta, Marfan syndrome and the craniosynostotic syndromes. C1 NICHHD,SECT CONNECT TISSUE DISORDERS,HERITABLE DISORDERS BRANCH,BETHESDA,MD 20892. NR 117 TC 18 Z9 19 U1 1 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0785-3890 J9 ANN MED JI Ann. Med. PD DEC PY 1996 VL 28 IS 6 BP 499 EP 510 DI 10.3109/07853899608999114 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA WC061 UT WOS:A1996WC06100005 PM 9017109 ER PT J AU Jacobs, JY Gallelli, JF AF Jacobs, JY Gallelli, JF TI Evaluation of antineoplastic drug package inserts from different countries SO ANNALS OF PHARMACOTHERAPY LA English DT Letter C1 NIH,WARREN G MAGNUSON CLIN CTR,OFF DIRECTOR,BETHESDA,MD 20892. RP Jacobs, JY (reprint author), HADASSAH MED ORG,KIRYAT HADASSAH,IL-91120 JERUSALEM,ISRAEL. NR 6 TC 0 Z9 0 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD DEC PY 1996 VL 30 IS 12 BP 1496 EP 1498 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VX904 UT WOS:A1996VX90400023 PM 8968467 ER PT J AU Xiao, W Player, MR Li, GY Zhang, WT Lesiak, K Torrence, PF AF Xiao, W Player, MR Li, GY Zhang, WT Lesiak, K Torrence, PF TI Synthesis and characterization of composite nucleic acids containing 2',5'-oligoriboadenylate linked to antisense DNA SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID 2-5A ANTISENSE; RNA TARGET; CHIMERAS AB Composite nucleic acids, known as 2-5A antisense chimeras, cause the 2-5A-dependent ribonuclease (RNase L) to catalyze the specific cleavage of RNA in cell free systems and in intact cells. Such 2-5A antisense chimeras are 5'-monophosphorylated, 2',5'-linked oligoadenylates covalently attached to antisense 3',5'-oligodeoxyribonucleotides by means of a linker containing two residues of 1,4-butanediol phosphate. Here we report a fully automated synthesis of 2-5A antisense chimeras on a solid support using phosphoramidite methodology with specific coupling time modifications and their subsequent purification by reverse-phase ion-pair and anion exchange HPLC, Purified 2-5A antisense chimeras were characterized by [H-1]NMR and [P-31]NMR, MALDIMS, and capillary gel electrophoresis, The synthetic 2',5'-linked oligoadenylate showed no phosphodiester isomerization to 3',5' during or after synthesis, In addition, we have developed facile methodologies to characterize the chimeras using digestion with various hydrolytic enzymes including snake venom phosphodiesterase I and nuclease P1. Finally, Maxam-Gilbert chemical sequencing protocols have been developed to confirm the entire sequence of these chimeric oligonucleotides. C1 NIDDK,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 21 TC 23 Z9 23 U1 0 U2 2 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 WIN PY 1996 VL 6 IS 4 BP 247 EP 258 DI 10.1089/oli.1.1996.6.247 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA WC495 UT WOS:A1996WC49500002 PM 9012860 ER PT J AU Tobin, GJ Ennis, WH Clanton, DJ Gonda, MA AF Tobin, GJ Ennis, WH Clanton, DJ Gonda, MA TI Inhibition of bovine immunodeficiency virus by anti-HIV-1 compounds in a cell culture-based assay SO ANTIVIRAL RESEARCH LA English DT Article DE bovine immunodeficiency virus; human immunodeficiency virus type 1; cell culture-based inhibition assay; antiviral compounds ID BIOLOGICALLY-ACTIVE PROVIRUSES; HIV PROTEASE INHIBITOR; REVERSE-TRANSCRIPTASE; VISNA VIRUS; MOLECULAR-CLONING; POTENT INHIBITOR; 2',3'-DIDEOXYNUCLEOSIDES; REPLICATION; INFECTION; TYPE-1 AB The bovine immunodeficiency virus (BIV) and human immunodeficiency virus types 1 and 2 (HIV-1 and -2) are members of the lentivirus genus of retroviruses. Although DNA sequences of these viruses have diverged considerably, the BIV genome organization, function of structural and regulatory genes, and replication cycle are very similar to that of HIV-1, making BIV a potentially useful model to study compounds with anti-HIV-l activity. A cell culture-based antiviral assay was developed to test compounds for inhibition of BIV replication. The assay uses an embryonic rabbit epithelial (EREp) cell line that is highly sensitive to BIV infection and cytopathology. The 50% effective concentrations (EC(50)) at which the virus was inhibited in EREp cells were determined for 13 nucleoside analog, non-nucleoside, tumor-suppressive, or membrane-surface inhibitory compounds. The nucleoside analogs (3'-azido-2',3'-dideoxythymidine, 2',3'-dideoxyinosine and 2',3'-dideoxycytosine), surface-membrane inhibitors (dextran sulfate, hypericin, Chicago Sky Blue and quinobene), the nucleoside reductase inhibitor (hydroxyurea), and a tumor-suppressive phorbol ester (prostratin) inhibited BIV with EC(50) values similar to those derived in HIV-1 lymphocyte (CD4(+))-based assays. BIV was markedly more resistant to inhibition with HIV-I-specific non-nucleoside reverse transcriptase inhibitors (NNRTIs) (thiazolobenzimidazole, oxathiin carboxanilide and thiocarbamate) than was HIV-1, which parallels results with NNRTIs in HIV-2 assays. C1 NCI,FREDERICK CANC RES & DEV CTR,AIDS DRUG SCREENING & DEV LAB,SAIC FREDERICK,FREDERICK,MD 21702. RP Tobin, GJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB CELL & MOL STRUCT,SAIC FREDERICK,FREDERICK,MD 21702, USA. NR 51 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD DEC PY 1996 VL 33 IS 1 BP 21 EP 31 DI 10.1016/S0166-3542(96)00990-4 PG 11 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA VV545 UT WOS:A1996VV54500003 PM 8955850 ER PT J AU Halliday, SM LackmanSmith, C Bader, JP Rice, WG Clanton, DJ Zalkow, LH Buckheit, RW AF Halliday, SM LackmanSmith, C Bader, JP Rice, WG Clanton, DJ Zalkow, LH Buckheit, RW TI Inhibition of human immunodeficiency virus replication by the sulfonated stilbene dye resobene SO ANTIVIRAL RESEARCH LA English DT Article DE human immunodeficiency virus; resobene; antiviral ID ANTI-HIV AGENT; REVERSE-TRANSCRIPTASE ACTIVITY; PRINCIPAL NEUTRALIZING DOMAIN; SOLUBLE CD4; ENVELOPE GLYCOPROTEINS; DEXTRAN SULFATE; CELL-LINES; TYPE-1; ENHANCEMENT; BINDING AB The anti-HIV sulfonated dye, resobene, was found to be a potent inhibitor of the attachment of HIV to target cells, the fusion of envelope- and CD4-expressing cells, and the cell-to-cell transmission of virus. Resobene inhibited the infection of phenotypically distinct, established human cell lines and fresh human peripheral blood lymphocytes and macrophages by laboratory-derived isolates of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), and a panel of biologically diverse primary clinical isolates, including syncytium-inducing and non-syncytium-inducing viruses and strains representative of the various virus clades found worldwide. The compound was also active against all drug-resistant virus isolates tested. Cell-based and biochemical mechanism of action studies demonstrated that the compound inhibits the attachment of infectious virus and fusion of virus-infected cells to uninfected target cells by binding to the cationic V3 loop of the envelope glycoprotein. Resobene effectively inhibited the infection of cell populations which do and do not express cell surface CD4. Resobene prevented infection of the cervical epithelial cell line ME180, suggesting the compound may effectively act as a topical microbicide to prevent the sexual transmission of HIV. C1 SO RES INST,FREDERICK RES CTR,VIROL RES GRP,FREDERICK,MD 21701. NCI,DIV CANC TREATMENT DIAG & CTR,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SAIC,LAB ANTIVIRAL DRUG MECH,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,ANTIAIDS VIRUS DURG SCREENING LAB,FREDERICK,MD 21702. GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332. FU NCI NIH HHS [N01-CM-37818] NR 32 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD DEC PY 1996 VL 33 IS 1 BP 41 EP 53 DI 10.1016/S0166-3542(96)00994-1 PG 13 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA VV545 UT WOS:A1996VV54500005 PM 8955852 ER PT J AU Mahmoodian, F Gosiewska, A Peterkofsky, B AF Mahmoodian, F Gosiewska, A Peterkofsky, B TI Regulation and properties of bone alkaline phosphatase during vitamin C deficiency in guinea pigs SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE alkaline phosphatase; osteocalcin; collagen; ascorbic acid; bone ID HUMAN-SKIN FIBROBLASTS; COLLAGEN-SYNTHESIS; MESSENGER-RNA; ASCORBIC-ACID; OSTEO-SARCOMA; SINGLE GENE; I COLLAGEN; RAT; EXPRESSION; KIDNEY AB The precise physiological role of alkaline phosphatase is unknown, although evidence suggests it is involved in bone mineralization. Previous studies showed that serum and bone alkaline phosphatase activity is decreased during vitamin C deficiency. Some effects of scurvy, such as inhibition of collagen synthesis, are related to weight loss and subsequent induction of insulin-like growth factor binding proteins and they can be duplicated in fasted guinea pigs receiving vitamin C, We found that decreased alkaline phosphatase activity in bone and serum during scurvy was not completely due to the ''fasting effect'' and that the decrease in serum was due to loss of bone isoenzyme activity, There also was a decrease in immunoreactive enzyme protein and alkaline phosphatase mRNA concentrations in bone of scorbutic animals, indicating that synthesis of the enzyme was inhibited, Sialylation and addition of the glycosylphosphatidylinositol anchor to the enzyme in bone tissue were not affected by scurvy, The concentration of mRNA for osteocalcin, a bone-specific marker, also fell during scurvy and to a much greater extent than either alkaline phosphatase or type I collagen mRNAs, while osteopontin mRNA concentrations increased. These results differ from the reported role of ascorbic acid on the pattern of expression of these proteins during differentiation of osteoblasts in culture. The decreased expression of collagen, alkaline phosphatase, and osteocalcin could explain the defects in bone caused by scurvy. (C) 1996 Academic Press, Inc. C1 NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 49 TC 25 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 1 PY 1996 VL 336 IS 1 BP 86 EP 96 DI 10.1006/abbi.1996.0535 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VW848 UT WOS:A1996VW84800011 PM 8951038 ER PT J AU Blauvelt, A AF Blauvelt, A TI Hepatitis C virus and human immunodeficiency virus infection can alter porphyrin metabolism and lead to porphyria cutanea tarda SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID NON-B-HEPATITIS; NON-A; LIVER-DISEASE; UNITED-STATES; ASSOCIATION; ANTIBODIES; PHOTOSENSITIVITY; MANIFESTATIONS; HIV RP Blauvelt, A (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,10 CTR DR MSC 1908,BETHESDA,MD 20892, USA. NR 34 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1996 VL 132 IS 12 BP 1503 EP 1504 DI 10.1001/archderm.132.12.1503 PG 2 WC Dermatology SC Dermatology GA VX641 UT WOS:A1996VX64100016 PM 8961882 ER PT J AU Kumra, S Frazier, JA Jacobsen, LK McKenna, K Gordon, CT Lenane, MC Hamburger, SD Smith, AK Albus, KE AlaghbandRad, J Rapoport, JL AF Kumra, S Frazier, JA Jacobsen, LK McKenna, K Gordon, CT Lenane, MC Hamburger, SD Smith, AK Albus, KE AlaghbandRad, J Rapoport, JL TI Childhood-onset schizophrenia - A double-blind clozapine-haloperidol comparison SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TARDIVE-DYSKINESIA; INDUCED AGRANULOCYTOSIS; WEIGHT-GAIN; OPEN TRIAL; ADOLESCENTS; CHILDREN; SEIZURES; PROGRESS; PATIENT; AGENTS AB Background: Childhood-onset schizophrenia is a rare bur severe form of the disorder that is often treatment-refractory. In this study, the efficacy and adverse effects of clozapine and haloperidol were compared for children and adolescents with early-onset schizophrenia. Methods: Twenty-one patients (mean [+/-SD] age, 14.0 +/- 2.3 years) with onset of Diagnostic an Statistical Manual of Mental Disorders, Revised Third Edition-defined schizophrenia that began by age 12 years and who had been nonresponsive to typical neuroleptics participated in the study. Patients were randomized to a 6-week double-blind parallel comparison of clozapine mean [+/-SD] final dose, 176 +/- 149 mg/d), or haloperidol, (16 +/- 8 mg/d). Results: Clozapine was superior to haloperidol on ail measures of psychosis (P = .04-.002). Positive and negative symptoms of schizophrenia improved. However, neutropenia and seizures were major concerns. To date, one third of the group has discontinued using clozapine. Conclusions: Clozapine has striking superiority for positive and negative symptoms in treatment-refractory childhood-onset schizophrenia. However, due to possibly increased toxic effects in this pediatric population, close monitoring for adverse events is essential. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. RP Kumra, S (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 68 TC 248 Z9 251 U1 3 U2 10 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 DEC PY 1996 VL 53 IS 12 BP 1090 EP 1097 PG 8 WC Psychiatry SC Psychiatry GA VX336 UT WOS:A1996VX33600002 PM 8956674 ER PT J AU Ferris, FL Murphy, RP AF Ferris, FL Murphy, RP TI The peril of the pilot study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID MACULAR DEGENERATION RP Ferris, FL (reprint author), NEI,BLDG 31,ROOM 6A52,30 CTR DR,BETHESDA,MD 20892, USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 1996 VL 114 IS 12 BP 1506 EP 1507 PG 2 WC Ophthalmology SC Ophthalmology GA VX337 UT WOS:A1996VX33700009 PM 8953984 ER PT J AU Hammond, EH Henson, DE Farrow, G Friedell, GH Gospodarowicz, M Heney, NM Herr, H Lerner, S Montie, JE Murphy, W Platz, C Prout, GR Shipley, WU Torti, F True, LD vonEschenbach, AC Coppock, DL Cunningham, MP Farrow, GM Gorstein, F Hutter, RVP Min, KW Nash, G Nielsen, ML Page, DL Rabson, AS Ruby, SG Scholosnagle, D Schwartz, IS Scully, RE Seiffert, J Smoron, GL Travers, H Webb, JH Weiss, LL Wick, MR AF Hammond, EH Henson, DE Farrow, G Friedell, GH Gospodarowicz, M Heney, NM Herr, H Lerner, S Montie, JE Murphy, W Platz, C Prout, GR Shipley, WU Torti, F True, LD vonEschenbach, AC Coppock, DL Cunningham, MP Farrow, GM Gorstein, F Hutter, RVP Min, KW Nash, G Nielsen, ML Page, DL Rabson, AS Ruby, SG Scholosnagle, D Schwartz, IS Scully, RE Seiffert, J Smoron, GL Travers, H Webb, JH Weiss, LL Wick, MR TI Practice protocol for the examination of specimens removed from patients with carcinoma of the urinary bladder, ureter, renal pelvis, and urethra SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID OF-AMERICAN-PATHOLOGISTS; SURGICAL PATHOLOGY; PROGNOSTIC FACTORS; CANCER-COMMITTEE; OVEREXPRESSION; CHECKLISTS AB This article details a practice protocol for the examination and reporting of specimens removed from patients with carcinoma of the urinary bladder, ureter, renal pelvis, or urethra. It was created by a multidisciplinary task force of pathologists and oncologists established by the Cancer Committee of the College of American Pathologists. Documentation for the protocol was obtained from the previously published protocol, the medical literature, personal experience, and consultation with colleagues. After creation and review by the task force, the protocol was sent to 1000 randomly selected practicing pathologists as a survey. Their comments and suggestions were addressed in the final version. The protocol was approved by the Board of Governors of the College of American Pathologists. C1 UNIV UTAH,SCH MED,SALT LAKE CITY,UT. NCI,EARLY DETECT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Hammond, EH (reprint author), LATTER DAY ST HOSP,DEPT PATHOL,8TH AVE & C ST,SALT LAKE CITY,UT 84143, USA. NR 25 TC 12 Z9 12 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 DEC PY 1996 VL 120 IS 12 BP 1103 EP 1110 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA WQ053 UT WOS:A1996WQ05300007 PM 15456174 ER PT J AU Ryu, JH Song, BJ Hong, S Huh, JW AF Ryu, JH Song, BJ Hong, S Huh, JW TI Purification and acetylation of protein X subunit of pyruvate dehydrogenase complex (PDC) from bovine kidney SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Article DE protein X; pyruvate dehydrogenase; purification; acetylation ID SACCHAROMYCES-CEREVISIAE; COMPONENT-X; KINASE; HEART; GENE AB Protein X is one of the subunits of pyruvate dehydrogenase complex. The biological role of this protein has not been fully elucidated, mainly because of the difficulty in its dissociation from the tightly bound dihydrolipoamide acetyltransferase-protein X subcomplex. We have found that the detachment of protein X from acetyltransferase subunit can be easily accomplished by the cycles of freezing and thawing process. Several lines of evidence including sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal amino acid sequence analysis and acetylation with [2-C-14] pyruvate confirmed that the purified protein is protein X. The purified intact form of protein X was acetylated by [2-C-14] pyruvate in the presence of pyruvate dehydrogenase subunit. The acetylation efficiency of this protein was lower than that of acetyltransferase and was not affected by the presence of acetyltransferase. C1 NIAAA, NEUROGENET LAB, ROCKVILLE, MD 20852 USA. SUNGKYUNKWAN UNIV, DEPT GENET ENGN, SUWON 440746, SOUTH KOREA. KOREA GREEN CROSS CORP, CENT RES INST, YONGIN KUN 449900, SOUTH KOREA. RP SOOKMYUNG WOMENS UNIV, COLL PHARM, YONGSAN KU, CHUNGNA DONG 2 KA, SEOUL 140742, SOUTH KOREA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU PHARMACEUTICAL SOC KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 EI 1976-3786 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD DEC PY 1996 VL 19 IS 6 BP 502 EP 506 DI 10.1007/BF02986019 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WA527 UT WOS:A1996WA52700013 ER PT J AU Curb, JD Masaki, K Rodriguez, BL Abbott, RD Burchfiel, CM Chen, RD Petrovitch, H Sharp, D Yano, K AF Curb, JD Masaki, K Rodriguez, BL Abbott, RD Burchfiel, CM Chen, RD Petrovitch, H Sharp, D Yano, K TI Peripheral artery disease and cardiovascular risk factors in the elderly - The Honolulu Heart Program SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE elderly; peripheral artery disease; risk factor ID BLOOD-PRESSURE INDEX; INTERMITTENT CLAUDICATION; WOMEN; MEN; ATHEROSCLEROSIS; POPULATION; MORTALITY; HAWAII AB Peripheral vascular disease as measured by the ankle/brachial blood pressure index (ABI) is associated with increased risk of mortality and morbidity. Few sources of data on the relationship of risk factors to ABI are available for the elderly, especially those >80 years of age, and minority populations. ABI measurements from the Honolulu Heart Program's fourth reexamination of 3450 ambulatory, elderly Japanese American men indicate that the prevalence of an abnormal ABI, defined as a ratio of <0.9, was 13.6%, increasing from 8.0% in those 71 to 74 years of age to 27.4% in those 85 to 93 years. Associations that were U or J shaped were present for a number of risk factors (higher rates of abnormality [ABI<0.9] in those in the lowest and highest risk factor quintiles) in a cross-sectional analysis. Risk factors measured at baseline were also predictive of an abnormal ABI 25 years later, even after adjustment for multiple risk factors. The odds ratio (OR) for an ABI<0.9 at the 80th percentile of cholesterol compared with that at the 20th percentile was 1.4; the OR for 1-hour postload glucose was 1.3, and for alcohol intake 1.2. The OR associated with hypertension was 1.8 and that for smoking, 2.9 (P<.05 for all ORs). These findings are consistent with ABI being a marker for generalized atherosclerotic disease in old and very old Japanese American men. C1 UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,DIV CLIN EPIDEMIOL,HONOLULU,HI 96822. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,DIV GERIATR MED,HONOLULU,HI 96822. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,BETHESDA,MD 20892. UNIV VIRGINIA,SCH MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22908. FU NHLBI NIH HHS [N01-HC-05102] NR 18 TC 62 Z9 66 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 DEC PY 1996 VL 16 IS 12 BP 1495 EP 1500 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA WA769 UT WOS:A1996WA76900012 PM 8977454 ER PT J AU Pras, E Schumacher, HR Kastner, DL Wilder, RL AF Pras, E Schumacher, HR Kastner, DL Wilder, RL TI Lack of evidence of mycobacteria in synovial tissue from patients with rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LYMPHOCYTES-T; RATS; DNA C1 HOSP UNIV PENN,PHILADELPHIA,PA 19104. NIAMSD,BETHESDA,MD. RP Pras, E (reprint author), CHAIM SHEBA MED CTR,IL-52621 TEL HASHOMER,ISRAEL. NR 8 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 1996 VL 39 IS 12 BP 2080 EP 2081 DI 10.1002/art.1780391221 PG 2 WC Rheumatology SC Rheumatology GA VX901 UT WOS:A1996VX90100020 PM 8961916 ER PT J AU Jensen, RT AF Jensen, RT TI Gastrinoma SO BAILLIERES CLINICAL GASTROENTEROLOGY LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA; ISLET-CELL-CARCINOMA; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; HEPATIC ARTERIAL CHEMOEMBOLIZATION; HUMAN GASTROINTESTINAL TISSUES; HELICOBACTER-PYLORI INFECTION; LONG-TERM TREATMENT; NEUROENDOCRINE TUMORS; PANCREATIC TUMORS RP Jensen, RT (reprint author), NIDDKD,DIGEST DIS BRANCH,NIH,BLDG 10,ROOM 9C-103,10 CTR DR,MSC 1804,BETHESDA,MD 20891, USA. NR 205 TC 24 Z9 24 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3528 J9 BAILLIERE CLIN GASTR JI Baillieres Clin. Gastroenterol. PD DEC PY 1996 VL 10 IS 4 BP 603 EP 643 DI 10.1016/S0950-3528(96)90016-0 PG 41 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WQ741 UT WOS:A1996WQ74100005 PM 9113315 ER PT J AU Horak, ID Kremer, AB Magrath, IT AF Horak, ID Kremer, AB Magrath, IT TI Management of histologically aggressive lymphomas with a high risk of CNS disease SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article ID T-CELL LEUKEMIA; NERVOUS-SYSTEM LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BONE-MARROW TRANSPLANTATION; NON-HODGKINS LYMPHOMAS; LYMPHOBLASTIC LYMPHOMA; BURKITTS-LYMPHOMA; RADIATION-THERAPY; INTERFERON-ALFA; ANTI-TAC C1 NCI,LYMPHOMA BIOL SECT,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. RP Horak, ID (reprint author), JANSSEN RES FDN,1125 TRENTON HARBOURTEN RD,TITUSVILLE,NJ 08650, USA. NR 60 TC 1 Z9 1 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD DEC PY 1996 VL 9 IS 4 BP 707 EP 726 DI 10.1016/S0950-3536(96)80050-3 PG 20 WC Hematology SC Hematology GA WM275 UT WOS:A1996WM27500006 PM 9138614 ER PT J AU Hyman, SE AF Hyman, SE TI Addiction: Taking the brain seriously SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Heyman's target article is an analytical tour de force, but it makes too hard a distinction between voluntary and riven behavior. It is more fruitful to think about brain and behavior as shifting, interacting ''agents,'' represented by multiple neural circuits. This has the virtue of better connecting behavioral analysis with wet neuroscience. C1 NIMH,ROCKVILLE,MD 20857. RP Hyman, SE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB MOL & DEV NEUROSCI,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 1996 VL 19 IS 4 BP 582 EP & PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA WY849 UT WOS:A1996WY84900012 ER PT J AU Lamb, ME AF Lamb, ME TI What is selected in group selection? SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Misunderstandings often develop when scientists from different backgrounds use the same words (e.g., ''selection'') when they mean different things by them. Theorists must therefore choose and define their terms carefully. In addition, proponents of ''new'' theories need to demonstrate empirically that theirs are more powerful than the existing theories they wish to supplant. Wilson & Sober have not yet done this. RP Lamb, ME (reprint author), NICHHD,BETHESDA,MD 20814, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 1996 VL 19 IS 4 BP 779 EP & PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA WY849 UT WOS:A1996WY84900102 ER PT J AU Westergaard, GC AF Westergaard, GC TI The lithic technology of Cebus apella and its implications for brain evolution and the preconditions of language in Homo habilis SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID CAPUCHIN MONKEYS; HANDEDNESS; MANIPULATION AB Wilkins & Wakefield (1995) provide a thoughtful contribution to our understanding of language origins. In this commentary I attempt to define the relationship between object-manipulation and primate brain function further by reviewing research on aimed throwing and the production and use of stone tools by tufted capuchin monkeys (Cebus apella). I propose that examining the relation between brain function and object-manipulating in Cebus will provide insight into the preconditions of language in our hominid ancestors. C1 NIH,ANIM CTR,POOLESVILLE,MD 20837. RP Westergaard, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD 20837, USA. NR 21 TC 1 Z9 1 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 1996 VL 19 IS 4 BP 792 EP & PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA WY849 UT WOS:A1996WY84900109 ER PT J AU Murray, EA Wise, SP AF Murray, EA Wise, SP TI Role of the hippocampus plus subjacent cortex but not amygdala in visuomotor conditional learning in rhesus monkeys SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID PREMOTOR CORTEX; FORNIX TRANSECTION; MEMORY SYSTEM; ASSOCIATION; LESIONS; REWARD; DISCONNECTION; DEFICITS; MOVEMENT; OBJECTS AB Rhesus monkeys were trained to learn a large series of visuomotor conditional associations, each involving the arbitrary coupling of a visual stimulus with 1 of 3 potentially correct forelimb movements. The monkeys then received bilateral aspiration lesions of either the amygdala plus subjacent cortex or the hippocampus plus subjacent cortex. Hippocampal but not amygdala removals significantly retarded the learning of new visuomotor associations. Neither lesion affected retention. The findings argue against a general role for the amygdala in associating information across modalities, construed broadly to include motor information. By contrast, the finding that the hippocampal formation and its subjacent cortex play a role in learning new sensorimotor associations supports the view that this region participates in the long-term storage of associative information or in the recall of recently acquired information. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD. RP Murray, EA (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 34 TC 61 Z9 62 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD DEC PY 1996 VL 110 IS 6 BP 1261 EP 1270 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA WA174 UT WOS:A1996WA17400005 PM 8986330 ER PT J AU Stratakis, CA Orban, Z Burns, AL Vottero, A Mitsiades, CS Marx, SJ Abbassi, V Chrousos, GP AF Stratakis, CA Orban, Z Burns, AL Vottero, A Mitsiades, CS Marx, SJ Abbassi, V Chrousos, GP TI Dideoxyfingerprinting (ddF) analysis of the type X collagen gene (COL10A1) and identification of a novel mutation (S671P) in a kindred with schmid metaphyseal chondrodysplasia SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Article ID DOMAIN; RESISTANCE AB Schmid metaphyseal chondrodysplasia (SMCD; MIM 156500) is an autosomal dominant disorder of the skeleton that is manifested in early childhood by short stature, coxa vara, and a waddling gait. Patients with SMCD have mutations in the gene that codes for the alpha-1 chain of collagen X (COL10A1); however, mutation analysis of this gene is hampered by its size. We studied a family with SMCD: the mother, a 36-year-old woman with a height of 149 cm, had mild bilateral coxa vara. Her two sons presented with short stature, bowed legs, and coxa vara in early childhood. DNA was extracted from peripheral lymphocytes from the three patients and subjected to PCR amplification by COL10A1 gene-specific primers. In addition to single-strand conformational polymorphism (SSCP) analysis of the COL10A1 gene, we used a novel method, dideoxy fingerprinting (ddF). The genetic defect in this family was found to be a previously unreported missense mutation (T-to-C transition) at nucleotide 2011. This change resulted in a Ser-to-Pro substitution at position 671 of the carboxy-terminus of the COL10A1 protein. In addition, the two boys, but not the mother, were found to carry a trinucleotide (CCC) deletion at position 2048 of the 3' untranslated region, a polymorphism of the COL10A1 gene, We conclude that ddF can be used in the analysis of the COL10A1 gene along with SSCP. The S671P substitution is novel, but located in the same region with the other reported COL10A1 mutations, con firming type X collagen as the locus for this disease. C1 NIDDKD,GENET & ENDOCRINOL SECT,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,CHILDRENS MED CTR,DEPT PEDIAT,DIV PEDIAT ENDOCRINOL,WASHINGTON,DC 20007. RP Stratakis, CA (reprint author), NICHHD,SECT PEDIAT ENDOCRINOL,DEV ENDOCRINOL BRANCH,NIH,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 8 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 DEC PY 1996 VL 59 IS 2 BP 112 EP 117 DI 10.1006/bmme.1996.0075 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA WD515 UT WOS:A1996WD51500004 PM 8986632 ER PT J AU Timmers, KI Clark, AE OmatsuKanbe, M Whiteheart, SW Bennett, MK Holman, GD Cushman, SW AF Timmers, KI Clark, AE OmatsuKanbe, M Whiteheart, SW Bennett, MK Holman, GD Cushman, SW TI Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein SO BIOCHEMICAL JOURNAL LA English DT Article ID INSULIN-STIMULATED TRANSLOCATION; GLUCOSE-TRANSPORTER ISOFORM; SYNAPTIC VESICLE DOCKING; PLASMA-MEMBRANE; SUBCELLULAR TRAFFICKING; POTENTIAL MECHANISM; 3T3-L1 ADIPOCYTES; GLUT4; LOCALIZATION; SYNTAXIN AB The vesicle-associated membrane proteins [VAMPs; vesicle SNAP receptors (v-SNAREs)] present on GLUT4-enriched vesicles prepared from rat adipose cells [Cain, Trimble and Lienhard (1992) J. Biol. Chem. 267, 11681-11684] have been identified as synaptobrevin 2 (VAMP 2) and cellubrevin (VAMP 3) by using isoform-specific antisera. Additional antisera identify syntaxins 2 and 4 as the predominant target membrane SNAP receptors (t-SNAREs) in the plasma membranes (PM), with syntaxin 3 at one-twentieth the level. Syntaxins 2 and 4 are enriched 5-10-fold in PM compared with low-density microsomes (LDM). Insulin treatment results in an 11-fold increase in immunodetectable GLUT4 in PM and smaller (approx, 2-fold) increases in VAMP 2 and VAMP 3, whereas the subcellular distributions of the syntaxins are not altered by insulin treatment. To determine which of the SNAP receptors (SNAREs) in PM might participate in SNARE complexes with proteins from GLUT4 vesicles, complexes were immunoprecipitated with anti-myc antibody from solubilized membranes after the addition of myc-epitope-tagged N-ethylmaleimide-sensitive fusion protein (NSF) and recombinant alpha-soluble NSF attachment protein (alpha-SNAP). These complexes contain VAMPs 2 and 3 and syntaxin 4, but not syntaxins 2 or 3. Complex formation requires ATP and is disrupted by ATP hydrolysis. When all membrane fractions are prepared from basal cells, few or no VAMPs and no syntaxin 4 are immunoprecipitated in SNARE complexes obtained from LDM alone (or from immunoisolated GLUT4 vesicles). The content of syntaxin 4 depends on the presence of PM, and participation of VAMPs 2 and 3 is enhanced 4-6-fold by the addition of solubilized GLUT4 vesicles to PM. The latter increase is greater than can be explained by the 2-fold higher levels of VAMPs added to the reaction mixture. When all membrane fractions are prepared from insulin-stimulated cells, SNARE complexes formed from PM alone contain similar levels of syntaxin 4 but 5-6-fold higher levels of VAMPs 2 and 3 compared with PM alone from basal cells. Addition of GLUT4 Vesicle proteins to PM from insulin-treated cells results in a further 2-fold increase in VAMP 2 recovered in SNARE complexes, Therefore the VAMPs in PM of insulin-treated but not basal cells, and in GLUT4-vesicles from cells in either condition, are in a form that readily forms a SNARE complex with PM t-SNAREs and NSF. Insulin seems to activate PM and/or GLUT4 vesicles so as to increase the efficiency of SNARE complex formation. C1 NIDDKD,EXPT DIABET METAB & NUTR SECT,DIABET BRANCH,NIH,BETHESDA,MD 20892. UNIV BATH,SCH BIOL & BIOCHEM,BATH BA2 7AY,AVON,ENGLAND. UNIV KENTUCKY,ALBERT B CHANDLER MED CTR,DEPT BIOCHEM,LEXINGTON,KY 40536. UNIV CALIF BERKELEY,DEPT MOL & CELL BIOL,BERKELEY,CA 94720. OI Whiteheart, Sidney/0000-0001-5577-0473 FU NHLBI NIH HHS [R01 HL056652] NR 32 TC 53 Z9 55 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 DEC 1 PY 1996 VL 320 BP 429 EP 436 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VX989 UT WOS:A1996VX98900011 PM 8973549 ER PT J AU Heyes, MP Achim, CL Wiley, CA Major, EO Saito, K Markey, SP AF Heyes, MP Achim, CL Wiley, CA Major, EO Saito, K Markey, SP TI Human microglia convert L-tryptophan into the neurotoxin quinolinic acid SO BIOCHEMICAL JOURNAL LA English DT Article ID KYNURENINE PATHWAY METABOLISM; CEREBROSPINAL-FLUID; NEUROACTIVE KYNURENINES; NEUROLOGICAL DISEASE; IMMUNE ACTIVATION; BRAIN; MECHANISM; 4-CHLORO-3-HYDROXYANTHRANILATE; 6-CHLOROTRYPTOPHAN; ASTROCYTES AB Immune activation leads to accumulations of the neurotoxin and kynurenine pathway metabolite quinolinic acid within the central nervous system of human patients. Whereas macrophages can convert L-tryptophan to quinolinic acid, it is not known whether human brain microglia can synthesize quinolinic acid. Human microglia, peripheral blood macrophages and cultures of human fetal brain cells (astrocytes and neurons) were incubated with [C-13(6)]L-tryptophan in the absence or presence of interferon gamma. [C-13(6)]Quinolinic acid was identified and quantified by gas chromatography and electron-capture negative-chemical ionization mass spectrometry. Both L-kynurenine and [C-13(6)]quinolinic acid were produced by unstimulated cultures of microglia and macrophages. Interferon gamma, an inducer of indoleamine 2,3-dioxygenase, increased the accumulation of L-kynurenine by all three cell types (to more than 40 mu M). Whereas large quantities of [C-13(6)]quinolinic acid were produced by microglia and macrophages (to 438 and 1410 nM respectively), minute quantities of [C-13(6)]quinolinic acid were produced in human fetal brain cultures (not more than 2 nM). Activated microglia and macrophage infiltrates into the brain might be an important source of accelerated conversion of L-tryptophan into quinolinic acid within the central nervous system in inflammatory diseases. C1 PRESBYTERIAN UNIV HOSP,DIV NEUROPATHOL,PITTSBURGH,PA 15213. NINCDS,VIRAL & MOL PATHOGENESIS LAB,BETHESDA,MD 20892. RP Heyes, MP (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 200 Z9 201 U1 1 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 1996 VL 320 BP 595 EP 597 PN 2 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VX989 UT WOS:A1996VX98900034 PM 8973572 ER PT J AU Higley, JD Mehlman, PT Poland, RE Taub, DM Vickers, J Suomi, SJ Linnoila, M AF Higley, JD Mehlman, PT Poland, RE Taub, DM Vickers, J Suomi, SJ Linnoila, M TI CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors SO BIOLOGICAL PSYCHIATRY LA English DT Article DE nonhuman primate; aggression; serotonin; impulsivity; cerebrospinal fluid testosterone ID CEREBROSPINAL-FLUID MONOAMINE; 5-HYDROXYINDOLEACETIC ACID; PERSONALITY DIMENSIONS; AMINE METABOLITES; PLASMA TESTOSTERONE; HOMOVANILLIC-ACID; VIOLENT OFFENDERS; IMPULSE CONTROL; FIRE SETTERS; NEUROENDOCRINE FINDINGS AB We studied the potential roles of testosterone and serotonin in various forms of aggressive and violent behaviors by measuring each biochemical and behavior in free-ranging adolescent male nonhuman primates. Our results showed that (1) CSF free testosterone concentrations were positively correlated with overall aggressiveness, but not with measures of impulsivity. (2) CSF 5-HIAA concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression, but not with overall rates of aggression, High rates of impulsive behavior were positively correlated with severe, unrestrained aggression, but not overall rates of aggression. (3) Dimensional analyses showed that while subjects with low CSF 5-HIAA exhibited high rates of aggression, high CSF testosterone further augmented rates and intensity of aggression in subjects with low CSF 5-HIAA. We conclude that high CSF free testosterone concentrations are associated with competitive aggression, while low CSF 5-HIAA concentrations are associated with severe aggression which results from impaired impulse control, and perseverance. (C) 1996 Society of Biological Psychiatry C1 NIAAA, CLIN STUDIES LAB, DICBR, BETHESDA, MD 20892 USA. LAB ANIM BREEDERS & SERV, YEMASSEE, SC USA. HARBOR UCLA MED CTR, DIV BIOL PSYCHIAT, TORRANCE, CA 90509 USA. US FDA, WASHINGTON, DC 20204 USA. RP Higley, JD (reprint author), NICHHD, COMPARAT ETHOL LAB,NIH,ANIM CTR,BLDG 112, POB 529, POOLESVILLE, MD 20837 USA. NR 67 TC 219 Z9 221 U1 2 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 1996 VL 40 IS 11 BP 1067 EP 1082 DI 10.1016/S0006-3223(95)00675-3 PG 16 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VT527 UT WOS:A1996VT52700001 PM 8931909 ER PT J AU Jacobsen, LK Hong, WL Hommer, DW Hamburger, SD Castellanos, FX Frazier, JA Giedd, JN Gordon, CT Karp, BI McKenna, K Rapoport, JL AF Jacobsen, LK Hong, WL Hommer, DW Hamburger, SD Castellanos, FX Frazier, JA Giedd, JN Gordon, CT Karp, BI McKenna, K Rapoport, JL TI Smooth pursuit eye movements in childhood-onset schizophrenia: Comparison with attention-deficit hyperactivity disorder and normal controls SO BIOLOGICAL PSYCHIATRY LA English DT Article DE eye tracking; schizophrenia children; ADHD; saccade ID TRACKING DYSFUNCTION; ANTIPSYCHOTIC MEDICATIONS; QUANTITATIVE-ANALYSIS; SACCADIC INTRUSIONS; TARDIVE-DYSKINESIA; NEGATIVE SYMPTOMS; PERFORMANCE; ABNORMALITIES; CHILDREN; NEUROLEPTICS AB Abnormalities of the smooth pursuit eye movements of adults with schizophrenia have been well described. We examined smooth pursuit eye movements in schizophrenic children, contrasting them with normal and attention-deficit hyperactivity disorder (ADHD) subjects, to determine whether there is continuity of eye movement dysfunction between childhood- and adult-onset forms of schizophrenia. Seventeen schizophrenic children with onset of illness by age 12, 18 ADHD children, and 22 normal children were studied while engaged in a smooth pursuit eye tracking task. Eye tracking variables were compared across the three groups. Schizophrenic children exhibited significantly greater smooth pursuit impairments than either normal or ADHD subjects. Within the schizophrenic group, there were no significant relationships between eye tracking variables and clinical variables, or ventricular/brain ratio. Childhood-onset schizophrenia is associated with a similar pattern of smooth pursuit abnormalities to that seen in later-onset schizophrenia. (C) 1996 Society of Biological Psychiatry C1 ZENECA PHARMACEUT,CNS CLIN RES,WILMINGTON,DE. NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP Jacobsen, LK (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,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 72 TC 52 Z9 54 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 1996 VL 40 IS 11 BP 1144 EP 1154 DI 10.1016/S0006-3223(95)00630-3 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VT527 UT WOS:A1996VT52700010 PM 8931918 ER PT J AU Fissore, RA He, CL VandeWoude, GF AF Fissore, RA He, CL VandeWoude, GF TI Potential role of mitogen-activated protein kinase during meiosis resumption in bovine oocytes SO BIOLOGY OF REPRODUCTION LA English DT Article ID MATURATION-PROMOTING FACTOR; GERMINAL VESICLE BREAKDOWN; SERINE-THREONINE KINASE; EPIDERMAL GROWTH-FACTOR; XENOPUS EGG EXTRACTS; MAP KINASE; MOUSE OOCYTES; MEIOTIC MATURATION; M-PHASE; CYTOPLASMIC MATURATION AB During meiotic maturation, numerous cytoplasmic and nuclear events take place that prepare the oocytes for fertilization. These changes are initiated by an increase in the activity of several kinases, most notably maturation-promoting factor, also called histone H1 kinase. Another kinase, mitogen-activated protein (MAP) kinase, is also stimulated during this period. In this study, we investigated the role of MAP kinase in bovine oocyte maturation. First, the kinetics of activation of histone H1 and MAP kinases during maturation were assessed simultaneously by evaluating their catalytic activities in vitro. We found that they are activated at approximately the same time, around germinal vesicle breakdown (GVBD). Then, at approximately 15 h of maturation, the activity of H1 kinase temporarily decreases, whereas MAP kinase remains high through the metaphase II stage. Second, the activation and catalytic activity of MAP kinase was directly evaluated by Western blotting and by an in-gel kinase assay. We determined that MAP kinase becomes activated and exhibits a decreased mobility through SDS-polyacrylamide gels, and that its catalytic activity increases as maturation progresses. In our system, most of the MAP kinase activity can be attributed to p42(MAPK2). Third, the activation pathway of MAP kinase was explored. In Xenopus oocytes, MAP kinase is activated by a kinase cascade that includes several upstream activators; one of them is the product of the proto-oncogene mos. In bovine oocytes, injection of Mos RNA elicited a rapid and maximal activation of MAP kinase that resulted in accelerated resumption of meiosis and GVBD. These results were thought to be mediated by an overexpression of a kinase-active Mos product because injection of a kinase-inactive Mos RNA failed to activate MAP kinase. Together, these results suggest a role for MAP kinase during the initiation and progression of meiosis in bovine oocytes. The data also suggest the presence of an MAP kinase-activating cascade that can be initiated by the Mos protein. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP Fissore, RA (reprint author), UNIV MASSACHUSETTS,DEPT VET & ANIM SCI,AMHERST,MA 01003, USA. NR 78 TC 131 Z9 138 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD DEC PY 1996 VL 55 IS 6 BP 1261 EP 1270 DI 10.1095/biolreprod55.6.1261 PG 10 WC Reproductive Biology SC Reproductive Biology GA VU778 UT WOS:A1996VU77800010 PM 8949882 ER PT J AU Shih, JH Louis, TA AF Shih, JH Louis, TA TI Tests of independence for bivariate survival data SO BIOMETRICS LA English DT Article DE bivariate failure times; covariance; cross ratio; martingale residuals ID CENSORED-DATA; RANK-TESTS; ASSOCIATION; DISTRIBUTIONS; MODEL AB We propose two test statistics based on the covariance process of the martingale residuals for testing independence of bivariate survival data. The first test statistic takes the supremum over time of the absolute value of the covariance process, and the second test statistic is a time-weighted summary of the process. We derive asymptotic properties of the two test statistics under the null hypothesis of independence. In addition, we derive the asymptotic distribution of the weighted test and construct optimal weights for contiguous alternatives to independence. Through simulations, we compare the performance of the proposed tests and the inner product of the Savage scores statistics of Clayton and Cuzick (1985, Journal of the Royal Statistical Society, Series A 148, 82-108). These demonstrate that the supremum test is generally more powerful with comparatively little power loss relative to their test when Clayton's family alternative holds, and the weighted test is more powerful when the weight is appropriately chosen. C1 UNIV MINNESOTA,DIV BIOSTAT,MINNEAPOLIS,MN 55455. RP Shih, JH (reprint author), NHLBI,OFF BIOSTAT RES,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 12 Z9 12 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1996 VL 52 IS 4 BP 1440 EP 1449 DI 10.2307/2532857 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VX804 UT WOS:A1996VX80400025 PM 8962462 ER PT J AU Choi, D Stables, JP Kohn, H AF Choi, D Stables, JP Kohn, H TI The anticonvulsant activities of functionalized N-benzyl 2-acetamidoacetamides. The importance of the 2-acetamido substituent SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID DRUG DEVELOPMENT PROGRAM; BENZYLACETAMIDE DERIVATIVES; ACID-DERIVATIVES; AMINO-ACIDS; COMPLEXES; SERIES AB Recent studies have demonstrated that substituted N-benzyl 2-acetamidoacetamides provide significant protection against maximal electroshock (MES)-induced seizures in mice and rats. In this study, we investigated whether the 2-acetamido moiety was necessary for anticonvulsant activity. Ten derivatives of the known anticonvulsant, N-benzyl 2-acetamido-2-phenyl acetamide were prepared in which the 2-acetamido group was replaced by hydrogen, methyl, oxygen, and halogen substituents. Evaluation of these compounds in the MES-induced seizure test demonstrated that both the hydroxy and the methoxy compounds provided full protection against MES-induced seizures in mice given ip at 100 mg/kg. Moreover, evaluation of the individual stereoisomers for the hydroxy compound showed that the principal activity resided in the (R)-isomer. These findings demonstrated that the 2-acetamido substituent is important but not obligatory for the prevention of MES-induced seizures. Further supporting evidence was provided by comparing the pharmacological activities of N-benzyl 2,3-dimethoxypropionamide with N-benzyl 2-acetamido-3-methoxypropionamide. The ED(50) value for the former in the MES test was 30 mg/kg (ip), which compared favorably with phenobarbital (ED(50) = 22 mg/kg), but the ED(50) value for N-benzyl 2-acetamido-3-methoxypropionamide was 8.3 mg/kg. Copyright (C) 1996 Elsevier Science Ltd C1 UNIV HOUSTON, DEPT CHEM, HOUSTON, TX 77204 USA. NINCDS, EPILEPSY BRANCH, NIH, BETHESDA, MD 20892 USA. NR 33 TC 16 Z9 16 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC PY 1996 VL 4 IS 12 BP 2105 EP 2114 DI 10.1016/S0968-0896(96)00225-8 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA WE007 UT WOS:A1996WE00700008 PM 9022975 ER PT J AU Hiddemann, W Longo, DL Coiffier, B Fisher, RI Cabanillas, F Cavalli, F Nadler, LM DeVita, VT Lister, TA Armitage, JO AF Hiddemann, W Longo, DL Coiffier, B Fisher, RI Cabanillas, F Cavalli, F Nadler, LM DeVita, VT Lister, TA Armitage, JO TI Lymphoma classification - The gap between biology and clinical management is closing SO BLOOD LA English DT Editorial Material ID MANTLE CELL LYMPHOMA; NEOPLASMS C1 UNIV GOTTINGEN,DEPT HEMATOL ONCOL,D-3400 GOTTINGEN,GERMANY. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. CTR HOSP LYON SUD,DEPT HEMATOL,F-69310 PIERRE BENITE,FRANCE. LOYOLA UNIV,CTR CANC,DIV HEMATOL ONCOL,MAYWOOD,IL 60153. MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77030. OSPED SAN GIOVANNI BELLINZONA,DIV ONCOL,BELLINZONA,SWITZERLAND. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. YALE UNIV,CTR CANC,NEW HAVEN,CT. ST BARTHOLOMEWS HOSP,DEPT MED ONCOL,LONDON,ENGLAND. UNIV NEBRASKA,DEPT INTERNAL MED,OMAHA,NE. NR 15 TC 109 Z9 115 U1 1 U2 1 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 DEC 1 PY 1996 VL 88 IS 11 BP 4085 EP 4089 PG 5 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200001 PM 8943841 ER PT J AU Grzegorzewski, KJ Komschlies, KL Franco, JL Ruscetti, FW Keller, JR Wiltrout, RH AF Grzegorzewski, KJ Komschlies, KL Franco, JL Ruscetti, FW Keller, JR Wiltrout, RH TI Quantitative and cell-cycle differences in progenitor cells mobilized by recombinant human interleukin-7 and recombinant human granulocyte colony-stimulating factor SO BLOOD LA English DT Article ID BLOOD STEM-CELLS; PERIPHERAL-BLOOD; BONE-MARROW; HEMATOLOGICAL RECOVERY; SUPPORTIVE CARE; RHG-CSF; IN-VIVO; MICE; TRANSPLANTATION; MYELOPOIESIS AB Administration of recombinant human interleukin-7 (rhIL-7) to mice increases the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU-GEMM]) from the bone marrow (BM) to peripheral organs, including blood, and also increases the number of primitive progenitor and stem cells in the peripheral blood (PB). We now report that combined treatment of mice with rhIL-7 and recombinant human granulocyte-colony stimulating factor (rhG-CSF) stimulates a twofold to 10-fold increase in the total number of PB CFU-c, and a twofold to fivefold increase in the total number of PB CFU-spleen at day 8 (CFU-S-8) over the increase stimulated by rhIL-7 or rhG-CSF alone. In addition, the quality of mobilized cells with trilineage, long-term marrow-repopulating activity is maintained or increased in mice treated with rhIL-7 and rhG-CSF compared with rhIL-7 or rhG-CSF alone. These differences in mobilizing efficiency suggest qualitative differences in the mechanisms by which rhIL-7 and rhG-CSF mobilize progenitor cells. In fact, the functional status of progenitor cells mobilized by rhIL-7 differs from that of cells mobilized by rhG-CSF in that the incidence of actively cycling (S-phase) progenitors obtained from the PB is about 20-fold higher for rhIL-7-treated mice than for mice treated with rhG-CSF. These results suggest the use of rhIL-7-mobilized progenitor/stem cells for gene-modification and tracking studies, and highlight different functions and rates of repopulation after reconstitution with PB leukocytes obtained from mice treated with rhIL-7 versus rhG-CSF. C1 SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. RP Grzegorzewski, KJ (reprint author), NCI,EXPT IMMUNOL LAB,LAB LEUKOCYTE BIOL,DIV BASIC SCI,FREDERICK CANC RES & DEV CTR,BLDG 560,FREDERICK,MD 21702, USA. NR 34 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1996 VL 88 IS 11 BP 4139 EP 4148 PG 10 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200008 PM 8943848 ER PT J AU Donahue, RE Byrne, ER Thomas, TE Kirby, MR Agricola, BA Sellers, SE Gaudernack, G Karlsson, S Lansdorp, PM AF Donahue, RE Byrne, ER Thomas, TE Kirby, MR Agricola, BA Sellers, SE Gaudernack, G Karlsson, S Lansdorp, PM TI Transplantation and gene transfer of the human glucocerebrosidase gene into immunoselected primate CD34(+)Thy-1(+) cells SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; HEMATOPOIETIC PROGENITOR CELLS; CD34+ MARROW-CELLS; IN-VIVO EXPRESSION; BONE-MARROW; NONHUMAN-PRIMATES; HOST RANGES; T-CELLS; GENERATION; LYMPHOMA AB In an attempt to improve our gene transfer efficiency into hematopoietic stem cells and to evaluate the capacity of immunoselected CD34(+)Thy-1(+)(CDw90) cells to reconstitute hematopoiesis following myeloablation, bone marrow (BM) transplantation was performed using autologous, immunoselected CD34(+)Thy-1(+)cells in rhesus macaques. BM samples were positively selected for cells that express CD34, further subdivided using high gradient immunomagnetic selection for cells that express Thy-1, and transduced using a 7-day supernatant transduction protocol with a replication-defective retroviral vector that contained the human glucocerebrosidase (GC) gene. Circulating leukocytes were evaluated using a semiquantitative polymerase chain reaction (PCR) assay for the human GC gene, with the longest surviving animal evaluated at day 558. Provirus was detected at all time points in both CD20(+) B cells and CD2(+) dim T cells, but long-term gene transfer was not observed in the granulocyte population. The CD2(+) dim population was phenotypically identified as being CD8(+) natural killer cells. By day 302 and day 330, both the CD2(+) bright and dim cell populations and sorted CD4(+) and CD8(+) cells had detectable provirus. Vector-derived GC mRNA was detected by reverse transcriptase (RT)-PCR analysis as far out as day 588. Thus, CD34(+)Thy-1(+) cells isolated using high gradient magnetic separation techniques can engraft, be transduced with a replication-defective retroviral vector, and contribute to CD20(+) B lymphocytes, CD8(+) T lymphocytes, and CD4(+) T lymphocytes; making them a suitable cell population to target for gene therapies involving lymphocytes. (C) 1996 by The American Society of Hematology. C1 TERRY FOX LAB,VANCOUVER,BC,CANADA. NORWEGIAN RADIUM HOSP,OSLO,NORWAY. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. RP Donahue, RE (reprint author), NHLBI,HEMATOL BRANCH,5 RES COURT,ROCKVILLE,MD 20850, USA. NR 26 TC 21 Z9 21 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 DEC 1 PY 1996 VL 88 IS 11 BP 4166 EP 4172 PG 7 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200011 PM 8943851 ER PT J AU Cooke, CB Krenacs, L StetlerStevenson, M Greiner, TC Raffeld, M Kingma, DW Abruzzo, L Frantz, C Kaviani, M Jaffe, ES AF Cooke, CB Krenacs, L StetlerStevenson, M Greiner, TC Raffeld, M Kingma, DW Abruzzo, L Frantz, C Kaviani, M Jaffe, ES TI Hepatosplenic T-cell lymphoma: A distinct clinicopathologic entity of cytotoxic gamma delta T-Cell origin SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; HEMOPHAGOCYTIC SYNDROME; SUBCUTANEOUS TISSUE; GENE REARRANGEMENTS; EXPRESSION; LINEAGE; RECEPTORS; DISEASE; LOCALIZATION AB We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T-cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2(+), CD3(+), CD4(-), CD5(-), CD7(+), CD16(+), CD57(-), CD25(-), T-cell receptor (TCR)delta(+), beta F1(-). CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TlA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation. This is a US government work. There are no restrictions on its use. C1 NCI,DIV CLIN SCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. DC GEN HOSP,WASHINGTON,DC. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 NR 47 TC 224 Z9 234 U1 0 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 DEC 1 PY 1996 VL 88 IS 11 BP 4265 EP 4274 PG 10 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200023 PM 8943863 ER PT J AU Rosenthal, J Thurman, GW Cusack, N Peterson, VM Malech, HL Ambruso, DR AF Rosenthal, J Thurman, GW Cusack, N Peterson, VM Malech, HL Ambruso, DR TI Neutrophils from patients after burn injury express a deficiency of the oxidase components p47-phox and p67-phox SO BLOOD LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; COLONY-STIMULATING FACTOR; CELL-FREE SYSTEM; ADENINE-DINUCLEOTIDE PHOSPHATE; SEVERE THERMAL-INJURY; PROTEIN KINASE-C; NADPH OXIDASE; RESPIRATORY BURST; POLYMORPHONUCLEAR LEUKOCYTES; MYELOPEROXIDASE DEFICIENCY AB Infection is a major cause of morbidity and mortality in patients after thermal injury. This predisposition to infections is related, in part, to abnormal polymorphonuclear leukocyte (PMN) function and a diminished respiratory burst. To evaluate the biochemical basis for the defective respiratory burst after major burns, the status of the oxidase enzyme system and its components was investigated. PMNs were isolated from 24 patients with 12% to 62% burns. Oxidase activity of intact PMNs, measured as superoxide anion (O-2(-)) generation or oxygen consumption, was decreased in burn compared with healthy controls. Subcellular fractions from patient PMNs generated less O-2(-) in the sodium dodecyl sulfate cell-free system, and this was related to a diminished contribution by cytosol but not by plasma membrane. Subsequently, cytosol was separated with CM-Sepharose, yielding two fractions; one contained the p47-phox and p67-phox (47/67 mix) and the other contained the remaining cytosolic components (run through [RT]). Although the contribution to oxidase activity made by RT from patient cytosol was similar to that of control, the activity of p47/67 mix from PMNs of burn patients was deficient. Quantitative assays using an immunoautoradiographic technique showed a consistent, but significant decrease in both p47-phox and p67-phox. The addition of purified or human recombinant p47-phox but not p67-phox corrected the diminished oxidase activity of cytosol from burn patients. Thus, decreased respiratory burst activity found in PMNs from individuals with thermal injury was associated with a specific, quantitative deficiency of p47-phox. (C) 1996 by The American Society of Hematology. C1 UNIV COLORADO,HLTH SCI CTR,SCH MED,DEPT PEDIAT,DENVER,CO 80262. UNIV COLORADO,SCH MED,DEPT SURG,DENVER,CO 80262. BELLE BONFILS MEM BLOOD CTR,DENVER,CO. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. FU NHLBI NIH HHS [K07-HL02036] NR 59 TC 35 Z9 36 U1 0 U2 1 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 DEC 1 PY 1996 VL 88 IS 11 BP 4321 EP 4329 PG 9 WC Hematology SC Hematology GA VV152 UT WOS:A1996VV15200029 PM 8943869 ER PT J AU Williams, S Wakisaka, A Zeng, QQ Barnes, J Martin, G Wechter, WJ Liang, CT AF Williams, S Wakisaka, A Zeng, QQ Barnes, J Martin, G Wechter, WJ Liang, CT TI Minocycline prevents the decrease in bone mineral density and trabecular bone in ovariectomized aged rats SO BONE LA English DT Article DE bone formation; bone resorption; minocycline; estrogen; trabecular connectivity; histomorphometry ID I IGF-I; GROWTH-FACTOR; ESTROGEN-TREATMENT; MASS; CELLS; INTERLEUKIN-6; OSTEOPOROSIS; OSTEOBLASTS; RESORPTION; EXPRESSION AB In the current study, we examined the effects of minocycline, on the osteopenia of ovariectomized aged rats, Old female rats were randomly divided into five groups: sham, ovariectomized control and ovariectomized treated with minocycline, 17 beta-estradiol, or both agents, Bone samples were collected 8 wk after the treatment, Ovariectomy reduced bone mineral density of the whole femur and at the condylar, distal metaphyseal and head-neck-trochanter regions 10%-19% and the loss of bone density was prevented by treatment with minocycline or 17 beta-estradiol. Histomorphometric analysis of distal femur showed ovariectomy reduced the trabecular bone area, the trabecular bone number, trabecular bone thickness and increased the trabecular bone separation, The microanatomic structure of trabecular bone also showed that the number of nodes, node to node, cortical to node, node to free end was reduced by ovariectomy, Treatment with minocycline attenuated the effect of ovariectomy on trabecular bone in aged animals, In contrast, cortical bone was not affected by ovariectomy or minocycline treatment, The effect of minocycline on bone turnover was also examined, Minocycline increased osteoid surface, mineralizing surface, mineral apposition rate, bone formation rate and reduced eroded surface. We have therefore concluded that the modest increase in bone mineral density and the improvement in the trabecular bone status noted in minocycline treated ovariectomized aged rats is likely due to an increase in bone formation coupled with a decrease in bone resorption. (C) 1996 by Elsevier Science Inc. C1 NIA,GERONTOL RES CTR,NATL INST HLTH,BALTIMORE,MD 21224. LOMA LINDA UNIV,LOMA LINDA,CA 92350. NR 35 TC 39 Z9 41 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD DEC PY 1996 VL 19 IS 6 BP 637 EP 644 DI 10.1016/S8756-3282(96)00302-X PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ104 UT WOS:A1996VZ10400011 PM 8968031 ER PT J AU Chanock, SJ Walsh, TJ AF Chanock, SJ Walsh, TJ TI Evolving concepts of prevention and treatment of invasive fungal infections in pediatric bone marrow transplant recipients SO BONE MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT 2nd Meeting on Marrow Transplantation in Children - Current Results and Controversies CY JUN 01-03, 1995 CL HILTON HEAD ISL, SC SP Amgen, Glaxo, Alpha Therapeut, Baxter, Caremark, Janssen, MedImmune, Rhone Poulenc Rorer, Bristol Myers Squibb, Burroughs Wellcome, Sandoz, SmithKline Beecham, Miles, Hoffman Laroche DE supportive care; mycosis; antifungal therapy; immunocompromised host ID LIPOSOMAL AMPHOTERICIN-B; IMMUNOCOMPROMISED PATIENTS; ANTIFUNGAL PROPHYLAXIS; NEUTROPENIC PATIENTS; RISK-FACTORS; GRANULOCYTOPENIC PATIENTS; DISSEMINATED CANDIDIASIS; PULMONARY ASPERGILLOSIS; FLUCONAZOLE PROPHYLAXIS; NEOPLASTIC DISEASES AB Fungal infections have emerged as a major complication of marrow transplantation in children, Most episodes occur within the first 100 days and are often difficult to diagnose, Until recently, a limited number of therapeutic options were available but with new antifungal agents, including azole compounds and less toxic preparations of amphotericin, there is promise for improvements in the prevention of fungal infections as well as the treatment of established infections. This review will summarize the current approach towards therapeutic options available for the supportive care of children undergoing marrow transplantation. RP Chanock, SJ (reprint author), NCI,PEDIAT BRANCH,NIH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 53 TC 9 Z9 10 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 DEC PY 1996 VL 18 SU 3 BP S15 EP S20 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA WA473 UT WOS:A1996WA47300005 PM 8971401 ER PT J AU Cupler, EJ LeonMonzon, M Miller, J SeminoMora, C Anderson, TL Dalakas, MC AF Cupler, EJ LeonMonzon, M Miller, J SeminoMora, C Anderson, TL Dalakas, MC TI Inclusion body myositis in HIV-1 and HTLV-1 infected patients SO BRAIN LA English DT Article DE inclusion body myositis; HIV-1; HTLV-1; superantigen ID ACQUIRED IMMUNODEFICIENCY SYNDROME; MONOCLONAL-ANTIBODY ANALYSIS; HUMAN FOAMY VIRUS; INFLAMMATORY MYOPATHIES; MONONUCLEAR-CELLS; TRANSGENIC MICE; POLYMYOSITIS; EXPRESSION; RETROVIRUS; DISEASE AB Sporadic inclusion body myositis (IBM) is the most common inflammatory myopathy affecting patients over the age of 50 years. Dysimmune and degenerative aetiologies have been postulated, but viral infections have not been associated with the disease. Two HIV-1 (human immunodeficiency virus type 1) infected men and one woman infected with HTLV-1 (human T cell leukaemia virus type 1) developed progressive proximal muscle weakness unrelated to antiretroviral therapy. Their muscle biopsies were studied by light and electron microscopy, by immunocytochemistry to determine the expression of major histocompatibility complex (MHC) molecules and identify the type of infiltrating cells and T cell receptor (TCR) subunits, and by reverse transcription-polymerase chain reaction (RT-PCR) and single or double immunocytochemistry to search for retrovirally infected endomysial cells. The clinical features were consistent with sporadic IBM. The muscle biopsies showed primary endomysial inflammation red-rimmed vacuoles, amyloid deposits, eosinophilic inclusions, and small round fibres in groups, all diagnostic of IBM. The muscle fibres expressed MHC class-I antigens and were invaded primarily by CD8+ T-lymphocytes preferentially bearing TCR V beta 5.1 and V beta 13 chains. The HIV-1 or HTLV-1 antigens were detected only on endomysial macrophages on or around muscle fibres, but not within the muscle fibres. We conclude that IBM occurs in HIV-1 and HTLV-1 infected individuals and has a clinical, histological and immunological pattern identical to sporadic IBM in the non-retrovirally infected patients. Retroviruses do not directly infect the muscle, but persistent retroviral infections may provide superantigenic stimulation and trigger an endomysial inflammatory response identical to that occurring in sporadic IBM. C1 NINCDS,NEUROMUSCULAR DIS SECT,NIH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT NEUROL,TORRANCE,CA 90509. NR 27 TC 71 Z9 72 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 1996 VL 119 BP 1887 EP 1893 DI 10.1093/brain/119.6.1887 PN 6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WE280 UT WOS:A1996WE28000006 PM 9009995 ER PT J AU Torrey, EF Rawlings, RR AF Torrey, EF Rawlings, RR TI Fluctuations in schizophrenic births by year SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID SEASON; RISK AB Background. It has previously been reported that births of individuals who later develop schizophrenia vary by birth year. Method. Birth data were analysed on 34 024 individuals diagnosed with DSM-III-R disorganised, catatonic, and undifferentiated schizophrenia using time series analysis. Results. Minor yearly fluctuations were observed but did not achieve statistical significance. Thus earlier findings reported in the literature could not be replicated using a different statistical approach. Conclusion. The findings do not support theories which assume major yearly fluctuations in the births of individuals with schizophrenia. Such theories include the perinatal effects of influenza, temperature variation, and the effects of severe weather. C1 NIMH,CTR NEUROSCI,ST ELIZABETHS HOSP,WASHINGTON,DC 20032. NIAAA,NIH,BETHESDA,MD 20892. NR 12 TC 6 Z9 6 U1 0 U2 0 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD DEC PY 1996 VL 169 IS 6 BP 772 EP 775 DI 10.1192/bjp.169.6.772 PG 4 WC Psychiatry SC Psychiatry GA VX570 UT WOS:A1996VX57000016 PM 8968637 ER PT J AU Alarcon, GS Tilley, B Cooper, S Clegg, DO Trentham, DE Pillemer, SR Neuner, R Fowler, S AF Alarcon, GS Tilley, B Cooper, S Clegg, DO Trentham, DE Pillemer, SR Neuner, R Fowler, S TI Another look at minocycline SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Letter ID PLACEBO-CONTROLLED TRIAL; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; THERAPY C1 UNIV VERMONT,COLL MED,BURLINGTON,VT. UNIV UTAH,MED CTR,SALT LAKE CITY,UT. BETH ISRAEL HOSP,BOSTON,MA 02215. NIH,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. HENRY FORD HLTH CTR,MIRA,INVESTIGATORS GRP,DETROIT,MI. RP Alarcon, GS (reprint author), UNIV ALABAMA,BIRMINGHAM,AL, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD DEC PY 1996 VL 45 IS 8 BP 6 EP 7 PG 2 WC Rheumatology SC Rheumatology GA WC708 UT WOS:A1996WC70800002 PM 8997812 ER PT J AU Goans, RE Weiss, GH Vieira, NE Sidbury, JB Abrams, SA Yergey, AL AF Goans, RE Weiss, GH Vieira, NE Sidbury, JB Abrams, SA Yergey, AL TI Calcium kinetics in glycogen storage disease type 1a SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE glycogen storage disease 1a; Von Gierke's disease; calcium metabolism; calcium kinetics; calcium stable isotopes ID PLASMA CALCIUM; BONE CALCIUM; CHILDREN; TRACER AB Glycogen storage disease type 1a (Von Gierke's disease) is one of the more common glycogen storage diseases (GSD). GSD 1a patients can have severe idiopathic osteopenia, often beginning at a young age. Since calcium tracer studies offer a sensitive probe of the bone microenvironment and of calcium deposition, kinetics might be disturbed in patients with GSD 1a. Plasma dilution kinetics obtained using the stable isotope Ca-42 are shown in this paper to be quite different between GSD 1a patients and age-matched controls. Comparison of kinetic parameters in these two populations is made using a new binding site model for describing calcium dynamics at the plasma-bone interface. This model describes reversible binding of calcium ions to postulated short-term and lone-term sites by a retention probability density function psi (t). Using this analysis, adult GSD subjects exhibited a significant decrease (P = 0.023) in the apparent half-life of a calcium ion on the longer-term site compared with controls. The general theory of calcium tracer dilution kinetics is then discussed in terms of a new model of short-term calcium homeostasis recently proposed by Bronner and Stein [5]. C1 NICHHD,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. DCRT,LAB PHYS SCI,NIH,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,NIH,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR UNIV,USDA ARS,CHILDRENS NUTR RES CTR,HOUSTON,TX 77030. OI Abrams, Steven/0000-0003-4972-9233 NR 19 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD DEC PY 1996 VL 59 IS 6 BP 449 EP 453 DI 10.1007/BF00369209 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VV310 UT WOS:A1996VV31000007 PM 8939770 ER PT J AU Schatzkin, A Freedman, LS Dorgan, J McShane, LM Schiffman, MH Dawsey, SM AF Schatzkin, A Freedman, LS Dorgan, J McShane, LM Schiffman, MH Dawsey, SM TI Surrogate end points in cancer research: A critique SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID HUMAN PAPILLOMAVIRUS INFECTION; CERVICAL INTRAEPITHELIAL NEOPLASIA; CELL NUCLEAR ANTIGEN; POSTMENOPAUSAL WOMEN; GENETIC ALTERATIONS; CARCINOMA SEQUENCE; COLORECTAL-CANCER; RELIABILITY; TRIALS; PLASMA AB Studies using surrogate end points of malignant disease may be smaller, shorter, and less expensive than studies with incident cancer end points, Researchers have proposed a broad range of histological, cellular, and molecular markers as surrogate end points for cancer (SECs), We define a valid SEC as follows: the effect of an intervention on (or the association of a risk factor with) the SEC is concordant with its effect on (or association with) incident cancer, Adenomatous polyps and persistent human papillomavirus infections are examples of reasonably valid SECs (for colorectal and cervical cancer, respectively) because these markers are necessary precursors of most of these malignancies, Inferences from other potential SECs, however, are problematic if there exist major alternative causal pathways to malignancy bypassing the SEC, Furthermore, in such circumstances, an SEC that is valid for one intervention or exposure may not be valid for another, Even for those end points without such major alternative pathways, an intervention could differentially affect two intermediate markers on the same pathway, thus disturbing the concordance between its effect on a given SEC and its effect on cancer, Thus, an understanding of the causal structure underlying the relations of interventions/exposures, potential SECs, and cancer is critical in evaluating SECs, Three questions are pertinent to elucidating this structure: (a) What is the relation of the SEC to cancer? (b) What is the relation of the intervention/exposure to the SEC? and (c) To what extent does the SEC mediate the relation between the intervention/exposure and cancer? Ecological, metabolic, observational epidemiological, and intervention studies may provide data relevant to one or more of these questions, Data on SEC variability are critical in evaluating whether marker findings have been attenuated by random sources of intra-individual variation, We emphasize the importance of conducting studies, especially SEC-cancer and intervention/exposure-SEC-cancer mediation studies, to evaluate problematic SECs such as epithelial cell hyperproliferation, For some time to come, hard and policy-relevant evidence on cancer etiology and prevention will emerge only from studies with cancer end points or, at a somewhat lower level of certainty, SECs that are (for the most part) obligatory steps on the causal pathway to malignant disease. RP Schatzkin, A (reprint author), NCI,DEPT HLTH & HUMAN SERV,NIH,9000 ROCKVILLE PIKE,EPN 211,BETHESDA,MD 20892, USA. NR 42 TC 41 Z9 41 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 DEC PY 1996 VL 5 IS 12 BP 947 EP 953 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VX384 UT WOS:A1996VX38400001 PM 8959315 ER PT J AU Longnecker, MP Bernstein, L PaganiniHill, A Enger, SM Ross, RK AF Longnecker, MP Bernstein, L PaganiniHill, A Enger, SM Ross, RK TI Risk factors for in situ breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CARCINOMA IN-SITU; REPLACEMENT THERAPY; ESTROGEN; WOMEN; EPIDEMIOLOGY AB Few data exist on risk factors for in situ breast carcinoma, We examined risk factors for lit situ breast carcinoma in data from two population-based case-control studies of breast cancer conducted among female residents of Los Angeles County, Cases with ill situ or invasive disease were identified through the cancer registry for Los Angeles County in the 1980s, We included all cases ages 40 years or younger diagnosed over a 5.5-year period and all cases ages 55-64 years diagnosed over a 3-year period, Control subjects were individually matched to cases by age (+/- 3 years), neighborhood of residence, and, for younger controls, parity (nulliparous versus parous), The analysis included 233 cases with in situ cancer, 2057 cases with invasive cancer, and 2203 controls, Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for screening mammography and established risk factors, In general, risk factors for in situ breast cancer were similar to those for invasive disease in this population, In premenopausal women, however, the risk of in situ breast cancer decreased with increasing body mass index, whereas for invasive disease, body mass index was unrelated to risk, In addition, in postmenopausal women with known age at menopause, use of unopposed estrogen replacement therapy was associated with increased risk of in situ disease [OR for ever use of estrogen alone was 1.60 (95% CI, 1.00-2.58)], whereas for invasive disease the OR was 1.23 (95% CI, 1.00-1.50), A similar difference was seen for combined hormone replacement therapy, Unmeasured increased screening among estrogen or combined replacement hormone users compared with nonusers could account for some of the association of in situ breast cancer risk with hormone replacement use. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. UNIV SO CALIF,KENNETH NORRIS JR COMPREHENS CANC CTR,LOS ANGELES,CA 90033. RP Longnecker, MP (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,MC A3-05,RES TRIANGLE PK,NC 27709, USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA17054, CA44546, N01-CN25404] NR 22 TC 48 Z9 49 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 DEC PY 1996 VL 5 IS 12 BP 961 EP 965 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VX384 UT WOS:A1996VX38400003 PM 8959317 ER PT J AU Rothman, N Hayes, RB Zenser, TV DeMarini, DM Bi, WF Hirvonen, A Talaska, G Bhatnagar, VK Caporaso, NE Brooks, LR Lakshmi, VM Feng, PW Kashyap, SK You, XJ Eischen, BT Kashyap, R Shelton, ML Hsu, FF Jaeger, M Parikh, DJ Davis, BB Yin, SN Bell, DA AF Rothman, N Hayes, RB Zenser, TV DeMarini, DM Bi, WF Hirvonen, A Talaska, G Bhatnagar, VK Caporaso, NE Brooks, LR Lakshmi, VM Feng, PW Kashyap, SK You, XJ Eischen, BT Kashyap, R Shelton, ML Hsu, FF Jaeger, M Parikh, DJ Davis, BB Yin, SN Bell, DA TI The glutathione S-transferase M1 (GSTM1) null genotype and benzidine-associated bladder cancer, urine mutagenicity, and exfoliated urothelial cell DNA adducts SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TRANS-STILBENE OXIDE; CARCINOGEN-METABOLISM; HOMOZYGOUS DELETION; EXPOSED WORKERS; SUSCEPTIBILITY; GENE; SMOKERS; POLYMORPHISM; COMMON; RISK AB Multiple studies in the general population have suggested that subjects with the glutathione S-transferase M1 (GSTM1)-null genotype, who lack functional GSTM1, are at higher risk for bladder cancer, To evaluate the impact of the GSTM1-null genotype on bladder cancer caused by occupational exposure to benzidine and to determine its influence on benzidine metabolism, we carried out three complementary investigations: a case-control study of bladder cancer among workers previously exposed to benzidine in China, a cross-sectional study of urothelial cell DNA adducts and urinary mutagenicity in workers currently exposed to benzidine in India, and a laboratory study of the ability of human GSTM1 to conjugate benzidine and its known metabolites in vitro, There was no overall increase in bladder cancer risk for the GSTM1-null genotype among 38 bladder cancer cases and 43 controls (odds ratio, 1.0; 95% confidence interval, 0.4-2.7), although there was some indication that highly exposed workers with the GSTM1-null genotype were at greater risk of bladder cancer compared to similarly exposed workers without this allele. However, the GSTM1 genotype had no impact on urothelial cell DNA adduct and urinary mutagenicity levels in workers currently exposed to benzidine, Furthermore, human GSTM1 did not conjugate benzidine or its metabolites, These results led us to conclude that the GSTM1-null genotype does not have an impact on bladder cancer caused by benzidine, providing a contrast to its association with elevated bladder cancer risk in the general population. C1 VET AFFAIRS MED CTR,ST LOUIS,MO 63125. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63125. US EPA,DIV ENVIRONM CARCINOGENESIS,RES TRIANGLE PK,NC 27711. CHINESE ACAD PREVENT MED,BEIJING,PEOPLES R CHINA. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. UNIV CINCINNATI,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. NATL INST OCCUPAT HLTH,AHMEDABAD 380016,GUJARAT,INDIA. TIANJIN BUR CHEM IND,INST LABOR HYG,TIANJIN,PEOPLES R CHINA. SHANGHAI INST OCCUPAT MED,SHANGHAI,PEOPLES R CHINA. RP Rothman, N (reprint author), NCI,NIH,DIV CANC EPIDEMIOL & GENET,EPN 418,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR-00954]; NIADDK NIH HHS [AM-20579]; NIEHS NIH HHS [1-P30-ES06096-01] NR 24 TC 27 Z9 30 U1 1 U2 2 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 DEC PY 1996 VL 5 IS 12 BP 979 EP 983 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VX384 UT WOS:A1996VX38400006 PM 8959320 ER PT J AU Harty, LC Guinee, DG Travis, WD Bennett, WP Jett, J Colby, TV Tazelaar, H Trastek, V Pairolero, P Liotta, LA Harris, CC Caporaso, NE AF Harty, LC Guinee, DG Travis, WD Bennett, WP Jett, J Colby, TV Tazelaar, H Trastek, V Pairolero, P Liotta, LA Harris, CC Caporaso, NE TI p53 mutations and occupational exposures in a surgical series of lung cancers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NICKEL REFINERY WORKERS; TUMOR-SUPPRESSOR GENE; CIGARETTE-SMOKING; OXIDATIVE DAMAGE; DNA; EXPRESSION; ANGIOSARCOMAS; ASSOCIATION; CHROMIUM AB p53 mutations are frequent in malignant lung tumors, Of 88 surgically treated lung cancers from cigarette smokers previously evaluated for p53 mutations, 45 tumors (51.1%) had mutations in exons 5-8 (D. G. Guinee, Jr, ef al., Carcinogenesis (Lend.), 16: 993-1002, 1995), We report here the examination of 13 occupational exposures and 13 high-risk occupations in relation to these p53 mutations, Two molecular abnormalities were associated with occupational exposures: (a) G:C-->T:A transversions on the coding (nontranscribed) strand (n = 13) were associated with chromate exposure and employment in the metal industry (P < 0.05) and marginally associated with nickel exposure (P = 0.056); and (b) G:C-->A:T transitions at non-CpG sites (n = 9) were associated with work in the petrochemical industry (P = 0.05), No association was found between p53 mutations and gender, cigarette pack-years, tumor histology, age at diagnosis, or family history of lung cancer, Because all three chromate-exposed subjects had large cell carcinomas exhibiting G: C-->T:A coding-strand transversions, follow-up of a cohort with this exposure should clarify the association with the p53 gene. C1 NCI, GENET EPIDEMIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NCI, HUMAN CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. ARMED FORCES INST PATHOL, DEPT PULM & MEDIASTINAL PATHOL, WASHINGTON, DC 20306 USA. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. NR 34 TC 21 Z9 22 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 1996 VL 5 IS 12 BP 997 EP 1003 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VX384 UT WOS:A1996VX38400009 PM 8959323 ER PT J AU Ohnuki, Y Reddel, RR Bates, SE Lehman, TA Lechner, JF Harris, CC AF Ohnuki, Y Reddel, RR Bates, SE Lehman, TA Lechner, JF Harris, CC TI Chromosomal changes and progressive tumorigenesis of human bronchial epithelial cell lines SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID IMMORTAL HUMAN FIBROBLASTS; SHORT ARM; INDEFINITE DIVISION; TUMOR PROGRESSION; HUMAN-LUNG; T-ANTIGEN; CARCINOMA; SENESCENCE; CANCER; REGION AB A simian virus 40 (SV40)-transformed human bronchial epithelial cell line, BEAS-2B, underwent progressive changes, including the development of tumorigenicity, during extended in vitro passaging. Karyotypic changes occurred in parallel with the phenotypic changes. For the first 12 passages following viral transformation, there were random karyotypic changes. Immortalization occurred between passages 12 and 21, corresponding with the accumulation of four characteristic abnormal chromosomes-m-1: add(15)(p11.1); m-2: der(8;9)(q10;q10); m-3: add(16)(p13); and m-4: mar4-and the loss of one homolog of chromosomes 8, 15, 16, 21, and 22. With further passaging (from 21 to 63), the acquisition of weak tumorigenicity was observed, accompanied by an increased frequency of cells containing all four common abnormal chromosomes, m-l through m-4, and missing one normal homolog of chromosomes 8, 15, 16, and 22. Four tumor cell lines (B39-TL, B39-TR, B61-T4 and B61-T7) were established from tumors induced by the injection of these weakly tumorigenic BEAS-2B 39th- and 61st- passage cells into athymic nude mice. One of the cell lines, B39-TL, is significantly more tumorigenic than the others. It is notable that B39-TL showed two specific abnormal chromosomes, del(3p);der(3;15) (q10;q10) and m-6; der(21)t(3;21)(p14.2;p12) inducing deletion of a short arm of chromosome 3. Fluorescence in situ hybridization analysis with a probe for protein tyrosine phosphatase-gamma demonstrated loss of heterozygosity in the 3p14 region. The development of step-wise karyotypic changes in this in vitro carcinogenesis model parallels changes documented in several common human cancers. (C) Elsevier Science Inc., 1996 C1 CHILDRENS MED RES INST,WESTMEAD,NSW,AUSTRALIA. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Ohnuki, Y (reprint author), HUNTINGTON MED RES INST,99 N EL MOLINO AVE,PASADENA,CA 91101, USA. RI Reddel, Roger/A-6635-2014 OI Reddel, Roger/0000-0002-6302-6107 NR 51 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD DEC PY 1996 VL 92 IS 2 BP 99 EP 110 DI 10.1016/S0165-4608(96)00156-2 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA VZ231 UT WOS:A1996VZ23100002 PM 8976365 ER PT J AU Ting, CC Wang, J Yang, YL AF Ting, CC Wang, J Yang, YL TI Interleukin-2 and interleukin-7 augment the cytolytic activity and expand the antitumor killing spectrum of alpha CD3-induced activated killer cells: Potential use in the immunotherapy of non-immunogenic tumors SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE cytokines; alpha CD3-induced killer cells; immunotherapy ID INFILTRATING LYMPHOCYTES; MONOCLONAL-ANTIBODY; MEDIATED-IMMUNITY; T-LYMPHOCYTES; IN-VITRO; INVIVO; SUFFICIENT; GENERATION; MELANOMA; EFFICACY AB This study investigates the effect of different cytokines on the growth and antitumor activity of the a CD3-induced killer cells CD3-AK, and the potential of the use of CD3-AK cells in cancer immunotherapy. Eight cytokines were tested. Only three (interleukin-2, -4 and 7) were able to support the growth of CD3-AK cells, which selectively killed different tumor targets of diversified origin. Culturing in interleukin-4 (IL-4) or IL-7 alone could maintain the growth of CD3-AK cells for 6-8 days. Only IL-2 could maintain long-term growth, but further addition of IL-4 exerted an inhibitory effect, which terminated the cell growth in 2 weeks. In contrast, despite the fact that 11,-7 inhibited the proliferation of CD3-AK cells cultured in IL-2, as determined by [H-3]thymidine uptake, the recovery of viable cells was not reduced. In 10 days, CD3-AK cells cultured in IL-2 alone or IL-2 plus IL-7 increased 160- or 176-fold respectively. There is an inverse relationship between the in vitro growth ability and Fas expression on the CD3-AK cells. Further, IL-7 increased the cytolytic activity of the CD3-AK cells two- to threefold. CD3-AK cells could be maintained in IL-2 or IL-2 plus IL-7 for 60-240 days or more. The long-term-cultured CD3-AK cells not only possessed a high level of cytolytic activity, but also showed a wide spectrum of killing with different tumor targets; the normally ''resistant'' targets, such as EL-4 lymphoma, fibrosarcoma, or melanoma, became susceptible. When the in vivo antitumor activity of the CD3-AK cells against a non-immunogenic tumor, EL-4, was tested by tumor-neutralization experiments, we found that only the long-term-cultured cells gave significant protection, with those maintained in both IL-2 and IL-7 giving the highest degree of protection. Thus, these long-term-cultured CD3-AK cells may have the potential to be used for immunotherapy of a variety of tumors whatever their immunogenicity. RP Ting, CC (reprint author), NCI,LAB IMMUNE CELL BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. NR 30 TC 8 Z9 9 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD DEC PY 1996 VL 43 IS 5 BP 283 EP 292 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA WF505 UT WOS:A1996WF50500005 PM 9024505 ER PT J AU Krizman, DB Chuaqui, RF Meltzer, PS Trent, JM Duray, PH Linehan, WM Liotta, LA EmmertBuck, MR AF Krizman, DB Chuaqui, RF Meltzer, PS Trent, JM Duray, PH Linehan, WM Liotta, LA EmmertBuck, MR TI Construction of a representative cDNA library from prostatic intraepithelial neoplasia SO CANCER RESEARCH LA English DT Article ID CLONING; CANCER; CELLS AB We report the construction of a plasmid-based cDNA library made from microdissected cells derived from prostatic intraepithelial neoplasia, Total RNA was extracted and converted to blunt-ended double-stranded cDNA by oligo(dT)-mediated reverse transcription followed by linker addition. A linker-specific primer with UDG-compatible ends was used to amplify the cDNA and the resulting PCR product was subcloned. A total of 154 clones were sequenced and results indicated that 81.5% of the clones derived from either known genes, anonymous expressed sequence tags, or novel transcripts with very little redundancy of screened clones. These results demonstrate the feasibility of constructing complex representative cDNA libraries from specific microdissected cell populations that represent microscopic precursor stages of cancer progression. This method should facilitate identification of transcripts specifically expressed in cells of a distinct histological origin and tumorigenic stage. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. RP Krizman, DB (reprint author), NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BLDG 49,ROOM 4A15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 18 TC 66 Z9 67 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 DEC 1 PY 1996 VL 56 IS 23 BP 5380 EP 5383 PG 4 WC Oncology SC Oncology GA VV562 UT WOS:A1996VV56200015 PM 8968089 ER PT J AU Petersen, LN Mamenta, EL Stevnsner, T Chaney, SG Bohr, VA AF Petersen, LN Mamenta, EL Stevnsner, T Chaney, SG Bohr, VA TI Increased gene specific repair of cisplatin induced interstrand crosslinks in cisplatin resistant cell lines, and studies on carrier ligand specificity SO CARCINOGENESIS LA English DT Article ID HUMAN OVARIAN-CANCER; MURINE LEUKEMIA-L1210 CELLS; DNA ADDUCT FORMATION; CYTO-TOXICITY; L1210 CELLS; PLATINUM RESISTANCE; ACQUIRED-RESISTANCE; CIS-DIAMMINEDICHLOROPLATINUM(II); LINKS; MECHANISM AB Development of resistance to cisplatin in previously treatment-responsive malignancies is a major obstacle to successful treatment, Enhanced DNA repair as well as enhanced replicative bypass of DNA adducts have been suggested to play a role in the development of resistance to cisplatin, However, the relative contribution of these mechanisms is unknown, Second generation platinum compounds containing the 1,2-diaminocyclohexane (dach) carrier ligand have been of particular interest in the studies of resistance mechanisms since they have been effective in treatment of cells resistant to cisplatin, We have investigated the formation and repair of interstrand crosslinks (ICL) in the mouse leukemia cell line L1210/0 and its carrier ligand specific resistant derivatives L1210/DDP and L1210/DACH after treatment with ethylenediamine (en)-Pt and diaminocyclohexane (dach)-Pt compounds, ICL in the overall genome were examined using a modification of the alkaline elution assay, A Southern blot technique was employed for the study of ICL in specific regions of the genome. In the overall genome we found decreased formation of ICL with either -en or -dach carrier ligands in the two resistant cell lines without carrier ligand specificity, Some carrier ligand specificity of ICL formation was observed in the dihydrofolate reductase (DHFR) gene, but it did not correlate with the carrier ligand specificity of resistance. At the level of the overall genome there was no difference in repair of ICL between the sensitive and the two resistant cell lines, When measured in the DHFR gene, however, there was enhanced repair of ICL in the two resistant cell lines compared with the sensitive cell line, The enhanced repair at the level of the gene did not display any carrier ligand specificity. C1 NIA,GENET MOL LAB,NIH,BALTIMORE,MD 21224. UNIV N CAROLINA,SCH MED,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. FU NCI NIH HHS [CA 34082] NR 46 TC 32 Z9 32 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 DEC PY 1996 VL 17 IS 12 BP 2597 EP 2602 DI 10.1093/carcin/17.12.2597 PG 6 WC Oncology SC Oncology GA WC820 UT WOS:A1996WC82000009 PM 9006094 ER PT J AU Selmin, O Lucier, GW Clark, GC Tritscher, AM VandenHeuvel, JP Gastel, JA Walker, NJ Sutter, TR Bell, DA AF Selmin, O Lucier, GW Clark, GC Tritscher, AM VandenHeuvel, JP Gastel, JA Walker, NJ Sutter, TR Bell, DA TI Isolation and characterization of a novel gene induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver SO CARCINOGENESIS LA English DT Article ID DOSE-RESPONSE RELATIONSHIPS; POLYMERASE CHAIN-REACTION; DIFFERENTIAL DISPLAY; MESSENGER-RNAS; CDNA LIBRARY; RECEPTOR; DIOXIN; EXPRESSION; CLONING; CANCER AB The differential display technique was used to identify genes whose expression was regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Expression of a novel sequence was up-regulated in a dose-dependent fashion in liver of Sprague-Dawley male rats exposed to both chronic and acute treatment with TCDD, as measured by densitometry of Northern blot analyses (P < 0.01). A rapid amplification of cDNA ends (RACE) procedure was used to isolate a 1.8 kb cDNA from a rat liver cDNA preparation, This cloned cDNA, called 25-Dx, was sequenced and found to encode a peptide of 223 amino acids, In control rats, the 25-Dx gene was expressed at high levels in lung and liver, A hydrophobic domain of 14 residues followed by a proline-rich domain, both located in the N-terminal region, showed 71% homology with the transmembrane domain of the precursor for the interleukin-6 receptor and a conserved consensus sequence found in the cytokine/growth factor/prolactin receptor superfamily respectively. C1 NIEHS,LAB COMPUTAT BIOL & RISK ANAL,RES TRIANGLE PK,NC 27709. JOHNS HOPKINS MED INST,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 35 TC 100 Z9 103 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 DEC PY 1996 VL 17 IS 12 BP 2609 EP 2615 DI 10.1093/carcin/17.12.2609 PG 7 WC Oncology SC Oncology GA WC820 UT WOS:A1996WC82000011 PM 9006096 ER PT J AU Higinbotham, KG Rice, JM Reed, CD Watatani, M Enomoto, T Anderson, LM Perantoni, AO AF Higinbotham, KG Rice, JM Reed, CD Watatani, M Enomoto, T Anderson, LM Perantoni, AO TI Variant mutational activation of the K-ras oncogene in renal mesenchymal tumors induced in newborn F344 rats by methyl(methoxymethyl)nitrosamine SO CARCINOGENESIS LA English DT Article ID POINT MUTATIONS; MICROSATELLITE INSTABILITY; LUNG CARCINOMAS; DNA-DAMAGE; MOUSE; CANCER; GENE; DIMETHYLNITROSAMINE; PROTOONCOGENE; TRANSVERSIONS AB Renal mesenchymal tumors were induced at high incidence in F344 rats by a single intraperitoneal injection of methyl(methoxymethyl) nitrosamine (DMN-OMe) within 48 h after birth, DNAs from 18 of 35 mesenchymal tumors contained transforming ras sequences in NIH3T3 transfection assays: K-ras (17/18) or N-ras (1/18), Single-stranded conformational polymorphism analysis or dideoxy sequencing of polymerase chain reaction-amplified K-rns gene fragments revealed that these neoplasms contained a variety of activating mutations in the K-ras oncogene, Alterations in codon 12 predominated and included GGT --> GAT transitions, GGT --> GTT or TGT transversions, and previously reported insertion mutations, although some tumors expressed more than one mutation and the pattern of mutations even varied within tumors, Mutations were also found in exons 2 and 3, In addition, tumor transplantability into syngeneic hosts correlated positively and significantly with K-ms activation, Renal mesenchymal tumors with transforming mutations in exon 1 were often successfully passaged (10/12) while tumors which lacked mutations in exon 1 were infrequently transplantable (2/14), While the observed base substitutions in K-rns are consistent with adduct formation, the presence of insertion mutations and intratumor heterogeneity of alterations suggest that ras activation in DMN-OMe-induced tumors is not necessarily an early event in tumorigenesis. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 35 TC 3 Z9 3 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 DEC PY 1996 VL 17 IS 12 BP 2625 EP 2630 DI 10.1093/carcin/17.12.2625 PG 6 WC Oncology SC Oncology GA WC820 UT WOS:A1996WC82000013 PM 9006098 ER PT J AU Munoz, EF Diwan, BA Calvert, RJ Weghorst, CM Anderson, J Rice, JM Buzard, GS AF Munoz, EF Diwan, BA Calvert, RJ Weghorst, CM Anderson, J Rice, JM Buzard, GS TI Transplacental mutagenicity of cisplatin: H-ras codon 12 and 13 mutations in skin tumors of SENCAR mice SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; MAJOR DNA ADDUCT; DRUG CISPLATIN; COLD SSCP; GENE; CARCINOGENESIS; AMPLIFICATION; CHEMOTHERAPY; MUTAGENESIS; PCR AB Cisplatin is an anticancer agent sometimes used in pregnant women, It is also a potent initiator of skin tumors in mice when administered transplacentally, For characterization of the transplacental mutagenicity of cisplatin, tumors initiated in fetal skin by cisplatin or 7,12-dimethylbenz-[n]anthracene (DMBA) and promoted by postnatal 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were analyzed for H-ms mutations by 'cold' single-strand conformation polymorphism analysis and direct sequencing, The expected high incidence of exon II codon 61 mutations (20/20) was found in transplacental DMBA-initiated tumors, with no exon I change, By contrast, 6/10 cisplatin tumors had seven mutations in codons 12 or 13 of exon I, all at GpG dinucleotides, Four of these were unique codon 13 GGC --> GTC changes, significantly different from the DMBA group and from historical TPA-only controls, The activation of codons 12 and 13 by cisplatin is in accord with the known in vitro preference of cisplatin for GpG sites for intrastrand cross-linking adduct formation, These results provide the first evidence that cisplatin can act transplacentally to cause specific mutations in fetal skin that are not seen in skin tumors caused by treatment of adult skin with this agent, This is evidence for unique molecular fetal carcinogenic pathways and underscores concern about human fetal risk due to maternal cisplatin treatment. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. US FDA,OFF SPECIAL NUTRIT,MOD LAB 1,CLIN RES & REVIEW STAFF,LAUREL,MD 20708. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 32 TC 15 Z9 15 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 DEC PY 1996 VL 17 IS 12 BP 2741 EP 2745 DI 10.1093/carcin/17.12.2741 PG 5 WC Oncology SC Oncology GA WC820 UT WOS:A1996WC82000029 PM 9006114 ER PT J AU Veech, RL Fell, DA AF Veech, RL Fell, DA TI Distribution control of metabolic flux SO CELL BIOCHEMISTRY AND FUNCTION LA English DT Article ID STEADY-STATE TREATMENT; TOP-DOWN APPROACH; CONTROL COEFFICIENTS; ENZYMATIC CHAINS; RAT-LIVER; SYSTEMS; YEAST; RESPIRATION; EFFECTOR; ENZYMES C1 OXFORD BROOKES UNIV,SCH BIOL & MOL SCI,OXFORD OX3 0BP,ENGLAND. NIAAA,METAB & MOL BIOL LAB,ROCKVILLE,MD 20852. RI Fell, David/B-2109-2009 OI Fell, David/0000-0001-6669-2247 NR 27 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0263-6484 J9 CELL BIOCHEM FUNCT JI Cell Biochem. Funct. PD DEC PY 1996 VL 14 IS 4 BP 229 EP 236 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VY020 UT WOS:A1996VY02000002 PM 8952041 ER PT J AU Knull, H Minton, AP AF Knull, H Minton, AP TI Structure within eukaryotic cytoplasm and its relationship to glycolytic metabolism SO CELL BIOCHEMISTRY AND FUNCTION LA English DT Review ID ACTIN-CONTAINING-FILAMENTS; RED-CELL MEMBRANE; RABBIT MUSCLE PHOSPHOFRUCTOKINASE; MICROTUBULE-ASSOCIATED PROTEINS; PERMEABILIZED L-929 CELLS; VASCULAR SMOOTH-MUSCLE; CROSS-LINKING PROTEINS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; F-ACTIN; SKELETAL-MUSCLE C1 NIDDKD, BIOCHEM PHARMACOL LAB, SECT PHYS BIOCHEM, NIH, BETHESDA, MD 20892 USA. RP Knull, H (reprint author), UNIV N DAKOTA, SCH MED, DEPT BIOCHEM, GRAND FORKS, ND 58202 USA. NR 124 TC 24 Z9 24 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0263-6484 J9 CELL BIOCHEM FUNCT JI Cell Biochem. Funct. PD DEC PY 1996 VL 14 IS 4 BP 237 EP 248 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VY020 UT WOS:A1996VY02000003 PM 8952042 ER PT J AU Sheikh, MS Garcia, M Zhan, QM Liu, YS Fornace, AJ AF Sheikh, MS Garcia, M Zhan, QM Liu, YS Fornace, AJ TI Cell cycle-independent regulation of p(21Waf1/Cip1) and retinoblastoma protein during okadaic acid-induced apoptosis is coupled with induction of Bax protein in human breast carcinoma cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID DEPENDENT KINASES; GROWTH ARREST; P53; DEATH; CANCER; GENE; EXPRESSION; INHIBITOR; BCL-2; LINES AB Okadaic acid (OA) is a serine/threonine protein phosphatase inhibitor and has been shown to induce apoptosis in a number of different tumor cell lines, including human breast carcinoma (HBC) cells. The molecular basis of OA-induced apoptosis remains to be investigated, Here, we demonstrate that the OA concentration that inhibits only protein phosphatase 1 and 2A was sufficient to induce apoptosis in HBC cells. In MCF-7 cells, the OA-induced apoptosis was coupled with the overexpression of endogenous p53, p21(Waf1/Cip1), and Bax proteins, whereas the Rb protein levels were decreased. OA also induced apoptosis and concomitantly enhanced the p21(Waf1/Clp1) and Bax levels in human papilloma virus protein EG-transfected variants of MCF-7 cells, in which p53 function had been disrupted, OA, by contrast, had no effect on the levels or the subcellular localization of Gadd45 and Bcl2 proteins in either wild-type or EG-transfected MCF-7 cells, Bcl-x(L), Bcl-x(s), and Bak levels were also unchanged after OA treatment in both cell types. OA-induced apoptosis and its effect on the expression of the above molecular markers occurred in the absence of any detectable changes in the cell cycle phase distribution. On the basis of our findings, we conclude the following: (a) OA-induced apoptosis in HBC cells occurs independently of cell cycle arrest; (b) the wild-type p53 function is not an absolute prerequisite for OA-induced cell death; and (c) OA-induced apoptosis is associated with up-regulation of endogenous p21(Waf1/Clp1) and Bax protein levels. C1 INSERM, U148, F-34090 MONTPELLIER, FRANCE. NIA, SECT GENE EXPRESS & AGING, GERONTOL RES CTR, NIH, BALTIMORE, MD 21224 USA. RP Sheikh, MS (reprint author), NCI, MOL PHARMACOL LAB, NIH, ROOM 5D02, BLDG 37, BETHESDA, MD 20892 USA. RI Fornace, Albert/A-7407-2008; Liu, Yusen/E-3527-2011 OI Fornace, Albert/0000-0001-9695-085X; NR 39 TC 48 Z9 48 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1996 VL 7 IS 12 BP 1599 EP 1607 PG 9 WC Cell Biology SC Cell Biology GA VX052 UT WOS:A1996VX05200002 PM 8959327 ER PT J AU Gorospe, M Shack, S Guyton, KZ Samid, D Holbrook, NJ AF Gorospe, M Shack, S Guyton, KZ Samid, D Holbrook, NJ TI Up-regulation and functional role of p21(Waf1/Cip1) during growth arrest of human breast carcinoma MCF-7 cells by phenylacetate SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; CYCLE CONTROL; PHENOTYPIC REVERSION; P53; DIFFERENTIATION; EXPRESSION; CANCER; INDUCTION; LEUKEMIA; GLIOMAS AB Phenylacetate (PA) and related aromatic fatty acids constitute a novel class of relatively nontoxic antineoplastic agents. These compounds induce tumor cytostasis and growth inhibition and differentiation of cancer cells, but little is known regarding the molecular events mediating these biological effects. Using human breast carcinoma MCF-7 cells as a model, we show here that PA-induced growth arrest is associated with enhanced expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1) and dephosphorylation of the retinoblastoma protein (PRB). The induction of p21(WAF1/CIP1) mRNA by PA was independent of the cellular p53 status. To directly assess the contribution of p21(Waf1/Cip1) to PA-mediated cytostasis, we compared the effects of PA in parental MCF-7 cells and cells expressing reduced levels of p21(Waf1/Cip1) protein (clones AS.3 and AS.4), accomplished through constitutive expression of antisense p21(Waf1/Cip1) transcripts. In contrast to parental cells, AS.3 and AS.4 cells did not show reduced pRB phosphorylation following PA treatment, indicating that p21(Waf1/Cip1) induction by PA is required for dephosphorylation (inactivation) of pRB, a known mediator of cell cycle control. A prominent role for p21(Waf1/Clp1) in mediating PA-induced growth arrest was further supported by the demonstration that embryonal fibroblasts derived from a p21(WAF1/CIP1) knockout mouse (p21(-/-) mouse embryonal fibroblasts) did not growth arrest following PA treatment, whereas PA effectively induced p21(WAF1/CIP1) mRNA and growth inhibition of the wild-type mouse embryonal fibroblasts. Taken together, our findings strongly support a role for p21(Waf1/Cip1) the PA-mediated inhibition of cell growth. C1 NIA,MOL & CELLULAR BIOL LAB,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. UNIV VIRGINIA,CTR CANC,EXPT THERAPEUT PROGRAM,CHARLOTTESVILLE,VA 22908. NR 43 TC 54 Z9 56 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 DEC PY 1996 VL 7 IS 12 BP 1609 EP 1615 PG 7 WC Cell Biology SC Cell Biology GA VX052 UT WOS:A1996VX05200003 PM 8959328 ER PT J AU Kenney, NJ Smith, GH Rosenberg, K Cutler, ML Dickson, RB AF Kenney, NJ Smith, GH Rosenberg, K Cutler, ML Dickson, RB TI Induction of ductal morphogenesis and lobular hyperplasia by amphiregulin in the mouse mammary gland SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EPIDERMAL GROWTH-FACTOR; BREAST-CANCER CELLS; EPITHELIAL-CELLS; FACTOR-ALPHA; FACTOR RECEPTOR; TRANSGENIC MICE; TGF-ALPHA; EXPRESSION; CRIPTO-1; DIFFERENTIATION AB As the juvenile mouse mammary gland matures, it undergoes extensive epithelial proliferation, leading to a network of ductal branching that transverses the organ. Recent evidence suggests that the epidermal growth factor-related peptide amphiregulin (AR) may play multiple roles in the proliferation, differentiation, and neoplastic conversion of the mouse mammary gland. Using a dual approach of recombinant AR in slow-release pellets and retroviral expression of AR, we explored the roles of this growth factor in the mouse mammary gland in vivo. We first noted that recombinant AR can reestablish longitudinal ductal proliferation in growth quiescent mammary glands of ovariectomized mice. Furthermore, retrovirally transduced mammary transplants overexpressing AR developed into hyperplastic tertiary ducts and hyperplastic lobules with increased lateral branching, apparent 9 weeks after transplantation into cleared mammary fat pads. This is the first study to demonstrate that AR can reestablish the early developmental activity of ductal mammary epithelium and induce hyperplasia in vivo. These data, coupled with previous findings that demonstrated nearly universal overexpression of AR in human breast cancer and rodent mammary tumorigenesis, suggest that AR may be an important intermediary in glandular maturation and early malignant progression. C1 GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 39 TC 42 Z9 43 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1996 VL 7 IS 12 BP 1769 EP 1781 PG 13 WC Cell Biology SC Cell Biology GA VX052 UT WOS:A1996VX05200021 PM 8959346 ER PT J AU Jeffers, M Rao, MS Rulong, S Reddy, JK Subbarao, V Hudson, E VandeWoude, GF Resau, JH AF Jeffers, M Rao, MS Rulong, S Reddy, JK Subbarao, V Hudson, E VandeWoude, GF Resau, JH TI Hepatocyte growth factor scatter factor-met signaling induces proliferation, migration, and morphogenesis of pancreatic oval cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FACTOR SCATTER FACTOR; EPITHELIAL-CELLS; PROTOONCOGENE PRODUCT; LIVER DEVELOPMENT; RECEPTOR; RAT; EXPRESSION; IDENTIFICATION; DIFFERENTIATION; INDUCTION AB Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector for cells expressing the Met tyrosine kinase receptor, In this investigation, we show that pancreatic oval cells express Met and exhibit a proliferative response to HGF/SF. Additionally, we found that oval cells treated transiently with this factor become ''scattered,'' whereas those exposed to HGF/SF for extended periods of time form branching tubular structures. These structures possess true lumens, which are lined by cells with ductal features, including apical microvilli, well-developed intercellular junctions, interdigitation of plasma membranes, and abundant cytoplasmic organelles. Interestingly, these ductal structures are formed by HGF/SF-treated cells cultured on plastic dishes in the absence of exogenous extracellular matrix components. Consistent with their ability to form ductal structures in vitro, we found that pancreatic oval cells form ductal adenocarcinomas in nude mice. This study supports the involvement of HGF/SF-Met signaling in the growth, migration, and morphogenesis of pancreatic oval cells and may have important implications for the expansion and morphogenic differentiation of these cells during developmental, regenerative, and neoplastic growth. C1 NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS INC,BASIC RES PROGRAM,FREDERICK,MD 21702. NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,CHICAGO,IL 60611. FU NIDDK NIH HHS [DK37958] NR 50 TC 37 Z9 38 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1996 VL 7 IS 12 BP 1805 EP 1813 PG 9 WC Cell Biology SC Cell Biology GA VX052 UT WOS:A1996VX05200024 PM 8959349 ER PT J AU Waller, CL Oprea, TI Chae, K Park, HK Korach, KS Laws, SC Wiese, TE Kelce, WR Gray, LE AF Waller, CL Oprea, TI Chae, K Park, HK Korach, KS Laws, SC Wiese, TE Kelce, WR Gray, LE TI Ligand-based identification of environmental estrogens SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MOLECULAR-FIELD ANALYSIS; POLYCHLORINATED HYDROXYBIPHENYLS; RECEPTOR; BINDING; COMFA; VALIDATION; REGRESSION; DIOXINS; MODELS; QSAR AB Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, was used to examine the estrogen receptor (ER) binding affinities of a series of structurally diverse natural, synthetic, and environmental chemicals of interest. The CoMFA/3D-QSAR model is statistically robust and internally consistent, and successfully illustrates that the overall steric and electrostatic properties of structurally diverse ligands for the estrogen receptor are both necessary and sufficient to describe the binding affinity. The ability of the model to accurately predict the En binding affinity of an external test set of molecules suggests that structure-based 3D-QSAR models may be used to supplement the process of endocrine disrupter identification through prioritization of novel compounds for bioassay. The general application of this 3D-QSAR model within a toxicological framework is, at present, limited only by the quantity and quality of biological data for relevant biomarkers of toxicity and hormonal responsiveness. C1 US EPA,REPROD TOXICOL DIV,NATL HLTH & ENVIRONM EFFECTS RES LAB,RES TRIANGLE PK,NC 27711. LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87545. NATL INST ENVIRONM HLTH SCI,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. RP Waller, CL (reprint author), US EPA,DIV EXPT TOXICOL,NATL HLTH & ENVIRONM EFFECTS RES LAB,RES TRIANGLE PK,NC 27711, USA. RI Oprea, Tudor/A-5746-2011; OI Oprea, Tudor/0000-0002-6195-6976; Korach, Kenneth/0000-0002-7765-418X NR 25 TC 183 Z9 186 U1 0 U2 13 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 DEC PY 1996 VL 9 IS 8 BP 1240 EP 1248 DI 10.1021/tx960054f PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA VV616 UT WOS:A1996VV61600004 PM 8951225 ER PT J AU Lee, VM Keefer, LK Archer, MC AF Lee, VM Keefer, LK Archer, MC TI An evaluation of the roles of metabolic denitrosation and alpha-hydroxylation in the hepatotoxicity of N-nitrosodimethylamine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ISOLATED RAT HEPATOCYTES; CONTROLLED BIOLOGICAL RELEASE; NITRIC-OXIDE GENERATION; DNA-DAMAGE; HUMAN-CELLS; LIVER; TOXICITY; AGENTS; METHYLAMINE; MECHANISMS AB N-Nitrosodimethylamine (NDMA) is a potent hepatotoxic agent in rats. NDMA causes cell death that does not correlate with known mechanisms of toxicity such as the production of oxidative stress or covalent binding to proteins. The following studies were designed to determine whether NDMA cytotoxicity is the result of metabolic denitrosation or alpha-hydroxylation of the nitrosamine. We determined the toxicity of various metabolites of NDMA in monolayer cultures of primary rat hepatocytes. NDMA was toxic at 0.1 mM in our cultures, but the metabolites formaldehyde, methanol, and methylamine were not toxic at this concentration. We used diazeniumdiolates that spontaneously release nitric oxide (NO) in aqueous media to deliver NO to hepatocytes in culture. The results show that, while NO released from diazeniumdiolates causes death in hepatocytes, the levels of NO produced during NDMA metabolism are insufficient to account for the toxicity of the nitrosamine. NDMA-dB, the fully deuteriated form of NDMA that undergoes approximately twice as much denitrosation in vivo as NDMA, was significantly less cytotoxic than NDMA. In contrast, N-nitroso-(acetoxymethyl)methylamine (AcO-NDMA), a stable precursor of the methanediazonium ion, was found to cause toxicity equivalent to NDMA on a molar basis. Altogether, our results with methylamine, formaldehyde, methanol, the diazeniumdiolates, and NDMA-d(6) indicate that NDMA toxicity is not the result of metabolic denitrosation, while the toxicity of AcO-NDMA provides strong evidence that the formation of the methanediazonium ion via alpha-hydroxylation leads to cell death. C1 UNIV TORONTO,FAC MED,DEPT NUTR SCI,TORONTO,ON M5S 3E2,CANADA. UNIV TORONTO,FAC MED,DEPT MED BIOPHYS,TORONTO,ON M5S 3E2,CANADA. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 67 TC 20 Z9 22 U1 0 U2 5 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 DEC PY 1996 VL 9 IS 8 BP 1319 EP 1324 DI 10.1021/tx960077u PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA VV616 UT WOS:A1996VV61600014 PM 8951235 ER PT J AU Porter, DW Nelson, VC Fivash, MJ Kasprzak, KS AF Porter, DW Nelson, VC Fivash, MJ Kasprzak, KS TI Mechanistic studies of the inhibition of MutT dGTPase by the carcinogenic metal Ni(II) SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ESCHERICHIA-COLI; DNA-SYNTHESIS; NUCLEOSIDE TRIPHOSPHATASE; MUTAGENIC SUBSTRATE; MOLECULAR-CLONING; TERNARY COMPLEXES; HYDROXYLATION; MUTATOR; 2'-DEOXYGUANOSINE; REPLICATION AB Promutagenic 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels are increased in DNA of animals exposed to carcinogenic metals, such as Ni(II). Besides being generated directly in genomic DNA, 8-oxo-dG may be incorporated there from 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool. The Escherichia coli dGTPase MutT, and analogous dGTPases in rats and humans, have been suggested as a defense against such incorporation because they hydrolyze 8-oxo-dGTP to 8-oro-7,8-dihydro-2'-deoxyguanosine 5'-monophosphate (8-oxo-dGMP). MutT and its mammalian counterparts are Mg(II)-dependent enzymes. Ni(II), in turn, is known to interact antagonistically with Mg(II) in biological systems. Thus, we hypothesized that Ni(II) might inhibit the activity of MutT. As an initial examination of this hypothesis, we conducted enzyme kinetic studies of MutT to determine the effect of Ni(II) on MutT activity and the mechanisms involved. As found, NI(II) inhibited MutT in a concentration-dependent manner when either dGTP or 8-oxo-dGTP was the nucleotide substrate. Ni(II) was determined to be an uncompetitive inhibitor of MutT with respect to Mg(II) when dGTP was the substrate, with apparent K-i of 1.2 mM Ni(II), and a noncompetitive inhibitor with respect to Mg(II) when 8-oxo-dGTP was the substrate, with apparent K-i of 0.9 mM Ni(II). Hence, the two metal cations did not compete with each other for binding at the MutT active site. This makes it difficult to predict Ni(II) effects on 8-oxo-dGTPases of other species. However, based upon the amino acid sequences of human and rat MutT-like dGTPases, their capacity for Ni(II) binding should be greater than that of MutT. Whether this could lead to stronger inhibition of those enzymes by Ni(II), or not, remains to be investigated. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. NR 36 TC 8 Z9 8 U1 0 U2 1 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 DEC PY 1996 VL 9 IS 8 BP 1375 EP 1381 DI 10.1021/tx9600816 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA VV616 UT WOS:A1996VV61600022 PM 8951243 ER PT J AU Lamb, ME Hershkowitz, I Sternberg, KJ Boat, B Everson, MD AF Lamb, ME Hershkowitz, I Sternberg, KJ Boat, B Everson, MD TI Investigative interviews of alleged sexual abuse victims with and without anatomical dolls SO CHILD ABUSE & NEGLECT LA English DT Article DE anatomical dolls; interview processes; investigative interviews ID CHILDRENS REPORTS; DETAILED DOLLS; CORRECT DOLLS; PROFESSIONALS; MEMORY AB Verbal and nonverbal responses by alleged victims of child sexual abuse were coded for length, amount of information, and the manner in which they were elicited by the interviewer. In 16 of the interviews, anatomical dolls were employed for the purposes of demonstration, whereas they were not used in another eight cases matched with respect to other characteristics of the children and the alleged events. Children interviewed with dolls provided an equivalent number of details and spoke as many words in the substantive portion of the interview as did children interviewed without dolls, and interviewers in the two groups used similar probes to elicit information. However, the average responses by the children were significantly longer and more detailed when dolls were not used. Children gave longer and more detailed responses to open-ended invitations when dolls were not used. Caution is necessary when interpreting these findings. Copyright (C) 1996 Elsevier Science Ltd C1 UNIV CINCINNATI, DEPT PSYCHIAT, CINCINNATI, OH USA. UNIV N CAROLINA, DEPT PSYCHIAT, CHAPEL HILL, NC USA. RP Lamb, ME (reprint author), NICHHD, SECT SOCIAL & EMOT DEV, 9190 ROCKVILLE PIKE, BETHESDA, MD 20814 USA. NR 26 TC 35 Z9 35 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD DEC PY 1996 VL 20 IS 12 BP 1251 EP 1259 DI 10.1016/S0145-2134(96)00121-4 PG 9 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA VV282 UT WOS:A1996VV28200013 PM 8985616 ER PT J AU Bornstein, MH Haynes, OM OReilly, AW Painter, KM AF Bornstein, MH Haynes, OM OReilly, AW Painter, KM TI Solitary and collaborative pretense play in early childhood: Sources of individual variation in the development of representational competence SO CHILD DEVELOPMENT LA English DT Article ID SOCIOECONOMIC-STATUS; SYMBOLIC PLAY; INFANT TEMPERAMENT; BEHAVIOR; MOTHER; ATTACHMENT; LANGUAGE; PARENTS; PERFORMANCE; ENVIRONMENT AB This study evaluates sources of individual variation in child pretense play as an expression of emerging mental representation. Family sociodemographic characteristics, maternal personological characteristics, and maternal affective and cognitive play behaviors, as well as children's gender, language competence, and play, were examined simultaneously. Naturalistic child solitary play and child collaborative play with mother were videorecorded in 141 20-month-olds. Child solitary play, child-initiated and mother-initiated collaborative play with mother, and maternal demonstrations and solicitations of play were then coded into nonsymbolic and symbolic acts. Zero-order relations obtained between child play and, respectively, child gender and language, family SES, and maternal verbal intelligence, personality, physical affection, and play demonstrations and solicitations. Structural equation modeling supported the following unique predictive relations: Child language and mothers' symbolic play positively influenced child collaborative play, and child gender and mothers' verbal intelligence predicted child solitary play. Child gender and mothers' verbal intelligence and physical affection influenced mothers' play and so influenced child collaborative play indirectly. The cognitive advantages of child play and maternal influences on child play are placed in an adaptive parenting framework. C1 W VIRGINIA UNIV,MORGANTOWN,WV 26506. RP Bornstein, MH (reprint author), NICHHD,BLDG 31,ROOM B2B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 96 TC 62 Z9 64 U1 1 U2 10 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD DEC PY 1996 VL 67 IS 6 BP 2910 EP 2929 DI 10.1111/j.1467-8624.1996.tb01895.x PG 20 WC Psychology, Educational; Psychology, Developmental SC Psychology GA WN235 UT WOS:A1996WN23500018 PM 9071765 ER EF