FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Saksida, LM Bussey, TJ AF Saksida, LM Bussey, TJ TI A neural network model of effects of lesions in perirhinal cortex. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Carnegie Mellon Univ, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. NIMH, Neuropsychol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 27 EP 27 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000091 ER PT J AU Moffat, S Szekely, C Zonderman, A Kabani, N Resnick, S AF Moffat, S Szekely, C Zonderman, A Kabani, N Resnick, S TI Longitudinal change in hippocampal volume as a function of apolipoprotein E genotype. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 28 EP 29 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000100 ER PT J AU Marks, AR Pietrini, P Basso, G Grafman, J AF Marks, AR Pietrini, P Basso, G Grafman, J TI Recent memory for item and order information: A pet study. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RI Basso, Gianpaolo/A-9208-2012 OI Basso, Gianpaolo/0000-0002-6245-9402 NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 31 EP 31 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000112 ER PT J AU Chao, LL Martin, A AF Chao, LL Martin, A TI Picture naming and word reading elicit commoncategory-related cortical activity SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 50 EP 51 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000212 ER PT J AU Adams, CM AF Adams, CM TI Multisensory selective attention. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIAAA, Brain Imaging & Electrophysiol Sect, LCS, DICBR,NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 52 EP 52 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000218 ER PT J AU Xu, B Grafman, J Gaillard, WD Ishii, K Vega-Bermudez, F Pietrini, P Reeves-tyer, P DiCamillo, P Theodore, WH AF Xu, B Grafman, J Gaillard, WD Ishii, K Vega-Bermudez, F Pietrini, P Reeves-tyer, P DiCamillo, P Theodore, WH TI Evidence of lateralized epicenters for the computation of speech codes: Rhyming words and pseudowords. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 52 EP 53 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000222 ER PT J AU Koechlin, E Corrado, G Pietrini, P Grafman, J AF Koechlin, E Corrado, G Pietrini, P Grafman, J TI Predictive and adaptative planning in humans: A double dissociation. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 62 EP 62 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000271 ER PT J AU Zalla, T Koechlin, E Basso, G Aquino, P Makale, M Pietrini, P Grafman, J AF Zalla, T Koechlin, E Basso, G Aquino, P Makale, M Pietrini, P Grafman, J TI Human brain response to winning and losing. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Inst Cognit Sci, F-69675 Bron, France. RI Basso, Gianpaolo/A-9208-2012 OI Basso, Gianpaolo/0000-0002-6245-9402 NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 63 EP 64 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000278 ER PT J AU Grossenbacher, PG Driver, JS AF Grossenbacher, PG Driver, JS TI Evidence for body-part-centered spatial frameworks in human attention. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, Bethesda, MD 20892 USA. UCL, Inst Cognit Neurosci, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 67 EP 67 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000298 ER PT J AU Levy, JA Parasuraman, R Greenwood, PM Weintraub, S Sunderland, T AF Levy, JA Parasuraman, R Greenwood, PM Weintraub, S Sunderland, T TI The lateralization of visuospatial attention under the influence of scopolamine in Alzheimer's disease. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Alzheimers Dis Ctr, Chicago, IL USA. Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. NIMH, Geriatr Psychiat Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 69 EP 69 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000311 ER PT J AU Greenwood, PM Parasuraman, R Sunderland, T AF Greenwood, PM Parasuraman, R Sunderland, T TI Deficient shifting and scaling of visuospatial attention in elderly occurs only in the presence of APOE. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 72 EP 72 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000328 ER PT J AU Hoffman, E Haxby, J AF Hoffman, E Haxby, J TI Functional neuroimaging of eye gaze and identity perception. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 77 EP 77 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000350 ER PT J AU van Turennout, M Ellmore, T Chao, L van Horn, J Martin, A AF van Turennout, M Ellmore, T Chao, L van Horn, J Martin, A TI Long-lasting reduction in neural activity after a single exposure to real and nonsense objects: An event-related fMRI study of perceptual priming. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 79 EP 79 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000358 ER PT J AU Lovelace, CT Grossenbacher, PG Crane, CA AF Lovelace, CT Grossenbacher, PG Crane, CA TI Functional connectivity underlying synesthetic perception: Theories and data. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Sect Clin & Expt Neurophysiol, Lab Brain & Cognit, Bethesda, MD 20892 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. Fielding Inst, Santa Barbara, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 1999 SU S BP 85 EP 85 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000391 ER PT J AU Lemkine, GF Goula, D Becker, N Paleari, L Levi, G Demeneix, BA AF Lemkine, GF Goula, D Becker, N Paleari, L Levi, G Demeneix, BA TI Optimisation of polyethylenimine-based gene delivery to mouse brain SO JOURNAL OF DRUG TARGETING LA English DT Article DE apoptosis; cationic polymers; CNS; in vivo gene transfer; synthetic vectors ID CENTRAL-NERVOUS-SYSTEM; IN-VIVO; CELL-DEATH; VECTOR; REGULATOR; MUSCLE; LUNG AB Polyethylenimine (PEI) is proving to be an efficient and versatile vector for gene delivery in vivo. However, a limiting factor is the relatively short duration of gene expression in some sites. Given the particularly high levels of expression seen in the short term we postulated that loss of expression could result from overloading the nucleus with foreign DNA. To address this problem we first followed DNA delivery and localisation with digoxin-labelled plasmid DNA complexed with 22 kD linear PEI and used these complexes for intraventricular injection into brains of anaesthetised newborn mice. At 24 h post injection, labelled DNA was found exclusively in the nuclear and perinuclear regions. We next carried out a dose response curve using decreasing amounts of DNA, either in a constant volume (2 mu l) or at a constant concentration (500 ng/mu l). In both conditions, transgene expression yield was maximum at 100 ng DNA per injection. Using this optimal amount of DNA increased yield of transgene expression significantly at 24 h and one week post-injection as compared to 1 mu g DNA, A final point addressed was whether co-expressing an anti-apoptotic gene could enhance gene expression in the longer term. Co-expressing brl-X-L with luciferase or LacZ significantly increased expression of both these genes at one week post-injection. C1 Museum Natl Hist Nat, Lab Physiol Gen & Comparee, CNRS, UMR 8572, F-75231 Paris 5, France. Adv Biotechnol Ctr, Natl Canc Inst, Lab Mol Morphogenesis, Genoa, Italy. RP Demeneix, BA (reprint author), Museum Natl Hist Nat, Lab Physiol Gen & Comparee, CNRS, UMR 8572, 7 Rue Cuvier, F-75231 Paris 5, France. RI Levi, Giovanni/B-4416-2013 FU Telethon [D.076] NR 18 TC 52 Z9 53 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1061-186X J9 J DRUG TARGET JI J. Drug Target. PY 1999 VL 7 IS 4 BP 305 EP + PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 281XV UT WOS:000085187500007 PM 10682909 ER PT J AU Part, P Wood, CM Gilmour, KM Perry, SF Laurent, P Zadunaisky, J Walsh, PJ AF Part, P Wood, CM Gilmour, KM Perry, SF Laurent, P Zadunaisky, J Walsh, PJ TI Urea and water permeability in the ureotelic gulf toadfish (Opsanus beta) SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article ID TROUT HEAD PREPARATION; NITROGEN-METABOLISM; SUBCELLULAR-LOCALIZATION; BATRACHOIDID FISHES; RAINBOW-TROUT; EXCRETION; AMMONIA; EVOLUTION; TRANSPORTER; PHYSIOLOGY AB The permeability of toadfish gills and skin to urea and water has been measured in order to investigate the mechanisms behind the pulsatile excretion of urea previously described in this species. A perfused gill preparation was used in the all studies and isolated pieces of skin mounted in an Ussing chamber in the skin studies. Simultaneously, urea and water permeability was measured in vivo in free swimming fish. In vivo the nonpulsing urea permeability was exceptionally low compared to other teleosts, while the tritiated water permeability was similar to that of other teleosts. The urea permeability increased 30-fold during a pulse while water permeability stayed unaffected. Compared to in vivo, tritiated water permeability was approximately 50% lower in the gills and the skin when measured directly in the isolated preparations. The urea permeability was almost identical between the three preparations. Four out of 20 perfused gill preparation showed a spontaneous urea pulse during perfusion. Several treatments were tested to elicit the pulse artificially but without success. Hormones and drugs tested were: arginine-vasotocin (AVT), 10(-10) M; adrenaline, 10(-7) M; isoprenaline, 10(-5) M; acetylcholine, 10(-7) and 10(-6) M; serotonin, 10(-7) and 10(-6) M; adenosine, 10(-6) M; cortisol, 10(-7) M; and combinations of AVT, adrenaline, and cortisol. Adrenaline and isoprenaline increased tritiated water permeability without affecting urea permeability. Gradually increasing the ammonia levels in the perfusate from 0.1 mM to 1.6 mM caused a slight increase in water permeability but a marked and progressive increase in urea permeability. No indications of an ammonia trapping mechanism in the gills were found. There was no effect of AVT (10(-10) mol l(-1)) in the urea permeability of the skin preparation while cortisol (10(-7) M) led to a modest increase in urea permeability. Based on a comparison between the in vivo and in vitro preparations used here, we conclude that the urea pulse in a urea-pulsing toadfish occurs through the gills and not the skin. We still do not know which internal mechanism or signal triggers the urea pulse in the toadfish. J. Exp. Zool. 283:1-12, 1999. (C) 1999 Wiley-Liss, Inc. C1 Commiss European Communities, Inst Environm, Joint Res Ctr, I-21020 Ispra, Italy. McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. Univ Glasgow, Div Environm & Evolutionary Biol, Glasgow, Lanark, Scotland. Univ Ottawa, Dept Biol, Ottawa, ON K1N 6N5, Canada. CNRS, Ctr Ecol Physiol Energet, F-67037 Strasbourg, France. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS,Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. RP Walsh, PJ (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS,Marine & Freshwater Biomed Sci Ctr, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. EM pwalsh@rsmas.miami.edu FU NIEHS NIH HHS [ES05705] NR 48 TC 17 Z9 17 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD JAN 1 PY 1999 VL 283 IS 1 BP 1 EP 12 DI 10.1002/(SICI)1097-010X(19990101)283:1<1::AID-JEZ2>3.0.CO;2-G PG 12 WC Zoology SC Zoology GA 153KL UT WOS:000077832200001 PM 9990735 ER PT J AU LeBeau, M Andollo, W Hearn, WL Baselt, R Cone, E Finkle, B Fraser, D Jenkins, A Mayer, J Negrusz, A Poklis, A Walls, C Raymon, L Robertson, M Saady, J AF LeBeau, M Andollo, W Hearn, WL Baselt, R Cone, E Finkle, B Fraser, D Jenkins, A Mayer, J Negrusz, A Poklis, A Walls, C Raymon, L Robertson, M Saady, J TI Recommendations for toxicological investigations of drug-facilitated sexual assaults SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; drug-facilitated; sexual assault; drug rape; date rape; forensic toxicology ID GC-MS; FLUNITRAZEPAM; URINE; BENZODIAZEPINES; BLOOD; HAIR; NCI AB The recent increase in reports of drug-facilitated sexual assaults has caused alarm in the general public and prompted forensic toxicologists from across North America to address the toxicological issues surrounding this matter. The authors have developed recommendations and guidelines to inform law enforcement, medical, and scientific personnel of the requirements for per forming successful toxicological examinations in cases of drug-facilitated rape. C1 Fed Bur Invest, FBI Lab, Chem Unit, Washington, DC 20535 USA. Dade Cty Med Examiner Dept, Miami, FL 33136 USA. Inst Chem Toxicol, Foster City, CA 94404 USA. Natl Inst Drug Abuse, Baltimore, MD 21224 USA. US FDA, Cincinnati, OH 45202 USA. Cuyahoga Cty Coroners Off, Cleveland, OH 44106 USA. Univ Toronto, Toronto, ON, Canada. Ctr Forens Sci, Toronto, ON M7A 2G8, Canada. Univ Illinois, Chicago, IL 60612 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Univ Miami, Miami, FL 33177 USA. Natl Med Serv, Willow Grove, PA 19090 USA. Virginia Div Forens Sci, Richmond, VA 23219 USA. RP LeBeau, M (reprint author), Fed Bur Invest, FBI Lab, Chem Unit, Washington, DC 20535 USA. NR 22 TC 108 Z9 116 U1 0 U2 16 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JAN PY 1999 VL 44 IS 1 BP 227 EP 230 PG 4 WC Medicine, Legal SC Legal Medicine GA 293AV UT WOS:000085830100039 PM 9987892 ER PT J AU Hoofnagle, JH AF Hoofnagle, JH TI Management of hepatitis C: current and future perspectives SO JOURNAL OF HEPATOLOGY LA English DT Article; Proceedings Paper CT EASL International Consensus Conference on Hepatitis C CY FEB 26-27, 1999 CL PARIS, FRANCE DE cirrhosis; consensus conferences; controlled trials; hepatitis C; hepatitis C virus; interferon; ribavirin ID NON-A; INTERFERON-ALPHA-2B; RIBAVIRIN; COMBINATION; VIRUS AB Chronic hepatitis C is now a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. In March 1997, the National Institutes of Health sponsored a Consensus Development Conference entitled "Management of Hepatitis C", The final statement from the Consensus Panel set forth clear, evidence-based guidelines and recommendations regarding the diagnosis, evaluation, prevention and therapy of hepatitis C, The conclusions of the Consensus Panel have been widely accepted and have brought some degree of uniformity to the management of hepatitis C, An important issue is how to keep such recommendations current in such a rapidly evolving area of medicine, In the 2 years since the Consenus Conference there have been important advances in the management of chronic hepatitis C. Two recommendations of the Consensus Panel deserve modification: first, on the clinical usefulness of genotyping of hepatitis C virus and second, on the optimal therapeutic regimen, Two large multicenter, prospective controlled trials have shown that the combination of alpha interferon with ribavirin pro,ides higher sustained virologic responses than interferon alone and that optimal therapy is a 24-week course for patients with genotypes 2 and 3 and a 48-week course for patients with genotype 1, Furthermore, therapy can be stopped at 24 weeks if HCV RNA is still present, Many clinical challenges remain. Major current needs are for accurate means of assessing the grade and stage of disease, for the likelihood of disease progression and of response to therapy as well as for viral eradication by treatment. Also important are new therapies for hepatitis C that might be used alone or in combination with interferon and ribavirin; therapies that could be applied to a wide variety of patients, with different stages of disease and with other co-morbitities. C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Bldg 31,Room 9A23, Bethesda, MD 20892 USA. NR 9 TC 39 Z9 40 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 1999 VL 31 SU 1 BP 264 EP 268 DI 10.1016/S0168-8278(99)80414-0 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 278HU UT WOS:000084983900049 PM 10622600 ER PT J AU Lyons, LA Kehler, JS O'Brien, SJ AF Lyons, LA Kehler, JS O'Brien, SJ TI Development of comparative anchor tagged sequences (CATS) for canine genome mapping SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT International Workshop on Canine Genetics - The Map, the Genes, the Diseases CY JUL 12-13, 1997 CL CORNELL UNIV, ITHACA, NEW YORK HO CORNELL UNIV ID LINKAGE MAP; MARKERS; PANEL; LOCI; DNA AB The development of a useful genetic map of the domestic dog would benefit by the inclusion of type I markers; coding genes that can connect the canine map to the homologous gene maps of other mammalian species. A group of 280 comparative anchor tagged sequences (CATS), and universal mammalian sequence tagged sites (UM-STS), were optimized for canine assessment. One hundred and five were screened for genetic polymorphism among nine canine breeds and three wild species of Canis in an attempt to promote gene mapping of comparative type I markers. Three categories of variation-size, restriction fragment length polymorphism (RFLP), and single-strand conformation polymorphism (SSCP)-were assessed. The data showed that 50% of the type I markers discriminate between species and 40% showed genetic variation among dog breeds. Although polymorphism incidence between nominated breeds for gene mapping is more limited than found for established reference pedigrees in other species, the concept and application of these CATS and UM-STS markers is useful in capturing the comparative information required for the full application and efficacy of the dog gene map. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. RP Lyons, LA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Bldg 560, Frederick, MD 21702 USA. NR 24 TC 15 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD JAN-FEB PY 1999 VL 90 IS 1 BP 15 EP 26 DI 10.1093/jhered/90.1.15 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 160HW UT WOS:000078225400004 PM 9987897 ER PT J AU Silver, S Wahl, SM Orkin, BA Orenstein, JM AF Silver, S Wahl, SM Orkin, BA Orenstein, JM TI Changes in circulating levels of HIV, CD4, and tissue expression of HIV in a patient with recent-onset ulcerative colitis treated by surgery - Case report SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE ulcerative colitis; CD4 T cells; HIV; inflammatory bowel disease ID IMMUNODEFICIENCY-VIRUS-INFECTION; CROHNS-DISEASE; REPLICATION; INCREASES; LOAD; TUBERCULOSIS; ACTIVATION; TYPE-1; AIDS AB Objective: To determine CD4(+) T-cell count and circulating and tissue levels of HIV before and after surgery in a patient with recent-onset ulcerative colitis. Study Design/Methods: CD4 lymphocytes and circulating and tissue HIV RNA levels were measured in an HIV-infected patient with ulcerative colitis before and after proctocolectomy. Results: Approximately 3 weeks prior to surgery for ulcerative colitis that was unresponsive to corticosteroids, the patient's CD4 count was 930 cells/mm(3) and fell to 313 cells/mm(3) within 10 days; the viral burden was similar to 80,000 RNA copies/mL. Tissue macrophages and lymphocytes in biopsy and resection specimens were shown to express high levels of PW RNA by in situ hybridization. Five days postoperatively, the patient became asymptomatic and was discharged on tapering prednisone without antiretroviral agents. After surgery, the patient's CD4 count progressively rose, while viral RNA levels precipitously dropped. At 3, 6, and 15 weeks postoperatively, CD4 and viral RNA counts were 622 cells/mm(3) and 31,300 RNA copies/mL, 843 cells/mm(3) and 11,400 RNA copies/mL, and 747 cells/mm(3) and 1500 RNA copies/mL, respectively. Conclusions: Circulating levels of HIV and CD4(+) cells, as well as tissue expression of HIV, apparently can be influenced by localized inflammatory processes such as those occurring in inflammatory bowel disease. C1 George Washington Univ, Sch Med & Hlth Sci, Dept Pathol, Washington, DC 20037 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Surg, Washington, DC 20037 USA. RP Orenstein, JM (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Pathol, Ross 502,2300 I St NW, Washington, DC 20037 USA. FU NIDCR NIH HHS [DE 12585] NR 22 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD JAN-FEB PY 1999 VL 2 IS 1 BP 52 EP 57 PG 6 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 245AW UT WOS:000083084900008 PM 10200600 ER PT J AU Hunt, SC Province, MA Atwood, LD Sholinsky, P Lalouel, JM Rao, DC Williams, RR Leppert, MF AF Hunt, SC Province, MA Atwood, LD Sholinsky, P Lalouel, JM Rao, DC Williams, RR Leppert, MF TI No linkage of the lipoprotein lipase locus to hypertension in Caucasians SO JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; genetics; lipids ID FAMILIAL COMBINED HYPERLIPIDEMIA; EXTENDED PEDIGREE; LPL GENE; DEFICIENCY; UTAH; INDIVIDUALS; PROBAND AB Objective A previous study has shown significant linkage of five markers near the lipoprotein lipase locus to systolic blood pressure, but not to diastolic blood pressure, in nondiabetic members of 48 Taiwanese families selected for noninsulin-dependent diabetes. However, lipoprotein lipase markers did not appear strongly linked to systolic blood pressure in a study of Mexican-Americans using a variety of selection schemes. The objective of the current study was to test whether markers near the lipoprotein lipase gene were linked to hypertension in Caucasians. Design To test for linkage of genetic markers in or near the lipoprotein lipase gene to hypertension in Caucasians, two sets of Caucasian hypertensive sibships were genotyped. The samples included 261 sibships (431 effective sibpairs) from four field centers of the National Heart, Lung and Blood Institute Family Heart Study and 211 sibships (282 effective sibpairs) from the Health Family Tree database in Utah. Results Two highly polymorphic markers in or near the lipoprotein lipase gene showed no evidence of excess allele sharing in either set of hypertensive sibships. Combining the two datasets resulted in 653 and 713 effective sibpairs for the two markers, sharing 0.495 +/- 0.30 and 0.486 +/- 0.28 alleles identical by descent compared to an expected sharing of 0.50. Multipoint analysis of the two loci also did not show linkage (P = 0.95). Conclusions We conclude that the lipoprotein lipase locus and nearby regions do not appear to be linked to hypertension in Caucasians. J Hypertens 1999, 17:39-43 (C) Lippincott Williams & Wilkins. C1 Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84108 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT 84108 USA. Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84108 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychiat & Genet, St Louis, MO 63110 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Hunt, SC (reprint author), Univ Utah, Sch Med, Dept Internal Med, 410 Chipeta Way,Room 167, Salt Lake City, UT 84108 USA. EM steve@ucvg.med.utah.edu FU NHLBI NIH HHS [HL56563, HL56565, HL56564] NR 22 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JAN PY 1999 VL 17 IS 1 BP 39 EP 43 DI 10.1097/00004872-199917010-00007 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 177XD UT WOS:000079235600007 PM 10100092 ER PT J AU Arudchandran, R Brown, MJ Song, JS Wank, SA Haleem-Smith, H Rivera, J AF Arudchandran, R Brown, MJ Song, JS Wank, SA Haleem-Smith, H Rivera, J TI Polyethylene glycol-mediated infection of non-permissive mammalian cells with semliki forest virus: application to signal transduction studies SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Semliki forest virus; polyethylene glycol; green fluorescent protein; signal transduction; protein expression ID HIGH-LEVEL EXPRESSION; SYSTEM; LEUKEMIA; KINASE; FUSION; LINES; VAV AB Semliki Forest Virus (SFV) vectors allow the subcloning of a gene of interest directly in the expression vector, thus avoiding the need to select and purify viral recombinants, making this viral expression system attractive over many others for mammalian protein expression. We now describe a novel and generally applicable method for infection of non-permissive mammalian cells with SFV, that greatly enhances the utility of this expression system. We demonstrate that the hygroscopic polymer poly (ethylene glycol), PEG, promotes the infectivity of cells by SFV under conditions that did not promote cell-cell fusion. We also found that the PEG-induced infection and expression of an exogenous protein (green fluorescent protein, GFP) did not elevate the basal tyrosine kinase activity, induce a stress-activated responses, or result in aberrant cell responses. Expression of GFP tagged-Vav, an activator of stress-activated protein kinase (SAPK/JNK), resulted in the expected induction of JNK activity and in the normal redistribution of Vav in response to engagement of the high affinity receptor for IgE (Fc epsilon RI). Thus, our findings that PEG allows the infection of non-permissive cells by SFV makes this system extremely attractive for expression of proteins in mammalian cells, and studies on signal transduction and cellular localization in immune and non-immune cells. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), Bldg 10,Room 9N228,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov NR 24 TC 12 Z9 14 U1 0 U2 2 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 JAN 1 PY 1999 VL 222 IS 1-2 BP 197 EP 208 DI 10.1016/S0022-1759(98)00161-6 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 155CD UT WOS:000077927600019 PM 10022386 ER PT J AU Hashino, T Winkler-Pickett, RT Mason, AT Ortaldo, JR Young, HA AF Hashino, T Winkler-Pickett, RT Mason, AT Ortaldo, JR Young, HA TI IL-13 production by NK cells: IL-13-producing NK and T cells are present in vivo in the absence of IFN-gamma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; LARGE GRANULAR LYMPHOCYTES; HUMAN B-CELLS; INTERFERON-GAMMA; CYTOKINE PRODUCTION; IMMUNE REGULATION; CD40 LIGAND; BETA-CHAIN; IN-VIVO; MICE AB In this study, we demonstrate that human Mt cells, human NK clones, the human NK cell line (NK3.3), and a population of murine NK cells can produce the type 2 cytokine IL-13 in response to IL-2 or phorbol myristate acetate plus ionomycin, IL-2 rapidly induced new IL-13 mRNA and protein synthesis in the NK3.3 cell line, Six of 12 human NK clones tested produced IL-13 protein in response to IL-2 or phorbol myristate acetate and ionomycin, Intracellular analysis revealed that similar to 2% of human peripheral NK cells produced IL-13 protein in response to IL-2, Isolated NK cells from SCID and RAG-2 knockout (-/-) mice that lack T and B cells as well as normal mice also can produce IL-13 mRNA and protein in response to IL-2, We hypothesized that in the absence of IFN-gamma, IL-13-producing NK cells may predominate in vivo. Utilizing IFN-gamma knockout (-/-) mice as a model system, IL-2-activated liver NK and T cells expressed 10-fold more IL-13 and IL-5 mRNA and protein than normal controls following IL-2 treatment in vitro. These results suggest that in the absence of IFN-gamma, an IL-13- and IL-5-producing NK and T cells predominate in vivo. The existence of this cell type has important implications in innate immunity given that the balance between IFN-gamma and IL-13/IL-5-producing NK cells may influence the early development of a cell-mediated or humoral immune response. C1 NCI, Expt Immunol Lab, Div Basic Sci,Biol Response Modifiers Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI, Expt Immunol Lab, Div Basic Sci,Biol Response Modifiers Program, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM youngh@mail.ncifcrf.gov RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 47 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1999 VL 162 IS 1 BP 51 EP 59 PG 9 WC Immunology SC Immunology GA 151YK UT WOS:000077748100008 ER PT J AU Liao, F Rabin, RL Smith, CS Sharma, G Nutman, TB Farber, JM AF Liao, F Rabin, RL Smith, CS Sharma, G Nutman, TB Farber, JM TI CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MOLECULAR-CLONING; DENDRITIC CELLS; LYMPHOCYTE CHEMOATTRACTANT; INDUCIBLE PROTEIN-10; MONOCLONAL-ANTIBODY; T-HELPER-2 CELLS; COUPLED RECEPTOR; HOMING RECEPTOR; BETA-CHEMOKINE AB CC-chemokine receptor (CCR) 6 is the only known receptor for macrophage inflammatory protein (MIP)-3 alpha, a CC chemokine chemotactic for lymphocytes and dendritic cells, Using anti-serum that we raised against the N-terminal residues of CCR6, we have characterized the surface expression of CCR6 on peripheral blood leukocytes and we have correlated CCR6 expression with responses to MIP-3 alpha. We found that CCR6 was expressed only on memory T cells, including most alpha(4)beta(7) memory cells and cutaneous lymphocyte-associated Ag-expressing cells, and on B cells, Accordingly, chemotaxis of T cells to MIP-3 alpha was limited to memory cells. Moreover, calcium signals on T cells in response to MIP-3 alpha were confined to CCR6-expressing cells, consistent with CCR6 being the only MIP-3 alpha receptor on peripheral blood T cells. Unlike many CC chemokines, MIP-3 alpha produced a calcium signal on freshly isolated T cells, and CCR6 expression was not increased by up to 5 days of treatment with IL-2 or by cross-linking CD3. Despite their surface expression of CCR6, freshly isolated B cells did not respond to MIP-3 alpha. In addition to staining peripheral blood leukocytes, our anti-serum detected CCR6 on CD34(+) bone marrow cell-derived dendritic cells, Our data are the first to analyze surface expression of CCR6, demonstrating receptor expression on differentiated, resting memory T cells, indicating differences in receptor signaling on T cells and B cells and suggesting that CCR6 and MIP-3 alpha may play a role in the physiology of resting memory T cells and in the interactions of memory T cells, B cells, and dendritic cells. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N-228, Bethesda, MD 20892 USA. NR 60 TC 301 Z9 309 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 JAN 1 PY 1999 VL 162 IS 1 BP 186 EP 194 PG 9 WC Immunology SC Immunology GA 151YK UT WOS:000077748100024 PM 9886385 ER PT J AU Brooks, AG Borrego, F Posch, PE Patamawenu, A Scorzelli, CJ Ulbrecht, M Weiss, EH Coligan, JE AF Brooks, AG Borrego, F Posch, PE Patamawenu, A Scorzelli, CJ Ulbrecht, M Weiss, EH Coligan, JE TI Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INHIBITORY RECEPTOR; INTRACELLULAR-TRANSPORT; CD94; PEPTIDES; COMPLEX; FAMILY AB The CD94/NKG2 receptors expressed by subpopulations of NK cells and T cells have been implicated as receptors for a broad range of both classical and nonclassical HLA class I molecules. To examine the ligand specificity of CD94/NKG2 proteins, a soluble heterodimeric form of the receptor was produced and used in direct binding studies with cells expressing defined HLA class I/peptide complexes. We confirm that CD94/NKG2A specifically interacts with HLA-E and demonstrate that this interaction is dependent on the association of HLA-E with peptide. Moreover, no interaction between CD94/NKG2A and classical HLA class I molecules was observed, as assayed by direct binding of the soluble receptor or by functional assays using CD94/NKG2A(+) NK cells. The role of the peptide associated with HLA-E in the interaction between HLA-E and CD94/NKG2A was also assessed. All class I leader sequence peptides tested bound to HLA-E and were recognized by CD94/NKG2A, However, amino acid variations in class I reader sequences affected the stability of HLA-E, Additionally, not all HLA-E/peptide complexes examined were recognized by CD94/NKG2A, Thus CD94/NKG2A recognition of HLA-E is controlled by peptide at two levels; first, peptide must stabilize HLA-E and promote cell surface expression, and second, the HLA-E/peptide complex must form the ligand for CD94/NKG2A. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIAID, Struct Biol Sect, NIH, Rockville, MD 20852 USA. Univ Munich, Inst Anthropol & Human Genet, D-8000 Munich, Germany. RP Coligan, JE (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 31 TC 124 Z9 128 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1999 VL 162 IS 1 BP 305 EP 313 PG 9 WC Immunology SC Immunology GA 151YK UT WOS:000077748100039 PM 9886400 ER PT J AU Jankovic, D Wynn, TA Kullberg, MC Hieny, S Caspar, P James, S Cheever, AW Sher, A AF Jankovic, D Wynn, TA Kullberg, MC Hieny, S Caspar, P James, S Cheever, AW Sher, A TI Optimal vaccination against Schistosoma mansoni requires the induction of both B cell- and IFN-gamma-dependent effector mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RADIATION-ATTENUATED CERCARIAE; PROTECTIVE IMMUNITY; IRRADIATED CERCARIAE; T-CELL; MURINE SCHISTOSOMIASIS; TOLERANCE INDUCTION; INDUCED RESISTANCE; CYTOKINE SYNTHESIS; TOXOPLASMA-GONDII; DEFICIENT MICE AB Mice immunized with radiation-attenuated cercariae of Schistosoma mansoni display resistance to challenge infection, which increases with multiple boosting. Protection in animals receiving a single vaccination is thought to involve a primarily cell-mediated, IFN-gamma-dependent mechanism, while humoral immunity has been shown to contribute to challenge rejection in multiply (three times) immunized mice. To better understand the respective contribution of the B lymphocyte and IFN-gamma-dependent effector arms in host resistance, we compared vaccine-induced immunity in B cell-deficient (mu MT) and IFN-gamma knockout (GKO) animals. Unexpectedly, after a single vaccination, B cell knockout (KO) mice displayed reduced protection against challenge infection, although they developed a normal IFN-gamma-dominated cytokine response. This defect in resistance was equivalent to that displayed by GKO animals, Moreover, whereas two additional vaccinations significantly increased the level of immunity in wild-type mice, the protection in B cell KO animals remained unchanged. In contrast, multiple vaccination resulted in increased but, nevertheless, defective resistance in GKO mice. Since FcR gamma KO mice, which lack functional Fc gamma RI, Fc gamma RIII, and Fc epsilon RI, show no defects in vaccine-induced resistance after immunization either one or three times, the B cell-dependent mechanism of protection involved does not appear to require FcR signaling, Together, these findings indicate that effective vaccination against schistosomes depends on the simultaneous induction of both humoral and cell-mediated immunity, a conclusion that may explain the limited success of most subunit vaccine protocols designed to preferentially induce either B cell- or IFN-gamma-dependent protective mechanisms. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Jankovic, D (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 4-126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM djankovic@atlas.niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 50 TC 102 Z9 113 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1999 VL 162 IS 1 BP 345 EP 351 PG 7 WC Immunology SC Immunology GA 151YK UT WOS:000077748100044 PM 9886405 ER PT J AU Nardelli, B Tiffany, HL Bong, GW Yourey, PA Morahan, DK Li, YL Murphy, PM Alderson, RF AF Nardelli, B Tiffany, HL Bong, GW Yourey, PA Morahan, DK Li, YL Murphy, PM Alderson, RF TI Characterization of the signal transduction pathway activated in human monocytes and dendritic cells by MPIF-1, a specific ligand for CC chemokine receptor 1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; CHEMOTACTIC PROTEIN-1; FUNCTIONAL EXPRESSION; CHEMOATTRACTANT; IDENTIFICATION; CLONING; MIP-1-ALPHA; MIP-1-BETA; INHIBITION; SYNERGISM AB The receptor specificity and signal transduction pathway has been identified and characterized for a truncated form of myeloid progenitor inhibitory factor-1 (MPIF1(24-99)). MPIF-1 binds specifically to sites, in particular CCR1, shared with macrophage inflammatory protein-la (MIP-la) on the surface of human monocytes and dendritic cells, as inferred by its ability to compete for [I-125]MIP-1 alpha, but not for [I-125]MIP-1 beta or [I-125]monocyte chemotactic protein-1 (MCP-1) binding to intact cells. Based on calcium flux. MPIF-1 is an agonist on CCR1-transfected HEK-293 cells, monocytes, and dendritic cells, but not on CCR5-, CCR8-, or CX(3)CR1-transfected cells. The inhibitory effect of guanosine 5'-O-(3-thio-triphosphate) (GTP-gamma S) or pertussis toxin pretreatment on MPIF-1 binding and calcium mobilization, respectively, indicates the involvement of G proteins in the interaction of MPIF-1 and its receptor(s). The increase in intracellular free calcium concentration following MPIF-1 treatment is mainly due to the influx of calcium from an extracellular pool. However, a portion of the intracellular free calcium concentration is derived from a phospholipase C inhibitor-sensitive intracellular pool. MPIF-1 induces a rapid dose-dependent release of [H-3]arachidonic acid from monocytes that is dependent on extracellular calcium and is blocked by phospholipase A(2) (PLA(2)) inhibitors. Furthermore, PLA(2) activation is shown to be necessary for filamentous actin formation in monocytes. Thus, the MPH-1 signal transduction pathway appears to include binding to CCR1; transduction by G proteins; effector function by phospholipase C, protein kinase C, calcium flux, and PLA(2); and cytoskeletal remodeling. C1 Human Genome Sci Inc, Dept Cell Biol, Rockville, MD 20850 USA. Human Genome Sci Inc, Dept Pharmacol, Rockville, MD 20850 USA. Human Genome Sci Inc, Dept Prot Express, Rockville, MD 20850 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Nardelli, B (reprint author), Human Genome Sci Inc, Dept Cell Biol, 9410 Key W Ave, Rockville, MD 20850 USA. EM bernardetta_nardelli@hgsi.com NR 36 TC 43 Z9 46 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1999 VL 162 IS 1 BP 435 EP 444 PG 10 WC Immunology SC Immunology GA 151YK UT WOS:000077748100056 PM 9886417 ER PT J AU Egwuagu, CE Sztein, J Mahdi, RM Li, WM Chao-Chan, C Smith, JA Charukamnoetkanok, P Chepelinsky, AB AF Egwuagu, CE Sztein, J Mahdi, RM Li, WM Chao-Chan, C Smith, JA Charukamnoetkanok, P Chepelinsky, AB TI IFN-gamma increases the severity and accelerates the onset of experimental autoimmune uveitis in transgenic rats SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETINOID-BINDING PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; INTERFERON-GAMMA; NITRIC-OXIDE; S-ANTIGEN; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; MICE; UVEORETINITIS; DISEASE AB Experimental autoimmune uveitis (EAU) is a predominantly Th1-mediated intraocular inflammatory disease that serves as a model for studying the immunopathogenic mechanisms of uveitis and organ-specific autoimmune diseases. Despite the well-documented role of IFN-gamma in the activation of inflammatory cells that mediate autoimmune pathology, recent studies in IFN-gamma-deficient mice paradoxically show that IFN-gamma confers protection from EAU. Because of the implications of these findings for therapeutic use of IFN-gamma, we sought to reexamine these results in the rat, another species that shares essential immunopathologic features with human uveitis and is the commonly used animal model of uveitis. We generated transgenic rats (TR) with targeted expression of IFN-gamma in the eye and examined whether constitutive ocular expression of IFN-gamma would influence the course of EAU. We show here that the onset of rat EAU is markedly accelerated and is severely exacerbated by IFN-gamma. In both wild-type and TR rats, we found that the disease onset is preceded by induction of ICAM-1 gene expression and is characterized by selective recruitment of T cells expressing a restricted TCR repertoire in the retina. In addition, these events occur 2 days earlier in TR rats. Thus, in contrast to the protective effects of IFN-gamma in mouse EAU, our data clearly show that intraocular secretion of IFN-gamma does not confer protection against EAU in the rat and suggest that IFN-gamma may activate distinct immunomodulatory pathways in mice and rats during uveitis. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Vet Res & Resources, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N116, Bethesda, MD 20892 USA. EM emeka@helix.nih.gov RI Sztein, Jorge/B-7165-2012 NR 52 TC 43 Z9 43 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1999 VL 162 IS 1 BP 510 EP 517 PG 8 WC Immunology SC Immunology GA 151YK UT WOS:000077748100066 PM 9886427 ER PT J AU Lem, L Riethof, DA Scidmore-Carlson, M Griffiths, GM Hackstadt, T Brodsky, FM AF Lem, L Riethof, DA Scidmore-Carlson, M Griffiths, GM Hackstadt, T Brodsky, FM TI Enhanced interaction of HLA-DM with HLA-DR in enlarged vacuoles of hereditary and infectious lysosomal diseases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEDIAK-HIGASHI-SYNDROME; INVARIANT CHAIN PEPTIDES; CLASS-II COMPARTMENTS; ANTIGEN-PROCESSING MUTANT; CELL-SURFACE; ENDOCYTIC COMPARTMENT; MONOCLONAL-ANTIBODIES; CHLAMYDIA-TRACHOMATIS; COXIELLA-BURNETII; B-LYMPHOCYTES AB Following biosynthesis, class II MHC molecules are transported through a lysosome-like compartment, where they acquire antigenic peptides for presentation to T cells at the cell surface. This compartment is characterized by the presence of HLA-DM, which catalyzes the peptide loading process, Here we report that the morphology and function of the class II loading compartment is affected in diseases with a phenotypic change in lysosome morphology, Swollen lysosomes are observed in cells from patients with the hereditary immunodeficiency Chediak-Higashi syndrome and in cells infected with Coxiella burnetii, the rickettsial organism that causes Q fever. In both disease states, we observed that HLA-DR and HLA-DM accumulate in enlarged intracellular compartments, which label with the lysosomal marker LAMP-I, The distribution of class I MHC molecules was not affected, localizing disease effects to the endocytic pathway. Thus, cellular mechanisms controlling lysosome biogenesis also affect formation of the class II loading compartment, Analysis of cell surface class II molecules revealed that their steady-state levers were not reduced on diseased cells. However, in both disease states, enhanced interaction between HLA-DR and HLA-DM was detected. In the Chediak-Higashi syndrome cells; this correlated with more efficient removal of the CLIP peptide. These findings suggest a mechanism for perturbation of Ag presentation by class II molecules and consequent immune deficiencies in both diseases. C1 Univ Calif San Francisco, George Williams Hooper Fdn, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. NIAID, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. RP Brodsky, FM (reprint author), Univ Calif San Francisco, George Williams Hooper Fdn, Dept Microbiol & Immunol, Box 0552, San Francisco, CA 94143 USA. FU NIAID NIH HHS [AI39152]; NIAMS NIH HHS [AR20684]; PHS HHS [5T32 A107334]; Wellcome Trust NR 48 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1999 VL 162 IS 1 BP 523 EP 532 PG 10 WC Immunology SC Immunology GA 151YK UT WOS:000077748100068 PM 9886429 ER PT J AU Shirai, M Arichi, T Chen, M Nishioka, M Ikeda, K Takahashi, H Enomoto, N Saito, T Major, ME Nakazawa, T Akatsuka, T Feinstone, SM Berzofsky, JA AF Shirai, M Arichi, T Chen, M Nishioka, M Ikeda, K Takahashi, H Enomoto, N Saito, T Major, ME Nakazawa, T Akatsuka, T Feinstone, SM Berzofsky, JA TI T cell recognition of hypervariable region-1 from hepatitis C virus envelope protein with multiple class II MHC molecules in mice and humans: Preferential help for induction of antibodies to the hypervariable region SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NON-B-HEPATITIS; CHRONIC NON-A; DIFFERENT DETERMINANTS; MONOCLONAL-ANTIBODIES; NUCLEOTIDE-SEQUENCE; HYPERIMMUNE SERUM; IMMUNE-RESPONSE; LYMPHOCYTES-T; ANTIGEN; EPITOPE AB Hypervariable region-1 (HVR1) from the hepatitis C virus (HCV) envelope protein is thought to be a target for neutralizing Abs, To explore HVR1 recognition by helper T cells, and their role in Ab responses, we attempted to generate helper T cells specific for HVR1 in mice of three MHC types, and with PBMC from HCV-infected HLA-diverse humans. In both species, HVR1 was presented by >1 class II MHC molecule to CD4(+) helper T cells and showed surprising interisolate cross-reactivity, The epitope for two DR4(+) patients was mapped to a more conserved C-terminal sequence containing a DR4 binding motif, possibly accounting for cross-reactivity, Strikingly, Abs to patients' own HVR1 sequences were found only in patients with T cell responses to HVR1, even though all had Abs to envelope protein, suggesting that induction of Abs to HVR1 depends on helper T cells specific for a sequence proximal to the Ab epitope, Thus, helper T cells specific for HVR1 may be functionally important in inducing neutralizing Abs to HCV, These results may be the first example of "T-B reciprocity," in which proximity of a helper T cell epitope determines Ab epitope specificity, in a human disease setting. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. Yamaguchi Univ, Sch Med, Dept Microbiol, Yamaguchi, Japan. Kagawa Med Sch, Dept Transfus Med, Kagawa 76107, Japan. Kagawa Med Sch, Dept Internal Med 3, Kagawa 76107, Japan. Nippon Med Sch, Dept Microbiol & Immunol, Tokyo 113, Japan. Tokyo Med & Dent Univ, Dept Internal Med 2, Tokyo 113, Japan. US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12, Bethesda, MD 20892 USA. NR 50 TC 44 Z9 46 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1999 VL 162 IS 1 BP 568 EP 576 PG 9 WC Immunology SC Immunology GA 151YK UT WOS:000077748100073 PM 9886434 ER PT J AU Clave, E Molldrem, J Hensel, N Raptis, A Barrett, AJ AF Clave, E Molldrem, J Hensel, N Raptis, A Barrett, AJ TI Donor-recipient polymorphism of the proteinase 3 gene: A potential target for T-cell alloresponses to myeloid leukemia SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE proteinase 3; graft-versus-leukemia; bone marrow transplantation; polymorphism ID WEGENERS GRANULOMATOSIS; SERINE PROTEASE; BCR-ABL; AUTOANTIGEN; MYELOBLASTIN; ANTIGENS; PEPTIDES; CLONING AB The curative effect of allogeneic bone marrow transplantation (BMT) is in part due to an alloresponse of donor lymphocytes against recipient leukemia termed the graft versus leukemia (GvL) effect. To identify target antigens for the GvL response on leukemia cells, we looked for polymorphism of proteinase 3, a primary granule protein overexpressed in myeloid leukemias. The study was carried out in 10 patients with hematologic diseases and their HLA-identical marrow donors. By polymerase chain reaction (PCR) -single sb:and conformation polymorphism assay, followed by direct sequencing of the PCR products, we found seven DNA polymorphisms. One of them encodes for either an isoleucine or a valine at position 119 of the amino acid sequence. Peptides that span the polymorphic site, at amino acids 115-124, were shown to bind in vitro to the HLA-A2 molecule. We screened 23 HLA-A2 patients with myeloid leukemia and their HLA-identical donors for this polymorphism. No relapse was found in the group of 4 evaluable patients who possessed at least one allele absent in their donor, whereas 7 of the 15 remaining evaluable patients relapsed. These data support the possibility that T-cell responses to allelic differences of proteinase 3 could be used as a basis for designing leukemia-specific adoptive T-cell therapy in acute and chronic myeloid leukemias. C1 NIH, Bone Marrow Transplantat Unit, Hematol Branch, NHLBI, Bethesda, MD 20892 USA. RP Clave, E (reprint author), NIH, Bone Marrow Transplantat Unit, Hematol Branch, NHLBI, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 18 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 1999 VL 22 IS 1 BP 1 EP 6 DI 10.1097/00002371-199901000-00001 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 157CB UT WOS:000078040600001 PM 9924693 ER PT J AU Beyrer, C Artenstein, AW Rugpao, S Stephens, H VanCott, TC Robb, ML Rinkaew, M Birx, DL Khamboonruang, C Zimmerman, PA Nelson, KE Natpratan, C AF Beyrer, C Artenstein, AW Rugpao, S Stephens, H VanCott, TC Robb, ML Rinkaew, M Birx, DL Khamboonruang, C Zimmerman, PA Nelson, KE Natpratan, C CA Chiang Mai HEPS Working Grp TI Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type I highly exposed, persistently seronegative female sex workers in northern Thailand SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MUCOSAL IMMUNE-RESPONSES; T-CELL ACTIVITY; HIV-1 INFECTION; DISEASE PROGRESSION; CHEMOKINE RECEPTOR; PERIPHERAL-BLOOD; DELETION ALLELE; CHILDREN BORN; SIV INFECTION; HTLV-III/LAV AB Characterization of persons highly exposed to human immunodeficiency virus (HIV)-1 who remain uninfected may help define protective immunity Seventeen HIV-l-seronegative Thai female sex workers (CSWs) with epidemiologic evidence of exposure to HIV-1 were studied for humoral immune responses and phenotypic and genotypic analyses of HLA class I and CCR5 allelic profiles. Infected CSWs and low-risk HIV-l-seronegative Thai women were controls. Highly exposed, persistently seronegative (HEPS) CSWs did not differ from HIV-infected CSWs in HIV risks, condom use, or sexually transmitted diseases. Significant differences were seen in humoral immune responses: gp160-specific IgA responses were detected in cervicovaginal lavage fluids in 6 of 13 HEPS CSWs but 0 of 21 seronegative subjects. All women had wild-type CCR5, HEPS CSWs were more likely to have the HLA-B18 phenotype and genotype than were matched controls (corrected P=.018), Epidemiologic exposure to HIV-1 without apparent infection, an unusual distribution of HLA class I alleles, and HIV-1 gp160-specific IgA responses suggest a biologic basis for this phenomenon. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD USA. Henry M Jackson Fdn, Rockville, MD USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand. Reg Off Communicable Dis Control, Chiang Mai, Thailand. Siriraj Hosp, Bangkok, Thailand. Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. UCL, Sch Med, London W1N 8AA, England. RP Beyrer, C (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, 615 N Wolfe St,Suite 7132, Baltimore, MD 21205 USA. EM cbeyrer@jhsph.edu FU PHS HHS [H4188732155] NR 70 TC 152 Z9 153 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1999 VL 179 IS 1 BP 59 EP 67 DI 10.1086/314556 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151MW UT WOS:000077725000009 PM 9841823 ER PT J AU Savarino, SJ Hall, ER Bassily, S Brown, FM Youssef, F Wierzba, TF Peruski, L El-Masry, NA Safwat, M Rao, M El Mohamady, H Abu-Elyazeed, R Naficy, A Svennerholm, AM Jertborn, M Lee, YJ Clemens, JD AF Savarino, SJ Hall, ER Bassily, S Brown, FM Youssef, F Wierzba, TF Peruski, L El-Masry, NA Safwat, M Rao, M El Mohamady, H Abu-Elyazeed, R Naficy, A Svennerholm, AM Jertborn, M Lee, YJ Clemens, JD CA PRIDE Study Grp TI Oral, inactivated, whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine: Results of the initial evaluation in children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Society-for-Microbiology CY MAY 02-08, 1997 CL MIAMI, FLORIDA SP Amer Soc Microbiol ID ANTIBODY-SECRETING CELLS; COLONIZATION FACTOR; MONOCLONAL-ANTIBODIES; IMMUNOSORBENT-ASSAY; ANTIGEN-II; DIARRHEA; IMMUNOGENICITY; ROTAVIRUS; IMMUNIZATION; RESPONSES AB Two randomized, double-blinded trials assessed the safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli (ETEC) plus cholera toxin B subunit vaccine in Egyptian children. Two doses of vaccine or E. coli K-12 were given 2 weeks apart to 105 6- to 12-year-olds and 97 2- to 5-year-olds. Safety was monitored for 3 days after each dose. Blood was collected before immunization and 7 days after each dose to measure immune responses. Few children reported postdosing symptoms, with no differences in the frequency of symptoms between treatment groups. Most vaccinees had an IgA antibody-secreting cell response against colonization factor antigen I(100%, 6-12 years; 95%, 2-5 years), coli surface antigen 2 (92%, 6-12 years; 83%, 2-5 years), and coli surface antigen 4 (93%, 6-12 years). Vaccination evoked a greater than or equal to 4-fold rise in antitoxic IgA and IgG titers in 93% and 81% of children, respectively, In conclusion, the oral ETEC vaccine was safe and immunogenic in 2- to 12-year-old children, justifying further evaluation in infants. C1 USN, Med Res Unit 3, Cairo, Egypt. Egyptian Minist Hlth, Benha, Egypt. Qalyubia Governorate, Governorate, Egypt. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Gothenburg Univ, Dept Med Microbiol & Immunol, S-41124 Gothenburg, Sweden. RP Savarino, SJ (reprint author), USN, Res Publicat Off, Med Res Unit 3, PSC 452,Box 5000, FPO, AE 09835 USA. FU NICHD NIH HHS [HD-0026-01] NR 38 TC 52 Z9 55 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1999 VL 179 IS 1 BP 107 EP 114 DI 10.1086/314543 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151MW UT WOS:000077725000015 PM 9841829 ER PT J AU O'Grady, NP Tropea, M Preas, HL Reda, D Vandivier, RW Banks, SM Suffredini, AF AF O'Grady, NP Tropea, M Preas, HL Reda, D Vandivier, RW Banks, SM Suffredini, AF TI Detection of macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta during experimental endotoxemia and human sepsis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Thoracic-Society CY MAY 16-22, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Thorac Soc ID TUMOR-NECROSIS-FACTOR; INTRAVENOUS ENDOTOXIN; PROTEIN-1-ALPHA MIP-1-ALPHA; EXPRESSION; FEVER; RATS; CHEMOKINES; CELLS; INHIBITION; CYTOKINES AB Macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta regulate leukocyte activation and trafficking, To assess the role of MIP-1 alpha and MIP-1 beta in human inflammation, healthy subjects were studied during experimental endotoxemia with prior administration of ibuprofen, a cyclooxygenase inhibitor, or dimeric p75 tumor necrosis factor (TNF)-alpha receptor, a TNF antagonist; septic patients were also studied. Following endotoxin, blood levels of both MIP-1 molecules rose acutely and fell to baseline by 6 h (P = .001). While MIP-1 mediates fever in animals independent of cyclooxygenase blockade, in subjects given endotoxin and ibuprofen, MIP-1 levels increased and fever was suppressed, MIP-1 levels were not diminished by inhibiting circulating TNF-alpha in humans. In septic patients, elevated levels of MIP-1 alpha and MIP-1 beta were detected within 24 h of sepsis and fell in parallel with TNF-alpha and interleukin-6 (P < .01). MIP-1 alpha and MIP-1 beta increase during acute inflammation but are not associated with fever in endotoxemic humans during cyclooxygenase blockade. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP O'Grady, NP (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Rm 7D-43,10 Ctr Dr,MSC-1662, Bethesda, MD 20892 USA. NR 43 TC 44 Z9 45 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1999 VL 179 IS 1 BP 136 EP 141 DI 10.1086/314559 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151MW UT WOS:000077725000018 PM 9841832 ER PT J AU Huang, SN Angus, CW Turner, RE Sorial, V Kovacs, JA AF Huang, SN Angus, CW Turner, RE Sorial, V Kovacs, JA TI Identification and characterization of novel variant major surface glycoprotein gene families in rat Pneumocystis carinii SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Keystone Symposium on Molecular and Cellular Biology, Opportunistic Infections in AIDS CY APR, 1998 CL KEYSTONE, COLORADO ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ANTIGENIC VARIATION; EXPRESSION SITE; TRYPANOSOMA-BRUCEI; CYTOKINE RESPONSES; PROTEIN ANCHORS; IN-VITRO; IMMUNIZATION; PURIFICATION; ATTACHMENT AB The major surface glycoprotein (MSG) is an abundant, immunodominant protein on the surface of the opportunistic pathogen Pneumocystis carinii, The current study identified two novel variant MSG (vMSG) gene families in rat I! carinii that are closely related to but distinct from MSG. These gene families encode proteins of similar to 90 kDa (v1MSG) and similar to 115 kDa (v2MSG). Compared with MSG, v1MSG is characterized by a deletion near the carboxyl terminus, The predicted v1MSG and v2MSG proteins are highly homologous to MSG at the carboxyl, but not the amino, terminus, Like MSG, they are cysteine-rich, Approximately 10% of the apparent molecular weight is due to N-linked glycosylation, Southern blotting studies demonstrated that, like MSG, v1MSG and v2MSG are the products of multicopy gene families. However, unlike MSG, each vMSG gene encodes a signal peptide, suggesting that the regulation of vMSG is different from that of MSG. C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 45 TC 12 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1999 VL 179 IS 1 BP 192 EP 200 DI 10.1086/314558 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151MW UT WOS:000077725000025 PM 9841839 ER PT J AU Jakob, T Brown, MJ Udey, MC AF Jakob, T Brown, MJ Udey, MC TI Characterization of E-cadherin-containing junctions involving skin-derived dendritic cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE adhesion; dendritic cell maturation; Langerhans cells ID ADHESION MOLECULE UVOMORULIN; TYROSINE KINASE SUBSTRATE; EPITHELIAL-CELLS; ADHERENS JUNCTIONS; LANGERHANS CELLS; HEMOPHILIC ADHESION; HUMAN EPIDERMIS; EXPRESSION; DESMOSOMES; COMPLEXES AB Adherens junctions are sites of contact between epithelial cells in which adhesion is mediated by homophilic interactions of classical cadherins that are linked to the cytoskeleton via catenins, E-cadherin constitutes the major adhesion molecule in adherens junctions of keratinocytes (KC) and mediates the binding of Langerhans cells to KC in vitro. To characterize structures responsible for E-cadherin-mediated binding of Langerhans cells, we utilized Langerhans cells-like fetal skin-derived dendritic cells (FSDDC) capable of E-cadherin-mediated adhesion. Confocal microscopy of FSDDC aggregates demonstrated colocalization of E-cadherin and catenins to areas of cell-cell contact. Immunopreciptiation confirmed a physical association of E-cadherin with intracellular catenins (alpha-, beta-, gamma-catenin/plakoglobin and p120(CAS)). Transmission electron microscopy of FSDDC aggregates revealed structures with features of adherens junctions in areas of cell-cell contact, and post-embedding immunoelectron microscopy localized beta-catenin to these regions. To characterize junctions that accounted for the adhesion of Langerhans cells-like dendritic cells and KC, disaggregated FSDDC were cocultured with primary murine KC, Transmission electron microscopy analysis of cocultures demonstrated FSDDC-KC contacts that were analogous to those seen in FSDDC aggregates. Confocal microscopy demonstrated focal accumulations of E-cadherin and colocalization of beta-catenin in areas of contact between KC and immature (Langerhans cell-like) dendritic cells, but not in areas of contact between KC and mature (lymph node dendritic cell-like) dendritic cells. E-cadherin in Langerhans cells appears to be localized in structures that resemble adherens junctions formed by nonpolarized epithelial cells. Loss of ability to form or maintain these structures after the induction of Langerhans cells activation/maturation likely results in the attenuation of Langerhans cells-KC adhesion that preceeds Langerhans cells emigration from the epidermis. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. RI Jakob, Thilo/J-1621-2012 NR 38 TC 25 Z9 26 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 1999 VL 112 IS 1 BP 102 EP 108 DI 10.1046/j.1523-1747.1999.00475.x PG 7 WC Dermatology SC Dermatology GA 153BR UT WOS:000077813300017 PM 9886272 ER PT J AU Ortaldo, JR AF Ortaldo, JR TI Positive and negative signaling by murine Ly-49 NK receptors: Analysis of structure/function. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1999 SU S MA 12 BP 11 EP 11 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 225QX UT WOS:000081973200015 ER PT J AU Kruth, H Zhang, WY AF Kruth, H Zhang, WY TI Macrophage reversal of LDL aggregation by plasminogen activation. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1999 SU S MA 65 BP 20 EP 20 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 225QX UT WOS:000081973200065 ER PT J AU McCartney-Francis, N Mizel, D Wahl, S AF McCartney-Francis, N Mizel, D Wahl, S TI Dysregulated IFN-gamma signaling pathways in TGF-beta 1 deficient mice. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1999 SU S MA 75 BP 21 EP 21 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 225QX UT WOS:000081973200073 ER PT J AU Schengrund, CL Kovac, P AF Schengrund, CL Kovac, P TI A simple, nonenzymatic method for desialylating polysialylated ganglio-N-tetraose series gangliosides to produce GM1 SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ganglioside GM1; Dowex-H+; sialic acid ID CELLS; BINDING AB Dowex-50w-H+ was used to catalyze the highly selective desialylation of polysialylated ganglio-N-tetraose series gangliosides to yield primarily GM1. High performance thin-layer chromatographic analysis of recovered lipid indicated that 60-70% of the recovered ganglioside was GM1. Identification of the major product as GM1 was confirmed by proton NMR spectra and lack of sialic acid release by Vibrio cholerae sialidase. C1 Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schengrund, CL (reprint author), Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. FU NINDS NIH HHS [NS35653] NR 22 TC 4 Z9 4 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 1999 VL 40 IS 1 BP 160 EP 163 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 153MB UT WOS:000077835900018 PM 9869662 ER PT J AU Shinomiya, K Kabasawa, Y Ito, Y AF Shinomiya, K Kabasawa, Y Ito, Y TI Countercurrent chromatographic separation of sugars and their p-nitrophenyl derivatives by cross-axis coil planet centrifuge SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID ROTARY SEALS; EFFICIENCY; APPARATUS; SYSTEMS; PHASE AB Sugars and their p-nitrophenyl (PNP) derivatives were separated by high-speed countercurrent chromatography using a cross-axis coil planet centrifuge (cross-axis CPC) equipped with a pair of eccentric coil assemblies. A polar two-phase solvent system composed of 1-butanol/acetic acid/water (4:1:5) was used for the separation of sucrose and fucose, and glucuronic acid (lactoid form) and galacturonic acid, while 1-butanol/ethanol/water (4:1:4) was used for the separation of free and lactoid forms of glucuronic acid. PNP-sugar derivatives such as neutral sugars, uronic acids, and amino sugars were separated with a less polar solvent system composed of n-hexane/ethyl acetate/1-butanol/methanol/water at various volume ratios. PNP-glucose derivatives were further separated according to the number of sugar chains, and five PNP-neutral sugars were resolved by adding 0.1 M sodium tetraborate in the two-phase solvent system. Overall results of experiments revealed that the cross-axis CPC is useful for the separation of polar compounds such as sugars. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. NR 15 TC 15 Z9 15 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1999 VL 22 IS 4 BP 579 EP 592 DI 10.1081/JLC-100101683 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 170VM UT WOS:000078827800009 ER PT J AU Rasooly, A Ito, Y AF Rasooly, A Ito, Y TI Toroidal coil Countercurrent Chromatography separation and analysis of staphylococcal enterotoxin a (SEA) in milk SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID FLOW-THROUGH CENTRIFUGE; ROTATING SEALS; FOODS AB Countercurrent Chromatography (CCC) utilizes continuous partitioning of solute between two immiscible solvent phases without a solid support. The absence of solid support makes CCC a suitable method for food analysis because it permits analysis of crude and complex materials that are not amenable to conventional solid-supported chromatography. CCC was evaluated for its ability to separate Staphylococcal enterotoxin A (SEA), a common cause of food poisoning, from milk. Although many foods can be analyzed for SEA directly by Western blot analysis, milk samples generally require some purification because the high concentration of milk proteins distorts SDS-PAGE mobility. Milk samples containing SEA were separated by toroidal coil CCC and the fractions were analyzed by Western immunoblotting. Fractions containing SEA were pooled, concentrated by ultrafiltration, and rechecked by Western immunoblotting. Concentrating the fractions increased the sensitivity of Western immunoblotting by approximately an order of magnitude. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Microbial Studies, Washington, DC 20204 USA. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Room 7N322, Bethesda, MD 20892 USA. NR 15 TC 12 Z9 12 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1999 VL 22 IS 9 BP 1285 EP 1293 DI 10.1081/JLC-100101732 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 200ZB UT WOS:000080569200002 ER PT J AU Ito, Y AF Ito, Y TI Centrifugal precipitation chromatography applied to fractionation of proteins with ammonium sulfate SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID ISOMERASE AB A novel chromatographic system introduced here internally generates a concentration gradient of ammonium sulfate (AS) along a long channel to fractionate proteins according to their solubility in AS solution. The separation column consists of a pair of discs with mutually mirror-imaged spiral channels that are separated by a semipermeable membrane. The disc assembly is mounted on a seal-less continuous flow centrifuge. A concentrated AS solution is introduced into the upper channel while a water solution is passed through the lower channel in the opposite direction in a rotating column. A mixture of proteins injected into the water channel moves along an AS gradient of increasing concentration that has been established in the water solution. Each protein species precipitates at a different AS concentration along the gradient. By decreasing the concentration of the AS solution its concentration in the water is decreased, causing the protein to redissolve and to reprecipitate further down the channel. The eluate is continuously monitored and collected using a fraction collector. The method has been demonstrated on separation of serum proteins and applied to purification of a recombinant ketosteroid isomerase from a crude E. coli lysate by adding an affinity ligand to the sample solution. A possible mechanism involved in this affinity separation is discussed. The method may be applied to other biopolymers such as DNA and RNA. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP NHLBI, Biophys Chem Lab, NIH, Bldg 10,Room 7N322,10 Ctr Dr,MSC 1676, Bethesda, MD 20892 USA. NR 6 TC 15 Z9 15 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6076 EI 1520-572X J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1999 VL 22 IS 18 BP 2825 EP 2836 DI 10.1081/JLC-100102062 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 249VJ UT WOS:000083353700010 ER PT J AU Ma, Y Ito, Y Berthod, A AF Ma, Y Ito, Y Berthod, A TI A chromatographic method for measuring k(F) of enantiomer-chiral selector complexes SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID SPEED COUNTERCURRENT CHROMATOGRAPHY; STATIONARY PHASES; SEPARATION; RESOLUTION AB The method uses high-speed countercurrent chromatography to retain a given concentration of the chiral selector (CS) in the liquid stationary phase. A minute amount of an enantiomeric analyte is eluted through the column to measure its retention time from which the distribution ratio of the analyte is computed. The experiment is repeated by varying the CS concentration in the stationary phase. Using a set of data thus obtained, plotting the CS concentration in the stationary phase against the relative distribution ratio of the analyte produces a straight line whose slope corresponds to the formation constant (K-f) of the CS-analyte complex. The validity of the method is demonstrated on a set of dinitrobenzoyl amino acids using N-dodecanoyl-L-proline-3,5-dimethylanilide as CS. The method will be useful for understanding the basic mechanism of enantioselectivity and designing effective chiral selectors. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Lyon 1, Sci Analyt Lab, F-69622 Villeurbanne, France. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, 10 Ctr Dr,MSC 1676, Bethesda, MD 20892 USA. RI Berthod, Alain/H-1724-2014 OI Berthod, Alain/0000-0002-7452-9527 NR 10 TC 11 Z9 13 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1999 VL 22 IS 19 BP 2945 EP 2955 DI 10.1081/JLC-100102070 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 258AN UT WOS:000083816000007 ER PT J AU Robinson, GW Karpf, ABC Kratochwil, K AF Robinson, GW Karpf, ABC Kratochwil, K TI Regulation of mammary gland development by tissue interaction SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE tissue interaction; steroid receptors; LEF-1; PTHrP; activin; milk proteins ID TOOTH DEVELOPMENT; HAIR DEVELOPMENT; MOUSE; MESENCHYME; EXPRESSION; INDUCTION; BMP-4; IDENTIFICATION; MORPHOGENESIS; FETAL AB Development of the mammary glands is initiated in the embryo but the major part of their development occurs in the adult. While development in puberty and pregnancy is dependent on hormones, prenatal and early postnatal development appear to progress autonomously. Mutual and reciprocal epithelial-mesenchymal interactions are critical for both phases of development. Specific steps such as the formation of the bud, the first appearance of hormone receptors, formation of the primary sprout and ductal elongation have been shown to be governed by epithelial-mesenchymal signaling. In recent years, some of the signaling molecules that are required in these processes have been identified through gene inactivation. We discuss the potential role of these factors in mediating growth and differentiation. In addition we provide evidence that mammary epithelial cells from late embryonic stages are already capable of synthesizing milk proteins when subjected to appropriate hormonal stimulation. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20982 USA. Austrian Acad Sci, Inst Mol Biol, A-5020 Salzburg, Austria. RP Robinson, GW (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Rm 101, Bethesda, MD 20982 USA. EM gertraur@bdg10.niddk.nih.gov RI Robinson, Gertraud/I-2136-2012 NR 32 TC 124 Z9 127 U1 1 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JAN PY 1999 VL 4 IS 1 BP 9 EP 19 DI 10.1023/A:1018748418447 PG 11 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 181WE UT WOS:000079465200002 PM 10219903 ER PT J AU Chepko, G Smith, GH AF Chepko, G Smith, GH TI Mammary epithelial stem cells: Our current understanding SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE epithelial stem cells; asymmetric mitosis; mitosis; mammary gland; morphogenesis ID TRUNCATED INT3 GENE; TUMOR VIRUS; MOUSE; DIFFERENTIATION; EXPRESSION; BREAST; MICE; MORPHOGENESIS; ORIENTATION; PARENCHYMA AB It has recently been shown that the progeny from a single cell may comprise the epithelial population of a fully developed lactating mammary outgrowth in mice. Serial transplantation of epithelial fragments from this clonally derived gland demonstrates that the subsequently generated outgrowths are also comprised of progeny from the original antecedent. Similarly, genetic analysis of contiguous portions of individual human mammary ducts within the same breast indicates their clonal derivation. These observations support the concept that multipotent tissue-specific epithelial stem cells are present among the parenchymal cells of the mammary gland. Here, we present the developing evidence for the presence of stem cells in virtually every renewing mammalian tissue as well as some classically considered to consist only of differentiated cells. Further, we review the present morphologic and biologic evidence for stem cells and lineage-limited progenitor cells in human and rodent mammary epithelium. Although a number of selective markers are known for various lineage-limited hematopoietic cells and their progeny, our understanding of the biology of the precursor cells for mammary epithelium is just beginning. Our purpose here is to develop further interest in the clarification of these issues in the biology of the mammary gland. C1 Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20007 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chepko, G (reprint author), Georgetown Univ, Lombardi Canc Ctr, NRB W412,3970 Reservoir Rd NW, Washington, DC 20007 USA. EM chepkog@gunet.georgetown.edu RI Chepko, Gloria/B-2235-2010 OI Chepko, Gloria/0000-0002-4691-9894 NR 58 TC 65 Z9 70 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JAN PY 1999 VL 4 IS 1 BP 35 EP 52 DI 10.1023/A:1018752519356 PG 18 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 181WE UT WOS:000079465200004 PM 10219905 ER PT J AU Hovey, RC McFadden, TB Akers, RM AF Hovey, RC McFadden, TB Akers, RM TI Regulation of mammary gland growth and morphogenesis by the mammary fat pad: A species comparison SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE mammary fat pad; morphogenesis; paracrine; epithelial-stromal interaction; hormone receptors; growth factors ID FACTOR MESSENGER-RNA; HUMAN INFANT BREAST; EPITHELIAL-CELLS; HORMONAL-REGULATION; PROGESTERONE RECEPTORS; PHYSIOLOGICAL STATES; PREPUBERTAL LAMBS; MALIGNANT BREAST; GENE-EXPRESSION; UNSATURATED FAT AB The growth and morphogenesis of mammary parenchyma varies substantially between species and is regulated by an array of systemic and local factors. Central to this regulation is the mammary fat pad, a matrix of adipose and connective tissue capable of mediating hormone action and synthesizing an array of growth regulatory molecules. In this article we highlight differences between the morphological development of the mammary parenchyma in rodents, humans, and ruminant dairy animals, placing emphasis on differences in the cellular composition and structure of the mammary fat pad. While a great deal remains to be understood about the ability of stroma to locally regulate mammary development, the significance of its contribution is becoming increasingly apparent. The actions of several steroid and peptide hormones appear to be mediated by an array of growth factors, proteases and extracellular matrix components synthesized by constituents of the mammary fat pad. Further, mammary adipose tissue represents a significant store of lipid which, by itself and through its derivatives, could influence the growth of mammary epithelium in diverse ways. This review describes the integral role of the mammary fat pad during mammogenesis, emphasizing the point that species differences must be addressed if local growth and morphogenic mechanisms within the mammary gland are to be resolved. C1 NIH, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. AgRes, Ruakura Res Ctr, Dairy Sci Grp, Hamilton, New Zealand. Virginia Polytech Inst & State Univ, Dept Dairy Sci, Blacksburg, VA 24061 USA. RP Hovey, RC (reprint author), NIH, Tumor Immunol & Biol Lab, Bldg 10,Room 5B47,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 96 TC 117 Z9 124 U1 2 U2 13 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JAN PY 1999 VL 4 IS 1 BP 53 EP 68 DI 10.1023/A:1018704603426 PG 16 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 181WE UT WOS:000079465200005 PM 10219906 ER PT J AU Marcus, PM Prorok, PC AF Marcus, PM Prorok, PC TI Reanalysis of the Mayo Lung Project data: the impact of confounding and effect modification SO JOURNAL OF MEDICAL SCREENING LA English DT Article DE lung neoplasms; mass screening; clinical trial; Mayo Lung Project ID CANCER AB Objectives-To examine whether age at entry, history of cigarette smoking, exposure to non-tobacco lung carcinogens, or previous pulmonary illnesses were confounders or effect modifiers of the relation between screening and lung cancer mortality in the Mayo Lung Project. Setting-The Mayo Lung Project was a randomised, controlled, clinical trial conducted between 1971 and 1986 in 9211 male smokers over the age of 45 in Minnesota (USA). The group screened received chest x ray examination and sputum cytology every four months for six years. The unscreened group were recommended to obtain usual care (annual chest x ray examination and sputum cytology). After follow up, lung cancer mortality was similar in both groups. Methods-Proportional hazard models were used to analyse data. A variable was considered a confounder if its inclusion in a model changed the rate ratio for screening by more than 15%; a variable was considered an effect modifier if its stratum-specific rate ratio for screening differed by a factor of two. Results-None of the four aforementioned variables changed the rate ratio associated with screening (1.07) by more than 2%. The effect of screening may have differed by years smoked (rate ratio for smoking fewer than 30 years 2.4; rate ratio for smoking 30 or more years 1.0), though we suspect that this result occurred by chance. Conclusion-Adjustment for or stratification by four established lung cancer risk factors did not alter the original findings of the Mayo Lung Project. C1 NCI, Biometry Branch, Div Canc Prevent, Bethesda, MD 20892 USA. RP Marcus, PM (reprint author), NCI, Biometry Branch, Div Canc Prevent, Execut Plaza N,Suite 344,6130 Execut Blvd,MSC 735, Bethesda, MD 20892 USA. NR 9 TC 21 Z9 21 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 1999 VL 6 IS 1 BP 47 EP 49 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 331WP UT WOS:000088041900011 PM 10321372 ER PT J AU Mason, RP Walter, MF Trumbore, MW Olmstead, EG Mason, PE AF Mason, RP Walter, MF Trumbore, MW Olmstead, EG Mason, PE TI Membrane antioxidant effects of the charged dihydropyridine calcium antagonist amlodipine SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Endothelial Dysfunction - A Novel Therapeutic Target CY MAY 27, 1998 CL RHODES, GREECE DE calcium channels; lipid peroxidation; membranes; calorimetry ID CHANNEL BLOCKERS; LIPID-PEROXIDATION; HEART-FAILURE; ACE-INHIBITORS; BINDING; INJURY; CHOLESTEROL; PROTECTION; NIFEDIPINE; VERAPAMIL AB The effect of the highly lipophilic calcium channel antagonist (CCA) amlodipine on membrane oxyradical damage was examined and compared to that of other CCA analogs and a sulfhydryl-containing ACE inhibitor in isolated membrane vesicles enriched with polyunsaturated fatty acids (PUFA). Under physiological-like conditions, the dihydropyridine CCA amlodipine significantly (P<0.001) inhibited lipid peroxide formation (>10(2) mu M) at concentrations as low as 10.0 nM. Under identical conditions, inhibition of lipid peroxide formation was not observed with representative CCA analogs (felodipine, verapamil, diltiazem) or the ACE inhibitor, captopril, at concentrations as high as 1.0 mu M. The potent antioxidant activity of amlodipine is attributed to distinct membrane physico-chemical interactions, High-resolution differential scanning calorimetry showed that amlodipine effected marked changes in membrane thermodynamic properties as compared to other CCA analogs, including a marked reduction in the thermal phase transition temperature (-2.6 degrees C), enthalpy (-4.8 J/g) and cooperative unit size (-59%), relative to control samples. These findings indicate that the chemical structure of amlodipine contributes to distinct membrane biophysical interactions that lead to potent lipid antioxidant effects, independent of calcium channel modulation. These findings provide insights into potential new mechanisms of action for the charged CCA amlodipine. (C) 1999 Academic Press. C1 Allegheny Univ Hlth Sci, Cardiovasc & Pulm Res Inst, MCP Hahneman Sch Med, Dept Biochem, Pittsburgh, PA 15212 USA. Allegheny Univ Hlth Sci, Cardiovasc & Pulm Res Inst, MCP Hahneman Sch Med, Dept Med, Pittsburgh, PA 15212 USA. NCI, NIH, Bethesda, MD 20892 USA. Gordon Coll, Dept Chem, Div Nat Sci, Wenham, MA USA. RP Mason, RP (reprint author), Allegheny Univ Hlth Sci, Cardiovasc & Pulm Res Inst, MCP Hahneman Sch Med, Dept Biochem, 320 E North Ave 10-ST, Pittsburgh, PA 15212 USA. FU NHLBI NIH HHS [HL22633] NR 21 TC 98 Z9 101 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JAN PY 1999 VL 31 IS 1 BP 275 EP 281 DI 10.1006/jmcc.1998.0867 PG 7 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 163VU UT WOS:000078427700025 PM 10072734 ER PT J AU Spande, TF Jain, P Garraffo, HM Pannell, LK Yeh, HJC Daly, JW Fukumoto, S Imamura, K Tokuyama, T Torres, JA Snelling, RR Jones, TH AF Spande, TF Jain, P Garraffo, HM Pannell, LK Yeh, HJC Daly, JW Fukumoto, S Imamura, K Tokuyama, T Torres, JA Snelling, RR Jones, TH TI Occurrence and significance of decahydroquinolines from dendrobatid poison frogs and a myrmicine ant: Use of H-1 and C-13 NMR in their conformational analysis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID DL-PUMILIOTOXIN-C; VENOM ALKALOIDS; SKIN ALKALOIDS; INDOLIZIDINES; QUINOLIZIDINES; PYRROLIZIDINES; SOLENOPSIS AB Structures for 2,5-disubstituted decahydroquinolines (DHQs) are reported for the two diastereomeric pairs cis-275B (14) and cis-275B' (15) and 5-epi-trans-269AB (18) and trans-269AB (19), all isolated from skin extracts of dendrobatid frogs, and for 5-epi-cis-275B' (16) and 5-epi-trans-275B (17) found in the extracts of virgin queens of a myrmicine ant [Solenopsis (Diplorhoptrum) azteca]. Detection of such DHQs in an ant, their first reported occurrence, strengthens a dietary hypothesis for the origin of the approximately 30 DHQs that have been detected in extracts of frog skin. NMR data on the two conformers of cis-decahydroquinoline permit assignment of ring conformations and stereochemistry to cis-DHQs of the "N-endo" type or the "N-exo" type. These conformations are also assigned on whether H-8a is equatorial or axial as determined with E-COSY or 1D-HOHAHA spectra. C1 NIH, Bioorgan Chem Lab, NIDDK, Bethesda, MD 20892 USA. Shimadzu Corp, Kanagawa 2591304, Japan. Toyo Polymer Co Ltd, Osaka 5640044, Japan. Osaka City Univ, Fac Sci, Osaka 585, Japan. Univ Puerto Rico, Dept Biol, San Juan, PR 00931 USA. USDA, Forest Serv, Int Inst Trop Forestry, Rio Piedras, PR 00928 USA. Los Angeles Cty Museum Nat Hist, Los Angeles, CA 90007 USA. Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. RP Spande, TF (reprint author), NIH, Bioorgan Chem Lab, NIDDK, Bldg 10, Bethesda, MD 20892 USA. EM Thomassp@bdg8.niddk.nih.gov NR 31 TC 75 Z9 76 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 1999 VL 62 IS 1 BP 5 EP 21 DI 10.1021/np980298v PG 17 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 159QX UT WOS:000078186300002 ER PT J AU Fuller, RW Westergaard, CK Collins, JW Cardellina, JH Boyd, MR AF Fuller, RW Westergaard, CK Collins, JW Cardellina, JH Boyd, MR TI HIV-inhibitory natural products. 50. Vismiaphenones D-G, new prenylated benzophenones from Vismia cayennensis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID INHIBITORY NATURAL-PRODUCTS; IMMUNODEFICIENCY-VIRUS TYPE-1; CLUSIA-ELLIPTICIFOLIA; CALOPHYLLUM-LANIGERUM; CALANOLIDE-A; ANTI-HIV; CHEMISTRY; GENUS; GUARAMIRANGAE; CONSTITUENTS AB Following anti-HIV bioassay-guided fractionation, four new prenylated benzophenones, vismiaphenones D-G (7-10), were isolated from extracts of leaves of Vismia cayennensis. The structures were elucidated by spectral analyses. Only vismiaphenone D (7) exhibited HIV-inhibitory activity in the NCI primary screen. C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Bldg 1052,Room 121, Frederick, MD 21702 USA. FU NCI NIH HHS [N01 CO 56000] NR 24 TC 44 Z9 49 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 1999 VL 62 IS 1 BP 67 EP 69 DI 10.1021/np980152w PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 159QX UT WOS:000078186300011 PM 9917284 ER PT J AU Fuller, RW Blunt, JW Boswell, JL Cardellina, JH Boyd, MR AF Fuller, RW Blunt, JW Boswell, JL Cardellina, JH Boyd, MR TI HIV-inhibitory natural products. 49. Guttiferone F, the first prenylated benzophenone from Allanblackia stuhlmannii SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CLUSIA; CAMBOGINOL; GARCINOL AB The HIV-inhibitory activity in extracts of Allanblackia stuhlmannii was tracked, via bioassay-guided fractionation, to a new member of the camboginol/guttiferone class of prenylated benzophenones, guttiferone F (1). The structure was solved by extensive NMR analyses and by acid-catalyzed conversion to 30-epi-cambogin (4). This is the first report of this compound type in the genus Allanblackia. C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Lab Drug Discovery Res & De, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Lab Drug Discovery Res & De, Bldg 1052,Room 121, Frederick, MD 21702 USA. NR 12 TC 66 Z9 69 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 1999 VL 62 IS 1 BP 130 EP 132 DI 10.1021/np9801514 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 159QX UT WOS:000078186300026 PM 9917299 ER PT J AU Lillrank, SM Lipska, BK Kolachana, BS Weinberger, DR AF Lillrank, SM Lipska, BK Kolachana, BS Weinberger, DR TI Attenuated extracellular dopamine levels after stress and amphetamine in the nucleus accumbens of rats with neonatal ventral hippocampal damage SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE hippocampus; microdialysis; dopamine; amphetamine; ibotenic acid; 5-HIAA ID EXPERIENCES DIFFERENTLY AFFECT; MEDIAL PREFRONTAL CORTEX; IN-VIVO MICRODIALYSIS; ANTEROGRADE TRANSPORT; LOCOMOTOR-ACTIVITY; INVIVO MEASUREMENT; HOMOVANILLIC-ACID; BRAIN DOPAMINE; CONSCIOUS RATS; RELEASE AB In vivo microdialysis was used to study the effects of restraint stress (30 min) and amphetamine (AMPH) (5 mg/kg, i.p.) in awake adult male rats with neonatal ventral hippocampal (VH) damage. Extracellular levels of dopamine (DA), dihydrophenylacetate (DOPAC), homovanillate (HVA) and 5-hydroxyindolacetate (5-HIAA) were measured in the nucleus accumbens (NA). There were no differences in the baseline levels of DA, DOPAC, HVA or 5-HIAA in the lesioned as compared to the sham rats. Release from restraint resulted in increased extracellular levels of DA in the sham but not in the lesioned animals. AMPH increased DA release in both sham operated and lesioned animals, but this increase was significantly attenuated in the lesioned rats. Our data suggest that this developmental lesion alters function of the dopaminergic system in response to environmental and pharmacological challenge. C1 NIMH, IRP, Clin Brain Disorders Branch, Ctr Neurosci, Bethesda, MD 20892 USA. RP Lipska, BK (reprint author), NIMH, IRP, Clin Brain Disorders Branch, Ctr Neurosci, Bldg G,Rm IN 124B, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 55 TC 61 Z9 61 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PY 1999 VL 106 IS 2 BP 183 EP 196 DI 10.1007/s007020050150 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 179TH UT WOS:000079344800009 PM 10226938 ER PT J AU Fredriksson, A Palomo, T Chase, T Archer, T AF Fredriksson, A Palomo, T Chase, T Archer, T TI Tolerance to a suprathreshold dose of L-Dopa in MPTP mice: effects of glutamate antagonists SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE C57 Bl/6 mice; MPTP; suprathreshold; L-Dopa -20mg/kg; chronic injections; tolerance; NMDA antagonists; MK-801; CGP 40116; reinstatement; synergism; parkinsonism ID FLUCTUATING PARKINSONS-DISEASE; CENTRAL CATECHOLAMINE NEURONS; MONOAMINE-DEPLETED MICE; MOTOR FLUCTUATIONS; NMDA-ANTAGONIST; RECEPTOR ANTAGONIST; TREATED MICE; LEVODOPA; MECHANISMS; NEUROTOXICITY AB Three experiments were performed to study the development and manipulation of tolerance to a suprathreshold dose of L-Dopa (20 mg/kg, s.c.) in MPTP-treated and control (saline-injected) C57 B1/6 mice. The motor activity reinstatement effect of this dose of L-Dopa upon MPTP-treated mouse behaviour deteriorated from the 13th injection (Test Day 8) of L-Dopa onwards and reached basal level (i.e. no stimulatory effects of the drug) by the 16th administration (Test Day 10). Administration of L-Dopa to control mice reduced locomotor and rearing activity throughout the tolerance development period (Test Days 1-12) during the first hour after injection, and then increased locomotor activity during the second hour. The effects of combining either a noncompetitive, MK-801, or a competitive, CGP 40116, glutamate antagonist with L-Dopa, following tolerance development, were assessed in MPTP mice on the 23rd day of L-Dopa administration (Test Day 13). MK-801 (0.1 mg/kg, s.c.) reinstated the locomotory and rearing behaviour induced by L-Dopa; CGP 40116 did so also to a greater extent in the dose range 0.01 to 0.03 mg/kg. These results indicate that MPTP-treated mice continue to offer a useful parkinsonian model also for the examination of different aspects of the "wearing-off'' phenomenon of L-Dopa tolerance and in particular the putative glutamatergic involvement. The clinical consequences may be far-reaching for the utility of L-Dopa in Parkinson's disease, whether the effects demonstrated be of a reinstatement or synergistic nature, once therapeutically adequate glutamate antagonists are more readily available. C1 Univ Gothenburg, Dept Psychol, SE-40530 Gothenburg, Sweden. Uppsala Univ, Dept Psychiat, Uppsala, Sweden. Hosp 12 Octubre, Serv Psiquiatria, E-28041 Madrid, Spain. NIH, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Archer, T (reprint author), Univ Gothenburg, Dept Psychol, Box 500, SE-40530 Gothenburg, Sweden. NR 56 TC 22 Z9 22 U1 1 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PY 1999 VL 106 IS 3-4 BP 283 EP 300 DI 10.1007/s007020050158 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 190UQ UT WOS:000079984000007 PM 10392537 ER PT J AU Gran, B Hemmer, B Martin, R AF Gran, B Hemmer, B Martin, R TI Molecular mimicry and multiple sclerosis - a possible role for degenerate T cell recognition in the induction of autoimmune responses SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article; Proceedings Paper CT 6th International Winter Conference on Neurodegeneration CY NOV 20-23, 1997 CL KITZBUHEL, AUSTRIA SP Schering, Germany, SmithKline Beecham, Germany, SmithKline Beecham, Austria ID MYELIN BASIC-PROTEIN; PEPTIDE COMBINATORIAL LIBRARIES; LIGANDS; SELECTION; DISEASE; CLONES; IDENTIFICATION; LYMPHOCYTES; ACTIVATION; SEQUENCES AB Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. The etiology is unknown, but several lines of evidence support the hypothesis that the pathogenesis is mediated by autoreactive T lymphocytes. Molecular mimicry has been proposed as a possible mechanism for the development of an autoimmune response to myelin antigens. According to this model, an immune reaction to self antigens could be initiated by T cells that cross-react with infectious agents that "mimic" the autoantigen, i.e. they share immunologic epitopes. It was previously thought that, in order for a cross-reaction of T cells to two different antigens to occur, a substantial amino acid sequence homology between the two antigens was required. More recent studies on the basic mechanisms of T cell antigen recognition have shown that, at least for some T cell clones, antigen recognition is more "degenerate" and sequence homology is not required for crossreactivity to occur. This article reviews the relevance of these recent advances in basic T cell receptor immunology to the occurrence of autoimmunity in the central nervous system. C1 NINDS, Neuroimmunol Branch, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore Med Sch, Dept Neurol, Baltimore, MD 21201 USA. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, Cellular Immunol Sect, NIH, Bldg 10,Room 5B-16,10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 43 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 1999 IS 55 BP 19 EP 31 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 188GD UT WOS:000079837700004 ER PT J AU Grunblatt, E Mandel, S Gassen, M Youdim, MBH AF Grunblatt, E Mandel, S Gassen, M Youdim, MBH TI Potent neuroprotective and antioxidant activity of apomorphine in MPTP and 6-hydroxydopamine induced neurotoxicity SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article; Proceedings Paper CT 6th International Winter Conference on Neurodegeneration CY NOV 20-23, 1997 CL KITZBUHEL, AUSTRIA SP Schering, Germany, SmithKline Beecham, Germany, SmithKline Beecham, Austria ID IRON CHELATOR DESFERRIOXAMINE; DEPENDENT LIPID-PEROXIDATION; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; PHEOCHROMOCYTOMA CELLS; OXIDATIVE STRESS; RADICAL SCAVENGER; MONOAMINE-OXIDASE; RAT-BRAIN; COMPLEX-I AB Apomorphine is a potent radical scavenger and iron chelator. In vitro apomorphine acts as a potent iron chelator and radical scavenger with IC(50) of 0.3 mu M for iron (2.5 mu M) induced lipid peroxidation in rat brain mitochondrial preparation, and it inhibits mice striatal MAO-A and MAO-B activities with IC(50) values of 93 mu M and 241 mu M. Apomorphine (1-10 mu M) protects rat pheochromocytoma (PC12) cells from 6-hydroxydopamine (150 mu M) and H(2)O(2) (0.6mM) induced cytotoxicity and cell death. The neuroprotective property of (R)-apomorphine, a dopamine D(1)-D(2) receptor agonist, has been studied in the MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. (R)-apomorphine (5-10 mg/kg, s.c.) pretreatment in C57BL mice, protects against MPTP (24 mg/kg, I.P) induced loss of nigro-striatal dopamine neurons, as indicated by striatal dopamine content, tyrosine hydroxylase content and tyrosine hydroxylase activity. It is suggested that the neuroprotective effect of (R)-apomorphine against MPTP neurotoxicity derives from its radical scavenging and MAO inhibitory actions and not from its agonistic activity, since the mechanism of MPTP dopaminergic neurotoxicity involves the generation of oxygen radical species induced-oxidative stress. C1 Technion Israel Inst Technol, Fac Med, Bruce Rappaport Family Res Inst, Eve Topf Fdn Ctr Neurodegenerat Dis, Haifa, Israel. Technion Israel Inst Technol, Fac Med, Bruce Rappaport Family Res Inst, US Natl Parkinsons Fdn Ctr Neurodegenerat Dis, Haifa, Israel. Dept Pharmacol, Haifa, Israel. Merck KGaA, Biomed Res CNS, Darmstadt, Germany. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIMH, Bethesda, MD 20892 USA. RP Youdim, MBH (reprint author), B Rappaport Family Med Sch Bldg,Efron St,POB 9697, IL-31096 Haifa, Israel. RI Grunblatt, Edna/A-6762-2016 OI Grunblatt, Edna/0000-0001-8505-7265 NR 54 TC 27 Z9 27 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 1999 IS 55 BP 57 EP 70 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 188GD UT WOS:000079837700007 ER PT J AU Cadet, JL Ordonez, S Burrell, S AF Cadet, JL Ordonez, S Burrell, S TI Comparative toxic effects of methamphetamine and dopamine in cell culture potentiation by serum withdrawal SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S192 EP S192 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500758 ER PT J AU Contreras, MA Greiner, RS Chang, MCJ Myers, CS Salem, N Rapoport, SI AF Contreras, MA Greiner, RS Chang, MCJ Myers, CS Salem, N Rapoport, SI TI Turnover of docosahexaenoate in brain phospholipids of rats chronically deprived of alpha-linolenic acid. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, LNS, Bethesda, MD 20892 USA. NIAAA, LMBB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S207 EP S207 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500820 ER PT J AU Huang, KP Huang, FL Chen, HC AF Huang, KP Huang, FL Chen, HC TI Hypoxia/ischemia induces dephosphorylation of rat brain GAP-43/neuromodulin in vivo SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S200 EP S200 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500792 ER PT J AU Igbavboa, U Hamilton, J Kim, HY Avdulov, NA Chochina, SV Wood, WG AF Igbavboa, U Hamilton, J Kim, HY Avdulov, NA Chochina, SV Wood, WG TI Phospholipid molecular species in synaptic plasma membranes of apoE-deficient and C57BL/6J mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 VA Med Ctr, Minneapolis, MN USA. Univ Minnesota, GRECC, Dept Pharmacol, Minneapolis, MN USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S21 EP S21 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500081 ER PT J AU Jakubik, J AF Jakubik, J TI Aspects of the regulation and molecular assembly of muscarinic acetylcholine receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Physiol, CR-14220 Prague, Czech Republic. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S160 EP S160 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500630 ER PT J AU Kim, HY Akbar, M AF Kim, HY Akbar, M TI Neuronal apoptosis is prevented by docosahexaenoic acid (22 : 6n-3) SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIAAA, Sect Mass Spectrometry, LMBB, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S10 EP S10 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500040 ER PT J AU McKay, R AF McKay, R TI From stem cells to synapses in the central nervous system SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, LMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S1 EP S1 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500004 ER PT J AU Movsesyan, V Dabagyan, E Whalin, M Guroff, G AF Movsesyan, V Dabagyan, E Whalin, M Guroff, G TI NGF blocks PC12 cells from entering mitosis and downregulated cyclin B1. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Inst Biotechnol, Yerevan 375056, Armenia. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S177 EP S177 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500699 ER PT J AU Rosenberger, TA Rapoport, SI Murphy, EJ AF Rosenberger, TA Rapoport, SI Murphy, EJ TI [1,1 3H] hexadecanol incorporation into rat brain: An effective model to study de novo ether lipid synthesis in awoke animals. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S209 EP S209 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500829 ER PT J AU Simpson, IA Liu, D Zheng, F Corpe, CP Koehler-Stee, E Li, K Rutherford, T Willing, L Vannucci, SJ AF Simpson, IA Liu, D Zheng, F Corpe, CP Koehler-Stee, E Li, K Rutherford, T Willing, L Vannucci, SJ TI Alterations in monocarboxylate & glucose transporters in ischemic rodent brain. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. Penn State Univ, Hershey, PA 17033 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S218 EP S218 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500863 ER PT J AU Tenn, CC Hope, BT Nakabeppu, Y Bateson, AN AF Tenn, CC Hope, BT Nakabeppu, Y Bateson, AN TI Induction of delta FosB and FosB-like proteins in rat striatum by chronic diazepam treatment SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Univ Alberta, Dept Pharmacol, Edmonton, AB, Canada. Univ Alberta, Dept Psychiat, Edmonton, AB, Canada. Univ Alberta, Div Neurosci, Edmonton, AB, Canada. NINDS, MPS, NIH, Bethesda, MD USA. Kyushu Univ, Dept Biochem, Fukuoka 812, Japan. RI Hope, Bruce/A-9223-2010; Nakabeppu, Yusaku/A-8902-2011 OI Hope, Bruce/0000-0001-5804-7061; NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S121 EP S121 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500477 ER PT J AU Simpson, IA Appel, NM Hokari, M Oki, J Holman, GD Maher, F Koehler-Stec, EM Vannucci, SJ Smith, QR AF Simpson, IA Appel, NM Hokari, M Oki, J Holman, GD Maher, F Koehler-Stec, EM Vannucci, SJ Smith, QR TI Blood-brain barrier glucose transporter: Effects of hypo- and hyperglycemia revisited SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE blood-brain barrier; diabetes; GLUT1; glucose transporters ID EXPERIMENTAL DIABETES-MELLITUS; RAT ADIPOSE-CELLS; MESSENGER-RNA; SKELETAL-MUSCLE; EXPRESSION; PROTEIN; INSULIN; GLUT4; METABOLISM; PERFUSION AB The transport of glucose across the blood-brain barrier (BBB) is mediated by the high molecular mass (55-kDa) isoform of the GLUT1 glucose transporter protein. In this study we have utilized the tritiated, impermeant photolabel 2-N-[4-(1-azi-2,2,2-trifluoroethyl)[2-H-3]propyl],3-bis(D-mannose-4-yloxy)-2-propylamine to develop a technique to specifically measure the concentration of GLUT1 glucose transporters on the luminal surface of the endothelial cells of the BBB, We have combined this methodology with measurements of BBB glucose transport and immunoblot analysis of isolated brain microvessels for labeled luminal GLUT1 and total GLUT1 to reevaluate the effects of chronic hypoglycemia and diabetic hyperglycemia on transendothelial glucose transport in the rat. Hypoglycemia was induced with continuous-release insulin pellets (6 U/day) for a 12- to 14-day duration; diabetes was induced by streptozotocin (65 mg/kg i.p,) for a 14- to 21-day duration. Hypoglycemia resulted in 25-45% increases in regional BBB permeability-surface area (PA) values for D-[C-14]glucose uptake, when measured at identical glucose concentration using the in situ brain perfusion technique. Similarily, there was a 23 +/- 4% increase in total GLUT1/mg of microvessel protein and a 52 +/- 13% increase in luminal GLUT1 in hypoglycemic animals, suggesting that both increased GLUT1 synthesis and a redistribution to favor luminal transporters account for the enhanced uptake. A corresponding (twofold) increase in cortical GLUT1 mRNA was observed by in situ hybridization, In contrast, no significant changes were observed in regional brain glucose uptake PA, total microvessel 55-kDa GLUT1, or luminal GLUT1 concentrations in hyperglycemic rats. There was, however, a 30-40% increase in total cortical GLUT1 mRNA expression, with a 96% increase in the microvessels. Neither condition altered the levels of GLUT3 mRNA or protein expression. These results show that hypoglycemia, but not hyperglycemia, alters glucose transport activity at the BBB and that these changes in transport activity result from both an overall increase in total BBB GLUT1 and an increased transporter concentration at the luminal surface. C1 NIDDK, Expt Diabet Metab & Nutr Sect, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. US FDA, NIH, Bethesda, MD 20014 USA. Penn State Univ, Coll Med, Hershey, PA 17033 USA. Texas Tech Univ, Hlth Sci Ctr, Amarillo, TX USA. Univ Bath, Dept Biochem, Bath BA2 7AY, Avon, England. RP Simpson, IA (reprint author), Bldg 10,Rm 5N102,10 Ctr Dr,1420, Bethesda, MD 20892 USA. NR 44 TC 172 Z9 176 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 1999 VL 72 IS 1 BP 238 EP 247 DI 10.1046/j.1471-4159.1999.0720238.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 149MQ UT WOS:000077609600028 PM 9886075 ER PT J AU Beebe, SC Kang, J AF Beebe, SC Kang, J TI Cerebral protein synthesis in a genetic mouse model of phenylketonuria SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S21 EP S21 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100085 ER PT J AU Brenneman, DE Gozes, I AF Brenneman, DE Gozes, I TI Pharmacology of neurotrophic peptides derived from activity dependent neurotrophic factor SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHD, Sec Dev Mol Pharmacol, Bethesda, MD 20892 USA. Tel Aviv Univ, Dept Clin Biochem, Sackler Sch Med, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S4 EP S4 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100016 ER PT J AU Chandross, KJ Cohen, RI Champagne, BY Hudson, LD AF Chandross, KJ Cohen, RI Champagne, BY Hudson, LD TI Characterization and purification of early glial progenitors using a transgenic approach. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, LDN, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S83 EP S83 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100332 ER PT J AU Chang, MCJ Chandrasekaran, K Seemann, R Rapoport, SI AF Chang, MCJ Chandrasekaran, K Seemann, R Rapoport, SI TI Chronic lithium treatment decreases the expression of cPLA2 mRNA in rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S11 EP S11 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100043 ER PT J AU Chang, RCC Hudson, P Wilson, B Chen, W Haddon, L Hong, JS AF Chang, RCC Hudson, P Wilson, B Chen, W Haddon, L Hong, JS TI Potassium chloride enhances lipopolysaccharide (LPS)-induced glial inflammatory responses SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S69 EP S69 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100277 ER PT J AU Chen, Y McCarron, RM Azzam, N Lenz, FA Spatz, M AF Chen, Y McCarron, RM Azzam, N Lenz, FA Spatz, M TI Human brain capillary endothelium: ET-1-induced Ca2+ mobilization and F-actin cytoskeleton is modified by NO. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Naval Med Res Ctr, RMP, Bethesda, MD USA. Johns Hopkins Univ Hosp, Baltimore, MD 21205 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S59 EP S59 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100236 ER PT J AU Cohen, RI Chandross, KJ Becker, KG Hudson, LD AF Cohen, RI Chandross, KJ Becker, KG Hudson, LD TI The role of Ephs and Ephrins in the development of oligodendrocytes SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIA, NA Array Unit, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S50 EP S50 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100199 ER PT J AU Contreras, MA Greiner, RS Chang, MCJ Myers, C Bell, JM Salem, N Rapoport, SI AF Contreras, MA Greiner, RS Chang, MCJ Myers, C Bell, JM Salem, N Rapoport, SI TI alpha-linolenic acid deprivation alters the in vivo turnover of docosahexaenoic acid in rat brain phospholipids. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIAAA, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S65 EP S65 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100261 ER PT J AU Foley, TD AF Foley, TD TI 4-hydroxynonenal inhibits synaptic plasma membrane ecto-ATPase activity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S33 EP S33 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100133 ER PT J AU Glazner, GW Boland, A Dresse, AE Camandola, S Rodriguez, RG Toborek, M Brenneman, DE Gozes, I Mattson, MP AF Glazner, GW Boland, A Dresse, AE Camandola, S Rodriguez, RG Toborek, M Brenneman, DE Gozes, I Mattson, MP TI Mechanisms of ADNF peptide protection against oxidative and excitotoxic neuronal death SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Surg, Lexington, KY 40536 USA. Univ Liege, Inst Pathol, Liege, Belgium. Univ Turin, Dept Med, I-10124 Turin, Italy. NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S4 EP S4 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100015 ER PT J AU Gozes, I Zamostiano, R Giladi, E Pinhasov, A Bassan, M Brenneman, DE AF Gozes, I Zamostiano, R Giladi, E Pinhasov, A Bassan, M Brenneman, DE TI Activity-dependent neuroprotective protein: Molecular structure and behavioral studies SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Tel Aviv Univ, Dept Clin Biochem, Sackler Sch Med, IL-69978 Tel Aviv, Israel. NICHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S4 EP S4 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100014 ER PT J AU Guroff, G AF Guroff, G TI The role of calcium uptake in neurotrophin-induced survival, protection, and synaptic plasticity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S89 EP S89 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100357 ER PT J AU Hill, JM Glazner, GW Lee, SJ Gozes, I Gressens, P Brenneman, DE AF Hill, JM Glazner, GW Lee, SJ Gozes, I Gressens, P Brenneman, DE TI Activity-dependent neurotrophic factor peptide regulation of growth in post-implantation embryos. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHD, LDN, Sect Dev & Mol Pharmacol, 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. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S3 EP S3 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100013 ER PT J AU Li, BS Veeranna Grant, P Pant, HC AF Li, BS Veeranna Grant, P Pant, HC TI Activation of mitogen-activated protein kinase (Erk1 and Erk2) cascade results in phosphorylation of NF-M tail domain in transfected NIH 3T3 cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S59 EP S59 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100235 ER PT J AU Rapoport, SI AF Rapoport, SI TI Measuring dynamics of brain phospholipid metabolism in vivo: Relation to signaling and neuroplasticity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S48 EP S48 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100192 ER PT J AU Rosenberger, TA Rapoport, SI Murphy, EJ AF Rosenberger, TA Rapoport, SI Murphy, EJ TI [1,1 H-3] hexadecanol incorporation into rat brain: A novel way to study de nova ether lipid synthesis in awake animals. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S48 EP S48 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100190 ER PT J AU Russell, JG Simpson, PB Smaili, SS AF Russell, JG Simpson, PB Smaili, SS TI Essential role of mitochondria in agonist evoked Ca2+ waves in Glial cells. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHD, Cellular & Mol Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S91 EP S91 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100363 ER PT J AU Salem, N Greiner, R Moriguchi, T Pawlosky, R AF Salem, N Greiner, R Moriguchi, T Pawlosky, R TI Function and metabolism of docosahexaenoic acid in the nervous system SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIAAA, NIH, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S47 EP S47 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100187 ER PT J AU Schengrund, CL Kovac, P AF Schengrund, CL Kovac, P TI Dowex-50W-H+ catalyzed hydrolysis of sialic acid from gangliosides SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S64 EP S64 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100257 ER PT J AU Stadtman, ER AF Stadtman, ER TI Oxidative stress-provoked protein oxidation. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S1 EP S1 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100004 ER PT J AU Stoll, J Galdzicki, Z AF Stoll, J Galdzicki, Z TI Alteration in cAMP production in hippocampal neurons cultured from the Trisomy 16 mouse SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Texas Tech Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79160 USA. NIA, Neurosci Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S36 EP S36 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100142 ER PT J AU Tanner, SL Dashiell, SM Quarles, RH AF Tanner, SL Dashiell, SM Quarles, RH TI Microtubule-associated protein 1B is present in cultured Schwann cells and does not co-localize with tubulin. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NCI, Myelin & Brain Dev Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S54 EP S54 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100216 ER PT J AU Vannucci, SJ Koehler-Stec, E Rutherford, T Willing, L Brucklacher, R Corpe, C Liu, D Simpson, IA AF Vannucci, SJ Koehler-Stec, E Rutherford, T Willing, L Brucklacher, R Corpe, C Liu, D Simpson, IA TI Alterations in monocarboxylate & glucose transporters in physiologic and pathologic conditions: Development & hypoxia-ischemia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. Penn State Univ, Hershey, PA 17033 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S47 EP S47 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100186 ER PT J AU Wakabayashi, T Messing, A Brenner, M AF Wakabayashi, T Messing, A Brenner, M TI Non-lethal detection of transgene expression in the CNS of founder mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53705 USA. Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S55 EP S55 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100221 ER PT J AU Williams, WM Stadtman, ER AF Williams, WM Stadtman, ER TI Detection of 4-hydroxy-2-nonenal (HNE) in cerebral microvessels of C57BL/6J mice as a function of age SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S29 EP S29 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100115 ER PT J AU Yarger, DE Ramassamy, C Krzywkowski, P Poirier, J Rapoport, SI Murphy, EJ AF Yarger, DE Ramassamy, C Krzywkowski, P Poirier, J Rapoport, SI Murphy, EJ TI Regional phospholipase A(2) activity in apolipoprotein E genotyped Alzheimer disease brains SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Cumberland Coll, Dept Biol, Williamsburg, KY 40769 USA. Douglas Hosp, Res Ctr, Verdun, PQ H4H 1R3, Canada. NIA, Neurosci Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S74 EP S74 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100294 ER PT J AU Yarger, DE Rapaport, SI Murphy, EJ AF Yarger, DE Rapaport, SI Murphy, EJ TI A continuous fluorometric assay for phospholipase A(2) activity in brain cytosol SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, Bethesda, MD 20892 USA. Cumberland Coll, Dept Biol, Williamsburg, KY 40769 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S66 EP S66 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100262 ER PT J AU Young, WS Iacangelo, A Luo, XZJ King, C Duncan, K Ginns, EI AF Young, WS Iacangelo, A Luo, XZJ King, C Duncan, K Ginns, EI TI Transgenic expression of green fluorescent protein in mouse oxytocin neurones SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE paraventricular; supraoptic; oxytocin; internal ribosomal entry site; green fluorescent protein ID CELL-SPECIFIC EXPRESSION; PHYSIOLOGICAL REGULATION; VASOPRESSIN TRANSGENE; GENE-EXPRESSION; MICE; SYSTEM; RATS AB Routine targeting of neurones for expression of exogenous genes would facilitate our ability to manipulate their internal milieu or functions, providing insight into physiology of neurones. The magnocellular neurones of the paraventricular and supraoptic nuclei of the hypothalamus have been the objects of limited success by this approach. Here we report on the placement of the enhanced green fluorescent protein (eGFP) coding sequence at various locations within an oxytocin transgene. Placement within the first exon yielded little to no expression, whereas placement in the third exon (as an in-frame fusion with the carboxyl terminus of the oxytocin preprohormone) resulted in cell-specific expression of eGFP in oxytocin neurones. Furthermore, placement of the eGFP sequence downstream of a picornavirus internal ribosomal entry site (IRES), also in the third exon, allowed expression of the eGFP as a separate protein. Other coding sequences should now be amenable to expression within oxytocin neurones to study their physiology. C1 NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, MSC 4068, Bethesda, MD 20892 USA. EM scott@codon.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 27 TC 30 Z9 31 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PY 1999 VL 11 IS 12 BP 935 EP 939 PG 5 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 264VH UT WOS:000084203300005 PM 10583728 ER PT J AU Warrick, JM Vakil, MF Tompkins, L AF Warrick, JM Vakil, MF Tompkins, L TI Spectral sensitivity of wildtype and mutant Drosophila melanogaster larvae SO JOURNAL OF NEUROGENETICS LA English DT Article DE color vision; lphA; LphB; L12 genetic variants ID COMPOUND EYE; GENE; PHOTOKINESIS; PHOTOTAXIS; SYSTEM; INPUT AB Wild-type (Canton-S) Drosophila melanogaster larvae are generally repelled by white light. Mutant larval photokinesis A (lphA) larvae are less strongly repelled than controls. Mutant Larval photokinesis B (LphB) larvae are unresponsive to light, as are larvae from LI2, an isofemale line whose progenitors were recently derived from a natural population. To characterize the behavior of larvae from the mutant stocks and the isofemale line more precisely, we determined the range of wavelengths that repel wild-type (Canton-S) D. melanogaster larvae and identified wavelengths to which larvae are most sensitive. In comparison to adult flies, Canton-S larvae are much less sensitive to white light and respond to a narrower range of wavelengths. The wavelengths to which Canton-S larvae are maximally sensitive are 500 nm (green), 420 nm (indigo), and 380 nm (ultraviolet). Mutant lphA larvae respond abnormally to green and indigo light but are as strongly repelled by ultraviolet light as controls. In contrast, mutant LphB larvae and larvae from the LI2 isofemale line are unresponsive to green, indigo, or ultraviolet light. Thus, lphA larvae have a wavelength-specific defect, while LphB and LI2 larvae are generally unresponsive to wavelengths that repel wild-type larvae. C1 Temple Univ, Dept Biol, Philadelphia, PA 19122 USA. RP Tompkins, L (reprint author), NIGMS, NIH, MSC 6200,45 Ctr Dr,Room 2AS-25N, Bethesda, MD 20892 USA. NR 17 TC 2 Z9 3 U1 2 U2 8 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PY 1999 VL 13 IS 3 BP 145 EP 156 DI 10.3109/01677069909083471 PG 12 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 256KN UT WOS:000083724600002 PM 10928215 ER PT J AU Quan, N Stern, EL Whiteside, MB Herkenham, M AF Quan, N Stern, EL Whiteside, MB Herkenham, M TI Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE tumor necrosis factor; interleukin-1 beta converting enzyme; interleukin-1 beta; interleukin-1 receptor antagonist; endotoxin ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; AREA POSTREMA; INTERLEUKIN-1-BETA; EXPRESSION; FEVER; PROJECTIONS; ENDOTOXIN; NUCLEUS AB Although it is generally accepted that pro-inflammatory cytokines produced by cells of the central nervous system play important roles in the communication between the central nervous system and the immune system during sepsis, it is not clear whether these cytokines are produced in the brain under subseptic conditions. In this study, we used in situ hybridization to examine the mRNA expression of the pro-inflammatory cytokines IL-1 beta and TNF alpha in the brains of rats 2 and 12 h after they were challenged by peripheral injections of lipopolysaccharide (LPS) ranging from 0.01 to 1000 mu g/kg. Unlike septic doses of LPS (> 500 mu g/kg), which induce global expression of pro-inflammatory cytokines in the brain, subseptic doses of LPS (0.01-10 mu g/kg) induced IL-1 beta and TNF alpha mRNA expression only in the choroid plexus, the circumventricular organs, and meninges. The expression of the cytokine-responsive immediate early gene I kappa B alpha was induced in the brain after doses of LPS as low as 0.1 mu g/kg. I kappa B alpha mRNA expression was confined to sites where rt-rp and TNF alpha were expressed. These results indicate that the induction and action of pro-inflammatory cytokines during subseptic infection occur at the blood-brain barrier and at circumventricular organs, which may be sites for elaboration of signal molecules that communicate peripheral immune status to the brain. Published by Elsevier Science B.V. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Quan, N (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Room 2D15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 26 TC 159 Z9 171 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN 1 PY 1999 VL 93 IS 1-2 BP 72 EP 80 DI 10.1016/S0165-5728(98)00193-3 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 160TM UT WOS:000078247200008 PM 10378870 ER PT J AU Stewart, RR Zigova, T Luskin, MB AF Stewart, RR Zigova, T Luskin, MB TI Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GATED K+ CHANNELS; CEREBELLAR GRANULE NEURONS; MAMMALIAN BRAIN; PROGENITOR CELLS; POLYSIALIC ACID; IONIC CURRENTS; IN-VITRO; EXPRESSION; CLONING; MIGRATION AB The progenitor cells from the anterior part of the neonatal subventricular zone, the SVZa, are unusual in that, although they undergo division, they have a neuronal phenotype. To characterize the electrophysiological properties of the SVZa precursor cells, recordings were made of potassium and sodium currents from SVZa cells that were removed from postnatal day 0-1 rats and cultured for 1 day. The properties of the delayed rectifier and A-type potassium currents were described by classical Hodgkin and Huxley analyses of activation and inactivation. In addition, cells were assessed under current clamp for their ability to generate action potentials. The A-type potassium current (I-K(A)) was completely inactivated at a holding potential of -50 mV. The remaining potassium current resembled the delayed rectifier current (I-K(DR)) in that it was blocked by tetraethylammonium (TEA; IC50 4.1 mM) and activated and inactivated slowly compared with I-K(A) The conductance-voltage (G-V) curve revealed that G increased continuously from 0.2 nS at -40 mV to a peak of 2.6 nS at +10 or +20 mV, and then decreased for voltages above +30 mV. Activation time constants were largest at -40 mV (similar to 11 ms) and smallest at 100 mV (similar to 1.5 ms). The properties of I-K(A) were studied in the presence of 20 mM TEA, to block I-K(DR), and from a holding potential of -15 mV, to inactivate both I-K(DR) and I-K(A). I-K(A) was then allowed to recover from inactivation to negative potentials during 200- to 800- ms pulses. Recovery from inactivation was fastest at -130 mV (similar to 21 ms) and slowest at -90 mV (similar to 135 ms). Inactivation was voltage independent from -60 to +60 mV with a time constant of -15 ms. At steady state, I-K(A) was half inactivated at -90 mV. G(K(A)) increased from 0.2 nS at -60 mV to a peak of 2.4 nS at +40 mV. Finally, the activation time constants ranged from -1.9 ms at -50 mV to 0.7 ms at +60 mV. The properties of I-K(A) resembled those of I-K(A) found in differentiating cerebellar granule neurons. Most SVZa cells had sodium currents (28/32: cells). However, in current clamp 1 1 of 12 cells were incapable of generating action potentials from voltages of -30 to -100mV, suggesting that the available current densities were too low to support excitability. C1 NIAAA, Mol & Cellular Neurobiol Lab, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA. RP Stewart, RR (reprint author), NIAAA, Mol & Cellular Neurobiol Lab, Park Bldg,Rm 118,12501 Washington Ave, Rockville, MD 20852 USA. FU CSAP SAMHSA HHS [LMCN-SP-01] NR 40 TC 27 Z9 27 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 1999 VL 81 IS 1 BP 95 EP 102 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 162NT UT WOS:000078353800009 PM 9914270 ER PT J AU Yagodin, S Collin, C Alkon, DL Sheppard, NF Sattelle, DB AF Yagodin, S Collin, C Alkon, DL Sheppard, NF Sattelle, DB TI Mapping membrane potential transients in crayfish (Procambarus clarkii) optic lobe neuropils with voltage-sensitive dyes SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; CHICK BRAIN-STEM; OLFACTORY-BULB; ELECTRICAL-ACTIVITY; NEURONAL-ACTIVITY; RECORDING SYSTEM; GABA; ACETYLCHOLINE; INTERNEURONS; ORGANIZATION AB Voltage-sensitive dyes NK 2761 and RH 155 were employed tin conjunction with a 12 x 12 photodiode array) to study membrane potential transients in optic lobe neuropils in the eye stalk of the crayfish Procambarus clarkii. By this means we investigated a pathway linking deutocerebral projection neurons, via hemiellipsoid body local interneurons, to an unidentified target (most likely neurons processing visual information) in the medulla terminalis. Rapid (10- to 20-ms duration), transient changes in absorption with the characteristics of action potentials were recorded from the optic nerve and the region occupied by deutocerebral projection neurons after stimulation of the olfactory globular tract in the optic nerve and were blocked by 1 mu M tetrodotoxin. Action potentials appeared to propagate to the glomerular layer of the hemiellipsoid body where synaptic responses were recorded from a restricted region of the hemiellipsoid body occupied by dendrites of hemiellipsoid body neurons. Action potentials were also recorded from processes of hemiellipsoid body neurons located in the medulla terminalis. Synaptic responses in the hemiellipsoid body and medulla terminalis were eliminated by addition to the saline of 500 mu M Cd2+ or 20 mM Co2+, whereas the action potential attributed to branches of deutocerebral projection neurons in the hemiellipsold body remained unaffected. Action potentials of hemiellipsoid body neurons in the medulla terminalis evoked postsynaptic potentials (50- to 200-ms duration) with an unidentified target in the medulla terminalis. Transient absorption signals were not detected in either the internal or external medulla nor were they recorded from other parts of the optic lobes in response to electrical stimulation of axons of the deutocerebral projection neurons. Functional maps of optical activity, together with electrophysiological and pharmacological findings, suggest that gamma-aminobutyric acid affects synaptic transmission in glomeruli of the hemiellipsoid body. Synapses of the olfactory pathway located in the medulla terminalis may act as a "filter," modifying visual information processing during olfactory stimulation. C1 Univ Cambridge, Dept Zool, Babraham Inst, Mol Signalling Lab, Cambridge CB2 3EJ, England. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21218 USA. NIH, Lab Adapt Syst, Bethesda, MD 20892 USA. RP Yagodin, S (reprint author), Univ Cambridge, Dept Zool, Babraham Inst, Mol Signalling Lab, Downing St, Cambridge CB2 3EJ, England. NR 46 TC 5 Z9 5 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 1999 VL 81 IS 1 BP 334 EP 344 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 162NT UT WOS:000078353800032 PM 9914293 ER PT J AU Duerr, JS Frisby, DL Gaskin, J Duke, A Asermely, K Huddleston, D Eiden, LE Rand, JB AF Duerr, JS Frisby, DL Gaskin, J Duke, A Asermely, K Huddleston, D Eiden, LE Rand, JB TI The cat-1 gene of Caenorhabditis elegans encodes a vesicular monoamine transporter required for specific monoamine-dependent behaviors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C- elegans; VMAT; vesicular transporter; cat-1; dopamine transport; serotonin transport ID MOUSE FETAL DEVELOPMENT; MALE MATING-BEHAVIOR; DENSE CORE VESICLES; C-ELEGANS; ACETYLCHOLINE TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS; FUNCTIONAL IDENTIFICATION; CHEMOSENSORY NEURONS; SYNAPTIC VESICLES; ENDOCRINE-CELLS AB We have identified the Caenorhabditis elegans homolog of the mammalian vesicular monoamine transporters (VMATs); it is 47% identical to human VMAT1 and 49% identical to human VMAT2. C. elegans VMAT is associated with synaptic vesicles in similar to 25 neurons, including ail of the cells reported to contain dopamine and serotonin, plus a few others. When C. elegans VMAT is expressed in mammalian cells, it has serotonin and dopamine transport activity; norepinephrine, tyramine, octopamine, and histamine also have high affinity for the transportee The pharmacological profile of C. elegans VMAT is closer to mammalian VMAT2 than VMAT1. The C. elegans VMAT gene is cat-1; cat-1 knock-outs are totally deficient for VMAT immunostaining and for dopamine-mediated sensory behaviors, yet they are viable and grow relatively well. The cat-1 mutant phenotypes can be rescued by C. elegans VMAT constructs and also (at least partially) by human VMAT1 or VMAT2 transgenes. It therefore appears that the function of amine neurotransmitters can be completely dependent on their loading into synaptic vesicles. C1 Oklahoma Med Res Fdn, Program Mol & Cell Biol, Oklahoma City, OK 73104 USA. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Rand, JB (reprint author), Oklahoma Med Res Fdn, Program Mol & Cell Biol, 825 NE 13th St, Oklahoma City, OK 73104 USA. OI Eiden, Lee/0000-0001-7524-944X FU NIGMS NIH HHS [GM38679, R01 GM038679] NR 67 TC 153 Z9 159 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 1999 VL 19 IS 1 BP 72 EP 84 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 153NP UT WOS:000077839400013 PM 9870940 ER PT J AU Svoboda, KR Adams, CE Lupica, CR AF Svoboda, KR Adams, CE Lupica, CR TI Opioid receptor subtype expression defines morphologically distinct classes of hippocampal interneurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE delta receptor; electrophysiology; enkephalin; GABA; hippocampus; inhibition; morphology; mu receptor; nonselective cation current; opioid receptor; oriens/alveus interneurons; potassium current ID ORIENS-ALVEUS INTERNEURONS; RAT HIPPOCAMPUS; PYRAMIDAL CELLS; INHIBITORY INTERNEURONS; STRATUM-ORIENS; CA1 REGION; GLUTAMATE RECEPTORS; GABA RELEASE; BRAIN-SLICES; NEURONS AB The inhibition of hippocampal pyramidal cells occurs via inhibitory interneurons making GABAergic synapses on distinct segments of the postsynaptic membrane. In area CA1 of the hippocampus, the activation of mu- and delta-opioid receptors inhibits these interneurons, thereby increasing the excitability of the pyramidal cells. Through the use of selective opioid agonists and biocytin-filled whole-cell electrodes, interneurons possessing somata located within stratum oriens of hippocampal slices were classified according to the location of their primary axon termination and the expression of mu- or delta-opioid receptors. Activation of these opioid receptor subtypes resulted in outward currents in the majority of interneurons, which is consistent with their inhibition. Post hoc morphological analysis revealed that those interneurons heavily innervating the pyramidal cell body layer were much more likely to express mu-opioid receptors, whereas cells with axons ramifying in the pyramidal neuron dendritic layers were more likely to express delta-opioid receptors, as defined by the generation of outward currents. This morphological segregation of interneuron projections suggests that mu receptor activation would diminish GABA release onto pyramidal neuron somata, thereby increasing their excitability acid output. Conversely, inhibition of interneurons via delta receptor activation would amplify afferent signaling to pyramidal neuron dendrites by reducing GABAergic inhibition of these structures. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Program Neurosci, Denver, CO 80262 USA. RP Lupica, CR (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA 07725]; NIMH NIH HHS [MH 44212] NR 58 TC 57 Z9 57 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 1999 VL 19 IS 1 BP 85 EP 95 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 153NP UT WOS:000077839400014 PM 9870941 ER PT J AU Bussey, TJ Muir, JL Aggleton, JP AF Bussey, TJ Muir, JL Aggleton, JP TI Functionally dissociating aspects of event memory: The effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat SO JOURNAL OF NEUROSCIENCE LA English DT Article DE episodic memory; event memory; spatial memory; object recognition; perirhinal cortex; postrhinal cortex; temporal lobe; rat ID FORNIX TRANSECTION; NEUROTOXIC LESIONS; PREFRONTAL CORTEX; TEMPORAL-LOBE; CORTICES; RECOGNITION; IMPAIRMENT; CINGULATE; ABLATION; MONKEYS AB Reciprocal interactions between the hippocampus and the perirhinal and parahippocampal cortices form core components of a proposed temporal lobe memory system. For this reason, the involvement of the hippocampus in event memory is thought to depend on its connections with these cortical areas. Contrary to these predictions, we found that NMDA-induced lesions of the putative rat homologs of these cortical areas (perirhinal plus postrhinal cortices) did not impair performance on two allocentric spatial tasks highly sensitive to hippocampal dysfunction, Remarkably, for one of the tasks there was evidence of a facilitation of performance. The same cortical lesions did, however, disrupt spontaneous object recognition and object discrimination reversal learning but spared initial acquisition of the discrimination. This pattern of results reveals important dissociations between different aspects of memory within the temporal robe. Furthermore, it shows that the perirhinal-postrhinal cortex is not a necessary route for spatial information reaching the hippocampus and that object familiarity-novelty detection depends on different neural substrates than do other aspects of event memory. C1 Cardiff Univ, Sch Psychol, Cardiff CF1 3YG, S Glam, Wales. RP Bussey, TJ (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. RI Bussey, Timothy/M-2758-2016; OI Bussey, Timothy/0000-0001-7518-4041; Aggleton, John/0000-0002-5573-1308 FU Wellcome Trust NR 28 TC 181 Z9 183 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 1999 VL 19 IS 1 BP 495 EP 502 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 153NP UT WOS:000077839400050 PM 9870977 ER PT J AU Wood, JD Lonser, RR Gogate, N Morrison, PF Oldfield, EH AF Wood, JD Lonser, RR Gogate, N Morrison, PF Oldfield, EH TI Convective delivery of macromolecules into the naive and traumatized spinal cords of rats SO JOURNAL OF NEUROSURGERY LA English DT Article DE bulk flow; convection; drug delivery; spinal cord; spinal cord injury; trauma; rat ID INFUSION; BRAIN AB Object. Many macromolecules have the potential to enhance recovery after injury and other lesions of the spinal cord, but because of the limited penetration of these compounds across the blood-spinal cord barrier, they cannot be used effectively. To determine if convective delivery could be used in a common animal model to investigate potential therapeutic macromolecules and to examine the effects of trauma on convective delivery in that model, the authors examined the distribution of a macromolecule in naive and traumatized rat spinal cords. Methods. Using convection, various infusion volumes ([Vi]; 1, 2, and 4 mu l) of C-14-albumin were infused into the dorsal columns of 13 naive and five traumatized rat spinal cords. Volume of distribution (Vd), homogeneity, percent age of recovery, and anatomical location were determined using quantitative autoradiography, scintillation analysis, calculation of kurtosis (K) value, and histological analysis. In the nontraumatized group, Vd was linearly proportional (R-2 = 0.98) to Vi (Vd/Vi, 4.3 +/- 0.6; mean +/-. standard deviation), with increases in Vd resulting from linear expansion (R-2 = 0.94) primarily in the craniocaudal dimension. In the traumatized spinal cords, the Vd/Vi ratio (3.7 +/- 0.5) was smaller (p < 0.02) and distributions were less confined to the craniocaudal dimension, with significantly larger cross-sectional distributions in the region of injury (p < 0.02) compared to the noninjured spinal cords. Histological analysis revealed that after infusion into the dorsal columns, albumin distribution in naive cords was limited to the dorsal white matter, but in the traumatized cords there was penetration into the central gray matter. The distribution of the infusate was homogeneous in the nontraumatized (K = -1.1) and traumatized (K = -1.1) spinal cords. Recovery of radioactivity was not significantly different (p > 0.05) between the nontraumatized (84.8 +/- 6.8%) and traumatized (79.7 +/- 12.1%) groups. Conclusions. Direct convective delivery of infusate can be used to distribute macromolecules in a predictable, homogeneous manner over significant volumes of naive and traumatized rat spinal cord. These characteristics make it a valuable tool to investigate the therapeutic potential of various compounds for the treatment of injury and spinal cord disease. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Intramural Res Resources, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37,MSC-1414, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 10 TC 32 Z9 32 U1 1 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 1999 VL 90 IS 1 SU S BP 115 EP 120 DI 10.3171/spi.1999.90.1.0115 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 169XH UT WOS:000078774400018 PM 10413135 ER PT J AU Lonser, RR Heiss, JD Oldfield, EH AF Lonser, RR Heiss, JD Oldfield, EH TI Syringomyelia, hemangioblastomas, and Chiari I malformation - Case illustration SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material DE Chiari malformation; hemangioblastoma; syringomyelia; von Hippel-Lindau disease C1 NIH, Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NIH, Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Bldg 10,Room 5D37,MSC-1414, Bethesda, MD 20892 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 1999 VL 90 IS 1 BP 169 EP 169 DI 10.3171/jns.1999.90.1.0169 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168TH UT WOS:000078708400026 PM 10413174 ER PT J AU Nikula, TK McDevitt, MR Finn, RD Wu, CC Kozak, RW Garmestani, K Brechbiel, MW Curcio, MJ Pippin, CG Tiffany-Jones, L Geerlings, MW Apostolidis, C Molinet, R Geerlings, MW Gansow, OA Scheinberg, DA AF Nikula, TK McDevitt, MR Finn, RD Wu, CC Kozak, RW Garmestani, K Brechbiel, MW Curcio, MJ Pippin, CG Tiffany-Jones, L Geerlings, MW Apostolidis, C Molinet, R Geerlings, MW Gansow, OA Scheinberg, DA TI Alpha-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized anti-CD33 antibodies: Pharmacokinetics, bioactivity, toxicity and chemistry SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE monoclonal antibodies; alpha-particles; Bi-213; Bi-212; CHX-A-DTPA; HuM195; M195 ID ACUTE MYELOGENOUS LEUKEMIA; PARTICLE-MEDIATED RADIOIMMUNOTHERAPY; MONOCLONAL-ANTIBODY; M195 ANTI-CD33; BI-212; THERAPY; RADIONUCLIDES; GENERATOR; TRIAL; IMMUNOREACTIVITY AB The alpha-particle-emitting radionuclides have several physical characteristics that make them attractive candidates for radioimmunotherapy: (a) high linear energy transfer; (b) short path lengths (50-80 mu m); and (c) limited ability of cells to repair damage to DNA. This article describes the pharmacokinetic, bioactivity, toxicity and chemical characteristics of cr-particle-emitting, Bi-213 and Bi-212 radiometal conjugated HuM195 (anti-CD33) constructs. Conjugation of HuM195 to SCN-CHX-A-DTPA resulted in the attachment of up to 10 chelating ligand molecules per antibody. Results: Radiolabeling efficiency of the CHX-A-DTPA-HuM195 construct with 213Bi was 78% +/- 10% (n = 46) after 10 min at specific activities of up to 1110 MBq/mg. The immunoreactivity of the Bi-213-labeled CHX-A-DTPA-HuM195 construct was 84% +/- 10% (n = 28) and was independent of the specific activity, The bismuth-labeled CHX-A-DTPA-HuM195 construct was rapidly internalized into the cell in a time-dependent manner ranging from 50% at 1 h to 65% at 24 h. Bi-205/Bi-206-labeled constructs were stable for at least 2 d in vitro in the presence of human serum at 37 degrees C. After injection into mice, there was no uptake or toss of bismuth to mouse tissues, which do not express CD33, or to the kidney, which has avidity for free bismuth. Mice injected intraperitoneally with doses of (Bi-213)CHX-A-DTPA-HuM195 ranging from 18.5 to 740 MBq/kg showed no toxicity, but at 2590 MBq/kg, two of the three mice died within 2 wk and a third mouse showed significant reductions in white blood cell counts. Mice injected intraveneously with doses of (Bi-213)CHX-A-DTPA-HuM195 up to 370 MBq/kg exhibited little toxicity, but 666 MBq/kg was above the MTD for mice. Leukemia cell killing in vitro with bismuth-labeled HuM195 showed dose- and specific activity-dependent killing of CD33+ HL60 cells; approximately 50% killing was observed when two bismuth atoms (50 fM radiolabeled antibody) were initially bound onto the target cell surface. Conclusion: Alpha-emitting antibodies are among the most potent cytotoxic agents known, yet are specific and appear safe in vivo. The physical and biochemical characteristics of the Bi-213 isotope and its generation, as well as the biochemistry of the Bi-213-labeled CHX-A-DTPA-HuM195 construct, make it possible to use the constructs safely and feasibly in humans at therapeutic levels. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. MAP Med Technol Inc, Tikkakoski, Finland. NCI, Chem Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Pharmactinium Inc, Wilmington, DE USA. Commiss European Communities, Joint Res Ctr, Inst Transuranium Elements, D-7500 Karlsruhe, Germany. RP Scheinberg, DA (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [P01 CA33049, R01 CA55349, U01 CA58260] NR 58 TC 129 Z9 129 U1 1 U2 11 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 1999 VL 40 IS 1 BP 166 EP 176 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 158KM UT WOS:000078114700041 PM 9935073 ER PT J AU Mahmoodian, F Peterkofsky, B AF Mahmoodian, F Peterkofsky, B TI Vitamin C deficiency in guinea pigs differentially affects the expression of type IV collagen, laminin, and elastin in blood vessels SO JOURNAL OF NUTRITION LA English DT Article DE guinea pigs; ascorbate; basement membrane collagen; elastin; laminin ID GROWTH-FACTOR-I; BASEMENT-MEMBRANE COLLAGEN; FACTOR-BINDING-PROTEINS; SMOOTH-MUSCLE CELLS; AMINO-ACID SEQUENCE; GENE-EXPRESSION; SKIN FIBROBLASTS; IGF-I; HORMONE INCREASES; DIABETIC RATS AB Vitamin C deficiency causes morphologic changes in the endothelial and smooth muscle compartments of guinea pig blood vessels. Endothelial cells synthesize the basement membrane components, type IV collagen and laminin, and smooth muscle cells synthesize elastin in blood vessels. Therefore, we examined the possibility that vitamin C deficiency affects the expression of these proteins. Decreased expression of types I and II collagens in other tissues of vitamin C-deficient guinea pigs is associated with weight loss and the consequent induction of insulin-like growth factor binding proteins; thus we also used food deprivation to induce weight loss. Female guinea pigs received a vitamin C-free diet, supplemented orally with ascorbate. Vitamin C-deficient guinea pigs received the same diet but no ascorbate, and the food-deprived group received no food, but were supplemented with vitamin C. Concentrations of mRNAs far basement membrane components and elastin in blood vessels were measured by Northern blotting; overall basement membrane metabolism was assessed by measuring immunoreactive laminin and type IV 7S collagen in serum. Laminin mRNA in blood vessels and serum laminin concentrations were unaffected by vitamin C deficiency. Concentrations of type IV collagen and elastin mRNAs in blood vessels were not significantly affected in moderately scorbutic guinea pigs (0-7% weight loss), but with increased weight loss, type IV collagen mRNA was 57% (P < 0.05) and elastin mRNA was 3% (P < 0.01) of normal values. In food-deprived guinea pigs, type IV collagen mRNA was 51% (P < 0.05) and elastin mRNA was 35% (P < 0.05) of normal. Serum type IV 7S collagen concentrations were 25% of normal in scorbutic guinea pigs with extensive weight loss. The lower expression of type IV collagen and elastin mRNAs in blood vessels may contribute to defects observed in blood vessels during scurvy. C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Peterkofsky, B (reprint author), NCI, Biochem Lab, Bethesda, MD 20892 USA. NR 50 TC 29 Z9 29 U1 2 U2 5 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1999 VL 129 IS 1 BP 83 EP 91 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 158VL UT WOS:000078138000014 PM 9915880 ER PT J AU Shah, JP AF Shah, JP TI Dimensions of "functional status" in trials or wasting SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Clinical Trials for the Treatment of Secondary Wasting and Cachexia - Selection of Appropriate Endpoints CY MAY 22-23, 1997 CL BETHESDA, MARYLAND SP US FDA, Off AIDS Res, Natl Canc Inst, NIMH, Bristol Myers Squibb, Abbott Labs, Serono Labs Inc, Amer Inst Canc Res, Roxane Labs, NIDA, SmithKline Beecham, NIA, Eli Lilly & Co C1 NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Shah, JP (reprint author), NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1999 VL 129 IS 1 SU S BP 279S EP 281S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 160PA UT WOS:000078238000014 PM 9915915 ER PT J AU Bennett, WP Hussain, SP Vahakangas, KH Khan, MA Shields, PG Harris, CC AF Bennett, WP Hussain, SP Vahakangas, KH Khan, MA Shields, PG Harris, CC TI Molecular epidemiology of human cancer risk: Gene-environment interactions and p53 mutation spectrum in human lung cancer SO JOURNAL OF PATHOLOGY LA English DT Review DE epidemiology; molecular biology; neoplasia; environment; p53; lung cancer ID GLUTATHIONE-S-TRANSFERASE; TUMOR-SUPPRESSOR GENE; DNA ADDUCT LEVELS; SQUAMOUS-CELL CARCINOMA; GERM-LINE POLYMORPHISMS; SKIN-CANCER; CIGARETTE-SMOKING; HEPATOCELLULAR-CARCINOMA; CHEMICAL CARCINOGENS; HUMAN LIVER AB The p53 tumour suppressor gene is at the crossroads of a network of cellular pathways including cell cycle checkpoints, DNA repair, chromosomal segregation, and apoptosis, These pathways hare evolved to maintain the stability of the genome during cellular stress from DNA damage, hypoxia, and activated oncogenes, The high frequency of p53 mutations in human cancer is a reflection of the importance of p53 involvement in this network of pathways during human carcinogenesis. An electronic database containing p53 mutations from more than 9000 cancers (http://www.iarc.fr/p53/homepage.html) can be used to generate hypotheses for further clinical, epidemiological, and laboratory investigations. For example, one can hypothesize that (a) p53 mutations vary in their pathobiological significance; (b) cellular content influences the selection of p53 mutations in clonally derived cancers; (c) the location and type of mutation within the p53 gene provide clues to functional domains in the gene product; and (d) the p53 mutation spectrum can be a molecular link between aetiological agents and human cancer. This review will focus on the role of p53 and cancer susceptibility genes in the molecular pathogenesis and epidemiology of human lung cancer. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Oulu, Dept Pharmacol & Toxicol, FIN-90220 Oulu, Finland. City Hope Natl Med Ctr, Div Human Genet, Duarte, CA 91010 USA. Beckman Res Inst, Duarte, CA 91010 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C05, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov RI Shields, Peter/I-1644-2012 NR 126 TC 129 Z9 137 U1 3 U2 8 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 1999 VL 187 IS 1 BP 8 EP 18 DI 10.1002/(SICI)1096-9896(199901)187:1<8::AID-PATH232>3.0.CO;2-Y PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 152RN UT WOS:000077790700003 PM 10341702 ER PT J AU Gill, S Vonderhaar, BK Peston, D Shousha, S AF Gill, S Vonderhaar, BK Peston, D Shousha, S TI Distribution of prolactin receptors in normal, benign and malignant breast tissue SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract C1 Charing Cross Hosp, Sch Med, Imperial Coll, Dept Histopathol, London W6 8RF, England. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PY 1999 VL 187 SU S BP 26A EP 26A PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 176VR UT WOS:000079173200102 ER PT J AU Riminucci, M Liu, B Corsi, A Shenker, A Spiegel, AM Robey, PG Bianco, P AF Riminucci, M Liu, B Corsi, A Shenker, A Spiegel, AM Robey, PG Bianco, P TI The histopathology of fibrous dysplasia of bone in patients with activating mutations of the Gs alpha gene: Site-specific patterns and recurrent histological hallmarks SO JOURNAL OF PATHOLOGY LA English DT Article DE bone; McCune-Albright syndrome; fibrous dysplasia; G protein; Gs alpha mutation; pathology; confocal microscopy ID MCCUNE-ALBRIGHT SYNDROME; STIMULATORY G-PROTEIN; G(S)ALPHA MUTATION; ADENYLYL CYCLASE; TEMPORAL BONE; LESIONS; SUBUNIT; IDENTIFICATION; SPECTRUM; CYST AB Gs alpha mutations and histopathology have been analysed in a series of 13 patients with fibrous dysplasia (FD) of bone, including 12 patients with the McCune-Albright syndrome (MAS) and one patient with monostotic FD, Activating mutations (either R201C or R201H) of the gene encoding the a subunit of the stimulatory G protein, Gs, were detected in all cases, including the case of monostotic FD, using a variety of techniques [reverse transcription-polymerase chain reaction (RT-PCR) with allele-specific primers, allele-specific oligonucleotide hybridization, and DNA sequencing], A spectrum of bone lesions associated with such mutations was identified and it was possible to recognize three primary, but distinct, histological patterns, defined here as Chinese writing type, sclerotic/Pagetoid type, and sclerotic/hypercellular type, which are characteristically associated with the axial/appendicular skeleton, cranial bones, or gnathic bones, respectively, Features of FD histopathology were characterized by confocal fluorescence microscopy, which allowed the definition of osteogenic cell shape changes and 'Sharpey fibre bone' as common denominators of all histological subtypes. Defining characteristics of the different subtypes, two of which diverge from standard descriptions of FD and have never been characterized before, were dependent on the amount and structure of bone tissue within the FD lesion. These data emphasize the non-random (site-specific) variability of FD histopathology in patients carrying activating mutations of the Gsa gene and provide additional evidence for the occurrence of Gs alpha mutations in cases of FD other than typical MAS. Copyright (C)1999 John Wiley & Sons, Ltd. C1 NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Aquila, Div Pathol, Dept Expt Med, I-67100 Laquila, Italy. Univ Rome La Sapienza, Dept Expt Med, Rome, Italy. NIH, NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA. RP Robey, PG (reprint author), NIDR, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr MSC 4320, Bethesda, MD 20892 USA. EM PROBEY@yoda.nidr.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.0519] NR 36 TC 103 Z9 107 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 1999 VL 187 IS 2 BP 249 EP 258 DI 10.1002/(SICI)1096-9896(199901)187:2<249::AID-PATH222>3.0.CO;2-J PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 159PP UT WOS:000078182900014 PM 10365102 ER PT J AU Berg, SL Reid, J Godwin, K Murry, DJ Poplack, DG Balis, FM Ames, MM AF Berg, SL Reid, J Godwin, K Murry, DJ Poplack, DG Balis, FM Ames, MM TI Pharmacokinetics and cerebrospinal fluid penetration of daunorubicin, idarubicin, and their metabolites in the nonhuman primate model SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE idarubicin; daunorubicin; cerebrospinal fluid; pharmacokinetics; metabolites ID C-13 ALCOHOL METABOLITES; PLASMA PHARMACOKINETICS; RESISTANCE; CANCER; CELLS AB Purpose: Idarubicin (4-demethoxy-daunorubicin) is more potent and less cardiotoxic than the commonly used anthracyclines, doxorubicin and daunorubicin. In addition, idarubicin is metabolized to an active metabolite, idarubicinol, in contrast to other anthracyclines whose alcohol metabolites are much less active than the parent drug. The current study was performed in nonhuman primates to determine the plasma and cerebrospinal fluid (CSF) pharmacokinetics of idarubicin and idarubicinol and to compare them to the pharmacokinetics of daunorubicin and daunorubicinol. Methods: A dose of 30 mg/m(2) of daunorubicin or 8 mg/m(2) of idarubicin was administered intravenously over 15 minutes. Plasma and CSF were sampled frequently from the end of the infusion to 72 to 96 hours after infusion. Drug and metabolite concentrations were measured using high-pressure liquid chromatography (HPLC). Results: Daunorubicin elimination from plasma was triphasic with a terminal half-life of 5.9 +/- 1.8 hours, area under the concentration-time curve (AUC) 22.5 +/- 9.2 mu mol/L . min, and clearance 2790 +/- 960 mL/min/m(2). Daunorubicinol elimination was biphasic with a terminal half-life 10.2 +/- 2.3 hours and an AUC 74.5 +/- 5.3 mu mol/L . min. Idarubicin elimination was triphasic with terminal half-life of 12.3 +/- 11.4 hours, a AUC 10.8 +/- 3.7 mu mol/L min, and clearance 1650 +/- 610 mL/min/m(2). Idarubicinol elimination was biphasic with a terminal half-lift 28.7 +/- 4.2 hours and AUC 67 +/- 9.8 mu mol/L min. CSF penetration was low for both parent drugs and their metabolites. CSF idarubicin was measurable at a single time point (1 hour after administration) for 2 animals, and was not measurable for the third. The CSF to plasma concentration ratio at that time point was 8% in 1 animal and 15% in the other. Idarubicinol was detected in 2 to 4 samples at various times, appearing as early as 1 hour in 1 animal and persisting as late as 48 hours in another. The CSF to plasma concentration ratio at corresponding time points was 1.9 +/- 0.6%. Daunorubicin was measurable for < 6 hours after intravenous administration. For individual animals, the mean CSF to plasma concentration ranged from 4% to 12%. Daunorubicinol was detectable by 1 hour in 2 of 3 animals and by 3 hours in the other, and remained detectable at 24 hours in 2 of 3. The terminal half-life of daunorubicinol in CSF was 8.8 +/- 1.3 hours, the AUC was 1.8 +/- 1.5 mu mol/L . min, and the AUC(CSF) to AUC(plasma) ratio was 2.4 +/- 1.9%. Conclusion: Idarubicin, idarubicinol, daunorubicin, and daunorubicinol penetrate poorly into the CSF after intravenous administration. C1 Texas Childrens Hosp, Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. Mayo Clin, Dept Oncol, Rochester, MN USA. RP Berg, SL (reprint author), Texas Childrens Hosp, Baylor Coll Med, Texas Childrens Canc Ctr, 6621 Fannin St MC3-3320, Houston, TX 77030 USA. FU NCI NIH HHS [CA13539-24, CA 15083] NR 17 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JAN-FEB PY 1999 VL 21 IS 1 BP 26 EP 30 DI 10.1097/00043426-199901000-00008 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 163VP UT WOS:000078427300006 PM 10029808 ER PT J AU Albandar, JM Brunelle, JA Kingman, A AF Albandar, JM Brunelle, JA Kingman, A TI Destructive periodontal disease in adults 30 years of age and older in the United states, 1988-1994 SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE National Health and Nutrition Examination Survey III; furcation epidemiology; periodontal diseases epidemiology; periodontal attachment loss epidemiology; periodontal pockets epidemiology; periodontitis epidemiology; blacks; Mexican Americans ID PREVALENCE; INFECTION; LESIONS AB Background: Accurate information on the prevalence and extent of periodontal diseases in the United States adult population is lacking. This study estimated the prevalence and extent of periodontal disease in the United States using data from the third National Health and Nutrition Examination Survey (NHANES III). Methods: A nationally representative sample was obtained during 1988 to 1994 by a stratified, multi-stage probability sampling design. A subsample of 9,689 dentate persons 30 to 90 years old who received a periodontal examination was used in this study, representing approximately 105.8 million civilian, non-institutionalized Americans in 1988 to 1994. Periodontal attachment loss, probing depth, and furcation involvement were assessed in 2 randomly selected quadrants per person. Attachment loss and probing depth were assessed at 2 sites per tooth, the mesiobuccal and mid-buccal surfaces. The periodontal status of each subject was assessed by criteria based on the extent and severity of probing depth and furcation involvement. These assessments were used to classify each subject as having a mild, moderate, or advanced form of the disease. In the analyses, weighted data were used to reflect the complex sampling method. Results: Prevalence of attachment loss greater than or equal to 3 mm was 53.1% for the population of dentate U.S. adults 30 to 90 years of age and, on average, 19.6% of teeth per person were affected. The prevalence of probing depth greater than or equal to 3 mm was 63.9% and, on average, 19.6% of teeth were affected. Fourteen percent of these persons had furcation involvement in one or more teeth. We estimate that at least 35% of the dentate U.S. adults aged 30 to 90 have periodontitis, with 21.8% having a mild form and 12.6% having a moderate or severe form. The prevalence and extent of attachment loss and the prevalence of periodontitis increase considerably with age. However, the prevalence of moderate and advanced periodontitis decreases in adults 80 years of age and older. This is most likely attributed to a combination of a high prevalence of tooth loss and gingival recession in the oldest age cohorts. Attachment loss and destructive periodontitis were consistently more prevalent in males than females, and more prevalent in blacks and Mexican Americans than whites. We estimate that in persons 30 years and older, there are approximately 56.2 and 67.6 million persons who, on average, have about a third of their remaining teeth affected by 2 3 mm attachment loss and probing depth, respectively. We also estimate that about 21 million persons have at least one site with greater than or equal to 5 mm attachment loss, and 35.7 million persons have periodontitis. These are conservative estimates based on partial-mouth examinations, and the true prevalence and extent of periodontal disease may be significantly higher than what is reported here. Conclusions: Periodontitis is prevalent in the U.S. adult population. The results show that black and Mexican American males have poorer periodontal health than the rest of the U.S. adult population. Primary and secondary preventive measures should therefore be specifically targeted towards these groups. C1 NIDCR, NIH, Bethesda, MD USA. RP Albandar, JM (reprint author), Univ Bergen, Fac Dent, Div Periodontol, Arstadveien 17, N-5009 Bergen, Norway. OI Albandar, Jasim M./0000-0001-7801-3811 NR 19 TC 403 Z9 423 U1 1 U2 26 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JAN PY 1999 VL 70 IS 1 BP 13 EP 29 DI 10.1902/jop.1999.70.1.13 PG 17 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 165KB UT WOS:000078519000003 PM 10052767 ER PT J AU Albandar, JM Kingman, A AF Albandar, JM Kingman, A TI Gingival recession, gingival bleeding, and dental calculus in adults 30 years of age and older in the United States, 1988-1994 SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE bleeding epidemiology; dental calculus epidemiology; gingival recession epidemiology; gingivitis epidemiology; periodontal diseases epidemiology; National Health and Nutrition Examination Survey III ID PERIODONTAL-DISEASE; PLAQUE; PREVALENCE AB Background: The aim of this study was to assess the prevalence and extent of gingival recession, gingival bleeding, and dental calculus in United States adults, using data collected in the third National Health and Nutrition Examination Survey (NHANES III). Methods: The study group consisted of 9,689 persons 30 to 90 years of age obtained by a stratified, multi-stage probability sampling method in 1988 to 1994. The weighted sample is representative of U.S. adults 30 years or older and represents approximately 105.8 million civilian, non-institutionalized Americans. Gingival recession, gingival bleeding, and dental calculus were assessed at the mesio-buccal and mid-buccal surfaces in 2 randomly selected quadrants, one maxillary and one mandibular. Data analysis accounted for the complex sampling design used. Results: We estimate that 23.8 million persons have one or more tooth surfaces with greater than or equal to 3 mm gingival recession; 53.2 million have gingival bleeding; 97.1 million have calculus; and 58.3 million have subgingival calculus; and the corresponding percentages are 22.5%, 50.3%, 91.8%, and 55.1% of persons, respectively. The prevalence, extent, and severity of gingival recession increased with age, as did the prevalence of subgingival calculus and the extent of teeth with calculus and gingival bleeding. Males had significantly more gingival recession, gingival bleeding, subgingival calculus, and more teeth with total calculus than females. Of the 3 race/ethnic groups studied, non-Hispanic blacks had the highest prevalence and extent of gingival recession and dental calculus, whereas Mexican Americans had the highest prevalence and extent of gingival bleeding. Mexican Americans had similar prevalence and extent of gingival recession compared with non-Hispanic whites. Gingival recession was much more prevalent and also more severe at the buccal than the mesial surfaces of teeth. Gingival bleeding also was more prevalent at the buccal than mesial surfaces, whereas calculus was most often present at the mesial than buccal surfaces. Conclusions: Dental calculus, gingival bleeding, and gingival recession are common in the U.S. adult population. In addition to their unfavorable effect on esthetics and self-esteem, these conditions also are associated with destructive periodontal diseases and root caries. Appropriate measures to prevent or control these conditions are desirable, and this may also be effective in improving the oral health of the U.S. adult population. C1 NIDCR, NIH, Bethesda, MD USA. RP Albandar, JM (reprint author), Univ Bergen, Fac Dent, Div Periodontol, Arstadvelen 17, N-5009 Bergen, Norway. EM Jasim.Albandar@odont.uib.no OI Albandar, Jasim M./0000-0001-7801-3811 NR 26 TC 198 Z9 209 U1 2 U2 14 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JAN PY 1999 VL 70 IS 1 BP 30 EP 43 DI 10.1902/jop.1999.70.1.30 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 165KB UT WOS:000078519000004 PM 10052768 ER PT J AU Figg, WD Raje, S Bauer, KS Tompkins, A Venzon, D Bergan, R Chen, A Hamilton, M Pluda, J Reed, E AF Figg, WD Raje, S Bauer, KS Tompkins, A Venzon, D Bergan, R Chen, A Hamilton, M Pluda, J Reed, E TI Pharmacokinetics of thalidomide in an elderly prostate cancer population SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TUMOR ANGIOGENESIS; PLASMA PHARMACOKINETICS; CHIRAL INVERSION; METASTASIS; METABOLITES; ENANTIOMERS; CARCINOMA; DISEASE AB Thalidomide, a glutamic acid derivative, has recently been shown to inhibit in vitro angiogenesis, the process of formation of new blood vessels. This Phase II study examined the pharmacokinetics of thalidomide in patients with clinically progressive hormone-refractory prostate cancer. Patients (aged 55 to 80 years) were randomized to two different arms, low dose versus high dose. Patients in the low-dose group were given 200 mg of thalidomide and patients in the high-dose group received 200 mg of thalidomide, with subsequent dose escalations to 1200 mg. Serial serum or blood samples were obtained for pharmacokinetic assessment after administration of a single oral dose or multiple daily dosing of thalidomide and were assayed by reversed-phase HPLC. Pharmacokinetic parameters for both the single and multiple dosing were calculated with ADAPT II. A one-compartment model best fit the data. After single dosing, the oral clearance and apparent volume of distribution for the low-dose regimen (n = 13) were 7.41 +/- 2.05 L/h and 66.93 +/- 34.27 L, respectively, whereas for the high-dose regimen (n = 11), these values were 7.21 +/- 2.89 L/h and 165.81 +/- 84.18 L, respectively. The elimination half-lives for the low and high dose were 6.52 +/- 3.81 and 18.25 +/- 14.08 h, respectively. After the multiple dosing of thalidomide, the oral clearance and apparent volume of distribution for the low-dose group (n = 10) were 6.35 +/- 1.64 L/h and 64.63 +/- 23.20 L, respectively, whereas for the high-dose group (n = 11), these values were 7.73 +/- 2.27 L/h and 167.85 +/- 82.08 L, respectively. The elimination half-lives for the low and high dose were 7.08 +/- 1.87 and 16.19 +/- 9.57 h, respectively. For both the single and multiple dosing of thalidomide, the apparent volume of distribution and half-life were significantly higher for the high-dose group than those for the low-dose group. The higher apparent volume of distribution may be attributable to several factors, such as change in absorption, protein binding, etc. A dose-proportional increase in thalidomide steady-state concentrations was seen after multiple daily dosing of thalidomide. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 28 TC 91 Z9 93 U1 2 U2 4 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD JAN PY 1999 VL 88 IS 1 BP 121 EP 125 DI 10.1021/js980172i PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 155RL UT WOS:000077960100018 PM 9874712 ER PT J AU Katsube, N Sunaga, K Aishita, H Chuang, DM Ishitani, R AF Katsube, N Sunaga, K Aishita, H Chuang, DM Ishitani, R TI ONO-1603, a potential antidementia drug, delays age-induced apoptosis and suppresses overexpression of glyceraldehyde-3-phosphate dehydrogenase in cultured central nervous system neurons SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CEREBELLAR GRANULE CELLS; AMYLOID PRECURSOR PROTEIN; MESSENGER-RNA LEVELS; ALZHEIMERS-DISEASE; INTRANUCLEAR INCLUSIONS; DEATH; TETRAHYDROAMINOACRIDINE; ACETYLCHOLINE; MEMORY; BRAIN AB Primary cultures of rat cerebral cortical cells and cerebellar granule cells die by an apoptotic mechanism after more than 2 weeks in cultures in the absence of medium change and glucose supplement, a process termed age-induced apoptosis of cultured neurons. Our preliminary study has shown that age-induced apoptosis of cerebellar granule cells is protected by pretreatment with tetrahydroaminoacridine (THA), an antidementia drug. In this study, we systematically compared the neuroprotective effects of THA with those of (S)-1-[N-(4-chlorobenzyl)succinamoyl]pyrrolidine-2-carbaldehyde (ONO-1603), a novel prolyl endopeptidase inhibitor and potential antidementia drug. Both ONO-1603 and MA effectively delay age-induced apoptosis of cerebral and cerebellar neurons, as demonstrated morphologically with toluidine blue and fluorescein diacetate/propidium iodide staining or biochemically by DNA laddering analysis on agarose gels. ONO-1603 is about 300 times more potent than THA, with a maximal protective effect at 0.03 and 10 mu M, respectively. ONO-1603 shows a wide protective range of 0.03 to 1 mu M in contrast to a narrow effective range of 3 to 10 mu M for THA. Moreover, ONO-1603 is nontoxic to neurons, even at the high concentration of 100 mu M, whereas MA elicits severe neurotoxicity at a dose of greater than or equal to 30 mu M. Both ONO-1603 and THA robustly suppress overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) mRNA and accumulation of GAPDH protein in a particulate fraction of cultured neurons undergoing age-induced apoptosis. Because we documented that GAPDH overexpression participates in neuronal apoptosis induced by various insults, we conclude that the neuroprotective actions of ONO-1603 and THA appear to be mediated by suppression of this protein overexpression. C1 Josai Univ, Grp Cellular Neurobiol, Sakado, Saitama 35002, Japan. Ono Pharmaceut Co Ltd, Minase Res Inst, Osaka, Japan. NIMH, Mol Neurosci Sect, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Ishitani, R (reprint author), Josai Univ, Grp Cellular Neurobiol, Sakado, Saitama 35002, Japan. NR 40 TC 46 Z9 55 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 1999 VL 288 IS 1 BP 6 EP 13 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 154CD UT WOS:000077870200002 PM 9862746 ER PT J AU Quezado, ZMN Hoffman, WD Banks, SM Danner, RL Eichacker, PQ Susla, GM Natanson, C AF Quezado, ZMN Hoffman, WD Banks, SM Danner, RL Eichacker, PQ Susla, GM Natanson, C TI Increasing doses of pentoxifylline as a continuous infusion in canine septic shock SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; IMPROVES SURVIVAL; FACTOR-ALPHA; SEPSIS; ENDOTOXEMIA; MODEL; HEMODYNAMICS; GRANULOCYTE; DYSFUNCTION; INHIBITION AB We investigated effects of pentoxifylline during septic shock. Two-year-old (10-12 kg), purpose-bred beagles were infected i.p. with Escherichia coli 0111:B4 (1.2-1.5 x 10(9) colony-forming units per kilogram b.wt.) in a fibrin clot and then immediately treated with one of five doses of pentoxifylline (0.5-20 mg.kg(-1).h(-1) i.v.) as a 36-h continuous infusion or placebo. All animals received antibiotics and fluid resuscitation. Pentoxifylline levels increased in a dose-dependent manner during (p =.001) and were undetectable 12 h after stopping the infusion. During infusion of pentoxifylline at all doses, there were increases (p =.003), and once the infusion was stopped, there were decreases (p =.049) in endotoxin levels compared with controls. After clot implantation, at all pentoxifylline doses there was a significant increase in tumor necrosis factor levels, compared with controls (p =.025). The relative risk of death was significantly increased with pentoxifylline therapy in a dose-dependent fashion (20 greater than or equal to 10 greater than or equal to 5.0 greater than or equal to 1.0 greater than or equal to 0.5 mg.kg(-1) p =.008). One hypothesis consistent with these data is that high pentoxifylline levels slowed endotoxin clearance, resulting in high levels of endotoxemia and increased proinflammatory mediator release and death. Pentoxifylline, used as a long-term continuous infusion as is commonly done clinically, can be harmful during Gram-negative septic shock. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP Natanson, C (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Room 7D43,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 41 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 1999 VL 288 IS 1 BP 107 EP 113 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 154CD UT WOS:000077870200016 PM 9862760 ER PT J AU Katz, JL Izenwasser, S Kline, RH Allen, AC Newman, AH AF Katz, JL Izenwasser, S Kline, RH Allen, AC Newman, AH TI Novel 3 alpha-diphenylmethoxytropane analogs: Selective dopamine uptake inhibitors with behavioral effects distinct from those of cocaine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NONHUMAN-PRIMATES; CAUDATE-PUTAMEN; RAT STRIATUM; BINDING; TRANSPORTER; RECEPTORS; BENZTROPINE; DRUGS; SITES; DERIVATIVES AB The pharmacological effects were assessed for a series of 3 alpha-diphenylmethoxy-1 alpha H,5 alpha H-tropane analogs which have structural similarities to cocaine. Like cocaine, these compounds displaced [H-3]WIN 35,428 binding from rat caudate and had affinities ranging from approximately 10-fold greater than cocaine (K-i = 11.8 nM) to relatively low affinity (K-i = 2000 nM). The compounds also inhibited dopamine uptake with potencies corresponding to their affinities for WIN 35,428 binding sites. Like the parent compound, benztropine, the 3 alpha-(diphenylmethoxy)tropane analogs displaced [H-3]pirenzepine from muscarinic M-1 receptors with affinities ranging from 2 to 120 nM. Cocaine produced dose-related increases in locomotor activity (horizontal ambulation) in Swiss Webster mice, whereas the 3 alpha-(diphenylmethoxy)tropane analogs generally had lower efficacy than cocaine. Compounds with fluoro-substituents in the phenyl rings generally were among those with efficacy approaching that of cocaine; those with chloro- and bromo-substituents were markedly less efficacious, despite having binding affinities comparable to those of the corresponding fluoro-substituted compounds. The 3 alpha-(diphenylmethoxy)tropane analogs were also examined in rats trained to discriminate saline from cocaine (10 mg/kg, i.p.). Cocaine produced a dose-related increase in responding on the cocaine-appropriate lever, reaching 100% at 10 mg/kg, Only the 4',4 "-difluoro-substituted analog produced effects similar to those of cocaine; the other compounds showed markedly reduced efficacy compared to cocaine. Drug interaction studies showed that the antimuscarinics, atropine and scopolamine, potentiated rather than attenuated the locomotor stimulant and cocaine-like discriminative-stimulus effects of cocaine, indicating that the antimuscarinic effects of the 3 alpha-diphenylmethoxytropane analogs did not contribute to their diminished cocaine-like activity. Studies of the time course of selected compounds indicated that their reduced cocaine-like efficacy was likely not due to behavioral observations being conducted at an inopportune time period. Because none of the 3 alpha-diphenylmethoxytropane analogs studied showed evidence that they were binding to more than one site, and because the structure activity relationships among these drugs are distinctly different from those obtained with cocaine, these data suggest that the 3 alpha-diphenylmethoxytropane analogs are accessing a different binding domain than that accessed by cocaine. Binding to this domain may produce a behavioral profile that is distinct from that of the cocaine-like dopamine uptake inhibitors. C1 NIDA, Intramural Res Program, Psychobiol Sect, NIH, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), NIDA, Intramural Res Program, Psychobiol Sect, NIH, POB 5180, Baltimore, MD 21224 USA. RI Izenwasser, Sari/G-9193-2012; OI Katz, Jonathan/0000-0002-1068-1159 NR 40 TC 77 Z9 78 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 1999 VL 288 IS 1 BP 302 EP 315 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 154CD UT WOS:000077870200041 PM 9862785 ER PT J AU Sun, ZR Xia, XF Guo, Q Xu, D AF Sun, ZR Xia, XF Guo, Q Xu, D TI Protein structure prediction in a 210-type lattice model: Parameter optimization in the genetic algorithm using orthogonal array SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE protein folding; genetic algorithm; lattice model; optimization; orthogonal array ID FOLDING SIMULATIONS; CYTOCHROME-B562 AB We have applied the orthogonal array method to optimize the parameters in the genetic algorithm of the protein folding problem. Our study employed a 210-type lattice model to describe proteins, where the orientation of a residue relative to its neighboring residue is described by two angles. The statistical analysis and graphic representation show that the two angles characterize protein conformations effectively. Our energy function includes a repulsive energy, an energy for the secondary structure preference, and a pairwise contact potential. We used orthogonal array to optimize the parameters of the population, mating factor, mutation factor, and selection factor in the genetic algorithm. By designing an orthogonal set of trials with representative combinations of these parameters, we efficiently determined the optimal set of parameters through a hierarchical search. The optimal parameters were obtained from the protein crambin and applied to the structure prediction of cytochrome B562. The results indicate that the genetic algorithm with the optimal parameters reduces the computing time to reach a converged energy compared to nonoptimal parameters. It also has less chance to be trapped in a local energy minimum, and predicts a protein structure which is closer to the experimental one. Our method may also be applicable to many other optimization problems in computational biology. C1 Tsing Hua Univ, Dept Biol Sci & Biotechnol, State Key Lab Biomembrane & Membrane Engn, Beijing 100084, Peoples R China. NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC Frederick,Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Xu, D (reprint author), Oak Ridge Natl Lab, Computat Biosci Sect, POB 2008, Oak Ridge, TN 37830 USA. NR 19 TC 15 Z9 19 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JAN PY 1999 VL 18 IS 1 BP 39 EP 46 DI 10.1023/A:1020643331894 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 169GZ UT WOS:000078740400005 PM 10071927 ER PT J AU Rotondo, A Pardini, L Armani, A Sarno, N Gemignani, A Presta, S Pfanner, C Mauri, M Goldman, D Dell'Osso, L Cassano, GB AF Rotondo, A Pardini, L Armani, A Sarno, N Gemignani, A Presta, S Pfanner, C Mauri, M Goldman, D Dell'Osso, L Cassano, GB TI Genetic association study of promoter region polymorphisms in tryptophan hydroxylase and serotonin transporter genes with obsessive compulsive disorder SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Pisa, Inst Psychiat, I-56100 Pisa, Italy. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 1999 VL 13 IS 3 BP 209 EP 209 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 236RA UT WOS:000082611300043 ER PT J AU Padmanabhan, V Lee, JS Beitins, IZ AF Padmanabhan, V Lee, JS Beitins, IZ TI Follicle-stimulating isohormones: regulation and biological significance SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Article; Proceedings Paper CT 5th International Symposium on Reproduction in Domestic Ruminants CY AUG 01-05, 1998 CL COLORADO SPRINGS, COLORADO SP InterAg, Intervet Int BV, Monsanto Co, Pharmacia & Upjohn Co, USDA, XY Inc, Select Sires ID GONADOTROPIN-RELEASING-HORMONE; HUMAN MENSTRUAL-CYCLE; HUMAN CHORIONIC-GONADOTROPIN; IN-VITRO BIOASSAY; LUTEINIZING-HORMONE; ISOFORM DISTRIBUTION; INVITRO BIOASSAY; SERUM GONADOTROPINS; CIRCULATING FSH; LUTEAL-PHASE AB Follicle-stimulating hormone (FSH) is a key hormone in the regulation of follicular development. Although the existence of FSH heterogeneity is well established, the physiological significance of this pleomorphism remains unknown. Observed changes in circulating FSH heterogeneity during critical reproductive events such as puberty and reproductive cyclicity suggest that different combinations of FSH isoforms reach the target sites during different physiological states to influence a variety of biological end points such as cellular growth, development, steroidogenesis and protein synthesis. Considering that these FSH isoforms have different physicochemical properties and potential to bind not only their cognate receptors but also structurally related, non-FSH receptors with various affinities, the regulatory implications of FSH heterogeneity in modulating the various FSH-induced functions are enormous. However, assigning functional significance to FSH heterogeneity has been hampered because of (1) difficulties associated with procurement of highly purified, naturally occurring, circulating FSH isoforms; (2) absence of reference standards that contain the entire repertoire of FSH isoforms present in biological fluids; and (3) specificity issues inherent to the detection systems used. if particular FSH isoforms do possess selective biological functions, specific combinations of FSH isoforms could be generated to regulate fertility in farm animals and humans. C1 Univ Michigan, Reprod Sci Program, Dept Pediat, Ann Arbor, MI 48109 USA. RP Padmanabhan, V (reprint author), Natl Inst Hlth, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RI Padmanabhan, Vasantha/C-8558-2017 OI Padmanabhan, Vasantha/0000-0002-8443-7212 NR 55 TC 2 Z9 2 U1 0 U2 0 PU JOURNALS OF REPRODUCTION FERTILITY LTD PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE CB5 8DT, ENGLAND SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PY 1999 SU 54 BP 87 EP 99 PG 13 WC Reproductive Biology SC Reproductive Biology GA 254HF UT WOS:000083605300008 ER PT J AU Zhou, HB Weinberg, CR AF Zhou, HB Weinberg, CR TI A semi-parametric mixture model in fertility studies SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE EM algorithm; fertility; latent variables; mixing distribution; moments; robustness ID EM ALGORITHM; CONCEPTION; FECUNDABILITY AB We describe a semiparametric mixture model for human fertility studies. The probability of conception is a product of two components. The mixing distribution, the component that introduces the heterogeneity among the menstrual cycles that come from different couples, is characterized nonparametrically by a finite number of moments. The second component, the intercourse-related probability is modeled parametrically to assess the possible exposure effects. We discuss an EM algorithm-based estimating procedure that incorporates the natural order in the moments. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JAN 1 PY 1999 VL 75 IS 2 BP 453 EP 462 DI 10.1016/S0378-3758(98)00160-8 PG 10 WC Statistics & Probability SC Mathematics GA 160ZG UT WOS:000078262800020 ER PT J AU Westcarr, S Farshori, P Wyche, J Anderson, WA AF Westcarr, S Farshori, P Wyche, J Anderson, WA TI Apoptosis and differentiation in the crypt-villus unit of the rat small intestine SO JOURNAL OF SUBMICROSCOPIC CYTOLOGY AND PATHOLOGY LA English DT Article DE apoptosis; differentiation; lactase; actin; occludin; fibronectin ID FACTOR TYPE-BETA; EPITHELIAL-CELLS; GENE-EXPRESSION; E-CADHERIN; GROWTH; DEATH; PHOSPHORYLATION; ENTEROCYTES; INVOLVEMENT; MIGRATION AB This investigation utilized immunocytochemical and fluorescent protocols to analyze the roles of cellular proliferation and apoptosis in the regulation of differentiation and senescence of the rat small intestinal mucosa. Specifically, the study localized apoptotic zones of the villus through the use of enzymatic tags; established the transition point between cell growth and differentiation, i.e. the point of no return where crypt cells differentiate into absorptive cells with barrier functions; and the role that plasmalemmal, cytoskeletal, junctional and extracellular matrix (ECM) elements may play in the regulation of differentiation and migration of epithelial cells from crypt to villus. Apoptosis was relegated to the villus tip forming a prominent 'apoptotic cuff' of cells. Close scrutiny of these cuffs reveals the presence of apoptotic cells adjacent to non-apoptotic (healthy) cells. Mid-villus epithelial cells were non-apoptotic and all cells in the crypt-villus unit expressed Bcl-2 activity. Intestinal lactase expression was prominent in post-mitotic cells along the villus, while cells in the crypt and base were negative For lactase activity In contrast, all the cells of the crypt-villus unit were intensely reactive for F-actin. Close scrutiny of isolated cells and frozen sections indicates specific localization of actin in me microvillus region, apical cytoplasm, basolateral and lateral plasmalemma which was in close proximity to fibronectin in the basement lamina. Occludin positive junctional networks were prominent at villus tips, where senescent and apoptotic cells were also most prominent, suggesting that tight junctional integrity was essential to barrier, digestive and absorptive functions in all regions of the mucosa. C1 Howard Univ, Dept Biol, Washington, DC 20059 USA. Natl Inst Deafness & Other Commun Disorders, Biol Cellulaire Lab, NIH, Bethesda, MD USA. Brown Univ, Dept Biol, Providence, RI 02912 USA. RP Anderson, WA (reprint author), Howard Univ, Dept Biol, 415 Coll St, Washington, DC 20059 USA. NR 45 TC 20 Z9 21 U1 0 U2 0 PU EDITRICE COMPOSITORI BOLOGNA PI BOLOGNA PA VIA STALINGRADO 97/2, I-40128 BOLOGNA, ITALY SN 1122-9497 J9 J SUBMICR CYTOL PATH JI J. Submicrosc. Cytol. Pathol. PD JAN PY 1999 VL 31 IS 1 BP 15 EP 30 PG 16 WC Pathology SC Pathology GA 245QF UT WOS:000083119100002 PM 10363352 ER PT J AU Sharp, WS Walter, JM Marsh, WL Ritchie, CF Hamburger, SD Castellanos, FX AF Sharp, WS Walter, JM Marsh, WL Ritchie, CF Hamburger, SD Castellanos, FX TI ADHD in girls: Clinical comparability of a research sample SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; sex differences; randomized clinical trials; methylphenidate; dextroamphetamine ID DEFICIT HYPERACTIVITY DISORDER; CROSSOVER TRIAL; RATING-SCALE; DOUBLE-BLIND; METHYLPHENIDATE; CHILDREN; BOYS; DEXAMPHETAMINE; NONRESPONDERS; GENDER AB Objective: The investigation of attention-deficit/hyperactivity disorder (ADHD) in girls raises complex questions of referral bias and selection criteria. The authors sought to determine whether they could recruit a research sample of comparably affected girls using a combination of sex-independent diagnostic criteria and sex-normed cutoffs on teacher ratings. They also report on the largest placebo-controlled crossover comparison of methylphenidate and dextroamphetamine in girls with ADHD. Method: Subjects were 42 girls with DSM-III-R/DSM-IV ADHD (combined type) contrasted to 56 previously studied boys with ADHD on comorbid diagnoses, behavioral ratings, psychological measures, psychiatric family history, and stimulant drug response. Results: Girls with ADHD were statistically indistinguishable from comparison boys on nearly all measures. Girls exhibited robust beneficial effects on both stimulants, with nearly all (95%) responding favorably to one or both drugs in this short-term trial. Dextroamphetamine produced significantly greater weight loss than methylphenidate. Conclusions: This highly selected group of ADHD girls was strikingly comparable with comparison boys on a wide range of measures. The results confirm that girls with ADHD do not differ from boys in response to methylphenidate and dextroamphetamine and that both stimulants should be tried when response to the first is not optimal. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Castellanos, FX (reprint author), Bldg 10,Room 3B-19,10 Ctr Dr, Bethesda, MD 20892 USA. NR 42 TC 71 Z9 71 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 1999 VL 38 IS 1 BP 40 EP 47 DI 10.1097/00004583-199901000-00018 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 154CN UT WOS:000077871100018 PM 9893415 ER PT J AU Ernst, M Zametkin, AJ Jons, PH Matochik, JA Pascualvaca, D Cohen, RM AF Ernst, M Zametkin, AJ Jons, PH Matochik, JA Pascualvaca, D Cohen, RM TI High presynaptic dopaminergic activity in children with Tourette's disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE tics; movement disorder; presynaptic dopaminergic activity; positron emission tomography; [fluorine-18]fluorodopa; caudate nucleus; midbrain ID OBSESSIVE-COMPULSIVE DISORDER; AMINO-ACID DECARBOXYLASE; LESCH-NYHAN DISEASE; BASAL GANGLIA; PARKINSONS-DISEASE; MONOZYGOTIC TWINS; TIC SEVERITY; IN-VIVO; L-DOPA; GILLES AB Objective: Tourette's disorder is characterized by chronic fluctuating motor and vocal ties. Despite extensive investigation of the neuropathophysiology of the disorder by a wide array of methodologies, its neurobiochemical substrate is still unclear. Converging evidence, however, suggests a primary role of the dopaminergic system, particularly within the basal ganglia. Method: This study examined the integrity of presynaptic dopaminergic function in children with Tourette's disorder, using positron emission tomography and the tracer [F-18]fluorodopa (FDOPA). Accumulation of FDOPA in synaptic terminals, a measure of DOPA decarboxylase activity, was quantified in caudate nucleus, putamen, frontal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum). Results: Subjects with Tourette's disorder showed higher FDOPA accumulation than controls in the left caudate nucleus (by 25%; p = .03) and right midbrain (by 53%; p = .08). Conclusion: These findings provide evidence of dopaminergic dysfunction in children with Tourette's disorder which affects both cell nuclei and nerve terminals. Based on the known regulation of DOPA decarboxylase activity by post- and presynaptic receptors, and by extracellular dopamine concentration, abnormal activity in this enzyme may reflect deficits in a variety of functional elements of the dopamine system. The precise mechanism underlying an up-regulation of DOPA decarboxylase activity needs to be identified in future studies. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIMH, Psychol & Psychopathol Lab, Bethesda, MD 20892 USA. NIDA, Neuroimaging Branch, Baltimore, MD 21224 USA. RP Ernst, M (reprint author), NIH, Bldg 36,Room 1A05,36 Convent Dr,MSC 4030, Bethesda, MD 20892 USA. NR 73 TC 60 Z9 61 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 1999 VL 38 IS 1 BP 86 EP 94 DI 10.1097/00004583-199901000-00024 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 154CN UT WOS:000077871100024 PM 9893421 ER PT J AU Slavkin, HC AF Slavkin, HC TI Does the mouth put the heart at risk? SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID ASSOCIATION C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 16 TC 22 Z9 23 U1 0 U2 2 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JAN PY 1999 VL 130 IS 1 BP 109 EP 113 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 154QM UT WOS:000077900000032 PM 9919040 ER PT J AU Dentino, AN Pieper, CF Rao, KMK Currie, MS Harris, T Blazer, DG Cohen, HJ AF Dentino, AN Pieper, CF Rao, KMK Currie, MS Harris, T Blazer, DG Cohen, HJ TI Association of interleukin-6 and other biologic variables with depression in older people living in the community SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CORTICOTROPIN-RELEASING HORMONE; FREELY-MOVING RATS; FACTOR-ALPHA; MAJOR DEPRESSION; SOLUBLE INTERLEUKIN-2; IMMUNE FUNCTION; PLASMA IL-6; WEIGHT-LOSS; SYMPTOMS AB OBJECTIVES: The prevalence of depression increases with age, as does the prevalence of higher levels of the cytokine interleukin-6 (IL-6). This analysis was performed to determine the association between increased levels of this cytokine and depression in a population-based sample. DESIGN: Cross-sectional cohort study. SETTING: Rural and urban counties in North Carolina. PARTICIPANTS: Community-dwelling older people. MEASUREMENTS: The association between IL-6 and other biologic variables with self-report depression was examined in 1686 persons aged 70 years and older in the third in-person survey wave (1991) of the Duke Established population for Epidemiologic Studies of the Elderly (EPESE). Bivariate associations were established by the Spearman correlation, adjusted for age. A stepwise linear logistic regression model was used to derive a final model to assess multivariable effects on CES-D scores. RESULTS: Depression was correlated with IL-6 (P = .011), D-Dimer (P = .017), alpha-1-globulin (P = .023), alpha-2-globulin (P = .002), and beta globulin (P = .012). After controlling for age, race, and gender, IL-6 levels remained the only biologic variable significantly associated with depression (P = .035). CONCLUSION: These data suggest that the inflammatory marker, IL-6, is associated with depression in older people in this cross-sectional study. These results are compatible with the hypothesis of cytokine (IL-6) stimulation in geriatric depression as part of an overall immunoendocrine dysregulation. C1 Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Claude D Pepper Older Amer Independence Ctr, Durham, NC 27710 USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. NIA, Epidemiol Demog & Bimetry Program, Bethesda, MD 20892 USA. RP Cohen, HJ (reprint author), Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Claude D Pepper Older Amer Independence Ctr, Box 3003, Durham, NC 27710 USA. FU NIA NIH HHS [5 P60 AG11268, N01 AG-1-2102] NR 43 TC 192 Z9 206 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 1999 VL 47 IS 1 BP 6 EP 11 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 156RY UT WOS:000078016900002 PM 9920223 ER PT J AU McCray, AT Loane, RF Browne, AC Bangalore, AK AF McCray, AT Loane, RF Browne, AC Bangalore, AK TI Terminology issues in user access to Web-based medical information SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 06-10, 1999 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB We conducted a study of user queries to the National Library of Medicine Web site over a three month period. Our purpose was to study the nature and scope of these queries in order to understand how to improve users' access to the information they are seeking on our site. The results show that the queries are primarily medical in content (94%), with only a small percentage (5.5%) relating to library services, and with a very small percentage (.5%) not being medically relevant at all. We characterize the data set, and conclude with a discussion of our plans to develop a UMLS-based terminology server to assist NLM Web users. C1 Natl Lib Med, Bethesda, MD USA. RP McCray, AT (reprint author), Natl Lib Med, Bethesda, MD USA. NR 12 TC 7 Z9 7 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 107 EP 111 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300024 ER PT J AU Rindflesch, TC Hunter, L Aronson, AR AF Rindflesch, TC Hunter, L Aronson, AR TI Mining molecular binding terminology from biomedical text SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 06-10, 1999 CL WASHINGTON, D.C. SP Amer Med Informat Assoc ID LANGUAGE AB Automatic access to information regarding macromolecular binding relationships would provide a valuable resource to the biomedical community We report on a pilot project to mine such information from the molecular biology literature. The program being developed takes advantage of natural language processing techniques and is supported by two repositories of biomolecular knowledge. A formative evaluation has been conducted on a subset of MEDLINE (R) abstracts. C1 NCI, NIH, Bethesda, MD 20892 USA. Natl Lib Med, Bethesda, MD 20894 USA. RP Rindflesch, TC (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. OI Hunter, Lawrence/0000-0003-1455-3370 NR 12 TC 6 Z9 6 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 127 EP 131 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300028 ER PT J AU Wilbur, WJ Hazard, GF Divita, G Mork, JG Aronson, AR Browne, AC AF Wilbur, WJ Hazard, GF Divita, G Mork, JG Aronson, AR Browne, AC TI Analysis of biomedical text for chemical names: A comparison of three methods SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 06-10, 1999 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB At the National Library of Medicine (NLM), a variety of biomedical vocabularies are found in data pertinent to its mission. In addition to standard medical terminology, there are specialized vocabularies including that of chemical nomenclature. Normal language tools including the lexically based ones used by the Unified Medical Language System (R) (UMLS (R)) to manipulate and normalize text do not work well on chemical nomenclature. In order to improve NLM's capabilities in chemical text processing, two approaches to the problem of recognizing chemical nomenclature were explored The first approach was a lexical one and consisted of analyzing text for the presence of a fixed set of chemical segments. The approach was extended with general chemical patterns and also with terms from NLM's indexing vocabulary, MeSH (R) and the NLM SPECIALIST (TM) lexicon. The second approach applied Bayesian classification to n-grams of text via two different methods. The single lexical method and two statistical methods, were tested against data from the 1999 UMLS Metathesaurus (R). One of the statistical methods had an overall classification accuracy of 97%. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Natl Lib Med, Div Specialized Informat Serv, Bethesda, MD 20894 USA. Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Wilbur, WJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 176 EP 180 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300038 ER PT J AU Rubin, DL Gennari, JH Srinivas, S Yuen, A Kaizer, H Musen, MA Silva, JS AF Rubin, DL Gennari, JH Srinivas, S Yuen, A Kaizer, H Musen, MA Silva, JS TI Tool support for authoring eligibility criteria for cancer trials SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 06-10, 1999 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB A critical component of authoring new clinical trial protocols is assembling a set of eligibility criteria for patient enrollment. We found that clinical protocols in three different cancer domains can be categorized according to a set of clinical states that describe various clinical scenarios for that domain. Classifying protocols in this manner revealed similarities among the eligibility criteria and permitted some standardization of criteria based on clinical state. We have developed an eligibility criteria authoring tool which uses a standard set of eligibility criteria and a diagram of the clinical states to present the relevant eligibility criteria to the protocol author. We demonstrate our ideas with phase-3 protocols from breast cancer, prostate cancer, and non-small cell lung cancer. Based on measurements of redundancy and percentage coverage of criteria included in our tool, we conclude that our model reduces redundancy in the number of criteria needed to author multiple protocols, and it allows some eligibility criteria to be authored automatically based on the clinical state of interest for a protocol. C1 VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. Stanford Univ, Sch Med, Stanford Med Informat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Div Oncol, Stanford, CA 94305 USA. NCI, Bethesda, MD 20892 USA. RP Rubin, DL (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA. OI Gennari, John/0000-0001-8254-4957 NR 4 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 369 EP 373 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300077 ER PT J AU Silva, J Wittes, R AF Silva, J Wittes, R TI Role of clinical trials informatics in the NCI's cancer informatics infrastructure SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 06-10, 1999 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB A Web-enabled Cancer Informatics Infrastructure (CII) will enable faster, better clinical trials, ultimately improving cancer care. To create the CIT the National Cancer Institute is forming public-private partnerships and building on existing activities, Key innovations include development of standards for cancer patient information and clinical research, management of patients using disease specific "clinical states" and use of drag and drop electronic protocol authoring. C1 NCI, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 950 EP 954 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300195 ER PT J AU Bean, CA Selden, CR Rindflesch, TC Aronson, AR AF Bean, CA Selden, CR Rindflesch, TC Aronson, AR TI From bibliography to test collection: Enhancing topical relevance assessment for bibliographic information retrieval system evaluation SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract ID MEDLINE C1 Natl Lib Med, Bethesda, MD 20894 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1022 EP 1022 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300220 ER PT J AU Chang, HF Nelson, SJ AF Chang, HF Nelson, SJ TI Presenting MeSH data over the web SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1037 EP 1037 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300235 ER PT J AU Kernberg, M Bidgood, WD AF Kernberg, M Bidgood, WD TI The integrated medical record: DICOM structured reporting SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 US Natl Lib Med, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1097 EP 1097 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300295 ER PT J AU Nelson, SJ Aronson, AR Doszkocs, TE Wilbur, WJ Bodenreider, O Chang, HF Mork, J McCray, AT AF Nelson, SJ Aronson, AR Doszkocs, TE Wilbur, WJ Bodenreider, O Chang, HF Mork, J McCray, AT TI Automated assignment of Medical Subject Headings SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1127 EP 1127 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300325 ER PT J AU Sorden, NN Chang, HF Nelson, SJ AF Sorden, NN Chang, HF Nelson, SJ TI Automated indexing of gene symbols SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1165 EP 1165 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300363 ER PT J AU Elliot, SJ Striker, LJ Stetler-Stevenson, WG Jacot, TA Striker, GE AF Elliot, SJ Striker, LJ Stetler-Stevenson, WG Jacot, TA Striker, GE TI Pentosan polysulfate decreases proliferation and net extracellular matrix production in mouse mesangial cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; GROWTH-FACTOR; PROGRESSIVE GLOMERULOSCLEROSIS; COLLAGEN-SYNTHESIS; GENE-EXPRESSION; GELATINASE-A; IV COLLAGEN; HEPARIN; RAT; METALLOPROTEINASES AB Glomerulosclerosis is characterized by extracellular matrix accumulation and is often associated with mesangial cell proliferation. Heparin-like molecules have been shown to decrease glomerulosclerosis in vivo, although their cellular site and mechanism of action is still unclear. In this study, a line of glomerular mesangial cells derived from normal mice was used to determine whether pentosan polysulfate (PPS) inhibited proliferation and altered extracellular matrix turnover. Cells treated with PPS showed a decrease in cell number beginning 24 h after treatment, which was maintained for 5 d, For matrix accumulation and degradation studies, cells were treated for 5 d and collagen types I and IV protein were measured by enzyme-linked immunosorbent assay as well as matrix metalloproteinases (MMP) measured by zymography. Collagen types I and type IV were significantly decreased in the media (P < 0.0001) and cell layer (P < 0.005) after treatment with PPS but not after treatment with heparin. By zymography, MMP-2 was significantly increased after treatment with PPS (P < 0.001) and heparin (P < 0.05). PPS and heparin also decreased MMP-9 (P < 0.001) after treatment. Reverse zymography showed the presence of tissue inhibitors of metal-loproteinases (TIMP)-1and -2 in control mesangial cells. Treatment with PPS and heparin increased TIMP-1, Zn addition, TIMP-3 was found in the medium of treated but not control cells. In conclusion, PPS alters extracellular matrix turnover through the induction of MMP-2 and alterations in the TIMP profile and may be useful in decreasing progressive glomerulosclerosis. C1 Univ Miami, Sch Med, Dept Med, Renal Cell Biol Lab, Miami, FL 33101 USA. NIDDKD, Metab Dis Branch, Renal Cell Biol Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Extracellular Matrix Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Striker, GE (reprint author), Univ Miami, Sch Med, Dept Med, Renal Cell Biol Lab, POB 016960 R126, Miami, FL 33101 USA. EM lstriker@newssun.med.miami.edu RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 37 TC 24 Z9 29 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 1999 VL 10 IS 1 BP 62 EP 68 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 154FN UT WOS:000077878300008 PM 9890310 ER PT J AU Cheung, AK Agodoa, LY Daugirdas, JT Depner, TA Gotch, FA Greene, T Levin, NW Leypoldt, JK Beck, GJ AF Cheung, AK Agodoa, LY Daugirdas, JT Depner, TA Gotch, FA Greene, T Levin, NW Leypoldt, JK Beck, GJ CA Hemodialysis Study Grp TI Effects of hemodialyzer reuse on clearances of urea and beta(2)-microglobulin SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DIALYZER REUSE; POLYSULFONE DIALYZERS; REMOVAL; DIALYSIS; ACID; EFFICIENCY; MEMBRANES; SURVIVAL; VOLUME; LOSSES AB Although dialyzer reuse in chronic hemodialysis patients is commonly practiced in the United States, performance of reused dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and beta(2)-microglobulin (beta(2)M) clearance by low-flux and high-flux dialyzers reprocessed with various germicides. The dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen peroxide combination (Renalin(R)), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of beta(2)M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodialysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the prescription of hemodialysis in centers practicing reuse. C1 Cleveland Clin Fdn, Dept Biostat & Epidemiol, HEMO Study, Data Coordinating Ctr, Cleveland, OH 44195 USA. Univ Utah, Salt Lake City, UT USA. NIH, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Univ Calif Davis, Sacramento, CA 95817 USA. Davies Med Ctr, San Francisco, CA USA. Beth Israel Med Ctr, New York, NY 10003 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Beck, GJ (reprint author), Cleveland Clin Fdn, Dept Biostat & Epidemiol, HEMO Study, Data Coordinating Ctr, WB4,9500 Euclid Ave, Cleveland, OH 44195 USA. EM gbeck@bio.ri.ccf.org NR 38 TC 83 Z9 91 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 1999 VL 10 IS 1 BP 117 EP 127 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 154FN UT WOS:000077878300015 PM 9890317 ER PT J AU Traynor, TR Schnermann, J AF Traynor, TR Schnermann, J TI Renin-angiotensin system dependence of renal hemodynamics in mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT Workshop on Function and Clinical Perspectives of Angiotensin II Subtype I (AT1) Receptors CY MAY 06-09, 1998 CL BUDAPEST, HUNGARY SP Astra Pharmaceuticals ID TUBULOGLOMERULAR FEEDBACK; BLOOD-PRESSURE; DEFICIENT MICE; RATS; INHIBITION; SECRETION AB Renin secretion from isolated, perfused, thick ascending limb/glomerulus preparations from mice, under baseline conditions, has been found to be approximately 10-fold higher than that observed with the same preparations from rabbits. Higher renin secretion rates appear to be accompanied by higher plasma renin activities in mice, compared with rats, rabbits, or humans. Experiments were performed to determine the extent of the renin-angiotensin system dependence of renal hemodynamics in mice. Administration of the type 1 angiotensin II (AT(1)) receptor blocker candesartan (10 mg/kg) to untreated control mice increased renal blood flow by 55% (from 1.8 +/- 0.2 to 2.8 +/- 0.2 ml/min) and decreased renal vascular resistance by 42% (from 55 +/- 7.5 to 31.8 +/- 2.3 mmHg . min/ml). Similarly, acute extracellular volume expansion increased renal blood flow by 84% and reduced renal vascular resistance by 48%, In mice with null mutations in either the AT(1) receptor or the angiotensin-converting enzyme gene, renal vascular resistance was significantly lower than in wild-type mice. Tubuloglomerular feedback, which is an angiotensin II-dependent vasoconstrictor response, was found to be abolished in both strains of knockout mice. Acute AT(1) receptor blockade by candesartan reduced tubuloglomerular feedback responses to a flow rate step change of 0 to 30 nl/min by approximately 80% (from 6.1 +/- 1.4 to 1.3 +/- 0.4 mmHg). Candesartan increased the steady-state autoregulatory index from 0.19 to 0.55 (in a pressure interval of 90 to 109 mmHg), suggesting reduced efficiency of steady-state autoregulation. These results indicate that the renin-angiotensin system exerts tonic control over renal vascular resistance in mice to a greater extent than previously observed in other mammalian species. C1 Univ Michigan, Dept Physiol, Ann Arbor, MI 48109 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10,Room 4D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM JurgenS@intra.niddk.nih.gov FU NIDDK NIH HHS [DK40042, DK09489, DK37448] NR 16 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 1999 VL 10 SU 11 BP S184 EP S188 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 155AB UT WOS:000077922400030 PM 9892161 ER PT J AU Weiss, SJ Panlilio, LV AF Weiss, SJ Panlilio, LV TI Blocking a selective association in pigeons SO JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR LA English DT Article; Proceedings Paper CT 1998 Winter Conference on Animal Learning and Behavior CY 1998 CL WINTER PARK, COLORADO DE selective associations; blocking; stimulus-reinforcer interaction; biological constraints on learning; species comparisons; treadle press; pigeons ID STIMULUS-REINFORCER INTERACTION; ATTENTION; CONTEXT AB Experiment 1 demonstrated for the first time a stimulus-reinforcer interaction in pigeons trained with free-operant multiple schedules of reinforcement. Pigeons that treadle pressed in the presence of a tone-light (TL) compound for food exhibited primarily Visual stimulus control on a stimulus-element test, whereas pigeons that avoided shock in TL exhibited auditory control. In Experiment 2, this selective association was blocked in pigeons pretrained with the biologically contingency-disadvantaged element of the compound (i.e., tone-food or light-shock) before TL training. When this pretraining preceded compound-stimulus training, control was now auditory in pigeons that treadle pressed for food and was visual in pigeons that avoided shock. Previous attempts at blocking this selective association were unsuccessful in pigeons (LoLordo, Jacobs, & Foree, 1982) but were successful in rats (Schindler & Weiss, 1985). Experiment 2 established that selective associations can be blocked in pigeons when the procedures that were effective with rats were systematically replicated. These results further demonstrate the cross-species generality of an associative attentional mechanism involving a biological constraint on learning in species with different dominant sensory systems. C1 American Univ, Dept Psychol, Washington, DC 20016 USA. Natl Inst Drug Abuse, Rockville, MD 20857 USA. RP Weiss, SJ (reprint author), American Univ, Dept Psychol, Washington, DC 20016 USA. EM sweiss@american.edu FU NIDA NIH HHS [DA-08651]; NIMH NIH HHS [MH-45545] NR 21 TC 7 Z9 7 U1 0 U2 0 PU SOC EXP ANALYSIS BEHAVIOR INC PI BLOOMINGTON PA INDIANA UNIV DEPT PSYCHOLOGY, BLOOMINGTON, IN 47405 USA SN 0022-5002 J9 J EXP ANAL BEHAV JI J. Exp. Anal. Behav. PD JAN PY 1999 VL 71 IS 1 BP 13 EP 24 DI 10.1901/jeab.1999.71-13 PG 12 WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental SC Psychology; Behavioral Sciences GA 164HM UT WOS:000078457600002 PM 10028692 ER PT J AU Caplan, LJ Schooler, C AF Caplan, LJ Schooler, C TI On the use of analogy in text-based memory and comprehension: The interaction between complexity of within-domain encoding and between-domain processing SO JOURNAL OF THE LEARNING SCIENCES LA English DT Article ID ADVANCE ORGANIZERS; SIMILARITY; MODELS; REPRESENTATIONS; INDUCTION; ACCESS AB In this article, we examine the role of analogy transfer in text comprehension. We tested the hypothesis that people would benefit more from manipulations encouraging the induction of common structure from source domains when they had previously engaged in complex encoding of those domains. Participants read sets of passages about analogous domains (i.e., topics). Each set included 1 or 2 source passages followed by a target passage. The independent variables were: (a) degree of complexity of source passage encoding; (b) amount of information about the nature of the analogy provided with the target passage (no information, a title stating that the domains were analogous, or a title stating that the domains were analogous plus a description of their common structure); and (c) number of source passages in a set (1 or 2). Participants then were tested on memory and inference for the target passage. For the memory measure, performance was better following complex encoding than following simple encoding only when the short title had been provided. For the inference measure, performance was better following complex encoding than following simple encoding only when 2 source passages had been provided. These findings support the hypothesis that complex source encoding provides the best support for the use of explicit analogy. More generally, they suggest that the effects of within-domain encoding complexity on analogical transfer depend on whether between-domain processing has been abstraction- or episode-based. C1 NIMH, Sect Socioenvironm Studies, NIH, Bethesda, MD 20892 USA. RP Caplan, LJ (reprint author), NIMH, Sect Socioenvironm Studies, NIH, Federal Bldg,Room B1A-14, Bethesda, MD 20892 USA. NR 43 TC 4 Z9 4 U1 1 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1050-8406 J9 J LEARN SCI JI J. Learn. Sci. PY 1999 VL 8 IS 1 BP 41 EP 70 DI 10.1207/s15327809jls0801_2 PG 30 WC Education & Educational Research; Psychology, Educational SC Education & Educational Research; Psychology GA 156UN UT WOS:000078020600002 ER PT J AU Haverkos, HW Turner, JF Moolchan, ET Cadet, JL AF Haverkos, HW Turner, JF Moolchan, ET Cadet, JL TI Relative rates of AIDS among racial/ethnic groups by exposure categories SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE AIDS; race/ethnicity; sexual behavior; sexually transmitted diseases ID UNITED-STATES; ADULTS; HETEROSEXUALS; PREVENTION; HISPANICS; BEHAVIORS; BLACK AB The relative rates of acquired immunodeficiency syndrome (AIDS) were calculated among racial/ethnic populations using Centers for Disease Control and Prevention HN (human immunodeficiency virus)/Surveillance reports assuming that racial/ethnic distributions reflect that of the US Census Data from 1990. For comparison, a rate of 1 was assigned to whites in each calculation. The overall relative rates were whites-1, African Americans-4.7, Hispanics-3, Asian/Pacific Islanders-0.4, and Native Americans-0.5. Acquired immunodeficiency syndrome surveillance data show higher rates of AIDS for African Americans and Hispanics compared with whites, Asians/Pacific Islanders, and Native Americans. The relative rates for African Americans and Hispanics compared with whites were highest for injecting drug users, heterosexual contact, and pediatric patients. These results led us to explore possible explanations for increased AIDS reporting in African Americans and Hispanics. We then explored available national datasets regarding those variables. The analyses indicate that variables such as access and receptivity to HIV prevention and treatment efforts, race/ethnicity, sexual behaviors, sexually transmitted diseases, socioeconomic status, and substance abuse interact in a complex fashion to influence HIV transmission and progression to AIDS in affected communities. C1 Natl Inst Drug Abuse, Natl Inst Hlth, Baltimore, MD USA. RP Haverkos, HW (reprint author), US FDA, HFD 530,5600 Fishers Ln, Rockville, MD 20837 USA. NR 34 TC 22 Z9 22 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JAN PY 1999 VL 91 IS 1 BP 17 EP 24 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 166UN UT WOS:000078595900004 PM 10063784 ER PT J AU Weller, EA Feuer, EJ Frey, CM Wesley, MN AF Weller, EA Feuer, EJ Frey, CM Wesley, MN TI Parametric relative survival regression using generalized linear models with application to Hodgkin's lymphoma SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE parametric model; relative survival; Weibull generalized linear model ID CHEMOTHERAPY; DISEASE; RATES AB Changes in survival rates during 1940-1992 for patients with Hodgkin's disease are studied by using population-based data. The aim of the analysis is to identify when the breakthrough in clinical trials of chemotherapy treatments started to increase population survival rates, and to find how long it took for the increase to level off, indicating that the full population effect of the breakthrough had been realized. A Weibull relative survival model is used because the model parameters are easily interpretable when assessing the effect of advances in clinical trials. However, the methods apply to any relative survival model that falls within the generalized linear models framework. The model is fitted by using modifications of existing software (SAS, GLIM) and profile likelihood methods. The results are similar to those from a cause-specific analysis of the data by Feuer and co-workers. Survival started to improve around the time that a major chemotherapy breakthrough (nitrogen mustard, Oncovin, prednisone and procarbazine) was publicized in the mid-1960s but did not level off for 11 years. For the analysis of data where the cause of death is obtained from death certificates, the relative survival approach has the advantage of providing the necessary adjustment for expected mortality from causes other than the disease without requiring information on the causes of death. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Geisinger Med Ctr, Danville, PA 17822 USA. Informat Management Syst, Silver Spring, MD USA. RP Weller, EA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM eweller@jimmy.harvard.edu NR 25 TC 7 Z9 7 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0035-9254 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 1999 VL 48 BP 79 EP 89 DI 10.1111/1467-9876.00141 PN 1 PG 11 WC Statistics & Probability SC Mathematics GA 165XD UT WOS:000078546400007 ER PT J AU Margolis, L Hatfill, S Chuaqui, R Vocke, C Emmert-Buck, M Linehan, WM Duray, PH AF Margolis, L Hatfill, S Chuaqui, R Vocke, C Emmert-Buck, M Linehan, WM Duray, PH TI Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor SO JOURNAL OF UROLOGY LA English DT Article DE prostate; cell culture; Rotating Wall Vessel Bioreactor ID EXPLANT CULTURE; GROWTH-FACTORS; CELL-LINE; DIFFERENTIATION; RAT; HYPERPLASIA; RECEPTOR AB Purpose: To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. Materials and Methods: Samples of normal. prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 X 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell. RNA assays. Results: We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta(2) receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. Conclusions: The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue. C1 NICHHD, NASA Ctr Three Dimens Tissue Culture, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NCI, Dept Surg Oncol, NIH, Bethesda, MD 20892 USA. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. RP Margolis, L (reprint author), NICHHD, NASA Ctr Three Dimens Tissue Culture, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 10D14, Bethesda, MD 20892 USA. NR 24 TC 50 Z9 54 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 1999 VL 161 IS 1 BP 290 EP 297 DI 10.1016/S0022-5347(01)62134-7 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 145NL UT WOS:000077377800091 PM 10037426 ER PT J AU Ott, DE Chertova, EN Busch, LK Coren, LV Gagliardi, TD Johnson, DG AF Ott, DE Chertova, EN Busch, LK Coren, LV Gagliardi, TD Johnson, DG TI Mutational analysis of the hydrophobic tail of the human immunodeficiency virus type 1 p6(Gag) protein produces a mutant that fails to package its envelope protein SO JOURNAL OF VIROLOGY LA English DT Article ID MATRIX PROTEIN; GAG PROTEINS; PARTICLE-PRODUCTION; GENE-TRANSFER; HIV-1; CELLS; GLYCOPROTEIN; SPECIFICITY; INFECTION; MEMBRANE AB The p6(Gag) protein of human immunodeficiency virus type I (HIV-1) is produced as the carboxyl-terminal sequence within the Gag polyprotein. The amino acid composition of this protein is high in hydrophilic and polar residues except for a patch of relatively hydrophobic amino acids found in the carboxyl-terminal 16 amino acids. Internal cleavage of p6(Gag) between Y-36 and P-37, apparently by the HIV-1 protease, removes this hydrophobic tail region from approximately 30% of the mature p6(Gag) proteins in HIV-1(MN). To investigate the importance of this cleavage and the hydrophobic nature of this portion of p6(Gap), site-directed mutations were made at the minor protease cleavage site and within the hydrophobic tail. The results showed that all of the single-amino-acid replacement mutants exhibited either reduced or undetectable cleavage at the site Set almost all were nearly as infectious as wild-type virus, demonstrating that processing at this site is not important for viral replication. However, one exception, Y36F, was 300-fold as infectious the wild type. In contrast to the single-substitution mutants, a virus with two substitutions in this region of p6(Gap), Y36S-L41P, could not infect susceptible cells. Protein analysis showed that while the processing of the Gag precursor was normal, the double mutant did not incorporate Env into virus particles. This mutant could be complemented with surface glycoproteins from vesicular stomatitis virus and murine leukemia virus, showing that the inability to incorporate Env was the lethal defect for the Y36S-L41P virus, However, this mutant was not rescued by an HIV-1 Env with a truncated gp41(TM) cytoplasmic domain, showing that it is phenotypically different from the previously described MA mutants that do not incorporate their full-length Env proteins. Cotransfection experiments with Y36S-L41P and wild-type proviral DNAs revealed that the mutant Gag dominantly blocked the incorporation of Env by wild-type Gag. These results show that the Y36S-L41P p6(Gag) mutation dramatically blacks the incorporation of HIV-1 Env, presumably acting late in assembly and early during budding. C1 NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC, Frederick, MD 21702 USA. RP Ott, DE (reprint author), NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC, Bldg 535,Room 433,Box B, Frederick, MD 21702 USA. EM ott@avpvx1.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 63 TC 38 Z9 38 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 19 EP 28 PG 10 WC Virology SC Virology GA 146YP UT WOS:000077461700003 PM 9847302 ER PT J AU Zheng, ZM He, PJ Baker, CC AF Zheng, ZM He, PJ Baker, CC TI Function of a bovine papillomavirus type 1 exonic splicing suppressor requires a suboptimal upstream 3 ' splice site SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SR-PROTEINS; ALTERNATIVE EXON; DOWNSTREAM EXON; MESSENGER-RNAS; TAT EXON-2; ENHANCER; SEQUENCES; BINDING; 3'-SPLICE-SITE AB Alternative splicing is an important mechanism for the regulation of bovine papillomavirus type 1 (BPV-I) gene expression during the virus life cycle. Previous studies in our laboratory have identified two purine-rich exonic splicing enhancers (ESEs), SEI and SE2, located between two alternative 3' splice sites at nucleotide (nt) 3225 and nt 3605, Further analysis of BPV-1 late-pre-mRNA splicing in vitro revealed a 48-nt pyrimidine-rich region immediately downstream of SEI that inhibits utilization of the nt 3225 3' splice site. This inhibitory element, which we named an exonic splicing suppressor (ESS), has a U-rich 5' end, a C-rich central part, and an AG-rich 3' end (Z. M. Zheng, P. He. and C. C. Baker, J. Virol. 70:4691-4699, 1996). The present study utilized in vitro splicing of both homologous and heterologous pre-mRNAs to further characterize the ESS, The BPV-1 ESS was inserted downstream of the 3' splice site in the BPV-1 late pre-mRNA, Rous sarcoma virus src pre-mRNA, human immunodeficiency virus tat-rev pre-mRNA, and Drosophila dsx pre-mRNA, all containing a suboptimal 3' splice site, and in the human P-globin pre-mRNA which contains a constitutive 3' splice site. These studies demonstrated that suppression of splicing by the BPV-I ESS requires an upstream suboptimal 3' splice site but not an upstream ESE, Furthermore, the ESS functions when located either upstream or downstream of BPV-1 SE1, Mutational analyses demonstrated that the function of the ESS is sequence dependent and that only the C-rich region of the ESS is essential for suppression of splicing in all the pre-mRNAs tested. C1 NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, Basic Res Lab, Div Basic Sci, NIH, Bldg 41,Room D305,41 Lib Dr MSC 5055, Bethesda, MD 20892 USA. NR 31 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 29 EP 36 PG 8 WC Virology SC Virology GA 146YP UT WOS:000077461700004 PM 9847303 ER PT J AU Zolotukhin, AS Felber, BK AF Zolotukhin, AS Felber, BK TI Nucleoporins Nup98 and Nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev SO JOURNAL OF VIROLOGY LA English DT Article ID MAP KINASE KINASE; PORE COMPLEX PROTEIN; SIMIAN RETROVIRUS TYPE-1; MESSENGER-RNA EXPORT; NUCLEOCYTOPLASMIC TRANSPORT; CHROMOSOME-TRANSLOCATION; MYELOID LEUKEMOGENESIS; HIV REV; CELLS; ELEMENT AB Human immunodeficiency virus type 1 (HIV-1) Rev contains a leucine-rich nuclear export signal that is essential for its nucleocytoplasmic export mediated by hCRM1. We examined the role of selected nucleoporins, which are located in peripheral structures of the nuclear pore complex and are thought to he involved in export, in Rev function in human cells. First, we found that upon actinomycin D treatment, Nup98, but not Nup214 or Nup153, is able to translocate to the cytoplasm of HeLa cells, demonstrating that Nup98 may act as a soluble factor. We further showed that Rev can recruit Nup98 and Nup214, but not Nup153, to the nucleolus. We also found that the isolated FG-containing repeat domains of Nup98 and Nup214, but not those of Nup153, competitively inhibit the Rev/RRE-mediated expression of HIV. Taken together, the recruitment of Nup98 and Nup214 by Rev and the competitive inhibition exhibited by their NP domains demonstrate direct participation of Nup98 and Nup214 in the Rev-hCRM1-mediated export. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Human Retrovirus Pathogenesis Grp, Frederick, MD 21702 USA. RP Felber, BK (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Human Retrovirus Pathogenesis Grp, Bldg 535,Rm 110, Frederick, MD 21702 USA. NR 53 TC 105 Z9 106 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 120 EP 127 PG 8 WC Virology SC Virology GA 146YP UT WOS:000077461700015 PM 9847314 ER PT J AU Luzuriaga, K Wu, HL McManus, M Britto, P Borkowsky, W Burchett, S Smith, B Mofenson, L Sullivan, JL AF Luzuriaga, K Wu, HL McManus, M Britto, P Borkowsky, W Burchett, S Smith, B Mofenson, L Sullivan, JL CA PACTG 356 Investigators TI Dynamics of human immunodeficiency virus type 1 replication in vertically infected infants SO JOURNAL OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; T-LYMPHOCYTE RESPONSES; IN-VIVO; HIV-1 INFECTION; VIRAL LOAD; CHILDREN; THERAPY; GENERATION; VIREMIA; PLASMA AB Plasma human immunodeficiency virus type 1 (HIV-1) turnover and kinetics were studied in children aged 15 days to 2 years following the initiation of a triple antiretroviral drug regimen consisting of zidovudine, lamivudine, and nevirapine. HIV-1 turnover was at least as rapid as that previously described in adults; turnover rates were more rapid in infants and children aged 3 months to 2 years than in infants less than 3 months of age. These data confirm the central role of HIV-1 replication in the pathogenesis of vertical HIV-1 infection and reinforce the importance of early, potent combination therapies for the long-term control of HIV-1 replication. C1 Univ Massachusetts, Sch Med, Dept Pediat, Program Mol Med, Worcester, MA 01605 USA. Harvard Univ, Sch Publ Hlth, Stata & Data Anal Ctr, Boston, MA 02115 USA. Boston Childrens Hosp, Boston, MA USA. NYU, Dept Pediat, New York, NY USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. RP Luzuriaga, K (reprint author), Univ Massachusetts, Sch Med, Dept Pediat, Program Mol Med, Room 318,Biotech 2,373 Plantat St, Worcester, MA 01605 USA. EM katherine.luzuriaga@ummed.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI-43220, AI-32907, U01 AI032907] NR 31 TC 60 Z9 62 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 362 EP 367 PG 6 WC Virology SC Virology GA 146YP UT WOS:000077461700041 PM 9847340 ER PT J AU Fearns, R Collins, PL AF Fearns, R Collins, PL TI Model for polymerase access to the overlapped L gene of respiratory syncytial virus SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; G(NS)-L INTERGENIC REGION; STRAND RNA VIRUS; GENOME ORGANIZATION; MESSENGER-RNA; SEQUENTIAL TRANSCRIPTION; MARBURG VIRUS; RHABDOVIRUS; SEQUENCES; ORDER AB The last two genes of respiratory syncytial virus (RSV), M2 and L, overlap by 68 nucleotides, an arrangement which has counterparts in a number of nonsegmented negative-strand RNA viruses. Thus, the gene-end (GE) signal of M2 lies downstream of the L gene start (CS) signal, separated by 45 nucleotides. Since RSV transcription ostensibly is sequential and unidirectional from a single promoter within the 3' leader region, it was unclear how the polymerase accesses the L GS signal. Furthermore, it was previously shown that 90% of transcripts which are initiated at the L GS signal are polyadenylated and terminated at the M2 GE signal, yielding a short, truncated L mRNA as the major transcription product of the L gene. Despite these apparent down-regulatory features, we show that the accumulation of full-length L mRNA during RSV infection is only sixfold less than that of its upstream neighbor, M2, We used cDNA-encoded genome analogs in an intracellular transcription assay to investigate the mechanism of transcription of the overlapped genes. Expression of L was found to be dependent on sequential transcription from the 3' end of the genome. Apart from the L GS signal, the only other strict requirement for initiation at L was the M2 GE signal. This implies that the polymerase accesses the L GS signal only following arrival at the M2 GE signal. Thus, polymerase which terminates at the M2 GE signal presumably scans upstream to initiate at the L GS signal. This also would provide a mechanism whereby polymerase which terminates prematurely during transcription of L could recycle from the M2 GE signal to the L GS signal, thereby accounting for the unexpectedly high level of synthesis of full length L mRNA. The sequence and spacing between the two signals were not critical. Furthermore, the polymerase also was capable of efficiently transcribing from an L GS signal placed downstream of the M2 CE signal, implying that the overlapping arrangement is not obligatory. When copies of the L GS signal were placed concurrently upstream and downstream of the M2 GE signal, both were utilized. This finding indicates that a polymerase situated at a GE signal is capable of scanning for a GS signal in either the upstream or downstream direction and thereafter initiating transcription. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 34 TC 42 Z9 44 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 388 EP 397 PG 10 WC Virology SC Virology GA 146YP UT WOS:000077461700044 PM 9847343 ER PT J AU Teng, MN Collins, PL AF Teng, MN Collins, PL TI Altered growth characteristics of recombinant respiratory syncytial viruses which do not produce NS2 protein SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION ELONGATION-FACTOR; SITE-SPECIFIC MUTAGENESIS; SENDAI-VIRUS; V-PROTEIN; GENE-EXPRESSION; CULTURED-CELLS; C-PROTEIN; RNA; PARAMYXOVIRUS; REPLICATION AB The second gene in the 3'-to-5' gene order in respiratory syncytial virus (RSV) encodes the nonstructural protein NS2, for which there is no assigned function. To study the function of NS2, we have used a recently developed reverse genetics system to ablate expression of NS2 in recombinant RSV, A full-length cDNA copy of the antigenome of RSV A2 strain under the control of a T7 promoter was modified by introduction of tandem termination codons within the NS2 open reading frame (NS2stop) or by deletion of the entire NS2 gene (Delta NS2), The NS2 knockout antigenomic cDNAs were cotransfected with plasmids encoding the N, P, L, and M2-1 proteins of RSV, each controlled by the T7 promoter, into cells infected with a vaccinia virus recombinant expressing T7 RNA polymerase. Recombinant NS2stop and Delta NS2 RSVs were recovered and characterized. Both types of NS2 knockout virus displayed pinpoint plaque morphology and grew more slowly than wild-type RSV, The expression of monocistronic mRNAs for the five genes examined (NS1, NS2, N, F, and L) was unchanged in cells infected with either type of NS2 knockout virus, except that no NS2 mRNA was detected with the Delta NS2 virus. Synthesis of readthrough mRNAs was affected only for the Delta NS2 virus, where the NS1-NS2, NS2-N, and NS1-NS2-N mRNAs were replaced with the predicted novel NS1-N mRNA, Upon passage, the NS2stop virus stock rapidly developed revertants which expressed NS2 protein and grew with similar plaque morphology and kinetics wild-type RSV, Sequence analysis confirmed that the termination codons had reverted to sense, albeit not the wild-type assignments, and provided evidence consistent with biased hypermutation, No revertants were recovered from recombinant Delta NS2 RSV, These results show that the NS2 protein is not essential for RSV replication, although its presence greatly improves virus growth in cell culture. The attenuated phenotype of these mutant viruses, coupled with the expected genetic stability associated with gene deletions, suggests that the Delta NS2 RSV is a candidate for vaccine development. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. RI Teng, Michael/I-5006-2012 OI Teng, Michael/0000-0002-0722-3659 NR 29 TC 77 Z9 82 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 466 EP 473 PG 8 WC Virology SC Virology GA 146YP UT WOS:000077461700053 PM 9847352 ER PT J AU Polacino, P Stallard, V Klaniecki, JE Montefiori, DC Langlois, AJ Richardson, BA Overbaugh, J Morton, WR Benveniste, RE Hu, SL AF Polacino, P Stallard, V Klaniecki, JE Montefiori, DC Langlois, AJ Richardson, BA Overbaugh, J Morton, WR Benveniste, RE Hu, SL TI Limited breadth of the protective immunity elicited by simian immunodeficiency virus SIVmne gp160 vaccines in a combination immunization regimen SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM PROTECTION; PLASMA VIRAL LOAD; ENVELOPE GLYCOPROTEINS; RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; HIV-1 CHALLENGE; T-LYMPHOCYTES; D RETROVIRUS; V1 DOMAIN; INFECTION AB We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against an intravenous challenge by the cloned homologous virus, E11S, In this study, we confirmed this observation and found that the vaccines were effective not only against virus grown on human T-cell lines but also against virus grown on macaque peripheral blood mononuclear cells (PBMC). The breadth of protection, however, was limited. In three experiments, 3 of 10 animals challenged with the parental uncloned SIVmne were completely protected. Of the remaining animals, three were transiently virus positive and four were persistently positive after challenge, as were 10 nonimmunized control animals. Protection was not correlated with levels of serum-neutralizing antibodies against the homologous SIVmne or a related virus, SIVmac251. To gain further insight into the protective mechanism, we analyzed nucleotide sequences in the envelope region of the uncloned challenge virus and compared them with those present in the PBMC of infected animals. The majority (85%) of the uncloned challenge virus was homologous to the molecular clone from which the vaccines were made (E11S type). The remaining 15% contained conserved changes in the V1 region (variant types). Control animals infected with this uncloned virus had different proportions of the two genotypes, whereas three of four immunized but persistently infected animals had > 99% of the variant types early after infection. These results indicate that the protective immunity elicited by recombinant gp160 vaccines is restricted primarily to the homologous virus and suggest the possibility that immune responses directed to the V1 region of the envelope protein play a role in protection. C1 Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Bristol Myers Squibb Pharmaceut Res Inst, Seattle, WA 98121 USA. Duke Univ, Med Ctr, Durham, NC USA. Natl Canc Inst, Frederick, MD USA. RP Hu, SL (reprint author), Univ Washington, Dept Pharmaceut, Box 357331, Seattle, WA 98195 USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCRR NIH HHS [P51 RR000166, RR00166]; NIAID NIH HHS [AI26503, AI65302] NR 59 TC 54 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 618 EP 630 PG 13 WC Virology SC Virology GA 146YP UT WOS:000077461700068 PM 9847367 ER PT J AU Bour, SP Aberham, C Perrin, C Strebel, K AF Bour, SP Aberham, C Perrin, C Strebel, K TI Lack of effect of cytoplasmic tail truncations on human immunodeficiency virus type 2 ROD Env particle release activity SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN RETROVIRUS; VPU PROTEIN; GLYCOPROTEIN; HIV-1; GENE; DOMAIN; AIDS AB In addition to its role in receptor binding, the envelope glycoprotein of certain human immunodeficiency virus type 2 (HIV-2) isolates, including ROD10, exhibits a biological activity that enhances the release of HIV-2, HIV-1, and simian immunodeficiency virus particles from infected cells. The present study aims at better defining the functional domains involved in this biological activity. To this end, we have characterized the envelope protein of the ROD14 isolate of HIV-2, which, despite 95% homology with the ROD10 envelope at the amino acid level, is unable to enhance viral particle release. Site-directed mutagenesis showed that the presence of a truncation in the cytoplasmic tail of the ROD14 envelope was not responsible for the lack of activity, as previously reported for the HIV-2 ST isolate (G, D, Ritter, Jr,, G, Yamshchikov, S, J, Cohen, and M, J, Mulligan, J, Virol, 70:2669-2673, 1996), Similarly, several modifications of the length of the ROD10 envelope cytoplasmic tail did not impair its ability to enhance particle release, suggesting that, in the case of the HIV-2 ROD isolate, particle release activity is not regulated by the length of the cytoplasmic tail. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Bour, SP (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 312,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sbour@nih.gov NR 23 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 778 EP 782 PG 5 WC Virology SC Virology GA 146YP UT WOS:000077461700088 PM 9847387 ER PT J AU Shors, T Keck, JG Moss, B AF Shors, T Keck, JG Moss, B TI Down regulation of gene expression by the vaccinia virus D10 protein SO JOURNAL OF VIROLOGY LA English DT Article ID EARLY TRANSCRIPTION FACTOR; HINDIII-D FRAGMENT; RNA-POLYMERASE; MESSENGER-RNAS; INTERMEDIATE GENE; LATE PROMOTER; GENOME; SEQUENCE; SYSTEM; MUTT AB Vaccinia virus genes are expressed in a sequential fashion, suggesting a role for negative as well as positive regulatory mechanisms. A potential down regulator of gene expression was mapped by transfection assays to vaccinia virus open reading frame D10, which encodes a protein with no previously known function, Inhibition was independent of the promoter type used for the reporter gene, indicating that the mechanism did not involve promoter sequence recognition. The inhibition was overcome, however, when the open reading frame of the reporter gene was preceded by the encephalomyocarditis virus internal ribosome entry site, which excludes the possibility of nonspecific metabolic or other antiviral effects and suggests that capped mRNAs or cap-dependent translation might be the target of the D10 product. The inducible overexpression of the D10 gene by a recombinant vaccinia virus severely inhibited viral protein synthesis, decreased the steady-state level of viral late mRNA, and blocked the formation of infectious virus. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 229,4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 47 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 791 EP 796 PG 6 WC Virology SC Virology GA 146YP UT WOS:000077461700091 PM 9847390 ER PT J AU Leberg, PL Ellsworth, DL AF Leberg, PL Ellsworth, DL TI Further evaluation of the genetic consequences of translocations on southeastern white-tailed deer populations SO JOURNAL OF WILDLIFE MANAGEMENT LA English DT Article DE allozymes; genetics; mtDNA; Odocoileus virginianus; population structure; reintroduction; restocking; Southeast; translocations; white-tailed deer ID UNITED-STATES; DISPERSAL; DISTANCE AB Restocking programs were significant components of initiatives that restored white-tailed deer (Odocoileus virginianus) populations to the southeastern United States. However, past studies have reached conflicting conclusions regarding the effectiveness and consequences of translocations on the genetic structure of southeastern deer. We conducted further analysis of published datasets via matrix comparison methods to resolve these differences. Our analysis suggests translocations have had substantial and persistent effects on the genetic composition of deer populations into which translocated individuals were released. Regional and long-distance translocations influenced local populations by reducing the relationship between genetic differentiation and geographic distance among populations,and concordance between patterns of mitochondrial DNA (mtDNA) and allozyme variation. Strong associations of geographic and genetic distance among populations not directly receiving restocked deer indicate the genetic contributions of translocations are localized due to limited dispersal. Coastal island populations may warrant additional protective measures because they retain much of the historic genetic structure of southeastern white-tailed deer and may represent reservoirs of unique genetic material. C1 Univ SW Louisiana, Dept Biol, Lafayette, LA 70504 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Leberg, PL (reprint author), Univ SW Louisiana, Dept Biol, Box 42451, Lafayette, LA 70504 USA. NR 23 TC 25 Z9 26 U1 1 U2 4 PU WILDLIFE SOC PI BETHESDA PA 5410 GROSVENOR LANE, BETHESDA, MD 20814-2197 USA SN 0022-541X J9 J WILDLIFE MANAGE JI J. Wildl. Manage. PD JAN PY 1999 VL 63 IS 1 BP 327 EP 334 DI 10.2307/3802516 PG 8 WC Ecology; Zoology SC Environmental Sciences & Ecology; Zoology GA 159WY UT WOS:000078199400035 ER PT J AU Rossouw, JE Hurd, S AF Rossouw, JE Hurd, S TI The Women's Health Initiative: Recruitment complete - Looking back and looking forward SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 NHLBI, Womens Hlth Initiat, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat, 1 Rockledge Ctr,Suite 300 MS 7966,6705 Rockledge, Bethesda, MD 20892 USA. NR 3 TC 16 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD JAN-FEB PY 1999 VL 8 IS 1 BP 3 EP 5 DI 10.1089/jwh.1999.8.3 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 174CH UT WOS:000079016200002 PM 10094073 ER PT J AU Boheler, KR AF Boheler, KR TI Commentary: Nuclear receptors and myosin heavy chain gene expression in the aged myocardium SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 NIA, Baltimore, MD 21224 USA. RP Boheler, KR (reprint author), NIA, Baltimore, MD 21224 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 1999 VL 54 IS 1 BP B28 EP B29 DI 10.1093/gerona/54.1.B28 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 159GE UT WOS:000078163200005 PM 10026652 ER PT J AU Long, XL Boluyt, MO O'Neill, L Zheng, JS Wu, GM Nitta, YK Crow, MT Lakatta, EG AF Long, XL Boluyt, MO O'Neill, L Zheng, JS Wu, GM Nitta, YK Crow, MT Lakatta, EG TI Myocardial retinoid X receptor, thyroid hormone receptor, and myosin heavy chain gene expression in the rat during adult aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MESSENGER-RNA; BINDING; ACID; TRIIODOTHYRONINE; HEART; ALPHA; YOUNG; BIOCHEMISTRY; PROMOTER; MUSCLE AB Although previous studies have shown that cardiac myosin heavy chain (MHC) composition undergoes a switch from the alpha- to beta-isoform in the heart during adult aging, the underlying mechanisms responsible for this switch are unknown. Cardiac MHC gene expression is regulated, in part, by thyroid hormone responsive elements present in the regulatory control regions of the alpha- and beta-MHC genes. Age-associated changes in the expression of thyroid hormone receptors (THRs) and/or retinoid X receptors (RXRs) the heterodimeric partner for THRs, could explain the age-associated changes in MHC expression. Accordingly, we measured mRNA levels for the cardiac muscle MHCs and the rat THR and RXR genes in the left ventricles of Wistar rats at 2, 6 and 24 months of age. Although there were no significant changes in RXR alpha or RXR beta mRNA levels with age, both alpha 1 and alpha 2 THR mRNA levels decreased significantly between 2 and 6 months of age. During this same time period, the mRNA levels for alpha-MNC declined by more than half; whereas beta-MHC mRNA levels remained low and unchanged. On the other hand, between 6 and 24 months, when mRNA levels for beta-MHC increased and alpha-MHC continued to decrease, there was a significant decline in THR beta 1 and RXR gamma mRNA levels accompanied by a reduction in the THR beta 1 and RXR gamma protein levels. These data show a pattern of change that suggests that Be decline in alpha-MHC gene expression may be biphasic and due to a decline in alpha 1 (and possibly alpha 2) THR levels between 2 and 6 months of age and a decline in THR beta 1 and RXR gamma levels at later stages. In contrast the increase in beta-MHC gene expression was associated only with the changes in THR beta 1 and RXR gamma mRNA and protein levels. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIA, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIA, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov NR 29 TC 28 Z9 29 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 1999 VL 54 IS 1 BP B23 EP B27 DI 10.1093/gerona/54.1.B23 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 159GE UT WOS:000078163200004 PM 10026651 ER PT J AU Ward, JM Tadesse-Heath, L Perkins, SN Chattopadhyay, SK Hursting, SD Morse, HC AF Ward, JM Tadesse-Heath, L Perkins, SN Chattopadhyay, SK Hursting, SD Morse, HC TI Splenic marginal zone B-cell and thymic T-cell lymphomas in p53-deficient mice SO LABORATORY INVESTIGATION LA English DT Article ID SPONTANEOUS TUMORIGENESIS; CALORIE RESTRICTION; HEMATOPOIETIC NEOPLASMS; DEFICIENT MICE; DNA; DEHYDROEPIANDROSTERONE; CHEMOPREVENTION; PROLIFERATION; INVOLVEMENT; MUTATIONS AB The molecular pathology and histogenesis of lymphomas in 56 retired breeder male and 14 12-week-old male homozygous p53-deficient (p53(-/-)) mice (C57BL/6TacfBR-[KO]p53 N4) were evaluated. Lymphomas were assessed by serial morphologic techniques, immunohistochemistry, flow cytometry, and analysis of T cell receptor (TCR) or immunoglobulin heavy chain (IgH) gene rearrangements. We found two common types of lymphomas. T-cell lymphomas arose in the thymus through a sequence of lymphocyte depletion, medullary hyperplasia, and unilateral lymphoma. Tumor cells were CD3(+), CD90(+), and usually TCR alpha/beta(+) and possessed clonal TCR beta gene rearrangements. Thymic lymphoblastic lymphomas (LL) were highly malignant and quickly metastasized to the splenic white pulp and liver, even when the thymus was only slightly increased in weight. In the spleen, a novel lymphoma was found. Marginal zone hyperplasia led to marginal zone lymphoma (MZL), a well-differentiated lymphoma that usually expressed CD45R (B220) and CD5 at low levels and that had clonal IgH gene rearrangements. IgH gene rearrangements were also seen in spleens with marginal zone hyperplasias only. Hyperplastic and neoplastic marginal zone B cells expressed IgM at low to normal levels, as seen by FAGS analysis and immunohistochemistry. These tumors only metastasized to the liver at a later stage, as they became less differentiated. Several mice had both types of tumors present in the spleen. Two B-cell lymphoblastic lymphomas of uncertain origin were also found. In this article, we discuss the possible mechanisms responsible for development of the lymphomas seen in these p53-deficient mice. C1 NCI, Frederick Canc Res & Dev Ctr, Vet & Tumor Pathol Sect, Div Basic Sci, Frederick, MD 21702 USA. NCI, Off Lab Anim Resources, Anim Sci Branch, Frederick, MD 21701 USA. NCI, Lab Nutr & Mol Regulat, Frederick, MD 21701 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. RP Ward, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Vet & Tumor Pathol Sect, Div Basic Sci, Fairview 201,POB B, Frederick, MD 21702 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 56 TC 32 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 BP 3 EP 14 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600001 PM 9952106 ER PT J AU Bryant-Greenwood, P Caballero-Ramos, C Braddock, D Tresser, N AF Bryant-Greenwood, P Caballero-Ramos, C Braddock, D Tresser, N TI Combining methods to make the diagnosis of Alzheimer's disease easy, reliable and cost effective SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 4 BP 4A EP 4A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600012 ER PT J AU Hewitt, SM Kingma, DW Merino, MJ Kleiner, DE AF Hewitt, SM Kingma, DW Merino, MJ Kleiner, DE TI EBV-associated spindle cell tumors in HIV patients at autopsy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 12 BP 6A EP 6A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600020 ER PT J AU Lei, J Walther, MM Howard, RM Klausner, RD Linehan, WM Lubensky, IA AF Lei, J Walther, MM Howard, RM Klausner, RD Linehan, WM Lubensky, IA TI Prevalence of microscopic renal lesions in grossly normal kidney parenchyma from von Hippel-Lindau patients SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 15 BP 6A EP 6A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600023 ER PT J AU Middleton, LP Palacios, DM Bryant, BR Krebs, P Otis, C Merino, MJ AF Middleton, LP Palacios, DM Bryant, BR Krebs, P Otis, C Merino, MJ TI Pleomorphic lobular carcinoma: Correlation between morphology, immunohistochemistry, and molecular analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Baystate Med Ctr, Springfield, MA 01199 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 142 BP 27A EP 27A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600150 ER PT J AU Palacios, DM Bryant, BR Zujewski, J Sobel, ME Merino, MJ AF Palacios, DM Bryant, BR Zujewski, J Sobel, ME Merino, MJ TI Genetic alterations at BRCA1 and BRCA2 loci in normal breast tissue of high risk breast cancer patients SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 149 BP 29A EP 29A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600157 ER PT J AU Fetsch, PA Cowan, K Weng, D Abati, A AF Fetsch, PA Cowan, K Weng, D Abati, A TI Detection of circulating tumor cells (CTC) and micrometastases (MM) in breast cancer utilizing cytology and immunocytochemistry (ICC). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 235 BP 43A EP 43A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600243 ER PT J AU Petsch, PA Powers, CN Zakowski, M Abati, A AF Petsch, PA Powers, CN Zakowski, M Abati, A TI Anti-alpha-inhibin: Marker of choice for the consistent distinction between Adrenocortical Carcinoma (ACC) and Renal Cell Carcinoma (RCC) in Fine Needle Aspirations (FNA). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. VCU MCV, Richmond, VA USA. MSKCC, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 236 BP 43A EP 43A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600244 ER PT J AU Moses, D Sorbara, L Raffeld, M Copeland, C Arora, K Abati, A AF Moses, D Sorbara, L Raffeld, M Copeland, C Arora, K Abati, A TI Epstein-Barr virus (EBV) in air-dried archival cerebrospinal fluid cytology: detection via conventional polymerase chain reaction (PCR) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 271 BP 49A EP 49A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600279 ER PT J AU Simsir, A Palacios, D Linehan, LM Merino, M Abati, A AF Simsir, A Palacios, D Linehan, LM Merino, M Abati, A TI Detection or loss of heterozygosity (LOH) for the vonHippel-Lindau gene locus (VHL) in primary and metastatic ovarian clear cell carcinoma (OVCCC): Utilization of microdissection (MD) and the polymerase chain reaction (PCR) in archival cytologic and histologic material. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 284 BP 51A EP 51A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600292 ER PT J AU Guo, X Kleiner, D Fischette, M Merino, MJ AF Guo, X Kleiner, D Fischette, M Merino, MJ TI Aggressive follicular variant of papillary carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 382 BP 67A EP 67A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600390 ER PT J AU Mauro, DJ Walther, M Yousem, S Jaffe, R Zhuang, Z Klausner, RD Linehan, WM Lubensky, IA AF Mauro, DJ Walther, M Yousem, S Jaffe, R Zhuang, Z Klausner, RD Linehan, WM Lubensky, IA TI Pheochromocytomas in von Hippel-Lindau disease: Comparative histopathologic analysis with MEN2, "familial, NOS" and sporadic pheochromocytomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. Childrens Hosp, Dept Pathol, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 388 BP 68A EP 68A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600396 ER PT J AU Vlad, LD Axiotis, CA Merino, MJ Green, W AF Vlad, LD Axiotis, CA Merino, MJ Green, W TI Fatty acid synthase is highly expressed in aggressive thyroid tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Vet Adm Hosp, Brooklyn, NY USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 398 BP 70A EP 70A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600406 ER PT J AU Lubensky, IA Schiffmann, R Sutliff, VE Goldin, E Tsokos, M AF Lubensky, IA Schiffmann, R Sutliff, VE Goldin, E Tsokos, M TI Gastric biopsy in mucolipidosis type IV: Lysosomal inclusions in parietal cells - A novel cause of achlorhydria and hypergastrinemia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NINDS, NCI, Pathol Lab, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 453 BP 79A EP 79A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600461 ER PT J AU Pack, SD Pak, E Karkera, JD Hwu, P Balan, KW Park, WS Pham, T Ault, DO Liotta, LA Detera-Wadleigh, SD Wadleigh, RG Zhuang, Z AF Pack, SD Pak, E Karkera, JD Hwu, P Balan, KW Park, WS Pham, T Ault, DO Liotta, LA Detera-Wadleigh, SD Wadleigh, RG Zhuang, Z TI Esophageal squamous cell carcinoma: Genetic analysis by using comparative genomic hybridization (CGH) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Washington, DC USA. Howard Univ, Washington, DC 20059 USA. NIMH, NIH, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 470 BP 82A EP 82A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600478 ER PT J AU Fernandez, PL Fernandez, E Phillips, J Enquist, E Linehan, M Klausner, R Merino, MJ AF Fernandez, PL Fernandez, E Phillips, J Enquist, E Linehan, M Klausner, R Merino, MJ TI VEGF is frequently expressed by renal clear cell carcinoma but it does not correlate with microvessel count. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Hosp Clin Barcelona, Barcelona, Spain. Univ Barcelona, Barcelona, Spain. NCI, NIH, Bethesda, MD 20892 USA. RI Sloane, Bonnie/A-1050-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 546 BP 95A EP 95A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600554 ER PT J AU Lubensky, IA Weirich, G Schmidt, L Zhuang, Z Pack, S Walther, MM Linehan, WM Zbar, B AF Lubensky, IA Weirich, G Schmidt, L Zhuang, Z Pack, S Walther, MM Linehan, WM Zbar, B TI Histopathology of hereditary and sporadic papillary renal cell tumors with c-met mutations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Immunobiol Lab, NIH, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 579 BP 100A EP 100A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600587 ER PT J AU Moch, H Schraml, P Bubendorf, L Kononen, J Gasser, T Mihatsch, MJ Kallioniemi, OP Sauter, G AF Moch, H Schraml, P Bubendorf, L Kononen, J Gasser, T Mihatsch, MJ Kallioniemi, OP Sauter, G TI Genomic screening for prognostic markers in renal cell carcinomas by cDNA-array and tumor-array technologies SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Basel, Inst Pathol, Basel, Switzerland. Univ Basel, Urol Clin, Basel, Switzerland. Natl Human Genome Res Inst, Canc Genet Lab, NIH, Bethesda, MD USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 587 BP 102A EP 102A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600595 ER PT J AU Palacios, DM Bryant, BR Sobel, ME Middleton, LP Linehan, M Merino, MJ AF Palacios, DM Bryant, BR Sobel, ME Middleton, LP Linehan, M Merino, MJ TI Do genetic changes support a relationship between renal oncocytoma and chromophobe renal cell carcinoma? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 594 BP 103A EP 103A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600602 ER PT J AU Wagner, U Moch, H Kononen, J Bubendorf, L Leighton, S Gasser, TC Mihatsch, MJ Kallioniemi, OP Sauter, G AF Wagner, U Moch, H Kononen, J Bubendorf, L Leighton, S Gasser, TC Mihatsch, MJ Kallioniemi, OP Sauter, G TI Evaluation of prognostic markers in urinary bladder cancer using tumor tissue arrays. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Basel, Inst Pathol, Basel, Switzerland. Univ Basel, Urol Clin, Basel, Switzerland. Natl Human Genome Res Inst, Canc Genet Lab, Bethesda, MD USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 632 BP 109A EP 109A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600644 ER PT J AU Weirich, G Junker, K Lubensky, I Amin, MB Pack, S Merino, M Storkel, S Schmidt, L Kumar, S Linehan, MW Zhuang, Z Zbar, B AF Weirich, G Junker, K Lubensky, I Amin, MB Pack, S Merino, M Storkel, S Schmidt, L Kumar, S Linehan, MW Zhuang, Z Zbar, B TI A morphologic, histochemical, ultrastructural and molecular genetic study of renal tumors in Familial Renal Oncocytoma (FRO) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, IRSP, Frederick, MD 21701 USA. NCI, Pathol Lab, Urol Oncol Branch, Bethesda, MD 20892 USA. Univ Jena, Dept Urol, D-6900 Jena, Germany. Univ Jena, Dept Urol, D-6900 Jena, Germany. Univ Witten Herdecke, Inst Pathol, Witten, Germany. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 635 BP 110A EP 110A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600647 ER PT J AU Vortmeyer, AO Devouassoux-Shisheboran, M Li, G Tavassoli, F Zhuang, Z AF Vortmeyer, AO Devouassoux-Shisheboran, M Li, G Tavassoli, F Zhuang, Z TI Microdissection-based analysis of mature ovarian teratoma. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. AFIP, Breast & Gyn Dept, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 652 BP 112A EP 112A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600664 ER PT J AU Devouassoux-Shisheboran, M Vortmeyer, AO Silver, SA Zhuang, Z Tavassoli, FA AF Devouassoux-Shisheboran, M Vortmeyer, AO Silver, SA Zhuang, Z Tavassoli, FA TI Evidence for a common etiologic pathway between mature ovarian teratomas and associated sarcomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 AFIP, Gyn & Breast Pathol, Washington, DC USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 667 BP 115A EP 115A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600679 ER PT J AU Facchetti, F Zhang, W Tironi, A Chilosi, M Notarangelo, LD Samelson, LE Chan, JKC AF Facchetti, F Zhang, W Tironi, A Chilosi, M Notarangelo, LD Samelson, LE Chan, JKC TI LAT: Novel immunohistochemical marker for T-cells and T-cell lymphomas in routinely processed tissues. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Brescia, Dept Pathol, I-25121 Brescia, Italy. Univ Brescia, Dept Pediat, I-25121 Brescia, Italy. NICHD, Cell Biol & Metab Branch, Bethesda, MD USA. Univ Verona, I-37100 Verona, Italy. Queen Elizabeth Hosp, Hong Kong, Hong Kong. RI Notarangelo, Luigi/F-9718-2016; Facchetti, Fabio/E-7190-2010 OI Notarangelo, Luigi/0000-0002-8335-0262; Facchetti, Fabio/0000-0003-4975-2388 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 796 BP 136A EP 136A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600808 ER PT J AU Fend, F Quintanilla-Martinez, L Kumar, S Blum, L Sorbara, L Jaffe, E Raffeld, M AF Fend, F Quintanilla-Martinez, L Kumar, S Blum, L Sorbara, L Jaffe, E Raffeld, M TI Low grade B-cell lymphomas with two immunopheno-typically distinct cell populations in the same anatomic site are true biclonal lymphomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 797 BP 137A EP 137A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600809 ER PT J AU Greiner, T Zahm, S Migliazza, A Weisenburger, D AF Greiner, T Zahm, S Migliazza, A Weisenburger, D TI Molecular epidemiology of BCL2 and BCL6 mutations in lymphomas associated with pesticide exposures SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. NCI, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 802 BP 137A EP 137A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600814 ER PT J AU Kumar, S Quintanilla-Martinez, L Fend, F Reyes, E Kingma, DW Sorbara, L Raffeld, M Jaffe, ES AF Kumar, S Quintanilla-Martinez, L Fend, F Reyes, E Kingma, DW Sorbara, L Raffeld, M Jaffe, ES TI Fulminant EBV+ T-cell lymphoproliferative disorder following acute/chronic EBV infection: A distinct clinicopathologic syndrome. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 823 BP 141A EP 141A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600835 ER PT J AU Kumar, S Kingma, DW Quintanilla-Martinez, L Sorbara, L Raffeld, M Banks, PM Jaffe, ES AF Kumar, S Kingma, DW Quintanilla-Martinez, L Sorbara, L Raffeld, M Banks, PM Jaffe, ES TI EBV+ primary gastrointestinal Hodgkin's disease: Association with inflammatory bowel disease and immunosuppression. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Hematopathol Sect, NIH, Bethesda, MD USA. UNC, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 822 BP 141A EP 141A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600834 ER PT J AU Quintanilla-Martinez, L Davies-Hill, T Sorbara, L Jaffe, ES Raffeld, M AF Quintanilla-Martinez, L Davies-Hill, T Sorbara, L Jaffe, ES Raffeld, M TI Loss of detectable p27(Kip1) protein expression in mantle cell lymphomas (MCL) is a result of its sequestration by cyclin D1: implications for pathogenesis. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 844 BP 144A EP 144A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600856 ER PT J AU Quintanilla-Martinez, L Thieblemont, C Fend, F Kumar, S Phillips, T Davies-Hill, T Angonin, R Berger, F Jaffe, ES Raffeld, M AF Quintanilla-Martinez, L Thieblemont, C Fend, F Kumar, S Phillips, T Davies-Hill, T Angonin, R Berger, F Jaffe, ES Raffeld, M TI Overexpression of cyclin E and loss of expression of p27 are associated with aggressive transformation of chronic lymphocytic leukemia (CLL). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Hop Besancon, Besancon, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 843 BP 144A EP 144A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600855 ER PT J AU Teruya-Feldstein, J Cheung, A Yao, X Setsuda, J Kingma, DW Jaffe, ES AF Teruya-Feldstein, J Cheung, A Yao, X Setsuda, J Kingma, DW Jaffe, ES TI MIP1-alpha expression in patients with hemophagocytic syndromes. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 855 BP 146A EP 146A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600867 ER PT J AU Yao, X Lopatin, U Teruya-Feldstein, J Dale, JK Cheung, A Setsuda, J Quintanilla-Martinez, L Raffeld, M Straus, SE Jaffe, ES AF Yao, X Lopatin, U Teruya-Feldstein, J Dale, JK Cheung, A Setsuda, J Quintanilla-Martinez, L Raffeld, M Straus, SE Jaffe, ES TI Elevated IL-10 mRNA and protein in patients with autoimmune lymphoproliferative syndrome (ALPS) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, LP, Hematopathol Sect, Bethesda, MD USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 874 BP 149A EP 149A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600886 ER PT J AU Picken, MM Duray, PH Cera, L Margolis, L Picken, RN AF Picken, MM Duray, PH Cera, L Margolis, L Picken, RN TI Pathogenicity studies of Borrelia spirochetes in experimental rabbit and bioreactor tissue culture models SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Loyola Univ, Med Ctr, Dept Pathol, Chicago, IL 60611 USA. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 896 BP 153A EP 153A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600908 ER PT J AU Mohr, VH Vortmeyer, AO Libutti, SK Walther, MM Linehan, WM Zhuang, Z Lubensky, IA AF Mohr, VH Vortmeyer, AO Libutti, SK Walther, MM Linehan, WM Zhuang, Z Lubensky, IA TI Multiple microcystic (serous) adenomas and cysts of pancreas in VHL patients: Histopathologic and molecular genetic analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 965 BP 165A EP 165A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600977 ER PT J AU Kumar, S Perlman, E Paek, S Zhang, H Meltzer, P Tsokos, M AF Kumar, S Perlman, E Paek, S Zhang, H Meltzer, P Tsokos, M TI Olfactory neuroblastomas (ONB) lack the EWS/FLI1 fusion by fluorescence in situ hybridization (FISH) analysis. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1053 BP 179A EP 179A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601065 ER PT J AU Beasley, MB Thunnissen, E Brambilla, E Hasleton, P Steele, R Koss, MN Hammar, S Colby, TV Sheppard, M Falk, R Travis, WD AF Beasley, MB Thunnissen, E Brambilla, E Hasleton, P Steele, R Koss, MN Hammar, S Colby, TV Sheppard, M Falk, R Travis, WD TI Pulmonary atypical carcinoid (AC): Predictors of survival in 104 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 AFIP, Washington, DC USA. CHU Grenoble, F-38043 Grenoble, France. Univ Manchester, Sch Med, Manchester, Lancs, England. Royal Brompton Hosp, London SW3 6LY, England. Princess Alexandra Hosp, Woolloongabba, Qld 4102, Australia. Univ Maastricht, Maastricht, Netherlands. NCI, NIH, Bethesda, MD 20892 USA. RI Brambilla, Elisabeth/L-8796-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1064 BP 181A EP 181A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601076 ER PT J AU Okby, N Jones, R Khan, M Travis, W Liotta, L Caporaso, N Tazelaar, H Pairolero, P Traslek, V Miothun, D Jett, J Harris, C AF Okby, N Jones, R Khan, M Travis, W Liotta, L Caporaso, N Tazelaar, H Pairolero, P Traslek, V Miothun, D Jett, J Harris, C TI p27 immunohistochemical expression in non-small cell lung carcinomas (NSCLC) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1087 BP 185A EP 185A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601099 ER PT J AU Okby, N Khan, M Nagashima, M Travis, W Caporaso, N Liotta, L Tazelaar, H Pairolero, P Miothun, D Traslek, V Jett, J Harris, C AF Okby, N Khan, M Nagashima, M Travis, W Caporaso, N Liotta, L Tazelaar, H Pairolero, P Miothun, D Traslek, V Jett, J Harris, C TI p73 loss of heterozygosity in non-small cell lung carcinomas (NSCLC) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1086 BP 185A EP 185A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601098 ER PT J AU Sanz-Ortega, J Saez, MC Sierra, E Bryant, B Sobel, ME Sanz-Esponera, J Merino, MJ AF Sanz-Ortega, J Saez, MC Sierra, E Bryant, B Sobel, ME Sanz-Esponera, J Merino, MJ TI LOH at chromosomes 3p21, 5q21, 9p21 and 17p in normal bronchial mucosa adjacent to non small cell lung cancer. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Hosp San Carlos, Madrid, Spain. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Sanz, Julian/G-5276-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1090 BP 185A EP 185A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601102 ER PT J AU Shen, R Bui, H Resau, J AF Shen, R Bui, H Resau, J TI Met. hepatocyte growth factor scatter factor (HGF/SF) expression in mesotheliomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Cincinnati VAMC, Cincinnati, OH USA. Univ Cincinnati, Cincinnati, OH 45221 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1093 BP 186A EP 186A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601105 ER PT J AU Geradts, J Birrer, M Fong, K Abbondanzo, SL Barrett, JC Lombardi, DP AF Geradts, J Birrer, M Fong, K Abbondanzo, SL Barrett, JC Lombardi, DP TI Loss and KAI1 expression in squamous and lymphoid neoplasms: An immunohistochemical study of archival tissues SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Oxford, Oxford OX1 2JD, England. Natl Canc Inst, Rockville, MD USA. Prince Charles Hosp, Brisbane, Qld 4032, Australia. Armed Forces Inst Pathol, Washington, DC 20306 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1123 BP 191A EP 191A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601135 ER PT J AU Hewitt, SM Herring, J Emmert-Buck, M Linehan, WM Duray, PH AF Hewitt, SM Herring, J Emmert-Buck, M Linehan, WM Duray, PH TI Methods of processing prostatectomy specimens to maximize teaching and research potential SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, Urol Oncol Branch, Pathol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1124 BP 191A EP 191A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601136 ER PT J AU Schraml, P Kononen, J Bubendorf, L Moch, H Bissig, H Leighton, S Mihatsch, M Kallioniemi, A Kallioniemi, OP Sauter, G AF Schraml, P Kononen, J Bubendorf, L Moch, H Bissig, H Leighton, S Mihatsch, M Kallioniemi, A Kallioniemi, OP Sauter, G TI Multi-tumor-arrays for amplification detection in multiple different tumor types. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NHGRI, Canc Genet Lab, Bethesda, MD USA. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1139 BP 194A EP 194A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601151 ER PT J AU Wellmann, A Thieblemont, C Sakai, A Pittaluga, S Jaffe, ES Siebert, P Raffeld, M AF Wellmann, A Thieblemont, C Sakai, A Pittaluga, S Jaffe, ES Siebert, P Raffeld, M TI Application of cDNA microarray technology for the identification of diagnostic markers. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Clontech Labs Inc, Palo Alto, CA USA. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1143 BP 194A EP 194A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601155 ER PT J AU Lung, FDT King, CR Roller, PP AF Lung, FDT King, CR Roller, PP TI Development of non-phosphorylated cyclic thioether peptide binding to the Grb2-SH2 domain SO LETTERS IN PEPTIDE SCIENCE LA English DT Article DE cyclic peptides; inhibitors; N-chloroacetyl peptide; signal transduction; solid-phase peptide synthesis ID AUTOMATED SYNTHESIS; C4 DOMAIN; POLYMERS; ADAPTER; EPITOPE AB One of the critical intracellular signaling pathways involves specific interactions between growth factor receptors and the adaptor protein Grb2. These interactions normally involve specific tyrosine phosphorylated regions in receptors and other cognate proteins. Following the lead of our recent findings that a phage library based non-phosphorylated disulfide linked 11-mer peptide inhibited such interactions, we report hers the synthesis of novel redox-stable cyclic peptide analogs. These include thioether cyclized and backbone cyclized structures. The thioether analog was prepared under mild conditions from an N-terminally chloroacetylated and C-terminally cysteine extended peptide precursor. The thioether peptide showed equipotent binding affinity for the Grb2-SH2 domain (IC50 = 10-15 mu M) when compared to the disulfide cyclized lead-peptide. The bioactive thioether linked peptide was demonstrated to offer advantages to the disulfide cyclized peptides under physiological conditions. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 19 TC 23 Z9 23 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5666 J9 LETT PEPT SCI JI Lett. Pept. Sci. PD JAN PY 1999 VL 6 IS 1 BP 45 EP 49 DI 10.1023/A:1008815410812 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 173XK UT WOS:000079004900006 ER PT J AU Thieblemont, C Pack, S Sakai, A Beaty, M Pak, E Vortmeyer, AO Wellmann, A Zhuang, Z Jaffe, ES Raffeld, M AF Thieblemont, C Pack, S Sakai, A Beaty, M Pak, E Vortmeyer, AO Wellmann, A Zhuang, Z Jaffe, ES Raffeld, M TI Allelic loss of 11q13 as detected by MEN1-FISH is not associated with mutation of the MEN1 gene in lymphoid neoplasms SO LEUKEMIA LA English DT Article DE MEN1; non-Hodgkin's lymphoma; tumor suppressor gene; chromosomal deletions ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TUMOR SUPPRESSOR GENES; PARATHYROID TUMORS; CHROMOSOME 11Q13; NON-HODGKIN; HEMATOLOGIC MALIGNANCIES; LINKAGE ANALYSIS; HUMAN DNA; TYPE-1; CANCER AB Deletions and rearrangements involving the long arm of chromosome 11 are not infrequent occurrences in the non-Hodgkin's lymphomas. Recently, a tumor suppressor gene, the multiple endocrine neoplasia type 1 gene (MEN1) was cloned and mapped to chromosome 11q13. To assess the potential involvement of this gene in lymphomagenesis, we examined 94 primary cases of lymphoma and 12 cell lines by a combination of fluorescent in situ hybridization and PCR-SSCP analysis. In our initial analysis of 41 primary B or T lymphomas, MEN1 FISH analysis revealed allelic deletions in 15 cases (three of four B cell chronic lymphocytic leukemias, six of 15 follicular lymphomas, three of nine diffuse large B cell lymphomas, two of five mantle cell lymphomas, one of four Burkitt's lymphoma). To discern whether the MEN1 gene was in fact the target of the deletions, we assessed 20 of these 41 cases and an additional 74 primary lymphomas and 12 cell lines for MEN1 gene mutations using PCR-SSCP analysis. Abnormal SSCP patterns were found in exon 2 in two of the primary lymphoma cases and in one of the cell lines, but not in any of the original cases that showed MEN1 deletions by FISH. Furthermore, sequencing analysis revealed that the abnormal SSCP patterns in exon 2 were the result of a previously described genetic polymorphism (S145S: AGC --> ACT), and in one sample, the result of this S145S polymorphism associated with a second nucleotide substitution at position 498 which left the encoded amino acid unchanged. Our study indicates that the 11q13 locus is a frequent target of deletion in lymphoid neoplasms, but that there are no associated mutations of the MEN1 gene. This suggests that the 11q deletions either target another gene in lymphomas, or that the MEN1 gene is inactivated through means other than mutation. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Raffeld, M (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2N110, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 65 TC 4 Z9 4 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 1999 VL 13 IS 1 BP 85 EP 91 DI 10.1038/sj.leu.2401216 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 160ZF UT WOS:000078262700014 PM 10049065 ER PT J AU Navid, F Mosijczuk, AD Head, DR Borowitz, MJ Carroll, AJ Brandt, JM Link, MP Rozans, MK Thomas, GA Schwenn, MR Shields, DJ Vietti, TJ Pullen, DJ AF Navid, F Mosijczuk, AD Head, DR Borowitz, MJ Carroll, AJ Brandt, JM Link, MP Rozans, MK Thomas, GA Schwenn, MR Shields, DJ Vietti, TJ Pullen, DJ TI Acute lymphoblastic leukemia with the (8;14)(q24;q32) translocation and FAB L3 morphology associated with a E-precursor immunophenotype: the Pediatric Oncology Group experience SO LEUKEMIA LA English DT Article DE B cell acute lymphoblastic leukemia; t(8;14); B-precursor acute lymphoblastic leukemia ID B-CELL LEUKEMIA; CHROMOSOME; CHILDHOOD; LYMPHOMA; INVOLVEMENT; SURVIVAL; CHILDREN; MARKERS AB Five pediatric patients are described with acute lymphoblastic leukemia (ALL) who at presentation had clinical findings suggestive of B cell ALL and lymphoblasts with FAB L3 morphology and the characteristic t(8;14)(q24;q32). However, the leukemia cells of all five patients failed to express surface immunoglobulin (slg) and kappa or lambda light chains. Based on initial immunophenotyping results consistent with B-precursor ALL, four of these cases were initially treated with conventional ALL chemotherapy. These four patients were switched to B cell ALL treatment protocols once cytogenetic results became available revealing the 8;14 translocation. The fifth case was treated with B cell ALL therapy from the outset. Four of the five patients are in complete remission at 64, 36, 29 and 13 months from diagnosis. One patient relapsed and died 6 months after initial presentation. These five unusual cases with clinical B cell ALL, the t(8;14), and FAB L3 morphology, but negative sig, demonstrate the importance of careful and multidisciplinary evaluation of leukemic cells with morphology, cytochemistry, immunophenotyping and cytogenetic analysis. Future identification of patients with this profile will allow us to expand our knowledge regarding prognostic significance and optimal treatment for this rare subgroup of patients. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Pediat Hematol Oncol Serv, Washington, DC 20307 USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. Univ Alabama, Med Genet Lab, Birmingham, AL 35294 USA. Washington Univ, Med Ctr, St Louis, MO USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Tulane Hosp Children, New Orleans, LA USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. Univ Mississippi, Med Ctr, Dept Pediat Hematol Oncol, Jackson, MS 39216 USA. RP Navid, F (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-69177, CA-03161, CA-29691] NR 13 TC 42 Z9 42 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 1999 VL 13 IS 1 BP 135 EP 141 DI 10.1038/sj.leu.2401244 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 160ZF UT WOS:000078262700022 PM 10049049 ER PT B AU Colaianni, LA AF Colaianni, LA BE Bakker, S TI The National Library of Medicine: Plans for international access to its information resources SO LIBRARIES WITHOUT LIMITS: CHANGING NEEDS - CHANGING ROLES LA English DT Proceedings Paper CT 6th European Conference of Medical and Health Libraries CY JUN 22-27, 1998 CL UTRECHT, NETHERLANDS SP European Assoc Hlth Informat & Lib C1 Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5626-8 PY 1999 BP 87 EP 92 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA BN30E UT WOS:000081459000021 ER PT J AU Greiner, RS Moriguchi, T Hutton, A Slotnick, BM Salem, N AF Greiner, RS Moriguchi, T Hutton, A Slotnick, BM Salem, N TI Rats with low levels of brain docosahexaenoic acid show impaired performance in olfactory-based and spatial learning tasks SO LIPIDS LA English DT Article; Proceedings Paper CT 3rd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 01-05, 1998 CL LYON, FRANCE SP Int Soc Study Fatty Acids & Lipids ID ESSENTIAL FATTY-ACIDS; LINOLENATE-LINOLEATE BALANCE; BEHAVIORAL-DEVELOPMENT; LIPID COMPOSITIONS; RHESUS-MONKEYS; ODOR MEMORY; DEFICIENCY; SUPPLEMENTATION; ABILITY; MICE AB Studies were carried out to determine if decreased levels of central nervous system docosahexaenoic acid (DHA), a result of consuming an n-3-deficient diet,had an effect on learning- and memory-related behaviors in adult male rats. Females were reared on an n-3-deficient or n-3-adequate diet beginning at 21 d of life. Their male pups, the F2 generation, were weaned to the diet of the dam and tested at 9-12 wk of age. An olfactory-based discrimination and Morris water maze task were used to assess performance. Whole brain was collected after the behavioral experiments and central nervous system fatty acid content was analyzed In olfactory bulb total lipid extracts. F2 generation male rats consuming the n-3-deficient diet had an 82% decrease in DHA compared to rats consuming the n-3-adequate diet. The n-3-deficient animals made significantly more total errors in a 7-problem, 2-odor discrimination task compared to the n-3-adequate group. Furthermore, the escape latency in the Morris water maze task was significantly longer for the n-3-deficient rats compared to the n-3-adequate rats. These results indicate that rats with decreased DHA levels in the central nervous system perform poorer in these tasks compared to rats with higher DHA levels and suggest the presence of learning deficits in these animals. C1 NIAAA, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. RP Salem, N (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, 12420 Parklawn Dr,Park 5 Bldg,Room 158, Rockville, MD 20852 USA. NR 27 TC 105 Z9 108 U1 1 U2 2 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PY 1999 VL 34 SU S BP S239 EP S243 DI 10.1007/BF02562305 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 215PA UT WOS:000081389000086 PM 10419165 ER PT J AU Kim, HY Edsall, L AF Kim, HY Edsall, L TI The role of docosahexaenoic acid (22 : 6n-3) in neuronal signaling SO LIPIDS LA English DT Article; Proceedings Paper CT 3rd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 01-05, 1998 CL LYON, FRANCE SP Int Soc Study Fatty Acids & Lipids ID C6 GLIOMA-CELLS; ACTIVATION C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Kim, HY (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. EM hykim@nih.gov NR 7 TC 18 Z9 19 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 J9 LIPIDS JI Lipids PY 1999 VL 34 SU S BP S249 EP S250 DI 10.1007/BF02562308 PG 2 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 215PA UT WOS:000081389000089 PM 10419168 ER PT J AU Pawlosky, R Hibbeln, J Wegher, B Sebring, N Salem, N AF Pawlosky, R Hibbeln, J Wegher, B Sebring, N Salem, N TI The effects of cigarette smoking on the metabolism of essential fatty acids SO LIPIDS LA English DT Article; Proceedings Paper CT 3rd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 01-05, 1998 CL LYON, FRANCE SP Int Soc Study Fatty Acids & Lipids C1 USDA, Human Nutr Res Ctr, Beltsville, MD 20705 USA. NIAAA, NIH, Rockville, MD 20852 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Pawlosky, R (reprint author), USDA, Human Nutr Res Ctr, Beltsville, MD 20705 USA. NR 2 TC 22 Z9 22 U1 0 U2 0 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PY 1999 VL 34 SU S BP S287 EP S287 DI 10.1007/BF02562319 PG 1 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 215PA UT WOS:000081389000100 PM 10419179 ER PT J AU Pawlosky, RJ Salem, N AF Pawlosky, RJ Salem, N TI A chronic ethanol-feeding study in rhesus monkeys SO LIPIDS LA English DT Article; Proceedings Paper CT 3rd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 01-05, 1998 CL LYON, FRANCE SP Int Soc Study Fatty Acids & Lipids AB This study describes the effect of chronic ethanol-feeding in rhesus monkeys. Animals which were maintained on a diet containing 18:2n-6 and 18:3n-3 as 1.4 and 0.08% of the calories, respectively, and consumed alcohol (mean 2.6 g kg(-1) d(-1)) had decreased amounts of 20:4n-6 and 22:6n-3 in their livers and plasma lipids compared with controls. Alcohol consumption did not appear to effect the absorption of H-2(5)-18:2n-6 and 18:3n-3 esters into the blood following an oral dose. There was an increase in H-2(5) enrichment in plasma 20:4n-6 and 22:6n-3, indicating that alcohol may have increased production of these fatty acids. There was a greater concentration of 4-hydroxynonenal in the plasma of alcohol-exposed monkeys compared to controls. C1 USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NIAAA, NIH, Rockville, MD 20852 USA. RP Pawlosky, RJ (reprint author), USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NR 4 TC 2 Z9 2 U1 0 U2 1 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PY 1999 VL 34 SU S BP S131 EP S132 DI 10.1007/BF02562261 PG 2 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 215PA UT WOS:000081389000042 PM 10419121 ER PT S AU Kim, HY Edsall, L Garcia, M Zhang, HJ AF Kim, HY Edsall, L Garcia, M Zhang, HJ BE Nigam, S PaceAsciak, CR TI The release of polyunsaturated fatty acids and their lipoxygenation in the brain SO LIPOXYGENASES AND THEIR METABOLITES: BIOLOGICAL FUNCTIONS SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Symposium on Lipoxygenases and Their Metabolites CY MAY 21-24, 1997 CL ST JULIAN, MALTA SP Hosp Sick Children, Toronto, Free Univ Berlin, NOAA Sea Grant Coll Program ID CENTRAL-NERVOUS-SYSTEM; ARACHIDONIC-ACID; RAT-BRAIN; GLIAL-CELLS; 12-LIPOXYGENASE; MELATONIN; PRODUCTS; NEURONS; IDENTIFICATION; STIMULATION AB Stimulation of neuronal tissues with neurotransmitters results in the release of the polyunsaturated fatty acids 20:4n6 and 22:6n3. Astroglial cells hydrolyze 20:4n6 and 22:6n3 equally well under both stimulated and basal conditions. Despite the high abundance of 22:6n3 in neuronal membranes, 20:4n6 is preferentially hydrolyzed from neuronal cells. These results suggest that 22:6n3 may be of more physiological importance in neuronal membranes as a membrane component rather than as a released free fatty acid, while in astroglia, release of 22:6n3 may also be a significant step involved in receptor-stimulated signaling processes. Oxygenation of these polyunsaturated fatty acids occurs in the brain. However, in contrast to the prevailing belief, lipid peroxidation rather than lipoxygenation is primarily responsible for their formation. In rodent brains, any significant lipoxygenation appears to occur only in the pineal. The production of hydroxylated polyunsaturated fatty acids in pineal may play a role in the pineal function especially in relation to melatonin synthesis. C1 NIAAA, NIH, Rockville, MD 20852 USA. RP NIAAA, NIH, Rockville, MD 20852 USA. EM hykim@dicbr.niaaa.nih.gov NR 34 TC 32 Z9 32 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 0-306-46044-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 447 BP 75 EP 85 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Physiology SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Physiology GA BM81M UT WOS:000079831500007 PM 10086184 ER PT J AU Davis, JC Manzi, S Yarboro, C Rairie, J Mcinnes, I Averthelyi, D Sinicropi, D Hale, VG Balow, J Austin, H Boumpas, DT Klippel, JH AF Davis, JC Manzi, S Yarboro, C Rairie, J Mcinnes, I Averthelyi, D Sinicropi, D Hale, VG Balow, J Austin, H Boumpas, DT Klippel, JH TI Recombinant human Dnase I (rhDNase) in patients with lupus nephritis SO LUPUS LA English DT Article DE dornase alpha; lupus; treatment ID GLOMERULAR-BASEMENT-MEMBRANE; CYSTIC-FIBROSIS PATIENTS; ANTI-DNA; DEOXYRIBONUCLEASE-I; COMPLEMENT PROFILES; ERYTHEMATOSUS SLE; PERIPHERAL-BLOOD; STRANDED-DNA; ANTIBODIES; DISEASE AB Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies to nucleoprotein antigens, including double-stranded DNA (dsDNA). The deposition of IgG dsDNA immune complexes in glomeruli is thought to be crucial for disease pathogenesis and complement activation. rhDNase catalyzes the hydrolysis of extracellular DNA and has been shown to delay the development of dsDNA antibodies, reduce proteinuria, and delay mortality in a lupus-prone murine model. We conducted a 40d, phase Ib, randomized, double-masked, placebo-controlled trial to determine the safety and pharmacokinetics of rhDNase, and to measure any changes in markers of disease activity in 17 patients with lupus nephritis. Patients were assigned to receive either: (1) 25 mu g/kg,rhDNase (n = 8); (2) 125 mu g/kg rhDNase (n = 6); or (3) placebo (n = 3) initial single intravenous (IV) dose followed by 10 subcutaneous (SC) doses. Skin biopsies performed on nine patients pre- and post-treatment were studied for immune complex deposition by immunofluorescence.Serum cytokine levels (sIL2-R, IL-6, IL-10, and TNF-alpha) were analyzed by ELISA. Cytokine secretion and antibody production were measured by ELISPOT analysis and ELISA. Serum hydrolytic activity of rhDNase was achieved after IV administration at 25 and 125 mu g/kg, but not after SC administration at either dose. A t1/2 of 3-4h was estimated from serum concentration profiles following IV administration. Serum dsDNA antibodies were unchanged (mean values: 33IU/mL vs 39IU/mL [pre- and post-treatment] for the 25 mu g/kg group, and 74IU/mL vs 74IU/mL for the 125 mu g/kg group, and 14IU/mL vs 20IU/mL for the placebo group). Complement levels (C3 and C4) and circulating immune complexes did not change appreciably during the treatment period for any of the groups. Serum cytokine profiles by ELISA revealed no changes in sIL-2 receptor, IL-6, IL-10, or TNF-alpha. There was no change in the number of cells secreting either Th1 or Th2 specific cytokines, nor in the number of cells secreting dsDNA antibodies. Neutralizing antibodies to rhDNase were not detected in serum at any time during the study. Immune complex deposition was unchanged in pre- and post-treatment in skin biopsies in both dose groups. rhDnase was well tolerated without significant adverse events following administration, and treatment was not associated with the development of neutralizing antibodies to rhDNase. Serum rhDNase concentrations capable of hydrolytic activity of rhDNase were achieved for a few hours following IV, but not SC administration. Serum markers of disease activity were unchanged during the study period. C1 NIAMS, Clin Invest Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA. Univ Pittsburgh, Med Ctr, Div Clin Immunol & Rheumatol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Davis, JC (reprint author), Univ Calif San Francisco, 533 Parnassus Ave,Box 0633, San Francisco, CA 94143 USA. NR 37 TC 71 Z9 76 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 1999 VL 8 IS 1 BP 68 EP 76 DI 10.1191/096120399678847380 PG 9 WC Rheumatology SC Rheumatology GA 163DG UT WOS:000078387000010 PM 10025601 ER PT J AU Koch, CA AF Koch, CA TI Cardiac tamponade in SLE SO LUPUS LA English DT Letter ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ECHOCARDIOGRAPHY C1 NICHD, DEB, NIH, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NICHD, DEB, NIH, Bldg 10,Rm 10N262, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008 OI Koch, Christian/0000-0003-3127-5739 NR 5 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 1999 VL 8 IS 3 BP 250 EP 250 DI 10.1191/096120399678847623 PG 1 WC Rheumatology SC Rheumatology GA 199HA UT WOS:000080473900015 PM 10342721 ER PT J AU Corn, M AF Corn, M TI Informatics and the road to professionalism SO M D COMPUTING LA English DT Editorial Material ID MEDICAL INFORMATICS; DISCIPLINE C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Corn, M (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD JAN-FEB PY 1999 VL 16 IS 1 BP 34 EP + PG 2 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 180LQ UT WOS:000079387800018 PM 10202421 ER PT J AU Alkon, DL AF Alkon, DL TI Molecular principles of associative memory that are conserved during the evolution of species SO MALACOLOGIA LA English DT Article; Proceedings Paper CT Unitas Malacologica - American-Malacological-Society Symposium on Interactions Between Man and Molluscs CY JUL 26-30, 1998 CL WASHINGTON, D.C. SP Amer Malacol Soc DE molecular mechanisms; Hermissenda; memory; Alzheimer's disease ID K+ AB Time domains of homeostatic adaptation encompass: 1.) the lifetime of the species (an evolutionary domain) in which predictive information with survival valve is incorporated into the genome, and 2.) the lifetime of organisms in which predictive information is stored within brain networks. Experiments over many years in our NIH lab have confirmed that behavioral, biophysical, and molecular mechanisms for storing learned information have been conserved in species as diverse as the nudibranch mollusc Hermissenda and mammals such as rat and rabbit. Further studies now indicate that these conserved molecular memory steps (e.g. K+ channel inactivation, PKC and calexcitin activation, and intracellular calcium release) are also consistent targets of the human syndrome known as Alzheimer's disease. These findings highlight the elegant economy of natural selection and the utility of animal models for investigating complex brain disorders such as Alzheimer's disease. C1 NINDS, Lab Adapt Syst, Bethesda, MD 20892 USA. RP Alkon, DL (reprint author), NINDS, Lab Adapt Syst, Bldg 36,Room 4A24,MSC4007, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 1 U2 2 PU INST MALACOL PI ANN ARBOR PA 2415 SOUTH CIRCLE DR, ANN ARBOR, MI 48103 USA SN 0076-2997 J9 MALACOLOGIA JI Malacologia PY 1999 VL 41 IS 2 BP 321 EP 329 PG 9 WC Zoology SC Zoology GA 287PH UT WOS:000085514300002 ER PT B AU Eddy, EM AF Eddy, EM BE Gagnon, C TI The effects of gene knockouts on spermatogenesis. SO MALE GAMETE: FROM BASIC SCIENCE TO CLINICAL APPLICATIONS LA English DT Proceedings Paper CT 8th International Symposium on Spermatology CY AUG 17-22, 1998 CL MONTREAL, CANADA ID GERM-CELL APOPTOSIS; FOLLICLE-STIMULATING-HORMONE; TISSUE-SPECIFIC EXPRESSION; DEFICIENT MICE; CHROMOSOME SYNAPSIS; TARGETED DISRUPTION; MALE-INFERTILITY; MUTANT MICE; SEXUAL-DIFFERENTIATION; CHROMATIN MODIFICATION C1 NIEHS, Gamete Biol Grp, Lab Reprod Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Grp, Lab Reprod Dev Toxicol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 88 TC 2 Z9 2 U1 0 U2 0 PU CACHE RIVER PRESS PI VIENNA PA 2850 OAK GROVE ROAD, VIENNA, IL 62995 USA BN 1-889899-03-8 PY 1999 BP 23 EP 36 PG 14 WC Reproductive Biology SC Reproductive Biology GA BQ95N UT WOS:000165104200004 ER PT J AU Bennett, LM Brownlee, HA Hagavik, S Wiseman, RW AF Bennett, LM Brownlee, HA Hagavik, S Wiseman, RW TI Sequence analysis of the rat Brca1 homolog and its promoter region SO MAMMALIAN GENOME LA English DT Article ID CANCER SUSCEPTIBILITY GENE; BREAST-CANCER; TRANSCRIPTIONAL ACTIVATION; SUBCELLULAR-LOCALIZATION; MOUSE CHROMOSOME-11; DNA-DAMAGE; EXPRESSION; DIFFERENTIATION; MUTATIONS; LOCATION AB Since the identification of the human breast and ovarian cancer gene, BRCA1, a large spectrum of germline mutations has been characterized that predispose women to developing these diseases. We have determined the complete coding sequence for the rat BRCA1 homolog and compared it with those of the mouse, dog, and human to help identify the important functional domains of the BRCA1 protein. The overall rat Brcal amino acid identity compared with the predicted mouse, dog, and human gene products is 81%, 69%, and 58%, respectively. In spite of this low overall homology, the amino terminal RING finger domain and one of two nuclear localization signals are highly conserved among these species. In addition, two BRCT domains at the carboxy terminus and a highly acidic region are relatively well conserved. We have also identified several putative regulatory elements through comparison of the bidirectional BRCA1 promoter regions among the rat, mouse, and human genes. These include motifs for CCAAT and GIC boxes, as well as potential SP1, CREB, and NFkB transcription factor binding sites. Finally, analysis of splice variants from rat mammary gland, ovary, testis, spleen, and liver tissues revealed that, while alternative transcripts are detectable, full-length transcripts are the predominant steady-state form. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Bennett, LM (reprint author), NIEHS, Mol Carcinogenesis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Bennett@nichs.nih.gov NR 44 TC 19 Z9 20 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JAN PY 1999 VL 10 IS 1 BP 19 EP 25 DI 10.1007/s003359900935 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 155GL UT WOS:000077920300004 PM 9892727 ER PT J AU Mishra, L Yu, P Cai, T Monga, SPS Mishra, B AF Mishra, L Yu, P Cai, T Monga, SPS Mishra, B TI Genomic structure, chromosomal mapping, and muscle-specific expression of a PH domain-associated intronless gene, cded/lior SO MAMMALIAN GENOME LA English DT Article ID PHOSPHOLIPASE C-GAMMA-1 GENE; PLECKSTRIN HOMOLOGY DOMAIN; FACTOR RECEPTOR GENE; PROMOTER REGION; CREATINE-KINASE; DNA; SEQUENCE; PROTEINS; IDENTIFICATION; TRANSCRIPTION AB The aim of our study was to isolate novel gene(s) involved in cell differentiation and embryonic liver development. Mouse cded/lior was identified from subtraction hybridization of embryonic liver cDNA libraries as well as an adult mouse liver genomic DNA library. The full open reading frame of cded/lior encodes a 131-amino acid protein with 71.88% overall similarity to the PH domain of rat PLC-gamma 1. A gapped search with the C-terminal region of CDED/LIOR revealed a 36-41% similarity to several proteins related to signal transduction and cell replication, such as ORC1 and KSR. Northern blot analysis of adult mouse tissues shows a strong 2.6-kb transcript restricted to heart and skeletal muscle. RT-PCR utilizing cded/lior-specific primers demonstrates cded/lior mRNAs in heart, brain, and liver tissue throughout mid-embryonic mouse gestation. cded/lior maps to the distal end of mouse Chromosome (Chr) 2. Analysis of the genomic structure for cded/lior demonstrated a single exon gene that is not an alternatively spliced isoform of PLC-gamma 1. Analysis of the cned/ lior promoter region revealed a high CC-content, high ratio of CpG/GpC, multiple CC-boxes, the lack of a TATA box, CTF/NFI element, and two MyoD-MCK binding sites. These characteristics are also found in several genes important in the regulation of cell growth or DNA synthesis, such as transforming growth factor-beta 1, c-Ha-ras, nerve growth factor, epidermal growth factor receptor, and DNA polymerase beta. These results suggest that cded/lior is a mesoderm/muscle-specific transcript that may be involved in the mesodermal inductive and regulatory interactions required for liver formation and embryonic development. C1 Dept Vet Affairs, Lab Dev Mol Biol, Washington, DC 20422 USA. Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA. NIH, Natl Ctr Human Genome Res, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. RP Mishra, L (reprint author), Dept Vet Affairs, Lab Dev Mol Biol, 151-W,50 Irving St NW, Washington, DC 20422 USA. NR 40 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JAN PY 1999 VL 10 IS 1 BP 62 EP 67 DI 10.1007/s003359900944 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 155GL UT WOS:000077920300013 PM 9892736 ER PT B AU Dawson, D Ginis, I Liu, J Spatz, M Hallenbeck, JM AF Dawson, D Ginis, I Liu, J Spatz, M Hallenbeck, JM BE Ito, U Fieschi, C Orzi, F Kuroiwa, T Klatzo, I TI Tumor necrosis factor-alpha-induced ischemic tolerance as manifested by microvascular and endothelial cell responses SO MATURATION PHENOMENON IN CEREBRAL ISCHEMIA III: DEFENSIVE MECHANISMS VERSUS APOPTOSIS - NEURONAL RECOVERY AND PROTECTION IN CEREBRAL INFARCTION LA English DT Proceedings Paper CT 3rd International Workshop on Maturation Phenomenon in Cerebral Ischemia CY APR 20-22, 1998 CL POZZILLI, ITALY ID FOCAL CEREBRAL-ISCHEMIA; GENE-EXPRESSION; BRAIN; PRETREATMENT; ADHESION; GERBIL; ICAM-1; LIPOPOLYSACCHARIDE; INTERLEUKIN-1; RESISTANCE AB In spontaneously hypertensive rats subjected to middle-cerebral-artery occlusion, a preconditioning exposure to the cytokine-stimulating agent, lipopolysaccharide (0.9 mg/kg), 3 days prior to the focal brain ischemia conferred a state of tolerance, in which the infarct volume was smaller and the degree of microvascular-perfusion impairment was reduced, compared with control animals preconditioned with saline. In addition, brain capillary endothelial cells from Wistar-Kyoto rats could be preconditioned by a 4-h exposure to 20 ng/ml tumor necrosis factor-alpha (TNF-alpha). A second exposure to TNF-alpha or to hypoxia 20 h after the preconditioning stimulated significantly less expression of intercellular adhesion molecule-1 (ICAM-1) in these endothelial cell cultures compared with controls. The results indicate that protection of the microcirculation is one aspect of TNF-alpha-induced tolerance and that endothelial-cell activation as manifested by ICAM-1 expression can be attenuated by preconditioning exposure to TNF-alpha. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20982 USA. RP Dawson, D (reprint author), NINDS, Stroke Branch, NIH, Bldg 36,Rm 4A03,36 Convent Dr MSC 4128, Bethesda, MD 20982 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-65023-7 PY 1999 BP 127 EP 133 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA BN80A UT WOS:000082967200016 ER PT B AU Sokoloff, L AF Sokoloff, L BE Ito, U Fieschi, C Orzi, F Kuroiwa, T Klatzo, I TI Mechanisms of regulation of cerebral blood flow SO MATURATION PHENOMENON IN CEREBRAL ISCHEMIA III: DEFENSIVE MECHANISMS VERSUS APOPTOSIS - NEURONAL RECOVERY AND PROTECTION IN CEREBRAL INFARCTION LA English DT Proceedings Paper CT 3rd International Workshop on Maturation Phenomenon in Cerebral Ischemia CY APR 20-22, 1998 CL POZZILLI, ITALY ID SENSITIVE POTASSIUM CHANNELS; INSULIN-INDUCED HYPOGLYCEMIA; DEPENDENT PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; K+ CHANNELS; OXIDATIVE-METABOLISM; VASCULAR-RESISTANCE; UNANESTHETIZED RATS; GLUCOSE-UTILIZATION; CORONARY-ARTERY AB The physiological mechanisms that regulate cerebral blood flow (CBF) have long been studied, but are still not fully defined. Neurogenic mechanisms probably exist, but their role is still undefined. Chemical mechanisms are widely believed to mediate a "coupling" between cerebral energy metabolism and CBF to assure adequate supply of substrates to meet the brain's energy demands. We have used two experimental models of cerebral glucose deprivation, i.e., insulin-induced hypoglycemia and glycolytic blockade by loading doses of 2-deoxyglucose, to examine mechanisms underlying the associated large increases in CBF, despite lowered energy metabolism in these conditions. Mechanisms excluded thus far are: (1) changes in blood pH and pCO(2), (2) direct insulin action, (3) increased lactate and decreased K+ levels in plasma induced by insulin, and (4) nitric oxide production. Both caffeine, an adenosine receptor antagonist, and glibenclamide, which blocks ATP-sensitive K+ channels, reduce until abolition the increases in CBF in these conditions in a dose-dependent manner. Adenosine receptors, which mediate vasodilation, and ATP-sensitive K+ (K-ATP) channels, which, when open, promote smooth-muscle relaxation, exist in vascular smooth muscle. We have measured and found, during glucose deprivation, marked rises in brain levels of adenosine and its degradation products, inosine and hypoxanthine, indicating increased adenosine release. There is evidence in a variety of tissues that adenosine-receptor activation stimulates cyclic adenosine monophosphate (cAMP) formation, which activates protein kinase A, an enzyme that phosphorylates proteins. There is also evidence that the activity of the K-ATP channels can be altered by such phosphorylation. These results suggest the following sequence: (1) when the ATP/ADP balance is shifted toward ADP by stimulation of Na+/K(+)ATPase activity, e.g., during functional activation, or by reduced ATP generation, e.g., during glucose or oxygen deprivation, some of the ADP is converted to AMP by adenylic kinase; (2) AMP is dephosphorylated by 5'-nucleotidase to produce adenosine; (3) adenosine activates adenosine receptors in vascular smooth muscle to produce cAMP, and (4) cAMP-dependent protein kinase A phosphorylates the K+ channels, which then open, allowing K+ efflux, membrane hyperpolarization, smooth-muscle relaxation and vasodilatation. Increasing adenosine diphosphate (ADP) and inorganic phosphate concentrations is known to stimulate glycolytic and oxidative metabolism. The shift in the ATP/ADP balance toward ADP accompanying functional activation would then not only lead to increased CBF, but also to increased energy metabolism, thus, resulting in their being related, not by a direct coupling mechanism, but as separate, yet correlated, consequences of one prior event. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Room 1A05, Bethesda, MD 20892 USA. NR 72 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-65023-7 PY 1999 BP 291 EP 307 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA BN80A UT WOS:000082967200035 ER PT S AU Rabkin, CS Sei, S AF Rabkin, CS Sei, S BE Melchers, F Potter, M TI Susceptibility genes for AIDS and AIDS-related lymphoma SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKINS-LYMPHOMA; DISEASE PROGRESSION; HIV-1 INFECTION; VARIANTS C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, HIV Clin Interface Lab, Frederick, MD 21702 USA. RP Rabkin, CS (reprint author), NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 111 EP 115 PG 5 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200014 PM 10396046 ER PT S AU Hilgenfeld, E Padilla-Nash, H Schrock, E Ried, T AF Hilgenfeld, E Padilla-Nash, H Schrock, E Ried, T BE Melchers, F Potter, M TI Analysis of B-cell neoplasias by spectral karyotyping (SKY) SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MULTIPLE-MYELOMA; ABNORMALITIES; IDENTIFICATION; TRANSLOCATIONS; LYMPHOMA; GENE AB B-cell neoplasias represent a heterogeneous group of diseases, including acute lymphocytic leukemia (ALL) and the broad spectrum of non-Hodgkin's lymphomas (NHL). Conventional cytogenetic analysis has revealed specific chromosomal aberrations in ALL as well as in NHL. Spectral karyotyping (SKY) is a novel molecular cytogenetic technique which allows the visualization of all human chromosomes in different colors, therefore greatly facilitating the recognition of chromosomal aberrations. The potential of SKY is exemplified by the fact that in our experience, 70% of the cases analyzed resulted in karyotypes where the majority of aberrations were either refined or new aberrations were detected when compared to their G-banding karyotypes. This also applies to the analysis of B-cell neoplasias. In hematologic malignancies, especially acute leukemias, specific chromosomal aberrations are of etiologic as well as diagnostic and prognostic importance. The identification of new recurrent chromosomal aberrations could therefore lead to a better characterization of disease entities or subgroups in ALL and NHL and further improve diagnosis, treatment stratification and ultimately prognosis. Interestingly, the comparison of the pattern of chromosomal aberrations in hematological neoplasias and carcinomas revealed striking differences. While about 50% of the aberrations in hematological malignancies are balanced translocations, such aberrations are exceedingly rare in epithelial cancers in which unbalanced structural and numerical aberrations prevail. C1 NCI, Dept Genet, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Univ Munster, D-4400 Munster, Germany. RP Hilgenfeld, E (reprint author), NCI, Dept Genet, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 18 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 169 EP 174 PG 6 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200021 PM 10396053 ER PT S AU Coleman, AE Ried, T Janz, S AF Coleman, AE Ried, T Janz, S BE Melchers, F Potter, M TI Recurrent non-reciprocal translocations of chromosome 5 in primary T(12;15)-positive BALB/c plasmacytomas SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID MURINE PLASMACYTOMAS; C-MYC; RECOMBINATIONS; INDUCTION; ABL AB The majority of inflammation-induced peritoneal BALB/c plasmacytomas (approximate to 90 %) harbor a balanced T(12;15) chromosomal translocation that deregulates the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, plasmacytomas take a long time to develop (average tumor latency approximate to 220 days), which suggests that additional tumor progression events may be required to complete oncogenesis. We hypothesized that such tumor progression events may take the form of secondary chromosomal aberrations that can be detected by spectral karyotyping (SKY), We screened the entire chromosome complement of 18 primary BALB/c plasmacytomas carrying the T(12;15) and found in nine tumors (50 % recurrence) secondary cytogenetic aberrations that involved bands D, E and F of chromosome (Chr) 5. The Chr 5D-F rearrangements were manifested predominantly as unbalanced translocations with various partner chromosomes, This finding led us to propose the existence of an important plasmacytoma progression locus in the central region of Chr 5, which presumably becomes involved in peritoneal plasmacytoma development by promiscuous chromosomal translocations. C1 NCI, Genet Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIH, Genome Technol Branch, NCHGR, Bethesda, MD 20892 USA. RP Coleman, AE (reprint author), NCI, Genet Lab, Div Basic Sci, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 175 EP 181 PG 7 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200022 PM 10396054 ER PT S AU Mushinski, JF Hanley-Hyde, J Rainey, GJ Kuschak, TI Taylor, C Fluri, M Stevens, LM Henderson, DW Mai, S AF Mushinski, JF Hanley-Hyde, J Rainey, GJ Kuschak, TI Taylor, C Fluri, M Stevens, LM Henderson, DW Mai, S BE Melchers, F Potter, M TI Myc-Induced cyclin D2 genomic instability in murine B cell neoplasms SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID C-MYC; GENE; EXPRESSION; AMPLIFICATION; LINES; MOUSE; RAT; OVEREXPRESSION; RECOMBINATION; ACTIVATION C1 NCI, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. Univ Maryland, Mol & Cell Biol Program, College Pk, MD 20742 USA. Basel Inst Immunol, CH-4005 Basel, Switzerland. RP Mushinski, JF (reprint author), NCI, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. RI Mai, Sabine/E-5667-2017 OI Mai, Sabine/0000-0002-5797-2201 NR 24 TC 8 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 183 EP 192 PG 10 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200023 PM 10396055 ER PT S AU Rabkin, CS AF Rabkin, CS BE Melchers, F Potter, M TI Epidemiology of B-cell lymphomas SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID NON-HODGKINS-LYMPHOMA; RISK-FACTORS; TIME TRENDS C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Rabkin, CS (reprint author), NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 235 EP 240 PG 6 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200029 PM 10396061 ER PT S AU Morse, HC Qi, CF Tadesse-Heath, L Chattopadhyay, SK Ward, JM Coleman, A Hartley, JW Fredrickson, TN AF Morse, HC Qi, CF Tadesse-Heath, L Chattopadhyay, SK Ward, JM Coleman, A Hartley, JW Fredrickson, TN BE Melchers, F Potter, M TI Novel aspects of murine B cell lymphomas SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID GERMINAL-CENTER FORMATION; SPONTANEOUS TUMORS; MICE; INFLAMMATION; EXPRESSION; BCL-6; P53 C1 NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, Registry Expt Canc, NIH, Bethesda, MD 20892 USA. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 13 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 249 EP 255 PG 7 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200031 PM 10396063 ER PT S AU Potter, M Kutkat, L AF Potter, M Kutkat, L BE Melchers, F Potter, M TI Inhibition of pristane-induced peritoneal plasmacytoma formation SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; B-CELLS; PROSTAGLANDIN E(2); RECEPTOR-GAMMA; BALB/C MICE; B-1 CELLS; ACTIVATION; AUTOIMMUNE; INDUCTION; INDOMETHACIN C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Potter, M (reprint author), NCI, Genet Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 48 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 351 EP 362 PG 12 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200043 PM 10396075 ER PT S AU Zhang, SL Mock, BA AF Zhang, SL Mock, BA BE Melchers, F Potter, M TI The role of p16(INK4a) (Cdkn2a) in mouse plasma cell tumors SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID INK4A LOCUS; SUSCEPTIBILITY; CHROMOSOME-4; RESISTANCE; MUTATIONS; P19(ARF); GENES; MICE C1 NCI, Genet Lab, DBS, NIH, Bethesda, MD 20892 USA. RP Zhang, SL (reprint author), NCI, Genet Lab, DBS, NIH, 37 Convent Dr,Bldg 37,Rm 2B-08, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 363 EP 368 PG 6 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200044 PM 10396076 ER PT S AU Felix, K Kelliher, K Bornkamm, GW Janz, S AF Felix, K Kelliher, K Bornkamm, GW Janz, S BE Melchers, F Potter, M TI Transgenic shuttle vector assays for assessing oxidative B-cell mutagenesis in vivo SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID BIG BLUE(R) RATS; MUTATION ANALYSIS; IN-VITRO; MOUSE; MICE; LACI; DNA; 7,12-DIMETHYLBENZANTHRACENE; NEUTROPHILS; MODEL AB The recent development of transgenic mutagenicity assays provides new opportunities for evaluating mutagenic processes in vivo. To assess mutant frequencies in tissue B cells, we decided to take advantage of two such assays that utilize the transgenic shuttle vectors, lambda LIZ and pUR288. Our main interest in this research is to test two basic premises of inflammation-induced plasmacytoma development in genetically susceptible BALB/c mice; i.e., the possibility that plasmacytoma precursor cells may become targets of phagocyte-mediated oxidative mutagenesis in situ and the prospect that plasmacytoma susceptibility/resistance genes may contribute to these phenotypes by enhancing/reducing oxidative mutagenesis in B cells. Based on our preliminary experience with the lambda LIZ and pUR288 transgenic in vivo mutagenicity tests, we propose to employ these assays as broadly applicable tools for assessing overall mutagenesis during normal and aberrant (malignant) B-cell development. Furthermore, transgenic shuttle vector assays appear to lend themselves as ideal methods to associate general B-cell mutagenesis with the peculiar, B cell-typical somatic hypermutation processes that target the V(D)J gene segment, the proto-oncogene bcl-6 and perhaps other, still unknown loci. C1 NCI, Genet Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. GSF, Inst Clin Mol Biol & Tumor Genet, Munich, Germany. RP Felix, K (reprint author), NCI, Genet Lab, Div Basic Sci, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 369 EP 377 PG 9 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200045 PM 10396077 ER PT S AU Warner, HR AF Warner, HR BE Zakeri, Z Lockshin, RA BenitezBribiesca, L TI Apoptosis: A two-edged sword in aging SO MECHANISMS OF CELL DEATH: THE SECOND ANNUAL CONFERENCE OF THE CELL DEATH SOCIETY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Annual Conference on Mechanisms of Cell Death CY JUL 17-18, 1998 CL CUNY, CELL DEATH SOC, NEW YORK, NEW YORK SP Calbinchem Novabiochem Corp, NIA, NIH, Oncogene Sci, CUNY, Queen Coll, St Johns Univ Grad Sch Arts & Sci, Upstate Biotechnol Inc HO CUNY, CELL DEATH SOC ID PROGRAMMED CELL-DEATH; INTERLEUKIN-1-BETA CONVERTING-ENZYME; MANGANESE SUPEROXIDE-DISMUTASE; IN-VIVO; ALZHEIMERS-DISEASE; LYMPHOPROLIFERATIVE SYNDROME; 1-BETA-CONVERTING ENZYME; INCREASES APOPTOSIS; HUMAN FIBROBLASTS; FAMILY PROTEASES AB Here we summarize briefly what is known about both the positive and negative impacts of apoptosis during aging in mammalian systems and also update an earlier review. It is important to understand both of these impacts to devise useful interventions. Such interventions include both physiological and molecular approaches, including transgenic interventions. The critical roles of the mitochondria in both generating reactive oxygen species, and in initiating apoptosis are recognized, suggesting that maintaining mitochondrial function could be an important therapeutic goal, especially in post-mitotic tissues. In contrast, the ability to eliminate unwanted, damaged and dysfunctional cells through apoptosis has anti-aging implications in mitotic tissues. C1 NIA, NIH, Biol Aging Program, Bethesda, MD 20892 USA. RP Warner, HR (reprint author), NIA, NIH, Biol Aging Program, Gateway Bldg,Suite 2C231, Bethesda, MD 20892 USA. NR 70 TC 36 Z9 37 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 1-57331-240-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 887 BP 1 EP 11 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BP49Q UT WOS:000085322200001 PM 10668459 ER PT J AU Samuel, DP Tsokos, M DeBaun, MR AF Samuel, DP Tsokos, M DeBaun, MR TI Hemihypertrophy and a poorly differentiated embryonal rhabdomyosarcoma of the pelvis SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE hemihypertrophy; sarcoma; rhabdomyosarcoma; LOH; 11p15.5; MyoD1 ID BECKWITH-WIEDEMANN SYNDROME; WILMS TUMOR; HETEROZYGOSITY; EXPRESSION; CHILDHOOD; MYOD1 AB Background. Asymmetry of the limbs (conventionally known as hemihypertrophy) is one of the overgrowth syndromes occurring sporadically in the general population at a frequency of approximately 1:86,000. Hemihypertrophy is also reported as part of the Beckwith-Wiedemann syndrome which has as its cardinal features omphalocele, macroglossia and gigantism with hypoglycemia, organomegaly, renal anomalies, hemihypertrophy, and embryonal tumors occurring less frequently. Various neoplasms are also associated with isolated hemihypertrophy. Wilms tumor, adrenocortical carcinoma, and hepatoblastoma are the most frequent. Rhabdomyosarcoma, neuroblastoma, phaeochromocytoma, and undifferentiated sarcoma of the lung are encountered only rarely. Loss of heterozygosity (LOH) of chromosome 11p15.5 is strongly associated with childhood embryonal tumors, particularly Wilms tumor, hepatoblastoma, and rhabdomyosarcoma. Procedure and Results. In this article, we describe an adolescent male with congenital asymmetry of the lower limbs who presented with a large poorly differentiated pelvic sarcoma. Conventional histologic, immunohistochemical, and ultrastructural studies of this tumor were insufficient far accurate subclassification. However, positive staining far MyoD1 (a recently identified embryonically expressed marker of muscle differentiation) and LOH at the tyrosine hydroxylase locus of chromosome 11p15.5 by molecular analysis favored the diagnosis of embryonal rhabdomyosarcoma over an undifferentiated sarcoma. Conclusions. This case stresses the importance of pursuing clinical findings when they occur in conditions with an increased risk of developing cancer, which in this case was asymmetry of a limb. Also illustrated by this patient is the need for early consideration of molecular diagnostic tests where available, to refine an uncertain pathologic diagnosis that may ultimately have an impact on treatment and prognosis, Med. Pediatr. Oncol. 32:38-43, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 NCI, Pediat Branch, NIH, Bethesda, MD 20895 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Div Canc Etiol, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Samuel, DP (reprint author), NCI, Pediat Branch, NIH, Bldg 10, Bethesda, MD 20895 USA. EM samueld@exchange.nih.gov NR 39 TC 11 Z9 11 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD JAN PY 1999 VL 32 IS 1 BP 38 EP 43 DI 10.1002/(SICI)1096-911X(199901)32:1<38::AID-MPO8>3.0.CO;2-H PG 6 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 149ZE UT WOS:000077636500008 PM 9917751 ER PT J AU Strickler, HD Rosenberg, PS Devesa, SS Fraumeni, JF Goedert, JJ AF Strickler, HD Rosenberg, PS Devesa, SS Fraumeni, JF Goedert, JJ TI Contamination of poliovirus vaccine with SV40 and the incidence of medulloblastoma SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE childhood cancer; virology; brain tumors; epidemiology ID DNA-SEQUENCES; CHILDHOOD; TUMORS C1 NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Strickler, HD (reprint author), NCI, Viral Epidemiol Branch, NIH, Execut Plaza N 434, Bethesda, MD 20892 USA. NR 9 TC 9 Z9 9 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD JAN PY 1999 VL 32 IS 1 BP 77 EP 78 DI 10.1002/(SICI)1096-911X(199901)32:1<77::AID-MPO21>3.0.CO;2-F PG 2 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 149ZE UT WOS:000077636500021 PM 9917764 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Choice and representation in health care SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article AB Choice is often thought to be critical in health care, especially to foster quality improvements and lower costs. However, it is also recognized that in the current system there is significant representation of consumers, members, and patients by physicians, employers, and health plans. Consent, accountability, and protections against conflicts of interest are necessary to ensure legitimate and effective representation. This article discusses the roles and responsibilities of physicians, employers, and other parties with respect to serving as representatives of health care consumers. The author concludes that to make representation more legitimate and effective in health care will require significant changes, which include (1) changing business to a stakeholder theory, (2) involving employees in health care coverage decisions, and (3) involving members of health plans in policy decisions. C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Ctr Eth Managed Care, Cambridge, MA 02138 USA. RP Emanuel, EJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 13 TC 7 Z9 7 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PY 1999 VL 56 SU 1 BP 113 EP 140 DI 10.1177/107755899773743909 PG 28 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 206VU UT WOS:000080901700007 PM 10354680 ER PT S AU Rettmann, ME Xu, CY Pham, DL Prince, JL AF Rettmann, ME Xu, CY Pham, DL Prince, JL BE Taylor, C Colchester, A TI Automated segmentation of sulcal regions SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION, MICCAI'99, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 2nd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 99) CY SEP 19-22, 1999 CL CAMBRIDGE, ENGLAND ID SURFACE; CORTEX; ATLAS AB Automatic segmentation and identification of cortical sulci play an important role in the study of brain structure and function. In this work, a method is presented for the automatic segmentation of sulcal regions of cortex. Unlike previous methods that extract the sulcal spaces within the cortex, the proposed method extracts actual regions of the cortical surface that surround sulci. Sulcal regions are. segmented from the medial surface as well as the lateral and inferior surfaces. The method first generates a depth map on the surface, computed by measuring the distance between the cortex and ail outer "shrink-wrap" surface. Sulcal regions are then extracted using a hierarchical algorithm that alternates between thresholding and region growing operations. To visualize the buried regions of the segmented cortical surface, ail efficient technique for mapping the surface to a sphere is proposed. Preliminary results are presented on the geometric analysis of sulcal regions for automated identification. C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIH, Lab Personal & Cognit, GRC, Baltimore, MD 21224 USA. RP Johns Hopkins Univ, Baltimore, MD 21218 USA. RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 19 TC 3 Z9 3 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-66503-X J9 LECT NOTES COMPUT SC PY 1999 VL 1679 BP 158 EP 167 PG 10 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Laboratory Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Medical Laboratory Technology; Radiology, Nuclear Medicine & Medical Imaging GA BS81S UT WOS:000171179200017 ER PT S AU Long, LR Thoma, GR AF Long, LR Thoma, GR BE Hanson, KM TI Segmentation and feature extraction of cervical spine x-ray images SO MEDICAL IMAGING 1999: IMAGE PROCESSING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1999 Conference - Image Processing CY FEB 22-25, 1999 CL SAN DIEGO, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE medical x-ray image; segmentation; image processing; radiograph; cervical spine; NHANES; image database; NLM AB As part of an R&D project in mixed text/image database design, the National Library of Medicine has archived a collection of 17,000 digitized x-ray images of the cervical and lumbar spine which were collected as part of the second National Health and Nutrition Examination Survey (NHANES II). To make this image data available and usable to a wide audience, we are investigating techniques for indexing the image content by automated or semi-automated means. Indexing of the images by features of interest to researchers in spine disease and structure requires effective segmentation of the vertebral anatomy. This paper describes work in progress toward this segmentation of the cervical spine images into anatomical components of interest, including anatomical landmarks for vertebral location, and segmentation and identification of individual vertebrae. Our work includes developing a reliable method for automatically fixing an anatomy-based coordinate system in the images, and work to adaptively threshold the images, using methods previously applied by researchers in cardioangiography. We describe the motivation for our work and present our current results in both areas. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Long, LR (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 5 TC 11 Z9 11 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3133-8 J9 P SOC PHOTO-OPT INS PY 1999 VL 3661 BP 1037 EP 1046 DI 10.1117/12.348497 PN 1&2 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BN14N UT WOS:000080862400104 ER PT S AU Hattery, D Chernomordik, V Loew, M Gannot, I Gandjbakhche, A AF Hattery, D Chernomordik, V Loew, M Gannot, I Gandjbakhche, A BE Boone, JM Dobbins, JT TI Time-resolved fluorescent imaging in tissue. SO MEDICAL IMAGING 1999: PHYSICS OF MEDICAL IMAGING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1999 Conference CY FEB 21-25, 1999 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc/Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE fluorescence; lifetime; fluorophore; photon; turbid; imaging; tissue optics; random walk; molecular tagging; diffusion ID BIOLOGICAL MEDIA; MODEL AB Fluorescence lifetime imaging is a useful tool for quantifying, site-dependent environmental conditions in tissue. Fluorophores exist with known lifetime dependencies on factors such as concentrations of O-2 and other specific molecules, as well as on temperature and pH. Extracting fluorophore lifetime for deeply embedded sites in turbid media such as tissue is made difficult by the multiple scattering of photons traveling through tissue. This scattering introduces photon arrival delays that have similar characteristics to the delays resulting from the excitation and subsequent emission of photons by fluorophores. Random walk theory (RWT) provides a framework in which the two sources of diffusion-like delays can be separated so that the part due to fluorescent lifetime can be quantified. We: derive a closed-form solution that predicts time-resolved photon arrivals from a deeply embedded fluorophore site. The solution requires that an average absorption coefficient be used. However, it is shown that this assumption introduces only a small error. This RWT-derived Solution is also shown to be valid for a range of geometries in which the fluorophore site is embedded at least 10 mean scattering lengths and in which the fluorophore lifetime is less than 1ns. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Hattery, D (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bldg 12A,Room 2041, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 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 0-8194-3131-1 J9 P SOC PHOTO-OPT INS PY 1999 VL 3659 BP 384 EP 391 DI 10.1117/12.349513 PG 8 WC Engineering, Biomedical; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BN32Q UT WOS:000081632400038 ER PT S AU Summers, RM Pusanik, LM Malley, JD Hoeg, JM AF Summers, RM Pusanik, LM Malley, JD Hoeg, JM BE Chen, CT Clough, AV TI Fractal analysis of virtual endoscopy reconstructions SO MEDICAL IMAGING 1999: PHYSIOLOGY AND FUNCTION FROM MULTIDIMENSIONAL IMAGES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1999 Conference CY FEB 21-25, 1999 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc/Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE magnetic resonance angiography; virtual endoscopy; virtual angioscopy; computer-aided diagnosis; vasculature; atherosclerosis; fractal surfaces; three-dimensional reconstruction; homozygous familial hypercholesterolemia ID 3-DIMENSIONAL MR-ANGIOGRAPHY; IMAGE QUALITY; DATA SETS; DIMENSION; BRONCHOSCOPY; INTERPOLATION; SURFACES; DISPLAY; IMPACT; AORTA AB Virtual endoscopy reconstructions of the body noninvasively provide morphologic information of gross structural abnormalities such as stenoses in airways or blood vessels and polyps in the colonic wall. Surface irregularity or roughness is another indication of abnormality potentially detectible on virtual endoscopy. In this paper, we show how fractal dimension can be used to quantify surface roughness and how these methods may be applied to virtual angioscopy to distinguish the thoracic aorta in a normal volunteer from that of a patient predisposed to atherosclerosis. Finally, we discuss some problems we encountered applying fractal analysis to small, noisy datasets. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 36 TC 6 Z9 6 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 0-8194-3132-X J9 P SOC PHOTO-OPT INS PY 1999 VL 3660 BP 258 EP 269 DI 10.1117/12.349595 PG 12 WC Engineering, Biomedical; Optics; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BN29K UT WOS:000081442700027 ER PT S AU Yim, PJ Summers, RM AF Yim, PJ Summers, RM BE Chen, CT Clough, AV TI Analytic surface reconstruction by local threshold estimation in the case of simple intensity contrasts SO MEDICAL IMAGING 1999: PHYSIOLOGY AND FUNCTION FROM MULTIDIMENSIONAL IMAGES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1999 Conference CY FEB 21-25, 1999 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc/Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE surface reconstruction; segmentation; watershed; marching-cubes algorithm; surface aliasing; interpolation ID SHAPE-BASED INTERPOLATION; IMAGE SEGMENTATION; MRI AB Surface reconstruction for 3D visualization requires both a segmentation of the image and at the least, a conversion of the data from an image format to a shape format. While the discrete pixel locations of the segmentation may be satisfactory for quantitative purposes, it is usually important for visual quality to remove such voxelation in the shape data prior to rendering. Removal of such voxelation, depending on the specific segmentation technique, may be problematic, involving excessive interpolation prior to segmentation or the application of pure surface smoothing in which important image information may be disregarded. An algorithm is presented here to address these problems. In this algorithm, a smoothly varying threshold level is determined such that that level falls within the interpolated intensity ranges of all the segmentation-boundary voxels. This threshold information is extrapolated to voxels adjacent to the boundary and then used to correct or normalize the original image in the vicinity of the boundary. Provided that the directionality of the contrast between the interior and exterior of the boundary is sufficiently consistent throughout the boundary, an isosurface of this normalized image is guaranteed to exist which falls within the voxels of the segmentation boundary. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Yim, PJ (reprint author), NIH, Dept Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA. NR 28 TC 8 Z9 7 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 0-8194-3132-X J9 P SOC PHOTO-OPT INS PY 1999 VL 3660 BP 288 EP 300 DI 10.1117/12.349599 PG 13 WC Engineering, Biomedical; Optics; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BN29K UT WOS:000081442700030 ER PT J AU Pei, XF Yu, QS Holloway, HW Brossi, A Greig, NH AF Pei, XF Yu, QS Holloway, HW Brossi, A Greig, NH TI Syntheses and biological evaluation of ring-C opened analogues of the cholinesterase inhibitors physostigmine, phenserine and cymserine SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article ID ANTICHOLINESTERASE ACTIVITY; ALZHEIMERS-DISEASE; CARBAMATE ANALOGS; ACETYLCHOLINESTERASE; BUTYRYLCHOLINESTERASE; (+)-PHYSOVENINE; PROTEIN AB The ring-C of natural, 3aS, (-)-physostigmine (1), (-)-phenserine (2) and (-)-cymserine (3) were cleaved by catalytic hydrogenation under acidic condition to give ring-C opened compounds (4-6). The tertiary amines (10-12) were prepared from methiodides (7-9) by reduction with NaBH4. Additionally, the unnatural, 3aR, enantiomer of ring-C opened phenserine (14) was synthesized from (+)-phenserine (13). All then were evaluated for anticholinesterase activity against human acetyl- and butyrylcholinesterase. Compounds 4-12 were found to have potent inhibitory activity and, with the exception of the methiodides (7-9), to retain the subtype selectivity provided them by their carbamate group. Interestingly, methiodide 8 possessed characteristics of potential value for treatment of mysathenia gravis. In contrast, compound 14 proved to be some 2 log-fold less active than its enantiomeric form (5). These studies conclusively demonstrate that the tricyclic structure of (-)-physostigmine (1) and analogs is not essential for their anticholinesterase action, and that such activity for ring C opened compounds, similar to (-) physostigmine and phenylcarbamates (1-3), is limited to their 3aS enantiomer. C1 Natl Inst Aging Intramural Program, Ctr Gerontol Res, Mol & Cellular Biol Lab, NIH, Baltimore, MD 21224 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), Natl Inst Aging Intramural Program, Ctr Gerontol Res, Mol & Cellular Biol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 23 TC 4 Z9 4 U1 1 U2 3 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PY 1999 VL 9 IS 1 BP 50 EP 60 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 175XL UT WOS:000079121200005 ER PT J AU Zaharevitz, DW Gussio, R Wiegand, A Jalluri, R Pattabiraman, N Kellogg, GE Pallansch, LA Yang, SS Buckheit, RW AF Zaharevitz, DW Gussio, R Wiegand, A Jalluri, R Pattabiraman, N Kellogg, GE Pallansch, LA Yang, SS Buckheit, RW TI Discovery of novel HIV-1 reverse transcriptase inhibitors using a combination of 3D database searching and 3D QSAR SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE INHIBITORS; BINDING-SITE; THERAPY; DESIGN; RESISTANCE; COMPLEXES; HINT AB 3D searches in a database of over 100,000 compounds were followed by evaluations of hits in a 3D QSAR model for the non-nucleoside binding site of HIV-1 reverse transcriptase. The procedure resulted in the identification of a set of novel and structurally diverse inhibitors and required testing of only 225 compounds. C1 NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. Serquest So Res Inst, Infect Dis Res Dept, Frederick, MD 21701 USA. Adv Biomed Comp Ctr, Frederick, MD 21702 USA. Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Sch Pharm, Richmond, VA 23298 USA. RP Zaharevitz, DW (reprint author), NCI, Dev Therapeut Program, Execut Pl N,Room 811,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Kellogg, Glen/A-8008-2011 NR 24 TC 5 Z9 5 U1 0 U2 0 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PY 1999 VL 9 IS 7-8 BP 551 EP 564 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 277CX UT WOS:000084916100009 ER PT S AU Klein, DC AF Klein, DC BE Olcese, J TI Serotonin N-acetyltransferase - A personal historical perspective SO MELATONIN AFTER FOUR DECADES: AN ASSESSMENT OF ITS POTENTIAL SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Hanseatic Endocrine Conference on Melantonin after 4 Decades CY AUG 27-30, 1998 CL HAMBURG, GERMANY SP Deutsch Forsch Gemeinsch, GEFE eV, Deutsch Gesell Endokrinol, IHF, Lundbeck A S, Bristol Myers Squibb, SmithKline Beecham Fdn, Schering AG, Becton Dickinson, Boehringer Mannheim, Buhlmann Labs AG, Genecraft, Sigma Aldrich, Dianova GmbH, IBL GmbH, Stockgrand Ltd, Servier ID HYDROXYINDOLE-O-METHYLTRANSFERASE; MAMMALIAN PINEAL-GLAND; MELATONIN SYNTHESIS; MESSENGER-RNA; CIRCADIAN-RHYTHM; CATALYTIC MECHANISM; EXPRESSION CLONING; DISULFIDE EXCHANGE; PROTEIN THIOL; STIMULATION AB This chapter is written as part of a 40 year celebration of the discovery of melatonin and it seems most appropriate to this invited author to contribute something of a personal historical nature. Accordingly, the subject matter of the chapter is my relationship with serotonin N-acetyltransferase and the people who participated in the major advances in understanding this protein. Readers wanting a detailed up-to-date 1998 accounting of what's known about the enzyme are directed to other publications (1-11); earlier reviews will also be of interest (12-16). C1 NICHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. NR 65 TC 8 Z9 8 U1 0 U2 3 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46134-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 460 BP 5 EP 16 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BQ61T UT WOS:000088969600002 PM 10810495 ER PT S AU Iuvone, PM Chong, NW Bernard, M Brown, AD Thomas, KB Klein, DC AF Iuvone, PM Chong, NW Bernard, M Brown, AD Thomas, KB Klein, DC BE Olcese, J TI Melatonin biosynthesis in chicken retina - Regulation of tryptophan hydroxylase and arylalkylamine N-acetyltransferase SO MELATONIN AFTER FOUR DECADES: AN ASSESSMENT OF ITS POTENTIAL SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Hanseatic Endocrine Conference on Melantonin after 4 Decades CY AUG 27-30, 1998 CL HAMBURG, GERMANY SP Deutsch Forsch Gemeinsch, GEFE eV, Deutsch Gesell Endokrinol, IHF, Lundbeck A S, Bristol Myers Squibb, SmithKline Beecham Fdn, Schering AG, Becton Dickinson, Boehringer Mannheim, Buhlmann Labs AG, Genecraft, Sigma Aldrich, Dianova GmbH, IBL GmbH, Stockgrand Ltd, Servier ID HYDROXYINDOLE-O-METHYLTRANSFERASE; ENDOGENOUS DOPAMINE RELEASE; LIGHT-INDUCED DECREASE; MESSENGER-RNA; CIRCADIAN REGULATION; PINEAL-GLAND; PHOTORECEPTOR METABOLISM; AMPHIBIAN RETINA; XENOPUS-LAEVIS; RABBIT RETINA AB Melatonin is synthesized from the amino acid tryptophan (tryptophan --> 5-hydroxytryptophan --> serotonin --> N-acetylserotonin --> melatonin). In the chick retina, mRNA levels and activities of two enzymes in this pathway, tryptophan hydroxylase (TPH) and arylalkylamine N-acetyltranferase (AA-NAT), display circadian rhythms. The dramatic nocturnal increase in melatonin production in this tissue in part reflects circadian clock-driven increases in mRNA encoding both enzymes. This appears to be translated into increases in both TPH and AA-NAT protein. In the case of AA-NAT, however, this translation is strongly dependent upon environmental lighting. Light acts through post-transcriptional mechanisms to regulate AA-NAT activity; a hypothetical mechanism is proteasomal proteolysis that is otherwise inhibited in the dark by second messengers. Accordingly, melatonin production in the retina, as in the chicken pineal gland, is thought to be regulated by two mechanisms. One is clock-driven changes in TPH and AA-NAT mRNAs, which in turn drive changes in the synthesis of the corresponding encoded proteins. The second is light-induced post-transcriptional degradation of AA-NAT. These mechanisms insure that retinal melatonin production follows a precise schedule that reflects daily changes in the environmental lighting. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. NICHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD USA. RP Iuvone, PM (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. FU NEI NIH HHS [R01-EY04864, R01 EY004864] NR 44 TC 16 Z9 16 U1 0 U2 2 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46134-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 460 BP 31 EP 41 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BQ61T UT WOS:000088969600004 PM 10810497 ER PT J AU Xu, B Perfetti, CA AF Xu, B Perfetti, CA TI Nonstrategic subjective threshold effects in phonemic masking SO MEMORY & COGNITION LA English DT Article ID VISUAL WORD RECOGNITION; INTERACTIVE ACTIVATION MODEL; BACKWARD-MASKING; LETTER PERCEPTION; LEXICAL ACCESS; PHONOLOGY; IDENTIFICATION; PSEUDOHOMOPHONES; ORTHOGRAPHY; REPETITION AB Three backward-masking experiments demonstrated that the magnitude of the phonemic mask reduction effect (MRE) is a function of subjective threshold and that the magnitude is also independent of stimulus-based response strategies. In all three experiments, a target word (e.g., bake) was backward masked by a graphemically similar nonword (e.g., BAWK), a phonemically similar nonword (e.g., BAIK), or an unrelated control (e.g., CRUG). Experiments 1 and 2 had a low percentage (9%) of trials with phonemic masks and differed only in baseline identification rate. Experiment 3 controlled baseline identification rate at below and above subjective threshold levels, with 9% phonemic trials. The results were that identification rates were higher with phonemic masks than with graphemic masks, irrespective of the low percentage of phonemic trials. However, the magnitude of the phonemic MRE became large only when the baseline identification rate was below subjective threshold. The pattern of the phonemic MRE was interpreted as a result of rapid automatic phonological activation, independent of stimulus-based processing strategies. C1 Univ Pittsburgh, Pittsburgh, PA USA. RP Xu, B (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, 5N 250 Bldg 10,Ctr MSC 140, Bethesda, MD 20892 USA. EM benxu@codon.nih.gov NR 39 TC 18 Z9 18 U1 1 U2 1 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0090-502X J9 MEM COGNITION JI Mem. Cogn. PD JAN PY 1999 VL 27 IS 1 BP 26 EP 36 DI 10.3758/BF03201210 PG 11 WC Psychology, Experimental SC Psychology GA 171MZ UT WOS:000078868900003 PM 10087853 ER PT J AU Koch, R de la Cruz, F AF Koch, R de la Cruz, F TI Historical aspects and overview of research on phenylketonuria SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Editorial Material DE phenylalanine; phenylketonuria; phenylalanine hydroxylase; newborn screening ID BRAIN; SPECTROSCOPY; PHENOTYPE; CHILDREN; GENOTYPE C1 Univ So Calif, Sch Med, Los Angeles, CA USA. NICHHD, Mental Retardat & Dev Disabil Branch, Bethesda, MD 20892 USA. RP Koch, R (reprint author), Childrens Hosp Los Angeles, POB 54700, Los Angeles, CA 90054 USA. NR 29 TC 4 Z9 4 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 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 1999 VL 5 IS 2 BP 101 EP 103 DI 10.1002/(SICI)1098-2779(1999)5:2<101::AID-MRDD1>3.0.CO;2-D PG 3 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 200KV UT WOS:000080539800001 ER PT J AU Koch, R Friedman, E Azen, C Hanley, W Levy, H Matalon, R Rouse, B Trefz, F Waisbren, S Michals-Matalon, K Acosta, P Guttler, F Ullrich, K Platt, L de la Cruz, F AF Koch, R Friedman, E Azen, C Hanley, W Levy, H Matalon, R Rouse, B Trefz, F Waisbren, S Michals-Matalon, K Acosta, P Guttler, F Ullrich, K Platt, L de la Cruz, F TI The international collaborative study of maternal phenylketonuria status report 1998 SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE Maternal Phenylketonuria Collaborative Study; phenylketonuria; phenylalanine; congenital heart disease; Wechsler Intelligence Quotient-Revised (WISC-R); Wechsler Adult Intelligence Quotient-Revised; (WAIS-R) ID UNITED-STATES AB The Maternal PKU Study began in 1984 and during the intervening years, 572 pregnancies in women with hyperphenylalaninemia (HPA) and 99 controls and their outcomes have been evaluated. Among Women with HPA who delivered a live infant, only 15.9% were treated and in metabolic control preconceptionally; however, another 18.4% were in control by 10 weeks. Compared to the results reported by Lenke and Levy in 1980, there is a marked improvement in outcome with treatment. Microcephaly was unusual in preconceptionally treated pregnancies with well-controlled phenylalanine-restricted diets. Even in pregnancies that established control after conception but before the 8th week, congenital heart disease did not occur in the offspring; however, it did occur in 12% of pregnancies not achieving control until after 10 weeks of pregnancy. The recommended level of blood phenylalanine during pregnancy is 120-360 mu mol/L. Best results were obtained by dose cooperation between the attending obstetrician and a metabolic team experienced in the care of persons with phenylketonuria. (C) 1999 Wiley-Liss, Inc. C1 Childrens Hosp Los Angeles, Div Med Genet, Los Angeles, CA 90027 USA. Univ So Calif, Dept Pediat, Los Angeles, CA 90027 USA. Hosp Sick Children, PKU Program, Toronto, ON M5G 1X8, Canada. Childrens Hosp & Med Ctr, Boston, MA USA. Univ Texas, Med Branch, Child Dev Div, Galveston, TX 77550 USA. Univ Tubingen, Reutlingen, Germany. Ross Labs, Columbus, OH USA. John F Kennedy Inst, DK-2600 Glostrup, Denmark. Univ Munster, Dept Pediat, D-4400 Munster, Germany. Univ Calif Los Angeles, Med Ctr, Dept Obstet & Gynecol, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA. NICHHD, Bethesda, MD 20892 USA. RP Koch, R (reprint author), Childrens Hosp Los Angeles, Div Med Genet, PKU 73,4650 Sunset Blvd, Los Angeles, CA 90027 USA. NR 9 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 1999 VL 5 IS 2 BP 117 EP 121 PG 5 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 200KV UT WOS:000080539800004 ER PT J AU Mirsky, AF Pascualvaca, DM Duncan, CC French, LM AF Mirsky, AF Pascualvaca, DM Duncan, CC French, LM TI A model of attention and its relation to ADHD SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE attention; ADHD; neuropsychology; learning disorders ID DEFICIT HYPERACTIVITY DISORDER; CONTINUOUS PERFORMANCE-TEST; SUSTAINED ATTENTION; PSYCHIATRIC STATUS; RESEARCH CRITERIA; URBAN CHILDREN; BOYS; ADOLESCENT; IMPULSIVITY; CHILDHOOD AB We present a neuropsychological model of attention in normal and disordered states, including attention deficit hyperactivity disorder (ADHD). The model is based on a factor analysis or: data derived from more than 600 children and adults. The robustness of the model is supported by its replication in a number of studies and its application in numerous investigations. It divides attention into a number of elements or factors including the capacities of encoding, focusing, and executing responses, sustaining attention, shifting attention, as well as a measure of response stability. The factors are assessed by measures derived from neuropsychological tests; we have posited a system of brain structures that maintains the elements of attention, each of which may be supported by a distinct cerebral region. We illustrate the use of the model in an investigation in progress of children referred to an inner-city family clinic for evaluation of ADHD. The ADHD study indicates that a number of aspects of attention are impaired in children diagnosed with ADHD, and that the deficient attention is probably not attributable to learning disorders. We also speculate on the possible role of immaturity of brain development in ADHD. Published 1999 Wiley-Liss, Inc.dagger C1 NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Clin Psychophysiol & Psychopharmacol Lab, Bethesda, MD 20814 USA. RP Mirsky, AF (reprint author), NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, NIH, Bldg 15K,Room 101A,15 N Dr MSC 2668, Bethesda, MD 20892 USA. NR 66 TC 36 Z9 37 U1 4 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 1999 VL 5 IS 3 BP 169 EP 176 DI 10.1002/(SICI)1098-2779(1999)5:3<169::AID-MRDD2>3.0.CO;2-K PG 8 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 229LR UT WOS:000082196500002 ER PT S AU Fukuto, JM Wink, DA AF Fukuto, JM Wink, DA BE Sigel, A Sigel, H TI Nitric oxide (NO): Formation and biological roles in mammalian systems SO METAL IONS IN BIOLOGICAL SYSTEMS, VOL 36: INTERRELATIONS BETWEEN FREE RADICALS AND METAL IONS IN LIFE PROCESSES SE METAL IONS IN BIOLOGICAL SYSTEMS LA English DT Review ID HYDROXY-L-ARGININE; SOLUBLE GUANYLATE-CYCLASE; CENTRAL-NERVOUS-SYSTEM; LONG-TERM POTENTIATION; MITOCHONDRIAL RESPIRATORY-CHAIN; SYNTHASE-CATALYZED CONVERSION; RESONANCE RAMAN-SPECTROSCOPY; SIGNAL-TRANSDUCTION SYSTEM; NEUTRAL AQUEOUS-SOLUTION; LOW-DENSITY-LIPOPROTEIN C1 Univ Calif Los Angeles, Sch Med, Dept Pharmacol, Ctr Hlth Sci, Los Angeles, CA 90095 USA. NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Fukuto, JM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Pharmacol, Ctr Hlth Sci, Los Angeles, CA 90095 USA. NR 213 TC 44 Z9 44 U1 0 U2 1 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0161-5149 BN 0-8247-1956-5 J9 MET IONS BIOL SYST JI Metal Ions Biol. Syst. PY 1999 VL 36 BP 547 EP 595 PG 49 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA BM76L UT WOS:000079715100017 PM 10093936 ER PT J AU Walker, FA Ribeiro, JMC Montfort, WR AF Walker, FA Ribeiro, JMC Montfort, WR TI Novel nitric oxide liberating heme proteins from the saliva of bloodsucking insects SO METAL IONS IN BIOLOGICAL SYSTEMS, VOL 36 SE METAL IONS IN BIOLOGICAL SYSTEMS LA English DT Review ID ELECTRON-PARAMAGNETIC-RESONANCE; IRON-NITROSYL COMPLEXES; FLY LUTZOMYIA-LONGIPALPIS; SOLUBLE GUANYLYL CYCLASE; MACROPHAGE NO SYNTHASE; BUG RHODNIUS-PROLIXUS; BILIN BINDING-PROTEIN; CYTOCHROME-C OXIDASE; SMOOTH-MUSCLE CELLS; AMINO-ACID SEQUENCE C1 Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA. Univ Arizona, Dept Biochem, Tucson, AZ 85721 USA. NIAID, Sect Med Entomol, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Walker, FA (reprint author), Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. RI Walker, Frances/O-4395-2016; OI Ribeiro, Jose/0000-0002-9107-0818 FU NHLBI NIH HHS [HL 54826]; NIAID NIH HHS [AI 18694] NR 232 TC 13 Z9 13 U1 0 U2 4 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0161-5149 J9 MET IONS BIOL SYST PY 1999 VL 36 BP 621 EP 663 PG 43 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA BM76L UT WOS:000079715100019 PM 10093938 ER PT B AU Waalkes, MP Nagamine, T Shimada, H Diwan, BA Coogan, TP Shiraishi, N Cherian, MG Goyer, RA AF Waalkes, MP Nagamine, T Shimada, H Diwan, BA Coogan, TP Shiraishi, N Cherian, MG Goyer, RA BE Klaassen, CD TI Further studies on the role of metallothionein in the antitumor effects of cadmium SO METALLOTHIONEIN IV LA English DT Proceedings Paper CT 4TH International Metallothionein Meeting (MT-97) CY 1997 CL KANSAS CITY, MO SP Monsanto, NIEHS, NCI, Bayer, Coca Cola, Soc Toxicol, Searle, DowElanco, Nickel Producers Environm Res Assoc, Univ Kansas, Med Ctr, Westin Crown Ctr Hotel ID B6C3F1 MOUSE-LIVER; GENE-EXPRESSION; HEPATOTOXICITY; RESISTANCE; LUNG C1 NIEHS, Natl Canc Inst, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, Natl Canc Inst, POB 12233, Res Triangle Pk, NC 27709 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 3-7643-5830-0 PY 1999 BP 569 EP 572 PG 4 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA BP39D UT WOS:000084979200084 ER PT B AU Anderson, LM Sipowicz, MA Yu, W Diwan, BA Birely, L Haines, DC Riggs, CW Kasprzak, KS AF Anderson, LM Sipowicz, MA Yu, W Diwan, BA Birely, L Haines, DC Riggs, CW Kasprzak, KS BE Sarkar, B TI Chromium(III) as male preconception carcinogen in mice SO METALS AND GENETICS LA English DT Proceedings Paper CT 2nd International Symposium on Metals and Genetics CY MAY 26-29, 1998 CL TORONTO, CANADA SP Hosp Sick Children, Toronto, Univ Toronto, Fac Med, Toronto ID CHILDHOOD-CANCER; HEXAVALENT CHROMIUM; OCCUPATIONAL EXPOSURE; PARENTAL OCCUPATION; LIVER TUMORIGENESIS; HYDROGEN-PEROXIDE; TERM EXPOSURE; GERM-CELLS; X-RAYS; RISK C1 NCI, Div Basic Sci, Comparat Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Anderson, LM (reprint author), NCI, Div Basic Sci, Comparat Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46101-3 PY 1999 BP 171 EP 182 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity; Toxicology SC Biochemistry & Molecular Biology; Genetics & Heredity; Toxicology GA BN44E UT WOS:000081933700011 ER PT J AU Lippincott-Schwartz, J Presley, JF Zaal, KJM Hirschberg, K Miller, CD Ellenberg, J AF Lippincott-Schwartz, J Presley, JF Zaal, KJM Hirschberg, K Miller, CD Ellenberg, J TI Monitoring the dynamics and mobility of membrane proteins tagged with green fluorescent protein SO METHODS IN CELL BIOLOGY, VOL 58 SE METHODS IN CELL BIOLOGY LA English DT Review ID LIVING CELLS; FUSION PROTEINS; GFP; VISUALIZATION; EXPRESSION; TRANSPORT; CHIMERAS; MITOSIS C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X NR 26 TC 36 Z9 36 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL ROAD, LONDON, ENGLAND NW1 7DX SN 0091-679X J9 METHOD CELL BIOL PY 1999 VL 58 BP 261 EP 281 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BQ96S UT WOS:000165166500016 PM 9891386 ER PT J AU Johnson, SL Bennett, P AF Johnson, SL Bennett, P TI Growth control in the ontogenetic and regenerating zebrafish fin SO METHODS IN CELL BIOLOGY, VOL 59 SE METHODS IN CELL BIOLOGY LA English DT Review ID LIMB REGENERATION; AXOLOTL; MUTANT; RERIO C1 Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. NICHHD, Mol Genet Lab, Unit Vertebrate Organogenesis, NIH, Bethesda, MD 20892 USA. RP Johnson, SL (reprint author), Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. FU NIGMS NIH HHS [R01 GM56988]; PHS HHS [P01 22486] NR 27 TC 46 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 1999 VL 59 BP 301 EP + PG 14 WC Cell Biology SC Cell Biology GA BQ13J UT WOS:000087259200016 PM 9891366 ER PT J AU Chitnis, AB Dawid, IB AF Chitnis, AB Dawid, IB TI Neurogenesis in zebrafish embryos SO METHODS IN CELL BIOLOGY, VOL 59 SE METHODS IN CELL BIOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD; BRACHYDANIO-RERIO; PRIMARY NEURONS; DANIO-RERIO; IDENTIFIED MOTONEURONS; RETICULOSPINAL NEURONS; HINDBRAIN SEGMENTATION; TRANSGENIC ZEBRAFISH; MUTANT ZEBRAFISH C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Chitnis, AB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 86 TC 10 Z9 10 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 1999 VL 59 BP 367 EP + PG 21 WC Cell Biology SC Cell Biology GA BQ13J UT WOS:000087259200020 PM 9891370 ER PT J AU Galperin, MY Frishman, D AF Galperin, MY Frishman, D TI Towards automated prediction of protein function from microbial genomic sequences SO METHODS IN MICROBIOLOGY, VOL 28 SE METHODS IN MICROBIOLOGY LA English DT Review ID COILED COILS; METHANOCOCCUS-JANNASCHII; MYCOPLASMA-GENITALIUM; SECONDARY STRUCTURE; BACTERIAL GENOMES; RETRIEVAL-SYSTEM; DOMAIN FAMILIES; YEAST GENOME; DATABASE; SEARCH C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Munich Informat Ctr Prot Sequences GSF, D-82152 Martinsried, Germany. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,Room 8N805, Bethesda, MD 20894 USA. OI Galperin, Michael/0000-0002-2265-5572 NR 65 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 USA SN 0580-9517 J9 METHOD MICROBIOL PY 1999 VL 28 BP 245 EP 263 PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA BQ26T UT WOS:000087752200012 ER PT J AU Rosa, P Stevenson, B Tilly, K AF Rosa, P Stevenson, B Tilly, K TI Genetic methods in Borrelia and other spirochaetes SO METHODS MICROBIOLOGY, VOL 29 SE METHODS IN MICROBIOLOGY LA English DT Review ID LYME-DISEASE AGENT; SPIROCHETE TREPONEMA-DENTICOLA; 32-KILOBASE CIRCULAR PLASMIDS; SURFACE PROTEIN-C; SERPULINA-HYODYSENTERIAE; LINEAR-PLASMID; LEPTOSPIRA-INTERROGANS; NUCLEOTIDE-SEQUENCE; ANTIGENIC VARIATION; OSPC GENE C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. RP Rosa, P (reprint author), NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 112 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0580-9517 J9 METHOD MICROBIOL PY 1999 VL 29 BP 209 EP 227 PG 19 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA BN57D UT WOS:000082271400007 ER PT B AU London, J AF London, J TI From dental plaque to oral biofilm: A molecular odyssey SO MICROBIAL ECOLOGY AND INFECTIOUS DISEASE LA English DT Proceedings Paper CT International Meeting on Microbial Ecology and Infectious Disease CY APR, 1998 CL MAALE HACHAMISHA, ISRAEL SP Israel Ctr Emering Dis ID PROLINE-RICH PROTEINS; GINGIVALIS RECOMBINANT FIMBRILLIN; SALIVA-COATED HYDROXYAPATITE; CELL-WALL POLYSACCHARIDES; PORPHYROMONAS-GINGIVALIS; STREPTOCOCCUS-GORDONII; ACTINOMYCES-VISCOSUS; BACTEROIDES-GINGIVALIS; NUCLEOTIDE-SEQUENCE; MONOCLONAL-ANTIBODIES C1 NIDR, NIH, Bethesda, MD 20892 USA. RP NIDR, NIH, Bethesda, MD 20892 USA. NR 93 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 1-55581-148-5 PY 1999 BP 53 EP 65 PG 13 WC Biotechnology & Applied Microbiology; Infectious Diseases SC Biotechnology & Applied Microbiology; Infectious Diseases GA BQ83Q UT WOS:000089740600004 ER PT S AU Hansford, RG Tsuchiya, N Pepe, S AF Hansford, RG Tsuchiya, N Pepe, S BE Brown, GC Nicholls, DG Cooper, CE TI Mitochondria in heart ischaemia and aging SO MITOCHONDRIA AND CELL DEATH SE Biochemical Society Symposia LA English DT Article; Proceedings Paper CT Biochemical-Society Symposium on Mitochondria and Cell Death CY JUL, 1998 CL SHEFFIELD UNIV, SHEFFIELD, ENGLAND SP Biochem Soc HO SHEFFIELD UNIV ID RAT-LIVER MITOCHONDRIA; CYTOCHROME-C; PYRUVATE-DEHYDROGENASE; ELECTRON-TRANSPORT; OXIDATIVE DAMAGE; APOPTOSIS; DNA; ACTIVATION; RELEASE; CALCIUM AB We have examined the effect of dietary polyunsaturated fatty acids (PUFAs) upon mitochondrial Ca2+ content and dehydrogenase activation in the rat heart. Diets were either a conventional low-fat chow (Ref) or were rich in n-3 PUFAs from fish oils (n-3) or n-6 PUFAs from animal fat (n-6). We found that the n-3 diet minimized the rise in mitochondrial Ca2+ seen in response to positive inotropic intervention with noradrenaline, and also minimized the activation of pyruvate dehydrogenase, which is Ca2+ dependent. As the work output of all three groups of hearts was the same, this observation may explain the previous finding of increased thermodynamic efficiency of the n-3 heart relative to the n-6 heart. When hearts were subjected to low-flow ischaemia (15 min), followed by 5 min of reperfusion, increases of mitochondrial Ca2+ were less in the n-3 group than in the n-6 group. In more prolonged ischaemia and reperfusion, n-3 feeding may confer protection against mitochondrial Ca2+ overload, opening of the permeability transition pore and cell death. Notably, the effects of n-3 feeding on mitochondrial functioning were most apparent in hearts from senescent rats (23 months). This is consistent with our finding that the decrease in mitochondrial membrane cardiolipin content, and increase in phosphatidylcholine, which occurred with aging in the Ref and n-6 groups, was totally prevented by n-3 feeding. Thus there are a number of reasons to regard an n-3-rich diet as being protective of the heart in aging mammals. C1 NIA, Genet Mol Lab, Mitochondria & Aging Sect, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. Kitasato Univ Hosp, Dept Cardiol, Sagamihara, Kanagawa 228, Japan. Baker Med Res Inst, Cardiac Surg Res & Transplantat Unit, Melbourne, Vic 3181, Australia. RP Hansford, RG (reprint author), NIA, Genet Mol Lab, Mitochondria & Aging Sect, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 20 Z9 21 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0067-8694 BN 1-85578-125-5 J9 BIOCHEM SOC SYMP JI Biochem. Soc. Symp. PY 1999 VL 66 BP 141 EP 147 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BP10N UT WOS:000084132600013 PM 10989664 ER PT J AU Weil, RJ Wu, YY Vortmeyer, AO Moon, YW Delgado, RM Fuller, BG Lonser, RR Remaley, AT Zhuang, ZP AF Weil, RJ Wu, YY Vortmeyer, AO Moon, YW Delgado, RM Fuller, BG Lonser, RR Remaley, AT Zhuang, ZP TI Telomerase activity in microdissected human gliomas SO MODERN PATHOLOGY LA English DT Article DE astrocytoma; ELISA; glioblastoma multiforme; meningioma; oligodendroglioma; telomere ID IMMORTAL CELLS; CANCER; RNA; EXPRESSION; DNA AB Future improvements in the diagnosis and treatment of human gliomas might rely on obtaining more specific information concerning the biologic characteristics of individual tumor cells. Telomerase, a ribonucleoprotein that synthesizes telomeres, has been reported to be expressed in a majority of human tumors, including several subtypes of brain tumor. We hypothesized that a quantitative assay for telomerase activity, combined with selective microdissection of tumor or normal brain cells, might reveal telomerase gain-of-function to be important in the pathogenesis of gliomas and that telomerase levels might have prognostic significance. We used tissue microdissection for selective analysis of tumor cells obtained from eight patients with glioma, one with a meningioma, and one with a primary B-cell lymphoma of the central nervous system. Normal brain tissue microdissected from another patient was used as a control. Telomerase activity was screened by an electrophoretic method and then assayed by a quantitative ELISA method. All of the eight gliomas had positive telomerase activity, as did the lymphoma The meningioma and normal brain were negative. Quantitative analysis of telomerase activity did not correlate with tumor grade nor predict outcome. Selective tissue microdissection, combined with qualitative and quantitative telomerase assays, permits rapid and reliable detection of telomerase activity in diverse brain tumor tissues. These preliminary findings suggest that telomerase reactivation is a frequent event in glioma tumorigenesis that can be sensitively and specifically detected in gliomas of all histologic grades. Furthermore, specific detection of telomerase reactivation represents another mechanism by which tumor formation and progression might become the target of novel therapeutics. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Clin, Dept Clin Pathol, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, Bethesda, MD USA. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A 33, Bethesda, MD 20892 USA. EM zpzhuang@helix.nih.gov NR 26 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 1999 VL 12 IS 1 BP 41 EP 46 PG 6 WC Pathology SC Pathology GA 159WA UT WOS:000078197200008 PM 9950161 ER PT J AU Lewin-Smith, M Wahl, SM Orenstein, JM AF Lewin-Smith, M Wahl, SM Orenstein, JM TI Human immunodeficiency virus-rich multinucleated giant cells in the colon: A case report with transmission electron microscopy, immunohistochemistry, and in situ hybridization SO MODERN PATHOLOGY LA English DT Article DE colon; HIV; multinucleated giant cells; TEM ID DENDRITIC LANGERHANS CELLS; LYMPHOID-TISSUES; HEMATOPOIETIC PROGENITORS; MACROPHAGES; INFECTION; NASOPHARYNGEAL; REPLICATION; HIV-1; GENERATION; SURFACE AB Multinucleated giant cells (MNGCs) expressing the human immunodeficiency virus (HN) are characteristically found in hyperplastic tonsils and adenoids, acquired immunodeficiency syndrome encephalitis, vacuolar myelopathy, and lymph nodes coinfected with opportunistic pathogens. We identified similar polykaryons in the hyperplastic gut-associated immune system of an HIV-infected patient, Colonic biopsy specimens from this patient with heme-positive stools were studied by light and transmission electron microscopy (TEM), immunohistochemistry, and irt situ hybridization for HIV-specific RNA. No bleeding source was identified by endoscopic or light microscopic examination of the biopsied tissues, There was diffuse and nodular lymphoid hyperplasia with germinal centers. HIV RNA-positive and p24 gag-positive Langhans'-type MNGCs and mononuclear cells (MNCs) were present within the lamina propria, The MNGCs and MNCs were identified as macrophages on the basis of TEM and expression of CD68, HAM56, and lysozyme markers, They also expressed S100 protein, a marker of dendritic/Langerhans' cells, but they lacked Birbeck granules by TEM, In situ hybridization demonstrated RNA expression by MNGCs, MNCs, and follicular dendritic cells. TEM revealed budding and mature HIV particles can the plasma membranes of MNGCs, MNCs, and follicular dendritic cells. We conclude, therefore, that hyperplastic gut-associated immune systems can contain HIV-positive MNGCs and MNCs of the type seen in tonsils and adenoids and opportunistic pathogen-infected lymph nodes. Associated with immune activation, macrophages can express markers of dendritic/Langerhans' cells, cell types derived from the same CD34-positive bone marrow progenitor. C1 George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. NIDR, Immunol Lab, NIH, Bethesda, MD USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Orenstein, JM (reprint author), George Washington Univ, Med Ctr, Dept Pathol, Ross 502,2300 Eye St NW, Washington, DC 20037 USA. FU NIDCR NIH HHS [N01-DE-12585] NR 23 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 1999 VL 12 IS 1 BP 75 EP 81 PG 7 WC Pathology SC Pathology GA 159WA UT WOS:000078197200013 PM 9950166 ER PT J AU Korn, I Gutkind, S Srinivasan, N Blundell, TL Allende, CC Allende, JE AF Korn, I Gutkind, S Srinivasan, N Blundell, TL Allende, CC Allende, JE TI Interactions of protein kinase CK2 subunits SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 2nd International Meeting on a Molecular and Cellular View of Protein Kinase CK2 CY SEP 24-26, 1997 CL VILLARD DE LANS, FRANCE DE protein kinase; CK2; p21; protein phosphatase 2A ID CASEIN KINASE; BETA-SUBUNIT; REGULATORY SUBUNITS; ALPHA-SUBUNIT; STRUCTURE PREDICTION; CELLULAR-REGULATION; SECONDARY STRUCTURE; CATALYTIC ACTIVITY; SIGNALING PATHWAY; CRYSTAL-STRUCTURE AB Several approaches have been used to study the interactions of the subunits of protein kinase CK2. The inactive mutant of CK2 alpha that has Asp 156 mutated to Ala (CK2 alpha A(156)) is able to bind the CK2 beta subunit and to compete effectively in this binding with wild-type subunits alpha and alpha'. The interaction between CK2 alpha A(156) and CK2 beta was also demonstrated by transfection of epitope-tagged cDNA constructs into COS-7 cells. Immunoprecipitation of epitope-tagged CK2 alpha A(156) coprecipitated the beta subunit and vice-versa. The assay of the CK2 activity of the extracts obtained from cells transiently transfected with these different subunits yielded some surprising results: The CK2 specific phosphorylating activity of these cells transfected with the inactive CK2 alpha A(156) was considerably higher than the control cells transfected with vectors alone. Assays of the immunoprecipitated CK2 alpha A(156) expressed in these cells, however, demonstrated that the mutant was indeed inactive. It can be concluded that transfection of the inactive CK2 alpha A(156) affects the endogenous activity of CK2. Transfection experiments with CK2 alpha and beta subunits and CK2 alpha A(156) were also used to confirm the interaction of CK2 with the general CDK inhibitor p21(WAF1/CIP1) co-transfected into these cells. Finally a search in the SwissProt databank for proteins with properties similar to those derived from the amino acid composition of CK2 beta indicated that CK2 beta is related to protein phosphatase 2A and to other phosphatases as well as to a subunit of some ion-transport ATPases. C1 Univ Chile, Programa Biol Celular & Mol, Inst Ciencias Biomed, Fac Med, Santiago 7, Chile. NIDR, Lab Cellular Dev & Oncol, Natl Inst Hlth, Bethesda, MD USA. Univ Cambridge, Dept Biochem, Cambridge, England. RP Allende, JE (reprint author), Univ Chile, Programa Biol Celular & Mol, Inst Ciencias Biomed, Fac Med, Casilla 70086, Santiago 7, Chile. RI Gutkind, J. Silvio/A-1053-2009 FU Wellcome Trust NR 41 TC 10 Z9 11 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 1999 VL 191 IS 1-2 BP 75 EP 83 DI 10.1023/A:1006818513560 PG 9 WC Cell Biology SC Cell Biology GA 172UE UT WOS:000078942600011 PM 10094395 ER PT J AU Cacace, AM Michaud, NR Therrien, M Mathes, K Copeland, T Rubin, GM Morrison, DK AF Cacace, AM Michaud, NR Therrien, M Mathes, K Copeland, T Rubin, GM Morrison, DK TI Identification of constitutive and Ras-inducible phosphorylation sites of KSR: Implications for 14-3-3 binding, mitogen-activated protein kinase binding, and KSR overexpression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MULTIPLE SIGNALING PATHWAYS; MAP KINASE; C-ELEGANS; SUBSTRATE RECOGNITION; TYROSINE KINASE; GENE ENCODES; TRANSDUCTION; DROSOPHILA; DOWNSTREAM; SEQUENCE AB Genetic and biochemical studies have identified kinase suppressor of Ras (KSR) to be a conserved component of Ras-dependent signaling pathways. To better understand the role of KSR in signal transduction, we have initiated studies investigating the effect of phosphorylation and protein interactions on KSR function. Here, we report the identification of five in vivo phosphorylation sites of KSR In serum-starved cells, KSR contains two constitutive sites of phosphorylation (Ser297 and Ser392), which mediate the binding of KSR to the 14-3-3 family of proteins. In the presence of activated Ras, KSR contains three additional sites of phosphorylation (Thr260, Thr274, and Ser443), all of which match the consensus motif (Px[S/T]P) for phosphorylation by mitogen-activated protein kinase (MAPK). Further, we find that treatment of cells with the MEK inhibitor PD98059 blocks phosphorylation of the Ras-inducible sites and that activated MAPK associates with KSR in a Ras-dependent manner. Together, these findings indicate that KSR is an in vivo substrate of MAPK. Mutation of the identified phosphorylation sites did not alter the ability of KSR to facilitate Ras signaling in Xenopus oocytes, suggesting that phosphorylation at these sites may serve other functional roles, such as regulating catalytic activity. Interestingly, during the course of this study, we found that the biological effect of KSR varied dramatically with the level of KSR protein expressed. In Xenopus oocytes, KSR functioned as a positive regulator of Ras signaling when expressed at low levels, whereas at high levels of expression, KSR blocked Ras-dependent signal transduction. Likewise, overexpression of Drosophila KSR blocked R7 photoreceptor formation in the Drosophila eye. Therefore, the biological function of KSR as a positive effector of Ras-dependent signaling appears to be dependent on maintaining KSR protein expression at low or near-physiological levels. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Basis Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Special Program Prot Chem, Frederick, MD 21702 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Howard Hughes Med Inst, Berkeley, CA 94720 USA. RP NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Basis Carcinogenesis Lab, POB B, Frederick, MD 21702 USA. EM morrisod@nciaxp.ncifcrf.gov OI Rubin, Gerald/0000-0001-8762-8703 NR 47 TC 144 Z9 145 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1999 VL 19 IS 1 BP 229 EP 240 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 150DE UT WOS:000077647100022 PM 9858547 ER PT J AU Calvo, S Venepally, P Cheng, J Buonanno, A AF Calvo, S Venepally, P Cheng, J Buonanno, A TI Fiber-type-specific transcription of the troponin I slow gene is regulated by multiple elements SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MUSCLE-SPECIFIC EXPRESSION; ADULT SKELETAL-MUSCLE; TRANSGENIC MICE; HUMAN ALDOLASE; MESSENGER-RNA; M-PROMOTER; MYOD; ENHANCER; PROTEINS; BINDING AB The regulatory elements that restrict transcription of genes encoding contractile proteins specifically to either slow- or fast-twitch skeletal muscles are unknown. As an initial step towards understanding the mechanisms that generate muscle diversity during development, we have identified a 128-bp troponin I slow upstream element (SURE) and a 144-bp troponin I fast intronic element (FIRE) that confer fiber type specificity in transgenic mice (M. Nakayama et al., Mel. Cell. Biol. 16:2408-2417, 1996). SURE and FIRE have maintained the spatial organization of four conserved motifs (3' to 5'): an E box, an AT-rich site (A/T2) that binds MEF-2, a CACC site, and a novel CAGG motif. Troponin I slow (TnIs) constructs harboring mutations in these motifs were analyzed in transiently and stably transfected Sol8 myocytes and in transgenic mice to assess their function. Mutations of the E-box, A/T2, and CAGG motifs completely abolish transcription from the TnI SURE. In contrast, mutation of the CACC motif had no significant effect in transfected myocytes or on the slow-specific transcription of the TnI SURE in transgenic mice. To assess the role of E boxes in fiber type specificity, a chimeric enhancer was constructed in which the E box of SURE was replaced with the E box from FIRE. This TnI E box chimera, which lacks the SURE NFAT site, confers essentially the same levels of transcription in transgenic mice as those conferred by wild-type SURE and is specifically expressed in slow-twitch muscles, indicating that the E box an its own cannot determine the fiber-type-specific expression of the TnI promoter. The importance of the 5' half of SURE, which bears little homology to the TnI FIRE, in muscle-specific expression was analyzed by deletion and linker scanning analyses. Removal of the 5' half of SURE (-846 to -811) results in the loss of expression in stably transfected but not in transiently expressing myocytes. Linker scanning mutations identified sequences in this region that are necessary for the function of SURE when integrated into chromatin. One of these sites (GTTAATCCG), which is highly homologous to a bicoid consensus site, binds to nuclear proteins from several mesodermal cells. These results show that multiple elements are involved in the muscle-specific activity of the TnIs promoter and that interactions between upstream and downstream regions of SURE are important for transcription in the context of native chromatin. C1 NICHHD, Mol Neurobiol Unit, NIH, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NICHHD, Mol Neurobiol Unit, NIH, Bldg 49,Room 5A-38,49 Convent Dr,MSC 4480, Bethesda, MD 20892 USA. NR 62 TC 72 Z9 74 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1999 VL 19 IS 1 BP 515 EP 525 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 150DE UT WOS:000077647100050 PM 9858575 ER PT J AU Dulin, NO Sorokin, A Reed, E Elliott, S Kehrl, JH Dunn, MJ AF Dulin, NO Sorokin, A Reed, E Elliott, S Kehrl, JH Dunn, MJ TI RGS3 inhibits G protein-mediated signaling via translocation to the membrane and binding to G alpha(11) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEINS; GLOMERULAR MESANGIAL CELLS; MAP KINASE ACTIVATION; PHOSPHOLIPASE-C; SACCHAROMYCES-CEREVISIAE; ALPHA-SUBUNITS; GAIP; DESENSITIZATION; EXPRESSION; PHEROMONE AB In the present study, we investigated the function and the mechanism of action of RGS3, a member of a family of proteins called regulators of G protein signaling (RGS). Polyclonal antibodies against RGS3 were produced and characterized. An 80-WDa protein was identified as RGS3 by immunoprecipitation and immunoblotting with anti-RGS3 antibodies in a human mesangial cell line (HMC) stably transfected with RGS3 cDNA. Coimmunoprecipitation experiments in RGS3-overexpressing cell lysates revealed that RGS3 bound to aluminum fluoride-activated G alpha(11) and to a lesser extent to G alpha(i3) and that this binding was mediated by the RGS domain of RGS3. A role of RGS3 in postreceptor signaling was demonstrated by decreased calcium responses and mitogen-activated protein (MAP) kinase activity induced by endothelin-1 in HMC stably overexpressing RGS3. Moreover, depletion of endogenous RGS3 by transfection of antisense RGS3 cDNA in NM 3T3 cells resulted in enhanced MAP kinase activation induced by endothelin-l. The study of intracellular distribution of RGS3 indicated its unique cytosolic localization. Activation of G proteins by AlF4-, NaF, or endothelin-1 resulted in redistribution of RGS3 from cytosol to the plasma membrane as determined by Western blotting of the cytosolic and particulate fractions with RGS3 antiserum as well as by immunofluorescence microscopy. Agonist-induced translocation of RGS3 occurred by a dual mechanism involving both C-terminal (RGS domain) and N-terminal regions of RGS3. Thus, coexpression of RGS3 with a constitutively active mutant of G alpha(11) (G alpha(11)-QL) resulted in the binding of RGS3, but not of its N-terminal fragment, to the membrane fraction and in its interaction with G alpha(11)-QL in vitro without any stimuli. However, both full-length RGS3 and its N-terminal domain translocated to the plasma membrane upon stimulation of intact cells with endothelin-1 as assayed by immunofluorescence microscopy. The effect of endothelin-l was also mimicked by calcium ionophore A23187, suggesting the importance of Ca2+ in the mechanism of redistribution of RGS3. These data indicate that RGS3 inhibits G protein-coupled receptor signaling by a complex mechanism involving its translocation to the membrane in addition to its established function as a GTPase-activating protein. C1 Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Cardiovasc Res Ctr, Milwaukee, WI 53226 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Dunn, MJ (reprint author), Med Coll Wisconsin, Dept Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM mdunn@mcw.edu FU NHLBI NIH HHS [R01 HL022563, HL 22563]; NIDDK NIH HHS [R01 DK041684, DK 41684] NR 37 TC 93 Z9 94 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1999 VL 19 IS 1 BP 714 EP 723 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 150DE UT WOS:000077647100069 PM 9858594 ER PT S AU Barrett, JC Horikawa, I Oshimura, M Kugoh, H Shimizu, M Carman, T Afshari, C AF Barrett, JC Horikawa, I Oshimura, M Kugoh, H Shimizu, M Carman, T Afshari, C BE Bohr, VA Clark, BFC Stevnsner, T TI Genetic basis for replicative cellular senescence of human cells SO MOLECULAR BIOLOGY OF AGING SE ALFRED BENZON SYMPOSIUM SERIES LA English DT Proceedings Paper CT 44th Alfred Benzon Symposium on Molecular Biology of Aging CY JUN 14-18, 1998 CL ROYAL DANISH ACAD SCI & LETTERS, COPENHAGEN, DENMARK SP Royal Danish Acad Sci & Letters HO ROYAL DANISH ACAD SCI & LETTERS ID TELOMERASE CATALYTIC SUBUNIT; IMMORTAL HUMAN FIBROBLASTS; HUMAN-DIPLOID FIBROBLASTS; ONE COMPLEMENTATION GROUP; GROWTH-ARREST; MAMMALIAN TELOMERASE; POSSIBLE INVOLVEMENT; INDEFINITE DIVISION; MULTIPLE PATHWAYS; RNA COMPONENT C1 NIEHS, Mol Carcinogenesis Lab, Environm Carcinogenesis Program, NIH, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, Environm Carcinogenesis Program, NIH, Res Triangle Pk, NC 27709 USA. NR 61 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD PI COPENHAGEN K PA 35 NORRE SOGADE POSTBOX 2148, DK-1016 COPENHAGEN K, DENMARK SN 0105-3639 BN 87-16-12176-7 J9 ALFRED BENZON SYMP S PY 1999 VL 44 BP 45 EP 60 PG 16 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology SC Biochemistry & Molecular Biology; Geriatrics & Gerontology GA BP88U UT WOS:000086496400004 ER PT S AU Bennett, SE Umar, A Kodama, S Barrett, JC Monnat, RJ Kunkel, TA AF Bennett, SE Umar, A Kodama, S Barrett, JC Monnat, RJ Kunkel, TA BE Bohr, VA Clark, BFC Stevnsner, T TI Evidence against a role for the Werner syndrome gene product in DNA mismatch repair SO MOLECULAR BIOLOGY OF AGING SE ALFRED BENZON SYMPOSIUM SERIES LA English DT Proceedings Paper CT 44th Alfred Benzon Symposium on Molecular Biology of Aging CY JUN 14-18, 1998 CL ROYAL DANISH ACAD SCI & LETTERS, COPENHAGEN, DENMARK SP Royal Danish Acad Sci & Letters HO ROYAL DANISH ACAD SCI & LETTERS ID SYNDROME CELL-LINES; MICROSATELLITE INSTABILITY; BLOOMS-SYNDROME; TUMOR-CELLS; HELICASE; MUTATIONS; DEFICIENCY; INTERACTS; HOMOLOG; CANCER C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU MUNKSGAARD PI COPENHAGEN K PA 35 NORRE SOGADE POSTBOX 2148, DK-1016 COPENHAGEN K, DENMARK SN 0105-3639 BN 87-16-12176-7 J9 ALFRED BENZON SYMP S PY 1999 VL 44 BP 214 EP 224 PG 11 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology SC Biochemistry & Molecular Biology; Geriatrics & Gerontology GA BP88U UT WOS:000086496400015 ER PT S AU Kraemer, KH Moriwaki, SI Tarone, RE Khan, SG Grossman, L AF Kraemer, KH Moriwaki, SI Tarone, RE Khan, SG Grossman, L BE Bohr, VA Clark, BFC Stevnsner, T TI DNA repair and aging: studies of xeroderma pigmentosum and normal cells SO MOLECULAR BIOLOGY OF AGING SE ALFRED BENZON SYMPOSIUM SERIES LA English DT Proceedings Paper CT 44th Alfred Benzon Symposium on Molecular Biology of Aging CY JUN 14-18, 1998 CL ROYAL DANISH ACAD SCI & LETTERS, COPENHAGEN, DENMARK SP Royal Danish Acad Sci & Letters HO ROYAL DANISH ACAD SCI & LETTERS ID SHUTTLE VECTOR PLASMID; SKIN-CANCER; MUTATIONS; SUNLIGHT C1 NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Kraemer, KH (reprint author), NCI, Mol Carcinogenesis Lab, Bldg 37, Bethesda, MD 20892 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD PI COPENHAGEN K PA 35 NORRE SOGADE POSTBOX 2148, DK-1016 COPENHAGEN K, DENMARK SN 0105-3639 BN 87-16-12176-7 J9 ALFRED BENZON SYMP S PY 1999 VL 44 BP 256 EP 261 PG 6 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology SC Biochemistry & Molecular Biology; Geriatrics & Gerontology GA BP88U UT WOS:000086496400018 ER PT S AU Bohr, VA Dianov, G Balajee, AS Nehlin, JO Gray, MD Brosh, R Dianova, I Machwe, A Orren, DK AF Bohr, VA Dianov, G Balajee, AS Nehlin, JO Gray, MD Brosh, R Dianova, I Machwe, A Orren, DK BE Bohr, VA Clark, BFC Stevnsner, T TI DNA repair and transcription in human premature aging syndromes SO MOLECULAR BIOLOGY OF AGING SE ALFRED BENZON SYMPOSIUM SERIES LA English DT Proceedings Paper CT 44th Alfred Benzon Symposium on Molecular Biology of Aging CY JUN 14-18, 1998 CL ROYAL DANISH ACAD SCI & LETTERS, COPENHAGEN, DENMARK SP Royal Danish Acad Sci & Letters HO ROYAL DANISH ACAD SCI & LETTERS ID SYNDROME CELL-LINES; RNA-POLYMERASE-II; COCKAYNE-SYNDROME; WERNER-SYNDROME; FINE-STRUCTURE; HUMAN-FIBROBLASTS; ESCHERICHIA-COLI; MISMATCH REPAIR; COUPLED REPAIR; SYNDROME GENE C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Mol Genet Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD PI COPENHAGEN K PA 35 NORRE SOGADE POSTBOX 2148, DK-1016 COPENHAGEN K, DENMARK SN 0105-3639 BN 87-16-12176-7 J9 ALFRED BENZON SYMP S PY 1999 VL 44 BP 262 EP 271 PG 10 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology SC Biochemistry & Molecular Biology; Geriatrics & Gerontology GA BP88U UT WOS:000086496400019 ER PT J AU Bates, S Hickman, ES Vousden, KH AF Bates, S Hickman, ES Vousden, KH TI Reversal of p53-induced cell-cycle arrest SO MOLECULAR CARCINOGENESIS LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; TUMOR-SUPPRESSOR GENE; G(1) ARREST; DNA-DAMAGE; MONOCLONAL-ANTIBODIES; CANCER-CELLS; P53; APOPTOSIS; E2F-1; INDUCTION AB Activation of the tumor suppressor protein p53 can lead to arrest in both G(1) and G(2) stages of the cell cycle and, in some cells, to apoptotic cell death. In this study, we showed that the p53 response to a chemotherapeutic drug, actinomycin D, was reversible in both normal and tumor cells, even when a substantial proportion of tumor cells were undergoing apoptosis. Despite the clear reversibility of the p53-induced cell-cycle arrest after removal of actinomycin D, a substantial proportion of the cells arrested in G(2) failed to resume normal cell-cycle progression and underwent another round of DNA synthesis. This endoreduplication probably reflects a function of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), which is expressed in response to p53. Our observation that this abnormal re-replication of DNA occurred in both transformed and untransformed cells after reversal of a p53 response may have implications for the eventual outcome of tumor therapies in which p53 is transiently expressed in a substantial number of normal as well as tumor cells. Published 1999 Wiley-Liss, Inc. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Bates, S (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Bldg 560,Room 22-96,W 7th St, Frederick, MD 21702 USA. NR 34 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 1999 VL 24 IS 1 BP 7 EP 14 DI 10.1002/(SICI)1098-2744(199901)24:1<7::AID-MC2>3.0.CO;2-5 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 164BF UT WOS:000078441500002 PM 10029405 ER PT J AU Yin, YX Solomon, G Deng, CX Barrett, JC AF Yin, YX Solomon, G Deng, CX Barrett, JC TI Differential regulation of p21 by p53 and Rb in cellular response to oxidative stress SO MOLECULAR CARCINOGENESIS LA English DT Article DE p53; apotosis; p21; Rb; oxidative stress ID WILD-TYPE P53; CYCLIN-DEPENDENT KINASES; TUMOR-SUPPRESSOR P53; DNA-BINDING PROTEIN; P53-DEPENDENT APOPTOSIS; TRANSCRIPTION FACTOR; ANTIOXIDANT PATHWAY; ANTICANCER AGENTS; GENE-EXPRESSION; HUMAN CANCER AB Oxidative stress to mammalian cells causes cellular damage and triggers inducible cellular responses leading to cell death by apoptosis. In this paper, we report that p53 was required for programmed cell death induced by oxidative stress in both mouse and human cells and that p53 transactivation was involved in induction of oxidative cell death. Furthermore, we show that p21 was highly responsive to oxidative stress in a p53-dependent manner and that ectopic expression of p21 could increase cellular susceptibility to oxidative stress in the absence of p53. However, p21 was not required for p53-directed oxidative cell death because mouse embryo fibroblasts MEFs lacking p21(p21(-/-) MEFs) were still susceptible to oxidative cell death. Interestingly, bar, a cell-death mediator regulated by p53, was overexpressed in p21(-/-) MEFs that underwent cell death by oxidative stress, suggesting a compensation for loss of p21 that may be responsible for the existence of cell-death responses in p21-knockout mouse fibroblasts. Finally, we provide evidence that the retinoblastoma gene product (Rb) is a negative regulator of p21 and a repressor of the cellular apoptotic process. Because p21 is regulated by p53 positively and by Rb negatively, p21 may be a link between p53 and Rb in determining cell fate after oxidative damage. (C) 1999 Wiley-Liss, Inc. C1 NIEHS, LMC, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Curriculum Genet & Mol Biol, Chapel Hill, NC USA. NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Yin, YX (reprint author), NIEHS, LMC, NIH, C2-15,Bldg 101,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. RI deng, chuxia/N-6713-2016 NR 69 TC 47 Z9 48 U1 3 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 1999 VL 24 IS 1 BP 15 EP 24 DI 10.1002/(SICI)1098-2744(199901)24:1<15::AID-MC3>3.0.CO;2-Y PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 164BF UT WOS:000078441500003 PM 10029406 ER PT J AU Haag, JD Brasic, GM Shepel, LA Newton, MA Grubbs, CJ Lubet, RA Kelloff, GJ Gould, MN AF Haag, JD Brasic, GM Shepel, LA Newton, MA Grubbs, CJ Lubet, RA Kelloff, GJ Gould, MN TI A comparative analysis of allelic imbalance events in chemically induced rat mammary, colon, and bladder tumors SO MOLECULAR CARCINOGENESIS LA English DT Article DE loss of heterozygosity; microsatellite instability; mutation ID MOUSE SKIN TUMORS; ALLELOTYPE ANALYSIS; SUPPRESSOR GENE; MISMATCH REPAIR; MICROSATELLITE INSTABILITY; INTESTINAL NEOPLASIA; MAJOR MODIFIER; HIGH-FREQUENCY; BREAST-CANCER; B6C3F1 MICE AB In this paper, patterns of allelic imbalances (Als) in chemically induced rat mammary, colon, and bladder tumors from (Wistar Furth x Fischer 344)F-1 rats are described and compared. Male F-1 rats were administered azoxymethane (AOM), and colon tumors were collected at 58 wk after treatment. Female F-1 rats were given either N-nitroso-N-methylurea (NMU) or N-butyl-(hydroxybutyl)-nitrosoamine (BBN), and mammary and bladder tumors were collected at 15 and 52 wk after treatment, respectively. DNA was extracted from a subset of 18 of the largest tumors from each group, and a genome scan was performed by using polymerase chain reaction and 90 polymorphic microsatellite markers. Als, such as loss of heterozygosity, gene duplication, and microsatellite instability, were observed at low frequencies in all of the tumor models. Thirty random Als were observed in the AOM-induced colon tumors but only four in the NMU-induced mammary tumors. In both these models, all the tumors were classified as adenocarcinomas, and most of the Als observed were confined to single tumors with atypical histopathology. In contrast, 27 random Als were identified in the BBN-induced bladder tumors. Als were observed in both transitional-cell carcinomas and papillomas, although most were in the carcinomas. Statistical analysis of the Al data revealed no significant nonrandom Als within or among the tumor models, although several of the infrequently observed Al events identified in the rat tumors may also be observed in the corresponding human tumor type. (C) 1999 Wiley-Liss, Inc. C1 Univ Wisconsin, Dept Oncol, Mcardle Lab Canc Res, Madison, WI 53792 USA. Univ Wisconsin, Dept Human Oncol, Madison, WI 53792 USA. Univ Wisconsin, Dept Biostat, Madison, WI 53792 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NCI, Chemoprevent Invest Studies Branch, Bethesda, MD 20892 USA. RP Haag, JD (reprint author), Univ Wisconsin, Dept Oncol, Mcardle Lab Canc Res, K4-332,600 Highland Ave, Madison, WI 53792 USA. RI Gould, Michael/C-7414-2014 FU NCI NIH HHS [N01-CN-25488-02] NR 52 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 1999 VL 24 IS 1 BP 47 EP 56 DI 10.1002/(SICI)1098-2744(199901)24:1<47::AID-MC7>3.0.CO;2-B PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 164BF UT WOS:000078441500007 PM 10029410 ER PT J AU Isaacs, JS Barrett, JC Weissman, BE AF Isaacs, JS Barrett, JC Weissman, BE TI Interference of proteins involved in the cytoplasmic sequestration of p53 with human papillomavirus EG-mediated degradation SO MOLECULAR CARCINOGENESIS LA English DT Article DE p53; human papillomavirus E6; stability; sequestration; neuroblastoma ID WILD-TYPE P53; TUMOR SUPPRESSOR GENE; CELL-LINE; E6 ONCOPROTEIN; DNA-DAMAGE; TRANSCRIPTIONAL ACTIVATION; NUCLEAR EXCLUSION; TRANSFORMED-CELLS; GROWTH; NEUROBLASTOMA AB The oncogenic human papillomaviruses (HPVs) are able to efficiently target p53 for degradation by the ubiquitin pathway. We previously demonstrated inefficient HPV EG-mediated degradation and resulting high steady-state levels of p53 in cell hybrids between a peripheral neuroepithelioma cell line and a cervical carcinoma cell line (HeLa). We now show that the p53 protein in these cell hybrids was cytoplasmically sequestered and exhibited sporadic punctate staining, which is characteristic of the p53 expression pattern observed in neuroblastic neuroblastoma (NB) cell lines, in which p53 is also sequestered. We hypothesized that the cytoplasmic sequestration of p53 in the cell hybrids might correlate with its inability to be rapidly degraded by I-IPV E6. Using NE cell lines as a model system to test this hypothesis, we demonstrated that the introduction of HPV E6 into two NE cell lines resulted in p53 insensitivity to HPV E6-mediated degradation. This was assessed by both pulse-chase analysis of p53 in metabolically labeled NE cells and western blotting. The enhanced stability of p53 was not due to a lack of HPV E6 expression or to a mutant conformation of the p53 protein. Our results therefore suggest that proteins involved in the cytoplasmic sequestration of p53 may also interfere with the ability of HPV E6 to target p53 for degradation. (C) 1999 Wiley-Liss, Inc. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Isaacs, JS (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Room 345,Bldg 237H, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA 63176] NR 61 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 1999 VL 24 IS 1 BP 70 EP 77 DI 10.1002/(SICI)1098-2744(199901)24:1<70::AID-MC10>3.0.CO;2-5 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 164BF UT WOS:000078441500010 PM 10029413 ER PT J AU Dell'Angelica, EC Shotelersuk, V Aguilar, RC Gahl, WA Bonifacino, JS AF Dell'Angelica, EC Shotelersuk, V Aguilar, RC Gahl, WA Bonifacino, JS TI Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor SO MOLECULAR CELL LA English DT Article ID MEMBRANE-PROTEIN; CYTOPLASMIC TAIL; SORTING SIGNALS; COAT PROTEINS; MEDIUM CHAINS; COMPLEX; TRANSPORT; EXPRESSION; INTERNALIZATION; COMPARTMENTS AB Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defective lysosome-related organelles. Here, we report the identification of two HPS patients with mutations in the P3A subunit of the heterotetrameric AP-3 complex. The patients' fibroblasts exhibit drastically reduced levels of AP-3 due to enhanced degradation of mutant beta 3A. The AP-3 deficiency results in increased surface expression of the lysosomal membrane proteins CD63, lamp-1, and lamp-2, but not of nonlysosomal proteins. These differential effects are consistent with the preferential interaction of the AP-3 mu 3A subunit with tyrosine-based signals involved in lysosomal targeting. Our results suggest that AP-3 functions in protein sorting to lysosomes and provide an example of a human disease in which altered trafficking of integral membrane proteins is due to mutations in a component of the sorting machinery. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 47 TC 437 Z9 445 U1 4 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JAN PY 1999 VL 3 IS 1 BP 11 EP 21 DI 10.1016/S1097-2765(00)80170-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 164AQ UT WOS:000078440100002 PM 10024875 ER PT J AU Hickman, AB Klein, DC Dyda, F AF Hickman, AB Klein, DC Dyda, F TI Melatonin biosynthesis: The structure of serotonin N-acetyltransferase at 2.5 angstrom resolution suggests a catalytic mechanism SO MOLECULAR CELL LA English DT Article ID REFINED CRYSTAL-STRUCTURE; ISOMORPHOUS REPLACEMENT; ANOMALOUS DIFFRACTION; ACETYL-COENZYME; PINEAL-GLAND; PROTEIN; ACID; PROGRAM; BINDING; DOMAIN AB Conversion of serotonin to N-acetylserotonin, the precursor of the circadian neurohormone melatonin, is catalyzed by serotonin N-acetyltransferase (AANAT) in a reaction requiring acetyl coenzyme A (AcCoA). AANAT is a globular protein consisting of an eight-stranded beta sheet flanked by five alpha helices; a conserved motif in the center of the beta sheet forms the cofactor binding site. Three polypeptide loops converge above the AcCoA binding site, creating a hydrophobic funnel leading toward the cofactor and serotonin binding sites in the protein interior. Two conserved histidines not found in other NATs are located at the bottom of the funnel in the active site, suggesting a catalytic mechanism for acetylation involving imidazole groups acting as general acid/base catalysts. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 39 TC 92 Z9 93 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JAN PY 1999 VL 3 IS 1 BP 23 EP 32 DI 10.1016/S1097-2765(00)80171-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 164AQ UT WOS:000078440100003 PM 10024876 ER PT J AU Gu, W Malik, S Ito, M Yuan, CX Fondell, JD Zhang, XL Martinez, E Qin, J Roeder, RG AF Gu, W Malik, S Ito, M Yuan, CX Fondell, JD Zhang, XL Martinez, E Qin, J Roeder, RG TI A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation SO MOLECULAR CELL LA English DT Article ID RNA-POLYMERASE-II; C-TERMINAL DOMAIN; REPEAT DOMAIN; SACCHAROMYCES-CEREVISIAE; ACTIVATION; HOLOENZYME; PROTEIN; YEAST; MUTATIONS; PHOSPHORYLATION AB A novel human complex that can either repress activator-dependent transcription mediated by PC4, or, at limiting TFIIH, act synergistically with PC4 to enhance activator-dependent transcription has been purified. This complex contains homologs of a subset of yeast mediator/holoenzyme components (including SRB7, SRB10, SRB11, MED6, and RGR1), homologs of other yeast transcriptional regulatory factors (SOH1 and NUT2), and, significantly, some components (TRAP220, TRAP170/hRGR1, and TRAP100) of a human thyroid hormone receptor-associated coactivator complex. The complex shows direct activator interactions but, unlike yeast mediator, can act independently of the RNA polymerase II CTD. These findings demonstrate both positive and negative functional capabilities for the human complex, emphasize novel (CTD-independent) regulatory mechanisms, and link the complex to other human coactivator complexes. C1 Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Roeder, RG (reprint author), Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NR 49 TC 214 Z9 227 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JAN PY 1999 VL 3 IS 1 BP 97 EP 108 DI 10.1016/S1097-2765(00)80178-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 164AQ UT WOS:000078440100010 PM 10024883 ER PT J AU Gabrea, A Bergsagel, PL Chesi, M Shou, YP Kuehl, WM AF Gabrea, A Bergsagel, PL Chesi, M Shou, YP Kuehl, WM TI Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell SO MOLECULAR CELL LA English DT Article ID MULTIPLE-MYELOMA; CHROMOSOMAL TRANSLOCATIONS; SEQUENTIAL SWITCH; B-LYMPHOCYTES; REGION; GENES; MAP; EXPRESSION; DOWNSTREAM; LOCUS AB Oncogenes are often dysregulated in B cell tumors as a result of a reciprocal translocation involving an immunoglobulin locus. The translocations are caused by errors in two developmentally regulated DNA recombination processes: V(D)J and IgH switch recombination. Both processes share the property of joining discontinuous sequences from one chromosome and releasing intervening sequences as circles that are lost from progeny cells. Here we show that these intervening sequences may instead insert in the genome and that during productive IgH mu-epsilon switch recombination in U266 myeloma tumor cells, a portion of the excised IgH switch intervening sequences containing the 3' alpha-1 enhancer has inserted on chromosome 11q13, resulting in overexpression of the adjacent cyclin D1 oncogene. C1 NCI, Dept Genet, Med Branch, Bethesda, MD 20889 USA. Cornell Univ, Weill Med Coll, Div Hematol & Oncol, Dept Med, New York, NY 10021 USA. RP Kuehl, WM (reprint author), NCI, Dept Genet, Med Branch, Bethesda, MD 20889 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [CA74265] NR 31 TC 74 Z9 74 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JAN PY 1999 VL 3 IS 1 BP 119 EP 123 DI 10.1016/S1097-2765(00)80180-X PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 164AQ UT WOS:000078440100012 PM 10024885 ER PT J AU Ochel, HJ Schulte, TW Nguyen, P Trepel, J Neckers, L AF Ochel, HJ Schulte, TW Nguyen, P Trepel, J Neckers, L TI The benzoquinone ansamycin geldanamycin stimulates proteolytic degradation of focal adhesion kinase SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE FAK; hsp90; geldanamycin; proteolysis ID PROTEIN-TYROSINE KINASE; ONCOGENIC TRANSFORMATION; HERBIMYCIN-A; IN-VIVO; PHOSPHORYLATION; PP125(FAK); INHIBITION; CELLS; EXPRESSION; DESTABILIZATION AB FAK is a nonreceptor tyrosine kinase involved in adhesion-mediated signal transduction whose level of expression Is related to the invasiveness of malignant tumors, In seeking strategies to downregulate FAK, we treated various cell lines in vitro with the benzoquinone ansamycin geldanamycin (GA) which was previously described as a tyrosine kinase inhibitor, but recently has been shown to exert its effects by interfering with the chaperone function of members of the hsp90 family of heat-shock proteins, We evaluated the effects of benzoquinone ansamycins on FAK steady-state protein level and FAR half-life in breast and prostate carcinoma, Ewing's sarcoma, and 3T3 fibroblasts, Our data demonstrate that GA stimulates the proteolytic degradation of FAK in all cell lines examined and markedly reduces the half-life of newly synthesized FAR protein without significantly altering the level of FAK mRNA. These data demonstrate FAR to be another tyrosine kinase sensitive to the destabilizing effects of benzoquinone ansamycins and further show that small molecule-mediated pharmacologic modulation of FAR protein level is a feasible approach to the interdiction of FAK function. C1 NCI, Med Branch, NIH, Rockville, MD 20850 USA. RP Neckers, L (reprint author), NCI, Med Branch, NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 47 TC 50 Z9 56 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 1999 VL 66 IS 1 BP 24 EP 30 DI 10.1006/mgme.1998.2774 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 168RP UT WOS:000078706700004 PM 9973544 ER PT J AU Wolford, JK Bogardus, C Prochazka, M AF Wolford, JK Bogardus, C Prochazka, M TI Genome-wide scan for CAG/CTG repeat expansions in Pimas with early onset of type 2 diabetes mellitus SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE trinucleotide repeat expansion; type 2 diabetes; Repeat Expansion Detection technique; Pima Indians ID FRIEDREICHS-ATAXIA; INSULIN-RESISTANCE; CTG REPEAT; INDIANS; GENE; HUMANS; NIDDM AB The expansion of polymorphic CAG/CTG repeats in specific genes causes several neurodegenerative disorders and in many instances the length of the disease-causing repeat correlates with the onset age and/or severity of symptoms, Type 2 diabetes mellitus has features in common with diseases resulting from trinucleotide repeat expansion, including a variable age of disease onset and penetrance, We have investigated whether CAG/CTG; repeat expansion contributes to the genetic etiology of type 2 diabetes in the Pima Indians, a population with the highest reported prevalence of this disease. Using the Repeat Expansion Detection (RED) method, we determined the size range in nondiabetic Pimas to be between (CAG)(20) and (CAG)(130) (mean repeat length = 195 bp), which is significantly larger than the mean size reported in Caucasians (150 bp), We compared the distribution of CAG/CTG repeat lengths among 40 Pimas with an early onset of type 2 diabetes (<22 years) and 38 nondiabetic subjects (>55 years). A 240-kp CAG/CTG RED product was found more frequently in early onset diabetics relative to nondiabetic controls (26% vs 11%), whereas a 210-bp band was more prominent in unaffected subjects (29% vs 13%); however, these differences were not statistically significant. In one Pima kindred, we also identified large RED products (greater than or equal to 360 bp) that displayed intergenerational instability among family members. However, these expansions were not associated with diabetes or any other clinical abnormalities in the carriers. We conclude that this unstable CAG/CTG repeat may represent a novel locus, consisting of large, but apparently nonpathogenic, unstable sequences. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Wolford, JK (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 23 TC 2 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 1999 VL 66 IS 1 BP 62 EP 67 DI 10.1006/mgme.1998.2775 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 168RP UT WOS:000078706700009 PM 9973549 ER PT J AU Wu, SM Leschek, EW Brain, C Chan, WY AF Wu, SM Leschek, EW Brain, C Chan, WY TI A novel luteinizing hormone receptor mutation in a patient with familial male-limited precocious puberty: Effect of the size of a critical amino acid on receptor activity SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE activating mutation; luteinizing hormone receptor; precocious puberty ID ACTIVATING MUTATIONS; GENE; HETEROGENEITY AB Familial male-limited precocious puberty (FMPP) is a form of luteinizing hormone-releasing hormone (LHRH)-independent isosexual precocious puberty caused! by gain-of-function mutations of the luteinizing hormone/chorionic gonadotropin receptor (hLHR), The most common mutation is 1733 A>G, which causes substitution of Asp-578 by Gay. In this study, a male infant presented at the age of 20 months with accelerated sexual development was analyzed for the presence of activating mutations of the hLHR. Analysis of exon 11 of the hLHR gene by genomic polymerase chain reaction (PCR), asymmetric PCR, and dideoxy sequencing identified a single base substitution 1734 T>A, which led to the replacement of Asp-578 by Glu. The same mutation was found in the mother. Expression of the mutated hLHR in HEK 293 cells demonstrated elevated basal levels of intracellular cAMP in the transfected cells confirming the constitutive activating nature of the mutated hLHR. A possible genotype-phenotype relationship of the hLHR mutations was examined by a comparison of the in vitro activities of the hLHRs carrying the Asp578Gly, Asp578Tyr, Asp578Trp, and Asp578Glu mutations in HEK 293 cells. A positive correlation between the size of the substituting amino acid and the basal level of intracellular cAMP of cells expressing the mutated receptor was demonstrated, (C) 1999 Academic Press. C1 Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ London St Georges Hosp, London, England. RP Chan, WY (reprint author), Georgetown Univ, Med Ctr, Dept Pediat, 8600 Reservoir Rd NW, Washington, DC 20007 USA. FU NICHD NIH HHS [HD31553] NR 22 TC 18 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 1999 VL 66 IS 1 BP 68 EP 73 DI 10.1006/mgme.1998.2780 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 168RP UT WOS:000078706700010 PM 9973550 ER PT J AU Merlet, F Weinstein, LS Goldsmith, PK Rarick, T Hall, JL Bisson, JP de Mazancourt, P AF Merlet, F Weinstein, LS Goldsmith, PK Rarick, T Hall, JL Bisson, JP de Mazancourt, P TI Identification and localization of G protein subunits in human spermatozoa SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE acrosome; equatorial segment; guanine nucleotide regulatory protein; immunohistochemistry; spermatozoa ID BINDING REGULATORY PROTEIN; SPERM ACROSOMAL EXOCYTOSIS; HETEROTRIMERIC G-PROTEIN; BETA-GAMMA-SUBUNITS; TRIMERIC G-PROTEINS; ZONA-PELLUCIDA; ALPHA-SUBUNITS; ADENYLYL-CYCLASE; PERTUSSIS TOXIN; MAMMALIAN SPERM AB Antibodies to alpha and beta subunits of guanine nucleotide regulatory proteins (G proteins) were used to identify which G proteins are present in mature human spermatozoa and to determine their subcellular localization. Immunoblots of membranes from spermatozoa demonstrate the presence of G alpha(i2), G alpha(i3), G alpha(q/11) and G beta(35) and the absence of G alpha(i1), G alpha(o), G alpha(s), G alpha(12), G alpha(13), G alpha(16), G alpha(z) and G beta(36). Indirect immunofluorescence demonstrates the presence of G alpha(q/11) in the acrosome, with the highest proportion in the equatorial segment. G alpha(i2) is present in the acrosome, midpiece and tailpiece and G alpha(i3) in the postnuclear cap, midpiece and tailpiece. The G beta(35) subunit is found mostly in the midpiece, with marginal labelling of the head, tailpiece and the equatorial segment of the acrosome. The distinct pattern of distribution of G proteins suggests that they may couple to receptors or effecters which also have discrete regions of localization in spermatozoa. These highly localized signal transduction pathways may regulate discrete functions, such as activation of the acrosome reaction, fusion with the oocyte and motility. C1 Hop R Poincare, Fac Med Paris Ouest, Lab Biochim & Biol Mol, F-92380 Garches, France. Hop Poissy, Lab Fecondat In Vitro, Poissy, France. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Ctr Reprod Res & Testing, Rockville, MD USA. Hop R Poincare, Fac Med Paris Ouest, Lab Biochim & Biol Mol, F-92380 Garches, France. RP de Mazancourt, P (reprint author), Hop R Poincare, Fac Med Paris Ouest, Lab Biochim & Biol Mol, F-92380 Garches, France. RI Weinstein, Lee/I-5575-2015; OI Weinstein, Lee/0000-0002-1899-5152 NR 62 TC 27 Z9 27 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD JAN PY 1999 VL 5 IS 1 BP 38 EP 45 DI 10.1093/molehr/5.1.38 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 161QT UT WOS:000078300900008 PM 10050660 ER PT J AU Lee, HS Shu, LM De Pascalis, R Giuliano, M Zhu, MZ Padlan, EA Hand, PH Schlom, J Hong, HJ Kashmiri, SVS AF Lee, HS Shu, LM De Pascalis, R Giuliano, M Zhu, MZ Padlan, EA Hand, PH Schlom, J Hong, HJ Kashmiri, SVS TI Generation and characterization of a novel single-gene-encoded single-chain immunoglobulin molecule with antigen binding activity and effector functions SO MOLECULAR IMMUNOLOGY LA English DT Article DE antitumor antibody; TAG-72 antigen; carcinoma; single gene; single-chain Ig; effector function ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; FUSION PROTEIN; IN-VIVO; B72.3; EXPRESSION; CC49 AB Monoclonal antibody (MAb) CC49 is a murine IgG1 that reacts with tumor-associated glycoprotein (TAG)-72, a pancarcinoma antigen. Clinical trials using radiolabeled CC49 for diagnostic imaging have demonstrated specific localization of more than 90% of carcinomas. The feasibility of adopting in vive gene inoculation methods for antibody-based immunotherapy requires introduction and expression of two genes, encoding immunoglobulin (Ig) heavy and light chains, in a single cell to generate a functional antibody. To circumvent the problems inherent in this approach, we have constructed a single-gene encoding a single-chain immunoglobulin (SCIg) that, unlike previously developed SCIgs, contains all IgG domains. To construct the novel SCIg, the carboxyl end of the constant region of the chimeric (c) CC49 kappa chain is joined, via a 30 residue Gly-Ser linker peptide, to the amino terminus of the CC49 heavy chain. To our knowledge, neither a linker peptide this long nor a linkage between the constant light (C-L) and variable heavy domains has been reported previously. Transfectomas developed by introducing the expression construct of the amplifiable gene in dihydrofolate reductase-deficient Chinese hamster ovary (CHO dhfr(-)) cells secrete a 160 kDa homodimeric molecule, SCIgcCC49. The in vitro antigen binding properties of SCIgcCC49 are comparable to those of cCC49 and SCIgcCC49 Delta C(H)1,a single-chain Ig deficient in constant heavy chain-1 (C(H)1) and C-L domains. The antibody-dependent cellular cytotoxicity (ADCC) of SCIgcCC49 and cCC49 were also comparable. This single-gene approach for generating an immunoglobulin molecule may facilitate in vive gene inoculation as well as ex vive transfection of patients' cultured tumor-infiltrating lymphocytes for immunotherapy protocols for a variety of diseases, including cancer. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. KIST, Korea Res Inst Biosci & Biotechnol, Antibody Engn Res Unit, Taejon 305600, South Korea. RP Kashmiri, SVS (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NR 30 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 1999 VL 36 IS 1 BP 61 EP 71 DI 10.1016/S0161-5890(98)00109-6 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 181TR UT WOS:000079459000007 PM 10369421 ER PT J AU Chernomordik, LV Leikina, E Kozlov, MM Frolov, VA Zimmerberg, J AF Chernomordik, LV Leikina, E Kozlov, MM Frolov, VA Zimmerberg, J TI Structural intermediates in influenza haemagglutinin-mediated fusion SO MOLECULAR MEMBRANE BIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Membrane Fusion - Mechanisms and Applications to Cell Biology, Drug Delivery and Gene Therapy CY JUL 14-18, 1998 CL SALAMANCA, SPAIN SP Int Union Pure & Applied Biophys, British council, Univ Salamanca, Excma, Diputacion Provincial Salamanca, Junta Castilla & Leon, Consejeria Educ & Cultura, DGES, Smithkline-Beecham DE membrane dimple; fusion; hemifusion; haemagglutinin; bending stress ID BIOLOGICAL MEMBRANE-FUSION; CELL-FUSION; CONFORMATIONAL CHANGE; VIRUS HEMAGGLUTININ; HEMIFUSION INTERMEDIATE; PHOSPHOLIPID-BILAYERS; PORE FORMATION; VIRAL FUSION; PH; LYSOPHOSPHATIDYLCHOLINE AB Fusion pore formation in the haemagglutinin (HA)-mediated fusion is a culmination of a multistep process, which involves low-pH triggered refolding of HA and rearrangement of mem brane lipid bilayers. This rearrangement was arrested or slowed down by either altering lipid composition of the membranes, or lowering the density of HA, and/or temperature. The results suggest that fusion starts with the lateral assembly of activated HA into multimeric complexes surrounding future fusion sites, The next fusion stage involves hemifusion, i.e. merger of only contacting membrane monolayers. Lysophosphatidylcholine reversibly arrests fusion prior to this hemifusion stage. In the normal fusion pathway, hemifusion is transient and is not accompanied by any measurable transfer of lipid probes between the membranes. A temperature of 4 degrees C stabilizes this 'restricted hemifusion' intermediate. The restriction of lipid flow through the restricted hemifusion site is HA-dependent and can be released by partial cleaving of low pH-forms of HA with mild proteinase K treatment. Lipid effects indicate that fusion proceeds through two different lipid-involving intermediates, which are characterized by two opposite curvatures of the lipid monolayer, Hemifusion involves formation of a stalk, a local bent connection between the outer membrane monolayers. Fusion pore formation apparently involves bending of the inner membrane monolayers, which come together in hemifusion. To couple low pH-induced refolding of HA with lipid rearrangements, it is proposed that the extension of the alpha-helical coiled coil of HA pulls fusion peptides inserted into the HA-expressing membrane and locally bends the membrane into a saddle-like shape. Elastic energy drives self-assembly of these HA-containing membrane elements into a ring-like complex and causes the bulging of the host membrane into a dimple growing towards the target membrane. Bending stresses in the lipidic top of the dimple facilitate membrane fusion. C1 NICHD, LCMB, NIH, Bethesda, MD USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. Frumkin Inst Electrochem, Moscow, Russia. RP Chernomordik, LV (reprint author), NICHD, LCMB, NIH, Bldg 10,Rm 10D04,10 Ctr Dr, Bethesda, MD USA. OI Frolov, Vadim/0000-0002-0653-5669 NR 55 TC 58 Z9 59 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PD JAN-MAR PY 1999 VL 16 IS 1 BP 33 EP 42 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 186AZ UT WOS:000079705700005 PM 10332735 ER PT J AU Blumenthal, R Morris, SJ AF Blumenthal, R Morris, SJ TI The influenza haemagglutinin-induced fusion cascade: effects of target membrane permeability changes SO MOLECULAR MEMBRANE BIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Membrane Fusion - Mechanisms and Applications to Cell Biology, Drug Delivery and Gene Therapy CY JUL 14-18, 1998 CL SALAMANCA, SPAIN SP Int Union Pure & Applied Biophys, British council, Univ Salamanca, Excma, Diputacion Provincial Salamanca, Junta Castilla & Leon, Consejeria Educ & Cultura, DGES, Smithkline-Beecham DE fusion; membranes; viruses; haemagglutinin; fusion pores ID HEMAGGLUTININ SURFACE-DENSITY; CELL-FUSION; LIPID BILAYERS; FLUORESCENCE; KINETICS; EVENTS; FIBROBLASTS; MICROSCOPY; HEMIFUSION; PH AB To define the stages in influenza haemagglutinin (HA)-mediated fusion the kinetics of fusion between cell pairs consisting of single influenza HA-expressing cells and single erythrocytes (RBC) which had been labelled with both a fluorescent lipid (Dil) in the membrane and a fluorescent solute (calcein) in the aqueous space have been monitored. It is shown that release of solute from the target cell occurs, following the formation of the hemi-fusion diaphragm. These results are discussed in terms of a model in which fusion peptide insertion into the target membrane induces lipid stalks, which results in the formation of a hemifusion diaphragm and a fusion pore. Bilayer expansion due to overproduction of these stalks can give rise to collateral damage of target membranes. C1 NCI, Expt & Computat Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Missouri, Sch Biol Sci, Div Biochem & Mol Biol, Kansas City, MO 64110 USA. RP Blumenthal, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, POB B,Bldg 469,Rm 213, Frederick, MD 21702 USA. NR 23 TC 16 Z9 16 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PD JAN-MAR PY 1999 VL 16 IS 1 BP 43 EP 47 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 186AZ UT WOS:000079705700006 PM 10332736 ER PT J AU Chanturiya, A Whitaker, M Zimmerberg, J AF Chanturiya, A Whitaker, M Zimmerberg, J TI Calcium-induced fusion of sea urchin egg secretory vesicles with planar phospholipid bilayer membranes SO MOLECULAR MEMBRANE BIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Membrane Fusion - Mechanisms and Applications to Cell Biology, Drug Delivery and Gene Therapy CY JUL 14-18, 1998 CL SALAMANCA, SPAIN SP Int Union Pure & Applied Biophys, British council, Univ Salamanca, Excma, Diputacion Provincial Salamanca, Junta Castilla & Leon, Consejeria Educ & Cultura, DGES, Smithkline-Beecham DE exocytosis; calcium; calcium-sensitive dyes; secretion ID PLASMA-MEMBRANE; AMPHOTERICIN-B; EXOCYTOSIS; INVITRO AB The fusion of sea urchin egg secretory vesicles to planar phospholipid bilayer membranes was studied by differential interference contrast (DIC) and fluorescent microscopy, in combination with electrical recordings of membrane conductance. A strong binding of vesicles to protein-free planar membranes was observed in the absence of calcium. Calcium-induced fusion of vesicles was detected using two independent assays: loss of the contents of individual vesicles visible by DIC microscopy; and vesicle content discharge across the planar membrane detected by an increase in the fluorescence of a dye. In both cases, no increase in the membrane conductance was observed unless vesicles were incubated with either Amphotericin B or digitonin prior to applying them to the planar membrane, an indication that native vesicles are devoid of open channels. Pre-incubation of vesicles with n-ethylmaleimide (NEM) abolished calcium-induced fusion, Fusion was also detected when vesicles were osmotically swollen to the point of lysis. In contrast, no fusion of vesicles to planar bilayers was seen when vesicles on plasma membrane (native cortices) were applied to a phospholipid membrane, despite good binding of vesicles to the planar membrane and fusion of vesicles to plasma membrane. It is suggested that cortical vesicles (CVs) have sufficient calcium-sensitive proteins for fusion to lipid membranes, but in native cortices granular fusion sites are oriented toward the plasma membrane. Removal of vesicles from the plasma membrane may allow fusion sites on vesicles access to new membranes. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Univ Newcastle Upon Tyne, Dept Physiol Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov NR 21 TC 11 Z9 11 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PD JAN-MAR PY 1999 VL 16 IS 1 BP 89 EP 94 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 186AZ UT WOS:000079705700012 PM 10332742 ER PT J AU Lewis, DEA Geanacopoulos, M Adhya, S AF Lewis, DEA Geanacopoulos, M Adhya, S TI Role of HU and DNA supercoiling in transcription repression: specialized nucleoprotein repression complex at gal promoters in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID PROTEIN HU; GALACTOSE OPERON; BINDING PROTEINS; MUTATIONS; GYRASE; GENE; REPLICATION; SITE; COUMERMYCIN; SUPPRESSION AB Efficient repression of the two promoters P1 and P2 of the gal operon requires the formation of a DNA loop encompassing the promoters, In vitro, DNA looping-mediated repression involves binding of the Gal repressor (GalR) to two gal operators (O-E and O-I) and binding of the histone-like protein HU to a specific locus (hbs) about the midpoint between O-E and O-I, and supercoiled DNA, Without DNA looping, GalR binding to OE partially represses P1 and stimulates P2, We investigated the requirement for DNA supercoiling and HU in repression of the gal promoters in vivo in strains containing a fusion of a reporter gene, gusA or lacZ, to each promoter individually, While the P1 promoter was found to be repressible in the absence of DNA supercoiling and HU, the repression of P2 was entirely dependent upon DNA supercoiling in vivo. The P2 promoter was fully derepressed when supercoiling was inhibited by the addition of coumermycin in cells, P2, but not P1, was also totally derepressed by the absence of HU or the O-I operator, From these results, we propose that the repression of the gal promoters in vivo is mediated by the formation of a higher order DNA-multiprotein complex containing Gain, HU and supercoiled DNA. In the absence of this complex, P1 but not P2 is still repressed by GalR binding to O-E. The specific nucleoprotein complexes involving histone-like proteins, which repress promoter activity while remaining sensitive to inducing signals, as discussed, may occur more generally in bacterial nucleoids. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 47 TC 60 Z9 61 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 1999 VL 31 IS 2 BP 451 EP 461 DI 10.1046/j.1365-2958.1999.01186.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 164GG UT WOS:000078454400005 PM 10027963 ER PT J AU Leskela, S Wahlstrom, E Hyyrylainen, HL Jacobs, M Palva, A Sarvas, M Kontinen, VP AF Leskela, S Wahlstrom, E Hyyrylainen, HL Jacobs, M Palva, A Sarvas, M Kontinen, VP TI Ecs, an ABC transporter of Bacillus subtilis: dual signal transduction functions affecting expression of secreted proteins as well as their secretion SO MOLECULAR MICROBIOLOGY LA English DT Article ID TEMPORALLY CONTROLLED EXPRESSION; ESCHERICHIA-COLI; OLIGOPEPTIDE PERMEASE; GENE; SPORULATION; COMPETENCE; MEMBRANE; SYSTEM; PROTEOLIPOSOMES; TRANSLOCATION AB ecs is a three-cistron operon of Bacillus subtilis, encoding proteins with similarity to the ATPase (EcsA) and hydrophobic components (EcsB) of ABC transporters. The ecsA26 point mutation was shown to cause a strong processing defect of a secreted a-amylase precursor (preAmyQ) and of three other exoproteins. Northern analysis of the level of amyQ mRNA showed that ecsA26 also decreases amyQ transcription. This effect too was pleiotropic, as judged by a drastic decrease in the expression from an exoprotease promoter of a reporter protein. A knockout mutation of the ecsB cistron caused a processing defect similar to ecsA26 but, unlike ecsA26, did not affect amyQ transcription. There was also no defect in transcription in the ecsA ecsB double mutant, Thus, an intact ecsB product was required for the downregulation of amyQ by the mutant ecsA, These results suggest a dual regulatory function for Ecs, in which Ecs, possibly as part of a signal transduction mechanism, regulates some component(s) of the protein secretion apparatus as well as secretory protein transcription in a co-ordinated fashion. C1 Natl Publ Hlth Inst, Vaccine Dev Lab, FIN-00300 Helsinki, Finland. NIDR, Oral Infect & Immunol Branch, NIH, Bethesda, MD 20892 USA. Agr Res Ctr, Food Res Inst, SF-31600 Jokioinen, Finland. RP Kontinen, VP (reprint author), Natl Publ Hlth Inst, Vaccine Dev Lab, Mannerheimintie 166, FIN-00300 Helsinki, Finland. RI Kontinen, Vesa/A-2260-2012 NR 40 TC 27 Z9 27 U1 3 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 1999 VL 31 IS 2 BP 533 EP 543 DI 10.1046/j.1365-2958.1999.01194.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 164GG UT WOS:000078454400012 PM 10027970 ER PT J AU Webster, MJ Vawter, MP Freed, WJ AF Webster, MJ Vawter, MP Freed, WJ TI Immunohistochemical localization of the cell adhesion molecules Thy-1 and L1 in the human prefrontal cortex: patients with schizophrenia, bipolar disorder, and depression SO MOLECULAR PSYCHIATRY LA English DT Article DE cell adhesion molecule; immunohistochemistry; immunoblot; bipolar disorder; schizophrenia; depression; prefrontal cortex ID N-CAM; HUMAN-BRAIN; POSTNATAL-DEVELOPMENT; IMMUNOHISTOLOGICAL LOCALIZATION; BIOCHEMICAL-CHARACTERIZATION; CORTICAL DEVELOPMENT; ENTORHINAL CORTEX; CEREBELLAR CORTEX; RAT CEREBELLUM; MOUSE AB L1 and Thy-1 are members of the immunoglobulin (Ig) superfamily of cell adhesion molecules (CAMs) that are vital for normal neural development. Abnormalities in CAM expression could lead to the histological abnormalities that have previously been described in the frontal cortex of patients with schizophrenia. A postmortem immunohistochemical study of L1 and Thy-1 in the normal human prefrontal cortex revealed positive immunostaining of axons in all layers of the cortex. Quantifying the intensity of immunostaining in the prefrontal cortex of patients with schizophrenia, bipolar disorder and depression failed to reveal any significant differences when compared to that of normal controls. C1 NIMH, Neurosci Ctr St Elizabeths, Stanley Fdn Res Program, Shanghai 200032, Peoples R China. NIDA, IRP, Baltimore, MD 21224 USA. RP Webster, MJ (reprint author), NIMH, Neurosci Ctr St Elizabeths, Stanley Fdn Res Program, 2700 Martin Luther King Jr Blvd SE, Shanghai 200032, Peoples R China. EM websterm@dirpc.nimh.nih.gov NR 49 TC 7 Z9 7 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 1999 VL 4 IS 1 BP 46 EP 52 DI 10.1038/sj.mp.4000450 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 157ZW UT WOS:000078092400010 PM 10089008 ER PT J AU Moriniere, S Saada, C Holbert, S Sidransky, E Galat, A Ginns, E Rapoport, JL Neri, C AF Moriniere, S Saada, C Holbert, S Sidransky, E Galat, A Ginns, E Rapoport, JL Neri, C TI Detection of polyglutamine expansion in a new acidic protein: a candidate for childhood onset schizophrenia? SO MOLECULAR PSYCHIATRY LA English DT Article DE polyglutamine; schizophrenia; candidate ID BIPOLAR DISORDER; CAG/CTG REPEATS; TRINUCLEOTIDE REPEATS; DISEASE; GENES; ASSOCIATION; CLONING; REVEALS; GENOME; SEARCH AB Polyglutamine expansion (PGE) encoded by a CAG repeat underlies eight inherited neurodegenerative diseases, among which is Huntington's disease. CAG expansion has also been reported in schizophrenia, suggesting a role for PGE. To investigate the potential role of PGE as a candidate for schizophrenia, we searched for PGE in nuclear families comprising a patient affected by childhood onset schizophrenia (COS, a rare and severe form of the disease) as a variation of the candidate gene approach for identifying susceptibility genes. We tested lymphoblastoid cell lines from COS patients (n = 32) by Western blot analysis with 1C2, a monoclonal antibody that specifically recognizes long polyglutamines. Eight of 11 unrelated black American COS patients showed a 60-kDa (approximately) band indicative of PGE. A strong 60-kDa band (suggestive of a large PGE) was detected in two of the eight positive patients. A weaker 60-kDa band (suggestive of a smaller and non pathogenic PGE) was detected in some unaffected parents or sibs of these two COS patients, and in six other black American COS patients. The strong and weak PGE signals were found to correspond to two different proteins. Unrelated black Americans unaffected by COS (n = 38) were negative for the strong 60-kDa PGE signal. Healthy white Americans (n = 53) were negative for both the strong and weak 60-kDa PGE signals. Two-dimensional gel analysis suggested that the strong PGE signal corresponds to an acidic (pl 4 approximately) protein and resulted in a more precise estimation (52-57 kDa) of its relative mass. This protein appeared to be not represented in Genbank, as suggested by the exclusion of several candidate CAG repeats. Our data suggest that this acidic protein might be a candidate for COS. C1 Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France. NIMH, Child Neurogenet Branch, Bethesda, MD 20892 USA. CEA, DIEP, Dept Ingn Prot, Saclay, France. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Neri, C (reprint author), Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, 27 Rue Juliette Dodu, F-75010 Paris, France. RI Neri, Christian/F-6729-2013 NR 23 TC 16 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 1999 VL 4 IS 1 BP 58 EP 63 DI 10.1038/sj.mp.4000448 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 157ZW UT WOS:000078092400012 PM 10089010 ER PT J AU Enoch, MA Goldman, D Barnett, R Sher, L Mazzanti, CM Rosenthal, NE AF Enoch, MA Goldman, D Barnett, R Sher, L Mazzanti, CM Rosenthal, NE TI Association between seasonal affective disorder and the 5-HT2A promoter polymorphism, -1438G/A SO MOLECULAR PSYCHIATRY LA English DT Article DE depression; seasons; receptors; serotonin; promoter regions (genetics); genotype ID AMINO-ACID SUBSTITUTIONS; LIGHT THERAPY; RECEPTOR; SEROTONIN; BEHAVIOR; GENE; FLUOXETINE; MOOD AB Genes involved in serotonin metabolism are good candidates for the pathogenesis of seasonal affective disorder (SAD). A functional variant in the serotonin transporter promoter, 5-HTTLPR, has recently been shown to be associated with SAD and seasonality. The purpose of this study was to determine whether -1438G/A, a polymorphism in the 5-HT2A promoter, is associated with SAD and seasonality, and whether it has additive effects with 5-HTTLPR on seasonality, Sixty-seven individuals with SAD and 69 normal volunteers, all screened with the SCID and diagnosed according to DSM-III-R criteria, were genotyped for the -1438G/A 5-HT2A promoter polymorphism. All had been previously genotyped for 5-HTTLPR and had been assessed for seasonality by the Global Seasonality Scale. There was a significant increase in the frequency of the -1438A variant allele of the 5-HT2A promoter polymorphism in SAD patients (0.47) compared to matched controls (0.36) (P < 0.01), The difference in genotype distribution was also significant (P < 0.05). We found no association between the -1438G/A polymorphism and seasonality scores, and there was no additive effect with 5-HTTLPR on seasonality, In conclusion, we have shown that the -1438G/A 5-HT2A promoter variant is associated with SAD but not with seasonality. We suggest that the association may instead be with the depressive symptoms of SAD, However, these results should be treated with caution until replicated because of the possibility of false-positive findings in case-control association studies. C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Psychobiol Branch, NIH, Bethesda, MD 20892 USA. RP Enoch, MA (reprint author), NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 29 TC 83 Z9 89 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 1999 VL 4 IS 1 BP 89 EP 92 DI 10.1038/sj.mp.4000439 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 157ZW UT WOS:000078092400018 PM 10089016 ER PT J AU Gopalan, G Centanni, JM Moss, S Donovan, PJ AF Gopalan, G Centanni, JM Moss, S Donovan, PJ TI A novel mammalian kinase, T/STK 30, is highly expressed in the germ line SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE serine/threonine kinase; germline; murine; spermatogenesis; oogenesis ID PROTEIN-KINASE; SPERMATOGENIC CELLS; MOUSE TESTIS; MEIOSIS; OOGENESIS; FEMALE; MICE; RNA; MAK; PHOSPHORYLATION AB In order to identify potential regulators of germ cell development in mammals we isolated serine/threonine kinases from adult testis because kinases have been found to play important roles in regulating both mitotic and meiotic cell cycles in a variety of organisms. One of the isolated genes, termed testis-derived serine/threonine kinase 30 (T/ STK 30) revealed homology to the rat male germ cell associated kinase (Mak) and to a key regulator of entry into meiosis, the SME1 kinase from Saccharomyces cerevisiae (S. cerevisiae). T/STK 30 is most abundantly expressed in the testis and ovary and at low levels in the brain, but not in other adult tissues, during embryogenesis or in proliferating somatic cells. T/STK 30 transcripts were not detected in RNA from a sterile Steel (SD mutant testis, further demonstrating that T/STK 30 expression in the testis is limited to germ cells. Analysis of T/STK 30 expression in the developing testis revealed that T/STK 30 transcripts are detected in RNA from testis 17 days postpartum, but not 7 days post partum, suggesting that T/STK30 expression is restricted to meiotic and postmeiotic germ cells. In situ hybridization analysis of T/STK 30 expression in the testis and ovary confirmed that this gene is highly expressed in germ cells. Thus T/STK 30 may be an important regulator of meiosis or postmeiotic differentiation in mammals. Mol. Reprod. Dev. 52:9-2 7, 1999. (C) 1999 Wiley-Liss, Inc. C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. NCI, ABL Basic Res Program, FCRDC, Frederick, MD 21701 USA. Ophidian Pharmaceut, Madison, WI USA. Univ Penn, Med Ctr, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. RP Thomas Jefferson Univ, Kimmel Canc Ctr, 233 S 10th St,706 BLSB, Philadelphia, PA 19107 USA. NR 36 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1040-452X EI 1098-2795 J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JAN PY 1999 VL 52 IS 1 BP 9 EP 17 DI 10.1002/(SICI)1098-2795(199901)52:1<9::AID-MRD2>3.0.CO;2-O PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 141NC UT WOS:000077149200002 ER PT J AU Gopalan, G Centanni, J Gilbert, DJ Copeland, NG Jenkins, NA Donovan, PJ AF Gopalan, G Centanni, J Gilbert, DJ Copeland, NG Jenkins, NA Donovan, PJ TI Novel mammalian kinase related to yeast and fly chromosome segregation regulators is exclusively expressed in the germline SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE serine/threonine kinase; meiosis; oogenesis; spermatogenesis; germline; murine ID MATURATION-PROMOTING FACTOR; TYPE-1 PROTEIN PHOSPHATASE; CYCLE-DEPENDENT EXPRESSION; MURINE CYCLIN; MOUSE; MEIOSIS; GENE; DROSOPHILA; AURORA; IPL1 AB Since kinases play important roles in regulating both mitotic and meiotic cell cycles in a variety of organisms, we sought to clone novel kinases that might regulate germ cell development in mammals. One of the kinases we identified, termed IAK3, is a member of a newly emerging subfamily of the serine/threonine kinase superfamily and mapped to mouse Chromosome 7. This kinase is related to genes identified in yeast and Drosophila which are regulators of chromosome segregation and to another mammalian kinase, IAK1, which is a new component of the centrosome and mitotic spindle. IAK3 transcripts are uniquely expressed in germ cells and are undetectable in proliferating somatic cells. Thus IAK3 may be a regulator of microtubule dynamics and/or chromosome segregation in the germline. Mol. Reprod. Dev. 52:18-28, 1999. (C) 1999 Wiley-Liss, Inc. C1 NCI, Mammalian Genet Lab, ABL Basic Res Program, FCRDC, Frederick, MD 21701 USA. RP Donovan, PJ (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, BLSB 706,233 S 10th St, Philadelphia, PA 19107 USA. EM pdonovan@lac.jci.tju.edu NR 41 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JAN PY 1999 VL 52 IS 1 BP 18 EP 28 DI 10.1002/(SICI)1098-2795(199901)52:1<18::AID-MRD3>3.0.CO;2-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 141NC UT WOS:000077149200003 ER PT S AU Drake, JW AF Drake, JW BE Caporale, LH TI The distribution of rates of spontaneous mutation over viruses, prokaryotes, and eukaryotes SO MOLECULAR STRATEGIES IN BIOLOGICAL EVOLUTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular Strategies in Biological Evolution CY JUN 27-29, 1998 CL NEW YORK, NEW YORK SP NY Acad Sci ID ESCHERICHIA-COLI; FREQUENCIES; SELECTION; EVOLUTION; STRAINS AB Although mutation has chaotic aspects, spontaneous mutation rates assume certain characteristic values when expressed per genome per genome duplication. The rate among lytic RNA viruses is roughly 1, while the rate among retroelements is roughly 0.2. The rate among viral and cellular microbes with DNA chromosomes is close to 0.0034. Mutation rates among higher eukaryotes, estimated from specific-locus studies, vary greatly. Most of this variation can be suppressed if the rates are expressed per cell division instead of per sexual generation, and if the genome size is taken to be only a little larger than the sum of the protein encoding sequences; then, the mutation rate is roughly 0.01. The reasons for different characteristic mutation rates among different organism groups remain mysterious and pose a substantial challenge to students of evolution. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 19 TC 110 Z9 113 U1 0 U2 12 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-192-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 870 BP 100 EP 107 DI 10.1111/j.1749-6632.1999.tb08870.x PG 8 WC Genetics & Heredity; Multidisciplinary Sciences SC Genetics & Heredity; Science & Technology - Other Topics GA BN31U UT WOS:000081585400011 PM 10415476 ER PT S AU Gotoh, H Zhu, DH Eddy, EM AF Gotoh, H Zhu, DH Eddy, EM BE Caporale, LH TI Protein binding to meiotic recombination hotspots in mouse testis SO MOLECULAR STRATEGIES IN BIOLOGICAL EVOLUTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular Strategies in Biological Evolution CY JUN 27-29, 1998 CL NEW YORK, NEW YORK SP NY Acad Sci ID SEQUENCE; GENE; P53 C1 Natl Inst Anim Hlth, Dept Immunol, Lab Mol Pathol, Tsukuba, Ibaraki 3050856, Japan. NIEHS, LRDT, Gamete Biol Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Gotoh, H (reprint author), Natl Inst Anim Hlth, Dept Immunol, Lab Mol Pathol, 3-1-1 Kannondai, Tsukuba, Ibaraki 3050856, Japan. NR 8 TC 3 Z9 3 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 1-57331-192-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 870 BP 351 EP 353 DI 10.1111/j.1749-6632.1999.tb08901.x PG 3 WC Genetics & Heredity; Multidisciplinary Sciences SC Genetics & Heredity; Science & Technology - Other Topics GA BN31U UT WOS:000081585400042 PM 10415496 ER PT S AU Holbeck, SL Strathern, EN AF Holbeck, SL Strathern, EN BE Caporale, LH TI EXO1 of Saccharomyces cerevisiae functions in mutagenesis during double-strand break repair SO MOLECULAR STRATEGIES IN BIOLOGICAL EVOLUTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular Strategies in Biological Evolution CY JUN 27-29, 1998 CL NEW YORK, NEW YORK SP NY Acad Sci ID RECOMBINATION; EXONUCLEASE; YEAST C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Strathern, EN (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, POB B,Bldg 539, Frederick, MD 21702 USA. NR 7 TC 7 Z9 7 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-192-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 870 BP 375 EP 377 DI 10.1111/j.1749-6632.1999.tb08906.x PG 3 WC Genetics & Heredity; Multidisciplinary Sciences SC Genetics & Heredity; Science & Technology - Other Topics GA BN31U UT WOS:000081585400047 PM 10415501 ER PT J AU Leopold, NA Bara-Jimenez, W Hallett, M AF Leopold, NA Bara-Jimenez, W Hallett, M TI Parkinsonism after a wasp sting SO MOVEMENT DISORDERS LA English DT Article DE hymenoptera; wasp; parkinsonism; extrapyramidal syndromes ID MULTIPLE-SCLEROSIS; NERVOUS-SYSTEM; NECROSIS; ALLERGY; DYSTONIA; VENOM; CELLS; BEE AB A 49-year-old man bad mild parkinsonism after being stung by a wasp, a member of the Hymenoptera order. His clinical course was stable for 6 months after which his condition rapidly progressed to a severe akinetic-rigid syndrome with evidence, on a magnetic resonance imaging brain scan, of marked destruction of the basal ganglia. The symptoms did not respond to standard antiparkinsonian medications. Repeated courses of plasmapheresis followed by monthly intravenous infusions of immunoglobulin and long-term administration of azathioprine halted and appeared to partially reverse his deterioration. The literature on the neurologic, particularly the extrapyramidal, manifestations of stings by insects of the Hymenoptera order is reviewed and the possible pathophysiological mechanisms of injury are discussed. Hymenoptera stings should be included in thr differential diagnosis of acute and chronic extrapyramidal syndromes. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Crozer Chester Med Ctr, Dept Med, Div Neurol, Upland, PA USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC-1428, Bethesda, MD 20892 USA. NR 32 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 1999 VL 14 IS 1 BP 122 EP 127 DI 10.1002/1531-8257(199901)14:1<122::AID-MDS1020>3.3.CO;2-J PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 243LN UT WOS:000082999200019 PM 9918354 ER PT J AU Pharr, V Litvan, I Brat, DJ Troncoso, J Reich, SG Stark, M AF Pharr, V Litvan, I Brat, DJ Troncoso, J Reich, SG Stark, M TI Ideomotor apraxia in progressive supranuclear palsy: A case study SO MOVEMENT DISORDERS LA English DT Article ID RICHARDSON-OLSZEWSKI SYNDROME; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; CEREBRAL-CORTEX; CRITERIA; TANGLES; PATTERN C1 NINDS, Cognit Neurosci Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. HM Jackson Fdn, Dev & Vet Head Injury Program, Bethesda, MD USA. Johns Hopkins Hosp, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Hosp, Dept Pathol, Baltimore, MD 21287 USA. RP Litvan, I (reprint author), Fed Bldg,Rm 714, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445 FU NIA NIH HHS [AG05146] NR 29 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 1999 VL 14 IS 1 BP 162 EP 166 DI 10.1002/1531-8257(199901)14:1<162::AID-MDS1031>3.0.CO;2-C PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 243LN UT WOS:000082999200030 PM 9918365 ER PT J AU Muller, FMC Lyman, CA Walsh, TJ AF Muller, FMC Lyman, CA Walsh, TJ TI Antimicrobial peptides as potential new antifungals SO MYCOSES LA English DT Article; Proceedings Paper CT 5th Congress of the European-Confederation-of-Medical-History/ 33th Scientific Meeting of the Deutschsprachige-Mykologische-Gesellschaft-EV CY JUN 03-06, 1999 CL DRESDEN, GERMANY SP European Confederat Med Mycol, Deutschsprachige Mykol Gesell EV, Saxon State Minist Social Hlth & Family Affairs DE peptides; antimicrobial activity; antifungal activity; synthetic derivatives; host defense ID PERMEABILITY-INCREASING PROTEIN; LACTOFERRIN-RELATED COMPOUNDS; CANDIDA-ALBICANS; CATIONIC PEPTIDES; HOST-DEFENSE; FUNGICIDAL PROPERTIES; FROG-SKIN; IN-VITRO; ANTIBIOTICS; INVITRO AB Ribosomally synthesized natural antimicrobial peptides (AP) and their synthetic derivatives are small, cationic, amphipathic molecules of 12-50 amino acids with unusually broad activity spectra. These peptides kill microorganisms by a common mechanism, which involves binding to the lipid bilayer of biological membranes, forming pores, and ultimately followed by cell lysis. Several AP from mammals, amphibians, insects, plants and their synthetic derivatives demonstrate promising in vitro activity against various pathogenic fungi including azole-resistant Candida albicans strains. In addition to their antimicrobial activity, some AP such as lactoferrin, interact with a variety of host cells and can increase the activity of natural killer and lymphokine activated killer cells. Pretreatment of polymorphonuclear neutrophil leukocytes (PMN) or monocytes with these AP also may upregulate superoxide release. AP as potential new antifungal agents offer some advantages, such as rapid killing of pathogenic fungi and the difficulty to raise mutants resistant to these peptides. AP are limited by their nonselective toxicity stability, immunogenicity and their costs of production. Potential clinical applications of AP in the future have to be further explored in preclinical and clinical studies to assess their impact as a new class of antifungals. C1 Univ Wurzburg, Inst Mol Infekt Biol, D-97070 Wurzburg, Germany. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Muller, FMC (reprint author), Univ Wurzburg, Inst Mol Infekt Biol, Rontgenring 11, D-97070 Wurzburg, Germany. NR 55 TC 9 Z9 10 U1 0 U2 7 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0933-7407 J9 MYCOSES JI Mycoses PY 1999 VL 42 SU 2 BP 77 EP 82 PG 6 WC Dermatology; Mycology SC Dermatology; Mycology GA 311YK UT WOS:000086914100017 PM 10865909 ER PT S AU Bonelli, L Camoriano, A Ravelli, P Missale, G Bruzzi, P Aste, H AF Bonelli, L Camoriano, A Ravelli, P Missale, G Bruzzi, P Aste, H BE Kumpulainen, JT Salonen, JT TI Reduction of the incidence of metachronous adenomas of the large bowel by means of antioxidants: A double blind randomized trial SO NATURAL ANTIOXIDANTS AND ANTICARCINOGENS IN NUTRITION, HEALTH AND DISEASE SE ROYAL SOCIETY OF CHEMISTRY SPECIAL PUBLICATIONS LA English DT Proceedings Paper CT 2nd International Conference on Natural Antioxidants and Anticarcinogens in Nutrition, Health and Disease CY JUN 24-27, 1998 CL HELSINKI, FINLAND ID COLORECTAL ADENOMAS; COLON-CANCER; ALPHA-TOCOPHEROL; DIETARY FACTORS; ASCORBIC-ACID; VITAMIN-E; SELENIUM; RISK; POLYPS; CHEMOPREVENTION C1 Natl Canc Inst, Unit Clin Epidemiol & Trial, Genoa, Italy. RP Bonelli, L (reprint author), Natl Canc Inst, Unit Clin Epidemiol & Trial, Genoa, Italy. NR 28 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 0260-6291 BN 0-85404-793-X J9 ROY SOC CH PY 1999 IS 240 BP 451 EP 455 DI 10.1533/9781845698409.7.451 PG 5 WC Medicine, General & Internal; Nutrition & Dietetics SC General & Internal Medicine; Nutrition & Dietetics GA BP13T UT WOS:000084220100080 ER PT J AU Beutler, JA McCall, KL Boyd, MR AF Beutler, JA McCall, KL Boyd, MR TI A novel geranylflavone from Macaranga schweinfurthii SO NATURAL PRODUCT LETTERS LA English DT Article DE flavone; Macaranga; isomacarangin AB Isomacarangin was isolated from Macaranga schweinfurthii (Euphorbiaceae) and characterized as 8-geranyl-kaempferol by spectroscopic methods. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 3 TC 9 Z9 11 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1057-5634 J9 NAT PROD LETT JI Nat. Prod. Lett. PY 1999 VL 13 IS 1 BP 29 EP 32 DI 10.1080/10575639908048487 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 181XX UT WOS:000079469700006 ER PT J AU Collins, FS AF Collins, FS TI Microarrays and macroconsequences SO NATURE GENETICS LA English DT Editorial Material C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bldg 31,Room 4B-09,31 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 38 Z9 38 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1999 VL 21 SU S BP 2 EP 2 DI 10.1038/4425 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 156NU UT WOS:000078008200002 ER PT J AU Duggan, DJ Bittner, M Chen, YD Meltzer, P Trent, JM AF Duggan, DJ Bittner, M Chen, YD Meltzer, P Trent, JM TI Expression profiling using cDNA microarrays SO NATURE GENETICS LA English DT Review ID GENE-EXPRESSION; HUMAN GENOME; SEQUENCE TAGS; HYBRIDIZATION; PATTERNS; SCALE; RNAS AB cDNA microarrays are capable of profiling gene expression patterns of tens of thousands of genes in a single experiment. DNA targets, in the form of 3' expressed sequence tags (ESTs), are arrayed onto glass slides (or membranes) and probed with fluorescent- or radioactively-labelled cDNAs. Here,we review technical aspects of cDNA microarrays, including the general principles, fabrication of the arrays, target labelling, image analysis and data extraction, management and mining. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Duggan, DJ (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 33 TC 1149 Z9 1223 U1 11 U2 103 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1999 VL 21 SU S BP 10 EP 14 DI 10.1038/4434 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 156NU UT WOS:000078008200005 PM 9915494 ER PT J AU Cole, KA Krizman, DB Emmert-Buck, MR AF Cole, KA Krizman, DB Emmert-Buck, MR TI The genetics of cancer - a 3D model SO NATURE GENETICS LA English DT Review ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; LASER CAPTURE MICRODISSECTION; ALLELIC LOSS; INVASIVE ADENOCARCINOMA; EXPRESSION PATTERNS; CHROMOSOME 8P12-21; PROGRESSION; CELLS; CDNA; MICROARRAY AB Gene expression microarrays hold great promise for studies of human disease states. There are significant technical issues specific to utilizing clinical tissue samples which have yet to be rigorously addressed and completely overcome. Precise, quantitative measurement of gene expression profiles:from specific cell populations is at hand, offering the scientific community the first comprehensive View of the in vivo molecular anatomy of normal cells and their diseased counterparts. Here. we propose a model-for integrating-in three dimensions-expression data obtained using the microarray. C1 NCI, Pathol Lab, Pathogenet Unit, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. NCI, Canc Genome Anat Project, Off Director, Bethesda, MD 20892 USA. RP Cole, KA (reprint author), NCI, Pathol Lab, Pathogenet Unit, Bldg 10, Bethesda, MD 20892 USA. EM mbuck@helix.nih.gov RI Cole, Kristina/M-3922-2015 NR 47 TC 107 Z9 108 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1999 VL 21 SU S BP 38 EP 41 DI 10.1038/4466 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 156NU UT WOS:000078008200010 PM 9915499 ER PT J AU Hacia, JG AF Hacia, JG TI Resequencing and mutational analysis using oligonucleotide microarrays SO NATURE GENETICS LA English DT Review ID DNA ANALYSIS; ARRAYS; HYBRIDIZATION; SEQUENCE; POLYMORPHISMS; DIAGNOSTICS; MICROCHIPS AB Oligonucleotide microarray (DNA chip)-based hybridization analysis is a promising new technology which potentially allows rapid and cost-effective screens for all possible mutations and sequence variations in genomic DNA. Here, I review current strategies and uses for DNA chip-based resequencing and mutational analysis, the underlying principles of experimental designs, and future efforts to improve the sensitivity and specificity of chip-based assays. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Hacia, JG (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bldg 49-3A14, Bethesda, MD 20892 USA. EM jhacia@nhgri.nih.gov NR 55 TC 374 Z9 400 U1 1 U2 19 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1999 VL 21 SU S BP 42 EP 47 DI 10.1038/4469 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 156NU UT WOS:000078008200011 PM 9915500 ER PT J AU Bassett, DE Eisen, MB Boguski, MS AF Bassett, DE Eisen, MB Boguski, MS TI Gene expression informatics - it's all in your mine SO NATURE GENETICS LA English DT Review ID DATABASE; HYBRIDIZATION; ARRAYS AB Technologies for whole-genome RNA expression studies are becoming increasingly reliable and accessible. However, universal standards to make the data more suitable for comparative analysis and for inter-operability with other information resources have yet to emerge. Improved access to large electronic data sets, reliable and consistent annotation and effective tools for 'data mining' are critical. Analysis methods that exploit large data warehouses of gene expression experiments will be necessary to realize the full potential of this technology. C1 Rosetta Inpharmat, Kirkland, WA 98034, Australia. Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Bassett, DE (reprint author), Rosetta Inpharmat, Kirkland, WA 98034, Australia. OI Eisen, Michael/0000-0002-7528-738X NR 37 TC 269 Z9 280 U1 3 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1999 VL 21 SU S BP 51 EP 55 DI 10.1038/4478 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 156NU UT WOS:000078008200013 PM 9915502 ER PT J AU Battey, J Jordan, E Cox, D Dove, W AF Battey, J Jordan, E Cox, D Dove, W TI An action plan for mouse genomics SO NATURE GENETICS LA English DT Editorial Material AB The mouse has become the leading animal model for studying biological processes in mammals. Creation of additional genomic and genetic resources will make the mouse an even more useful model for the research community. On the basis of recommendations from the scientific community, the National Institutes of Health (NIH) plans to support grants to generate a 'working draft' sequence of the mouse genome by 2003, systematic mutagenesis and phenotyping centres, repositories for mouse strain maintenance, distribution and cryopreservation and training fellowships in mouse pathobiology. C1 Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Univ Wisconsin, Sch Med, Mcardle Lab Canc Res, Madison, WI 53706 USA. RP Battey, J (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH Bldg 31,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 69 Z9 69 U1 1 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1999 VL 21 IS 1 BP 73 EP 75 DI 10.1038/5012 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 155RT UT WOS:000077960700012 PM 9916794 ER PT J AU Karet, FE Finberg, KE Nelson, RD Nayir, A Mocan, H Sanjad, SA Rodriguez-Soriano, J Santos, F Cremers, CWRJ Di Pietro, A Hoffbrand, BI Winiarski, J Bakkaloglu, A Ozen, S Dusunsel, R Goodyer, P Hulton, SA Wu, DK Skvorak, AB Morton, CC Cunningham, MJ Jha, V Lifton, RP AF Karet, FE Finberg, KE Nelson, RD Nayir, A Mocan, H Sanjad, SA Rodriguez-Soriano, J Santos, F Cremers, CWRJ Di Pietro, A Hoffbrand, BI Winiarski, J Bakkaloglu, A Ozen, S Dusunsel, R Goodyer, P Hulton, SA Wu, DK Skvorak, AB Morton, CC Cunningham, MJ Jha, V Lifton, RP TI Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness SO NATURE GENETICS LA English DT Article ID DIFFERENTIAL EXPRESSION; INNER-EAR; HETEROGENEITY; ASSOCIATION; EXCHANGER; CHILDREN; ISOFORM; CELLS; DNA AB H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease. C1 Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Med, New Haven, CT 06510 USA. Univ Utah, Hlth Sci Ctr, Dept Pediat, Salt Lake City, UT USA. Univ Istanbul, Dept Pediat Nephrol, Istanbul, Turkey. Karadeniz Tekn Univ, Dept Pediat Nephrol, Trabzon, Turkey. King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh 11211, Saudi Arabia. Hosp Cruces, Dept Pediat, Bilbao, Spain. Univ Oviedo, Div Pediat Nephrol, Oviedo, Spain. Acad Ziekenhuis, Dept Otorhinolaryngol, Nijmegen, Netherlands. Serv Osped Rilievo Nazl, Serv Nefrol Pediat, Naples, Italy. Whittington Hosp, Dept Nephrol, London N19 5NF, England. Karolinska Inst, Dept Pediat, Huddinge, Sweden. Hacettepe Univ, Dept Pediat Nephrol, Ankara, Turkey. Erciyes Univ, Dept Pediat Nephrol, Kayseri, Turkey. Montreal Childrens Hosp, Div Pediat Nephrol, Montreal, PQ H3H 1P3, Canada. Childrens Hosp, Dept Nephrol, Birmingham B16 8ET, W Midlands, England. Natl Inst Deafness & Other Commun Disorders, Rockville, MD USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Postgrad Inst Med Educ & Res, Dept Nephrol, Chandigarh 160012, India. RP Lifton, RP (reprint author), Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, 295 Congress Ave, New Haven, CT 06510 USA. EM richard.lifton@yale.edu RI Cremers, C.W.R.J./L-4254-2015 FU NIDCD NIH HHS [DCO3402]; Wellcome Trust NR 41 TC 410 Z9 429 U1 0 U2 10 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1999 VL 21 IS 1 BP 84 EP 90 DI 10.1038/5022 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 155RT UT WOS:000077960700014 PM 9916796 ER PT J AU Petralia, RS Esteban, JA Wang, YX Partridge, JG Zhao, HM Wenthold, RJ Malinow, R AF Petralia, RS Esteban, JA Wang, YX Partridge, JG Zhao, HM Wenthold, RJ Malinow, R TI Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses SO NATURE NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; GLUTAMATE RECEPTORS; HIPPOCAMPAL SLICES; RAT-BRAIN; NEURONS; SUBUNITS; LIGHT; LTP; LOCALIZATION; EXPRESSION AB Early in postnatal development, glutamatergic synapses transmit primarily through NMDA receptors. As development progresses, synapses acquire AMPA receptor function. The molecular basis of these physiological observations is not known. Here we examined single excitatory synapses with immunogold electron-microscopic analysis of AMPA and NMDA receptors along with electrophysiological measurements. Early in postnatal development, a significant fraction of excitatory synapses had NMDA receptors and lacked AMPA receptors. As development progressed, synapses acquired AMPA receptors with little change in NMDA receptor number. Thus, synapses with NMDA receptors but no AMPA receptors can account for the electrophysiologically observed 'silent synapse'. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. RP Malinow, R (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. RI Esteban, Jose/L-4944-2014 OI Esteban, Jose/0000-0002-3759-3300 NR 32 TC 352 Z9 364 U1 1 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 1999 VL 2 IS 1 BP 31 EP 36 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 163MK UT WOS:000078409300010 PM 10195177 ER PT J AU Chirgadze, DY Hepple, JP Zhou, HJ Byrd, RA Blundell, TL Gherardi, E AF Chirgadze, DY Hepple, JP Zhou, HJ Byrd, RA Blundell, TL Gherardi, E TI Crystal structure of the NK1 fragment of HGF/SF suggests a novel mode for growth factor dimerization and receptor binding SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID FACTOR SCATTER FACTOR; C-MET RECEPTOR; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; DOMAIN; IDENTIFICATION; PROTEIN; ANTAGONIST; ACTIVATION; RESOLUTION AB Although ligand-induced receptor dimerization is a common prerequisite for receptor activation, the mode by which different growth factors bind their receptors and cause them to dimerize varies considerably. Here we report the crystal structure at 2.5 Angstrom resolution of NK1, a receptor-binding fragment and a natural splice variant of hepatocyte growth factor/scatter factor (HGF/SF). NK1 assembles as a homodimer in the asymmetric unit, revealing a novel mode of growth factor dimerization produced by close packing of the N domain of one subunit and the kringle domain of the other, thus bringing the two linkers in dose proximity. The structure suggests the presence of a binding site for heparan sulfate chains and a mechanism by which the NK1 dimer may engage two receptor molecules through clusters of amino acids located on each protomer and on opposite surfaces of the homodimer. We also report that short (14-mer) heparin fragments effectively dimerize NK1 in solution, implying that heparan sulfate chains may stabilize the NK1 dimer, These results provide a basis for the agonistic activity of NK1 and have implications for the mechanism of receptor binding of HCF/SF. C1 Univ Cambridge, Ctr Mrc, Growth Factors Grp, Cambridge CB2 2QH, England. Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Gherardi, E (reprint author), Univ Cambridge, Ctr Mrc, Growth Factors Grp, Hills Rd, Cambridge CB2 2QH, England. RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 FU Wellcome Trust NR 52 TC 89 Z9 91 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JAN PY 1999 VL 6 IS 1 BP 72 EP 79 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 153FA UT WOS:000077821000017 PM 9886295 ER PT J AU Beer, B Kurth, R Bukreyev, A AF Beer, B Kurth, R Bukreyev, A TI Characteristics of filoviridae: Marburg and Ebola viruses SO NATURWISSENSCHAFTEN LA English DT Review ID HEMORRHAGIC-FEVER; GUINEA-PIGS; EXPERIMENTAL-INFECTION; NUCLEOPROTEIN GENE; SEQUENCE-ANALYSIS; RHESUS-MONKEYS; MESSENGER-RNA; DISEASE; GLYCOPROTEIN; PROTEINS AB Filoviruses are enveloped, nonsegmented negative-stranded RNA viruses. The two species, Marburg and Ebola virus, are serologically, biochemically, and genetically distinct. Marburg virus was first isolated during an outbreak in Europe in 1967, and Ebola virus emerged in 1976 as the causative agent of two simultaneous outbreaks in southern Sudan and northern Zaire. Although the main route of infection is known to be person-to-person transmission by intimate contact, the natural reservoir for filoviruses still remains a mystery. C1 Paul Ehrlich Inst, D-63225 Langen, Germany. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Kurth, R (reprint author), Paul Ehrlich Inst, Paul Ehrlich Str 51-59, D-63225 Langen, Germany. NR 91 TC 24 Z9 27 U1 2 U2 37 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1042 EI 1432-1904 J9 NATURWISSENSCHAFTEN JI Naturwissenschaften PD JAN PY 1999 VL 86 IS 1 BP 8 EP 17 DI 10.1007/s001140050562 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 161DR UT WOS:000078273800002 PM 10024977 ER PT J AU Kumaravel, TS Lohani, A Mambo, E Evans, MK AF Kumaravel, TS Lohani, A Mambo, E Evans, MK TI The adaptive response in the scid mouse model: Is DNA-PKCS required? SO NEOPLASMA LA English DT Article; Proceedings Paper CT 1999 Comet Assay Workshop CY MAY 29-JUN 02, 1999 CL SMOLENICE, SLOVAKIA DE adaptive response; severe combined immunodeficient mouse; DNA-PKcs; comet assay; gamma irradiation; apoptosis ID DEPENDENT PROTEIN-KINASE; STRAND BREAK REPAIR; HUMAN-LYMPHOCYTES; IONIZING-RADIATION; X-RAYS; RADIOADAPTIVE RESPONSE; ATAXIA-TELANGIECTASIA; CATALYTIC SUBUNIT; EXCISION-REPAIR; DAMAGE AB We examined the role of DNA-PKcs in the adaptive response using the severe combined immunodeficient (SCID) mouse model that lacks functionally active DNA-PKcs molecules. We used DNA repair as measured by single cell gel electrophoresis (Comet Assay) and apoptosis as endpoints to evaluate the adaptive response in two SCID cell lines. Additionally, we have examined the expression of the base excision repair (BER) enzyme AP endonuclease (APE) and the expression of NER related proteins p21, GADD45 and ERCC3 in an attempt to identify the induction of BER or NER pathways in adapted and non-adapted cells. Our data suggests that the adaptive response is present in SCID cells, implying that DNA-PKcs is not required for the adaptive response. In SCID as well as in normal fibroblasts, the expression of APE was markedly increased and prolonged in the adapted cells. This suggests that low priming doses of ionizing radiation may accentuate the BER pathway induced by the subsequent high dose and confer a survival advantage measured by lower percentages of apoptosis and more efficient repair of DNA damage. The presence of the adaptive response in radiation-sensitive SCID cells known to be defective in double strand break repair and nucleotide excision repair may be related to an intact and inducible base excision repair mechanism. C1 NIA, Genet Mol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Kumaravel, TS (reprint author), NIA, Genet Mol Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 30 TC 0 Z9 1 U1 0 U2 0 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57 NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0028-2685 J9 NEOPLASMA JI Neoplasma PY 1999 VL 46 SU S BP 34 EP 37 PG 4 WC Oncology SC Oncology GA 306DG UT WOS:000086580800017 ER PT J AU Arah, IH Dixon, SC Horti, J Figg, WD AF Arah, IH Dixon, SC Horti, J Figg, WD TI Enhanced activity of estramustine, vinblastine, etoposide, and suramin in prostate carcinoma SO NEOPLASMA LA English DT Article DE hormone refractory prostate cancer; prostate specific antigen; chemotherapy ID PHASE-II TRIAL; CONTINUOUS-INFUSION; ORAL ETOPOSIDE; CELL-LINE; NITROGEN-MUSTARD; GROWTH-FACTOR; CANCER CELLS; LNCAP MODEL; ANTIGEN; CHEMOTHERAPY AB Following hormonal therapy, few treatment regimens have activity in metastatic prostate cancer. Cytotoxic agents have minimal activity in this disease. However, combinations of cytotoxic agents may be beneficial. The activity of estramustine, vinblastine, etoposide, and suramin on cell growth was evaluated. Prostate specific antigen (PSA) is routinely used as it surrogate marker for disease progression. Many pharmacological agents alter PSA levels independently of their effect on tumor growth, the effect of these agents on PSA secretion was determined. Each agent was evaluated alone and in combination with the other drugs in two prostate cancer cell lines. In LNCaP cells, estramustine and suramin were cytostatic, while vinblastine and etoposide were cytotoxic. Estramustine down-regulated etoposide PSA secretion, while suramin had no effect. The effects of etoposide and vinblastine on PSA secretion were not evaluable. In PC-3 cells, only etoposide was cytotoxic. Tandem combinations were more cytotoxic than single agents in both cell lines. The addition of a third agent to the tandem combination produced less cytotoxicity. In our hands, the best combinations were estramustine/vinblastine, suramin/vinblastine, and suramin/etoposide. These combinations yielded 20-60% higher cytotoxicity than any of the drugs alone. C1 NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD 20892 USA. RP Horti, J (reprint author), NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 58 TC 2 Z9 2 U1 0 U2 0 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57 NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0028-2685 J9 NEOPLASMA JI Neoplasma PY 1999 VL 46 IS 2 BP 117 EP 123 PG 7 WC Oncology SC Oncology GA 211QR UT WOS:000081172600008 PM 10466436 ER PT J AU Bartosova, Z Horak, ID Pirsel, M Bohr, VA AF Bartosova, Z Horak, ID Pirsel, M Bohr, VA TI Lack of correlation between repair of DNA interstrand cross-links and differential sensitivity of G(0) and proliferating CD4(+) lymphocytes towards cisplatin SO NEOPLASMA LA English DT Article DE cisplatin; interstrand cross-link; gene-specific DNA repair; G(0) and proliferating lymphocytes ID PERIPHERAL-BLOOD LYMPHOCYTES; NUCLEOTIDE EXCISION-REPAIR; TUMOR-CELL LINE; DRUG ACCUMULATION; DAMAGED DNA; GENE; INDUCTION; EXPRESSION; ADDUCTS; CIS-DIAMMINEDICHLOROPLATINUM(II) AB G(0) cells in a tumor are insensitive to the chemotherapeutical agents. The nature of this resistance is nor completely understood. One of the factors modulating sensitivity of cells may he DNA repair of drug induced DNA damage. In this study we have compared gene-specific formation and repair of cisplatin-induced interstrand cross-links (ICL) in human Go and proliferating CD4(+) lymphocytes. Cisplatin killing of G(0)CD(4+) lymphocytes is inefficient, and these cells resemble those in a tumor. After exposure to cisplatin under similar conditions, the frequency of ICL introduced is twice as high in the proliferating compared to the resting lymphocytes. Repair of ICL was measured in the housekeeping gene, dihydrofolate reductase (DHFR), in the proliferation inducible c-myc gene, and in the inactive delta-globin gene. We observed similar relative rates and extent of ICL repair in all three genes studied, in G(0) or proliferating CD4+ lymphocytes. The mechanisms responsible for the resistance of G(0) CD4+ lymphocytes towards cisplatin are discussed. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Slovak Acad Sci, Inst Canc Res, Bratislava 83391, Slovakia. RP Bartosova, Z (reprint author), NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RI Pirsel, Miroslav/A-9996-2008 NR 49 TC 1 Z9 1 U1 0 U2 0 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57 NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0028-2685 J9 NEOPLASMA JI Neoplasma PY 1999 VL 46 IS 6 BP 342 EP 348 PG 7 WC Oncology SC Oncology GA 283XM UT WOS:000085301400003 PM 10732862 ER PT J AU Richmond, BJ Oram, MW Wiener, MC AF Richmond, BJ Oram, MW Wiener, MC TI Response features determining spike times SO NEURAL PLASTICITY LA English DT Article ID SPATIOTEMPORAL FIRING PATTERNS; PRECISELY REPLICATING PATTERNS; CAT VISUAL-CORTEX; SINGLE NEURONS; CORTICAL-NEURONS; BEHAVING MONKEY; FRONTAL-CORTEX; VARIABILITY; DEPENDENCE; TRAINS AB Interpreting messages encoded in single neuronal responses requires knowing which features of the responses carry information. That the number of spikes is an important part of the code has long been obvious. In recent years, it has been shown that modulation of the firing rate with about 25 ms precision carries information that is not available from the total number of spikes across the whole response. It has been proposed that patterns of exactly timed (1 ms precision) spikes, such as repeating triplets or quadruplets, might carry information that is not available from knowing about spike count and rate modulation. A model using the spike count distribution, the low-pass filtered PSTH (bandwidth below 30 Hz), and, to a small degree, the interspike interval distribution predicts the numbers and types of exactly-timed triplets and quadruplets that are indistinguishable from those found in the data. From this it can be concluded that the coarse (<30 Hz) sequential correlation structure over time gives rise to the exactly timed patterns present in the recorded spike trains. Because the coarse temporal structure predicts the fine temporal structure, the information carried by the fine temporal structure must be completely redundant with that carried by the coarse structure. Thus, the existence of precisely timed spike patterns carrying stimulus-related information does not imply control of spike timing at precise time scales. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA. RI Oram, Michael/A-2558-2010 NR 40 TC 12 Z9 12 U1 0 U2 0 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0792-8483 J9 NEURAL PLAST JI Neural. Plast. PY 1999 VL 6 IS 4 BP 133 EP 145 DI 10.1155/NP.1999.133 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 260BN UT WOS:000083928600006 PM 10714266 ER PT J AU Hengemihle, JM Long, JM Betkey, J Jucker, M Ingram, DK AF Hengemihle, JM Long, JM Betkey, J Jucker, M Ingram, DK TI Age-related psychomotor and spatial learning deficits in 129/SvJ mice SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; animal behavior; eye pathology; genetics; maze learning; transgenic mice ID INBRED MOUSE STRAINS; PRECURSOR PROTEIN GENE; WATER MAZE PERFORMANCE; TRAIT LOCI ANALYSES; BEHAVIORAL PHENOTYPES; LOCOMOTOR-ACTIVITY; MOTOR-PERFORMANCE; SINGLE-GENE; F1 HYBRIDS; SUBSTRAINS AB The 129 mouse strain has been widely used to construct mutations that model behavioral aging in humans. The current study found significant age-related declines in both psychomotor and swim maze performance of 5-, 17-, and 27-month-old 129/SvJ mice. However, the age differences in swim maze acquisition were inconsistent with poor performance in the probe trial which assesses spatial memory. This inconsistency may result from the high degree of genetic polymorphisms and age-related Visual pathology which afflicts this mouse strain. Therefore, we concluded that 129/SvJ mice present a problematic model of mammalian cognitive aging and involve a risk for behavioral contamination in studies involving mutant mice derived from this strain. (C) 1999 Elsevier Science Inc. All rights reserved. C1 NIA, Cellular & Mol Biol Lab, Mol Physiol & Genet Sect, Intramural Res Program,Gerontol Res Ctr, Baltimore, MD 21224 USA. Denison Univ, Granville, OH 43023 USA. Univ Basel, Inst Pathol, Dept Neuropathol, CH-4003 Basel, Switzerland. RP Ingram, DK (reprint author), NIA, Cellular & Mol Biol Lab, Mol Physiol & Genet Sect, Intramural Res Program,Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 31 TC 17 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN-FEB PY 1999 VL 20 IS 1 BP 9 EP 18 DI 10.1016/S0197-4580(99)00016-0 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 226AQ UT WOS:000081998500002 PM 10466889 ER PT J AU Long, JM Kalehua, AD Muth, NJ Calhoun, ME Jucker, M Hengemihle, JM Ingram, DL Mouton, PR AF Long, JM Kalehua, AD Muth, NJ Calhoun, ME Jucker, M Hengemihle, JM Ingram, DL Mouton, PR TI Stereological analysis and microglia in aging mouse hippocampus (vol 19, pg 497, 1998) SO NEUROBIOLOGY OF AGING LA English DT Correction C1 NIA, Mol Physiol & Genet Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Essex Community Coll, Dept Psychol, Baltimore, MD 21237 USA. Univ Basel, Inst Pathol, Dept Neuropathol, CH-4003 Basel, Switzerland. Johns Hopkins Sch Med, Dept Pathol & Neuropathol Lab, Baltimore, MD 21205 USA. RP Long, JM (reprint author), NIA, Mol Physiol & Genet Sect, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN-FEB PY 1999 VL 20 IS 1 BP 91 EP 91 DI 10.1016/S0197-4580(99)00034-2 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 226AQ UT WOS:000081998500014 ER PT J AU Dimitrov, M Phipps, M Zahn, TP Grafman, J AF Dimitrov, M Phipps, M Zahn, TP Grafman, J TI A thoroughly modern gage SO NEUROCASE LA English DT Article DE orbitofrontal; ventromedial frontal; social cognition ID FRONTAL-LOBE DAMAGE; PREFRONTAL CORTEX; BRAIN; PATIENT; LESIONS; EMPATHY; CONSEQUENCES; ADULTS; INJURY AB We describe a 50-year-old male patient (MGS) with a right frontal ventromedial lesion who showed preserved general cognitive, abstract thinking and problem-solving abilities, in contrast to gross impairment in his social competence, social decision making and social conduct. MGS also demonstrated diminished sensitivity to socially relevant stimuli and situational nuances, impairment in sexual behavior, lost sense of responsibility, and disinhibition. We interpret his neurobehavioral profile, identical to the one of the famous 19th century patient Phineas Gage, in the light of the hypothesis that emotion and social conduct regulation depend on the ventromedial frontal cortex. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM jgr@box-j.nih.gov OI Phipps, Michael/0000-0001-8398-5404; Grafman, Jordan H./0000-0001-8645-4457 NR 56 TC 47 Z9 47 U1 7 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PY 1999 VL 5 IS 4 BP 345 EP 354 DI 10.1080/13554799908411987 PG 10 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 232XQ UT WOS:000082395600008 ER PT J AU Kawamura, M Schwartz, JP Nomura, T Kopin, IJ Goldstein, DS Huynh, TT Hooper, DR Harvey-White, J Eisenhofer, G AF Kawamura, M Schwartz, JP Nomura, T Kopin, IJ Goldstein, DS Huynh, TT Hooper, DR Harvey-White, J Eisenhofer, G TI Differential effects of chemical sympathectomy on expression and activity of tyrosine hydroxylase and levels of catecholamines and DOPA in peripheral tissues of rats SO NEUROCHEMICAL RESEARCH LA English DT Article DE tyrosine hydroxylase; sympathetic nervous system; 6-hydroxydopamine; norepinephrine; dopamine; mRNA ID PANCREAS; SYSTEM; CELLS AB Tyrosine hydroxylase (TH) mRNA and activity and concentrations of 3,4-dihydroxyphenylalanine (DOPA) and catecholamines were examined as markers of sympathetic innervation and catecholamine synthesis in peripheral tissues of sympathectomized and intact rats. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA) markedly decreased norepinephrine and to a generally lesser extent TH activities and dopamine in most peripheral tissues (stomach, lung, testis, duodenum, pancreas, salivary gland, spleen, heart, kidney, thymus). Superior cervical ganglia, adrenals and descending aorta were unaffected and vas deferens showed a large 92% decrease in norepinephrine, but only a small 38% decrease in TH activity after 6-OHDA. Presence of chromaffin cells or neuronal cell bodies in these latter tissues, indicated by consistent expression of TH mRNA, explained the relative resistance of these tissues to 6-OHDA. Stomach also showed consistent expression of TH mRNA before, but not after 6-OHDA, suggesting that catecholamine synthesizing cells in gastric tissue are sensitive to the toxic effects of 6-OHDA. Tissue concentrations of DOPA were mainly unaffected by 6-OHDA, indicating that much of the DOPA in peripheral tissues is synthesized independently of local TH or sympathetic innervation. The differential effects of chemical sympathectomy on tissue catecholamines, DOPA, TH mRNA and TH activity demonstrate that these variables are not simple markers of sympathetic innervation or catecholamine synthesis. Other factors, including presence of neuronal cell bodies, parenchymal chromaffin cells, non-neuronal sites of catecholamine synthesis and alternative sources of tissue DOPA, must also be considered when tissue catecholamines, DOPA and TH are examined as markers of sympathetic innervation and local catecholamine synthesis. C1 NINCDS, NIH, Clin Neurosci Branch, Bethesda, MD 20892 USA. Nippon Zoki Pharmaceut Co, Inst Bioact Sci, Kobe, Hyogo 67314, Japan. RP Eisenhofer, G (reprint author), NINCDS, NIH, Clin Neurosci Branch, Bldg 10,Room 4D20,10 Ctr Dr,MSC 1424, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov NR 25 TC 18 Z9 18 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JAN PY 1999 VL 24 IS 1 BP 25 EP 32 DI 10.1023/A:1020919828028 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 161EA UT WOS:000078274700004 PM 9973233 ER PT S AU Elenkov, IJ Webster, EL Torpy, DJ Chrousos, GP AF Elenkov, IJ Webster, EL Torpy, DJ Chrousos, GP BE Cutolo, M Masi, AT Bijlsma, JWJ Chikanza, IC Bradlow, HL Castagnetta, L TI Stress, corticotropin-releasing hormone, glucocorticoids, and the immune/inflammatory response: Acute and chronic effects SO NEUROENDOCRINE IMMUNE BASIS OF THE RHEUMATIC DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Conference on the Neuroendocrine Immune Basis of the Rheumatic Diseases CY SEP 18-20, 1998 CL GENOA, ITALY SP Italian Soc Rheumatol, European Neuroendocrine assoc, Univ Genova, Dept Internal Med, Sch Med, Novartis Farma, Hoffmann la Roche, Basel, Roche, Milan, Searle Monsanto Italiana, Boehringer Ingelheim, Procter & Gamble Pharmaceut, Bayers, Minist Univ Ricerca Sci Tecnologica, Italy ID BLOOD MONONUCLEAR-CELLS; FACTOR-RECEPTOR SUBTYPE; RAT-BRAIN; IN-VITRO; FUNCTIONAL EXPRESSION; NERVOUS-SYSTEM; MOUSE SPLEEN; FACTOR CRF; IDENTIFICATION; PITUITARY AB Corticotropin-releasing hormone (CRH) influences the immune system indirectly, through activation of the hypothalamic-pituitary-adrenal axis and sympathetic system, and directly through local modulatory actions of peripheral (immune) CRH. We recently demonstrated that catecholamines and histamine potently inhibited interleukin (IL)-12 and stimulated IL-10, whereas glococorticoids suppressed IL-12, but did not affect IL-10 production ex vivo, Thus, both glucocorticoids and catecholamines, the end products of the stress system, and histamine, a product of activated mast cells, may selectively suppress cellular immunity and favor humoral immune responses. We localized immunoreactive CRH in experimental carrageenin-induced aseptic inflammation and, in humans, in inflamed tissues from patients,vith several autoimmune diseases, In addition, we demonstrated that CRH activated mast cells via a CRH receptor type 1-dependent mechanism, leading to release of histamine and hence vasodilatation and increased vascular permeability. Thus, activation of the stress system, through direct and indirect effects of CRH, may influence the susceptibility of an individual to certain autoimmune, allergic, infectious or neoplastic diseases, Antalarmin, a novel nonpeptide CRH antagonist, prevented several proinflammatory effects of CRH, thus revealing its therapeutic potential in some forms of inflammation. C1 NICHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 59 TC 138 Z9 148 U1 0 U2 16 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-215-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 876 BP 1 EP 13 DI 10.1111/j.1749-6632.1999.tb07618.x PG 13 WC Endocrinology & Metabolism; Immunology; Multidisciplinary Sciences; Neurosciences; Rheumatology SC Endocrinology & Metabolism; Immunology; Science & Technology - Other Topics; Neurosciences & Neurology; Rheumatology GA BN31X UT WOS:000081586100002 PM 10415589 ER PT S AU Wilder, RL Elenkov, IJ AF Wilder, RL Elenkov, IJ BE Cutolo, M Masi, AT Bijlsma, JWJ Chikanza, IC Bradlow, HL Castagnetta, L TI Hormonal regulation of tumor necrosis factor-alpha, interleukin-12 and interleukin-10 production by activated macrophages - A disease-modifying mechanism in rheumatoid arthritis and systemic lupus erythematosus? SO NEUROENDOCRINE IMMUNE BASIS OF THE RHEUMATIC DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Conference on the Neuroendocrine Immune Basis of the Rheumatic Diseases CY SEP 18-20, 1998 CL GENOA, ITALY SP Italian Soc Rheumatol, European Neuroendocrine assoc, Univ Genova, Dept Internal Med, Sch Med, Novartis Farma, Hoffmann la Roche, Basel, Roche, Milan, Searle Monsanto Italiana, Boehringer Ingelheim, Procter & Gamble Pharmaceut, Bayers, Minist Univ Ricerca Sci Tecnologica, Italy ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; BLOOD MONONUCLEAR-CELLS; BONE-MINERAL DENSITY; X DBA/2 MICE; AUTOIMMUNE-DISEASES; CYTOKINE PRODUCTION; REPLACEMENT THERAPY; TNF-ALPHA; POSTMENOPAUSAL WOMEN AB Rheumatoid arthritis (RA) and systemic lupus ergthematosus (SLE) frequently develop and progress in settings in which sympathoadrenomedullary and gonadal hormone levels are changing, e.g., during pregnancy, postpartum period, menopause, estrogen administration. This paper addresses the view that adrenal and gonadal hormonal deficiency facilitates excessive macrophage production of TNF-alpha and IL-12 that characterizes RA, whereas excessive estrogen action is suggested to play an essential role in the production of IL-10 in patients with SLE. Disease activity in SLE, in contrast to RA, appeals to be associated with high-level production of IL-10, relative to the proinflammatory cytokines, TNF-alpha and IL-12. Accutnulating data suggest that novel therapeutic approaches may ultimately be developed from continued investigation of the role of the neuroendocrine factors in RA and SLE. C1 NIAMSD, Inflammatory Joint Dis Sect, NIH, Bethesda, MD 20892 USA. NIAMSD, Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Wilder, RL (reprint author), NIAMS, Inflammatory Joint Dis Sect, NIH, Bldg 10,Room 9N228,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. NR 151 TC 45 Z9 47 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-215-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 876 BP 14 EP 31 DI 10.1111/j.1749-6632.1999.tb07619.x PG 18 WC Endocrinology & Metabolism; Immunology; Multidisciplinary Sciences; Neurosciences; Rheumatology SC Endocrinology & Metabolism; Immunology; Science & Technology - Other Topics; Neurosciences & Neurology; Rheumatology GA BN31X UT WOS:000081586100003 PM 10415590 ER PT J AU Woody, MA Welniak, LA Richards, S Taub, DD Tian, ZG Sun, R Longo, DL Murphy, WJ AF Woody, MA Welniak, LA Richards, S Taub, DD Tian, ZG Sun, R Longo, DL Murphy, WJ TI Use of neuroendocrine hormones to promote reconstitution after bone marrow transplantation SO NEUROIMMUNOMODULATION LA English DT Review DE prolactin; growth hormone; immune parameters; hematopoiesis; transplantation ID GROWTH-FACTOR-I; NATURAL-KILLER ACTIVITY; HUMAN LYMPHOCYTE-T; THYMIC EPITHELIAL-CELLS; DWARF MOUSE; PROLACTIN RECEPTORS; NK-CELLS; SALMONELLA-TYPHIMURIUM; IMMUNOLOGICAL CAPACITY; PROGENITOR CELLS AB A survey of the previous literature and the data shown here indicate that neuroendocrine hormones such as growth hormone and prolactin may be of potential clinical use after bone marrow transplantation (BMT) to promote hematopoietic and immune recovery, The amounts of hormones used in our model do not promote weight gain suggesting that their lymphohematopoietic actions were independent of their anabolic effects. While the hormones may not produce the same extent of immune/hematopoietic effects when compared to conventional hematopoietic and immune stimulating cytokines (i.e. IL-2 or G-CSF), their pleiotropic effects and limited toxicity after systemic administration makes them attractive to test in the post-BMT setting, However, more work needs to be performed to understand the mechanism(s) of their action, particularly with regard to T-cell function and development. C1 NCI, IRSP, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Leukocyte Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Genzyme Corp, Framingham, MA 01701 USA. NIA, Baltimore, MD 21224 USA. Shandong Acad Med Sci, Jinan, Peoples R China. RP Murphy, WJ (reprint author), NCI, IRSP, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 567,Rm 210, Frederick, MD 21702 USA. EM murphyw@ncifcrf.gov RI Tian, Zhigang/J-3512-2013 NR 101 TC 25 Z9 25 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD JAN-APR PY 1999 VL 6 IS 1-2 BP 69 EP 80 DI 10.1159/000026366 PG 12 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 167LQ UT WOS:000078635100009 PM 9876237 ER PT J AU Tolosa, E Ashwell, JD AF Tolosa, E Ashwell, JD TI Thymus-derived glucocorticoids and the regulation of antigen-specific T-cell development SO NEUROIMMUNOMODULATION LA English DT Article DE steroids; glucocorticoids; thymocyte development; thymocyte selection; autoimmunity ID SYSTEMIC LUPUS-ERYTHEMATOSUS; NONOBESE DIABETIC MICE; POSITIVE SELECTION; THYMOCYTE APOPTOSIS; NURSE CELLS; RECEPTOR EXPRESSION; CD4+CD8+ THYMOCYTES; IMMUNE-RESPONSES; EPITHELIAL-CELLS; LPR MICE AB Bidirectional interactions of both a stimulatory and inhibitory nature occur between the neuroendocrine and the immune systems, and these interactions play an important modulatory role during T-cell ontogeny. Specifically, glucocorticoids potently induce apoptosis in thymocytes a nd activated T cells, bur can also rescue these cells from activation-induced cell death. The objective of this review is to discuss current data on the interactions of the immune system with steroid hormones in the thymus and to describe a model that includes glucocorticoids in the shaping of the peripheral T-cell antigen-specific repertoire and deals with their potential role in the generation of autoimmune disease. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Room 1B-40,Bldg 10, Bethesda, MD 20892 USA. NR 70 TC 15 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD JAN-APR PY 1999 VL 6 IS 1-2 BP 90 EP 96 DI 10.1159/000026368 PG 7 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 167LQ UT WOS:000078635100011 PM 9876239 ER PT J AU Theodore, WH Bhatia, S Hatta, J Fazilat, S DeCarli, C Bookheimer, SY Gaillard, WD AF Theodore, WH Bhatia, S Hatta, J Fazilat, S DeCarli, C Bookheimer, SY Gaillard, WD TI Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures SO NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; RESONANCE-IMAGING EVIDENCE; COMPLEX PARTIAL SEIZURES; BLOOD-FLOW; VOLUME MEASUREMENTS; GLUCOSE-METABOLISM; QUANTITATIVE MRI; DENTATE GYRUS; CONVULSIONS; SCLEROSIS AB Background: Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration. Objective: To determine whether epilepsy duration is related to HF atrophy. Methods: We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes. Results: Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration. Conclusions: A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures. C1 NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, 10-5N-250, Bethesda, MD 20892 USA. RI DeCarli, Charles/B-5541-2009 NR 39 TC 153 Z9 155 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 1 PY 1999 VL 52 IS 1 BP 132 EP 136 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 215VD UT WOS:000081403400027 PM 9921860 ER PT J AU Haxby, JV Ungerleider, LG Clark, VP Schouten, JL Hoffman, EA Martin, A AF Haxby, JV Ungerleider, LG Clark, VP Schouten, JL Hoffman, EA Martin, A TI The effect of face inversion on activity in human neural systems for face and object perception SO NEURON LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; HUMAN VISUAL-CORTEX; RECOGNITION; PET; KNOWLEDGE AB The differential effect of stimulus inversion on face and object recognition suggests that inverted faces are processed by mechanisms for the perception of other objects rather than by face perception mechanisms. We investigated the face inversion using functional magnetic resonance imaging (fMRI). The principal effect of face inversion on was an increased response in ventral extrastriate regions that respond preferentially to another class of objects (houses). In contrast, house inversion did not produce a similar change in face-selective regions. Moreover, stimulus inversion had equivalent, minimal effects for faces in in face-selective regions and for houses in house-selective regions. The results suggest that the failure of face perception systems with inverted faces leads to the recruitment of processing resources in object perception systems, but this failure is not reflected by altered activity in face perception systems. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. RP Haxby, JV (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009; Clark, Vincent/B-3343-2010 OI Clark, Vincent/0000-0002-9151-2102 NR 37 TC 395 Z9 400 U1 4 U2 34 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN PY 1999 VL 22 IS 1 BP 189 EP 199 DI 10.1016/S0896-6273(00)80690-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 163MV UT WOS:000078410300024 PM 10027301 ER PT S AU Cohen, LG Chen, R Celnik, P AF Cohen, LG Chen, R Celnik, P BE Grafman, J Christen, Y TI Functional relevance of cortical plasticity SO NEURONAL PLASTICITY: BUILDING A BRIDGE FROM THE LABORATORY TO THE CLINIC SE RESEARCH AND PERSPECTIVES IN NEUROSCIENCES LA English DT Proceedings Paper CT Meeting of the Foundation Ipsen on Neuronal Plasticity CY OCT 06, 1997 CL PARIS, FRANCE SP Fdn Ipsen ID TRANSCRANIAL MAGNETIC STIMULATION; UPPER-LIMB AMPUTATION; CEREBRAL BLOOD-FLOW; SPINAL-CORD INJURY; HUMAN MOTOR CORTEX; EARLY BLIND HUMANS; VISUAL-CORTEX; BRAIN-STIMULATION; OCCIPITAL CORTEX; PHANTOM-LIMB AB Different reports have demonstrated cortical plasticity associated with large hemispheric lesions, skill acquisition and use. However, it is not clear if this plasticity is always useful in terms of compensatory function. A patient who had a hemispherectomy during childhood is presented as an example of functionally relevant plasticity in the motor domain. At the time of testing, he was able to voluntarily move the affected arm. Transcranial stimulation demonstrated the development of different cortical representations for both arms in the remaining hemisphere. Therefore, the remaining hemisphere took over some of the functions of the missing hemisphere. Functional relevance of cortical plasticity can be also demonstrated when reorganization takes place across sensory modalities. Cortical areas normally processing visual information can be activated by somatosensory input. To determine if this activation contributes to behavioral performance in tactile discrimination tasks, repetitive transcranial magnetic stimulation was delivered to different scalp positions during reading of Braille and embossed Roman letters by blind and sighted subjects. Stimulation of the occipital areas disrupted reading and induced phantom tactile sensations in the early blind, but not in sighted volunteers. The occipital cortex is not only active in association with, but is one of the important functional components of the network mediating tactile discrimination in the blind. Determination of the functional role played by plasticity in each setting is important for the establishment of rational strategies for promoting recovery of function in humans. C1 NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 89 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6082 BN 3-540-64357-5 J9 RES PER NEUROSCI JI Res. Perspect. Neurosci. PY 1999 BP 65 EP 77 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BN80L UT WOS:000082969500005 ER PT S AU Grafman, J Litvan, I AF Grafman, J Litvan, I BE Grafman, J Christen, Y TI Evidence for four forms of neuroplasticity SO NEURONAL PLASTICITY: BUILDING A BRIDGE FROM THE LABORATORY TO THE CLINIC SE RESEARCH AND PERSPECTIVES IN NEUROSCIENCES LA English DT Proceedings Paper CT Meeting of the Foundation Ipsen on Neuronal Plasticity CY OCT 06, 1997 CL PARIS, FRANCE SP Fdn Ipsen ID VISUAL-CORTEX; SYNAPTIC PLASTICITY; HUMAN BRAIN; RECOVERY; INJURY; MOTOR; PERSPECTIVE; MECHANISMS; CHILDREN; BEHAVIOR AB We suggest that at least four major forms of functional neuroplasticity can be studied in normal human subjects and patients. The four forms of functional neuroplasticity are homologous area adaptation, cross-modal reassignment, map expansion, and compensatory masquerade. Homologous area adaptation is the assumption of a particular cognitive process by a homologous region in the opposite hemisphere. Cross-modal reassignment occurs when structures previously devoted to processing a particular kind of sensory input now accept input from a new sensory modality. Map expansion is the enlargement of a functional brain region on the basis of performance. Compensatory masquerade is a novel allocation of a particular cognitive process to perform a task. By focusing on these four forms of functional neuroplasticity, several fundamental questions about how functional cooperation between brain regions is achieved can be addressed. C1 NINDS, Cognit Neurosci Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, Med Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 31 TC 16 Z9 16 U1 2 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6082 BN 3-540-64357-5 J9 RES PER NEUROSCI JI Res. Perspect. Neurosci. PY 1999 BP 131 EP 139 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BN80L UT WOS:000082969500009 ER PT S AU Brenneman, DE Hauser, J Phillips, TM Davidson, A Bassan, M Gozes, I AF Brenneman, DE Hauser, J Phillips, TM Davidson, A Bassan, M Gozes, I BE Sandman, CA Strand, FL Beckwith, B Chronwall, BM Flynn, FW Nachman, RJ TI Vasoactive intestinal peptide - Link between electrical activity and glia-mediated neurotrophism SO NEUROPEPTIDES: STRUCTURE AND FUNCTION IN BIOLOGY AND BEHAVIOR SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 20th Winter Neuropeptide Conference CY FEB 06-09, 1999 CL INT NEUROPEPTIDE SOC, BRECKENRIDGE, COLORADO SP Biomeasure Inc, Cephalon Inc, Int Neuropeptide Soc, Merck, NICHHD, Ortho Mcneil Pharmaceut, Summit Fdn HO INT NEUROPEPTIDE SOC ID NEURONAL CELL-DEATH; RAT ASTROCYTES; IL-6 SECRETION; NEXIN-I; SURVIVAL; SYNERGISM; IDENTIFICATION; INTERLEUKIN-1; RECEPTORS; CULTURES AB Vasoactive intestinal peptide has neurotrophic and neuroprotective properties that influence the survival of activity-dependent neurons in the central nervous system. Investigations of the mechanism of this neurotrophic peptide indicated that these actions are contingent on interactions with astroglia, The complex mixture of neurotrophic mediators released from astroglia include cytokines, a protease inhibitor, and activity-dependent neurotrophic factor, a protein with apparent structural similarities to hsp60, Investigations of ADNF resulted in the discovery of active peptides of extraordinary potency and broad neuroprotective properties. These studies indicate that a nine-ami no acid core peptide of ADNF had significantly greater neuroprotective properties in comparison to the parent growth factor and these advantages identify ADNF-9 as an attractive lead compound for drug development. C1 NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Immunochem Lab, Washington, DC USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Brenneman, DE (reprint author), NICHD, LDN, SDMP, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 27 TC 24 Z9 26 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 1-57331-224-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 897 BP 17 EP 26 DI 10.1111/j.1749-6632.1999.tb07875.x PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BP49Y UT WOS:000085327400002 PM 10676432 ER PT S AU Hill, JM Glazner, GW Lee, SJ Gozes, I Gressens, P Brenneman, DE AF Hill, JM Glazner, GW Lee, SJ Gozes, I Gressens, P Brenneman, DE BE Sandman, CA Strand, FL Beckwith, B Chronwall, BM Flynn, FW Nachman, RJ TI Vasoactive intestinal peptide regulates embryonic growth through the action of activity-dependent neurotrophic factor SO NEUROPEPTIDES: STRUCTURE AND FUNCTION IN BIOLOGY AND BEHAVIOR SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 20th Winter Neuropeptide Conference CY FEB 06-09, 1999 CL INT NEUROPEPTIDE SOC, BRECKENRIDGE, COLORADO SP Biomeasure Inc, Cephalon Inc, Int Neuropeptide Soc, Merck, NICHHD, Ortho Mcneil Pharmaceut, Summit Fdn HO INT NEUROPEPTIDE SOC ID CULTURED MOUSE EMBRYOS; NEURONAL SURVIVAL; ENVELOPE PROTEIN; SONIC-HEDGEHOG; MESSENGER-RNA; EXPRESSION; RECEPTOR; RAT; DIFFERENTIATION; PREVENTION AB Activity-dependent neurotrophic Factor is a potent, neuroprotective protein released from astroglia by VIP and accounts in part for the neuroprotective properties of this neuropeptide The growth-regulatory actions of VIP during embryogenesis may also occur indirectly through the release of activity-dependent neurotrophic factor. Whole cultured day-9 mouse embryos treated with activity-dependent neurotrophic factor (10(-13) M) far 4 hr grew 3,1 somites, compared with 1.6 somites in control embryos, Treated embryos appeared morphologically normal and exhibited significant increases in cross-sectional area, protein, and DNA content and bromodeoxyuridine incorporation,Anti-activity-dependent neurotrophic factor significantly inhibited growth. Go-treatment of embryos with anti activity-dependent neurotrophic factor inhibited VIP-stimulated growth; however, anti-VIP did not inhibit activity-dependent neurotrophic factor-induced growth. These data Indicate that an activity-dependent neurotrophic factor like substance is an endogenous embryonic growth factor and that VIP-regulated growth occurs, at least in part, through activity dependent neurotrophic factor. C1 NICHHD, Sect Dev & Mol Pharmacol, NIH, Bethesda, MD 20892 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40383 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Hop Robert Debre, Serv Neuropediat, F-75019 Paris, France. RP Hill, JM (reprint author), NICHD, LDN, NIH, Bldg 49,Room 5A38,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 12 Z9 13 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 1-57331-224-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 897 BP 92 EP 100 DI 10.1111/j.1749-6632.1999.tb07881.x PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BP49Y UT WOS:000085327400008 PM 10676438 ER PT S AU Spong, CY Lee, SJ McCune, SK Gibney, G Abebe, DT Brenneman, DE Hill, JM AF Spong, CY Lee, SJ McCune, SK Gibney, G Abebe, DT Brenneman, DE Hill, JM BE Sandman, CA Strand, FL Beckwith, B Chronwall, BM Flynn, FW Nachman, RJ TI Regulation of postimplantation mouse embryonic growth by maternal vasoactive intestinal peptide SO NEUROPEPTIDES: STRUCTURE AND FUNCTION IN BIOLOGY AND BEHAVIOR SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 20th Winter Neuropeptide Conference CY FEB 06-09, 1999 CL INT NEUROPEPTIDE SOC, BRECKENRIDGE, COLORADO SP Biomeasure Inc, Cephalon Inc, Int Neuropeptide Soc, Merck, NICHHD, Ortho Mcneil Pharmaceut, Summit Fdn HO INT NEUROPEPTIDE SOC ID VIP MESSENGER-RNA; T-LYMPHOCYTES; RAT-BRAIN; EXPRESSION AB Vasoactive intestinal peptide (VIP) is an identified regulator of growth in the embryonic day (E) 9-11 mouse. Mouse embryonic and extraembryonic tissues were studied to identify the source of VIP at this critical time, VIP mRNA was detected in the decidua/trophoblast at E8 and declined until E10, after which it was not detectable, VIP mRNA was not apparent in the embryo until E11-E12, At E9, cells in decidua had VIP as well as lymphocyte marker (delta and CD3) immunoreactivity. VIP binding sites were dense in the decidua/trophoblast at E6, which gradually decreased until Pill, VIP binding sites were detected in embryonic neuroepithelium by E9, The transient presence of VIP binding sites and mRNA in the decidua/trophoblast correlate with the identified period of VIP growth regulation, when VIP mRNA is absent in the embryo, Therefore, these findings suggest that maternal decidual lymphocytes are the source of VIP that regulate early postimplantation embryonic growth. C1 NICHD, Sect Dev & Mol Pharmacol, LDN, NIH, Bethesda, MD 20892 USA. George Washington Univ, Childrens Natl Med Ctr, Div Neonatol, Dept Pediat, Washington, DC 20010 USA. RP Hill, JM (reprint author), NICHD, Sect Dev & Mol Pharmacol, LDN, NIH, Bldg 49,5A-38,MSC 4480,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 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 1-57331-224-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 897 BP 101 EP 108 DI 10.1111/j.1749-6632.1999.tb07882.x PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BP49Y UT WOS:000085327400009 PM 10676439 ER PT S AU Gozes, I Bassan, M Zamostiano, R Pinhasov, A Davidson, A Giladi, E Perl, O Glazner, GW Brenneman, DE AF Gozes, I Bassan, M Zamostiano, R Pinhasov, A Davidson, A Giladi, E Perl, O Glazner, GW Brenneman, DE BE Sandman, CA Strand, FL Beckwith, B Chronwall, BM Flynn, FW Nachman, RJ TI A novel signaling molecule for neuropeptide action: Activity-dependent neuroprotective protein SO NEUROPEPTIDES: STRUCTURE AND FUNCTION IN BIOLOGY AND BEHAVIOR SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 20th Winter Neuropeptide Conference CY FEB 06-09, 1999 CL INT NEUROPEPTIDE SOC, BRECKENRIDGE, COLORADO SP Biomeasure Inc, Cephalon Inc, Int Neuropeptide Soc, Merck, NICHHD, Ortho Mcneil Pharmaceut, Summit Fdn HO INT NEUROPEPTIDE SOC ID VASOACTIVE-INTESTINAL-PEPTIDE; E-DEFICIENT MICE; GROWTH-FACTOR PRECURSOR; CENTRAL-NERVOUS-SYSTEM; APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; NEUROTROPHIC FACTOR; OXIDATIVE STRESS; CHOLINERGIC IMPAIRMENTS; FATTY NEUROPEPTIDE AB The complete coding sequence of a novel protein (828 amino acids, pi 5,99), a potential new mediator of vasoactive intestinal peptide (VIP) activity was recently revealed. The expression of this molecule, activity-dependent neuroprotective protein (ADNP), was augmented in the presence of VIP, in cerebral cortical astrocytes, The mRNA transcripts encoding ADNP mere enriched in the mouse hippocampus and cerebellum. The protein deduced sequence contained the following: (1) a unique peptide, NAPVSIPQ, sharing structural and immunological homologies with the previously reported, activity-dependent neurotrophic factor (ADNF) and exhibiting neuroprotection in vitro and in vivo; (2) a glutaredoxin active site; and (3) a classical zinc binding domain, Comparative studies suggested that the peptide, NAPVSIPQ (NAP), was more efficacious than peptides derived from ADNF, ADNP, a potential mediator of VIP-associated neuronal survival, and the new peptide, a potential lead compound for drug design, are discussed below. C1 Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NICHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 56 TC 34 Z9 34 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-224-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 897 BP 125 EP 135 DI 10.1111/j.1749-6632.1999.tb07884.x PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BP49Y UT WOS:000085327400011 PM 10676441 ER PT S AU Youdim, MBH Grunblatt, E Mandel, S AF Youdim, MBH Grunblatt, E Mandel, S BE Trembly, B Slikker, W TI The pivotal role of iron in NF-kappa B activation and nigrostriatal dopaminergic neurodegeneration - Prospects for neuroprotection in Parkinson's disease with iron chelators SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MD SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID NECROSIS-FACTOR-ALPHA; DEPENDENT LIPID-PEROXIDATION; SUBSTANTIA-NIGRA; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; RAT-BRAIN; GLUTATHIONE DEPLETION; CEREBROSPINAL-FLUID; POTENT INHIBITORS; RADICAL SCAVENGER AB R-Apomorphine (APO) the catechol-derived dopamine D(1)-D(2) receptor agonist has been shown to be highly potent iron chelator and radical scavenger and inhibitor of membrane lipid peroxidation in vitro, in vivo and in cell culture employing PC12 cells. Its potency has been compared to the prototype iron chelator desferrioxamine (desferal), dopamine, nifedipine and dopamine D(2) receptor agonists, bromocriptine, lisuride, pergolide and prami-pexole, APO also inhibits brain and mitochondrial protein oxidation. IIE vivo APO protects against MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyropyridine)- induced striatal dopaminergic neurodegeneration in C57 black mice with as low as 5 mg/kg, APO is a reversible competitive inhibitor of monoamine oxidase (MAO) A and B with IC(50) values of 93 and 214 uM, respectively, The iron chelating and radical scavenging actions of desferal and APO explains their ability to inhibit iron and 6-hydroxydopamine (6-OHDA)-induced neurodegeneration and activation of redox-sensitive transcription factor NF-kappa B and the subsequent transactivation of promoters of genes involved in inflammatory cytokines,Iron is thought to play a pivotal role in neurodegeneration, and APO may be an ideal drug to investigate neuroprotection in parkinson's disease where iron and oxidative stress have been implicated in the pathogenesis of nigrostriatal dopamine neuron degeneration. C1 Technion Israel Inst Technol, Fac Med, Haifa, Israel. US Natl Parkinsons Fdn, Bruce Rappaport Family Res Inst, Ctr Neurodegenerat Dis, Haifa, Israel. US Natl Parkinsons Fdn, Dept Pharmacol, Ctr Neurodegenerat Dis, Haifa, Israel. NIMH, Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. RP Youdim, MBH (reprint author), B Rappaport Family Med Sci Bldg,Efron Str,POB 969, IL-31096 Haifa, Israel. EM youdim@tx.technion.ac.il RI Grunblatt, Edna/A-6762-2016 OI Grunblatt, Edna/0000-0001-8505-7265 NR 82 TC 63 Z9 64 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-223-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 7 EP 25 DI 10.1111/j.1749-6632.1999.tb07977.x PG 19 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700002 PM 10668410 ER PT S AU Chiueh, CC AF Chiueh, CC BE Trembly, B Slikker, W TI Neuroprotective properties of nitric oxide SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MD SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID CARDIOPLEGIC ISCHEMIC ARREST; S-NITROSOGLUTATHIONE; OXIDATIVE STRESS; LIPID-PEROXIDATION; IN-VIVO; DOPAMINE NEURONS; RELAXING FACTOR; CARBON-DIOXIDE; GLUTATHIONE; SUPEROXIDE AB The discoveries of physiological roles of nitric oxide (. NO) as the mediator of endothelium-derived relaxing factor (EDRF) action and the activator of guanylyl cyclase to increase cyclic guanosine monophosphate (cGMP), which lead to vasorelaxation in the cardiovascular system, have been awarded with the 1998 Nobel Prize of Medicine. The present review discusses putative beneficial effects of . NO in the central nervous system (CNS). In addition to its prominent roles of the regulation of cerebral blood flow and the modulation of cell to cell communication in the brain, recent in vitro and in vivo results indicated that . NO is a potent antioxidative agent. . NO terminates oxidant stress in the brain by (i) suppressing iron-induced generation of hydroxyl radicals (. OH) via the Fenton reaction, (ii) interrupting the chain reaction of lipid peroxidation, (iii) augmenting the antioxidative potency of reduced glutathione (GSH) and (iv) inhibiting cysteine proteases. It is apparent that . NO-a relative long half-life nitrogen-centered weak radical-scavenges those short-lived, highly reactive free radicals such as superoxide anion (O-2(.-)),. OH, peroxyl lipid radicals (LOO .) and thiyl radicals (i.e., GS .), yielding reactive nitrogen species including nitrites, nitrates, S-nitrosoglutathione (GSNO) and peroxynitrite (ONOO-). GSN is 100-fold more potent than GSH; it completely inhibits the weak peroxidative effect of ONOO-. Moreover, CO2 and . NO neutralize prooxidative effects of ONOO-. CO2 prevents protein oxidation but not 3-nitrotyrosine formation caused by ONOO-. Finally, neuroprotective effects of GSNO and . NO have been demonstrated in brain preparations in vivo. These novel neuroprotective properties of . NO and GSNO may have their physiological significance, since oxidative stress depletes GSH while increasing GS . and . NO formation in astroglial and endothelial cells, resulting in the generation of a more potent antioxidant GSNO and providing additional neuroprotection at mu M concentrations. This putative GSNO pathway (GSH --> GS . --> GSNO --> . NO + GSSG --> GSH) may be an important Dart of endogenous antioxidative defense system, which could protect neurons and other brain cells against oxidative stress caused by oxidants, iron complexes, proteases and cytokines. In conclusion, . NO is a potent antioxidant against oxidative damage caused by reactive oxygen species, which are generated by Fenton reaction or other mechanisms in the brain via redox cycling of iron complexes. C1 NIMH, Clin Sci Lab, Unit Neurodegenerat & Neuroprotect, Clin Ctr,NIH, Bethesda, MD 20892 USA. RP NIMH, Clin Sci Lab, Unit Neurodegenerat & Neuroprotect, Clin Ctr,NIH, Bldg 10,Rm 3D-41, Bethesda, MD 20892 USA. EM chiueh@helix.nih.gov NR 61 TC 139 Z9 143 U1 1 U2 10 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-223-1; 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 301 EP 311 DI 10.1111/j.1749-6632.1999.tb08007.x PG 11 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700027 PM 10668435 ER PT S AU Herning, RI Better, W Nelson, R Gorelick, D Cadet, JL AF Herning, RI Better, W Nelson, R Gorelick, D Cadet, JL BE Trembly, B Slikker, W TI The regulation of cerebral blood flow during intravenous cocaine administration in cocaine abusers SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID HUMANS; VASCULITIS; STROKE; BRAIN AB Cocaine abuse is associated with heightened risk of life-threatening neurological complications such as strokes, seizures, and transient ischemic attacks, We used transcranial Doppler (TCD) sonography, a continuous measure of cerebral blood flow velocity, to better understand the changes in cerebral hemodynamics produced by cocaine administration, which may lead to an increased risk for stroke in cocaine abusers. Heart rate and blood pressure were also measured. Blood flow velocity of seven cocaine abusers was studied during placebo, 10-, 25-, and 50-mg intravenous (i.v.) injections of cocaine, A significant increase in mean and systolic velocity which lasted for about two minutes was observed with all doses of cocaine, with no change in the placebo condition. This increase in systolic velocity indicates that cocaine produces an immediate and brief period of vasoconstriction in large arteries of the brain. The present results elucidate the time course of cocaine's acute cerebrovascular effects and provide a better understanding of etiology of cocaine-related stroke and transient ischemic attacks. C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Herning, RI (reprint author), NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 25 TC 12 Z9 12 U1 1 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 489 EP 494 DI 10.1111/j.1749-6632.1999.tb08030.x PG 6 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700046 PM 10668454 ER PT S AU Slikkker, W Youdim, M Palmer, GC Hall, E Williams, C Trembly, B AF Slikkker, W Youdim, M Palmer, GC Hall, E Williams, C Trembly, B BE Trembly, B Slikker, W TI The future of neuroprotection SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MARYLAND SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NIMH, Fogarty Int Ctr, NIH, Bethesda, MD USA. Astra Arcus USA, Rochester, NY USA. Parke Davis Pharmaceut Res, Neurosci Therapeut, Ann Arbor, MI USA. Univ Aukland, Dept Paediat, Aukland, New Zealand. Vet Affairs Med Ctr, Neurosurg Sect, Togus, ME USA. RP Slikkker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 0 TC 32 Z9 32 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 1-57331-222-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 529 EP 533 DI 10.1111/j.1749-6632.1999.tb08035.x PG 5 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700050 PM 10668458 ER PT J AU Foundas, AL Faulhaber, JR Kulynych, JJ Browning, CA Weinberger, DR AF Foundas, AL Faulhaber, JR Kulynych, JJ Browning, CA Weinberger, DR TI Hemispheric and sex-linked differences in Sylvian fissure morphology: A quantitative approach using volumetric magnetic resonance imaging SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID PLANUM TEMPORALE ASYMMETRY; DEVELOPMENTAL DYSLEXIA; CEREBRAL ASYMMETRIES; HUMAN-BRAIN; CORTEX; MORPHOMETRY; HANDEDNESS; SURFACE; REAPPRAISAL; LATERALITY AB Objective: In a sample of right-handed adults, volumetric magnetic resonance imaging (MRI) was used to reinvestigate hemispheric and sex-linked differences in Sylvian fissure (SF) morphology. Background: Asymmetries of the SF exist with a predominant leftward asymmetry consistently reported in postmortem studies. These anatomic asymmetries may reflect asymmetric allocation of adjacent opercula, with some investigators positing a relationship with planum temporale asymmetries, as the postcentral SF is more asymmetric than the anterior segment. Sex-related differences have also been reported with reduced asymmetries in women relative to men. Method: Using in vivo MRI surface renderings, SF asymmetries were studied in a group of consistently right-handed men (n = 12) and women (n = 12). Anterior and postcentral SF lengths were measured. Results: Overall, there was a significant leftward asymmetry of the horizontal SF (anterior and postcentral) in men and women. Whereas there was a significant leftward asymmetry of the postcentral SF, there was no significant asymmetry of the anterior SF. There was an increase in the parietal operculum anterior to the posterior ascending ramus (PAR) in the left hemisphere and posterior to the PAR in the right hemisphere when SF asymmetries were leftward, with the length of the anterior parietal operculum positively correlated with postcentral SF length. Conclusions: These findings demonstrate that the SF is asymmetric but that clear sex-related effects do not exist in consistently right handed subjects. C1 Tulane Univ, Sch Med, Dept Psychiat & Neurol, New Orleans, LA 70112 USA. Dept Vet Affairs Med Ctr, Neurol Serv, New Orleans, LA USA. St Elizabeths Hosp, NIMH, Intramural Res Program, Washington, DC USA. RP Foundas, AL (reprint author), Tulane Univ, Sch Med, Dept Psychiat & Neurol, 1430 Tulane Ave, New Orleans, LA 70112 USA. FU NIDCD NIH HHS [K08 DC00135] NR 43 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JAN PY 1999 VL 12 IS 1 BP 1 EP 10 PG 10 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 173MA UT WOS:000078983300001 PM 10082328 ER PT J AU Bahro, M Molchan, SE Sunderland, T Herscovitch, P Schreurs, BG AF Bahro, M Molchan, SE Sunderland, T Herscovitch, P Schreurs, BG TI The effects of scopolamine on changes in regional cerebral blood flow during classical conditioning of the human eyeblink response SO NEUROPSYCHOBIOLOGY LA English DT Article DE classical conditioning; eyeblink; scopolamine; positron emission tomography; regional cerebral blood flow; memory; human ID NICTITATING-MEMBRANE RESPONSE; POSITRON-EMISSION TOMOGRAPHY; CENTRAL CHOLINERGIC BLOCKADE; CINGULATE CORTEX; SOMATOSENSORY STIMULATION; ALZHEIMERS-DISEASE; MAMMALIAN BRAIN; MEMORY; RABBITS; ATTENTION AB We examined the effects of scopolamine on the functional anatomy of classical conditioning of the human eyeblink response. Ten healthy young normal female volunteers (mean age +/- SEM: 26.7 +/- 0.9 years) were administered 0.4 mg scopolamine intravenously 1 h before regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and (H2O)-O-15. Scans occurred during three sequential phases: (1) explicitly unpaired presentations of the unconditioned stimulus (airpuff to the right eye) and conditioned stimulus (binaural tone), (2) paired presentations of the two stimuli (associative learning) and (3) explicitly unpaired presentation of the stimuli (extinction phase). Scopolamine impaired acquisition of the conditioned eyeblink response (54.7 +/- 4.9%) relative to 18 untreated subjects from two previous PET studies. Regions that showed significant relative increases in rCBF during conditioning included the right lateral occipital cortex, the right inferior occipital cortex, the right lateral temporo-occipital cortex, the left medial temporo-occipital cortex, the posterior cingulate, the right cerebellum/brain stem area and the medial cerebellum. Significant relative decreases in rCBF were measured in the thalamus, the left putamen/insula area, the right putamen and the left and middle cerebellar cortex. The data partially replicate previous findings in unmedicated young volunteers of conditioning-specific rCBF changes in the cingulate cortex, the cerebellar cortex, the insula and the lateral temporo-occipital cortex. Our finding of decreased rCBF in the thalamus and increased rCBF in the occipital cortex may be attributable to effects of scopolamine per se rather than conditioning. Our data lend further support to the notion that classical conditioning involves distributed changes in multiple systems within the central nervous system. C1 NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. NINDS, Behav Neurosci Unit, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Bahro, M (reprint author), Univ Bern, Dept Psychiat, Div Geriatr Psychiat, Bolligenstr 111, CH-3000 Bern 60, Switzerland. OI Schreurs, Bernard/0000-0002-5776-0807 NR 59 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 1999 VL 39 IS 4 BP 187 EP 195 DI 10.1159/000026582 PG 9 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 200BA UT WOS:000080517800003 PM 10343183 ER PT J AU Wiggs, CL Weisberg, J Martin, A AF Wiggs, CL Weisberg, J Martin, A TI Neural correlates of semantic and episodic memory retrieval SO NEUROPSYCHOLOGIA LA English DT Article DE PET; semantic knowledge; explicit memory; cued recall; color ID POSITRON EMISSION TOMOGRAPHY; LONG-TERM-MEMORY; MAGNETIC-RESONANCE; VERBAL MEMORY; TEMPORAL-LOBE; HUMAN BRAIN; PET IMAGES; RETROSPLENIAL AMNESIA; HIPPOCAMPAL-FORMATION; PREFRONTAL CORTEX AB To investigate the functional neuroanatomy associated with retrieving semantic and episodic memories, we measured changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) while subjects generated single word responses to achromatic line drawings of objects. During separate scans, subjects either named each object, retrieved a commonly associated color of each object (semantic condition), or recalled a previously studied uncommon color of each object (episodic condition). Subjects were also scanned while staring at Visual noise patterns to provide a low level perceptual baseline. Relative to the low level baseline, all three conditions revealed bilateral activations of posterior regions of the temporal lobes, cerebellum, and left lateralized activations in frontal regions. Retrieving semantic information, as compared to object naming, activated left inferior temporal, left superior parietal, and left frontal cortices. In addition, small regions of right frontal cortex were activated. Retrieving episodic information, as compared to object naming, activated bilateral medial parietal cortex, bilateral retrosplenial cortex, right frontal cortex, thalamus, and cerebellum. Direct comparison of the semantic and episodic conditions revealed bilateral activation in temporal and frontal lobes in the semantic task (left greater than right), and activation in medial parietal cortex, retrosplenial cortex, thalamus, and cerebellum (but not right frontal regions) in the episodic task. These results support the assertion that distinct neural structures mediate semantic and episodic memory retrieval. However, they also raise questions regarding the specific roles of left temporal and right frontal cortices during episodic memory retrieval, in particular. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Wiggs, CL (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 83 TC 162 Z9 164 U1 5 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 1999 VL 37 IS 1 BP 103 EP 118 PG 16 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 148TL UT WOS:000077548900012 PM 9920476 ER PT J AU Dimitrov, M Grafman, J Soares, AHR Clark, K AF Dimitrov, M Grafman, J Soares, AHR Clark, K TI Concept formation and concept shifting in frontal lesion and Parkinson's disease patients assessed with the California Card Sorting Test SO NEUROPSYCHOLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; MONOZYGOTIC TWINS DISCORDANT; TEST-PERFORMANCE; COGNITIVE DEFICITS; PREFRONTAL CORTEX; LOBE LESIONS; HEAD-INJURY; SCHIZOPHRENIA; ACTIVATION; SPECT AB Concept formation and shifting abilities of 17 frontal lesion (FL) and 8 Parkinson's disease (PD) patients were assessed with the California Card Sorting Test. FL patients demonstrated a significantly greater number of perseverative responses and deficits in strategy planning, strategy initiation, and concept formation and did not benefit from abstract cues in comparison with their matched normal control (NC) participants. PD patients also demonstrated an increased number of perseverative responses under selected conditions in comparison with their matched NCs, but their ability to explain their sorts, to extract and express the sorting principles, and to sort with the help of abstract and concrete cues depended on their general cognitive status. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 53 TC 34 Z9 34 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 1999 VL 13 IS 1 BP 135 EP 143 DI 10.1037/0894-4105.13.1.135 PG 9 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 162HA UT WOS:000078338800016 PM 10067785 ER PT J AU Uhl, GR AF Uhl, GR TI Molecular genetics of substance abuse vulnerability: A current approach SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID DRUG-ABUSE; KNOCKOUT MICE; DISORDERS; ALCOHOL; TWIN; COMORBIDITY; ADOPTION; MODELS C1 NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP POB 5180, Baltimore, MD 21224 USA. NR 35 TC 25 Z9 25 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 1999 VL 20 IS 1 BP 3 EP 9 DI 10.1016/S0893-133X(98)00061-X PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 141LH UT WOS:000077145100002 PM 9885780 ER PT J AU Elman, I Goldstein, DS Eisenhofer, G Folio, J Malhotra, AK Adler, CM Pickar, D Breier, A AF Elman, I Goldstein, DS Eisenhofer, G Folio, J Malhotra, AK Adler, CM Pickar, D Breier, A TI Mechanism of peripheral noradrenergic stimulation by clozapine SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; norepinephrine; clozapine; catecholamine; fluphenazine; spillover ID PLASMA-CATECHOLAMINES; NOREPINEPHRINE; SCHIZOPHRENIA; HUMANS; EFFICACY; PATTERN; ACID; FATE AB Elevated plasma norepinephrine (NE) levels is a relatively consistent clinical effect of clozapine. Plasma NE levels reflect an interplay of release, reuptake, metabolism, and excretion. To explore the mechanism of clozapine-induced plasma NE elevation, we measured arterial plasma levels of NE and other catechols during intravenous infusion of tritium-labeled NE (H-3-NE) in schizophrenic patients treated with clozapine, fluphenazine, or placebo. Clozapine treated patients had markedly higher levels of NE than did the patients treated with fluphenazine or placebo. NE spillover averaged move than three times higher in clozapine-treated patients; whereas NE clearance did not differ among the groups. Production of H-3-dihydroxyphenylglycol (H-3-DHPG), a purely intraneuronal metabolite of H-3-NE in clozapine-treated patients was normal, indicating that clozapine did not affect neuronal uptake of NE. Because plasma levels of DHPG and dihydroxyphenylacetic acid (DOPAC), deaminated metabolites of catecholamines, in clozapine-treated patients were normal, clozapine also did not seem to inhibit intraneuronal monoamine oxidase (MAO). High plasma NE levels in clozapine-treated patients, therefore, resulted from increased NE spillover rather than decreased reuptake, metabolism, or clearance. [Neuropsychopharmacology 20:29-34, 1999] Published by Elsevier Science Inc. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, W End House,16 Blossom St, Boston, MA 02114 USA. NR 30 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 1999 VL 20 IS 1 BP 29 EP 34 DI 10.1016/S0893-133X(98)00047-5 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 141LH UT WOS:000077145100004 PM 9885782 ER PT J AU Holt, DJ Herman, MM Hyde, TM Kleinman, JE Sinton, CM German, DC Hersh, LB Graybiel, AM Saper, CB AF Holt, DJ Herman, MM Hyde, TM Kleinman, JE Sinton, CM German, DC Hersh, LB Graybiel, AM Saper, CB TI Evidence for a deficit in cholinergic interneurons in the striatum in schizophrenia SO NEUROSCIENCE LA English DT Article DE schizophrenia; striatum; cholinergic; interneuron; human; basal ganglia ID ALZHEIMERS-DISEASE; BASAL GANGLIA; IMMUNOREACTIVE NEURONS; ANTIPSYCHOTIC-DRUGS; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; VENTRAL STRIATUM; WILSONS-DISEASE; CAUDATE-PUTAMEN; SENILE DEMENTIA AB Neurochemical and functional abnormalities of the striatum have been reported in schizophrenic brains, but the cellular substrates of these changes are not known. We hypothesized that schizophrenia may involve an abnormality in one of the key modulators of striatal output, the cholinergic interneuron. We measured the densities of cholinergic neurons in the striatum in schizophrenic and control brains in a blind analysis, using as a marker of this cell population immunoreactivity for choline acetyltransferase, the synthetic enzyme of acetylcholine. As an independent marker, we used immunoreactivity for calretinin, a protein which is co-localized with choline acetyltransferase in virtually all of the cholinergic interneurons of the striatum. A significant decrease in choline acetyltransferase-positive and calretinin-positive cell densities was found in the schizophrenic cases compared with controls in the striatum as a whole [for the choline acetyltransferase-positive cells: controls: 3.21 +/- 0.48 cells/mm(2) (mean +/- S.D.), schizophrenics: 2.43 +/- 0.68 cells/mm(2):, P < 0.02]. The decrease was patchy in nature and most prominent in the ventral striatum (for the choline acetyltransferase-positive cells: controls: 3.47 +/- 0.59 cells/mm2, schizophrenics: 2.52 +/- 0.64 cells/mm(2); P < 0.005) which included the ventral caudate nucleus and nucleus accumbens region. Three of the schizophrenic cases with the lowest densities of cholinergic neurons had not been treated with neuroleptics for periods from more than a month to more than 20 years. A decrease in the number or function of the cholinergic interneurons of the striatum may disrupt activity in the ventral striatal-pallidal-thalamic-prefrontal cortex pathway and thereby contribute to abnormalities in function of the prefrontal cortex in schizophrenia. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA USA. Univ Chicago, Comm Neurobiol, Chicago, IL 60637 USA. NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Kentucky, Dept Biochem, Lexington, KY 40536 USA. MIT, Dept Brain & Cognit Sci, Boston, MA USA. RP Saper, CB (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. FU NIMH NIH HHS [MH-10522]; NINDS NIH HHS [NS25529] NR 92 TC 98 Z9 98 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 1 BP 21 EP 31 DI 10.1016/S0306-4522(99)00279-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 239EH UT WOS:000082755500005 PM 10613493 ER PT J AU Mizoguchi, H Narita, M Oji, DE Suganuma, C Nagase, H Sora, I Uhl, GR Cheng, EY Tseng, LF AF Mizoguchi, H Narita, M Oji, DE Suganuma, C Nagase, H Sora, I Uhl, GR Cheng, EY Tseng, LF TI The mu-opioid receptor gene-dose dependent reductions in G-protein activation in the pons/medulla and antinociception induced by endomorphins in mu-opioid receptor knockout mice SO NEUROSCIENCE LA English DT Article DE knockout mice; [S-35]GTP gamma S binding; endomorphins; antinociception; mu-opioid receptors; pons/medulla ID NEUROBLASTOMA SH-SY5Y CELLS; MORPHINE-INDUCED ANALGESIA; GAMMA-S BINDING; RAT-BRAIN; GUANOSINE-5'-O-(3-THIO)TRIPHOSPHATE BINDING; AGONIST EFFICACY; OPIATE RECEPTOR; MEMBRANES; POTENT; AUTORADIOGRAPHY AB There appear to be different relationships between mu-opioid receptor densities and the acute and neuroadaptive mu-opioid agonist-induced responses of the multiple opioid neuronal systems, including important pons/medulla circuits. The recent success in creating mu-opioid receptor knockout mice allows studies of mu-opioid agonist-induced pharmacological and physiological effects in animals that express no, one or two copies of the mu-opioid receptor gene. We now report that the binding of mu-opioid receptor ligand, [H-3][D-Ala(2),NHPhe(4),Gly-ol]enkephalin to membrane preparations of the pons/medulla was reduced by half in heterozygous mu-opioid receptor knockout mice and eliminated in homozygous mu-opioid receptor knockout mice. The endogenous mu-opioid agonist peptides endomorphin-1 and -2 activate G-proteins in the pons/medulla from wild-type mice in a concentration-dependent fashion, as assessed using [S-35]guanosine-5'-o-(3-thio)triphosphate binding. This stimulation was reduced to half of the wild-type levels in heterozygous mice and eliminated in homozygous knockout mice. The intracerebroventricular injection of either endomorphin-1 or endomorphin-2 produced marked antinociception in the hot-plate and tail-flick tests in wild-type mice. These antinociceptive actions were significantly reduced in heterozygous mu-opioid receptor knockout mice, and virtually abolished in homozygous knockout mice. The mu-opioid receptors are the principal molecular targets for endomorphin-induced G-protein activation in the pons/medulla and the antinociception caused by the intracerebroventricular administration of mu-opioid agonists. These data support the notion that there are limited physiological mu-opioid receptor reserves for inducing G-protein activation in the pons/medulla and for the nociceptive modulation induced by the central administration of endomorphin-1 and -2. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. Toray Ind Inc, Basic Res Lab, Kanagawa 248, Japan. NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol & Neurosci, Baltimore, MD 21224 USA. RP Tseng, LF (reprint author), Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. FU NIDA NIH HHS [DA 03811] NR 35 TC 50 Z9 51 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 1 BP 203 EP 207 DI 10.1016/S0306-4522(99)00298-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 239EH UT WOS:000082755500022 PM 10613510 ER PT J AU Zhang, L Ma, W Barker, JL Rubinow, DR AF Zhang, L Ma, W Barker, JL Rubinow, DR TI Sex differences in expression of serotonin receptors (subtypes 1A and 2A) in rat brain: A possible role of testosterone SO NEUROSCIENCE LA English DT Article DE serotonin; receptors; gender; testosterone; brain ID MESSENGER-RNA EXPRESSION; MEDIAL PREOPTIC NUCLEUS; 5-HT1A RECEPTOR; INSITU HYBRIDIZATION; 5-HYDROXYTRYPTAMINE(2A) RECEPTORS; IMMUNOREACTIVE FIBERS; BINDING-SITES; FEMALE RATS; CORTEX; CORTICOSTERONE AB Sexual differences in the expression of messenger RNA and in the binding of serotonin receptors (subtypes 1A and 2A) were studied by in situ hybridization and autoradiography {[H-3]8-hydroxy-2(di-n-propylamino)tetralin and [H-3]ketanserin binding} in the rat brain. Serotonin-1A receptor messenger RNA showed distinct expression patterns for female and male rats. Expression of serotonin-1A receptor messenger RNA was greater in males in subregions of the hypothalamus and amygdala, and less in males in subregions of the hippocampus. No significant differences in the distribution of serotonin-1A receptor binding sites were found between the sexes. Serotonin-2A receptor messenger RNA expression was comparable in males and females in all brain regions except the ventromedial hypothalamic nuclei, where lower levels were seen in females. However, the binding of serotonin-2A receptor measured with [H-3]ketanserin was significantly higher in females in all regions of the hippocampus. In a separate study, gonadectomy in males significantly increased serotonin-1A messenger RNA content in the cortex, hypothalamus, hippocampus, amygdala and dorsal raphe, and decreased serotonin-2A messenger RNA in ventromedial hypothalamic nuclei only. Almost all gonadectomy-induced changes were reversed by concomitant administration of testosterone. Our data provide evidence for region-specific sex differences in serotonin receptor subtype 1A and 2A transcription and concentration in the rat brain, and further suggest a modulatory role of testosterone in serotonin (particularly subtype 1A) receptor expression. Gender and gonadal steroid effects on central serotonergic systems may underlie the reported sexual dimorphisms in affective state regulation, response to psychopharmacological agonists or pituitary adrenal activation. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,Room 3N238,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. NR 53 TC 96 Z9 98 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 1 BP 251 EP 259 DI 10.1016/S0306-4522(99)00234-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 239EH UT WOS:000082755500027 PM 10613515 ER PT J AU Eisch, AJ Lammers, CH Yajima, S Mouradian, MM Nestler, EJ AF Eisch, AJ Lammers, CH Yajima, S Mouradian, MM Nestler, EJ TI In vivo regulation of glial cell line-derived neurotrophic factor-inducible transcription factor by kainic acid SO NEUROSCIENCE LA English DT Article DE GDNF; TGF-beta; seizure-regulation; hippocampus; accumbens; in situ hybridization ID MIDBRAIN DOPAMINERGIC-NEURONS; SEIZURE-INDUCED CHANGES; BRAIN DAMAGE SYNDROME; C-RET PROTOONCOGENE; IN-VIVO; NERVOUS-SYSTEM; BINDING-SITES; RAT-BRAIN; MESSENGER-RNA; TYROSINE KINASE AB A putative transcription factor induced in vitro by glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta was recently cloned and characterized [Yajima S, er al. (1997) J. Neurosci. 17, 8657-8666]. The messenger RNA of this protein, termed murine GDNF-inducible transcription factor (mGIF, hereafter referred to as GIF), is localized within cortical and hippocampal regions of brain, suggesting that GIF might be regulated by perturbations of these brain regions. In an effort to learn more about the role of GIF in vivo, we examined GIF messenger RNA in the brains of rats treated with the glutamatergic agonist kainic acid. This treatment is known to induce seizures and alter the messenger RNA expression of several growth factors, including GDNF, in several brain regions. Rats were given intraperitoneal saline (1 ml/kg) or kainic acid (15 mg/kg) and were killed at various time-points for in situ hybridization of brain sections with a GIF messenger RNA riboprobe. In saline-treated rats, GIF messenger RNA was present at low levels in cerebral colter, hippocampus and hippocampal remnants such as the taenia tecta. Kainic acid treatment induced robust increases in GIF messenger RNA in several brain regions, including cerebral cortex, hippocampus, caudate-putamen, nucleus accumbens, and several nuclei of the amygdala and hypothalamus. Most brain regions showed the greatest increase in GIF messenger RNA 4-6 h after kainic acid administration and a return towards normal levels at 48 h. The CA3 region of hippocampus, however, showed a more rapid increase in GIF messenger RNA that was also evident 48 h after kainic acid administration. These results demonstrate that GIF messenger RNA can be regulated in vivo, and that this novel factor warrants further study as a central mediator of GDNF and perhaps other neurotrophic factors. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, Lab Mol Psychiat,Dept Psychiat, New Haven, CT 06508 USA. Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, Dept Neurobiol, New Haven, CT 06508 USA. NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Nestler, EJ (reprint author), Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, Lab Mol Psychiat,Dept Psychiat, 34 Park St, New Haven, CT 06508 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 56 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 2 BP 629 EP 636 DI 10.1016/S0306-4522(99)00302-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 245YE UT WOS:000083135600026 PM 10579223 ER PT J AU Jezova, D Ochedalski, T Glickman, M Kiss, A Aguilera, G AF Jezova, D Ochedalski, T Glickman, M Kiss, A Aguilera, G TI Central corticotropin-releasing hormone receptors modulate hypothalamic-pituitary-adrenocortical and sympathoadrenal activity during stress SO NEUROSCIENCE LA English DT Article DE corticotropin-releasing hormone; ACTH; corticosterone; catecholamines; tyrosine hydroxylase; stress ID SPLANCHNIC NERVE-STIMULATION; MESSENGER-RIBONUCLEIC-ACID; PARAVENTRICULAR NUCLEUS; RAT HYPOTHALAMUS; LOCUS-COERULEUS; IMMOBILIZATION STRESS; ANGIOTENSIN-II; ADRENAL-CORTEX; C-FOS; BRAIN AB The role of brain corticotropin-releasing hormone receptors in modulating hypothalamic-pituitary-adrenal and sympathoadrenal responses to acute immobilization stress was studied in conscious rats under central corticotropin-releasing hormone receptor blockade by intracerebroventicular injection of a peptide corticotropin-releasing hormone receptor antagonist. Blood for catecholamines, adrenocorticotropic hormone and corticosterone levels was collected through vascular catheters, and brains were removed at 3 h for in situ hybridization for tyrosine hydroxylase messenger RNA in the locus coeruleus, and corticotropin-releasing hormone and corticotropin-releasing hormone receptor messenger RNA in the hypothalamic paraventricular nucleus. Central corticotropin-releasing hormone receptor blockade reduced the early increases in plasma epinephrine and dopamine, but not norepinephrine, during stress. Immobilization stress increased tyrosine hydroxylase messenger RNA levels in the locus coeruleus by 36% in controls, but not in corticotropin-releasing hormone antagonist-injected rats. In control rats, corticotropin-releasing hormone messenger RNA and type 1 corticotropin-releasing hormone receptor messenger RNA in the paraventricular nucleus increased after stress (P < 0.01), and these responses were attenuated by central corticotropin-releasing hormone receptor blockade. In contrast, central corticotropin-releasing hormone antagonist potentiated plasma adrenocorticotropic hormone responses, but slightly attenuated plasma corticosterone responses to stress. The inhibition of plasma catecholamine and locus coeruleus tyrosine hydroxylase messenger RNA responses to stress by central corticotropin-releasing hormone receptor blockade supports the notion that central corticotropin-releasing hormone regulates sympathoadrenal responses during stress. The attenuation of stress-induced corticotropin-releasing hormone and corticotropin-releasing hormone receptor messenger RNA responses by central corticotropin-releasing hormone receptor blockade suggests direct or indirect positive feedback effects of corticotropin-releasing hormone receptor ligands on corticotropin-releasing hormone expression, whereas additional mechanisms potentiate adrenocorticotropic hormone responses at the pituitary level. In addition, changes in neural activity by central corticotropin-releasing hormone are likely to modulate adrenocortical responsiveness during stress. Published by Elsevier Science Ltd. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia. RP Aguilera, G (reprint author), NICHHD, NIH, 10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. NR 47 TC 42 Z9 47 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 3 BP 797 EP 802 DI 10.1016/S0306-4522(99)00333-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 247ZM UT WOS:000083250900012 PM 10579570 ER PT J AU Tao-Cheng, JH Zhou, FC AF Tao-Cheng, JH Zhou, FC TI Differential polarization of serotonin transporters in axons versus soma-dendrites: An immunogold electron microscopy study SO NEUROSCIENCE LA English DT Article DE volume transmission; extrasynaptic transmission; synaptic cleft; raphe nucleus; specific serotonin reuptake inhibitor; immunocytochemistry ID ADULT-RAT; NUCLEUS-ACCUMBENS; ULTRASTRUCTURAL RELATIONSHIPS; DOPAMINE TRANSPORTER; TERMINALS; LOCALIZATION; NEURONS; BRAIN; MDMA; METHYLENEDIOXYMETHAMPHETAMINE AB In spite of the conventional belief that neurotransmitter uptake occurs at the synapses, we demonstrated previously that serotonin transporters and the high-affinity uptake of serotonin were not confined to the terminals but rather occurred throughout the axons [Zhou F. C. et al. (1998) Brain Res. 805, 241-254]. In the present study, the detailed distribution of serotonin transporters over various parts of the neuron was illustrated and analysed morphometrically using a pre-embedding immunogold method with a characterized serotonin transporter antibody at the electron microscopic level. Our findings reveal a highly polarized distribution of serotonin transporters between axons and soma-dendrites in two aspects. (1) On the plasma membrane, serotonin transporter-immunogold is extremely low on soma-dendrites and synaptic junctions, but consistently dense along the axons and perisynaptic area. (2) In contrast, serotonin transporter labeling in the cytoplasm is concentrated in soma and dendrites, particularly on the membranes of rough endoplasmic reticulum, Golgi complexes and tubulovesicular structures, but low in the axoplasm. The extensive distribution of serotonin transporter along the axolemma suggests a broad range of uptake sites beyond synaptic junctions, and is consistent with the notion that the major mode of transmission for serotonin neurons is through volume (extrasynaptic) transmission. The highly polarized distribution also indicates that the major serotonin uptake sites are on axons and not on soma-dendrites. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Indiana Univ, Sch Med, Dept Anat, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Program Med Neurobiol, Indianapolis, IN 46202 USA. NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. RP Zhou, FC (reprint author), Indiana Univ, Sch Med, Dept Anat, 635 Barnhill Dr,MS 508, Indianapolis, IN 46202 USA. FU NIAAA NIH HHS [P50AA07611-11]; NIMH NIH HHS [MH 50602] NR 42 TC 50 Z9 52 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 3 BP 821 EP 830 DI 10.1016/S0306-4522(99)00373-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 247ZM UT WOS:000083250900015 PM 10579573 ER PT J AU Gottschalk, W Kim, DS Chin, H Stanley, EF AF Gottschalk, W Kim, DS Chin, H Stanley, EF TI High-voltage-activated calcium channel messenger RNA expression in the 140-3 neuroblastoma-glioma cell line SO NEUROSCIENCE LA English DT Article DE T type; low-voltage-activated; calcium channel; alpha(1) subunit ID VERTEBRATE SENSORY NEURONS; BETA-GAMMA-SUBUNITS; T-TYPE; FUNCTIONAL EXPRESSION; CA2+ CHANNELS; G-PROTEIN; GANGLION NEURONS; XENOPUS-OOCYTES; HEK293 CELLS; GUINEA-PIG AB Expression of calcium channel alpha(1) subunits in oocytes or cell Lines has proven to be a powerful method in the analysis of structure-function relations, but these experimental systems are of Limited value in the examination of neuron-specific functions such as transmitter release. Cell lines derived from neurons are often capable of these functions, but their intrinsic calcium channel alpha(1) subunits are complicating factors in experimental design. We have examined the biophysical and molecular properties of calcium channels in a little studied neuroblastoma-glioma hybrid cell Line, 140-3, a dose relative of the NG108-15 cell line, to test whether this cell line might serve a role as an expression system for neural mechanisms. This cell was selected as it contains an intact transmitter release mechanism yet secretes Little in response to depolarization. Patch-clamp recording revealed only a prominent low-threshold, rapidly inactivating calcium current with a single-channel conductance of similar to 7 pS that was identified as T type. A search for calcium channel al subunit messenger RNA in the 140-3 cells with three different tests only revealed alpha(1C), whereas alpha(1A)-alpha(1C) were present in the parent NG108-15 line. We made a particular effort to search for alpha(1E), since this subunit has been associated with a low-voltage-activated current. Our findings suggest that, since the principal nerve terminal-associated calcium channels (alpha(1A), alpha(1B), alpha(1E)) are absent in the 140-3 cell, this cell line may prove a particularly useful model for the analysis of the role of high-voltage-activated calcium channels in complex functions of neuronal cells. Published by Elsevier Science Ltd. C1 NINDS, Synapt Mechanisms Sect, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Stanley, EF (reprint author), NINDS, Synapt Mechanisms Sect, NIH, Bethesda, MD 20892 USA. NR 48 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 3 BP 975 EP 983 DI 10.1016/S0306-4522(99)00341-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 247ZM UT WOS:000083250900032 PM 10579590 ER PT J AU Wang, Y Qin, ZH Nakai, M Chen, RW Chuang, DM Chase, TN AF Wang, Y Qin, ZH Nakai, M Chen, RW Chuang, DM Chase, TN TI Co-stimulation of cyclic-AMP-linked metabotropic glutamate receptors in rat striatum attenuates excitotoxin-induced nuclear factor-kappa B activation and apoptosis SO NEUROSCIENCE LA English DT Article DE NF-kappa B; metabotropic glutamate receptor; ionotropic glutamate receptor; apoptosis; neurodegeneration ID METHYL-D-ASPARTATE; CEREBELLAR GRANULE NEURONS; SYNAPTIC TRANSMISSION; CORTICAL-NEURONS; CALCIUM CURRENTS; GLOBAL-ISCHEMIA; MESSENGER-RNA; MOUSE-BRAIN; CELL-DEATH; EXPRESSION AB Interactions between glutamatergic mechanisms mediated by receptors of the ionotropic and metabotropic classes in the central nervous system are complex and incompletely understood. To explore the consequences of these interactions on excitotoxicity, we examined the influence of group II and group III selective metabotropic glutamate receptor agonists on the N-methyl-D-aspartate-induced apoptotic destruction of GABAergic neurons in rat striatum. The intrastriatal administration of a group III metabotropic glutamate receptor agonist (amino-4-phosphonobutyric acid, 900-1800 nmol), but not of a group II agonist [(2S,1'S,2'S)-(carboxycyclopropyl)glycine, 100-1800 nmol] produced internucleosomal DNA fragmentation. Similarly, amino-4-phosphonobutyric acid (600 nmol) but not (2S,1'S,2'S)-(carboxycyclopropyl)glycine (100-1800 nmol) destroyed some striatal neurons as indicated by a loss of D1 dopamine receptors and 67,000 mel, wt glutamate decarboxylase (glutamate decarboxylase-67) messenger RNA. On the other hand, the intensity of internucleosomal DNA fragmentation induced by N-methyl-D-aspartate (150 nmol) was substantially decreased by the intrastriatal co-administration of either (2S,1'S,2'S)-(carboxycyclopropyl)glycine or amino-4-phosphonobutyric acid (100-600 nmol). Both (2S,1'S,2'S)-(carboxycyclopropyl)glycine and amino-4-phosphonobutyric acid also reduced the N-methyl-D-aspartate-induced loss of striatal D1 dopamine receptors by 67% and 68% (both P < 0.001), and glutamate decarboxylase-67 messenger RNA by 68% and 61%, respectively. Furthermore, both (2S, 1'S,2'S)(carboxycyclopropyl)glycine and amino-4-phosphonobutyric acid also attenuated the N-methyl-D-aspartate-induced decline in striatal I kappa B-alpha protein levels by 62% and 37%, as well as the increase in nuclear transcription factor nuclear factor-kappa B binding activity by 135% and 94% (both P < 0.001), and the subsequent rise in p53 and c-Myc protein levels. These results suggest that stimulation of cyclic-AMP-linked metabotropic glutamate receptors inhibits ionotropic glutamate receptor-mediated activation of apoptotic cascades involving I kappa B-alpha degradation and nuclear factor-kappa B nuclear translocation, as well as p53 and c-Myc induction. Certain selective metabotropic glutamate receptor agonists might thus find utility as adjuncts to N-methyl-D-aspartate antagonists in the protection against the neurotoxicity initiated by excessive ionotropic glutamate receptor stimulation. Published by Elsevier Science Ltd. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, 10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. NR 71 TC 25 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 4 BP 1153 EP 1162 DI 10.1016/S0306-4522(99)00264-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA 256PW UT WOS:000083735000012 PM 10625054 ER PT J AU Feng, L Wang, CY Jiang, H Oho, C Dugich-Djordjevic, M Mei, L Lu, B AF Feng, L Wang, CY Jiang, H Oho, C Dugich-Djordjevic, M Mei, L Lu, B TI Differential signaling of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor in cultured ventral mesencephalic neurons SO NEUROSCIENCE LA English DT Article DE GDNF; BDNF; MAPK; CREB; mesencephalic; PD098059 ID ACTIVATED PROTEIN-KINASE; MIDBRAIN DOPAMINERGIC-NEURONS; RECEPTOR TYROSINE KINASE; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; RAT MODEL; IN-VIVO; GROWTH-FACTOR; RET RECEPTOR; TRANSDUCTION EVENTS AB In the ventral mesencephalon, two neurotrophic factors, brain-derived neurotrophic factor and glial cell Line-derived neurotrophic factor, have been shown previously to have similar effects on the survival of dopaminergic neurons. Here, we compared the signaling mechanisms for brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, focusing on the mitogen-associated protein kinase and the transcription factor cyclic-AMP responsive element-binding protein. Double staining experiments indicated that many neurons co-expressed the receptors for glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor, c-RET and TrkB, suggesting that they are responsive to both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Although both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor induced a rapid phosphorylation of mitogen-associated protein kinase and cyclic-AMP responsive element-binding protein, there were significant differences in the kinetics and pharmacology of the phosphorylation. The phosphorylation of mitogen-associated protein kinase by glial cell line-derived neurotrophic factor was transient; within 2 h, the level of mitogen associated protein kinase phosphorylation returned to baseline. In contrast, the effect of brain-derived neurotrophic factor was long lasting: the mitogen-associated protein kinase remained phosphorylated for up to 4 h after brain-derived neurotrophic factor treatment. PD098059, a specific inhibitor for mitogen-associated protein kinase kinase, completely blocked the glial cell Line derived neurotrophic factor signaling through mitogen-associated protein kinase, but had no effect on brain-derived neurotrophic factor-induced mitogen-associated protein kinase phosphorylation. Both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor induced the phosphorylation of cyclic-AMP responsive element-binding protein in the nuclei of ventral mesencephalon neurons. However, PD098059 blocked the cyclic-AMP responsive element-binding protein phosphorylation induced by glial cell line-derived neurotrophic factor, but not that by brain-derived neurotrophic factor. These results indicate that, although both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor act on ventral mesencephalon neurons, the two factors have different signaling mechanisms, which may mediate their distinctive biological functions. C1 NICHD, Unit Synapse Dev & Plast, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Chinese Acad Sci, Shanghai Res Ctr Life Sci, Shanghai 200031, Peoples R China. Chinese Acad Sci, Shanghai Brain Res Inst, Shanghai 200031, Peoples R China. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA. RP Lu, B (reprint author), NICHD, Unit Synapse Dev & Plast, Dev Neurobiol Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012; Mei, Lin/G-8755-2012 NR 67 TC 27 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 93 IS 1 BP 265 EP 273 DI 10.1016/S0306-4522(99)00129-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 212BJ UT WOS:000081196200025 PM 10430490 ER PT J AU Baffi, JS Palkovits, M Castillo, SO Mezey, E Nikodem, VM AF Baffi, JS Palkovits, M Castillo, SO Mezey, E Nikodem, VM TI Differential expression of tyrosine hydroxylase in catecholaminergic neurons of neonatal wild-type and Nurr1-deficient mice SO NEUROSCIENCE LA English DT Article DE Nurr1; orphan nuclear receptor; catecholaminergic cell groups; tyrosine hydroxylase; central nervous system; in situ hybridization ID NUCLEAR RECEPTORS; NGFI-B; TRANSCRIPTION FACTOR; HORMONE RECEPTORS; ORPHAN RECEPTORS; NURR1 GENE; RAT-BRAIN; ADULT-RAT; IDENTIFICATION; SUPERFAMILY AB The orphan nuclear receptor Nurr1 is a transcription factor that belongs to the steroid/thyroid hormone receptor superfamily and is expressed in many regions of the brain. To determine the physiological role of Nurr1, we previously generated mice with a null mutation in the Nurr1 gene. Nurr1-null mice appear to develop normally but die within 12 h after birth. Subsequent analysis revealed the absence of neurotransmitter dopamine and tyrosine hydroxylase immunoreactivity in the central dopaminergic area of newborn pups. Herein, using in situ hybridization histochemistry, we show that Nurr1 is expressed only in subset of catecholamine producing neurons (A2 partly, A8-A10 and A11 catecholaminergic cell groups), and is excluded from the norepinephrine producing neurons (A1, A2, A5-A6 catecholaminergic cell groups). Nurr1 was not expressed in the dopamine synthesizing cell groups (A12-A16 catecholaminergic cell groups) of the diencephalon and the olfactory bulb. As previously shown and confirmed in this study, tyrosine hydroxylase immunoreactivity was absent in the substantia nigra and ventral tegmental area of Nurr1-deficient mice. However, the loss of Nurr1 expression in A2 and A11 dopaminergic neurons did not affect their tyrosine hydroxylase immunoreactivity. This study begins to dissect cues necessary for understanding the complex regulation of the catecholaminergic biosynthetic pathway with regard to local, chemical and developmental changes in the brain. Published by Elsevier Science Ltd. C1 NIDDK, GBB, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. NIMH, Genet Sect, NIH, Bethesda, MD 20892 USA. RP Nikodem, VM (reprint author), NIDDK, GBB, NIH, Bldg 10,Room 8N317,10 Ctr Dr,MSC 1766, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 26 TC 31 Z9 32 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 93 IS 2 BP 631 EP 642 DI 10.1016/S0306-4522(99)00124-4 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 222FL UT WOS:000081772800025 PM 10465447 ER PT J AU Hill, JM Lee, SJ Dibbern, DA Fridkin, M Gozes, I Brenneman, DE AF Hill, JM Lee, SJ Dibbern, DA Fridkin, M Gozes, I Brenneman, DE TI Pharmacologically distinct vasoactive intestinal peptide binding sites: CNS localization and role in embryonic growth SO NEUROSCIENCE LA English DT Article DE vasoactive intestinal peptide; activity-dependent neurotrophic factor; pituitary adenylyl cyclase-activating peptide; embryonic growth; receptor ID CYCLASE-ACTIVATING POLYPEPTIDE; CULTURED MOUSE EMBRYOS; RAT-BRAIN; NEURONAL SURVIVAL; PITUITARY-GLAND; MESSENGER-RNA; RECEPTORS; VIP; CELLS; PACAP AB In vitro autoradiography with [I-125]vasoactive intestinal peptide revealed that the vasoactive intestinal peptide analogue, stearyl-norleucine(17) vasoactive intestinal peptide, reported to be inactive at adenylyl cyclase-linked receptors in astrocytes, displaced a subset of vasoactive intestinal peptide binding sites on rat brain sections. These sites were widespread in adult rat brains and enriched in the olfactory bulb and thalamus, and corresponded to previously demonstrated GTP-insensitive vasoactive intestinal peptide binding sites. Stearyl-norleucine(17) vasoactive intestinal peptide also identified receptors in rat lung and liver. In the adult brain, the stearyl-norleucine analog displaced only GTP-insensitive vasoactive intestinal peptide binding sites. In contrast, stearyl-norleucine(17) vasoactive intestinal peptide-displaceable sites in the embryonic day 9 mouse appeared to include both GTP-sensitive and GTP-insensitive binding sites. This observation suggested the presence of an embryonic vasoactive intestinal peptide receptor with distinct pharmacological properties. Treatment of whole cultured mouse embryos with stearyl-norleucine(17) vasoactive intestinal peptide resulted in stimulation of embryonic growth, with the stearyl-norleucine analog equipotent to vasoactive intestinal peptide, but less efficacious at higher concentrations (10(-7) M). Embryonic growth was inhibited by pituitary adenylyl cyclase-activating peptide and 8-bromoadenosine 3',5'-cyclic monophosphate. In addition, 8-bromoadenosine 3',5'-cyclic monophosphate inhibited stearyl-norleucine(17) vasoactive intestinal peptide-stimulated growth. The results of the current study support the hypothesis that vasoactive intestinal peptide regulation of early postimplantation embryonic growth occurs, at least in part, independently of adenylyl cyclase stimulation. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Hill, JM (reprint author), NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. NR 44 TC 35 Z9 35 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 93 IS 2 BP 783 EP 791 DI 10.1016/S0306-4522(99)00155-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 222FL UT WOS:000081772800039 PM 10465461 ER PT J AU Ren, RF Lah, JJ Diehlmann, A Kim, ES Hawver, DB Levey, AI Beyreuther, K Flanders, KC AF Ren, RF Lah, JJ Diehlmann, A Kim, ES Hawver, DB Levey, AI Beyreuther, K Flanders, KC TI Differential effects of transforming growth factor-beta s and glial cell line-derived neurotrophic factor on gene expression of presenilin-1 in human post-mitotic neurons and astrocytes SO NEUROSCIENCE LA English DT Article DE Alzheimer's disease; presenilin 1; hNT cells; astrocytes; transforming growth factor-beta; glial cell line-derived neurotrophic factor ID FAMILIAL ALZHEIMERS-DISEASE; TGF-BETA; MESSENGER-RNA; NTERA-2 CELLS; DEVELOPMENTAL REGULATION; AMYLOID PEPTIDE; II RECEPTOR; BRAIN; MUTATION; PROTEINS AB Mutations in the presenilin-1 gene are linked to the majority of early-onset familial Alzheimer's disease cases. We have previously shown that the expression of transforming growth factor-beta is altered in Alzheimer's patients, compared to controls. Here we examine presenilin-1 expression in human post-mitotic neurons (hNT cells), normal human astrocytes, and human brain tumor cell lines following treatment with three isoforms of transforming growth factor-beta, or glial cell line-derived neurotrophic factor, a member of the transforming growth factor-beta superfamily. As the NT2/D1 teratocarcinoma cell line is treated with retinoic acid to induce differentiation to hNT cells, presenilin-1 messenger RNA expression is dramatically increased. Furthermore, there is a 2-3-fold increase in presenilin-1 messenger RNA expression following treatment of hNT cells with growth factors and similar results are found by Western blotting and with immunohistochemical staining for presenilin-1 protein. However, treatment of normal human astrocytes with cytokines results in minimal changes in presenilin-1 messenger RNA and protein, interestingly, the expression of presenilin-1 in human U87 MG astrocytoma and human SK-N-SH neuroblastoma cells is only increased when cells are treated with glial cell line-derived neurotrophic factor or transforming growth factor-beta 3. These findings suggest that endogenous presenilin-1 gene expression in human neurons can be induced by growth factors present in normal and diseased brain tissue. Cytokines may play a major role in regulating expression of presenilin-1 which may affect its biological actions in physiological and pathological conditions. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Univ Heidelberg, Lab Mol Neuropathol, D-69120 Heidelberg, Germany. NIA, Biochem Lab, Baltimore, MD 21224 USA. RP Flanders, KC (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RI Levey, Allan/F-2104-2011 OI Levey, Allan/0000-0002-3153-502X NR 54 TC 14 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 93 IS 3 BP 1041 EP 1049 DI 10.1016/S0306-4522(99)00215-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 226KG UT WOS:000082018700022 PM 10473269 ER PT J AU Clifford, JJ Tighe, O Croke, DT Kinsella, A Sibley, DR Drago, J Waddington, JL AF Clifford, JJ Tighe, O Croke, DT Kinsella, A Sibley, DR Drago, J Waddington, JL TI Conservation of behavioural topography to dopamine D-1-like receptor agonists in mutant mice lacking the D-1A receptor implicates a D-1-like receptor not coupled to adenylyl cyclase SO NEUROSCIENCE LA English DT Article DE D-1-like dopamine receptors; adenylyl cyclase; mutant mice; D-1A knockout; behaviour ID RAT-BRAIN; MOLECULAR-BIOLOGY; RESPONSES; STIMULATION; ACTIVATION; EXPRESSION; DEFICIENT; A-68930; NUCLEUS AB Though D-1-like dopamine receptors [D-1A/B] are defined in terms of linkage to the stimulation of adenylyl cyclase, with D-1A assumed to be the functionally prepotent subtype, evidence suggests the existence of another, novel D-1-like receptor without such coupling. To investigate these issues we challenged mutant mice having targeted gene deletion of the D-1A receptor with selective agonists and used an ethologically-based assessment technique to resolve resultant behavioural topography. D-1-like-dependent behaviour was substantially conserved in D-1A-null mice relative to wild-types following challenge with each of two selective D-1-like agents: A 68930 (0.068-2.0 mg/kg s.c.) which exhibits full efficacy to stimulate adenylyl cyclase, and SKF 83959 (0.016-2.0 mg/kg s.c.) which fails to stimulate adenylyl cyclase, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine. Furthermore, responsivity to the selective D-2-like agonist RU 24213 (0.1-12.5 mg/kg s.c.) was conserved in D-1A-null mice, indicating the integrity of D-1-like:D-2-like interactions at the level of behaviour. These data are consistent with behavioural primacy of a D-1-like receptor other than D-1A [or D-1B] that is coupled to a transduction system other than/additional to adenylyl cyclase. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Royal Coll Surg Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. Royal Coll Surg Ireland, Dept Biochem, Dublin 2, Ireland. Dublin Inst Technol, Dept Math, Dublin 8, Ireland. NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. RP Waddington, JL (reprint author), Royal Coll Surg Ireland, Dept Clin Pharmacol, St Stephens Green, Dublin 2, Ireland. FU NIMH NIH HHS [N01MH30003] NR 40 TC 56 Z9 58 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 93 IS 4 BP 1483 EP 1489 DI 10.1016/S0306-4522(99)00297-3 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 233PV UT WOS:000082436000030 PM 10501473 ER PT J AU Hohmann, AG Herkenham, M AF Hohmann, AG Herkenham, M TI Cannabinoid receptors undergo axonal flow in sensory nerves SO NEUROSCIENCE LA English DT Article DE peripheral; anterograde transport; neurosecretion; anandamide; dorsal root ganglia ID STIMULUS-EVOKED ACTIVITY; CORD DORSAL HORN; SPINAL-CORD; RAT-BRAIN; OPIOID RECEPTORS; CB1 RECEPTORS; LOCALIZATION; EXPRESSION; NEURONS; AGONIST AB Cannabinoids modulate nociceptive processing through central and peripheral mechanisms. The present study was conducted to evaluate axonal flow of cannabinoid receptors from the dorsal root ganglion to the periphery and to identify the putative involvement of CB1 and/or CB2 receptor subtypes. The sciatic nerve was tightly ligated to dam the how of cannabinoid receptors to the periphery. The densities of cannabinoid receptors proximal and distal to one or two tightly constrictive ligatures was evaluated using in vitro receptor binding and high-resolution emulsion autoradiography, In both models, [H-3]CP55,940 binding accumulated proximal as opposed to distal to the ligature. These data indicate that axonal transport of cannabinoid receptors to the periphery was occluded by tight constriction of the sciatic nerve, In situ hybridization histochemistry revealed that dorsal root ganglia cells synthesize CB1 but not CB2 receptor messenger RNA. By contrast, CB2 messenger RNA was highly expressed in sections of rat spleen that were processed together with the dorsal root ganglia, as previously described. These data demonstrate that neuronal cannabinoid CB1 receptors are synthesized in cells of the dorsal root ganglia and inserted on terminals in the periphery. (C) 1999 IBRO, Published by Elsevier Science Ltd. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Hohmann, AG (reprint author), Natl Inst Dent & Craniofacial Res, Cellular Neurosci Sect, Pain & Neurosensory Mechanisms Branch, Bldg 49,Room 1A11, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 35 TC 120 Z9 123 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 92 IS 4 BP 1171 EP 1175 DI 10.1016/S0306-4522(99)00220-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 211VJ UT WOS:000081182300003 PM 10426476 ER PT J AU Kong, LY Maderdrut, JL Jeohn, GH Hong, JS AF Kong, LY Maderdrut, JL Jeohn, GH Hong, JS TI Reduction of lipopolysaccharide-induced neurotoxicity in mixed cortical neuron/glia cultures by femtomolar concentrations of pituitary adenylate cyclase-activating polypeptide SO NEUROSCIENCE LA English DT Article DE cell culture; cell death; microglia; neuroprotection; nitric oxide; pituitary adenylate cyclase-activating polypeptide ID VASOACTIVE-INTESTINAL-PEPTIDE; NECROSIS-FACTOR-ALPHA; DIFFERENTIAL SIGNAL-TRANSDUCTION; CEREBELLAR GRANULE NEURONS; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE; PACAP RECEPTOR; HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; SPLICE VARIANTS AB Stimulation of murine primary mixed cortical neuron/glia cultures with lipopolysaccharide, an endotoxin, was used as a model for inflammatory disorders of the central nervous system. Lipopolysaccharide (20 mu g/ml) increased the secretion of lactate dehydrogenase, a marker for cell injury, and nitric oxide into the culture medium. The lipopolysaccharide induced release of lactate dehydrogenase into the culture medium was reduced by pituitary adenylate cyclase-activating polypeptide (PACAP) at 10(-14)-10(-12) M. The 27- and 38-amino-acid forms of PACAP were equipotent and their dose-response curves were U-shaped. PACAP6-38, a specific type I PACAP receptor antagonist, blocked the reduction by PACAP38 of the Lipopolysaccharide-induced release of lactate dehydrogenase. The lipopolysaccharide-induced secretion of nitric oxide into the culture medium was reduced by PACAP at 10(-14-)10(-12) M and 10(-8)-10(-6) M. The 27- and 38-amino-acid forms of PACAP were equipotent, PACAP6-38 blocked the reduction of the lipopolysaccharide-induced secretion of nitric oxide by PACAP38 at 10(-12) M, but not at 10(-8) M. Vasoactive intestinal polypeptide reduced the lipopolysaccharide-induced release of lactate dehydrogenase into the culture medium at 10(-14)-10(-12) M, but these concentrations of vasoactive intestinal polypeptide had no effect on the lipopolysaccharide-induced secretion of nitric oxide. PACAP6-38 did not effect the reduction of the lipopolysaccharide-induced release of lactate dehydrogenase into the culture medium by 10(-12) M vasoactive intestinal polypeptide, These results indicate that stimulation of type I PACAP receptors by femtomolar concentrations of PACAP can prevent neuron death in a model for inflammatory disorders of the CNS. These results suggest that PACAP is also an extraordinarily potent inhibitor of some microglial functions. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Tulane Univ, Hebert Ctr, US Japan Biomed Res Labs, Belle Chasse, LA 70037 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 47 TC 44 Z9 44 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 91 IS 2 BP 493 EP 500 DI 10.1016/S0306-4522(98)00606-X PG 8 WC Neurosciences SC Neurosciences & Neurology GA 190RA UT WOS:000079977200009 PM 10366006 ER PT J AU Ruskin, DN Bergstrom, DA Mastropietro, CW Twery, MJ Walters, JR AF Ruskin, DN Bergstrom, DA Mastropietro, CW Twery, MJ Walters, JR TI Dopamine agonist-mediated rotation in rats with unilateral nigrostriatal lesions is not dependent on net inhibitions of rate in basal ganglia output nuclei SO NEUROSCIENCE LA English DT Article DE substantia nigra pars reticulata; entopeduncular nucleus; D-1 receptor; Fos; SKF38393; apomorphine ID NIGRA PARS RETICULATA; C-FOS EXPRESSION; SUBSTANTIA-NIGRA; RECEPTOR STIMULATION; SUBTHALAMIC NUCLEUS; GLOBUS-PALLIDUS; 6-HYDROXYDOPAMINE-LESIONED RATS; STRIATOPALLIDAL NEURONS; RESERPINE TREATMENT; UNIT-ACTIVITY AB Current models of basal ganglia function predict that dopamine agonist-induced motor activation is mediated by decreases in basal ganglia output. This study examines the relationship between dopamine agonist effects on firing rate in basal ganglia output nuclei and rotational behavior in rats with nigrostriatal lesions. Extracellular single-unit activity ipsilateral to the lesion was recorded in awake, locally-anesthetized rats. Separate rats were used for behavioral experiments. Low i.v. doses of D-1 agonists (SKF 38393, SKF 81297, SKF 82958) were effective in producing rotation, yet did not change average firing rate in the substantia nigra pars reticulata or entopeduncular nucleus. At these doses, firing rate effects differed from neuron to neuron, and included increases, decreases, and no change. Higher i.v. doses of D1 agonists were effective in causing both rotation and a net decrease in rate of substantia nigra pars reticulata neurons. A low s.c. dose of the D-1/D-2 agonist apomorphine (0.05 mg/kg) produced both rotation and a robust average decrease in firing rate in the substantia nigra pars reticulata, yet the onset of the net firing rate decrease (at 13-16 min) was greatly delayed compared to the onset of rotation (at 3 min). Immunostaining for the immediate-early gene Fos indicated that a low i.v,dose of SKF 38393 (that produced rotation but not a net decrease in firing rate in basal ganglia output nuclei) induced Fos-like immunoreactivity in the striatum and subthalamic nucleus, suggesting an activation of both inhibitory and excitatory afferents to the substantia nigra and entopeduncular nucleus. In addition, D-1 agonist-induced Fos expression in the striatum and subthalamic nucleus was equivalent in freely-moving and awake, locally-anesthetized rats. The results show that decreases in firing rate in basal ganglia output nuclei are not necessary for dopamine agonist-induced motor activation. Motor-activating actions of dopamine agonists may be mediated by firing rate decreases in a small subpopulation of output nucleus neurons, or may be mediated by other features of firing activity besides rate in these nuclei such as oscillatory firing pattern or interneuronal firing synchrony. Also, the results suggest that dopamine receptors in both the striatum and at extrastriatal sites (especially the subthalamic nucleus) are likely to be involved in dopamine agonist influences on firing rates in the substantia nigra pars reticulata and entopeduncular nucleus. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ruskin, DN (reprint author), NINDS, Expt Therapeut Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 56 TC 21 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 91 IS 3 BP 935 EP 946 DI 10.1016/S0306-4522(98)00689-7 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 195JV UT WOS:000080248000010 PM 10391472 ER PT J AU Jayanthi, S Ladenheim, B Andrews, AM Cadet, JL AF Jayanthi, S Ladenheim, B Andrews, AM Cadet, JL TI Overexpression of human copper zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (ecstasy) SO NEUROSCIENCE LA English DT Article DE MDMA; superoxide dismutase; transgenic mice; antioxidant enzymes; biogenic amines ID MDMA ECSTASY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SEROTONIN NEUROTOXICITY; LIPID-PEROXIDATION; FREE-RADICALS; RAT-BRAIN; NEURONS; ACID; NEURODEGENERATION; DOPAMINE AB Administration of 3,4-methylenedioxymethamphetamine (4 x 20 mg/kg) to non-transgenic CD-I mice caused marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and 5-hydroxytryptamine in the caudate-putamen. There were no significant changes in serotonergic markers in the hippocampus and frontal cortex. Homozygous and heterozygous copper/zinc superoxide dismutase transgenic mice show partial protection against the toxic effects of 3,4-methylenedioxymethamphetamine on striatal dopaminergic markers. In addition, 3,4-methylenedioxymethamphetamine injections caused marked decreases in copper/zinc superoxide dismutase activity in the frontal cortex, caudate-putamen and hippocampus of wild-type mice. Moreover, there were concomitant 3,4-methylenedioxymethamphetamine-induced decreases in catalase activity in the caudate-putamen and hippocampus, decreases in glutathione peroxidase activity in the frontal cortex as well as increases in lipid peroxidation in the frontal cortex: caudate-putamen, and hippocampus of wild-type mice. In contrast, administration of 3,4-methylenedioxymethamphetamine to homozygous superoxide dismutase transgenic mice caused no significant changes in antioxidant enzyme activities nor in lipid peroxidation. These results provide further substantiation of a role for oxygen-based radicals in 3,4-methylenedioxymethamphetamine-induced neurotoxicity. The present data also suggest that free radicals generated during 3,4-methylenedioxymethamphetamine administration may perturb antioxidant enzymes. Consequently. there might be further overproduction of free radicals with associated peroxidative damage to cell membranes and associated terminal degeneration. C1 NIDA, Mol Neuropsychiat Sect, NIH, Bethesda, MD 20892 USA. NIDA, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, Bethesda, MD 20892 USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 NR 44 TC 56 Z9 56 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 91 IS 4 BP 1379 EP 1387 DI 10.1016/S0306-4522(98)00698-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 198RK UT WOS:000080437600018 PM 10391444 ER PT J AU Hohmann, AG Herkenham, M AF Hohmann, AG Herkenham, M TI Localization of central cannabinoid CB1 receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: A double-label in situ hybridization study SO NEUROSCIENCE LA English DT Article DE anandamide; digoxigenin; substance P; CGRP; somatostatin; dorsal root ganglia ID GENE-RELATED PEPTIDE; PRIMARY SENSORY NEURONS; PRIMARY AFFERENT NEURONS; STIMULUS-EVOKED ACTIVITY; CENTRAL-NERVOUS-SYSTEM; INHIBIT N-TYPE; SUBSTANCE-P; INSITU HYBRIDIZATION; SPINAL-CORD; NEUROPATHIC PAIN AB In situ hybridization histochemistry was used to show the distribution of messenger RNA for central cannabinoid CB1 receptors in dorsal root ganglia of the rat. CB1 messenger RNA was highly expressed in neuronal subpopulations of rat dorsal root ganglia. The phenotypes of neurons that express messenger RNA for CB1 were subsequently examined by combining a S-35-labeled ribonucleotide probe for CB1 messenger RNA with digoxigenin-labeled riboprobes for preprotachykinin A (substance P precursor), alpha-calcitonin gene-related peptide and preprosomatostatin (somatostatin precursor) messenger RNAs. Qualitative examination revealed expression of CB1 messenger RNA predominantly in medium- and large-sized cells distributed throughout the dorsal root ganglia. The majority of neurons expressing substance P messenger RNA were CBI messenger RNA negative and smaller in size than the CB1 messenger RNA-positive cells. Only 13% of substance P messenger RNA-positive cells expressed CB1 messenger RNA. A similar degree of co-localization was observed with alpha-calcitonin gene-related peptide: 10% of cells expressing messenger RNA for this neuropeptide were CB1 messenger RNA positive. Colocalization of CB1 and somatostatin messenger RNAs was observed in less than 0.5% of somatostatin messenger RNA-positive cells. The data suggest that subpopulations of neurons in rat dorsal root ganglia are capable of synthesizing cannabinoid receptors and inserting them on terminals in the superficial dorsal horn. These findings provide anatomical evidence for cannabinoid modulation of primary afferent transmission. Although an anatomical basis for cannabinoid-mediated suppression of release of neurogenic peptides from nociceptive primary afferents is provided, our results demonstrate that the majority of CB1 messenger RNA-positive neurons in the dorsal root ganglia contain transmitters and/or neuromodulators other than the neuropeptides examined herein. C1 NIMH, Sect Funct Neuroanat, Bethesda, MD 20892 USA. RP Hohmann, AG (reprint author), NIMH, Sect Funct Neuroanat, Bldg 36,Room 2D15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 61 TC 194 Z9 201 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 90 IS 3 BP 923 EP 931 DI 10.1016/S0306-4522(98)00524-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 182TY UT WOS:000079515300020 PM 10218792 ER PT J AU Carta, AR Gerfen, CR AF Carta, AR Gerfen, CR TI Lack of a role for the D-3 receptor in clozapine induction of c-Fos demonstrated in D-3 dopamine receptor-deficient mice SO NEUROSCIENCE LA English DT Article DE dopamine; D-3 receptor; clozapine; c-fos; striatum ID ATYPICAL ANTIPSYCHOTIC-DRUGS; NUCLEUS-ACCUMBENS; GENE-EXPRESSION; RAT-BRAIN; NEURONS; D2; D1; FOREBRAIN; STRIATUM; D3 AB The role of the D-3 dopamine receptor in mediating the effects of clozapine was analysed using in situ hybridization histochemistry to measure the induction of the immediate early gene c-fos in different brain areas of mice lacking a functional D-3 dopamine receptor compared to wild type mice. Clozapine treatment (15 and 30 mg/kg, s.c.) resulted in a' dose-dependent pattern of induction of c-fos messenger RNA in the striatum, accumbens and septal area, with a non-significant increase in the prefrontal cortex. There was no difference detected in any of these areas in the level of induction between mice lacking the D-3 receptor (D-3-/-) and wild type (D-3+/+) To determine which types of neurons in the striatum and accumbens displayed clozapine (30 mg/kg) induction of c-fos messenger RNA, a double-labeling experiment was performed using a radioactive c-fos messenger RNA probe and a digoxigenin-labeled enkephalin messenger RNA probe, the latter used as a marker of D-2-containing neurons. Clozapine-induced c-fos was detected in 20% of enkephalin-positive striatal neurons and 15% of enkephalin-positive accumbens neurons, and in both areas in about 10% of enkephalin-negative, putative D-1 neurons, in both D-3+/+ and D-3-/- mice. These results demonstrate that clozapine induction of c-fos messenger RNA is not dependent on the D-3 dopamine receptor subtype in the striatum or nucleus accumbens. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Gerfen, CR (reprint author), NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. NR 29 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 90 IS 3 BP 1021 EP 1029 DI 10.1016/S0306-4522(98)00498-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 182TY UT WOS:000079515300029 PM 10218801 ER PT J AU Xi, D Chin, H Gainer, H AF Xi, D Chin, H Gainer, H TI Analysis of synaptotagmin I-IV messenger RNA expression and developmental regulation in the rat hypothalamus and pituitary SO NEUROSCIENCE LA English DT Article DE synaptotagmin; exocytosis; peptide secretion; hypothalamus; development; quantitative RT-PCR ID POLYMERASE CHAIN-REACTION; QUANTITATIVE RT-PCR; POSTNATAL-DEVELOPMENT; MOLECULAR MACHINERY; GENE-EXPRESSION; CALCIUM SENSOR; CELL-LINES; BRAIN; NEUROENDOCRINE; VASOPRESSIN AB Synaptotagmins are a large family of synaptic vesicle membrane proteins, that appear to be involved in neurotransmitter secretion from small secretory vesicles. We have quantitatively analysed the messenger RNA levels of synaptotagmin I-IV isoforms in adult hypothalamic and pituitary tissues in order to determine which of: these isoforms dominate in these tissues which mainly secrete peptides from large dense core vesicles. We also studied the expression of these isoforms during prenatal (E15, and E17) and postnatal (P1, P7, P14 and P21) rat hypothalamic development. In order to assay small individual samples (e.g., pituitary and embryonic tissues). we employed quantitative reverse transcription-polymerase chain reaction methods. Our results show that synaptotagmin I messenger RNA is the most abundant isoform in all tissues, and is about 5.4- or 38-fold higher in hypothalamus than in neurointermediate and anterior pituitary lobe, respectively. Synaptotagmin II. which is very abundant in cerebellum, is relatively low in hypothalamus (5% of cerebellum) and virtually absent from the pituitary. Synaptotagmin III is about 10 times greater in the neural tissues versus the pituitary, and synaptotagmin IV was the least abundant isoform in all the tissues. Developmental analyses of the synaptotagmin isoforms in rat hypothalamus shows that all isoforms are at low levels during embryonic stages and increase postnatally. Synaptotagmin I and II have similar patterns and rise to maximum (adult) levels around P14, whereas synaptotagmin III and IV I each their maximum levels considerably earlier, at P1. These data show that synaptotagmin I is the dominant isoform in both predominantly peptide secreting systems (e.g., in pituitary tissues) and in neurotransmitter secreting systems (e.g., in cerebellum). While the developmental expression patterns of synaptotagmin I and II parallels the temporal development of synaptogenesis in the nervous system, the early maximal expression of synaptotagmin III and IV suggests that these isoforms may have other functions during early postnatal development. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Room 4D-20, Bethesda, MD 20892 USA. NR 35 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN PY 1999 VL 88 IS 2 BP 425 EP 435 DI 10.1016/S0306-4522(98)00234-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 130EJ UT WOS:000076506700009 PM 10197764 ER PT J AU MacArthur, L Ren, K Pfaffenroth, E Franklin, E Ruda, MA AF MacArthur, L Ren, K Pfaffenroth, E Franklin, E Ruda, MA TI Descending modulation of opioid-containing nociceptive neurons in rats with peripheral inflammation and hyperalgesia SO NEUROSCIENCE LA English DT Article DE descending control; nociception; spinal cord; dynorphin; enkephalin; inflammation ID PREPROENKEPHALIN MESSENGER-RNA; DORSAL HORN NEURONS; SPINAL-CORD; DEOXYRIBONUCLEIC-ACID; PAIN; MODEL; GENE; INHIBITION; PROJECTION; SYSTEMS AB Inflammation and hyperalgesia induce a dramatic up-regulation of opioid messenger RNA and peptide levels in nociceptive neurons of the spinal dorsal horn. Descending axons modulate nociceptive transmission at the spinal level during inflammatory pain, and may play a role in the development of persistent pain. The role of descending bulbospinal pathways in opioid-containing nociceptive neurons was examined. Removal of descending inputs to the spinal cord was performed by complete spinal transection at the midthoracic level. Seven days after spinal transection, rats received a unilateral hindpaw injection of complete Freund's adjuvant, a noxious stimulus that produces inflammation and hyperalgesia. Tissues from the L-4 and L-5 segments of the spinal cord were removed and analysed by northern blotting and immunocytochemistry. Spinal transection resulted in a Further increase in both dynorphin and enkephalin messenger RNA content following complete Freund's adjuvant injection. There was a similar distribution and number of dynorphin-immunoreactive cells in transected rats compared to rats which received sham surgery. These data suggest that increased dynorphin messenger RNA ipsilateral to inflammation, in rats without descending axons, was due to increased expression within the same cells and not to recruitment of additional dynorphin-expressing cells. This reflects a greater dynamic response of nociceptive neurons to noxious stimuli in the absence of descending modulation. Therefore, the net effect of descending afferents on spinal nociceptive circuits may be to reduce the response of opioid-containing neurons to noxious stimulation from the periphery. C1 NIDR, Cellular & Mol Mechanisms Sect, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Ruda, MA (reprint author), NIDR, Cellular & Mol Mechanisms Sect, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. NR 30 TC 34 Z9 34 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN PY 1999 VL 88 IS 2 BP 499 EP 506 DI 10.1016/S0306-4522(98)00204-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 130EJ UT WOS:000076506700015 PM 10197770 ER PT J AU Fields, RD Schwab, ME Silver, J AF Fields, RD Schwab, ME Silver, J TI Does CNS myelin inhibit axon regeneration? SO NEUROSCIENTIST LA English DT Article DE NI35/250; axon regeneration; proteoglycan; gliosis; oligodendrocytes; astrocytes; myelin; spinal cord injury; extracellular matrix ID CHONDROITIN SULFATE PROTEOGLYCANS; NEURITE GROWTH-INHIBITORS; RAT SPINAL-CORD; NERVOUS-SYSTEM; EXTRACELLULAR-MATRIX; REACTIVE GLIOSIS; ADULT AXONS; OUTGROWTH; MOLECULES; NEURONS AB Membrane proteins on oligodendrocytes and CNS myelin (NI35/250) have been shown to block axon outgrowth in culture, and this is thought to be one of the major reasons for severely limited regeneration of severed axons in the CNS of higher vertebrates, In a recent study, adult dorsal root ganglion (DRG) neurons, which are sensitive to these inhibitory proteins, regenerated successfully after transplantation into two white matter tracts of the rat brain without any intervention to suppress the inhibitory activity of CNS myelin, The results and implications of these two studies are considered. C1 NICHD, Neurocytol & Physiol Unit, NIH, Bethesda, MD 20892 USA. EM fields@helix.nih.gov RI Schwab, Martin/B-6818-2016 NR 50 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD JAN PY 1999 VL 5 IS 1 BP 12 EP 18 DI 10.1177/107385849900500103 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 162GM UT WOS:000078337600012 ER PT J AU O'Donovan, MJ AF O'Donovan, MJ TI Robustness and self-regulation in the production of neural activity by developing networks SO NEUROSCIENTIST LA English DT Review DE spinal development; self-regulation; spontaneous activity ID DEVELOPING SPINAL-CORD; CHICK-EMBRYO; LUMBOSACRAL MOTONEURONS; MOTOR-ACTIVITY; NEURONS; GLYCINE; SYSTEM; GABA; DIFFERENTIATION; ORGANIZATION AB Spontaneous activity is an important regulator of network development throughout the nervous system. Activity produced in different parts of the developing nervous system shares many features, which suggests that it does not depend on the detailed architecture of developing networks but rather on their common properties. Insights into the mechanisms responsible for generating spontaneous activity have come from recent studies of the spinal cord, Developing spinal networks are hyperexcitable and their immature synapses are subject to activity-dependent synaptic depression. The conjunction of these properties, which may be common throughout the developing nervous system, is responsible for the spontaneous, episodic activity expressed by spinal networks. These properties endow developing spinal networks with an extremely robust mechanism for generating spontaneous activity that is resistant to major pharmacological and surgical perturbations. C1 NINDS, Sect Dev Neurobiol, Neural Control Lab, NIH, Bethesda, MD 20892 USA. EM odonovan@codon.nih.gov NR 49 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD JAN PY 1999 VL 5 IS 1 BP 41 EP 47 DI 10.1177/107385849900500106 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 162GM UT WOS:000078337600015 ER PT J AU Watson, JC Oldfield, EH AF Watson, JC Oldfield, EH TI The surgical management of spinal dural vascular malformations SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID CORD ARTERIOVENOUS-MALFORMATIONS; CLINICAL-FEATURES; MEDULLARY VEINS; MR-ANGIOGRAPHY; FISTULAS; MYELOPATHY; EMBOLIZATION; PHASE; INTERRUPTION; DIAGNOSIS AB Spinal dural arteriovenous fistulas (AVFs) are the most common spinal vascular malformation. The spinal dural AVF is a disease of adults, primarily men, that is a cause of subacute progressive lower extremity myelopathy. The challenge for the optimum management of these patients is in making an accurate, early diagnosis. Definitive surgical intervention by interruption of the intradural draining vein is the treatment of choice. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Watson, JC (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Rm 5D37, Bethesda, MD 20892 USA. NR 47 TC 16 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JAN PY 1999 VL 10 IS 1 BP 73 EP + PG 16 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 328PF UT WOS:000087858700006 PM 9855650 ER PT S AU Horwitz, B AF Horwitz, B BE Lindblad, T Padgett, ML Kinser, J TI Modeling of functional brain imaging data SO NINTH WORKSHOP ON VIRTUAL INTELLIGENCE/DYNAMIC NEURAL NETWORKS: ACADEMIC/INDUSTRIAL/NASA/DEFENSE TECHNICAL INTERCHANGE AND TUTORIALS SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT 9th Workshop on Virtual Intelligence/Dynamic Neural Networks CY JUN 22-28, 1998 CL ROYAL INST TECHNOL, STOCKHOLM, SWEDEN SP NASA, SPIE - Int Soc Opt Engn, IEEE Ind Applicat Soc HO ROYAL INST TECHNOL DE brain; cognition; visual processing; positron emission tomography (PET); functional magnetic resonance imaging (fMRI); human; working memory ID CEREBRAL BLOOD-FLOW; HUMAN EXTRASTRIATE CORTEX; POSITRON EMISSION TOMOGRAPHY; WORKING-MEMORY TASK; NEURONAL-ACTIVITY; VISUAL-CORTEX; PREFRONTAL CORTEX; PET-RCBF; OBJECT; FACE AB The richness and complexity of data sets obtained from functional neuroimaging studies of human cognitive behavior, using techniques such as positron emission tomography and functional magnetic resonance imaging, have until recently not been exploited by computational neural modeling methods. In this article, following a brief introduction to functional neuroimaging methodology, two neural modeling approaches for use with functional brain imaging data are described. One, which uses structural equation modeling, examines the effective functional connections between various brain regions during specific cognitive tasks. The second employs large-scale neural modeling to relate functional neuroimaging signals in multiple, interconnected brain regions to the underlying neurobiological time-varying activities in each region. These two modeling procedures are illustrated using a visual processing paradigm. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Rm 6C414,MSC 1588,9000 Rockville Pike, Bethesda, MD 20892 USA. EM horwitz@helix.nih.gov NR 69 TC 0 Z9 0 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 0-8194-3202-4 J9 P SOC PHOTO-OPT INS PY 1999 VL 3728 BP 35 EP 44 DI 10.1117/12.343050 PG 10 WC Engineering, Aerospace; Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Optics SC Engineering; Computer Science; Optics GA BM94V UT WOS:000080215800003 ER PT J AU Wink, DA Kim, S Coffin, D Cook, JC Vodovotz, Y Chistodoulou, D Jourd'heuil, D Grisham, MB AF Wink, DA Kim, S Coffin, D Cook, JC Vodovotz, Y Chistodoulou, D Jourd'heuil, D Grisham, MB TI Detection of S-nitrosothiols by fluorometric and colorimetric methods SO NITRIC OXIDE, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID NITRIC-OXIDE; METALLOTHIONEIN; NITROSYLATION; GLUTATHIONE; NITROSATION; INHIBITION; KINETICS; PROTEIN; BIOLOGY; ASSAYS C1 NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. NCI, Comparat Carcinogenesis Lab, FRDC, Frederick, MD 21702 USA. Cardiol Res Fdn, Washington, DC 20010 USA. Medlant Res Inst, Washington, DC 20010 USA. Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, Shreveport, LA 71130 USA. RP Wink, DA (reprint author), NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. NR 28 TC 36 Z9 37 U1 2 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 301 BP 201 EP 211 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BM67R UT WOS:000079435000021 PM 9919568 ER PT J AU Jourd'heuil, D Laroux, FS Kang, D Miles, AM Wink, DA Grisham, MB AF Jourd'heuil, D Laroux, FS Kang, D Miles, AM Wink, DA Grisham, MB TI Stability of S-nitrosothiols in presence of copper, zinc superoxide dismutase SO NITRIC OXIDE, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID NITRIC-OXIDE; GLUTATHIONE; DECOMPOSITION; NITROSOGLUTATHIONE; NITROSOHEMOGLOBIN; MECHANISM; PLASMA; IONS C1 Louisiana State Univ, Med Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. Boston Univ, Dept Biol, Boston, MA 02215 USA. Grambling State Univ, Grambling, LA 71245 USA. NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Jourd'heuil, D (reprint author), Louisiana State Univ, Med Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. FU NIDDK NIH HHS [DK43785] NR 18 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 301 BP 220 EP 227 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BM67R UT WOS:000079435000023 PM 9919570 ER PT J AU Wink, DA Vodovotz, Y Grisham, MB DeGraff, W Cook, JC Pacelli, R Krishna, M Mitchell, JB AF Wink, DA Vodovotz, Y Grisham, MB DeGraff, W Cook, JC Pacelli, R Krishna, M Mitchell, JB TI Antioxidant effects of nitric oxide SO NITRIC OXIDE, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID DENSITY-LIPOPROTEIN OXIDATION; OXIDIZED LIPID DERIVATIVES; HYDROGEN-PEROXIDE; MYOCARDIAL-ISCHEMIA; SODIUM-NITROPRUSSIDE; ESCHERICHIA-COLI; REPERFUSION; SUPEROXIDE; CYTOTOXICITY; MECHANISMS C1 NCI, Radiat Biol Branch, Tumor Biol Sect, Bethesda, MD 20892 USA. Cardiol Res Fdn, Washington, DC 20010 USA. Medlant Res Inst, Washington, DC 20010 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Tumor Biol Sect, Bethesda, MD 20892 USA. NR 59 TC 72 Z9 77 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 301 BP 413 EP 424 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BM67R UT WOS:000079435000043 PM 9919590 ER PT B AU Thorgeirsson, SS Santoni-Rugiu, E Factor, VM AF Thorgeirsson, SS Santoni-Rugiu, E Factor, VM BE Fleig, WE TI Analysis of genetic events during mouse hepatocarcinogenesis in transgenic models SO NORMAL AND MALIGNANT LIVER CELL GROWTH SE FALK SYMPOSIUM LA English DT Proceedings Paper CT International Falk Workshop on Normal and Malignant Liver Cell Growth CY JAN 29-30, 1998 CL HALLE, GERMANY C1 Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), Expt Carcinogenesis Lab, NCI Bldg 37,Rm 3C28,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8748-1 J9 FALK SYMP PY 1999 VL 103C BP 127 EP 127 PG 1 WC Oncology; Cell Biology; Gastroenterology & Hepatology; Pathology SC Oncology; Cell Biology; Gastroenterology & Hepatology; Pathology GA BM43C UT WOS:000078696200011 ER PT J AU Kim, MK Seidel, J Le, N Kim, IS Yoo, TM Barker, C Kobayashi, H Green, MV Carrasquillo, JA Paik, CH AF Kim, MK Seidel, J Le, N Kim, IS Yoo, TM Barker, C Kobayashi, H Green, MV Carrasquillo, JA Paik, CH TI Evaluation of Tc-99m-mercaptoacetyltriglycine-biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE pharmacokinetics; uptake; excretion; hyperbilirubinemia ID DECONVOLUTIONAL ANALYSIS; HEPATIC-FUNCTION; SCINTIGRAPHY; DISEASE; QUANTIFICATION; DIAGNOSIS AB We evaluated Tc-99m-labeled mercaptoacetyltriglycine (Tc-99m-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (r(max)) and half clearance time (HCT) with those of Tc-99m-labeled diisopropyl-iminodiacetic acid (Tc-99m-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent (Tc-99m-MAG3 biocytin or Tc-99m-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma camera equipped with a pinhole collimator, Dynamic images showed rapid hepatic uptake of Tc-99m-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas Tc-99m-disofenin coinjected with bilirubin showed a higher blood background than Tc-99m-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, r(max) and HCT. The r(max) was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearance curve from plots of time versus liver activity. Tc-99m-MAG3-biocytin without bilirubin coinjection showed an r(max) of 8.9 +/- 1.3 and an HCT of 399 +/- 36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for Tc-99m-disofenin with bilirubin were significantly (p < 0.01) affected by 14 mg/kg of bilirubin coinjection: r(max) was decreased from 7.9 +/- 2.5 to 1.4 +/- 0.2 and HCT was increased from 292 +/- 32 s to 782 +/- 133 s. Tc-99m-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels. NUCL MED BIOL 26;1: 43-49 1999. (C) 1998 Elsevier Science Inc. C1 NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Paik, CH (reprint author), NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bldg 21,Room 136, Bethesda, MD 20892 USA. EM paik@nmdhst.cc.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 21 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 1999 VL 26 IS 1 BP 43 EP 49 DI 10.1016/S0969-8051(98)00077-8 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151ZR UT WOS:000077751100007 PM 10096500 ER PT J AU Kennel, SJ Stabin, M Yoriyaz, H Brechbiel, M Mirzadeh, S AF Kennel, SJ Stabin, M Yoriyaz, H Brechbiel, M Mirzadeh, S TI Treatment of lung tumor colonies with Y-90 targeted to blood vessels: Comparison with the alpha-particle emitter Bi-213 SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE lung; tumor; beta-particle emitter; Y-90; Yttrium-90 ID NUDE-MICE; CANCER XENOGRAFTS; BONE-MARROW; RADIOIMMUNOTHERAPY; INVIVO; MODEL; CELLS AB An in vivo lung tumor model system for radioimmunotherapy of lung metastases was used to test the relative effectiveness of the vascular-targeted beta-particle emitter Y-90, and alpha-particle emitter, Bi-213. Yttrium-90 was shown to be stably bound by CHXa" DTPA-MAb 201B conjugates and delivered efficiently to lung tumor blood vessels. Dosimetry calculations indicated that the lung received 16.2 Gy/MBq from treatment with Y-90 MAb 201B, which was a sevenfold greater absorbed dose than any other organ examined. Therapy was optimal for Y-90 with 3 MBq injected. Bismuth-213 MAb 201B also delivered a similar absorbed dose (15Gy/MBq) to the lung. Yttrium-90 was found to be slightly more effective against larger tumors than Bi-213, consistent with the larger range of 2 MeV beta particles from Y-90 than the 8 MeV alpha particles from Bi-213. Treatment of EMT-6 tumors growing in immunodeficient SCID mice with Y-90 or Bi-213 MAb 201 resulted in significant destruction of tumor colonies; however, Y-90 MAb 201B was toxic for the SCID mice, inflicting acute lung damage. In another tumor model, IC-12 rat tracheal carcinoma growing in SCID mouse lungs, Y-90 therapy was more effective than 213Bi at destroying lung tumors. However, Y-90 MAb 201B toxicity for the lung limited any therapeutic effect. We conclude that, although vascular-targeted Y-90 MAb can be an effective therapeutic agent, particularly for larger tumors, in this model system, acute damage to the lung may limit its application. NUCL MED BIOL 26;1:149-157, 1999. (C) 1998 Elsevier Science Inc. C1 Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. Oak Ridge Inst Sci & Educ, Div Med Sci, Oak Ridge, TN 37831 USA. IPEN, CN EN SP, Sao Paulo, Brazil. NCI, NIH, DCS, Bethesda, MD 20892 USA. RP Kennel, SJ (reprint author), Oak Ridge Natl Lab, Div Life Sci, Bldg 4500S,MS-6101, Oak Ridge, TN 37831 USA. EM sj9@ornl.gov FU NIAAA NIH HHS [IAA NO. 97-053] NR 32 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 1999 VL 26 IS 1 BP 149 EP 157 DI 10.1016/S0969-8051(98)00069-9 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 151ZR UT WOS:000077751100022 PM 10096515 ER PT J AU Benson, DA Boguski, MS Lipman, DJ Ostell, J Ouellette, BFF Rapp, BA Wheeler, DL AF Benson, DA Boguski, MS Lipman, DJ Ostell, J Ouellette, BFF Rapp, BA Wheeler, DL TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSED SEQUENCE TAGS; HUMAN GENOME; GENERATION; BLAST AB The GenBank (Registered Trademark symbol) sequence database incorporates DNA sequences from all available public sources, primarily through the direct submission of sequence data from individual laboratories and from large-scale sequencing projects. Most submitters use the Banklt (Web) or Sequin programs to format and send sequence data. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome and protein structure information. MEDLINE (Registered Trademark symbol) abstracts from published articles describing the sequences are included as an additional source of biological annotation through the PubMed search system. Sequence similarity searching is offered through the BLAST series of database search programs. In addition to FTP, Email, and server/client versions of Entrez and BLAST, NCBI offers a wide range of World Wide Web retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the URL:http://www.ncbi.nlm.nih.gov. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Benson, DA (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 17 TC 436 Z9 447 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1999 VL 27 IS 1 BP 12 EP 17 DI 10.1093/nar/27.1.12 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156CC UT WOS:000077983000003 PM 9847132 ER PT J AU Pesole, G Liuni, S Grillo, G Ippedico, M Larizza, A Makalowski, W Saccone, C AF Pesole, G Liuni, S Grillo, G Ippedico, M Larizza, A Makalowski, W Saccone, C TI UTRdb: a specialized database of 5 ' and 3 ' untranslated regions of eukaryotic mRNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MESSENGER-RNA DEGRADATION; TRANSLATIONAL REGULATION; IRON-METABOLISM; GENE-EXPRESSION; SEQUENCE; PROTEIN; SELENOCYSTEINE; INSERTION; ELEMENTS AB The 5' and 3' untranslated regions of eukaryotic mRNAs may play a crucial role in the regulation of gene expression controlling mRNA localization, stability and translational efficiency. For this reason we developed UTRdb (http://bigarea.area,ba.cnr.it:8000/BioWWW/#UTRdb), a specialized database of 5' and 3' untranslated sequences of eukaryotic mRNAs cleaned from redundancy. UTRdb entries are enriched with specialized information not present in the primary databases including the presence of nucleotide sequence patterns already demonstrated by experimental analysis to have some functional role. All these patterns have been collected in the UTRsite database so that it is possible to search any input sequence for the presence of annotated functional motifs, Furthermore, UTRdb entries have been annotated for the presence of repetitive elements. C1 Univ Bari, Dipartmento Biochim & Biol Mol, I-70126 Bari, Italy. Univ Basilicata, DBAF, Dipartimento Biol, I-85100 Potenza, Italy. CNR, Area Ric, I-70126 Bari, Italy. CNR, Ctr Studio Mitocondri & Metab Energet, I-70126 Bari, Italy. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Pesole, G (reprint author), Univ Bari, Dipartmento Biochim & Biol Mol, Via Orabona 4, I-70126 Bari, Italy. RI Pesole, Graziano/C-1408-2009; Pesole, Graziano/E-9051-2014; Makalowski, Wojciech/I-2843-2016; Grillo, Giorgio/F-7617-2015 OI Pesole, Graziano/0000-0003-3663-0859; Pesole, Graziano/0000-0003-3663-0859; Grillo, Giorgio/0000-0002-0137-5811 NR 29 TC 34 Z9 36 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1999 VL 27 IS 1 BP 188 EP 191 DI 10.1093/nar/27.1.188 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156CC UT WOS:000077983000047 PM 9847176 ER PT J AU Ponting, CP Schultz, J Milpetz, F Bork, P AF Ponting, CP Schultz, J Milpetz, F Bork, P TI SMART: identification and annotation of domains from signalling and extracellular protein sequences SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ALIGNMENT; PREDICTION; PROFILE AB SMART is a simple modular architecture research tool and database that provides domain identification and annotation on the WWW (http://coot.embl-heidelberg.de/SMART). The tool compares query sequences with its databases of domain sequences and multiple alignments whilst concurrently identifying compositionally biased regions such as signal peptide, transmembrane and coiled coil segments. Annotated and unannotated regions of the sequence can be used as queries in searches of sequence databases. The SMART alignment collection represents more than 250 signalling and extracellular domains. Each alignment is curated to assign appropriate domain boundaries and to ensure its quality. In addition, each domain is annotated extensively with respect to cellular localisation, species distribution, functional class, tertiary structure and functionally important residues. C1 Univ Oxford, Fibrinolysis Res Unit, Old Observ, Oxford OX1 3RH, England. European Mol Biol Lab, D-69012 Heidelberg, Germany. RP Ponting, CP (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A, Bethesda, MD 20894 USA. RI Schultz, Joerg/B-9346-2008; Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X FU Wellcome Trust NR 26 TC 189 Z9 194 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1999 VL 27 IS 1 BP 229 EP 232 DI 10.1093/nar/27.1.229 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156CC UT WOS:000077983000058 PM 9847187 ER PT J AU Marchler-Bauer, A Addess, KJ Chappey, C Geer, L Madej, T Matsuo, Y Wang, Y Bryant, SH AF Marchler-Bauer, A Addess, KJ Chappey, C Geer, L Madej, T Matsuo, Y Wang, Y Bryant, SH TI MMDB: Entrez's 3D structure database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GERMLINE MUTATIONS; PHOSPHATASE VHR; COWDEN-DISEASE; TOOL; GENE AB The three dimensional structures for representatives of nearly half of all protein families are now available in public databases. Thus, no matter which protein one investigates, it is increasingly likely that the 3D structure of a homolog will be known and may reveal unsuspected structure-function relationships. The goal of Entrez's 3D-structure database is to make this information accessible and usable by molecular biologists (http://www.ncbi.nlm.nih.gov/Entrez). To this end Entrez provides two major analysis tools, a search engine based on sequence and structure 'neighboring' and an integrated visualization system for sequence and structure alignments. From a protein's sequence 'neighbors' one may rapidly identify other members of a protein family, including those where 3D structure is known. By comparing aligned sequences and/or structures in detail, using the visualization system, one may identify conserved features and perhaps infer functional properties. Here we describe how these analysis tools may be used to investigate the structure and function of newly discovered proteins, using the PTEN gene product as an example. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 14 TC 22 Z9 23 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1999 VL 27 IS 1 BP 240 EP 243 DI 10.1093/nar/27.1.240 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156CC UT WOS:000077983000061 PM 9847190 ER PT J AU Makalowska, I Ferlanti, ES Baxevanis, AD Landsman, D AF Makalowska, I Ferlanti, ES Baxevanis, AD Landsman, D TI Histone sequence database: sequences, structures, post-translational modifications and genetic loci SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ALIGNMENT; CHROMATIN AB The Histone Sequence Database is an annotated and searchable collection of all available histone and histone fold sequences and structures. particular emphasis has been placed on documenting conflicts between similar sequence entries from a number of source databases, conflicts that are not necessarily documented in the source databases themselves. New additions to the database include compilations of post-translational modifications for each of the core and linker histones, as well as genomic information in the form of map loci for the human histone gene complement, with the genetic loci linked to Online Mendelian Inheritance in Man (OMIM). The database is freely accessible through the World Wide Web at either http://genome.nhgri.nih.gov/histones/ or http://www. ncbi.nlm.nih.gov/Baxevani/HISTONES. C1 NIH, Genome Technol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Landsman, D (reprint author), NIH, Genome Technol Branch, Natl Human Genome Res Inst, Bldg 49,Room 2C-76, Bethesda, MD 20892 USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 15 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1999 VL 27 IS 1 BP 323 EP 324 DI 10.1093/nar/27.1.323 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156CC UT WOS:000077983000088 PM 9847217 ER PT J AU Banerjee-Basu, S Ferlanti, ES Ryan, JF Baxevanis, AD AF Banerjee-Basu, S Ferlanti, ES Ryan, JF Baxevanis, AD TI The homeodomain resource: sequences, structures and genomic information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; DNA COMPLEX; CRYSTAL-STRUCTURE; ANTENNAPEDIA HOMEODOMAIN; ENGRAILED HOMEODOMAIN; RESOLUTION; SPECIFICITY AB The Homeodomain Resource is a comprehensive collection of sequence, structure and genomic information on the homeodomain protein family. Available through the Resource are both full-length and domain-only sequence data, as well as X-ray and NMR structural data for proteins and protein-DNA complexes. Also available is information on human genetic diseases and disorders in which proteins from the homeodomain family play an important role; genomic information includes relevant gene symbols, cytogenetic map locations, and specific mutation data. Search engines are provided to allow users to easily query the component databases and assemble specialized data sets. The Homeodomain Resource is available through the World Wide Web at http://genome.nhgri.nih.gov/homeodomain. C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bldg 49,Room 2C-76, Bethesda, MD 20892 USA. NR 18 TC 10 Z9 10 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1999 VL 27 IS 1 BP 336 EP 337 DI 10.1093/nar/27.1.336 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156CC UT WOS:000077983000091 PM 9847220 ER PT J AU Marquez, VE Russ, P Alonso, R Siddiqui, MA Shin, KJ George, C Nicklaus, MC Dai, F Ford, H AF Marquez, VE Russ, P Alonso, R Siddiqui, MA Shin, KJ George, C Nicklaus, MC Dai, F Ford, H TI Conformationally restricted nucleosides. The reaction of adenosine deaminase with substrates built on a bicyclo[3.1.0]hexane template SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XIII International Round Table Conference on Nucleosides, Nucleotides and their Biological Applications CY SEP 06-10, 1998 CL MONTPELLIER, FRANCE ID BIOLOGICAL-ACTIVITY; SUGAR RING; INHIBITORS; MOLECULES; ANALOGS AB Adenosine deaminase (ADA) can discriminate between two distinct (North and South), conformationally rigid substrate conformers. (N)-methanocarba-2'dA (4) is deaminated 100 times faster than the antipodal (S)-methanocarba-2'dA (5), whereas a non-rigid analogue, aristeromycin (6), is deaminated at an intermediate rate. These results are in agreement with crystallographic data from ADA-ribonucleoside complexes showing the furanose ring of the bound purine in a C3'-endo (North) conformation. The data presented here suggests that 4 and 5 are useful probes to ascertain conformational preferences by purine metabolizing enzymes. C1 NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Marquez, VE (reprint author), NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RI Nicklaus, Marc/N-4183-2014 NR 16 TC 31 Z9 31 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 1999 VL 18 IS 4-5 BP 521 EP 530 DI 10.1080/15257779908041487 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 214ZK UT WOS:000081357300003 PM 10432643 ER PT J AU Meier, C Knispel, T Marquez, VE De Clercq, E Balzarini, J AF Meier, C Knispel, T Marquez, VE De Clercq, E Balzarini, J TI cycloSal-2 '-ara(ribo) -fluoro-2 ',3 '-dideoxyadenosine monophosphates - An effort to solve the structure-activity relationship of 2 '-fluoro-ddA SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XIII International Round Table Conference on Nucleosides, Nucleotides and their Biological Applications CY SEP 06-10, 1998 CL MONTPELLIER, FRANCE ID HUMAN-IMMUNODEFICIENCY-VIRUS; 2',3'-DIDEHYDRO-2',3'-DIDEOXYADENOSINE D4A; 2',3'-DIDEOXYADENOSINE; DERIVATIVES; PURINE; NUCLEOTIDES; DELIVERY; DDA; HIV AB Novel lipophilic cycloSal-triesters 3 and 4 from the ara- and ribo-configurated 2'-fluorinated ddAs 1 and 2, respectively, were prepared. The title compounds 3 and 4 delivered the corresponding monophosphates and thus, increasing the bioactivity or convert a formerly inactive compound into a RT inhibitor. C1 Univ Hamburg, Inst Organ Chem, D-20146 Hamburg, Germany. NCI, NIH, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. RP Meier, C (reprint author), Univ Hamburg, Inst Organ Chem, Martin Luther King Pl 6, D-20146 Hamburg, Germany. NR 23 TC 3 Z9 3 U1 0 U2 2 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 1999 VL 18 IS 4-5 BP 907 EP 912 DI 10.1080/15257779908041598 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 214ZK UT WOS:000081357300114 PM 10432708 ER PT J AU Verheijen, JC Bayly, SF Player, MR Torrence, PF van der Marel, GA van Boom, JH AF Verheijen, JC Bayly, SF Player, MR Torrence, PF van der Marel, GA van Boom, JH TI 2-5A-PNA complexes: A novel class of antisense compounds SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XIII International Round Table Conference on Nucleosides, Nucleotides and their Biological Applications CY SEP 06-10, 1998 CL MONTPELLIER, FRANCE ID POLYAMIDE AB This paper presents the fully automated solid phase synthesis of 2-5A-PNA hybrids. These stable antisense probes cause RNase L mediated hydrolysis of target RNA sequences. C1 Leiden Inst Chem, NL-2300 RA Leiden, Netherlands. NIDDK, Sect Biomed Chem, NIH, Bethesda, MD 20982 USA. RP van Boom, JH (reprint author), Leiden Inst Chem, POB 9502, NL-2300 RA Leiden, Netherlands. NR 4 TC 3 Z9 3 U1 0 U2 3 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 1999 VL 18 IS 6-7 BP 1485 EP 1486 DI 10.1080/07328319908044761 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 222VK UT WOS:000081805900111 PM 10474229 ER PT J AU Cramer, H Geselowitz, DA Torrence, PF AF Cramer, H Geselowitz, DA Torrence, PF TI Using fluorescence resonance energy transfer (FRET) for measuring 2-5A analogues ability to activate RNase L SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article; Proceedings Paper CT XIII International Round Table Conference on Nucleosides, Nucleotides and their Biological Applications CY SEP 06-10, 1998 CL MONTPELLIER, FRANCE AB The development of a method for measuring the ability of 2-5A analogues to activate the cleavage of an oligoribonucleotide substrate by RNase L is described. This method is based on fluorescence resonance energy transfer. The method is easily performed with 96-well plates, allowing for quantitative high-throughput analyses of 2-5A analogues under different reaction conditions. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Torrence, PF (reprint author), NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 2 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 1999 VL 18 IS 6-7 BP 1523 EP 1525 DI 10.1080/07328319908044776 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 222VK UT WOS:000081805900126 PM 10474231 ER PT S AU Jacobson, KA Hoffmann, C Kim, YC Camaioni, E Nandanan, E Jang, SY Guo, DP Ji, XD von Kugelgen, I Moro, S Ziganshin, AU Rychkov, A King, BF Brown, SG Wildman, SS Burnstock, G Boyer, JL Mohanram, A Harden, TK AF Jacobson, KA Hoffmann, C Kim, YC Camaioni, E Nandanan, E Jang, SY Guo, DP Ji, XD von Kugelgen, I Moro, S Ziganshin, AU Rychkov, A King, BF Brown, SG Wildman, SS Burnstock, G Boyer, JL Mohanram, A Harden, TK BE Illes, P Zimmermann, H TI Molecular recognition in P2 receptors: Ligand development aided by molecular modeling and mutagenesis SO NUCLEOTIDES AND THEIR RECEPTORS IN THE NERVOUS SYSTEMS SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT IUPHAR Satellite Conference on Nucleotides and Their Receptors in the Nervous System CY AUG 01-02, 1998 CL LEIPZIG, GERMANY SP Int Union Pharmacol Sci, Deutsch Forsch Gemeinschaft, Bundes Minist Bild & Forsch ID SITE-DIRECTED MUTAGENESIS; HUMAN P2Y(1) RECEPTOR; PHOSPHOLIPASE-C; ADENYLYL-CYCLASE; ANTAGONISTS; P-2Y-PURINOCEPTORS; IDENTIFICATION; PURINOCEPTORS; DERIVATIVES; SPECIFICITY C1 NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. Kazan Med Inst, Kazan, Russia. Royal Free Hosp Med, Autonon Neurosci Inst, London, England. Univ N Carolina, Chapel Hill, NC USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009; Erathodiyil, Nandanan/A-8333-2010; OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493; Ziganshin, Ayrat/0000-0002-9087-7927; Camaioni, Emidio/0000-0002-8529-0849 FU Intramural NIH HHS [Z01 DK031116-20, Z01 DK031127-01, Z99 DK999999] NR 25 TC 24 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50082-0 J9 PROG BRAIN RES PY 1999 VL 120 BP 119 EP 132 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Physiology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Physiology GA BN80C UT WOS:000082968000010 PM 10550992 ER PT S AU Dunwiddie, TV Jacobson, KA Diao, LH AF Dunwiddie, TV Jacobson, KA Diao, LH BE Illes, P Zimmermann, H TI An adenosine A(3) receptor-selective agonist does not modulate calcium-activated potassium currents in hippocampal CA1 pyramidal neurons SO NUCLEOTIDES AND THEIR RECEPTORS IN THE NERVOUS SYSTEMS SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT IUPHAR Satellite Conference on Nucleotides and Their Receptors in the Nervous System CY AUG 01-02, 1998 CL LEIPZIG, GERMANY SP Int Union Pharmacol Sci, Deutsch Forsch Gemeinschaft, Bundes Minist Bild & Forsch ID CENTRAL-NERVOUS-SYSTEM; RAT HIPPOCAMPUS; PHOSPHOLIPASE-C; A(2A) RECEPTORS; I-AHP; CELLS; INHIBITION; INVITRO; ACCOMMODATION; RESPONSES C1 Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO USA. Vet Adm, Med Res Serv, Denver, CO USA. NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Dunwiddie, TV (reprint author), Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NINDS NIH HHS [R01 NS 29173, R01 NS029173] NR 32 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50082-0 J9 PROG BRAIN RES PY 1999 VL 120 BP 275 EP 285 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Physiology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Physiology GA BN80C UT WOS:000082968000022 PM 10551004 ER PT J AU Leidy, NK AF Leidy, NK TI Psychometric properties of the functional performance inventory in patients with chronic obstructive pulmonary disease SO NURSING RESEARCH LA English DT Article DE functional status; chronic obstructive pulmonary disease; health outcomes ID STATUS QUESTIONNAIRE; HEALTH-STATUS; STATUS INSTRUMENTS; CHRONIC-BRONCHITIS; SOCIAL-BEHAVIOR; LIFE; DISABILITY; QUALITY; INDEX; SATISFACTION AB Background: The Functional Performance Inventory (FPI) is a subjective measure of the performance dimension of functional status, based on an explicit analytical framework and the experiences of patients themselves. Objectives: To describe the conceptual foundation of the instrument, the procedures used to maximize content validity, and the results of the initial psychometric testing of the FPI in patients with chronic obstructive pulmonary disease (COPD). Method: Items and response structure for the instrument were drawn from the literature and qualitative interviews with 12 men and women with COPD. Twenty-four clinical and scientific experts participated in content validation. To assess the FPI's psychometric characteristics, 154 patients participated in a cross-sectional mail survey; 54 took part in a 2-week reproducibility assessment. Forty relatives were also included in validity testing. Results: The instrument was internally consistent (alpha = .96) and reproducible (ICC = .85). Validity was evident in the significant (p < .001) correlations found between the FPI total score and the Functional Status Questionnaire (activities of daily living, r= .68; instrumental activities of daily living, r= .68), Duke Activity Status Index (r= .61), Bronchitis-Emphysema Symptom Checklist (r = -.59), Basic Need Satisfaction Inventory (r = .61), and Cantril's Ladder of Life Satisfaction (r = .63). The relationship between patient FPI score and relative perception of functioning, using the Katz Adjustment Scale for Relatives, was also significant (socially expected activities, r = .53; free-time activities, r = .49, p < .01). The instrument discriminated between patients with severe and moderate levels of perceived severity and activity limitation (t = 8.52, p <.001) and patients with FEV, greater than and less than 1.0 liter (t = 4.25, p < .001). Conclusions: Results suggest that the FPI is a useful measure of functional performance in patients with COPD. Further development of the spiritual activities and work and school domains is in order, as is additional study of the instrument's responsiveness to change. C1 MEDTAP Int, Ctr Hlth Outcomes Res, Bethesda, MD 20814 USA. NIH, Natl Inst Nursing Res, Div Intramural Res, Bethesda, MD 20892 USA. RP Leidy, NK (reprint author), MEDTAP Int, Ctr Hlth Outcomes Res, 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA. FU NINR NIH HHS [Z01 NR00008-01] NR 44 TC 54 Z9 54 U1 0 U2 3 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JAN-FEB PY 1999 VL 48 IS 1 BP 20 EP 28 DI 10.1097/00006199-199901000-00004 PG 9 WC Nursing SC Nursing GA 160AL UT WOS:000078208100004 PM 10029398 ER PT J AU Sparks, SM AF Sparks, SM TI Electronic publishing and nursing research SO NURSING RESEARCH LA English DT Article C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Sparks, SM (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 3 TC 2 Z9 2 U1 1 U2 1 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JAN-FEB PY 1999 VL 48 IS 1 BP 50 EP 54 DI 10.1097/00006199-199901000-00008 PG 5 WC Nursing SC Nursing GA 160AL UT WOS:000078208100008 PM 10029402 ER PT J AU Hartman, TJ Dorgan, JF Virtamo, J Tangrea, JA Taylor, PR Albanes, D AF Hartman, TJ Dorgan, JF Virtamo, J Tangrea, JA Taylor, PR Albanes, D TI Association between serum alpha-tocopherol and serum androgens and estrogens in older men SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Epidemiological-Research CY JUN 24-26, 1998 CL CHICAGO, ILLINOIS SP Soc Epidemiol Res ID BENIGN PROSTATIC HYPERPLASIA; VITAMIN-E; ADRENAL-CORTEX; HORMONE LEVELS; BETA-CAROTENE; MEGAVITAMIN-E; CANCER; CARCINOMA; SECRETION; PLASMA AB There is evidence supporting a role for sex hormones in the etiology of prostate cancer. Supplementation with alpha-tocopherol reduced prostate cancer in the alpha-Tocopherol, beta-Carotene Prevention Study (ATBC Study). The objective of this study was to assess the relation of baseline levels of serum alpha-tocopherol and serum sex hormones in older men. A cross-sectional analysis of serum alpha-tocopherol and sex hormone concentrations was conducted within a subset of the ATBC Study. Serum was collected in the morning after an overnight fast at baseline from 204 men ages 50-69 years participating in the ATBC Study and free of prostate cancer. Hormones were measured by radioimmunoassay, and alpha-tocopherol was measured by high-performance liquid chromatography by standard procedures. Multivariate linear regression was used to evaluate the association of serum cu-tocopherol with nine androgens and estrogens after controlling for age, body mass index, hormone assay batch, and serum cholesterol. Serum alpha-tocopherol was significantly inversely associated with serum androstenedione, testosterone, sex hormone-binding globulin, and estrone. The difference in hormone concentration per milligram of alpha-tocopherol was 1.8-2.6% for these four hormones. These results indicated that alpha-tocopherol is related to concentrations of several sex hormones in older men and may have implications for the observed protective effect of supplemental vitamin E in relation to prostate cancer in the ATBC Study. C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. RP Hartman, TJ (reprint author), NCI, Div Clin Sci, 6006 Execut Blvd,Suite 321,MSC 7058, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN-45165] NR 40 TC 20 Z9 24 U1 0 U2 1 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 1999 VL 35 IS 1 BP 10 EP 15 DI 10.1207/S1532791410-15 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 264LH UT WOS:000084183400004 PM 10624701 ER PT J AU Hoque, A Patt, YZ Yoffe, B Groopman, JD Greenblatt, MS Zhang, YJ Santella, RM AF Hoque, A Patt, YZ Yoffe, B Groopman, JD Greenblatt, MS Zhang, YJ Santella, RM TI Does anatoxin B-1 play a role in the etiology of hepatocellular carcinoma in the United States? SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID HEPATITIS-B-VIRUS; TUMOR-SUPPRESSOR GENE; AFLATOXIN-ALBUMIN ADDUCTS; REPUBLIC-OF-CHINA; P53 GENE; MUTATIONAL HOTSPOT; LIVER-TISSUE; DNA ADDUCTS; CODON 249; SERUM AB Previous research showed that risk factors associated with hepatocellular carcinoma (HCC) include infection with hepatitis B (HBV) and hepatitis C (HCV) viruses, exposure to aflatoxin B-1 (AFB(1)), and liver cirrhosis, due primarily to alcohol consumption. To determine whether AFB(1) may play a role in HCC in the United States, a search for AFB(1) adducts and p53 alterations, potentially induced by AFB(1), was conducted in the United States in 23 HCC patients with available tissue samples. The presence of AFB(1), tumor-DNA and -serum lysine adducts and mutant p53 product was determined by immunoassays and codon 249 p53 mutation by restriction enzyme analysis. HBV and HCV serology and serum HBV-DNA were also determined. Thirteen patients were positive for HBV by HBs antigen or anti-HBc antigen or by polymerase chain reaction for HBV-DNA sequences. Nine patients were free of HBV and HCV markers; 5 of 22 sera tested were anti-HCV positive, p53 Protein expression, determined by immunohistochemical staining, was present in 5 of the 23 tumor tissues, whereas p53 codon 249 mutations were not observed in the 5 cases in which tissue was available for study. AFB(1) tumor-DNA adducts were present in 3 of 19 tumor tissues, and in 1 of these 3 samples p53 protein was also detected. Sera from only 5 of the patients were tested for AFB(1)-lysine adducts, and all were positive. Irt these five patients, neither p53 protein nor a mutation on. codon 249 was detected. The demonstration that AFB(1)-DNA and -lysine adducts are present in HCC patients in the United States is intriguing but requires further substantiation because of the small number of subjects in this pilot study. To elucidate the pathogenetic significance of these findings, further investigation, including studies in larger patient cohorts and properly selected controls, is warranted. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol & Digest Dis, Div Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21218 USA. NCI, Carcinogenesis Lab, Bethesda, MD 20892 USA. Columbia Univ, Sch Publ Hlth, New York, NY 10032 USA. RP Patt, YZ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol & Digest Dis, Div Med, 1515 Holcombe Blvd,MD 078, Houston, TX 77030 USA. FU NIEHS NIH HHS [ESO-5116] NR 38 TC 11 Z9 12 U1 1 U2 1 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 1999 VL 35 IS 1 BP 27 EP 33 DI 10.1207/S1532791427-33 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 264LH UT WOS:000084183400006 PM 10624703 ER PT J AU Cohen, LA Zhao, Z Pittman, B Lubet, R AF Cohen, LA Zhao, Z Pittman, B Lubet, R TI S-allylcysteine, a garlic constituent, fails to inhibit N-methylnitrosourea-induced rat mammary tumorigenesis SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID DNA-ADDUCTS; ORGANOSULFUR COMPOUNDS; DIALLYL DISULFIDE; CHEMOPREVENTION; CARCINOGENESIS; SUPPRESSES; TUMORS; 4-HPR AB Epidemiological and experimental studies suggest that consumption of garlic may protect against several types of cancer. Moreover, a plausible hypothesis has been proposed that the biological effects of garlic can be attributed to the enhancing action of a variety of organosulfur compounds, present in garlic, on hepatic phase II carcinogen detoxification enzymes. We have used the N-methylnitrosourea (NMU)-induced rat mammary amor model to test the chemopreventive effects of a water-soluble organosulfur constituent derived from aged garlic, S-allylcysteine (SAC). Rats were fed diets supplemented with 666 and 2,000 ppm SAC beginning seven days before initiation with NMU (55 days of age) to termination (18 wk post-NMU), at which time mammary tumors were enumerated At neither dose did SAC exert an inhibitory effect on any index of tumor development, including incidence, latency multiplicity, or volume, compared with untreated controls. Weight gains in all groups were similar. Assay of serum SAC levels in supplemented groups indicated that SAC concentrations were beneath the limits of detection of the high-performance liquid chromatography system used. These results contradict previous animal model studies indicating that SAC acts as an inhibitory agent in experimental mammary tumorigenesis; reasons for this discrepancy include the possibility that SAC may exhibit nonlinear dose effects. C1 Amer Hlth Fdn, Div Nutr & Epidemiol, Valhalla, NY 10595 USA. NCI, Chemoprevent Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, LA (reprint author), Amer Hlth Fdn, Div Nutr & Epidemiol, 1 Dana Rd, Valhalla, NY 10595 USA. FU NCI NIH HHS [CN-55163] NR 29 TC 17 Z9 17 U1 0 U2 0 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 1999 VL 35 IS 1 BP 58 EP 63 DI 10.1207/S1532791458-63 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 264LH UT WOS:000084183400010 PM 10624707 ER PT J AU Potischman, N Carroll, RJ Iturria, SJ Mittl, B Curtin, J Thompson, FE Brinton, LA AF Potischman, N Carroll, RJ Iturria, SJ Mittl, B Curtin, J Thompson, FE Brinton, LA TI Comparison of the 60-and 100-item NCI-block questionnaires with validation data SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRES; HISTORY QUESTIONNAIRE; BREAST-CANCER; DIETARY; LIMITATIONS; REPRODUCIBILITY; RISK AB Large epidemiological studies often require short food frequency questionnaires (FFQ) to minimize the respondent burden or to control for confounding from dietary factors. In this analysis, we compared the extensively used National Cancer institute-Block 60- and 100-item FFQs with one another and with usual intake as estimated from 12 clays of validation data. The analysis focused on nutrients from different aspects of the diet, including energy, fat, saturated fat, p-carotene, dietary fiber, and vitamin C. By use of an errors-in-variables analysis, the correlations of usual intake with the two types of FFQs for these nutrients were not different. Attenuation coefficients, a measure of misclassification error, far both FFQs were of similar magnitude and indicated that substantial attenuation of logistic regression coefficients would result from either FFQ. Our results confirm previous analyses describing the validity and utility of the 60-item FFQ (Epidemiology 1, 58-64, 1990) and indicate that it is essentially equivalent to the 100-item FFQ for epidemiological analyses of major nutrients. C1 Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. Westat Inc, Rockville, MD 20850 USA. Informat Management Syst, Silver Spring, MD 20904 USA. RP Potischman, N (reprint author), Univ Massachusetts, Dept Biostat & Epidemiol, Arnold House, Amherst, MA 01003 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [CA-57030] NR 21 TC 30 Z9 30 U1 0 U2 4 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 1999 VL 34 IS 1 BP 70 EP 75 DI 10.1207/S15327914NC340110 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 224KF UT WOS:000081896500010 PM 10453444 ER PT J AU Schrauwen, P Walder, K Ravussin, E AF Schrauwen, P Walder, K Ravussin, E TI Human uncoupling proteins and obesity SO OBESITY RESEARCH LA English DT Review DE uncoupling proteins; energy expenditure; obesity; humans ID BROWN ADIPOSE-TISSUE; SKELETAL-MUSCLE; NONSHIVERING THERMOGENESIS; THYROID-HORMONE; ENERGY-EXPENDITURE; PROTON TRANSPORT; GENE-EXPRESSION; UP-REGULATION; BODY-WEIGHT; OB PROTEIN AB Uncoupling protein (UCP) 2 and UCP3 are newly discovered proteins that can uncouple ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting energy metabolism efficiency. In contrast to UCP1, which is only present in brown adipose tissue, UCP2 has a wide tissue distribution, whereas UCP3 is expressed predominantly in skeletal muscle. Some evidence of a role for UCPs in modulating metabolic rate was provided by linkage and association studies. Furthermore, UCP3 gene expression was found to correlate negatively with body mass index and positively with sleeping metabolic rate in Pima Indians. Treatment with thyroid hormone increases expression of the UCP2 and UCP3 genes. Other regulators of UCP2 and UCP3 gene expression are beta(3)-adrenergic agonists and glucocorticoids. Surprisingly, fasting has a stimulatory effect on UCP2 and UCP3 mRNA levels, possibly explained by the effects of free fatty acid on UCP2 and UCP3 gene expression. C1 NIH, Clin Diabet & Nutr Sect, NIDDKD, Phoenix, AZ 85016 USA. Maastricht Univ, Dept Human Biol, NL-6200 MD Maastricht, Netherlands. RP Schrauwen, P (reprint author), NIH, Clin Diabet & Nutr Sect, NIDDKD, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 51 TC 67 Z9 72 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JAN PY 1999 VL 7 IS 1 BP 97 EP 105 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 174VK UT WOS:000079056600013 PM 10023736 ER PT J AU McNellis, D Hirtz, D AF McNellis, D Hirtz, D TI If tocolytic magnesium sulfate is associated with excess total pediatric mortality, what is its impact? SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP McNellis, D (reprint author), NICHHD, NIH, 6100 Bldg,Room 4B-03, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 1999 VL 93 IS 1 BP 159 EP 159 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 154JF UT WOS:000077885200037 PM 9916978 ER PT S AU Hofrichter, J Thompson, PA Munoz, V Jas, GS Henry, E Hagen, SJ Lapidus, L Eaton, WA AF Hofrichter, J Thompson, PA Munoz, V Jas, GS Henry, E Hagen, SJ Lapidus, L Eaton, WA BE Kuwajima, K Arai, M TI Dynamics of alpha-helices, beta-hairpins and loops SO OLD AND NEW VIEWS OF PROTEIN FOLDING SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 24th Taniguchi International Symposium, Division of Biophysics CY MAR 03-07, 1999 CL KISARAZU, JAPAN SP Taniguchi Fdn ID PROTEIN-FOLDING KINETICS; LASER TEMPERATURE-JUMP; SINGLE-DOMAIN PROTEINS; UNFOLDED CYTOCHROME-C; ELECTRON-TRANSFER; MOLTEN GLOBULE; FAST EVENTS; MECHANISM; DIFFUSION; PATHWAYS AB Using rapid kinetic techniques, we have begun to characterize the kinetics of the fundamental structural elements of proteins - loops, alpha-helices and beta-hairpins. The relaxation time for formation of stable helices is about 200 ns while that for formation of the C-terminal hairpin from protein GB1 is about 4 mu s, about 20 times slower. Using a simple statistical mechanical model, we have been able to provide a consistent framework within which these results can be interpreted. The model considers the native state as the only folded state. The unfolded state is stabilized by conformational entropy and the native state by hydrogen bonds and sidechain-sidechain interactions. The model suggests that the barrier for two-state folding systems will increase as the number of native residues in the transition state increases. In other words, the folding rate should be closely related to the contact order of the transition state. C1 NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RP Hofrichter, J (reprint author), NIH, Chem Phys Lab, Bldg 5, Bethesda, MD 20892 USA. NR 46 TC 0 Z9 0 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 0-444-50291-2 J9 INT CONGR SER PY 1999 VL 1194 BP 53 EP 62 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BP25Q UT WOS:000084507600006 ER PT J AU Saeki, T Takashima, S Tachibana, M Koga, M Hiyama, E Salomon, DS Holland, JF Ohnuma, T AF Saeki, T Takashima, S Tachibana, M Koga, M Hiyama, E Salomon, DS Holland, JF Ohnuma, T TI Inhibitory effect of telomere-mimic phosphorothioate oligodeoxy nucleotides (S-ODNS) on human tumor cell lines SO ONCOLOGY LA English DT Article; Proceedings Paper CT Conference on the Treatment of Hormone-Dependent Tumors (THDT) CY JAN 30, 1999 CL TOKYO, JAPAN DE telomerase; phosphorothioate oligodeoxy nucleotides; breast cancer; colon cancer ID CANCER AB To clarify the inhibitory effect of telomere-mimic oligonucleotides on human cancer cell lines, we synthesized 18-mers (18T; n = 3), 24-mers (24T; n = 4) and 30-mers (30T; n = 5) of telomere-mimic phosphorothioate oligodeoxy nucleotides [5'-d(TTA GGG)n-3'] and examined their effects on the proliferation of human tumor cells by XTT assay. After 7 days of continuous exposure to 24T and 30T at concentrations ranging from 0.1 to 10 mu M, concentration-dependent cell growth inhibition was observed in MCF-7 clone E3, ZR-75-1, MDA-MB 231, Cole 201 and WiDr. All of these cell lines highly expressed telomerase using the telomeric repeat amplification protocol. None of these tumor cell lines were affected by 18T. In MCF-7, ZR-75-1 and Cole 201 cell lines, a more than 50 % growth inhibition was obtained by 3 mu M of 24T and 30T whereas, in MDA-MB 231 and WiDr cell lines, cell growth inhibition was less than 50%. 30T was more effective than 24T. Estrogen-dependent growth of both MCF-7 and ZR-75-1 was inhibited by 3 mu M of 24T and 30T, however, in the absence of estrogen, no growth inhibition was seen. The MCF-10A cell line, which was developed from normal human breast tissue and expressed telomerase only weakly, was inhibited by 10 mu M of 18T. In conclusion, these observations indicate that S-ODNs inhibit tumor growth in cell lines expressing telomerase in a concentration-dependent manner and that cell growth inhibition is dependent on the length of S-ODNs. In addition, the short-length S-ODNs may inhibit growth of cells weakly expressing telomerase, but not of cells with high telomerase expression. C1 Natl Shikoku Canc Ctr, Matsuyama, Ehime 7900007, Japan. Ehime Univ, Matsuyama, Ehime 790, Japan. Hiroshima Univ, Hiroshima, Japan. NCI, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Saeki, T (reprint author), Natl Shikoku Canc Ctr, 13 Horinouchi, Matsuyama, Ehime 7900007, Japan. NR 18 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 1999 VL 57 SU 2 BP 27 EP 35 DI 10.1159/000055272 PG 9 WC Oncology SC Oncology GA 254UY UT WOS:000083631600005 PM 10545800 ER PT J AU Khan, QA Vousden, KH Dipple, A AF Khan, QA Vousden, KH Dipple, A TI Lack of p53-mediated G1 arrest in response to an environmental carcinogen SO ONCOLOGY LA English DT Article DE p53; p21(waf1/cip1); 5-methylchrysene; G1 arrest ID CELL-CYCLE ARREST; WILD-TYPE P53; DNA-DAMAGE; GENE AMPLIFICATION; HUMAN FIBROBLASTS; G(1) ARREST; INDUCTION; PROTEIN; CANCER; 5-METHYLCHRYSENE AB The environmental carcinogen, 5-methylchrysene, is a component of cigarette smoke. Its reactive metabolite, anti-5-methylchrysene-1,2-dihydrodiol-3,4-epoxide (5-MeCDE) mainly reacts with the N-2-position of guanine residues in the DMA molecule, In this study, we demonstrate that the tumor suppressor protein p53 is stabilized in response to DNA damage by 5-MeCDE but fails to induce the cells' protective mechanism of G1 arrest in the human breast carcinoma cell line, MCF-7, In contrast, actinomycin D treatment of these cells did lead to G1 arrest. Western analyses revealed that, though both actinomycin D and 5-MeCDE treatment stabilized p53, only trace levels of p21(waf1/cip1) were seen in the latter case. This lack of p21(waf1/cip1) expression in 5-MeCDE-treated cells is attributed to a stealth characteristic of this environmental carcinogen that allows it to damage DNA and still escape the p53-mediated cellular defense mechanism of G1 arrest. C1 NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Virol & Carcinogenesis Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Khan, QA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick, MD 21702 USA. NR 34 TC 25 Z9 27 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 1999 VL 57 IS 3 BP 258 EP 264 DI 10.1159/000012040 PG 7 WC Oncology SC Oncology GA 247PN UT WOS:000083229300011 PM 10545796 ER PT J AU Ohsaki, Y Gross, AJ Le, PT Oie, H Johnson, BE AF Ohsaki, Y Gross, AJ Le, PT Oie, H Johnson, BE TI Human small cell lung cancer cells produce brain natriuretic peptide SO ONCOLOGY LA English DT Article DE lung neoplasm; ectopic hormone syndromes; small cell lung cancer; brain natriuretic peptide ID LINES; SECRETION; TUMOR; HYPONATREMIA; VASOPRESSIN; CARCINOMA; RECEPTOR; HORMONE; GROWTH; SODIUM AB The tumoral production of brain natriuretic peptide (BNP) was studied using 9 small cell lung cancer (SCLC) cell lines which were established from patients with small cell lung cancer. BNP cDNA fragment was generated from 20 mu g total RNA which was prepared from the human right cardiac atrium by reverse transcription-based polymerase chain reaction. Expression of BNP mRNA was detected in 30 mu g total cellular RNA from these cell lines by RNase protection assays in 5 of 9 SCLC cell lines. Radioimmunoassays using I-125-radiolabeled human BNP(1-32) and antihuman BNP(1-32) antibody detected immunoreactivity in cell pellets from SCLC cell lines which had detectable BNP mRNA. BNP immunoreactivity in the cell pellets corresponds with the data from BNP mRNA analyses. We conclude that SCLC cells have detectable BNP mRNA by RNase protection assay and BNP immunoreactivity in the cells. C1 NCI, USN, Med Oncol Branch,NIH, Natl Naval Med Ctr, Bethesda, MD 20892 USA. RP Ohsaki, Y (reprint author), Asahikawa Med Coll, Dept Med 1, Nishikagura 4-5-3, Asahikawa, Hokkaido 078, Japan. NR 25 TC 15 Z9 15 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 1999 VL 56 IS 2 BP 155 EP 159 DI 10.1159/000011957 PG 5 WC Oncology SC Oncology GA 170JF UT WOS:000078802000011 PM 9949302 ER PT J AU Abernathy, TV Lee, KB Parker, RJ Reed, E AF Abernathy, TV Lee, KB Parker, RJ Reed, E TI The measurement of cadmium in biological materials, using graphite furnace atomic absorption spectrometry with Zeeman background correction SO ONCOLOGY REPORTS LA English DT Article DE cadmium; atomic absorption spectrometry ID CHINESE-HAMSTER CELLS; MAMMALIAN-CELLS; CHLORIDE; CARCINOGENICITY; RESISTANCE; INDUCTION; CANCER; ZINC; INHIBITION; MAGNESIUM AB Cadmium (Cd), a toxic heavy metal and probable carcinogen in humans, appears to have potential anti-cancer activity in pre-clinical systems. This observation led us to develop a method for measuring cellular Cd and DNA-bound Cd following micromolar exposures to cadmium dichloride. Cultured human ovarian cancer cell lines were used. Following low level exposures to cadmium dichloride (CdCl2), atomic absorption spectrometry with Zeeman background correction was used to measure total cell associated Cd in wet-ashed cells, and the lower limits of detection was at 100 pg of Cd per 10(6) cells. In cellular DNA isolated by cesium chloride density gradient centrifugation, levels of 1.5 Cd lesions (Cd molecules) per 10(6) nucleotides were reproducibly detected. Standard curves with 'spiked' samples yielded 76.4+/-6.7% recovery when using picogram quantities of Cd. Manipulation of the total amount of biological material used, can further improve detection limits. Thus, this method is suitable for the detection of Cd in biological matrixes after low levels of Cd exposure, and shows good performance in terms of the level of sensitivity and reproducibility. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 12C103, Bethesda, MD 20892 USA. NR 31 TC 4 Z9 4 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JAN-FEB PY 1999 VL 6 IS 1 BP 155 EP 159 PG 5 WC Oncology SC Oncology GA 150LG UT WOS:000077665900028 PM 9864420 ER PT J AU Song, KM Cowan, KH Sinha, BK AF Song, KM Cowan, KH Sinha, BK TI In vivo studies of adenovirus-mediated p53 gene therapy for cis-platinum-resistant human ovarian tumor xenografts SO ONCOLOGY RESEARCH LA English DT Article DE cis-platinum; drug resistance; adenovirus; p53 gene; gene therapy; combination gene therapy; ovarian carcinoma ID WILD-TYPE P53; CANCER-CELLS; IN-VIVO; CISPLATIN RESISTANCE; DRUG-RESISTANCE; SUPPRESSOR GENE; LUNG-CANCER; APOPTOSIS; EFFICACY; CAMPTOTHECIN AB We have recently reported that mutations of the tumor suppressor p53 gene are associated with the development of resistance to cis-platinum in human ovarian cancer cells. and that adenovirus-mediated reintroduction of the wild-type p53 (wtp53) gene in ovarian tumor cells resulted in the sensitization of tumor cells to cis-diamminedichloroplatinum (II) (CDDP). The purpose of this study was to evaluate whether IP treatment of CDDP-resistant tumor cells expressing mutant p53 (mutp53) with a recombinant adenovirus expressing wtp53 (Adwtp53) would result in the sensitization of resistant cells to CDDP. In order to determine whether IP injection of a recombinant adenovirus would result in expression of the transgene in tumor cells growing intraperitoneally. we first injected A2780/CP cells in nude mice and 10 days later the mice were injected IP with a recombinant adenovirus expressing beta-galactosidase (Adp-gal). Twenty-four hours following IP injection of Adp-gal, tumors were removed and stained for beta-gal. While tumors showed extensive staining for beta-gal, indicating internalization of adenovirus and the expression of the transgene in tumors, no expression of beta-gal protein was detected in liver. IP treatment of A2780/CP tumor xenografts with Adwtp53 caused extensive tumor cell death, which was further enhanced by CDDP. Treatment with Adwtp53 (5 x 10(7) pfu/day. 3-5 treatments) resulted in a significant decrease in tumor volume and increase in animal survival compared to either no treatment or treatment with vector alone without p53 gene. Additional therapy with CDDP (1 mg/kg/day x 3-4) further reduced tumor volume and increased survival (30-40%), suggesting that combination therapy of Adwtp53 and CDDP was better than single agents alone. Our results indicate that IP dosing with adenovirus-mediated wtp53 gene therapy could be beneficial in combination with CDDP for the treatment of ovarian tumors expressing mutp53. C1 NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD 20892 USA. RP Sinha, BK (reprint author), 10817 Game Preserve Rd, Gaithersburg, MD 20878 USA. NR 30 TC 16 Z9 20 U1 0 U2 3 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 1999 VL 11 IS 3 BP 153 EP 159 PG 7 WC Oncology SC Oncology GA 241RJ UT WOS:000082896100006 PM 10527075 ER PT J AU Stiemer, R Duijvestijn, A Wiggert, B Whitcup, S Zierhut, M AF Stiemer, R Duijvestijn, A Wiggert, B Whitcup, S Zierhut, M TI "High endothelial venules": expression kinetic in IRBP-induced EAU SO OPHTHALMOLOGE LA English DT Article DE experimental autoimmune uveitis interphotoreceptor retinoid binding protein; high endothelial venules; lymphocyte homing ID EXPERIMENTAL AUTOIMMUNE UVEITIS; MECHANISMS; DIFFERENTIATION; LYMPHOCYTES; ALPHA AB Experimental autoimmune uveitis (EAU) is a T-cell-mediated disease expressing high endothelial venules (HEVs) in the retina. HEVs could be responsable for the absorption of activated T-cells. The purpose of this study was to investigate the kinetics of HEV expression in the murine IRBP (interphotoreceptor retinoid binding protein) induced EAU. Methods: B10.A mice were immunized sub-cutanously with IRBP. The eyes were analysed on days 10, 18, 24 and 28 (n = 5 for each time point). While HEVs were identified with the mAb MECA 325. the control mAb MECA 20 stained all endothelial cells. Results: HEVs were detectable in the intact retina from day 10. Presence of HEVs peaked on day 18 and decreased by day 28, when maximal inflammation and retinal destruction was detectable. Conclusion: HEV expression could play a central role in the onset of EAU, allowing homing and migration of inflammatory cells into the eye. C1 Univ Tubingen, Augenklin, Abt 1, D-72076 Tubingen, Germany. Univ Limburg, Natl Eye Inst, NL-6200 MD Maastricht, Netherlands. NEI, NIH, Bethesda, MD 20892 USA. RP Stiemer, R (reprint author), Univ Tubingen, Augenklin, Abt 1, Schleichstr 12-16, D-72076 Tubingen, Germany. NR 16 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-293X J9 OPHTHALMOLOGE JI Ophthalmologe PD JAN PY 1999 VL 96 IS 1 BP 40 EP 44 DI 10.1007/s003470050374 PG 5 WC Ophthalmology SC Ophthalmology GA 162NU UT WOS:000078353900009 PM 10067334 ER PT J AU Lin, T Lewis, RA Nussbaum, RL AF Lin, T Lewis, RA Nussbaum, RL TI Molecular confirmation of carriers for Lowe syndrome SO OPHTHALMOLOGY LA English DT Article ID OCULOCEREBRORENAL SYNDROME; MUTATIONS; GENE AB Objective: To determine the sensitivity and specificity of ocular examination for the carrier state of Lowe syndrome in females known to be either carriers or noncarriers by direct DNA diagnosis. Design: Nonrandomized cohort study. Participants: Thirty-one females at risk for carrying Lowe syndrome in 3 families. Methods: Slit-lamp biomicroscopy after pupillary dilation was performed by a single observer (RAL) who was masked as to carrier status as determined by allele-specific detection of mutations in genomic DNA. Results: Carrier assessment predetermined by slit-lamp biomicroscopic examination yielded only one false-negative in a young girl 5 years of age and no false-positives among 31 female members examined. Conclusions: Slit-lamp examination is a highly accurate and sensitive test for carrier detection in Lowe syndrome, particularly in women of reproductive age. C1 Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Nussbaum, RL (reprint author), Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, 49 Convent Dr,MSC4472, Bethesda, MD 20892 USA. NR 9 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 1999 VL 106 IS 1 BP 119 EP 122 DI 10.1016/S0161-6420(99)90012-X PG 4 WC Ophthalmology SC Ophthalmology GA 155MU UT WOS:000077951600041 PM 9917791 ER PT S AU Chernomordik, V Gandjbakhche, AH Hebden, JC Zaccanti, G AF Chernomordik, V Gandjbakhche, AH Hebden, JC Zaccanti, G BE Chance, B Alfano, RR Tromberg, BJ Katzir, A TI Random walk model of the effect of lateral boundaries on time-resolved measurements in optical tomography SO OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE III, 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 III CY JAN 24-28, 1999 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc DE time-resolved transillumination; quantitative imaging; random walk; Monte Carlo simulations; contrast functions ID TRANSILLUMINATION EXPERIMENTS; TISSUE; DISTRIBUTIONS; SPECTROSCOPY; MEDICINE; CONTRAST; MEDIA; LIGHT AB The effect of lateral boundaries on time-resolved measurements of light transmitted through slabs of finite thickness is considered in the framework of a random walk model of photon transport in tissue. A model for a single lateral boundary is derived from the result obtained previously for an infinite slab by employing a standard technique known as the method of images. The predictions of the model are compared with time of flight data from Monte Carlo simulations (University of Florence) and experiments (University College London) using a homogenous phantom having tissue-like optical properties. Agreements in both cases are very good, indicating that the simple formalism of the random walk model is quite adequate to describe the influence of the side boundaries of the tissue slab on the observed characteristics of the transmitted light. The same methodology is applied to assess the influence of side boundaries on the time-dependent contrast functions observed in time-resolved transillumination experiments when an abnormally scattering and absorbing target is embedded in the slab. The potential use of suggested lateral boundary corrections in optical tomography is briefly discussed. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Chernomordik, V (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 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 0-8194-3067-6 J9 P SOC PHOTO-OPT INS PY 1999 VL 3597 BP 136 EP 145 DI 10.1117/12.356804 PG 10 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BN68N UT WOS:000082585500016 ER PT S AU Chernomordik, V Hattery, D Gandjbakhche, AH Pifferi, A Taroni, P Torricelli, A Valentini, G Cubeddu, R Hebden, JC AF Chernomordik, V Hattery, D Gandjbakhche, AH Pifferi, A Taroni, P Torricelli, A Valentini, G Cubeddu, R Hebden, JC BE Chance, B Alfano, RR Tromberg, BJ Katzir, A TI Quantitative imaging in time-resolved transillumination experiments using time-dependent contrast functions SO OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE III, 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 III CY JAN 24-28, 1999 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc DE time-resolved transillumination; quantitative imaging; random walk; contrast functions; breast screening ID MEDICINE AB We have developed a random walk model that uses time-dependent contrast functions to quantify the cross-section and the diffusion and absorption coefficients of an optically abnormal target from time-of-flight (TOE) data obtained in time-resolved transillumination experiments'. To substantiate our methodology we have used two different sets of data. The first set of data, provided by colleagues at University College London, are TOF measurements obtained using a solid phantom whose thickness (55mm), optical properties (absorption, mu(a)=0.006mm(-1), transport corrected scattering, mu(sc)'=0.7mm(-1)), and characteristics of its abnormal target (size=5mm, optical properties twice those of the background) are close to those of a human breast. The second set of data, provided by colleagues at Politecnico di Milan, are TOF measurements on a 50mm thick phantom (mu(a)=0.01mm(-1), mu(sc)'=1mm(-1)) in which two 10mm abnormal targets (one abnormally scattering, mu(sc)'=2mm(-1); one abnormally absorbing and scattering, mu(a)=0.04mm(-1), mu(sc)'=2mm(-1)), are embedded. None of these data includes very short path photons whose measurements are clinically impractical. Using our time-dependent contrast functions, we were able to estimate the size and optical properties of the targets with an error margin of 3-25%. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Chernomordik, V (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RI Taroni, Paola/C-4709-2012; Pifferi, Antonio/C-4688-2012; OI Taroni, Paola/0000-0001-7486-0001; Pifferi, Antonio/0000-0002-2261-2089; Torricelli, Alessandro/0000-0002-6878-8936; Valentini, Gianluca/0000-0002-6340-3021 NR 7 TC 1 Z9 1 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 0-8194-3067-6 J9 P SOC PHOTO-OPT INS PY 1999 VL 3597 BP 398 EP 402 DI 10.1117/12.356834 PG 5 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BN68N UT WOS:000082585500043 ER PT J AU Ruggieri, M Pavone, V Polizzi, A Albanese, S Magro, G Merino, M Duray, PH AF Ruggieri, M Pavone, V Polizzi, A Albanese, S Magro, G Merino, M Duray, PH TI Unusual form of recurrent giant cell granuloma of the mandible and lower extremities in a patient with neurofibromatosis type 1 SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID LESIONS; MANIFESTATIONS; SKULL AB We report on a girl with familial neurofibromatosis type 1 (Nfl) who at age 11 had multiple osteolytic lesions of the right mandible and the distal femoral and proximal tibial metaphyses bilaterally No other skeletal component was affected, and no abnormalities were present on skeletal radiographs of her parents. Histologic examination of the mandibular and right femoral lesions revealed a "multinucleated giant cell process." Results of repeated routine laboratory and bone metabolic studies were within normal limits. The lack of reliable histologic criteria and the diagnostic problems in distinguishing among central giant cell granulomata, giant cell tumors of the jaw, cherubism, brown tumors resulting from (occult) hyperparathyroidism, Jaffe-Campanacci syndrome, McCune-Albright syndrome, Noonan-like/multiple giant cell lesion syndrome, and multiple nonossifying fibromas of bone are discussed. C1 Univ Catania, Dept Paediat, Div Paediat Neurol, I-95125 Catania, Italy. Univ Catania, IBFSNC, I-95125 Catania, Italy. Oxford Radcliffe Hosp, NHS Trust, Dept Clin Genet, Oxford, England. Catania Univ, Dept Dent, Catania, Italy. Catania Univ, Dept Anat Pathol, Catania, Italy. NCI, Pathol Lab, Dept Human Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Ruggieri, M (reprint author), Univ Catania, Dept Paediat, Div Paediat Neurol, Viale A Doria 6, I-95125 Catania, Italy. NR 35 TC 26 Z9 27 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 1999 VL 87 IS 1 BP 67 EP 72 DI 10.1016/S1079-2104(99)70297-0 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 157KF UT WOS:000078059500015 PM 9927083 ER PT J AU Schwartz, AV Kelsey, JL Maggi, S Tuttleman, M Ho, SC Jonsson, PV Poor, G de Castro, JAS Xu, L Matkin, CC Nelson, LM Heyse, SP AF Schwartz, AV Kelsey, JL Maggi, S Tuttleman, M Ho, SC Jonsson, PV Poor, G de Castro, JAS Xu, L Matkin, CC Nelson, LM Heyse, SP TI International variation in the incidence of hip fractures: Cross-national project on osteoporosis for the World Health Organization program for research on aging SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE hip fracture; hospital discharge data; incidence rates; international comparison; osteoporosis ID EUROPE; RATES AB A cross-national study of hip fracture incidence was carried out in five geographic areas Beijing, China; Budapest, Hungary; Hong Kong: Porto Alegre, Brazil: and Reykjavik, Iceland - during the years 1990-1992. Cases of hip fracture among women and men of age 20 years and older were identified using hospital discharge data in conjunction with medical records, operating room logs, and radiology logs. Estimated incidence rates varied widely, with Beijing reporting the lowest rates (age-adjusted rate per 100 000 population for men 20 years and older = 45.4: women = 39.6) and Reykjavik the highest rates (men = 141.3; women = 274.1). Rates were higher for women than for men in every area except Beijing. In every area except Budapest, review of the operating room or radiology logs identified additional cases that were not reported in the discharge list, increasing the estimated number of hip fractures by 11% to 62%, depending on the area. Review of medical records identified miscoding of hip fractures (ICD9 820) as 'shaft of femur and other femur fractures' (ICD9 821) in the discharge lists of every area except Budapest, increasing the estimated number of hip fractures by 1% to 30%. The final estimates of hip fracture incidence taking into account all investigated sources of undercount and overcount ranged from 15% lower to 89% higher than an estimate based on the discharge diagnoses alone. Although these results indicate substantial limitations in relying on hospital discharge data alone to estimate hip fracture incidence rates, the extent of errors found in the discharge lists is smaller than the large international variation found here and previously reported in incidence rates. The findings support the conclusion that the differences reported among countries mainly reflect genuine variation in the hip fracture incidence rates. C1 Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA. CNR, Program Aging, Padua, Italy. NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD USA. Chinese Univ Hong Kong, Dept Community & Family Med, Shatin, Hong Kong. Univ Iceland, Dept Med, Reykjavik City Hosp, Reykjavik, Iceland. Natl Inst Rheumatol & Physiotherapy, Dept Rheumatol & Metab Bone & Joint Dis, Budapest, Hungary. Univ Fed Rio Grande Sul, Fac Med, Dept Internal Med & Endocrinol, Porto Alegre, RS, Brazil. Peking Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing, Peoples R China. RP Schwartz, AV (reprint author), Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, HRP Bldg T213C, Stanford, CA 94305 USA. FU NIAMS NIH HHS [1-Y02-AR-30002] NR 20 TC 137 Z9 141 U1 0 U2 5 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 1999 VL 9 IS 3 BP 242 EP 253 DI 10.1007/s001980050144 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194DQ UT WOS:000080177200010 PM 10450414 ER PT S AU Miles, FA AF Miles, FA BE Cohen, B Hess, BJM TI Short-latency visual stabilization mechanisms that help to compensate for translational disturbances of gaze SO OTOLITH FUNCTION IN SPATIAL ORIENTATION AND MOVEMENT SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Otolith Function in Spatial Orientation and Movement - Symposium in Memory of Volker Henn CY MAY 18-19, 1998 CL ZURICH, SWITZERLAND SP Zurich Univ Hosp, Betty & David Koetser Fdn Brain Res ID OPTIC FLOW STIMULI; OCULAR FOLLOWING RESPONSES; LINEAR VESTIBULOOCULAR REFLEX; HUMAN OPTOKINETIC NYSTAGMUS; VERGENCE EYE-MOVEMENTS; SUPERIOR TEMPORAL AREA; MACAQUE MONKEY; VIEWING DISTANCE; FUNCTIONAL-PROPERTIES; BINOCULAR DISPARITY AB Recent studies in primates have revealed short latency visual tracking mechanisms that help to stabilize the eyes during translational disturbances of the observer, and so operate as backups to otolith-mediated vestibule-ocular reflexes. One such mechanism generates version eye movements to help stabilize gaze when the moving observer looks off to one side, utilizing binocular disparity to help single cut the images in the plane of fixation (ocular following). Two others generate vergence eye movements to help maintain binocular alignment on objects that he ahead: one responds to the radial patterns of optic flow (radial-flow vergence) and the ether to the changes in binocular parallax (disparity vergence). Accumulating evidence suggests that, despite their short latency, all are mediated by the medial superior temporal area of cortex. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Miles, FA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convert Dr, Bethesda, MD 20892 USA. EM fam@lsr.nei.nih.gov NR 57 TC 10 Z9 10 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 1-57331-217-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 871 BP 260 EP 271 DI 10.1111/j.1749-6632.1999.tb09190.x PG 12 WC Multidisciplinary Sciences; Neurosciences; Otorhinolaryngology SC Science & Technology - Other Topics; Neurosciences & Neurology; Otorhinolaryngology GA BN24W UT WOS:000081273000020 PM 10372077 ER PT J AU Levine, M Wang, YH Rumsey, SC AF Levine, M Wang, YH Rumsey, SC TI Analysis of ascorbic acid and dehydroascorbic acid in biological samples SO OXIDANTS AND ANTIOXIDANTS, PT A SE METHODS IN ENZYMOLOGY LA English DT Review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COULOMETRIC ELECTROCHEMICAL DETECTION; HUMAN-PLASMA; HUMAN-NEUTROPHILS; VITAMIN-C; ACCUMULATION; TRANSPORT C1 NIH, Mol & Clin Nutr Sect, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIH, Mol & Clin Nutr Sect, Bldg 10, Bethesda, MD 20892 USA. NR 16 TC 52 Z9 53 U1 0 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 299 BP 65 EP 76 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BM67P UT WOS:000079431900006 PM 9916197 ER PT J AU Lewisch, SA Levine, RL AF Lewisch, SA Levine, RL TI Determination of 2-oxohistidine by amino acid analysis SO OXIDANTS AND ANTIOXIDANTS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID OXIDATIVELY MODIFIED PROTEINS; HUMAN GROWTH-HORMONE; CATALYZED OXIDATION; HISTIDINE-RESIDUES; 2-OXO-HISTIDINE; MECHANISM; SITE C1 AtheroGen Inc, Norcross, GA 30071 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Lewisch, SA (reprint author), AtheroGen Inc, Norcross, GA 30071 USA. RI Levine, Rodney/D-9885-2011 NR 11 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 300 BP 120 EP 124 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BM67Q UT WOS:000079432700015 PM 9919516 ER PT J AU Chae, HZ Kang, SW Rhee, SG AF Chae, HZ Kang, SW Rhee, SG TI Isoforms of mammalian peroxiredoxin that reduce peroxides in presence of thioredoxin SO OXIDANTS AND ANTIOXIDANTS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID ALKYL HYDROPEROXIDE REDUCTASE; THIOL-SPECIFIC ANTIOXIDANT; SACCHAROMYCES-CEREVISIAE; SALMONELLA-TYPHIMURIUM; CLONING; PROTEIN; PURIFICATION; CELLS; GENE; FAMILY C1 Chonnam Natl Univ, Coll Sci, Dept Biol, Kwangju, South Korea. NHLBI, Lab Cell Signalling, NIH, Bethesda, MD 20892 USA. RP Chae, HZ (reprint author), Chonnam Natl Univ, Coll Sci, Dept Biol, Kwangju, South Korea. NR 23 TC 171 Z9 173 U1 2 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 300 BP 219 EP 226 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BM67Q UT WOS:000079432700023 PM 9919524 ER PT J AU Moskovitz, J Berlett, BS Poston, JM Stadtman, ER AF Moskovitz, J Berlett, BS Poston, JM Stadtman, ER TI Methionine sulfoxide reductase in antioxidant defense SO OXIDANTS AND ANTIOXIDANTS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID RESIDUES; PROTEINS; EXPRESSION; OXIDATION; GENE C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Moskovitz, J (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. NR 16 TC 48 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 300 BP 239 EP 244 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BM67Q UT WOS:000079432700025 PM 9919526 ER PT S AU Rapoport, SI AF Rapoport, SI BE Blass, JP McDowell, FH TI Functional brain imaging in the resting state and during activation in Alzheimer's disease - Implications for disease mechanisms involving oxidative phosphorylation SO OXIDATIVE/ENERGY METABOLISM IN NEURODEGENERATIVE DISORDERS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Oxidative/Energy Metabolism in Neurodegenerative Disorders CY MAR 19-22, 1999 CL NEW YORK, NY SP New York Acad Sci, Winifred Masterson Burke Med Res Inst Inc, NIA, NIH, MitoKor, Amer Fed Aging Res, Warner Lambert Co, Parke Davis Pharmaceut Res ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; OXIDASE COX ACTIVITY; CYTOCHROME-OXIDASE; MESSENGER-RNA; GENE-EXPRESSION; NEURONAL-ACTIVITY; NEUROFIBRILLARY TANGLES; ENERGY-METABOLISM; APOLIPOPROTEIN-E AB In vivo brain imaging of patients with Alzheimer's disease (AD) using positron emission tomography (PET) demonstrates progressive reductions in resting-state brain glucose metabolism and blood now in relation to dementia severity, more so in association than primary cortical regions. Duping cognitive or psychophysical stimulation, blood now and metabolism in the affected regions can increase to the same extent in mildly demented AD patients as in age-matched controls, suggesting that energy delivery is not rate limiting. Activation declines with dementia severity, and is markedly reduced in severely demented patients. These results suggest that there is an initial "normal" functionally-responsive stage in AD, followed by a late less responsive stage. Studies of biopsied and postmortem brain indicate that the initial stage is accompanied by selective and potentially reversible down-regulation of the brain enzymes, including cytochrome oxidase, which mediate mitochondrial oxidative-phosphorylation. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. EM sir@helix.nih.gov NR 77 TC 27 Z9 27 U1 5 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-209-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 893 BP 138 EP 153 DI 10.1111/j.1749-6632.1999.tb07823.x PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Ornithology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Zoology GA BP50E UT WOS:000085330600012 PM 10672235 ER PT S AU Mattson, MP Pedersen, WA Duan, WZ Culmsee, C Camandola, S AF Mattson, MP Pedersen, WA Duan, WZ Culmsee, C Camandola, S BE Blass, JP McDowell, FH TI Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases SO OXIDATIVE/ENERGY METABOLISM IN NEURODEGENERATIVE DISORDERS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oxidative/Energy Metabolism in Neuridegenerative Disorders CY MAR 19-22, 1999 CL NEW YORK, NEW YORK SP New York Acad Sci, Winifred Masterson Burke Med Res Inst Inc, NIA, NIH, MitoKor, Amer Fed Aging Res, Warner Lambert Co, Parke Davis Pharmaceut Res ID AMYLOID BETA-PEPTIDE; MANGANESE SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION PRODUCT; IMPAIRS GLUCOSE-TRANSPORT; PRECURSOR PROTEIN PROTECT; ISCHEMIC BRAIN INJURY; OXIDATIVE STRESS; HIPPOCAMPAL-NEURONS; SECRETED FORMS; GLUTAMATE TRANSPORT AB Synaptic degeneration and death of nerve cells are defining features of Alzheimer's disease (AD) and Parkinson's disease (PD), the two mast prevalent age-related neurodegenerative disorders. In AD, neurons in the hippocampus and basal forebrain (brain regions that subserve learning and memory functions) are selectively vulnerable. In PD dopamine-producing neurons in the substantia nigra-striatum (brain regions that control body movements) selectively degenerate. Studies of postmortem brain tissue from AD and PD patients hare provided evidence for increased levels of oxidative stress, mitochondrial dysfunction and impaired glucose uptake in,vulnerable neuronal populations. Studies of animal and cell culture models of AD and PD suggest that increased levels of oxidative stress (membrane Lipid peroxidation, in particular) may disrupt neuronal energy metabolism and ion homeostasis, by Impairing the function of membrane ion-motive ATPases and glucose and glutamate transporters. Such oxidative and metabolic compromise may thereby render neurons vulnerable to excitotoxicity and apoptosis. Studies of the pathogenic mechanisms of D-linked mutations in amyloid precursor protein (APP) and presenilins strongly support central roles for perturbed cellular calcium homeostasis and aberrant proteolytic processing of APP as pivotal events that lead to metabolic compromise in neurons. Specific molecular "players" in the neurodegenerative processes in AD and PD are being identified and include Par-4 and caspases (bad guys) and neurotrophic factors and stress proteins (good guys), Interestingly, while studies continue to elucidate cellular and molecular events occurring in the brain in AD and PD, recent data suggest that both AD and PD can manifest systemic alterations in energy metabolism (e.g., increased insulin resistance and dysregulation of glucose metabolism). Emerging evidence that dietary restriction can forestall the development of AD and PD is consistent with a major ''metabolic" component to these disorders, and provides optimism that these devastating brain disorders of aging may be largely preventable. C1 NIA, Neurosci Lab, GRC 4F01, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, GRC 4F01, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 96 TC 212 Z9 222 U1 2 U2 15 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-209-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 893 BP 154 EP 175 DI 10.1111/j.1749-6632.1999.tb07824.x PG 22 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Ornithology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Zoology GA BP50E UT WOS:000085330600013 PM 10672236 ER PT S AU Liu, LI Rapoport, SI Chandrasekaran, K AF Liu, LI Rapoport, SI Chandrasekaran, K BE Blass, JP McDowell, FH TI Regulation of mitochondrial gene expression in differentiated PC12 cells SO OXIDATIVE/ENERGY METABOLISM IN NEURODEGENERATIVE DISORDERS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oxidative/Energy Metabolism in Neuridegenerative Disorders CY MAR 19-22, 1999 CL NEW YORK, NEW YORK SP New York Acad Sci, Winifred Masterson Burke Med Res Inst Inc, NIA, NIH, MitoKor, Amer Fed Aging Res, Warner Lambert Co, Parke Davis Pharmaceut Res ID DISEASE C1 Univ Maryland, Dept Anesthesiol, Baltimore, MD 21201 USA. NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. RP Chandrasekaran, K (reprint author), Univ Maryland, Dept Anesthesiol, Baltimore, MD 21201 USA. NR 4 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 1-57331-209-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 893 BP 341 EP 344 DI 10.1111/j.1749-6632.1999.tb07850.x PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Ornithology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Zoology GA BP50E UT WOS:000085330600039 PM 10672262 ER PT S AU Zarchin, N Meilin, S Rifkind, AJ Mayevsky, A AF Zarchin, N Meilin, S Rifkind, AJ Mayevsky, A BE Eke, A Delpy, DT TI Hemodynamic, metabolic, ionic and electrical responses to cortical spreading depression in aging rats SO OXYGEN TRANSPORT TO TISSUE XXI SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the International-Society-on-Oxygen-Transport-to-Tissue (ISOTT 98) CY AUG 23-28, 1998 CL BUDAPEST, HUNGARY SP Int Soc Oxygen Transport Tissue, Alliance Pharmaceut, Hemox Therapeut, Radiometer Copenhagen, Berlex Biosic ID OXIDE SYNTHASE ACTIVITY; BLOOD-FLOW; CEREBRAL-CORTEX; MOUSE-BRAIN; CATS C1 Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel. NIA, LCMB, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Zarchin, N (reprint author), Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel. NR 25 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46281-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 471 BP 223 EP 230 PG 8 WC Cell Biology; Hematology; Medicine, Research & Experimental; Physiology SC Cell Biology; Hematology; Research & Experimental Medicine; Physiology GA BP58J UT WOS:000085570200027 PM 10659151 ER PT B AU Miller, LH AF Miller, LH BE Coluzzi, M TI Evolution of the human genome under selective pressure from malaria: applications for control SO PARASSITOLOGIA, VOL 41, NOS 1-3, SEPTEMBER 1999 LA English DT Proceedings Paper CT Malariology Centenary Conference on the Malaria Challenge After One Hundred Years of Malariology CY NOV 16-19, 1998 CL ACAD NAZL LINCEI, ROME, ITALY SP Acad Nazl Lincei, Royal Soc Trop Med & Hyg, Soc Italiana Parassitol HO ACAD NAZL LINCEI DE human polymorphisms; malaria; pathogenesis; Plasmodium falciparum; P-vivax ID PLASMODIUM-FALCIPARUM MALARIA; NATURAL-SELECTION; CEREBRAL MALARIA; RESISTANCE; RECEPTOR; ERYTHROCYTES; THALASSEMIA; CHILDREN; ANTIGENS; AFRICA AB Research on the molecular basis for resistance of humans to malaria has been vigorous during the last 10 years, with new discoveries and extension of work from previous decades. Much of the work has important implications both for understanding pathogenesis and for applications for control of disease. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Miller, LH (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr, Bethesda, MD 20892 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU LOMBARDO EDITORE PI 00161 ROME PA VIA VERONA 22, 00161 ROME, ITALY PY 1999 BP 77 EP 82 PG 6 WC Parasitology SC Parasitology GA BQ03E UT WOS:000086914700009 ER PT J AU Feng, YR Biggar, RJ Gee, D Norwood, D Zeichner, SL Dimitrov, DS AF Feng, YR Biggar, RJ Gee, D Norwood, D Zeichner, SL Dimitrov, DS TI Long-term telomere dynamics: Modest increase of cell turnover in HIV-infected individuals followed for up to 14 years SO PATHOBIOLOGY LA English DT Article DE telomeres; HIV; AIDS; pathogenesis ID HUMAN FIBROBLASTS; LENGTH; CD4(+); PATHOGENESIS; LYMPHOCYTES; SUBSET; CD8(+) AB To quantify the long-term dynamics of telomere lengths and the effect of HIV infection on lymphocyte turnover rates, we measured in a blinded study longitudinal samples from 6 individuals using a highly accurate method based on two-dimensional calibration of DNA sizes. For two uninfected controls followed 8 and 10 years the average telomeric terminal restriction fragment (TRF) shortening rate in peripheral blood mononuclear cells (PBMCs) was 50 and 60 bp/year, respectively, in agreement with previous measurements of cross-sectional samples. The TRF lengths of PBMCs from two slow progressors followed for 14 years declined by a rate of 120 +/- 10 bp/year, i.e. 2-fold higher than the rate of TRF shortening for uninfected individuals. The rate of TRF shortening was higher in CD8 (140 +/- 10 bp/year) than in CD4 (100 +/- 10 bp/year) cells. The CD8 cell TRFs of the two fast progressors shortened faster (240 +/- 10 bp/year) and the rate of CD4 cell TRF shortening in one of the fast progressors was 160 bp/year. These data suggest that HIV infection causes only a modest increase in the lymphocyte turnover which we speculate could be due to chronic activation of the immune system, and may not result in the exhaustion of its regenerative capacity and immuno-pathogenesis. C1 NCI, Lab Expt & Computat Biol, Div Basic Sci, FCRDC,NIH, Ft Detrick, MD 21702 USA. NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancies Branch, NIH, Bethesda, MD 20892 USA. RP Dimitrov, DS (reprint author), NCI, Lab Expt & Computat Biol, Div Basic Sci, FCRDC,NIH, Bldg 469,Rm 216,POB B,Miller Dr, Ft Detrick, MD 21702 USA. NR 21 TC 14 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD JAN-FEB PY 1999 VL 67 IS 1 BP 34 EP 38 DI 10.1159/000028048 PG 5 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 161XR UT WOS:000078315400005 PM 9873226 ER PT J AU Sanz-Ortega, J Bryant, B Sanz-Esponera, J Asenjo, JA Saez, MC Torres, A Balibrea, JL Sobel, ME Merino, MJ AF Sanz-Ortega, J Bryant, B Sanz-Esponera, J Asenjo, JA Saez, MC Torres, A Balibrea, JL Sobel, ME Merino, MJ TI LOH at the APC/MCC gene (5Q21) is frequent in early stages of non-small cell lung cancer SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE lung cancer; chromosome 5p21; LOH; microdissection ID HETEROZYGOSITY; CARCINOMAS; LESIONS; POPULATIONS; PROGRESSION; LOSSES; 18Q; P53 AB Lung cancer is the leading cause of death in both women and men in the United States and many European countries. Molecular cytogenetic and LOH analyses of non-small cell lung cancer have shown somatic genetic alterations in a variety of chromosomes, such as 1p, 3p, 5q, 8p, 9p, 11p, 11q and 17p. Allelic deletions of the known tumor suppressor gene APC at 5q21 are frequently observed in advanced stages of lung cancer and have been correlated with poor prognosis in previous reports. We investigated 33 cases of NSCL for LOH at 5q21: 22 squamous cell and 11 adenocarcinomas. Normal and tumor cells were microdissected from paraffin embedded tissues and PCR amplification was performed utilising the specific markers D5S299 and D5S346 at 5q21 and PYGM at 11q13, respectively. Clinicopathological data, survival and recurrence rates were obtained in all cases. We detected LOH at 5q21 in 4/9 (44%) informative adenocarcinomas and in 13/16 (81%) informative SCC. LOH was frequent in early stages (12/15 stage I cases) and did not correlate with recurrence or poor survival. Our results show that LOH at 5q21 is more frequent in squamous cell carcinomas than in adenocarcinomas, is frequent in early stages of the disease, and does not have prognostic significance. C1 Hosp Univ San Carlos, Madrid, Spain. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Sanz-Ortega, J (reprint author), Dept Anat Patol, Martin Lagos SN, E-28040 Madrid, Spain. RI Sanz, Julian/G-5276-2013 NR 25 TC 17 Z9 18 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 1999 VL 195 IS 10 BP 677 EP 680 PG 4 WC Pathology SC Pathology GA 247RL UT WOS:000083233700003 PM 10549031 ER PT J AU Pham, DL Prince, JL AF Pham, DL Prince, JL TI An adaptive fuzzy C-means algorithm for image segmentation in the presence of intensity inhomogeneities SO PATTERN RECOGNITION LETTERS LA English DT Article DE image segmentation; fuzzy C-means; intensity inhomogeneities; magnetic resonance imaging ID MR-IMAGES AB We present a novel algorithm for obtaining fuzzy segmentations of images that are subject to multiplicative intensity inhomogeneities, such as magnetic resonance images. The algorithm is formulated by modifying the objective function in the fuzzy C-means algorithm to include a multiplier field, which allows the centroids for each class to vary across the image. First and second order regularization terms ensure that the multiplier field is both slowly varying and smooth. An iterative algorithm that minimizes the objective function is described, and its efficacy is demonstrated on several test images. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. NIA, Lab Personal & Cognit, GRC, NIH, Baltimore, MD 21224 USA. RP Prince, JL (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. EM prince@jhu.edu RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 21 TC 248 Z9 273 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD JAN PY 1999 VL 20 IS 1 BP 57 EP 68 DI 10.1016/S0167-8655(98)00121-4 PG 12 WC Computer Science, Artificial Intelligence SC Computer Science GA 162FT UT WOS:000078335800008 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM Murray, DL Overturf, GD Prober, CG Saari, T Weiner, LB Whitley, RJ Peter, G Pickering, LK Baker, CJ Hirsch, AT Jacobs, RF MacDonald, NE Schwartz, B Orenstein, WA Hardegree, MC Rabinovich, NR Breiman, RF AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM Murray, DL Overturf, GD Prober, CG Saari, T Weiner, LB Whitley, RJ Peter, G Pickering, LK Baker, CJ Hirsch, AT Jacobs, RF MacDonald, NE Schwartz, B Orenstein, WA Hardegree, MC Rabinovich, NR Breiman, RF TI Poliomyelitis prevention: Revised recommendations for use of inactivated and live oral poliovirus vaccines SO PEDIATRICS LA English DT Article AB Since 1997 when the American Academy of Pediatrics (AAP) issued revised guidelines for the prevention of poliomyelitis, substantial progress in global eradication of poliomyelitis has occurred and the use of inactivated poliovirus vaccine (IPV) has increased considerably in the United States with a corresponding decrease in the use of oral poliovirus vaccine (OPV). Surveys indicate that the majority of physicians now routinely immunize chit dren with the sequential IPV-OPV or IPV-only regimens. Nevertheless, vaccine-associated paralytic poliomyelitis (VAPP) continues to occur, albeit infrequently, in children who have received the OPV-only regimen and their contacts. To reduce further the risk of VAPP, the AAP now recommends that children in the United States receive IPV for the first 2 doses of the polio vaccine series in most circrumstances. Exceptions include a parent's refusal to permit the number of injections necessary to administer the other routinely recommended vaccines at the 2- and 4-month visits. Either IPV or OPV can be administered for the third and fourth doses. Assuming continuing progress toward global eradication, a recommendation of IPV-only immunization for children in the United States is anticipated by 2001. C1 AAP Council Pediat Practice, New York, NY USA. Canadian Pediat Soc, Calgary, AB, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD USA. Natl Vaccine Program Off, Washington, DC USA. NR 5 TC 21 Z9 21 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 1999 VL 103 IS 1 BP 171 EP 172 PG 2 WC Pediatrics SC Pediatrics GA 157KW UT WOS:000078060900043 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM TI Recommended childhood immunization schedule - United States, January December 1999 SO PEDIATRICS LA English DT Article C1 AAP Council Pediat Practice, New York, NY USA. Canadian Pediat Soc, Calgary, AB, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD USA. Natl Vaccine Program Off, Washington, DC USA. NR 6 TC 18 Z9 18 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 1999 VL 103 IS 1 BP 182 EP 185 PG 4 WC Pediatrics SC Pediatrics GA 157KW UT WOS:000078060900045 ER PT B AU Higashimoto, Y Lewis, MS Kennedy, P Gronenborn, AM Clore, GM Appella, E Sakaguchi, K AF Higashimoto, Y Lewis, MS Kennedy, P Gronenborn, AM Clore, GM Appella, E Sakaguchi, K BE Shimonishi, Y TI Effects of mutations on tetramer formation of tumor suppressor protein p53 SO PEPTIDE SCIENCE - PRESENT AND FUTURE LA English DT Proceedings Paper CT 1st International Peptide Symposium CY NOV 30-DEC 05, 1997 CL KYOTO, JAPAN SP Amer Peptide Soc, Australian Peptide Soc, European Peptide Soc, Japanese Peptide Soc, Chem Soc Japan, Pharmaceut Soc Japan, Japan Soc Biosci, Biotechnol & Agrochem, Protein Res Fdn, Japan Natl Tourist Org C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Higashimoto, Y (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5271-8 PY 1999 BP 303 EP 305 PG 3 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BN21Y UT WOS:000081131800103 ER PT J AU Koh, SWM Leyton, J Moody, TW AF Koh, SWM Leyton, J Moody, TW TI Bombesin activates MAP kinase in non-small cell lung cancer cells SO PEPTIDES LA English DT Article DE GRP receptor; second messengers; MAP kinase; lung cancer; PD98059 ID GASTRIN-RELEASING PEPTIDE; SWISS 3T3 CELLS; PROTEIN-KINASE; RECEPTOR ANTAGONIST; GROWTH-FACTORS; NEUROMEDIN-B; CARCINOMA; INVITRO; STIMULATION; EXPRESSION AB The effects of bombesin (BB) on mitogen activated protein (MAP) kinase were investigated using non-small cell lung cancer (NSCLC) cells. By Western blot, both 42 and 44 kDalton forms of MAP kinase were present in NCI-H1299 and NCI-H838 cells. Addition of BE to NCI-H1299 cells resulted in phosphorylation of the MAP kinase substrate myelin basic protein (MBP). Phosphorylation of MBP was maximal 6 min after the addition of 10 nM BE to NCI-H1299 cells. Addition of gastrin releasing peptide (GRP) or GRP(14-27) but not GRP(1-16) to NCI-H1299 cells caused MBP phosphorylation. The effects of BE were inhibited by BW2258U89, a BE receptor antagonist, and PD98059, a MAP kinase kinase inhibitor. Also, PD98059 inhibited the clonal growth of NCI-H1299 cells. These data suggest that MAP kinase may be an important regulatory enzyme in NSCLC. (C) 1999 by Elsevier Science Inc. C1 Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA. NCI, Cell & Canc Biol Dept, Med Branch, Rockville, MD 20850 USA. RP Koh, SWM (reprint author), Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA. EM moodyt@bprb.nci.nih.gov NR 41 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PY 1999 VL 20 IS 1 BP 121 EP 126 DI 10.1016/S0196-9781(98)00144-2 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 174HG UT WOS:000079028200015 PM 10098632 ER PT J AU Smith, RD AF Smith, RD TI Marked ion dependence of (125)I-angiotensin I binding to atypical sites on Mycoplasma hyorhinis SO PEPTIDES LA English DT Article DE atypical angiotensin receptors; salt; IEC-18 cells; alkali metal chlorides; sodium halides; disuccinimidylsuberate ID ANGIOTENSIN-II; HIGH-AFFINITY; RECEPTOR; DISTINCT; CELLS; IDENTIFICATION; EXPRESSION; AT(1) AB (125)I-Ang I binding to atypical sites on Mycoplasma hyorhinis-contaminated IEC-18 cell membranes increased with increasing pH and [NaCl] (ED(50) at 500 mM; maximal 13-fold increase at 2 M NaCl). Alkali metal chlorides and sodium halides increased binding with rank orders of Na(+) < K(+) < Rb(+) < Cs(+) = Li(+) and F(-) < Cl(-) < Br(-) < I. Covalent cross-linking of (125)I-Ang I labeled a discrete band of 97 kDa. These findings suggest that the site is not a G protein-coupled receptor, but may play a role in the sensing by Mycoplasma of the ionic composition and/or pH of its environment. (C) 1999 Elsevier Science Inc. All rights reserved. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Smith, RD (reprint author), 96 Shelford Rd, Cambridge CB2 2NF, England. EM rds29@hermes.cam.ac.uk NR 22 TC 1 Z9 1 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 J9 PEPTIDES JI Peptides PY 1999 VL 20 IS 2 BP 165 EP 169 DI 10.1016/S0196-9781(98)00163-6 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 213KW UT WOS:000081272600002 PM 10422870 ER PT J AU Liu, MF Zeng, J Robey, FA AF Liu, MF Zeng, J Robey, FA TI Tyrosine phosphorylation induced by C4 peptide constructs from HIV Gp120 SO PEPTIDES LA English DT Article DE peptomer; gp120; synthetic peptide; signal transduction; HUT78; T cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; HUMAN LYMPHOCYTES-T; KINASE P56LCK; CONFORMATIONAL SWITCH; CHEMOKINE RECEPTORS; CELL ACTIVATION; CYCLIC-PEPTIDES; CD4 RECEPTOR; HTLV-III/LAV AB Treatment of HUT78 cells with CD4-binding peptide constructs derived from the C4 domain of HIV-1 gp120 results in autophosphorylation of a src-related kinase, p56(lck). This leads to p56(lck) activation and the subsequent phosphorylation of tyrosine residues in several intracellular proteins. The phosphorylation is specific to the C4 peptides as no new phosphorylation occurs when the cells are treated with control peptides or polymers. The induction of tyrosine phosphorylation by the C4 peptide constructs depends on the capability of the peptide to assume a helical conformation because similar peptide constructs that were not able to form helices did not induce cellular tyrosine phosphorylation. (C) 1999 Elsevier Science Inc. All rights reserved. C1 NIDR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Robey, FA (reprint author), NIDR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. NR 43 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PY 1999 VL 20 IS 2 BP 185 EP 191 DI 10.1016/S0196-9781(98)00158-2 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 213KW UT WOS:000081272600005 PM 10422873 ER PT B AU Yao, ZJ Ye, B Zhao, H Yan, XJ Wu, L Barford, D Wang, SM Zhang, ZY Burke, TR AF Yao, ZJ Ye, B Zhao, H Yan, XJ Wu, L Barford, D Wang, SM Zhang, ZY Burke, TR BE Tam, JP Kaumaya, PTP TI Structure-based design of small molecule protein-tyrosine phosphatase inhibitors SO PEPTIDES: FRONTIERS OF PEPTIDES SCIENCE LA English DT Proceedings Paper CT 15th American Peptide Symposium CY JUN 14-19, 1997 CL NASHVILLE, TN SP Amer Peptide Soc, Vanderbilt Univ ID SUBSTRATE-SPECIFICITY C1 NCI, Med Chem Lab, DBS, NIH, Bethesda, MD 20892 USA. RP Yao, ZJ (reprint author), NCI, Med Chem Lab, DBS, NIH, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5160-6 PY 1999 BP 183 EP 185 PG 3 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA BP45W UT WOS:000085202200072 ER PT B AU Majer, P Smrcina, M Majerova, E Guerassina, TA Eissenstat, MA AF Majer, P Smrcina, M Majerova, E Guerassina, TA Eissenstat, MA BE Tam, JP Kaumaya, PTP TI Facile stereoselective synthesis of gamma-amino acids from the corresponding alpha-amino acids SO PEPTIDES: FRONTIERS OF PEPTIDES SCIENCE LA English DT Proceedings Paper CT 15th American Peptide Symposium CY JUN 14-19, 1997 CL NASHVILLE, TN SP Amer Peptide Soc, Vanderbilt Univ ID DERIVATIVES; INHIBITION; GLUTAMATE; ANALOGS C1 NCI, Struct Biochem Program, SAIC, Frederick Res & Dev Ctr, Frederick, MD 21702 USA. RP Majer, P (reprint author), NCI, Struct Biochem Program, SAIC, Frederick Res & Dev Ctr, Frederick, MD 21702 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5160-6 PY 1999 BP 317 EP 318 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA BP45W UT WOS:000085202200135 ER PT B AU Bryant, SD Guerrini, R Salvadori, S Bianchi, C Tomatis, R Attila, M Lazarus, LH AF Bryant, SD Guerrini, R Salvadori, S Bianchi, C Tomatis, R Attila, M Lazarus, LH BE Tam, JP Kaumaya, PTP TI Opioidmimetic peptides containing alpha-aminoisobutyric acid SO PEPTIDES: FRONTIERS OF PEPTIDES SCIENCE LA English DT Proceedings Paper CT 15th American Peptide Symposium CY JUN 14-19, 1997 CL NASHVILLE, TN SP Amer Peptide Soc, Vanderbilt Univ ID DELTA-OPIOID RECEPTOR; RESIDUES; RECOGNITION C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Bryant, SD (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5160-6 PY 1999 BP 473 EP 474 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA BP45W UT WOS:000085202200206 ER PT B AU Roller, PP Lung, FDT Mutoh, M O'Connor, PM AF Roller, PP Lung, FDT Mutoh, M O'Connor, PM BE Tam, JP Kaumaya, PTP TI Functional site studies with peptide segments of Cdk inhibitory proteins SO PEPTIDES: FRONTIERS OF PEPTIDES SCIENCE LA English DT Proceedings Paper CT 15th American Peptide Symposium CY JUN 14-19, 1997 CL NASHVILLE, TN SP Amer Peptide Soc, Vanderbilt Univ ID CYCLIN; IDENTIFICATION C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Roller, PP (reprint author), NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5160-6 PY 1999 BP 547 EP 548 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA BP45W UT WOS:000085202200236 ER PT B AU Lung, FDT Sastry, L Wang, SM Lou, BS Barchi, JJ King, CR Roller, PP AF Lung, FDT Sastry, L Wang, SM Lou, BS Barchi, JJ King, CR Roller, PP BE Tam, JP Kaumaya, PTP TI Novel non-phosphorylated peptides binding to the Grb2-SH2 domain SO PEPTIDES: FRONTIERS OF PEPTIDES SCIENCE LA English DT Proceedings Paper CT 15th American Peptide Symposium CY JUN 14-19, 1997 CL NASHVILLE, TN SP Amer Peptide Soc, Vanderbilt Univ ID SPECIFICITY C1 NCI, Med Chem Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Lung, FDT (reprint author), NCI, Med Chem Lab, Div Basic Sci, Bethesda, MD 20892 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5160-6 PY 1999 BP 582 EP 583 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA BP45W UT WOS:000085202200253 ER PT B AU Lazarus, LH Salvadori, S Balboni, G Guerrini, R Bianchi, C Cooper, PS Bryant, SD AF Lazarus, LH Salvadori, S Balboni, G Guerrini, R Bianchi, C Cooper, PS Bryant, SD BE Tam, JP Kaumaya, PTP TI Generation of new Dmt-Tic delta opioid antagonists: N-alkylation SO PEPTIDES: FRONTIERS OF PEPTIDES SCIENCE LA English DT Proceedings Paper CT 15th American Peptide Symposium CY JUN 14-19, 1997 CL NASHVILLE, TN SP Amer Peptide Soc, Vanderbilt Univ ID TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID; PEPTIDES; DIKETOPIPERAZINES; RESIDUE C1 NIEHS, Res Triangle Pk, NC 27707 USA. RP Lazarus, LH (reprint author), NIEHS, Res Triangle Pk, NC 27707 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5160-6 PY 1999 BP 603 EP 604 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA BP45W UT WOS:000085202200262 ER PT B AU Majer, P Collins, JR Pan, WX Gulnik, SV Lee, A Gustchina, E Erickson, JW AF Majer, P Collins, JR Pan, WX Gulnik, SV Lee, A Gustchina, E Erickson, JW BE Tam, JP Kaumaya, PTP TI Rational design and synthesis of conformationally constrained inhibitors of human cathepsin D SO PEPTIDES: FRONTIERS OF PEPTIDES SCIENCE LA English DT Proceedings Paper CT 15th American Peptide Symposium CY JUN 14-19, 1997 CL NASHVILLE, TN SP Amer Peptide Soc, Vanderbilt Univ ID ALZHEIMER-DISEASE; CANCER C1 NCI, Struct Biochem Program, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Majer, P (reprint author), NCI, Struct Biochem Program, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5160-6 PY 1999 BP 670 EP 671 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA BP45W UT WOS:000085202200293 ER PT B AU Nomizu, M Kuratomi, Y Kim, WH Song, SY Hoffman, MP Kleinman, HK Yamada, Y AF Nomizu, M Kuratomi, Y Kim, WH Song, SY Hoffman, MP Kleinman, HK Yamada, Y BE Tam, JP Kaumaya, PTP TI Biological functions of synthetic peptides derived from the laminin alpha 1 chain G domain SO PEPTIDES: FRONTIERS OF PEPTIDES SCIENCE LA English DT Proceedings Paper CT 15th American Peptide Symposium CY JUN 14-19, 1997 CL NASHVILLE, TN SP Amer Peptide Soc, Vanderbilt Univ ID TERMINAL GLOBULAR DOMAIN; IDENTIFICATION C1 NIDR, CDBRB, NIH, Bethesda, MD 20892 USA. RP Nomizu, M (reprint author), NIDR, CDBRB, NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5160-6 PY 1999 BP 735 EP 736 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA BP45W UT WOS:000085202200320 ER PT S AU Burke, RE AF Burke, RE BE Binder, MD TI Revisiting the notion of 'motor unit types' SO PERIPHERAL AND SPINAL MECHANISMS IN THE NEURAL CONTROL OF MOVEMENT SE Progress in Brain Research LA English DT Review CT Satellite Symposium of the Society-for-Neuroscience CY NOV 04-06, 1998 CL UNIV ARIZONA, TUCSON, AZ HO UNIV ARIZONA ID CAT MEDIAL GASTROCNEMIUS; SUCCINATE-DEHYDROGENASE ACTIVITY; FIBER-TYPE COMPOSITIONS; DEEP LUMBRICAL MUSCLE; TIBIALIS ANTERIOR; HINDLIMB MUSCLES; SYNAPTIC INPUT; RAT; CLASSIFICATION; NEURONS C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. EM reburke@helix.nih.gov NR 73 TC 20 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50288-2 J9 PROG BRAIN RES JI Prog. Brain Res. PY 1999 VL 123 BP 167 EP 175 DI 10.1016/S0079-6123(08)62854-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA BP61M UT WOS:000085689500015 PM 10635714 ER PT J AU Rosenthal, JP AF Rosenthal, JP TI Drug discovery, economic development and conservation: The International Cooperative Biodiversity Groups - Preface SO PHARMACEUTICAL BIOLOGY LA English DT Editorial Material C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Rosenthal, JP (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 1999 VL 37 SU S BP 5 EP 5 DI 10.1076/1388-0209(200010)37:SUP;1-W;FT005 PG 1 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 375MC UT WOS:000165402200001 ER PT J AU Rosenthal, JP Beck, D Bhat, A Biswas, J Brady, L Bridbord, K Collins, S Cragg, G Edwards, J Fairfield, A Gottlieb, M Gschwind, LA Hallock, Y Hawks, R Hegyeli, R Johnson, G Keusch, GT Lyons, EE Miller, R Rodman, J Roskoski, J Siegel-Causey, D AF Rosenthal, JP Beck, D Bhat, A Biswas, J Brady, L Bridbord, K Collins, S Cragg, G Edwards, J Fairfield, A Gottlieb, M Gschwind, LA Hallock, Y Hawks, R Hegyeli, R Johnson, G Keusch, GT Lyons, EE Miller, R Rodman, J Roskoski, J Siegel-Causey, D TI Combining high risk science with ambitious social and economic goals SO PHARMACEUTICAL BIOLOGY LA English DT Article DE drug discovery; economic development; biodiversity conservation; natural products; research; training; patents; traditional knowledge ID DRUG; AGREEMENTS; DISCOVERY; LEADS; HITS AB Great strides have been made during the past decade in understanding the interelatedness of human health, economic welfare and environmental quality. Among these is the certainty that improvements in health may be impeded or reversed by poverty and destruction of the natural resources that diverse biological species provide. The International Cooperative Biodiversity Groups (ICBG) represent an experimental effort supported by three agencies of the U.S. Government to integrate research in natural products drug discovery with efforts to build the scientific and economic capacity of developing countries as well as enhance the skills and incentives needed to conserve biological diversity. These groups are unique, public-private collaborations that have been carrying out interdisciplinary research and development projects for up to seven years in 12 countries in Latin America, Africa and Asia. In addition to research on species in 230 plant families and 25 arthropod orders, over 1400 individuals have received technical training, and potential therapies for several parasitic diseases, tuberculosis and crop diseases are in development. The ICBGs have also developed novel research and intellectual property agreements and have become important testing grounds in national and global discussions regarding access, informed consent and benefit-sharing associated with generic resources. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Foreign Agr Serv, USDA, Washington, DC 20250 USA. NIDA, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Natl Sci Fdn, Biosci Directorate, Arlington, VA 22230 USA. NCI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Rosenthal, JP (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr, Bethesda, MD 20892 USA. NR 52 TC 26 Z9 27 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 1999 VL 37 SU S BP 6 EP 21 DI 10.1076/1388-0209(200010)37:SUP;1-W;FT006 PG 16 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 375MC UT WOS:000165402200002 ER PT B AU Sokoloff, L Kuang, TY Horinaka, N Kennedy, C AF Sokoloff, L Kuang, TY Horinaka, N Kennedy, C BE Krieglstein, J TI Are cerebral circulation and energy metabolism really tightly coupled? SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1998 LA English DT Proceedings Paper CT 7th International Symposium on the Pharmacology of Cerebral Ischemia CY JUL 27-29, 1998 CL MARBURG, GERMANY SP Deutsch Foesch Gemeinsch, Bonn, Philipps Univ, Marburg, Biotrend Chemikalien GmbH, Koln, Gesell Med Sondentechnik mbH, Mielkendorg, Hoechst Marion Roussel, Bad Soden, Janssen-Cilag, Neuss, Knoll AG, Ludwigshafen, Perimed AB, Jarfalla, Willmar Schwabe Arzneimmittel GmbH, Karlsruhe, Tech & Sci Equipment GmbH, Bad Homburg ID SENSITIVE POTASSIUM CHANNELS; INSULIN-INDUCED HYPOGLYCEMIA; DEPENDENT PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; BLOOD-FLOW; K+ CHANNELS; ADENOSINE CONCENTRATION; ELECTRICAL-STIMULATION; OXIDATIVE-METABOLISM; VASCULAR-RESISTANCE AB In the current vogue of functional brain imaging of signals related to cerebral blood flow (CBF) by PET or magnetic resonance techniques it is tacitly assumed that local CBF is "tightly coupled" to local metabolic and functional activities in brain. This concept has persisted for decades despite frequently encountered examples of their dissociation. Recent studies of CBF during cerebral glucose deprivation by either insulin-induced hypoglycemia or glycolytic blockade with pharmacologic doses of 2-deoxyglucose have suggested mechanisms tending to favor correlation between CBF and metabolism in brain but not obligatory coupling or linkage. During glucose deprivation there are large increases in CBF despite reductions in energy metabolism. Both caffeine, an adenosine receptor antagonist, and glibenclamide, which blocks ATP-sensitive K+ (K-ATP) channels, reduce in a dose-dependent manner to the point of abolition these increases in CBF. Adenosine receptors that mediate vasodilation, and K-ATP channels which when open promote smooth muscle relaxation, exist in vascular smooth muscle. During glucose deprivation levels of adenosine and its degradation products rise markedly in brain, indicating increased adenosine formation. There is evidence in a variety of tissues that adenosine receptor activation stimulates cyclic AMP formation which activates protein kinase A and protein phosphorylation. There is also evidence that the activity of the K-ATP channels can be altered by such phosphorylation. The following sequence is suggested: 1) ADP and inorganic phosphate (Pi) levels rise from stimulation of ATP hydrolysis by Na+, K+-ATPase activity during functional activation or from reduced ATP regeneration during glucose or oxygen deprivation; 2) some of the ADP is converted to AMP by adenylic kinase; 3) AMP is dephosphorylated to adenosine by 5'-nucleotidase; 4) adenosine acting at adenosine A, receptors stimulates G-protein-coupled adenylyl cyclase activity and cyclic AMP formation in vascular smooth muscle; 5) cyclic AMP-dependent protein kinase A phosphorylates K+ channels causing them to open, allowing K+ efflux, membrane hyperpolarization, smooth muscle relaxation, and vasodilatation. Raising ADP and Pi concentrations is known to stimulate both glycolysis and oxidative metabolism. Therefore, shifting the ATP/ADP balance toward ADP, either by ATP overutilization during functional activation or by underproduction during substrate insufficiency, leads to increases in both CBF and energy metabolism, thus resulting in their being related, not by direct linkage through some coupling mechanism, but as independent yet correlated consequences of one prior event. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NR 63 TC 0 Z9 0 U1 1 U2 1 PU MEDPHARM GMBH SCIENTIFIC PUBL PI STUTTGART PA BIRKENWALDSTRASSE 44, D-7000 STUTTGART, GERMANY BN 3-88763-070-X PY 1999 BP 3 EP 16 PG 14 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Peripheral Vascular Disease SC Neurosciences & Neurology; Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA BN55B UT WOS:000082191900001 ER PT B AU Ginis, I Dawson, D Liu, J Spatz, M Hallenbeck, J AF Ginis, I Dawson, D Liu, J Spatz, M Hallenbeck, J BE Krieglstein, J TI Microvascular and endothelial cell responses to ischemic tolerance induced by TNF-alpha SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1998 LA English DT Proceedings Paper CT 7th International Symposium on the Pharmacology of Cerebral Ischemia CY JUL 27-29, 1998 CL MARBURG, GERMANY SP Deutsch Foesch Gemeinsch, Bonn, Philipps Univ, Marburg, Biotrend Chemikalien GmbH, Koln, Gesell Med Sondentechnik mbH, Mielkendorg, Hoechst Marion Roussel, Bad Soden, Janssen-Cilag, Neuss, Knoll AG, Ludwigshafen, Perimed AB, Jarfalla, Willmar Schwabe Arzneimmittel GmbH, Karlsruhe, Tech & Sci Equipment GmbH, Bad Homburg ID TUMOR-NECROSIS-FACTOR; FOCAL CEREBRAL-ISCHEMIA; ICAM-1 EXPRESSION; GENE-EXPRESSION; BRAIN; ADHESION; GERBIL; DAMAGE; LIPOPOLYSACCHARIDE; INTERLEUKIN-1 C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Ginis, I (reprint author), NINDS, Stroke Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU MEDPHARM GMBH SCIENTIFIC PUBL PI STUTTGART PA BIRKENWALDSTRASSE 44, D-7000 STUTTGART, GERMANY BN 3-88763-070-X PY 1999 BP 389 EP 394 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Peripheral Vascular Disease SC Neurosciences & Neurology; Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA BN55B UT WOS:000082191900040 ER PT B AU Marler, JR AF Marler, JR BE Krieglstein, J TI Thrombolysis in acute stroke SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1998 LA English DT Proceedings Paper CT 7th International Symposium on the Pharmacology of Cerebral Ischemia CY JUL 27-29, 1998 CL MARBURG, GERMANY SP Deutsch Foesch Gemeinsch, Bonn, Philipps Univ, Marburg, Biotrend Chemikalien GmbH, Koln, Gesell Med Sondentechnik mbH, Mielkendorg, Hoechst Marion Roussel, Bad Soden, Janssen-Cilag, Neuss, Knoll AG, Ludwigshafen, Perimed AB, Jarfalla, Willmar Schwabe Arzneimmittel GmbH, Karlsruhe, Tech & Sci Equipment GmbH, Bad Homburg ID TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE ISCHEMIC STROKE; URGENT THERAPY; TRIAL; REDUCTION; MINUTES; DAMAGE C1 NINDS, Div Stroke Trauma & Neurodegenerat Disorders, Clin Trial Grp, Bethesda, MD 20892 USA. RP Marler, JR (reprint author), NINDS, Div Stroke Trauma & Neurodegenerat Disorders, Clin Trial Grp, 7550 Wisconsin Ave,Room 8A08, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU MEDPHARM GMBH SCIENTIFIC PUBL PI STUTTGART PA BIRKENWALDSTRASSE 44, D-7000 STUTTGART, GERMANY BN 3-88763-070-X PY 1999 BP 499 EP 507 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Peripheral Vascular Disease SC Neurosciences & Neurology; Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA BN55B UT WOS:000082191900052 ER PT J AU Zoller, U Yagi, H Jerina, DM AF Zoller, U Yagi, H Jerina, DM TI Stereoselective synthesis and properties of bay-region episulfides of benzo[a]pyrenes SO PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS LA English DT Article AB The bay-region diol episulfides of benzo[a]pyrene (BaP), DES-1 (1b) and DES-2 (2b), were stereoselectively synthesized from the diol epoxides DE-2 (2a) and DE-1 (la) respectively, apparently via the intermediacy of a five-membered 1,3-oxythiolane 4. The DESs are thermodynamically unstable (desulfurization), but remarkably stable under hydrolytic conditions. C1 Univ Haifa, Dept Sci Educ Chem, IL-36006 Kiryat Tivon, Israel. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Zoller, U (reprint author), Univ Haifa, Dept Sci Educ Chem, IL-36006 Kiryat Tivon, Israel. NR 5 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 RG1 8JL, BERKS, ENGLAND SN 1042-6507 J9 PHOSPHORUS SULFUR JI Phosphorus Sulfur Silicon Relat. Elem. PY 1999 VL 153 BP 307 EP 308 PG 2 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 333NY UT WOS:000088137200022 ER PT J AU Bicout, DJ Rubin, RJ AF Bicout, DJ Rubin, RJ TI Classification of microtubule histories SO PHYSICAL REVIEW E LA English DT Article ID DARK-FIELD MICROSCOPY; DYNAMIC INSTABILITY; INDIVIDUAL MICROTUBULES; GTP-CAP; HYDROLYSIS; KINETICS; INVITRO AB A microtubule of a given length undergoes all possible scenarios of transitions between growing and shrinking phases, so-called microtubule dynamic instability. In this Paper we utilize a minimal two-state model proposed by Kill [Proc. Natl. Acad. Sci. USA 81, 6728 (1984)] that is equivalent to a two-state random walk. Using a technique for classifying discrete random walk configurations by introducing a counting variable in evolution equations, we have derived expressions for probability densities (which contain information about all transition histories) of phase transitions before the complete disappearance of a microtubule. As a result, the mean lifetime of a microtubule turns out to be equal to the total lifetime of growing and shrinking phases times the average number of transitions. An attractive feature of this simple model is that elementary formulas relating statistical averages to rate parameters are obtained. [S1063-651X(99)02001-2]. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bicout, DJ (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 136, Bethesda, MD 20892 USA. EM bicout@speck.niddk.nih.gov; R1R@CU.NIH.GOV NR 19 TC 18 Z9 18 U1 0 U2 4 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 1999 VL 59 IS 1 BP 913 EP 920 DI 10.1103/PhysRevE.59.913 PN B PG 8 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 158JJ UT WOS:000078112000034 ER PT J AU Strey, HH Parsegian, VA Podgornik, R AF Strey, HH Parsegian, VA Podgornik, R TI Equation of state for polymer liquid crystals: Theory and experiment SO PHYSICAL REVIEW E LA English DT Article ID DNA DOUBLE HELICES; ENHANCED ELECTROSTATIC FORCES; HYDRATION FORCES; DOUBLE-LAYER; OSMOTIC-STRESS; PHASES; POLYELECTROLYTES; ELECTROPHORESIS; MOLECULES; PACKING AB The first part of this paper develops a theory for the free energy of lyotropic polymer nematic liquid crystals. We use a continuum model with macroscopic elastic moduli for a polymer nematic phase. By evaluating the partition function, considering only harmonic fluctuations, we derive an expression for the free energy of the system. We find that the configurational entropic part of the free energy enhances the effective repulsive interactions between the chains. This configurational contribution goes as the fourth root of the direct interactions. Enhancement originates from the coupling between bending fluctuations and the compressibility of the nematic array normal to the average director. In the second part of the paper we use osmotic stress to measure the equation of state for DNA liquid crystals in 0.1M to 1M NaCl solutions. These measurements cover five orders of magnitude in DNA osmotic pressure. At high osmotic pressures the equation of state, dominated by exponentially decaying hydration repulsion, is independent of the ionic strength. At lower pressures the equation of state is dominated by fluctuation enhanced electrostatic double layer repulsion. The measured equation of state for DNA fits well with our theory for all salt concentrations. We are able to extract the strength of the direct electrostatic double layer repulsion. This is an alternative way of measuring effective charge densities along semiflexible polyelectrolytes. [S1063-651X(99)11401-6]. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP NICHHD, Lab Phys & Struct Biol, NIH, Bldg 12A-2041, Bethesda, MD 20892 USA. RI Strey, Helmut/B-5456-2009; Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 54 TC 91 Z9 97 U1 1 U2 22 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD JAN PY 1999 VL 59 IS 1 BP 999 EP 1008 DI 10.1103/PhysRevE.59.999 PN B PG 10 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 158JJ UT WOS:000078112000045 ER PT J AU Yagi, H Vepachedu, S Sayer, JM Chang, RL Cui, XX Zoller, U Jerina, DM AF Yagi, H Vepachedu, S Sayer, JM Chang, RL Cui, XX Zoller, U Jerina, DM TI Synthesis and properties of bay-region episulfides of benzo[a]pyrene SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE synthesis of PAH-episulfides; solvolytic reactivity; cytotoxicity and mutagenicity of diol episulfides ID SOLVOLYSIS; EPOXIDES AB A highly efficient, general method was developed for conversion of epoxides to the corresponding episulfides with dimethylthioformamide in the presence of BF3. Et2O at low temperature (-20 degrees C). Thus, the 9,10-epoxide of 7,8,9,10-tetrahydrobenzo[a]pyrene (3) and 4-methoxystyrene oxide (6) were converted to the corresponding episulfides (4) and (7), respectively, in over 90% yield. Highly stereoselective conversions of (+/-)-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (DE-1, 1a) and its diastereomeric 9,10-isomer (DE-2, 2a) to the corresponding diol episulfide-2b (DES-2) and -1b (DES-1), respectively, were also achieved by this method. These episulfides showed remarkable stability towards aqueous acid (>10(5) less reactive than the corresponding epoxides). Studies in Chinese hamster V-79 cells indicated that 1b and 2b have very low toxicity and mutagenicity compared to 2a. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20982 USA. Rutgers State Univ, Coll Pharm, Dept Biol Chem, Canc Res Lab, Piscataway, NJ 08855 USA. Haifa Univ Oranim, Dept Sci Educ Chem, IL-36006 Kiryat Tivon, Israel. RP Yagi, H (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20982 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 17 IS 1-4 BP 85 EP 94 DI 10.1080/10406639908020604 PG 10 WC Chemistry, Organic SC Chemistry GA 297HE UT WOS:000086076200010 ER PT J AU Sayer, JM Shah, JH Liang, CY Xie, GJ Kroth, H Yagi, H Liu, XH Yeh, HJC Jerina, DM AF Sayer, JM Shah, JH Liang, CY Xie, GJ Kroth, H Yagi, H Liu, XH Yeh, HJC Jerina, DM TI Effect of absolute configuration on the optical and NMR properties of oligonucleotides containing benzo[a]pyrene abducts at N-6 of deoxyadenosine SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE benzo[a]pyrene diol epoxides; deoxyadenosine adducts; oligonucleotides; thermal denaturation; ultraviolet spectra; NMR ID DG MISMATCH OPPOSITE; N-6-AMINO GROUP; TRANS ADDITION; DNA DUPLEX; NONANUCLEOTIDE DUPLEX; SOLUTION CONFORMATION; ADDUCT SITE; INTERCALATION; MUTATIONS; SYN AB For oligonucleotide duplexes derived from trans opening of benzo[a]pyrene diol epoxides (BaP DEs) by the exocyclic N-6-amino group of deoxyadenosine (dA), the hydrocarbon is intercalated toward the 5'-end of the modified strand when the configuration at the site of attachment of the base to the hydrocarbon (C-10) is R, and toward the 3'-end when this configuration is S. In oligonucleotide 11-mer duplexes modified by BaP DE-1 (benzylic 7-OH and epoxide oxygen cis) and DE-2 (7-OH and epoxide oxygen trans), as well as 7,8,9,10-tetrahydro BaP 9,10-epoxide, 10R adducts had consistently higher (5-9 degrees C) T-m values than the corresponding 10S adducts. Dodecamer duplexes from the HPRT gene with trans opened 10S (but not those with 10R) BaP DE-2 adducts at either of two adjacent dA residues exhibited blue shifts at similar to 350 nm at temperatures well below the T-m. We propose that these blue shifts result from a conformation in which the hydrocarbon is not stacked with the DNA bases. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Sayer, JM (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 17 IS 1-4 BP 95 EP 104 DI 10.1080/10406639908020605 PG 10 WC Chemistry, Organic SC Chemistry GA 297HE UT WOS:000086076200011 ER PT J AU Szeliga, J Zhang, FJ Harvey, RG Dipple, A AF Szeliga, J Zhang, FJ Harvey, RG Dipple, A TI DNA adducts formed by the fjord-region dihydrodiol epoxide of benzo[S]picene SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE DNA adducts; benzo[s]picene; anti dihydrodiol epoxide ID COVALENT NUCLEOSIDE ADDUCTS; 11,12-DIHYDRODIOL 13,14-EPOXIDE; 3,4-DIOL 1,2-EPOXIDES; CYTOSINE BASES; ADENINE; GUANINE AB Anti benzo[s]picene 9,10-dihydrodiol 11,12-epoxide was reacted with calf thymus DNA and with its constituent deoxyribonucleotides. The origin of DNA adducts was established by comparison of their HPLC retention times and UV spectra with those of the nucleotide-derived adduct-markers. The low binding of the dihydrodiol epoxide to DNA (2%) and to deoxyguanylic and deoxyadenylic acids precluded an NMR study, and assignment of cis or trans epoxide ring opening was made by analogy to other anti dihydrodiol epoxide adducts. The adduct ratio for dGuo/dAdo in DNA was 24/76 and the ratios of dGuo cis/dGuo trans and dAdo cis/dAdo trans were 40/60 and 6/94, respectively. C1 NCI, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. Univ Chicago, Ben May Inst, Chicago, IL 60637 USA. RP Szeliga, J (reprint author), NCI, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. NR 22 TC 0 Z9 0 U1 0 U2 3 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 17 IS 1-4 BP 115 EP 124 DI 10.1080/10406639908020607 PG 10 WC Chemistry, Organic SC Chemistry GA 297HE UT WOS:000086076200013 ER PT J AU Poirier, MC Weston, A Schoket, B Shamkhani, H Pan, CF Mc Diarmid, MA Scott, BG Deeter, DP Heller, JM Jacobson-Kram, D Rothman, N AF Poirier, MC Weston, A Schoket, B Shamkhani, H Pan, CF Mc Diarmid, MA Scott, BG Deeter, DP Heller, JM Jacobson-Kram, D Rothman, N TI Polycyclic aromatic hydrocarbon biomarkers of internal exposure in US Army soldiers serving in Kuwait in 1991 SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE DNA adducts; urinary metabolites; human biomonitoring; ambient monitoring ID BURNING OIL-WELLS; WHITE BLOOD-CELLS; DNA-ADDUCTS; BENZOPYRENE; CONSUMPTION; SENSITIVITY; URINE; BEEF AB Biomarkers of exposure were applied to a cohort of U.S. Army soldiers who were deployed to Kuwait and Saudi Arabia in 1991 in the aftermath of the Persian Gulf War. The U.S. Army Environmental Hygiene Agency (currently the U.S Army Center for Health Promotion and Preventive Medicine) monitored air and soil for ambient PAHs. In addition, a group of 61 soldiers kept diaries of daily activities. These soldiers provided blood and urine samples in June in Germany before deployment to Kuwait, in August after 8 weeks in Kuwait, and in October, one month after the return to Germany. DNA, prepared from white blood cells, was assayed for PAH-DNA adducts by immunoassay and bulky aromatic adducts by P-32-postlabeling, Urinary 1-hydroxypyrene-glucuronide (1-OH-PG) was determined by synchronous fluorescence spectrometry. Contrary to expectations, environmental monitoring showed low ambient PAH levels in the areas where these soldiers were working in Kuwait. In addition, literature values for ambient PAH monitoring in Germany in 1990 suggest that the soldiers may have been exposed to higher levels of ambient PAHs in Germany than in Kuwait. Blood cell DNA adduct levels were lowest in Kuwait and increased significantly after the return to Germany. Also, urinary 1-OH-PG levels were lowest in Kuwait and highest in Germany. This study demonstrates modulations in PAH exposure biomarker levels that appear to correlate with ambient PAH exposure. C1 NCI, LCCTP, NIH, Bethesda, MD 20892 USA. Natl Inst Publ Hlth, H-1097 Budapest, Hungary. Ctr Dis Control, NIOSH, HELD, Morgantown, WV 26505 USA. Kaiser Permanente, Gaithersburg, MD USA. Mt Sinai Med Ctr, Dept Community Med, New York, NY 10029 USA. Univ Maryland, Sch Med, Occupat Hlth Project, Baltimore, MD 21201 USA. USA, Command & Gen Staff Coll, Ft Leavenworth, KS 66027 USA. USA, MEDDAC, RSA, AL 35809 USA. USA, CHPPM, Aberdeen Proving Ground, MD 21010 USA. MA Bioserv Inc, Rockville, MD 20850 USA. NCI, OEB, DCEG, NIH, Bethesda, MD 20892 USA. RP Poirier, MC (reprint author), NCI, LCCTP, NIH, Bethesda, MD 20892 USA. NR 20 TC 7 Z9 7 U1 1 U2 1 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 17 IS 1-4 BP 197 EP 208 DI 10.1080/10406639908020615 PG 12 WC Chemistry, Organic SC Chemistry GA 297HE UT WOS:000086076200021 ER PT J AU Lin, B Doan, L Yagi, H Jerina, DM Whalen, D AF Lin, B Doan, L Yagi, H Jerina, DM Whalen, D TI Quantitative aspects of the effects of halide and azide ions on the acid-catalyzed hydrolysis of (+/-)-7 beta-8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE benzo[a]pyrene diol epoxides; hydrolysis; halohydrins ID EPOXIDE HYDROLYSIS; CHLORIDE-ION; MECHANISMS; OXIDE; PH AB Mechanisms of the acid-catalyzed reactions of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7, 8, 9, 10-tetrahydrobenzo[a]pyrene (1) in 1:9 dioxane-water solutions containing varying concentrations of KCl, KBr, NaI, NaN3 and NaClO4 are discussed. C1 Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21228 USA. NCI, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Lin, B (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21228 USA. OI Lin, Binshan/0000-0002-8481-302X NR 15 TC 1 Z9 1 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 79 EP 88 DI 10.1080/10406639908020575 PG 10 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100010 ER PT J AU Khan, QA Vousden, KH Dipple, A AF Khan, QA Vousden, KH Dipple, A TI 'Stealth properties' contribute to the potent action of polycyclic aromatic hydrocarbon carcinogens SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE p53; cell cycle; stealth carcinogen; actinomycin D; benzo[g]chrysene; 5-methylchrysene ID DIOL EPOXIDE METABOLITES; DNA-ADDUCTS; DIHYDRODIOL-EPOXIDES; CELLULAR-RESPONSE; MOUSE SKIN; P53; CELLS; 5-METHYLCHRYSENE; BENZOCHRYSENE; BENZOPYRENE AB Dihydrodiol epoxides are carcinogenic metabolites of polycyclic aromatic hydrocarbons. The effects of two such compounds, benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide and 5-methylchrysene 1,2-dihydrodiol 3,4-epoxide, on the progress of the human mammary carcinoma cell, MCF-7, through the cell cycle was investigated. Unlike other DNA damaging agents, such as actinomycin D, these carcinogens did not arrest MCF-7 cells in the G1 phase of the cell cycle and the cells began DNA replication despite the damage in the DNA template. The dihydrodiol epoxides, like actinomycin D, induced the p53 protein that normally mediates G1 arrest through transcriptional activation of p21(waf1/cip1), in these cells. However, increased cellular p21(waf1/cip1) levels were not found in the hydrocarbon-treated cells. Thus, these carcinogens did not trigger the major 'guardian of the genome' cellular defense mechanism mediated by p53. This stealth characteristic may be an important contributor to the carcinogenic action of these agents. C1 NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Virol & Carcinogenesis Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Khan, QA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick, MD 21702 USA. NR 31 TC 1 Z9 1 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 89 EP 98 DI 10.1080/10406639908020576 PG 10 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100011 ER PT J AU Page, JE Liang, CY Sayer, JM Jerina, DM Dipple, A AF Page, JE Liang, CY Sayer, JM Jerina, DM Dipple, A TI Site-specific mutagenesis with benzo[a]pyrene-deoxyribonucleoside adducts SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE mutation; benzo[a]pyrene; site-specific; deoxyadenosine adduct; diol epoxide ID ESCHERICHIA-COLI PLASMID; (+)-ANTI-BENZOPYRENE DIOL EPOXIDE; SEQUENCE CONTEXT; (+)-ANTI-DIOL EPOXIDE; DNA-ADDUCTS; SUPF GENE; IN-VITRO; BENZOPYRENE; MUTATIONS; CELLS AB The various methods that have been used in site-specific mutagenesis studies with DNA adducts from hydrocarbon diol epoxides are briefly reviewed. The single-stranded M13 approach pioneered by Lawrence and his colleagues offers the advantage that DNA repair processes should not reduce mutation frequencies since they should lead to vector destruction. The application of this approach to an evaluation of the mutagenic effects arising from a benzo[a]pyrene-deoxyadenosine adduct is shown. Substantial numbers of A-->T and A-->G base substitution mutations were obtained along with a few A-->C mutations. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Page, JE (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NR 22 TC 1 Z9 1 U1 1 U2 1 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 99 EP 108 DI 10.1080/10406639908020577 PG 10 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100012 ER PT J AU Cai, YN Marcus, C Guengerich, FP Gelboin, HV Baird, WM AF Cai, YN Marcus, C Guengerich, FP Gelboin, HV Baird, WM TI Role of cytochrome P450 1A1 and 1B1 in metabolic activation of dibenzo[a,l]pyrene by microsomes from the human mammary carcinoma cell line MCF-7 SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE cytochrome P450; dibenzo[a, l]pyrene; DNA adducts; human mammary carcinoma cell line ID MUTAGENICITY AB Incubation of DB[a,l]P with microsomes from TCDD-treated MCF-7 cells produced mainly (-) anti DB[a,l]P-11,12-diol 13,14-epoxide-dAdo adducts. Addition of antibodies against CYP1A1 and CYP1B1 inhibited the formation of DNA adducts up to 88% and 51%, respectively. The level of P450 1B1 protein was dramatically elevated, but P450 1A1 protein is not detectable by blottings in MCF-7 cells treated with 5 mu M or 8 mu M DB[a,l]. MCF-7 cells treated with TCDD or B[a]P contained elevated P450 1A1 and P450 1B1. The current results demonstrate that both P450 1A1 and P450 1B1 are involved in metabolic activation of DB [a,l]P in MCF-7 cells treated with TCDD and suggest that P450 1B1 may be the major DB [a,l]P activating enzyme in MCF-7 cells treated with DB[a,l]P. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47906 USA. Univ New Mexico, Dept Pharmacol & Toxicol, Albuquerque, NM 87131 USA. Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. Vanderbilt Univ, Ctr Mol Toxicol, Sch Med, Nashville, TN 37232 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Cai, YN (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47906 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 109 EP 118 DI 10.1080/10406639908020578 PG 10 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100013 ER PT J AU Desai, D Krzeminski, J Lin, JM Chadha, A Miyata, N Yagi, H Jerina, DM Amin, S AF Desai, D Krzeminski, J Lin, JM Chadha, A Miyata, N Yagi, H Jerina, DM Amin, S TI Syntheses and identification of benzo[c]chrysene metabolites SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE benzo[c]chrysene; in vitro metabolism; mutagenicity ID REGION DIOL-EPOXIDES; MOUSE SKIN; BENZOPHENANTHRENE; BENZO(C)PHENANTHRENE; DNA AB Like other PAHs, chrysenes are thought to exert their carcinogenicity via metabolic activation of proximally carcinogenic dihydrodiols to diol epoxides as ultimate carcinogens. Benzo[c] chrysene (B[c]C) is structurally intriguing among the PAH because it features both a bay region and a fjord region. Although B[c]C is carcinogenic and mutagenic, few data are available on its metabolic activation or the nature of its metabolites. We have synthesized the B[c]C trans-1,2-, 7,8-, and 9,10-dihydrodiols from the appropriate methoxy-substituted bislaphthyl olefins by photochemical cyclization. B[c]C was metabolized with S9 liver fraction from phenobarbital/beta-naphthoflavone-treated rats. Dihydrodiols were formed on both terminal rings as well as in the K-region. 2-, 3-, and 10-HydroxyB[c]C were also identified as metabolites. In mutagenicity studies toward S. typhimurium TA100, 1,2-dihydrodiol was more mutagenic than B[c]C at doses above 1.25 mu g/plate, whereas 9,10-dihydrodiol was toxic at doses above 1.25 1.25 mu g/plate. C1 Amer Hlth Fdn, Valhalla, NY 10595 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Desai, D (reprint author), Amer Hlth Fdn, 1 Dana Rd, Valhalla, NY 10595 USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 16 IS 1-4 BP 255 EP 264 DI 10.1080/10406639908020592 PG 10 WC Chemistry, Organic SC Chemistry GA 297HD UT WOS:000086076100027 ER PT J AU Szeliga, J Harvey, RG Cortez, C Dipple, A AF Szeliga, J Harvey, RG Cortez, C Dipple, A TI DNA adducts from syn 7-methylbenz[a]anthracene 3,4-dihydrodiol 1,2-epoxide SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE DNA adducts; 7-methylbenz[a]anthracene; syn dihydrodiol epoxide; circular dichroism ID REGION 3,4-DIOL 1,2-EPOXIDES; METABOLIC-ACTIVATION; 11,12-DIHYDRODIOL 13,14-EPOXIDE; CYTOSINE BASES; DIOL-EPOXIDE; CARCINOGENS; ADENINE; GUANINE AB DNA adducts derived from reaction of the racemic bay region syn 7-methylbenz[a]anthracene 3,4-dihydrodiol 1,2-epoxide with calf thymus DNA in vitro were tentatively identified. Eight markers (four deoxyguanosine and four deoxyadenosine adducts) were obtained from separate reactions of the racemic syn dihydrodiol epoxide with deoxyguanylic and deoxyadenylic acids. The nucleoside of origin of individual DNA products was established by comparing HPLC retention times and UV spectra of DNA adducts with those of the adduct markers. All DNA adducts eluted with retention times and had UV spectra that corresponded to the purine nucleoside adducts. Circular dichroism spectra of the marker adducts allowed assignment of S and R configuration at C-1, the site of attachment of the hydrocarbon residue to the nucleoside. The CD spectra were comprised of four pairs of spectra that were mirror images of one another. Each pair consisted of the two cis or two trans products resulting from epoxide ring opening of each dihydrodiol epoxide enantiomer by the exocyclic amino group of the deoxyguanosine or deoxyadenosine residues. Since the adducts obtained were insufficient for NMR studies, assignment of cis and trans structures was made by comparison of elution sequence and circular dichroism data with those of the known syn benz[a]anthracene dihydrodiol epoxide adducts. The ratio of dGuo/dAdo adducts in DNA was 1.5, close to the ratio reported for syn benz[a]anthracene dihydrodiol epoxide. DNA adducts accounted for 27% of the original dihydrodiol epoxide used. The ratios of dGuo/dAdo modifications were 58/42 and 69/31 for the 3S,4R-dihydrodiol 1S,2R-epoxide and the 3R,4S-dihydrodiol 1R,2S-epoxide enantiomers, respectively. Approximately 75% of total DNA adducts was derived from the 3S,4R-dihydrodiol 1S,2R-epoxide enantiomer and these were largely cis adducts. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. Univ Chicago, Ben May Inst, Chicago, IL 60637 USA. RP Szeliga, J (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 13 IS 1 BP 41 EP 53 DI 10.1080/10406639908020542 PG 13 WC Chemistry, Organic SC Chemistry GA 178TY UT WOS:000079284400005 ER PT J AU Desai, D Krzeminski, J Lin, JM Jerina, D Amin, S AF Desai, D Krzeminski, J Lin, JM Jerina, D Amin, S TI Syntheses of major and minor metabolites of benzo[c]chrysene SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article DE benzo[c]chrysene metabolites; synthesis; photocyclization ID REGION DIOL-EPOXIDES; TUMORIGENICITY; BENZO(C)PHENANTHRENE AB Benzo[c]chrysene (B[c]C), a weakly carcinogenic polycyclic aromatic hydrocarbon (PAH), has been detected in coal tar and crude oil. Its structure is intriguing in that it has a bay region and a fjord region in the same molecule. To study in vitro metabolism of B[c]C and to identify the metabolites of this compound, synthetic standards were needed. In this communication, we report the synthesis of B[c]C and its three proximate carcinogenic metabolites; namely, (+/-)-trans-1, 2-dihydro-1, 2-dihydroxyB[c]C (B[c]C-1,2-diol), (+/-)-trans-7,8-dihydro-7,8-dihydroxyB[c] (B[c]C-7,8-diol), and (+/-)-trans-9, 10-dihydro-9, 10-dihydroxyB[c]C (B[c]C-9,10-diol) from methoxy substituted dinaphthyl-ethylenes by photochemical cyclization. Major and minor phenolic metabolites of B[c]C were also synthesized. C1 Amer Hlth Fdn, Organ Synth Facil, Valhalla, NY 10595 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Desai, D (reprint author), Amer Hlth Fdn, Organ Synth Facil, 1 Dana Rd, Valhalla, NY 10595 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 1999 VL 13 IS 3 BP 301 EP 312 DI 10.1080/10406639908020552 PG 12 WC Chemistry, Organic SC Chemistry GA 274AW UT WOS:000084742400005 ER PT J AU Yordanov, AT Gansow, OA Brechbiel, MW Rogers, LM Rogers, RD AF Yordanov, AT Gansow, OA Brechbiel, MW Rogers, LM Rogers, RD TI The preparation and X-ray crystallographic characterization of lead(II) calix[4]arenesulfonate complex SO POLYHEDRON LA English DT Article DE lead; complex; calix[4]arenesulfonate; organic clay; X-ray structure ID TRANSITION-METAL COMPLEXES; MONOCLONAL-ANTIBODY; WATER; CALIXARENES; CHEMISTRY AB The reaction of tetrasodium calix[4]arenesulfonate with lead(II) nitrate gives a complex with 2:1 metal-ligand stoichiometry. The complex has been characterized by elemental and X-ray crystal structure analysis. The latter reveals a layered structure consisting of alternating hydrophilic and hydrophobic layers. All Pb(II) ions have different coordination environments and show an unusually high degree of hydration in the solid state. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 23 TC 25 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-5387 J9 POLYHEDRON JI Polyhedron PY 1999 VL 18 IS 7 BP 1055 EP 1059 DI 10.1016/S0277-5387(98)00393-3 PG 5 WC Chemistry, Inorganic & Nuclear; Crystallography SC Chemistry; Crystallography GA 195CQ UT WOS:000080231900018 ER PT J AU Shinomiya, K Kabasawa, Y Ito, Y AF Shinomiya, K Kabasawa, Y Ito, Y TI Effect of elution modes on protein separation by cross-axis coil planet centrifuge with two different types of coiled columns SO PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY LA English DT Article ID PERFORMING COUNTERCURRENT CHROMATOGRAPHY; POLYMER PHASE SYSTEMS; STATIONARY-PHASE; ROTARY SEALS; ACCELERATION; EFFICIENCY; APPARATUS; RETENTION; SPEED AB Effect of elution modes on protein separation was investigated using cross-axis coil planet centrifuge (cross-axis CPC) with two different types of coiled columns, i.e., eccentric coil and toroidal coil assemblies. Myoglobin and lysozyme were separated with an aqueous two-phase solvent system composed of 12.5% (w/w) polyethylene glycol 1000 and 12.5% (w/w) dibasic potassium phosphate. The substantial effect of elution modes was observed by the toroidal coil, while the negative result was given at the eccentric coil. Using the toroidal coil, higher peak resolution of proteins was attained at the tail to head elution mode. In the outward lower phase mobile elution mode, the satisfactory separation was obtained by both eccentric coil and toroidal coil assemblies. However, in the inward upper phase mobile elution mode, the toroidal coil produced a broad and asymmetric myoglobin peak. The analysis using polyacrylamide gel electrophoresis revealed that the toroidal coil partially separated the components originally present in the myoglobin sample. As the result, a modified equation was devised to express the peak resolution (Rs) using the lysozyme peak. The overall results indicated that the toroidal coil produced better partition efficiency than the eccentric coil under the optimized experimental condition including the direction of the Coriolis force acting on the mobile phase in the toroidal coil. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. NR 16 TC 15 Z9 15 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6068 J9 PREP BIOCHEM BIOTECH JI Prep. Biochem. Biotechnol. PY 1999 VL 29 IS 2 BP 139 EP 150 DI 10.1080/10826069908544886 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 190LC UT WOS:000079963600002 PM 10231893 ER PT S AU Kennedy, CJ Giraud-Carrier, C Bristol, DW AF Kennedy, CJ Giraud-Carrier, C Bristol, DW BE Zytkow, JM Rauch, J TI Predicting chemical carcinogenesis using structural information only SO PRINCIPLES OF DATA MINING AND KNOWLEDGE DISCOVERY SE Lecture Notes in Artificial Intelligence LA English DT Article; Proceedings Paper CT 3rd European Conference on Principles of Data Mining and Knowledge Discovery in Databases (PKDD 99) CY SEP 15-18, 1999 CL UNIV ECON, LAB INTELLIGENT SYST, PRAGUE, CZECH REPUBLIC SP Komercni Banka HO UNIV ECON, LAB INTELLIGENT SYST AB This paper reports on the application of the Strongly Typed Evolutionary Programming System (STEPS) to the PTE2 challenge, which consists of predicting the carcinogenic activity of chemical compounds from their molecular structure and the outcomes of a number of laboratory analyses. Most contestants so fax have relied heavily on results of short term toxicity (STT) assays. Using both types of information made available, most models incorporate attributes that make them strongly dependent on STT results. Although such models may prove to be accurate and informative, the use of toxicological information requires time cost and in some cases substantial utilisation of laboratory animals. If toxicological information only makes explicit, properties implicit in the molecular structure of chemicals, then provided a sufficiently expressive representation language, accurate solutions may be obtained from the structural information only. Such solutions may offer more tangible insight into the mechanistic paths and features that govern chemical toxicity as well as prediction based on virtual chemistry for the universe of compounds. C1 Univ Bristol, Dept Comp Sci, Bristol BS8 1UB, Avon, England. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Univ Bristol, Dept Comp Sci, Merchant Venturers Bldg, Bristol BS8 1UB, Avon, England. EM kennedy@cs.bris.ac.uk; cgc@cs.bris.ac.uk; U.S.A.bristol@niehs.nih.gov NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-66490-4 J9 LECT NOTES ARTIF INT PY 1999 VL 1704 BP 360 EP 365 PG 6 WC Computer Science, Artificial Intelligence SC Computer Science GA BS61Q UT WOS:000170570600043 ER PT J AU Gold, PW Chrousos, GP AF Gold, PW Chrousos, GP TI The endocrinology of melancholic and atypical depression: Relation to neurocircuitry and somatic consequences SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-of-American-Physicians CY APR, 1997 CL WASHINGTON, D.C. SP Assoc Amer Physicians DE amygdala; corticotropin-releasing hormone; depression; hypercortisolism; hypocortisolism; prefrontal cortex ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; RECEPTOR MESSENGER-RNA; HORMONE-SECRETION INVITRO; MEDIAL PREFRONTAL CORTEX; MAJOR DEPRESSION; RAT-BRAIN; CUSHINGS-SYNDROME; FACTOR CRF; PARAVENTRICULAR NUCLEUS AB The cardinal clinical manifestations of major depression with melancholic features include sustained anxiety and dread for the future as well as evidence of physiological hyperarousal (e.e., sustained hyperactivity of the two principal effecters of the stress response, the corticotropin-releasing-hormone, or CRH, system, and the locus ceruleus-norepinephrine, or LC-NE, system). Sustained stress system activation in melancholic depression is thought to confer both behavioral arousal as well as the hypercortisolism, sympathetic nervous system activation, and inhibition of programs for growth and reproduction that consistently occur in this: disorder. Data also suggest that activation of the CRH and LC systems in melancholia are involved in the long-term medical consequences of depression such as premature coronary artery disease and osteoporosis, the two-three-fold preponderance of females in the incidence of major depression, and the mechanism of action of antidepressant drugs. In addition, recent data reveal important bidirectional interactions between stress-system hormonal factors in depression and neural substrates implicated in many discrete behavioral alterations in depression (e.g., the medial prefrontal cortex. important in shifting affect based on internal and external cues, the mesolimbic dopaminergic reward system, and the amygdala fear system). We have also advanced data indicating that the hypersomnia, hyperphagia, lethargy, fatigue, and relative apathy of the syndrome of atypical depression are associated with concomitant hypofunctioning of the CRH and LC-NE systems. These data indicate the need for an entirely different therapeutic strategy than that used in melancholia for the treatment of atypical depression, and they suggest that this subtype of major depression will be associated with its own unique repertoire of long-term medical consequences. C1 NIMH, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Gold, PW (reprint author), NIMH, NIH, 10 Ctr Dr,Bldg 10,2D46-1284, Bethesda, MD 20892 USA. NR 90 TC 199 Z9 204 U1 1 U2 13 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JAN-FEB PY 1999 VL 111 IS 1 BP 22 EP 34 DI 10.1046/j.1525-1381.1999.09423.x PG 13 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 168NU UT WOS:000078699800005 PM 9893154 ER PT J AU Samelson, LE AF Samelson, LE TI Adaptor proteins and T-cell antigen receptor signaling SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review ID C-CBL PROTOONCOGENE; TYROSINE KINASES; PHOSPHATIDYLINOSITOL-3 KINASE; VAV PROTOONCOGENE; MOLECULAR-CLONING; EXCHANGE PROTEIN; P85 SUBUNIT; SH3 BINDING; GRB2; ACTIVATION C1 NICHHD, Cell Biol & Metab Branch, Sect Lymphocyte Signaling, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NICHHD, Cell Biol & Metab Branch, Sect Lymphocyte Signaling, NIH, Bethesda, MD 20892 USA. NR 53 TC 25 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PY 1999 VL 71 IS 3-4 BP 393 EP 403 DI 10.1016/S0079-6107(98)00050-9 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 184EN UT WOS:000079597600006 PM 10354706 ER PT S AU Bogardus, C Ravussin, E Norman, R Pratley, RE Permana, PA Prochazka, M Baier, L Bennett, PH Knowler, WC Hanson, RL AF Bogardus, C Ravussin, E Norman, R Pratley, RE Permana, PA Prochazka, M Baier, L Bennett, PH Knowler, WC Hanson, RL BE GuyGrand, B TI Genome-wide scan for obesity susceptibility genes in Pima Indians SO PROGRESS IN OBESITY RESEARCH: 8 SE PROGRESS IN OBESITY RESEARCH LA English DT Proceedings Paper CT 8th International Congress on Obesity CY AUG 29-SEP 03, 1998 CL PARIS, FRANCE SP Int Assoc Study Obesity ID RESTING METABOLIC-RATE; TWINS REARED APART; BODY-MASS INDEX; ENERGY-EXPENDITURE; DIABETES-MELLITUS; WEIGHT-GAIN; LOCI; RISK; FAT; PREDICTOR C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Bogardus, C (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St,Room 541, Phoenix, AZ 85016 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY & CO PI LONDON PA 13 SMITHS YARD, SUMMERLEY ST, LONDON SW18 4HR, ENGLAND SN 0962-7936 BN 0-86196-581-7 J9 PROG OBES R PY 1999 BP 129 EP 134 PG 6 WC Anatomy & Morphology; Endocrinology & Metabolism; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Anatomy & Morphology; Endocrinology & Metabolism; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BP16V UT WOS:000084261200017 ER PT S AU Yanovski, SZ AF Yanovski, SZ BE GuyGrand, B TI Diagnosis and prevalence of eating disorders in obesity SO PROGRESS IN OBESITY RESEARCH: 8 SE PROGRESS IN OBESITY RESEARCH LA English DT Proceedings Paper CT 8th International Congress on Obesity CY AUG 29-SEP 03, 1998 CL PARIS, FRANCE SP Int Assoc Study Obesity ID BULIMIA-NERVOSA; SELF-REPORT; GENERAL PSYCHOPATHOLOGY; CLINICAL INTERVIEW; COMMUNITY SAMPLE; SURGERY PATIENTS; BINGE; WOMEN; QUESTIONNAIRE; POPULATION AB Binge eating disorders (BED) among obese individuals are best conceptualized as diagnoses "in evolution." The optimal criteria that win provide a clinically significant differentiation between those whose binge eating is severe enough to be diagnosed with an eating disorder from those who do not requires additional studies. Many individuals who do not meet criteria for BED fail to do so because their frequency of binge eating does meet the admittedly arbitrary cutoff of two days weekly, although some studies find little difference between those with subthreshold BED and those with more meet full criteria.(9.43) The type and frequency of inappropriate compensatory behaviors separating BED from non-purging bulimia nervosa (NBN), and better definition of the type and amount of food constituting a binge episode are also important areas for additional research. The recognition that eating disorders present fairly frequently in obese individuals seeking treatment provides the practitioner with the opportunity to better identify the heterogeneous factors that may impact on the development and maintenance of obesity. Such recognition may lead to more targeted and effective treatments for obese individuals. C1 NIDDK, Bethesda, MD 20892 USA. RP Yanovski, SZ (reprint author), NIDDK, Bldg 45,Room 6AN-18, Bethesda, MD 20892 USA. NR 55 TC 4 Z9 5 U1 4 U2 5 PU JOHN LIBBEY & CO PI LONDON PA 13 SMITHS YARD, SUMMERLEY ST, LONDON SW18 4HR, ENGLAND SN 0962-7936 BN 0-86196-581-7 J9 PROG OBES R PY 1999 BP 229 EP 236 PG 8 WC Anatomy & Morphology; Endocrinology & Metabolism; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Anatomy & Morphology; Endocrinology & Metabolism; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BP16V UT WOS:000084261200029 ER PT J AU Gao, AC Lou, W Ichikawa, T Denmeade, SR Barrett, JC Isaacs, JT AF Gao, AC Lou, W Ichikawa, T Denmeade, SR Barrett, JC Isaacs, JT TI Suppression of the tumorigenicity of prostatic cancer cells by gene(s) located on human chromosome 19p13.1-13.2 SO PROSTATE LA English DT Article DE chromosome 19; prostate; tumor suppression ID METASTATIC ABILITY; MAMMARY-CANCER; RAS ONCOGENE; EXPRESSION; ADENOCARCINOMA; ESTABLISHMENT; LOCALIZATION; INSTABILITY; ACQUISITION; CLONING AB BACKGROUND. In previous reports, we used microcell fusion-mediated chromosomal transfer to introduce normal human chromosomes into highly metastatic rat prostatic cancer cells to map the location of tumor and metastasis suppressor genes. The gene for prostate-specific antigen as well as several classes of genes, including cell adhesion molecules, previously demonstrated to be altered during prostate cancer progression, were mapped to human chromosome 19. METHODS. A normal human chromosome 19 was introduced into Dunning-R3327 AT6.1 rat and TSU-prl human prostatic cancer cells by microcell-mediated chromosome transfer to test the suppressive effects of this chromosome on prostate cancer. Five independent hybrid clones from Dunning-R3327 AT6.1 rat prostatic cancer cells and four independent hybrid clones from TSU-prl human prostatic cancer cells were isolated, karyotyped, allelotyped, and analyzed for in in vitro and in vivo growth characteristics. RESULTS. Introduction of human chromosome 19 into both the rat and human prostatic cancer cells resulted in alteration of cell morphology in vitro and suppression of tumorigenicity in vivo in athymic nude mice. Highly polymorphic SSR2 markers mapped to human chromosome 19 were used to determine the portions of human chromosome 19 retained in the hybrids. These analyses identified a region localized on human chromosome 19p13.1-13.2 that is responsible fur the tumor suppression of both rat and human prostatic cancer cells. The expression of several genes previously mapped to this human chromosome 19p13.1-13.2 region (i.e., ICAM-1, Notch3, and Stau) were analyzed to evaluate if they could be candidate suppresser genes for prostate cancer cell growth in vivo, but no expression patterns consistent with those predicted for a suppressor gene were observed. CONCLUSIONS. Human chromosome 19p13.1-13.2 contains potential tumor suppressor gene(s) for prostate cancer. (C) 1999 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, James Buchanan Brady Urol Inst,Dept Urol, Baltimore, MD USA. Chiba Univ, Sch Med, Dept Urol, Chiba 260, Japan. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Isaacs, JT (reprint author), Johns Hopkins Oncol Ctr, 422 N Bond St, Baltimore, MD 21231 USA. FU NCI NIH HHS [CA 58236] NR 33 TC 33 Z9 35 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 0270-4137 J9 PROSTATE JI Prostate PD JAN 1 PY 1999 VL 38 IS 1 BP 46 EP 54 DI 10.1002/(SICI)1097-0045(19990101)38:1<46::AID-PROS6>3.0.CO;2-9 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 147FA UT WOS:000077476900006 PM 9973109 ER PT J AU Kelloff, GJ Lieberman, R Brawer, MK Crawford, ED Labrie, F Miller, GJ AF Kelloff, GJ Lieberman, R Brawer, MK Crawford, ED Labrie, F Miller, GJ TI Strategies for chemoprevention of prostate cancer SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE chemoprevention; HGPIN; clinical study design ID VITAMIN-D-RECEPTOR; INTRAEPITHELIAL NEOPLASIA; CLINICAL-TRIALS; CARCINOMA; EXPRESSION; PREVENTION; GROWTH; CELLS; 1-ALPHA,25-DIHYDROXYVITAMIN-D-3; INHIBITOR AB Because prostate cancer has a long latency and high incidence, it is a good target for chemoprevention by agents such as retinoids, antiandrogens, antiestrogens, and vitamin D analogs. Phase II chemoprevention trials are frequently conducted on cohorts of patients with previous cancers or premalignant lesions who are scheduled for prostate cancer surgery; such trials are currently in progress with several agents. Prostatic intraepithelial neoplasia (PIN) can be used as a surrogate endpoint biomarker for prostate cancer incidence. Studies of men with high-grade PIN (HGPIN) are particularly useful in that they require a much smaller cohort of 200-400 patients instead of the 18 000 patients required for typical Phase III trials. Even with a smaller sample size, statistically significant evidence of cancer prevention is achieved due to the high probability of HGPIN progressing to cancer (35-55%). A Bayesian sequential monitoring system allows interim analysis of biomarker modulation as early as the completion of 30 patients. Putting all these strategies together will help inhibit, delay, or modulate the natural history of prostate carcinogenesis. C1 NCI, Div Canc Prenent, Chemoprevent Branch, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Laval, Med Ctr, Quebec City, PQ, Canada. RP Kelloff, GJ (reprint author), NCI, Div Canc Prenent, Chemoprevent Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 43 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD JAN PY 1999 VL 2 SU 1 BP 27 EP 33 DI 10.1038/sj.pcan.4500274 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 165FL UT WOS:000078509900007 ER PT J AU Saif, MW Figg, WD Hewitt, S Brosky, K Reed, E Dahut, W AF Saif, MW Figg, WD Hewitt, S Brosky, K Reed, E Dahut, W TI Malignant ascites as only manifestation of metastatic prostate cancer SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE cancer; hormone refractory; androgen independent; urology; PSA; prostatic ID ADENOCARCINOMA AB Prostate cancer is the most common malignancy in men in the US. Both at diagnosis and throughout the disease progression it can metastasize to multiple organs (bone and lymph being the most common). Effusions (either pleural or abdominal) are relatively uncommon, but usually occur as a result of soft tissue lesions. Herein we report on a patient with androgen independent prostate cancer and an elevated PSA with disease confined to ascites of the abdomen. C1 NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Pathol Lab, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Branch, Div Clin Sci, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016; OI Hewitt, Stephen/0000-0001-8283-1788 NR 13 TC 4 Z9 4 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PY 1999 VL 2 IS 5-6 BP 290 EP 293 DI 10.1038/sj.pcan.4500385 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 309LE UT WOS:000086768700013 ER PT J AU Miyazawa, S Jernigan, RL AF Miyazawa, S Jernigan, RL TI Self-consistent estimation of inter-residue protein contact energies based on an equilibrium mixture approximation of residues SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE empirical potential; quasi-chemical approximation; statistical potential; knowledge-based potential; protein fold recognition ID QUASI-CHEMICAL APPROXIMATION; GLOBULAR-PROTEINS; LATTICE MODEL; 3-DIMENSIONAL STRUCTURE; STRUCTURE PREDICTION; BOLTZMANN-LIKE; AMINO-ACIDS; MEAN FORCE; POTENTIALS; SEQUENCE AB Pairwise contact energies for 20 types of residues are estimated self-consistently from the actual observed frequencies of contacts with regression coefficients that are obtained by comparing "input" and predicted values with the Bathe approximation for the equilibrium mixtures of residues interacting. This is premised on the fact that correlations between the "input" and the predicted values are sufficiently high although the regression coefficients themselves can depend to some extent on protein structures as well as interaction strengths. Residue coordination numbers are optimized to obtain the best correlation between "input" and predicted values for the partition energies. The contact energies self-consistently estimated this way indicate that the partition energies predicted with the Bethe approximation should be reduced by a factor of about 0.3 and the intrinsic pairwise energies by a factor of about 0.6. The observed distribution of contacts can be approximated with a small relative error of only about 0.08 as an equilibrium mixture of residues, if many proteins were employed to collect more than 20,000 contacts. Including repulsive packing interactions and secondary structure interactions further reduces the relative errors. These new contact energies are demonstrated by threading to have improved their ability to discriminate native structures from other non-native folds. (C) 1999 Wiley-Liss, Inc. C1 NCI, Lab Expt & Computat Biol, DBS, NIH, Bethesda, MD 20892 USA. Gunma Univ, Fac Technol, Gunma, Japan. RP Jernigan, RL (reprint author), NCI, Lab Expt & Computat Biol, DBS, NIH, Room B-116,Bldg 12B,MSC 5677, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 45 TC 111 Z9 113 U1 0 U2 9 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 PD JAN 1 PY 1999 VL 34 IS 1 BP 49 EP 68 PG 20 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 151FZ UT WOS:000077711200005 PM 10336383 ER PT J AU Panchenko, A Marchler-Bauer, A Bryant, SH AF Panchenko, A Marchler-Bauer, A Bryant, SH TI Threading with explicit models for evolutionary conservation of structure and sequence SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article; Proceedings Paper CT 3rd Meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP3) CY DEC, 1998 CL PACIFIC GROVE, CALIFORNIA DE protein threading; structure prediction; protein evolution ID PROTEIN; ALIGNMENTS; DATABASE; PRODUCT; FOLD AB We have attempted to predict the three-dimensional structures of 19 proteins for the GASPS experiment, each showing less than 25% sequence identity with known structures. Predictions were based on a threading method that aligns the target sequence with the conserved cores of structural templates, as identified from structure-structure alignments of the template with homologous neighbors. Alternative alignments were scored using contact potentials and a position-specific score matrix derived from sequence neighbors of the template. We find that this method identified the correct structural family for 11 of the 19 targets and predicted the remaining 8 targets to be similar to "none" of the templates, avoiding false positives. Threading alignments are relatively accurate for 10 of the 11 targets, including alignments for 6 of 7 identified at CASP3 as fold-recognition targets. These predictions were ranked "first place" by the GASPS assessor when compared to fold-recognition predictions made by other methods. It appears that threading with family-specific models for structure and sequence conservation has improved threading prediction accuracy. Published 1990 Wiley-Liss, Inc.dagger. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 27 TC 13 Z9 13 U1 1 U2 1 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 1999 SU 3 BP 133 EP 140 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 240AU UT WOS:000082804100018 ER PT J AU Marchler-Bauer, A Bryant, SH AF Marchler-Bauer, A Bryant, SH TI A measure of progress in fold recognition? SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article; Proceedings Paper CT 3rd Meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP3) CY DEC, 1998 CL PACIFIC GROVE, CALIFORNIA DE protein structure; threading; structure prediction; fold recognition; structure comparison ID PROTEIN AB We present a retrospective analysis of CASP3 threading predictions, applying evaluation and assessment criteria used at CASP3. Our purpose is twofold, First, we wish to ask whether measures of model accuracy are comparable between CASP3 and CASP2, even though they have been calculated differently. me find that these quantities are effectively the same, and that either may be used to compare model accuracy. Secondly, we wish to assess progress in fold recognition by comparing the numbers of CASP2 and CASP3 models that cross specific accuracy thresholds. We find that the number of accurate models at CASP3 drops sharply as the targets become more difficult, with less extensive similarity to known structures, exactly the pattern seen at CASP2. CASP3 teams do not seem to have predicted accurate models for targets of greater difficulty, and for a given difficulty range the best CASP3 models seem no more accurate than the best models at CASP2, At CASP3, however, we find greater numbers of accurate models for medium-difficulty targets, with extensive similarity to a known structure but no shared sequence motifs. Threading methods would appear to have become more reliable for modeling based on remote evolutionary relationships. Published 1999 Wiley-Liss, Inc.dagger. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 19 TC 9 Z9 9 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 1999 SU 3 BP 218 EP 225 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 240AU UT WOS:000082804100028 ER PT J AU Ostrowski, LE Andrews, KL Potdar, PD Nettesheim, P AF Ostrowski, LE Andrews, KL Potdar, PD Nettesheim, P TI Ciliated-cell differentiation and gene expression SO PROTOPLASMA LA English DT Article; Proceedings Paper CT 3rd International Malpighi Symposium CY APR 15-17, 1998 CL MONTEREY, CALIFORNIA DE cilia; dynein; epithelium; trachea; differentiation; cloning ID DYNEIN HEAVY-CHAIN AB Ciliated cells play an integral role in the defense mechanisms of the respiratory system. By the coordinated beating of their cilia they provide the force necessary to clear potentially harmful material from the airways. We have been investigating the regulation of ciliated-cell differentiation and gene expression. Using a culture system that allows us to positively or negatively regulate the development of the ciliated-cell phenotype, we have previously reported that the expression of axonemal dynein heavy chain mRNAs are regulated in parallel with the development of ciliated cells. To identify other genes important to the development or function of ciliated cells, differential display was used to compare mRNA isolated from cultures of ciliated or nonciliated rat tracheal epithelial cells. Two novel genes, KPL1 and KPL2, have been identified whose expression is increased in parallel with ciliated-cell differentiation. Two transcripts of KPL1 are expressed in a tissue-specific pattern; KPL1 is particularly highly expressed in brain. The sequence of KPL1 predicts a 188 or 223 amino acid protein which contains a pleckstrin homology domain. Pleckstrin homology domains have been shown to bind inositolphosphates and G-proteins and function as signal-dependent membrane adapters. KPL1 therefore may function in a signal transduction pathway important to the development or maintenance of the ciliated-cell phenotype. KPL2 shows more limited distribution and is predominantly expressed in tissues which contain axonemes. KPL2 is predicted to encode a 1744 amino acid protein which contains many functional motifs, including nuclear localization signals, an ATP-binding domain, a proline-rich region, and a calponin homology domain. KPL2 may thus be involved in transmitting signals to the nucleus during ciliated-cell differentiation. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Ostrowski, LE (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, 6019 Thurston Bowles Bldg, Chapel Hill, NC 27599 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0033-183X J9 PROTOPLASMA JI Protoplasma PY 1999 VL 206 IS 4 BP 245 EP 248 DI 10.1007/BF01288212 PG 4 WC Plant Sciences; Cell Biology SC Plant Sciences; Cell Biology GA 199RG UT WOS:000080495000008 ER PT J AU Ivkovich, D Collins, KL Eckerman, CO Krasnegor, NA Stanton, ME AF Ivkovich, D Collins, KL Eckerman, CO Krasnegor, NA Stanton, ME TI Classical delay eyeblink conditioning in 4- and 5-month-old human infants SO PSYCHOLOGICAL SCIENCE LA English DT Article; Proceedings Paper CT Symposium on Human Classical Eyeblink Conditioning, at the 1998 Meeting of the American-Psychological-Society CY MAY, 1998 CL WASHINGTON, D.C. SP Amer Psychol Soc ID INTERSTIMULUS-INTERVAL; RAT; ONTOGENY AB Simple delay classical eyeblink conditioning, using a tone conditioned stimulus (CS) and airpuff unconditioned stimulus (US), was studied in cross-sectional samples of 4- and 5-month-old healthy, full-term infants. Infants received two identical training sessions, 1 week apart. Ar both ages, infants experiencing paired tones and air-puffs demonstrated successful conditioning over two sessions, relative to control subjects who had unpaired training. Conditioning was not evident, however, during the first session. Two additional groups of 5-month-olds received varied experiences during Session 1, either unpaired presentations of the CS and US or no stimulus exposure, followed by paired conditioning during Session 2. Results from these groups suggest that the higher level of conditioning observed following two sessions of paired conditioning was not the result of familiarity with the testing environment or the stimuli involved but, rather; the result of retention of associative learning not expressed during the first conditioning session. C1 Duke Univ, Dept Expt Psychol, Durham, NC 27708 USA. US EPA, Washington, DC 20460 USA. NICHHD, Bethesda, MD 20892 USA. RP Ivkovich, D (reprint author), Duke Univ, Dept Expt Psychol, Durham, NC 27708 USA. NR 21 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD JAN PY 1999 VL 10 IS 1 BP 4 EP 8 DI 10.1111/1467-9280.00097 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 167GT UT WOS:000078624700002 ER PT J AU Munzar, P Baumann, MH Shoaib, M Goldberg, SR AF Munzar, P Baumann, MH Shoaib, M Goldberg, SR TI Effects of dopamine and serotonin-releasing agents on methamphetamine discrimination and self-administration in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE methamphetamine; dopamine; serotonin; phentermine; fenfluramine; drug-discrimination; self-administration; rat ID L-DEPRENYL SELEGILINE; D-AMPHETAMINE; STIMULUS PROPERTIES; NUCLEUS-ACCUMBENS; CONDITIONED REWARD; RHESUS-MONKEYS; D-FENFLURAMINE; COCAINE; DEXFENFLURAMINE; PHENTERMINE AB To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter TV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenflur amine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration. C1 NIDA, Preclin Pharmacol Lab, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. NIDA, Clin Psychopharmacol Sect, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. Masaryk Univ, Fac Med, Dept Pharmacol, CS-66243 Brno, Czech Republic. Inst Psychiat, Sect Behav Pharmacol, London SE5 8AF, England. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Lab, Addict Res Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 60 TC 59 Z9 59 U1 3 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 1999 VL 141 IS 3 BP 287 EP 296 DI 10.1007/s002130050836 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 161CW UT WOS:000078271700008 PM 10027510 ER PT J AU Stolerman, IP Naylor, C Elmer, GI Goldberg, SR AF Stolerman, IP Naylor, C Elmer, GI Goldberg, SR TI Discrimination and self administration of nicotine by inbred strains of mice SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; mecamylamine; drug discrimination; self-administration; mice; strain differences ID STIMULUS PROPERTIES; CHRONIC TOLERANCE; RATS; REINFORCEMENT; ETHANOL; ALCOHOL; MECAMYLAMINE; AMPHETAMINE; ANTAGONISTS; RESPONSES AB These studies aim to characterize the discriminative stimulus effects of nicotine in two inbred strains of mice that differ in many pharmacological responses, and to investigate the feasibility of IV self-administration studies with nicotine in one of the strains. For discrimination studies, three groups of C57BL/6 and one group of DBA/2 mice were trained in a two-lever operant conditioning paradigm with a tandem VI-30 " FR-10 schedule of food reinforcement. After 40 training sessions, accuracy reached 57.5, 77.5 and 90.0% in C57BL/6 mice trained with (-)-nicotine (SC) in doses of 0.4, 0.8 and 1.6 mg/kg, respectively (n = 8). DBA/2 mice trained with 0.8 mg/kg nicotine attained similar (73.3%) accuracy (n = 9). Results from extinction tests showed that all groups of mice yielded orderly dose-response curves for nicotine (0.03-1.6 mg/kg), but stimulus control remained notably weaker for the mice trained with 0.4 mg/kg nicotine than for any other group. Overall rates of responding in the undrugged state were lower for DBA/2 than for C57BL/6 mice; DBA/2 mice were also slightly less sensitive than C57BL/6 mice to the response rate-reducing effect of nicotine. The nicotine antagonist mecamylamine (1.5 mg/kg SC) blocked the discriminative stimulus effect of the training dose of nicotine in all groups. The results of the IV self-administration study suggest that nicotine (0.1 mg/kg) can serve as a positive reinforcer in drug-naive C57BL/6J mice (n = 13). Behaviour maintained by 0.1 mg/kg nicotine injections was significantly greater than behaviour maintained by vehicle injections, and it was maintained under an intermittent schedule of reinforcement (FR4). The methods described provide possible approaches for genetic analyses of strain differences in sensitivity to the discriminative and reinforcing stimulus properties of nicotine. C1 Inst Psychiat, Sect Behav Pharmacol, London SE5 8AF, England. NIDA, Preclin Pharmacol Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Stolerman, IP (reprint author), Inst Psychiat, Sect Behav Pharmacol, De Crespigny Pk, London SE5 8AF, England. OI Stolerman, Ian/0000-0002-2703-5137 NR 48 TC 69 Z9 69 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 1999 VL 141 IS 3 BP 297 EP 306 DI 10.1007/s002130050837 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 161CW UT WOS:000078271700009 PM 10027511 ER PT J AU Anderson, NB Scott, PA AF Anderson, NB Scott, PA TI Making the case for psychophysiology during the era of molecular biology SO PSYCHOPHYSIOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 18, 1997 CL CAPE COD, MASSACHUSETTS SP Soc Psychophysiol Res DE molecular biology; psychophysiology; social research; behavioral research; levels of analysis; interdisciplinary ID CANCER SUSCEPTIBILITY GENE; CREUTZFELDT-JAKOB DISEASE; ELEVATED BLOOD-PRESSURE; CARDIOVASCULAR REACTIVITY; ESSENTIAL-HYPERTENSION; PARKINSONS-DISEASE; RACIAL-DIFFERENCES; HIV-1 INFECTION; CANDIDATE GENE; HUMAN HOMOLOG AB The Office of Behavioral and Social Sciences Research (OBSSR) at the National Institutes of Health opened in 1995 to facilitate the advancement of research on social and behavioral influences on health. The establishment of the OBSSR coincided with the ascendancy of molecular biology, with its emphasis on more reductionistic influences on health. This greater emphasis on genetic aspects of health has the potential to produce a widening chasm between biomedical research and social, behavioral, and psychological research. We discuss the chasm between sociobehavioral and biomedical research during what might be considered the era of molecular biology and propose the concept of levels of analysis as a unifying framework for research in the health sciences, using research on hypertension in African Americans as a representative example. We also argue for the primacy of psychophysiological research in bridging the chasm and furthering a multilevel perspective and summarize some of the activities of the OBSSR that are relevant to this perspective. C1 NIH, OBSSR, Bethesda, MD 20892 USA. RP Anderson, NB (reprint author), NIH, OBSSR, Bldg 1,Room 326,1 Ctr Dr, Bethesda, MD 20892 USA. NR 99 TC 24 Z9 24 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 1999 VL 36 IS 1 BP 1 EP 13 DI 10.1017/S0048577299972001 PG 13 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 158BJ UT WOS:000078095900001 PM 10098375 ER PT J AU Stassen, HH Coppola, R Gottesman, II Torrey, EF Kuny, S Rickler, KC Hell, D AF Stassen, HH Coppola, R Gottesman, II Torrey, EF Kuny, S Rickler, KC Hell, D TI EEG differences in monozygotic twins discordant and concordant for schizophrenia SO PSYCHOPHYSIOLOGY LA English DT Article DE EEG; schizophrenia; concordance; discrimination ID QUANTITATIVE EEG; RESTING EEG; NEGATIVE SCHIZOPHRENIA; FIRST-EPISODE; PATTERNS; ABNORMALITIES; SIMILARITY; PSYCHOSIS; RELATIVES; VARIABLES AB In an electroencephalographic (EEG) study of 27 pairs of monozygotic (MZ) twins discordant for schizophrenia, 13 pairs of MZ twins concordant for schizophrenia, 40 pairs of healthy MZ twins, and 91 healthy, unrelated subjects with repeated assessments, we investigated (a) the trait quality of brainwave patterns with respect to interindividual differences, intraindividual stability over time, and within-pair MZ concordance; (b) the EEG characteristics that enable discrimination between affected and unaffected individuals; and (c) the EEG characteristics that reflect the severity of illness. In comparison with healthy control subjects, the MZ twins who were discordant and concordant for schizophrenia exhibited a much lower within-pair EEG concordance, so that EEG abnormalities associated with schizophrenia and manifested differently in the co-twins concordant for schizophrenia seemed to reflect nongenetic, pathological developments of genetically identical brains. C1 Psychiat Univ Hosp, Dept Res, CH-8029 Zurich, Switzerland. NIMH, Neuropsychiat Res Hosp, Washington, DC 20032 USA. Univ Virginia, Dept Psychol, Charlottesville, VA USA. RP Stassen, HH (reprint author), Psychiat Univ Hosp, Dept Res, POB 68, CH-8029 Zurich, Switzerland. RI G, I/D-8042-2011 FU NIMH NIH HHS [MH 41176] NR 63 TC 24 Z9 24 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 1999 VL 36 IS 1 BP 109 EP 117 DI 10.1017/S0048577299970713 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 158BJ UT WOS:000078095900012 PM 10098386 ER PT J AU Kruk, PA Bohr, VA AF Kruk, PA Bohr, VA TI Telomeric length in individuals and cell lines with altered p53 status SO RADIATION ONCOLOGY INVESTIGATIONS LA English DT Article DE telomere; telomerase; p53; cancer-prone syndrome ID LI-FRAUMENI SYNDROME; ATAXIA-TELANGIECTASIA GENE; CANCER-PRONE FAMILY; SACCHAROMYCES-CEREVISIAE; DNA-DAMAGE; IMMORTAL CELLS; FANCONI-ANEMIA; YEAST TELOMERE; RNA COMPONENT; PROTEIN AB Telomeres play an important role in maintaining chromosomal stability and are often shortened in transformed cells, p53 is the most commonly mutated gene in cancers and its status is thought to reflect the level of genomic stability. We measured telomeric length by Southern blot analysis in cells from cancer-prone syndromes and in selected cancer cells with altered p53 status. Mean telomeric lengths in the cancer-prone syndromes Li-Fraumeni syndrome, Fanconi's anemia, and Ataxia telangiectasia, were shorter in the affected individuals than in their unaffected parents, We also found that altered p53 expression in selected cancer cell model systems may be associated with shortened telomeric length, but did not appear to be associated with significant alterations in telomerase activity, (C) 1999 Wiley-Liss, Inc. C1 Univ S Florida, Dept Pathol, Tampa, FL 33612 USA. NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Kruk, PA (reprint author), Univ S Florida, Dept Pathol, 12901 Bruce B Downs Blvd,MDC 11, Tampa, FL 33612 USA. RI Kruk, Patricia/I-6489-2012 NR 45 TC 12 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-7541 J9 RADIAT ONCOL INVESTI JI Radiat. Oncol. Investig. PY 1999 VL 7 IS 1 BP 13 EP 21 DI 10.1002/(SICI)1520-6823(1999)7:1<13::AID-ROI2>3.0.CO;2-7 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 231VN UT WOS:000082332300002 PM 10030619 ER PT J AU Vodovotz, Y Coffin, D DeLuca, AM McKinney, L Cook, JA Wink, D Mitchell, JB AF Vodovotz, Y Coffin, D DeLuca, AM McKinney, L Cook, JA Wink, D Mitchell, JB TI Induction of nitric oxide production in infiltrating leukocytes following in vivo irradiation of tumor-bearing mice SO RADIATION ONCOLOGY INVESTIGATIONS LA English DT Article DE radiation; nitric oxide; tumor; macrophage; mouse ID GROWTH-FACTOR-BETA; MACROPHAGE TUMORICIDAL ACTIVITY; FACTOR GENE-EXPRESSION; IONIZING-RADIATION; SYNTHASE ACTIVITY; L-ARGININE; IFN-GAMMA; IN-VIVO; TRANSFORMING GROWTH-FACTOR-BETA-1; ACTIVATED MACROPHAGES AB Nitric oxide (NO) has been implicated both in regression and progression of tumors due to its production by both tumor cells and infiltrating leukocytes. Ionizing radiation causes the regression of tumors, and can augment the production of NO by macrophages in vitro. We examined the cellular and systemic production of NO in mice in which radiation-resistant RIF-1 fibrosarcoma cells were implanted subcutaneously and were then either irradiated or sham-treated at the tumor site. Ten days following implantation of the tumors, CD45- tumor cells and CD45+ leukocytes were derived from resected tumors immediately after irradiation with 60 Gy, a dose previously reported to reduce tumor growth. Leukocytes from tumors of irradiated hosts produced spontaneously up to four-fold more NO than did either leukocytes from unirradiated mice or CD45- tumor cells from either unirradiated or irradiated mice. Between days 10-14 following tumor implantation, serum NO2-/NO3- increased in both irradiated and unirradiated mice to an equal extent, culminating in levels higher than those of non-tumor-bearing mice. Though NO production is elevated in macrophages treated with 1-10 Gy of radiation in vitro, higher doses may be required by tumor-infiltrating macrophages in vivo and thus may indicate that tumor-infiltrating macrophages are deactivated. Published 1999 Wiley-Liss, Inc.(dagger). C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Armed Forces Radiat Res Inst, Bethesda, MD USA. RP Vodovotz, Y (reprint author), Cardiovasc Res Fdn, 110 Irving St NW,Suite 4B-1, Washington, DC 20010 USA. NR 70 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-7541 J9 RADIAT ONCOL INVESTI JI Radiat. Oncol. Investig. PY 1999 VL 7 IS 2 BP 86 EP 97 DI 10.1002/(SICI)1520-6823(1999)7:2<86::AID-ROI4>3.0.CO;2-L PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 231VP UT WOS:000082332400004 PM 10333249 ER PT J AU Inskip, PD Hatch, EE Stewart, PA Heineman, EF Ziegler, RG Dosemeci, M Parry, D Rothman, N Boice, JD Wilcosky, TC Watson, DJ Shapiro, WR Selker, RG Fine, HA Black, PM Loeffler, JS Linet, MS AF Inskip, PD Hatch, EE Stewart, PA Heineman, EF Ziegler, RG Dosemeci, M Parry, D Rothman, N Boice, JD Wilcosky, TC Watson, DJ Shapiro, WR Selker, RG Fine, HA Black, PM Loeffler, JS Linet, MS TI Study design for a case-control investigation of cellular telephones and other risk factors for brain tumours in adults SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID OCCUPATIONAL CASE-CONTROL; N-NITROSO COMPOUNDS; CANCER MORTALITY; UNITED-STATES; TUMORS; EXPOSURE; CHILDREN; MALIGNANCIES; HISTORIES; TRENDS AB The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case-control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of rumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age greater than or equal to 18 y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the cases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene-environment interactions. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Res Triangle Inst, Epidemiol & Med Studies Program, Res Triangle Pk, NC 27709 USA. St Josephs Hosp & Med Ctr, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Boice, JD (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 38 TC 22 Z9 22 U1 3 U2 8 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD, KENT, ENGLAND TN23 1YW SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 1999 VL 86 IS 1 BP 45 EP 52 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 239ZY UT WOS:000082801900006 ER PT J AU Baris, D Linet, M Auvinen, A Kaune, WT Wacholder, S Kleinerman, R Hatch, E Robison, L Niwa, S Haines, C Tarone, RE AF Baris, D Linet, M Auvinen, A Kaune, WT Wacholder, S Kleinerman, R Hatch, E Robison, L Niwa, S Haines, C Tarone, RE TI Temporal and other exposure aspects of residential magnetic fields measurement in relation to acute lymphoblastic leukaemia in children: The National Cancer Institute Children's Cancer Group study SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT International Workshop on Exposure Metrics and Dosimetry for EMF Epidemiology of the National Radiation Protection Board CY SEP 07-09, 1998 CL CHILTON, ENGLAND SP Natl Radiat Protect Board, WHO, Int Commiss Nonionising Radiat Protect, Mobile Mfg Forum, GSM MoU Assoc, Natl Grid Co PLC ID CHILDHOOD; LEUKEMIA AB Case-control studies have used a variety of measurements to evaluate the relationship of children's exposure to magnetic fields (50 or 60 Hz) with childhood leukaemia and other childhood cancers. In the absence of knowledge about which exposure metrics may be biologically meaningful, studies during the past 10 years have often used time-weighted average (TWA) summaries of home measurements. Recently, other exposure metrics have been suggested, usually based on theoretical considerations or limited laboratory data. In this paper, the rationale anti associated preliminary studies undertaken are described as well as feasibility and validity issues governing the choice of the primary magnetic field exposure assessment methods and summary metric used to estimate children's exposure in the National Cancer Institute/Children's Cancer Group (NCI/CCG) case-control study. Also provided are definitions and discussion of the strengths and weaknesses of the various exposure metrics used in exploratory analyses of the NCI/CCG measurement data. Exposure metrics evaluated include measures of central tendency (mean, median, 30th to 70th percentiles), peak exposures (90th and higher percentiles, peak values of the 24h measurements), and measurements of short-term temporal variability (rate of change). This report describes correlations of the various metrics with the time-weighted average for the 24 h period (TWA-24-h). Most of the metrics were found to be positively and highly correlated with TWA-24-h, but lower correlations of TWA-24-h with peak exposure and with rate of change were observed. To examine further the relation between TWA and alternative metrics, similar exploratory analysis should be considered for existing data sets and for forthcoming measurement investigations of residential magnetic fields and childhood leukaemia. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Radiat & Nucl Safety Author, Helsinki, Finland. EM Factors, Richland, WA USA. Univ Minnesota, Div Pediat Epidemiol & Clin Res, Minneapolis, MN USA. Childrens Canc Grp, Arcadia, CA USA. Westat Inc, Rockville, MD USA. RP Baris, D (reprint author), NCI, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN Room 415, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478; Auvinen, Anssi/0000-0003-1125-4818 NR 14 TC 3 Z9 3 U1 0 U2 0 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD, KENT, ENGLAND TN23 1YW SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 1999 VL 83 IS 1-2 BP 53 EP 60 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 193VN UT WOS:000080157900010 ER PT J AU Mahaffey, JA Alavanja, MCR Parkhurst, MA Berger, E Brownson, RC AF Mahaffey, JA Alavanja, MCR Parkhurst, MA Berger, E Brownson, RC TI Estimation of radon exposure history for analysis of a residential epidemiological study SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID LUNG-CANCER; NONSMOKING WOMEN; INDOOR RADON; PAST EXPOSURE; RISK; MISSOURI; CR-39; GLASS AB Traditional methods for assessing radon exposure in epidemiological studies have used current ambient detector measurements as surrogates for concentrations decades ago in past residences occupied by study subjects. Substantial temporal and spatial variability has been found which challenges the validity of this practice. As an alternative, CR-39 surface monitors were attached to selected glass objects to measure alpha emissions from radon progeny and infer past exposures of subjects. The validity of the use of surface monitors to detect alpha emissions in glass was successfully demonstrated by comparing results of these monitors with pulse ionisation chamber measurements. Subsequently, surface monitor and ambient detector results were compared, and factors such as household smoking and use of windows for measurement were examined. Individually, both the surface monitor and the ambient detector methodologies each gave highly repeatable results (Pearson product-moment correlations of 0.81 and 0.97, respectively), but the consistency between the two technologies was only satisfactory (correlation of 0.53). C1 Pacific NW Lab, Richland, WA 99352 USA. NCI, Bethesda, MD 20814 USA. Informat Management Serv Inc, Silver Spring, MD 20904 USA. St Louis Univ, Sch Publ Hlth, St Louis, MO 63108 USA. RP Mahaffey, JA (reprint author), Pacific NW Lab, POB 999, Richland, WA 99352 USA. NR 18 TC 11 Z9 11 U1 0 U2 1 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD, KENT, ENGLAND TN23 1YW SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 1999 VL 83 IS 3 BP 239 EP 247 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 225KP UT WOS:000081959300006 ER PT B AU Ron, E AF Ron, E GP NCRP NCRP TI Radiation effects on the thyroid: Emphasis on iodine-131 SO RADIATION PROTECTION IN MEDICINE: CONTEMPORARY ISSUES SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 35th Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurement CY APR 07-08, 1999 CL ARLINGTON, VA SP Natl Council Radiat Protect ID CHERNOBYL ACCIDENT; HODGKINS-DISEASE; CANCER MORTALITY; CHILDHOOD; I-131; HYPERTHYROIDISM; NEOPLASMS; CHILDREN; COHORT; RISK C1 NCI, Bethesda, MD 20892 USA. RP Ron, E (reprint author), NCI, Bethesda, MD 20892 USA. NR 56 TC 1 Z9 1 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 USA BN 0-929600-62-2 J9 P NAT C RAD PY 1999 IS 21 BP 201 EP 226 PG 26 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BT45S UT WOS:000173048200011 ER PT J AU Kleinerman, RA AF Kleinerman, RA TI Cancer after radiotherapy for hereditary retinoblastoma: Genetic susceptibility and radiation exposure SO RADIATION RESEARCH LA English DT Meeting Abstract ID RISK C1 NCI, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 1999 VL 151 IS 1 BP 99 EP 100 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 154VQ UT WOS:000077910400019 ER PT J AU Sandler, DP AF Sandler, DP TI Indoor radon and lung cancer risk: A case-control study in Connecticut and Utah SO RADIATION RESEARCH LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 4 TC 9 Z9 9 U1 0 U2 2 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 1999 VL 151 IS 1 BP 103 EP 104 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 154VQ UT WOS:000077910400022 ER PT J AU Alavanja, MCR AF Alavanja, MCR TI Cumulative residential radon exposure and risk of lung cancer in Missouri: A population-based case-control study SO RADIATION RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 1999 VL 151 IS 1 BP 104 EP 104 PG 1 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 154VQ UT WOS:000077910400023 ER PT J AU Lubin, J AF Lubin, J TI Discussion: Indoor radon and risk of lung cancer SO RADIATION RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 5 TC 19 Z9 23 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 1999 VL 151 IS 1 BP 105 EP 107 PG 3 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 154VQ UT WOS:000077910400025 ER PT J AU Bouville, A Ron, E AF Bouville, A Ron, E TI Iodine-131 exposure from atmospheric testing - The problem and its significance SO RADIATION RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 1999 VL 151 IS 1 BP 116 EP 117 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 154VQ UT WOS:000077910400035 ER PT J AU Smirniotopoulos, JG Lonergan, GJ Abbott, RM Choyke, PL Czum, JM Dalrymple, NC DoDai, D Feigin, DS Ho, VB Leyendecker, JR Rovira, MJ AF Smirniotopoulos, JG Lonergan, GJ Abbott, RM Choyke, PL Czum, JM Dalrymple, NC DoDai, D Feigin, DS Ho, VB Leyendecker, JR Rovira, MJ TI Image interpretation session: 1998 SO RADIOGRAPHICS LA English DT Editorial Material DE arteriovenous malformations, pulmonary; emphysema, pulmonary; histiocytosis; melanoma; neurofibromatosis; sarcoidosis; sclerosis, tuberous; temporal bone, neoplasms; thymus, cysts; von Hippel-Landau disease ID LANGERHANS CELL HISTIOCYTOSIS; VONHIPPEL-LINDAU DISEASE; SWYER-JAMES SYNDROME; RADIOLOGIC-PATHOLOGICAL CORRELATION; THYROGLOSSAL DUCT CARCINOMA; ENDOLYMPHATIC SAC TUMORS; T1-WEIGHTED MR-IMAGES; TUBEROUS SCLEROSIS; CT FINDINGS; GASTROINTESTINAL SARCOIDOSIS C1 Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. Armed Forces Inst Pathol, Dept Radiol, Washington, DC 20306 USA. Wilford Hall USAF Med Ctr, Dept Radiol, San Antonio, TX 78236 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. Henry M Jackson Fdn Advancement Mil Med, Dept Radiol, Bethesda, MD USA. Tripler Army Med Ctr, Dept Radiol, Honolulu, HI 96859 USA. Madigan Army Med Ctr, Tacoma, WA 98431 USA. RP Smirniotopoulos, JG (reprint author), Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. RI Smirniotopoulos, James/D-3726-2011 NR 77 TC 5 Z9 5 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JAN-FEB PY 1999 VL 19 IS 1 BP 205 EP 233 PG 29 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 158GB UT WOS:000078106700017 PM 10939917 ER PT J AU Baratti, C Barnett, AS Pierpaoli, C AF Baratti, C Barnett, AS Pierpaoli, C TI Comparative MR imaging study of brain maturation in kittens with T1, T2, and the trace of the diffusion tensor SO RADIOLOGY LA English DT Article DE animals; brain, growth and development; brain, MR; magnetic resonance (MR), relaxometry ID WATER DIFFUSION; WHITE-MATTER; WEIGHTED MR; RELAXATION-TIME; RESTRICTED DIFFUSION; CEREBRAL-ISCHEMIA; ACUTE STROKE; RAT; PARAMETERS; COEFFICIENT AB PURPOSE: To assess the time-course of the relaxation times and the orientationally averaged water diffusion coefficient D-oav in postnatal brain development. MATERIALS AND METHODS: Multisection maps of T1, T2, and the trace of the diffusion tensor (Trace[D] = 3 x D-oav) were obtained in four kittens at eight time points. RESULTS: In the adult, D-oav was about 700 mu m(2)/sec in both white and gray matter. In the newborn, D-oav was 1,100-1,350 mu m(2)/sec in white matter and 1,000 mu m(2)/sec in gray matter. For ail anatomic regions and time points, the correlation between D-oav and 1/T2 was high (R-2 = 0.87, P << .001). T1 showed a lower correlation with D-oav and a higher sensitivity to myelinization than did T2. CONCLUSION: Although D-oav shows dramatic changes in the maturing brain, the high correlation between D-oav and T2 indicates that tittle additional information can be obtained by measuring this diffusion parameter during normal brain development. This contrasts with previous findings in brain ischemia, where D-oav and T2 appear to be uncorrelated. After including the authors' data and published iontophoretic measurements in a simple model of diffusion in tissues, the authors suggest that the underlying mechanisms of D-oav reduction in brain maturation and ischemia are different. D-oav changes during development are mainly affected by events occurring in the cellular compartment, while changes in extracellular volume fraction and tortuosity, which are thought to determine the reduction in D-oav during ischemia, are probably of secondary importance. C1 NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. RP Pierpaoli, C (reprint author), NINDS, Neuroimaging Branch, NIH, Bldg 10,Rm 4N252,10 Ctr Dr, Bethesda, MD 20892 USA. RI Pierpaoli, Carlo/E-1672-2011 NR 52 TC 104 Z9 108 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1999 VL 210 IS 1 BP 133 EP 142 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 150YC UT WOS:000077692800026 PM 9885598 ER PT J AU Frank, JA Ostuni, JL Yang, YH Shiferaw, Y Patel, A Qin, JN Mattay, VS Lewis, BK Levin, RL Duyn, JH AF Frank, JA Ostuni, JL Yang, YH Shiferaw, Y Patel, A Qin, JN Mattay, VS Lewis, BK Levin, RL Duyn, JH TI Technical solution for an interactive functional MR imaging examination: Application to a physiologic interview and the study of cerebral physiology SO RADIOLOGY LA English DT Article DE brain, blood flow; brain, MR; brain neoplasms, MR; magnetic resonance (MR), technology ID HIGH-RESOLUTION MEASUREMENT; FREQUENCY-SHIFTED BURST; TRACER BOLUS PASSAGES; MAGNETIC-RESONANCE; BLOOD-FLOW; ECHO-PLANAR; HUMAN BRAIN; 1.5 T; VOLUME; INVERSION AB Studies with functional magnetic resonance (MR) imaging produce large unprocessed raw data sets in minutes. The analysis usually requires transferring of the data to an off-line workstation, and this process frequently occurs after the subject has left the MR unit. The authors describe a hardware configuration and processing software that captures whole-brain raw data files as they are being produced from the MR unit. It then performs the reconstruction, registration, and statistical analysis, and displays the results in seconds after completion of the MR image acquisition. C1 NIMH, Ctr Clin, Lab Diagnost Radiol Res, Clin Brain Disorders Branch,NIH, Bethesda, MD 20892 USA. NINDS, In Vivo NMR Res Ctr, Bethesda, MD 20892 USA. RP Frank, JA (reprint author), NIMH, Ctr Clin, Lab Diagnost Radiol Res, Clin Brain Disorders Branch,NIH, Bldg 10,Rm B1N256,10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010; Patel, Anand/B-1441-2009 OI Patel, Anand/0000-0002-6570-8582 NR 44 TC 14 Z9 16 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1999 VL 210 IS 1 BP 260 EP 268 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 150YC UT WOS:000077692800047 PM 9885618 ER PT J AU Herring, CJ Qin, J AF Herring, CJ Qin, J TI An on-line preconcentrator and the evaluation of electrospray interfaces for the capillary electrophoresis mass spectrometry of peptides SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID EXTRACTION; IDENTIFICATION AB A unique preconcentrator was constructed for on-line preconcentration using capillary electrophoresis generating concentration detection limits for peptides in the mid-picomolar range. Several common sheathless electrospray configurations were constructed in conjunction with the preconcentrator and were compared. It was found that a palladium wire interface was the most reliable interface and the problems encountered using this interface are discussed. A tryptic digest of the myosin I heavy chain kinase that contains two phosphopeptides was separated by capillary electrophoresis using this interface and the on-line preconcentrator, Copyright (C) 1999 John Wiley & Sons, Ltd. C1 NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Qin, J (reprint author), Baylor Coll Med, Dept Biochem & Cell Biol, Smith Res Bldg,Room S328,1 Baylor Plaza, Houston, TX 77030 USA. NR 23 TC 43 Z9 43 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1999 VL 13 IS 1 BP 1 EP 7 DI 10.1002/(SICI)1097-0231(19990115)13:1<1::AID-RCM435>3.0.CO;2-A PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 156EF UT WOS:000077987900001 PM 9921685 ER PT J AU Garraffo, HM Spande, TF Jones, TH Daly, JW AF Garraffo, HM Spande, TF Jones, TH Daly, JW TI Ammonia chemical ionization tandem mass spectrometry in structure determination of alkaloids. I. Pyrrolidines, piperidines, decahydroquinolines, pyrrolizidines, indolizidines, quinolizidines and an azabicyclo[5.3.0]decane SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article AB CI-MS/MS of alkaloids with ammonia reagent gas and collision-induced dissociation provides unique structural information for certain mono- and bi-cyclic alkaloids, This technique was applied to solve the structures of 195C, a 4,6-disubstituted quinolizidine alkaloid found in frog skin and an ant, and 275A, a novel 3,5-disubstituted azabicyclo[5.3.0]decane found in frog skin. Copyright (C) 1999 John Whey & Sons, Ltd. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 12 TC 16 Z9 16 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1999 VL 13 IS 15 BP 1553 EP 1563 DI 10.1002/(SICI)1097-0231(19990815)13:15<1553::AID-RCM658>3.3.CO;2-L PG 11 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 222NE UT WOS:000081791000001 PM 10421897 ER PT B AU Luke, BT AF Luke, BT BE Truhlar, DG Howe, WJ Hopfinger, AJ Blaney, J Dammkoehler, RA TI Applications of distributed computing to conformational searches SO RATIONAL DRUG DESIGN SE IMA VOLUMES IN MATHEMATICS AND ITS APPLICATIONS LA English DT Proceedings Paper CT Workshop on Mathematical and Computational Issues in Drug Design CY APR 07-11, 1997 CL MINNEAPOLIS, MN SP Natl Sci Fdn, Minnesota Supercomput Inst, USA, Res Off, Univ Minnesota, Inst Math & Its Applicat, Univ Minnesota, Inst Supercomp ID ANGIOTENSIN-CONVERTING ENZYME; HYDROGEN-BOND INTERACTIONS; MULTIPLE-MINIMA PROBLEM; OCCURRING AMINO-ACIDS; NONBONDED INTERACTIONS; MOLECULAR-DYNAMICS; ENERGY PARAMETERS; INHIBITORS; PARALLELIZATION; POLYPEPTIDES AB Distributed Computing, as opposed to Parallel Computing, separates the overall goal of the calculation into isolated tasks and performs some or all of the tasks concurrently on different computers. This is very different from the data-parallel computing that is currently performed on shared-memory, or single-image, multiple-processor architectures, and provides an opportunity to try new techniques for problems important to Molecular Modeling and Drug Discovery. In this paper, two applications of distributed computing to conformational searches of molecules are described. The first application finds all low-energy, stable conformations of molecules that show varying degrees of activity as inhibitors of the angiotensin-converting enzyme (ACE). The goal is to find a 3-dimensional arrangement of certain atoms in one or more low-energy conformations of all active inhibitors that are absent from all low-energy conformations of molecules that are inactive. If such an arrangement is found, this putative pharmacophore can be used to test other compounds of unknown activity. The second application of distributed computing is to find the lowest-energy conformation (e.g. the global minimum) for a series of enkephalins; Met-enkephalin, Leu-enkephalin, and (D)Ala(2)-(D)Leu(5)-enkephalin (DADLE). The conformational searches are performed using three different genetic methods; the first is a "standard" Genetic Algorithm (GA) that only marginally qualifies as a distributed program as it is applied here, the second uses Evolutionary Programming (EP) and produces more of a distributed program, and the third uses a Parallel Genetic Algorithm (PGA) which is almost purely a distributed computing procedure. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Luke, BT (reprint author), NCI, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. RI Truhlar, Donald/G-7076-2015 OI Truhlar, Donald/0000-0002-7742-7294 NR 35 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-98753-3 J9 IMA V MATH PY 1999 VL 108 BP 191 EP 206 PG 16 WC Mathematics, Applied; Pharmacology & Pharmacy SC Mathematics; Pharmacology & Pharmacy GA BP72G UT WOS:000085971100014 ER PT S AU Marx, SJ Agarwal, SK Kester, MB Heppner, C Kim, YS Skarulis, MC James, LA Goldsmith, PK Saggar, SK Park, SY Spiegel, AM Burns, AL Debelenko, LV Zhuang, Z Lubensky, IA Liotta, LA Emmert-buck, MR Guru, SC Manickam, P Crabtree, J Erdos, MR Collins, FS Chandrasekharappa, SC AF Marx, SJ Agarwal, SK Kester, MB Heppner, C Kim, YS Skarulis, MC James, LA Goldsmith, PK Saggar, SK Park, SY Spiegel, AM Burns, AL Debelenko, LV Zhuang, Z Lubensky, IA Liotta, LA Emmert-buck, MR Guru, SC Manickam, P Crabtree, J Erdos, MR Collins, FS Chandrasekharappa, SC BE Conn, PM TI Multiple endocrine neoplasia type 1: Clinical and genetic features of the hereditary endocrine neoplasias SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 54: PROCEEDINGS OF THE 1998 CONFERENCE SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Article; Proceedings Paper CT 54th Meeting of Recent Progress in Hormone Research CY 1998 CL STEVENSON, WASHINGTON SP Endocrine Soc ID ZOLLINGER-ELLISON-SYNDROME; TUMOR-SUPPRESSOR GENE; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; COMPARATIVE GENOMIC HYBRIDIZATION; CA2+-SENSING RECEPTOR GENE; SPORADIC PITUITARY-TUMORS; HUMAN PARATHYROID TUMORS; PLASMA CHROMOGRANIN-A AB MEN I is a syndrome of parathyroid adenomas, gastrinomas, prolactinomas, and other endocrine tumors. Collagenomas and facial angiofibromas are newly recognized but common skin expressions, Many tumors in MEN1 are benign: however, many entero-pancreatic neuroendocrine tumors and foregut carcinoid tumors are malignant. MEN1 is thus the expression of a cancer gene but without available prevention or cure for malignancy. Hereditary (as compared to sporadic) endocrine tumors show early onset age and multiplicity, because each cell of the body has "one hit" by inheritance. Multiple neoplasia syndromes with endocrine tumor(s) all include nonendocrine components; their known defective genes seem mainly to disturb cell accumulation. Hereditary neoplasia/hyperplasia of one endocrine tissue reflects a defect that is tissue selective and directed at cell secretion. Though the hereditary endocrine neoplasias are rare, most of their identified genes also contribute to common sporadic endocrine neoplasms. Hereditary tumors may be caused by activation of an oncogene (e.g., RET) or, more often, by inactivation of a tumor suppressor gene (e.g., P53. MEN1). Recently, MEN1 was identified by positional cloning. This strategy included narrowing the gene candidate interval, identifying many or all genes in that interval, and testing the newly identified candidate genes for mutation in MEN1 cases. MEN1 was identified because it showed mutation in 14 of 15 MEN1 cases. NIH testing showed germline MEN1 mutations in 47 of 50 MENI index cases and in seven of eight cases with sporadic MEN1. Despite proven capacity to find germline MENI mutation, NIH testing found no MEN1 mutation among five families with isolated hyperparathyroidism, suggesting that this often arises from mutation of other gene(s). Analogous studies in Japan found that familial isolated pituitary rumors also did not show MENI germline mutation. MENI mutation testing can now be considered for cases of MEN1 and its phenocopies and for asymptomatic members of families with known MENI mutation. Germline MEN1 testing does not have the urgency of RET testing in MEN2a and 2b, as MENI testing does nor commonly lead to an important intervention. Somatic MEN1 mutation was found in sporadic tumors: parathyroid adenoma (21%), gastrinoma (33%), insulinoma (17%), and bronchial carcinoid (36%). For each of these, MEN1 was the known gene most frequently mutated. MEN1 has a widely expressed mRNA that encodes a protein (menin) of 610 amino acids. The protein sequence is not informative about domains or functions. The protein was mainly nuclear. Menin binds to JunD, an AP-1 transcription factor, inhibiting JunD's activation of transcription. Most of the germline and somatic MEN1 mutations predict truncation of menin, a likely destructive change. Inactivating MEN1 mutations in germline and in sporadic neoplasms support prior predictions that MEN1 is a tumor suppressor gene. Germline MEN1 mutation underlies all or most cases of MEN1 (familial or sporadic). Somatic MEN1 mutation is the most common gene mutation in many sporadic endocrine tumor types. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIDDKD, Metab Dis Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 225 TC 112 Z9 114 U1 0 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4410 USA SN 0079-9963 BN 0-879225-33-6 J9 RECENT PROG HORM RES PY 1999 VL 54 BP 397 EP 439 PG 43 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA BR61K UT WOS:000166956400016 PM 10548885 ER PT J AU Gladen, BC Tabacova, S Baird, DD Little, RE Balabaeva, L AF Gladen, BC Tabacova, S Baird, DD Little, RE Balabaeva, L TI Variability of lipid hydroperoxides in pregnant and nonpregnant women SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE lipid peroxides; oxidative stress; pregnancy; seasons ID PEROXIDATION PRODUCTS; VITAMIN-E; PLASMA; ANTIOXIDANTS; LIPOPEROXIDE; GLUTATHIONE AB Lipid peroxidation is thought to be important in numerous disease states, including pregnancy complications. Study of its role requires markers, but the variability of available markers in non-diseased populations has not been well-characterized. We examined the variability over time of blood lipid hydroperoxides, as measured by iodometric analysis, in 49 healthy young women, 21 nonpregnant and 28 pregnant. Lipid hydroperoxides from the same woman were very similar from one day to the next but were less stable over periods of a month or more, The correlation between measurements on consecutive days was 0.98; the correlation between measurements a month or more apart was 0.11.Variability over time was not attributable to seasonal effects or, among the pregnant women, to differences over the course of pregnancy, Knowledge of the variability of this and other markers of oxidative damage enables the development of appropriate study designs. (C) 1999 Elsevier Science Inc. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Natl Ctr Hyg Ecol & Nutr, Sofia, Bulgaria. RP Gladen, BC (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 NR 18 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 1999 VL 13 IS 1 BP 41 EP 44 DI 10.1016/S0890-6238(98)00054-9 PG 4 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 169UG UT WOS:000078766700004 PM 10080298 ER PT J AU Lee, SH Shiao, YH Kasprzak, KS AF Lee, SH Shiao, YH Kasprzak, KS TI Nonradioactive mRNA differential display in polyacrylamide mini-gels SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID MESSENGER-RNA AB Nonradioactive methods in comparison to those using radionuclides are now becoming popular because of safety, environmental, and cost concerns. The modified technique described here is much faster, easier, and safer than the conventional procedure utilizing radioactive material and large-formatted polyacrylamide gel, or other nonradioactive DD techniques. Also, it maintains good reproducibility and specificity. This DD protocol offers a rapid and reliable nonradioactive method for comparing gene expression patterns in various research. C1 Soonchunhyang Univ, Coll Med, Dept Biochem, Cheon An 330090, South Korea. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. RP Lee, SH (reprint author), Soonchunhyang Univ, Coll Med, Dept Biochem, Cheon An 330090, South Korea. NR 8 TC 2 Z9 2 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 USA SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PY 1999 VL 106 IS 1-2 BP 108 EP 114 PG 7 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA 377YF UT WOS:000165553300010 PM 11127802 ER PT J AU Seo, YR Lee, SH Han, SS Ryu, JC AF Seo, YR Lee, SH Han, SS Ryu, JC TI Effect of p53 tumor suppressor on nucleotide excision repair in human colon carcinoma cells treated with 4-nitroquinoline 1-oxide SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID WILD-TYPE P53; DNA-DAMAGE; UV; RESISTANCE; PROTEIN; GADD45 AB In probing the mechanism of nucleotide excision repair (NER) in response to 4-nitroquinoline 1-oxide (4NQO)-induced DNA damage, the effect of p53 tumor suppressor was investigated. The effect of p53 protein on the repair of damaged DNA was examined by comet assay. Expression of p53 and p21(Waf1/Cip1) proteins was measured by the Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry, respectively. Compared to RKO cells having the wild-type p53 gene, increased cytotoxicity by 4NQO was observed in RKOmp53 cells with a mutation in p53 protein. DNA single strand breaks (SSB), indicative of the DNA repair, were considerably increased in 4NQO-treated RKO cells. Also, the expression of p53 and p21 proteins was significantly increased in 4NQO-treated RKO cells. In RKOmp53 cells, no effect of 4NQO on p21 expression was observed. Our findings suggest that 4NQO-induced NER is p53-dependent and involves up-regulation of its downstream regulator, p21(Waf1/Cip1) proteins. C1 Korea Inst Sci & Technol, Toxicol Lab, Seoul 130650, South Korea. Korea Univ, Grad Sch Biotechnol, Cell Biol Lab, Seoul 136701, South Korea. NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Ryu, JC (reprint author), Korea Inst Sci & Technol, Toxicol Lab, Seoul 130650, South Korea. NR 17 TC 8 Z9 9 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 USA SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PY 1999 VL 104 IS 2 BP 157 EP + PG 9 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA 270MK UT WOS:000084539400004 PM 10634308 ER PT J AU Whitcup, SM Park, WS Gasch, AT Eagle, RC Filie, AC Nussenblatt, RB Zhuang, ZP Chan, CC AF Whitcup, SM Park, WS Gasch, AT Eagle, RC Filie, AC Nussenblatt, RB Zhuang, ZP Chan, CC TI Use of microdissection and molecular genetics in the pathologic diagnosis of retinoblastoma SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE diffuse retinoblastoma; loss of heterozygosity; microdissection; retinoblastoma; retinoblastoma gene ID POLYMERASE-CHAIN-REACTION; SIMULATING RETINOBLASTOMA; INTRAOCULAR LYMPHOMA; SUSCEPTIBILITY GENE; HETEROZYGOSITY; MUTATIONS; SEQUENCE; CANCER; LOCUS; RISK AB Background/Purpose: Retinoblastoma results from mutations or loss of both alleles of the retinoblastoma gene. Although retinoblastoma is usually recognized clinically, some forms of the disease can elude diagnosis. The purpose of this study was to determine whether the use of molecular genetics to detect a loss of heterozygosity (LOH) in the retinoblastoma gene could assist the ocular pathologist in the diagnosis of this malignancy. Methods: Deoxyribonucleic acid (DNA) was obtained from tumor cells microdissected from three ocular specimens from two patients with diffuse retinoblastoma. Polymerase chain reaction was used to detect two microsatellite markers (D13S153 and D13S118) of the retinoblastoma gene. Loss of heterozygosity was identified when one of the two polymorphic alleles was present in the DNA from normal tissue but absent or reduced in the DNA obtained from tumor cells. Results: Loss of heterozygosity was identified in all three specimens from the two patients with diffuse retinoblastoma. In one patient, the diagnosis of retinoblastoma was based on identification of LOH from tumor cells obtained from vitrectomy. Conclusions: This study demonstrates that identification of LOH in retinoblastoma cells not only can contribute to our understanding of the molecular genetics of this tumor, but also can help the ocular pathologist in the diagnosis of atypical forms of the disease. C1 NCI, NIH, Bethesda, MD 20892 USA. Wills Eye Hosp, Philadelphia, PA USA. RP Whitcup, SM (reprint author), NEI, 10 Ctr Dr,Bldg 10 Room 10N 202, Bethesda, MD 20892 USA. NR 34 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1999 VL 19 IS 4 BP 318 EP 324 DI 10.1097/00006982-199907000-00009 PG 7 WC Ophthalmology SC Ophthalmology GA 403KX UT WOS:000167042000010 PM 10458298 ER PT J AU Weisz, JM Humayun, MS De Juan, E Del Cerro, M Sunness, JS Dagnelie, G Soylu, M Rizzo, L Nussenblatt, RB AF Weisz, JM Humayun, MS De Juan, E Del Cerro, M Sunness, JS Dagnelie, G Soylu, M Rizzo, L Nussenblatt, RB TI Allogenic fetal retinal pigment epithelial cell, transplant in a patient with geographic atrophy SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE allogenic; macular degeneration; fetal; geographic atrophy; retinal pigment epithelium; transplant ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; MACULAR DEGENERATION; SUBRETINAL SPACE; IN-VITRO; CHORIOCAPILLARIS; DEBRIDEMENT; RESPONSES AB Purpose: To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). Methods: A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. Results: The patient's Vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the revel of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. Conclusion: Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis, A very weak immune response against proteins associated with photoreceptors is also of concern. C1 Johns Hopkins Med Inst, Wilmer Ophthalmol Inst, Dept Ophthalmol, Baltimore, MD 21205 USA. Univ Rochester, Sch Med, Dept Ophthalmol, Rochester, NY USA. NEI, NIH, Bethesda, MD 20892 USA. RP De Juan, E (reprint author), Johns Hopkins Hosp, Wilmer Ophthalmol Inst, Room 719,600 N Wolfe St, Baltimore, MD 21287 USA. RI Rizzo, Luiz Vicente/B-4458-2009 FU NEI NIH HHS [R01 EY08552] NR 23 TC 55 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1999 VL 19 IS 6 BP 540 EP 545 DI 10.1097/00006982-199911000-00011 PG 6 WC Ophthalmology SC Ophthalmology GA 403KZ UT WOS:000167042200011 PM 10606456 ER PT B AU Redmond, TM AF Redmond, TM BE Hollyfield, JG Anderson, RE LaVail, MM TI The RPE65-deficient mouse as a model for RPE65-associated Leber's congenital amaurosis and related disorders SO RETINAL DEGENERATIVE DISEASES AND EXPERIMENTAL THERAPY LA English DT Proceedings Paper CT 8th International Symposium on Retinal Degeneration CY JUL 20-25, 1998 CL SCHLUCHSEE, GERMANY SP Fdn Fighting Blindness, Retinal Preservat Fdn, Deutsch Forsch Gemeinschaft, Pro Retina, CIBA Vis ID RETINAL-PIGMENT EPITHELIUM; RECESSIVE RETINITIS-PIGMENTOSA; RPE65 MESSENGER-RNA; BINDING-PROTEIN; MEMBRANE-RECEPTOR; GENE-TRANSFER; VISUAL CYCLE; MONOCLONAL-ANTIBODIES; MICROSOMAL PROTEIN; VITAMIN-A AB The retinal pigment epithelium (RPE)-specific protein RPE65 has been speculated to play a role in the vitamin A metabolism of the outer retina. Recently, mutations in the human RPE65 gene have been associated with Leber's congenital amaurosis, a disorder characterized by blindness at birth, and autosomal recessive childhood-onset severe retinal dystrophies. We have developed an RPE65-deficient mouse and have described its phenotype. The RPE65-deficient mouse phenotype parallels that of the human disorders. This phenotype can be explained by a disruption of the RPE visual cycle causing a lack of Il-cis-retinal chromophore. Consequently, it is feasible to use this mouse as a model to test possible therapies for the human diseases. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Redmond, TM (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 44 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46193-5 PY 1999 BP 35 EP 42 DI 10.1007/978-0-585-33172-0_4 PG 8 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BQ63L UT WOS:000089018400004 ER PT B AU Becerra, SP Alberdi, E Martinez, A Montuenga, LM Cayouette, M Gravel, C AF Becerra, SP Alberdi, E Martinez, A Montuenga, LM Cayouette, M Gravel, C BE Hollyfield, JG Anderson, RE LaVail, MM TI Pigment epithelium-derived factor (PEDF) in the retina - Protective effect against photoreceptor cell degeneration SO RETINAL DEGENERATIVE DISEASES AND EXPERIMENTAL THERAPY LA English DT Proceedings Paper CT 8th International Symposium on Retinal Degeneration CY JUL 20-25, 1998 CL SCHLUCHSEE, GERMANY SP Fdn Fighting Blindness, Retinal Preservat Fdn, Deutsch Forsch Gemeinschaft, Pro Retina, CIBA Vis ID CEREBELLAR GRANULE CELLS; PROTEASE INHIBITORY ACTIVITY; NEURITE-PROMOTING FACTOR; NEUROTROPHIC ACTIVITY; INTERPHOTORECEPTOR MATRIX; NONINHIBITORY SERPIN; BOVINE EYES; EXPRESSION; IDENTIFICATION; PROTEOGLYCANS C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46193-5 PY 1999 BP 519 EP 526 DI 10.1007/978-0-585-33172-0_49 PG 8 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BQ63L UT WOS:000089018400049 ER PT J AU Dillner, J Andersson-Ellstrom, A Hagmar, B Schiller, J AF Dillner, J Andersson-Ellstrom, A Hagmar, B Schiller, J TI Against: High risk genital papillomavirus infections are not spread vertically SO REVIEWS IN MEDICAL VIROLOGY LA English DT Editorial Material ID VIRUS-LIKE PARTICLES; CERVICAL INTRAEPITHELIAL NEOPLASIA; IMMUNOGLOBULIN-G ANTIBODIES; HPV DNA; SERUM ANTIBODIES; ESOPHAGEAL CANCER; TYPE-16 INFECTION; SEXUAL-BEHAVIOR; WOMEN; CAPSIDS AB The Medline-indexed literature on risk factors for HPV infection and HPV transmission is critically reviewed. Principles for assay validation and interpretation, reliability of different study designs and principles for interpretation of conflicting reports are discussed. The conclusions arrived at can be summarised as: (1) There is overwhelming epidemiological evidence that the only quantitatively important mode of transmission of infection with oncogenic genital HPV types is sexual. (2) There is also evidence that benign genital HPV types can be transmitted sexually, but the epidemiological data on the benign virus types are less extensive and less clear. (3) Perinatal HPV transmission is unequivocally demonstrated only for the rare disease juvenile respiratory papillomatosis. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Karolinska Inst, Ctr Microbiol & Tumor Biol, Dept Virol, S-17177 Stockholm, Sweden. Natl Publ Hlth Inst, Dept Infect Dis Epidemiol, Helsinki, Finland. Ctr Publ Hlth Res, Karlstad, Sweden. Natl Hosp Norway, Dept Cytol, Oslo, Norway. NCI, Bethesda, MD 20892 USA. RP Dillner, J (reprint author), Karolinska Inst, Ctr Microbiol & Tumor Biol, Dept Virol, Box 280, S-17177 Stockholm, Sweden. NR 63 TC 28 Z9 30 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD JAN-MAR PY 1999 VL 9 IS 1 BP 23 EP 29 DI 10.1002/(SICI)1099-1654(199901/03)9:1<23::AID-RMV233>3.0.CO;2-S PG 7 WC Virology SC Virology GA 174ZP UT WOS:000079066700005 PM 10371669 ER PT J AU Horowits, R AF Horowits, R TI The physiological role of titin in striated muscle SO REVIEWS OF PHYSIOLOGY BIOCHEMISTRY AND PHARMACOLOGY, VOL 138 SE REVIEWS OF PHYSIOLOGY BIOCHEMISTRY AND PHARMACOLOGY LA English DT Review ID FROG SKELETAL-MUSCLE; Z-LINE REGION; SINGLE CARDIAC MYOFIBRILS; STRETCHED SKINNED FIBERS; THICK FILAMENT MOVEMENT; ELASTIC PROPERTIES; IMMUNOELECTRON MICROSCOPY; CONNECTIN FILAMENTS; MONOCLONAL-ANTIBODIES; RESTING TENSION C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Horowits, R (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. NR 108 TC 43 Z9 44 U1 2 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0303-4240 J9 REV PHYSIOL BIOCH P PY 1999 VL 138 BP 57 EP 96 DI 10.1007/BF02346660 PG 40 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Physiology GA BP97L UT WOS:000086798800004 PM 10396138 ER PT J AU Eddy, EM AF Eddy, EM TI Role of heat shock protein HSP70-2 in spermatogenesis SO REVIEWS OF REPRODUCTION LA English DT Article ID DEVELOPMENTALLY-REGULATED EXPRESSION; GERM-CELL APOPTOSIS; GENE FAMILY; MOLECULAR CHAPERONES; RAT TESTIS; SYNAPTONEMAL COMPLEX; IMMOBILIZING PROTEIN; HSP70-RELATED GENE; CDC2 PROTEIN; MOUSE AB The HSP70 heat-shock proteins are molecular chaperones that assist other proteins in their folding, transport and assembly into complexes. Most of these proteins are either constitutively expressed or their expression is induced by heat shock and other stresses. However, two members of the Hsp70 family (HSP70-2 and HSC70T in mice) are regulated developmentally and expressed specifically in spermatogenic cells. The HSP70-2 protein is synthesized during the meiotic phase of spermatogenesis and is abundant in pachytene spermatocytes. The knockout approach was used to determine whether HSP70-2 is a chaperone for proteins involved in meiosis. Male mice lacking HSP70-2 were infertile while females lacking HSP70-2 were fertile. Spermatogenic cell development was arrested in prophase of meiosis I at the G2-M-phase transition and late pachytene spermatocytes were eliminated by apoptosis, resulting in an absence of spermatids. HSP70-2 is required for Cdc2 to form a heterodimer with cyclin B1, suggesting that it is a chaperone necessary for the progression of meiosis in the germ cells of male mice. HSP70-2 is also associated with the synaptonemal complex and desynapsis is disrupted in male mice lacking this protein. Homologues of HSP70-2 are present in the testes of many animals, suggesting that the role of this spermatogenic cell chaperone is conserved across phyla. C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 62 TC 128 Z9 140 U1 1 U2 6 PU JOURNALS OF REPRODUCTION FERTILITY LTD PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE CB5 8DT, ENGLAND SN 1359-6004 J9 REV REPROD JI Rev. Reprod. PD JAN PY 1999 VL 4 IS 1 BP 23 EP 30 DI 10.1530/ror.0.0040023 PG 8 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 179VA UT WOS:000079349100004 PM 10051099 ER PT J AU Baird, DD AF Baird, DD TI Characteristics of fertile menstrual cycles SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article; Proceedings Paper CT International Symposium on Environment, Life-Style and Fertility CY DEC 07-10, 1997 CL AARHUS, DENMARK DE conception; estrogen; fecundability; hormones; luteinizing hormone; progesterone ID CONCEPTION; PREGNANCY; WOMEN C1 NIEHS, Epidemiol Branch A3 05, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch A3 05, POB 12233, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 NR 7 TC 3 Z9 3 U1 0 U2 0 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 1999 VL 25 SU 1 BP 20 EP 22 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 184GK UT WOS:000079602600007 PM 10235401 ER PT J AU Levine, RJ AF Levine, RJ TI Seasonal variation of semen quality and fertility SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article; Proceedings Paper CT International Symposium on Environment, Life-Style and Fertility CY DEC 07-10, 1997 CL AARHUS, DENMARK DE biological clock; births; human; photoperiod; light; season; sperm count ID CIRCANNUAL RHYTHM; SUMMER; DETERIORATION; PATTERNS; WORKERS AB At many locations in the northern hemisphere human sperm counts are reduced during the summer. Experiments with rhesus monkeys suggest that such seasonal variation may be induced by an endogenous biological clock reset annually by changes in the length of daylight. Little is known about seasonal variation in human female reproductive function, although fecundity may be lower during the summer, as it is for men. Variation in fecundity could help explain seasonal patterns of birth in countries such as the United States, where there is a deficit of spring births. But the relationship to patterns of birth in Canada and Europe, where the birth rate is highest during late winter and spring, is unclear. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Levine, RJ (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Bldg,Room 7B03, Bethesda, MD 20892 USA. NR 22 TC 26 Z9 28 U1 0 U2 0 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 1999 VL 25 SU 1 BP 34 EP 37 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 184GK UT WOS:000079602600012 PM 10235406 ER PT J AU Newcomer, JW Craft, S Fucetola, R Moldin, SO Selke, G Paras, L Miller, R AF Newcomer, JW Craft, S Fucetola, R Moldin, SO Selke, G Paras, L Miller, R TI Glucose-induced increase in memory performance in patients with schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Review DE cognition; glucose; learning ID LONG-TERM POTENTIATION; POSITRON EMISSION TOMOGRAPHY; MILD SENILE DEMENTIA; CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; CARD SORTING TEST; GROWTH FACTOR-I; ELDERLY HUMANS; ALZHEIMER-TYPE; RAT-BRAIN AB Previous investigations have found that increasing circulating glucose availability can increase memory performance in rodents, healthy humans, and individuals with dementia of the Alzheimer's type. In this study, patients with schizophrenia, healthy control subjects, and controls with bipolar affective disorder were tested using double-blind treatment with either 50 g anhydrous dextrose plus 4 mg sodium saccharin (for "taste") or 23.7 mg saccharin alone, followed by cognitive testing on a complex battery, At this glucose dose, verbal memory performance on a paragraph recall task was increased during the glucose condition relative to the saccharin condition in the patients with schizophrenia; this effect was not detected in either the psychiatric or normal controls. The results provide preliminary support for the hypothesis that memory performance can be improved in patients with schizophrenia by increasing circulating glucose availability and suggest the importance of further evaluation of therapeutic manipulations of glucose availability. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychol, St Louis, MO 63110 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Seattle Amer Lake Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. NIMH, Genet Branch, Rockville, MD 20857 USA. Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. Univ Missouri, Columbia, MO USA. Albany Med Coll, Albany, NY 12208 USA. RP Newcomer, JW (reprint author), Washington Univ, Sch Med, Dept Psychiat, 4940 Childrens Pl, St Louis, MO 63110 USA. FU NCRR NIH HHS [5M01 RR-00036]; NIMH NIH HHS [MH-01510, R01 MH-53363] NR 109 TC 48 Z9 52 U1 2 U2 5 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1999 VL 25 IS 2 BP 321 EP 335 PG 15 WC Psychiatry SC Psychiatry GA 203QQ UT WOS:000080718700011 PM 10416734 ER PT J AU Dawkins, K Lieberman, JA Lebowitz, BD Hsiao, JK AF Dawkins, K Lieberman, JA Lebowitz, BD Hsiao, JK TI Antipsychotics: Past and future - National Institute of Mental Health Division of Services and Intervention Research Workshop, July 14, 1998 SO SCHIZOPHRENIA BULLETIN LA English DT Article DE antipsychotic drugs; atypical antipsychotic drugs; typical antipsychotic drugs; clozapine; risperidone; olanzapine; quetiapine; ziprasidone ID TREATMENT-REFRACTORY SCHIZOPHRENIA; TREATMENT-RESISTANT SCHIZOPHRENIA; CHILDHOOD-ONSET SCHIZOPHRENIA; BLIND OLANZAPINE TRIAL; CLOZAPINE TREATMENT; TARDIVE-DYSKINESIA; RISK-FACTORS; HALOPERIDOL; RISPERIDONE; PLACEBO AB A workshop on "Antipsychotics: Past and Future" was convened by the National Institute of Mental Health (NIMH), Division of Services and Intervention Research (DSIR), on July 14, 1998, to review the results of recent antipsychotic drug research, discuss current standards of treatment, and identify areas needing further study. There has been a proliferation of new antipsychotic medications and a rapid increase in their clinical utilization. The new atypicals are beginning to supplant the older typical neuroleptic antipsychotics, and the scientific and ethical issues raised by this transition prompted the workshop. Given the apparent, albeit not fully defined, advantages of atypical drugs, particularly their safety profiles, the question is whether more comparisons with typical antipsychotics are warranted and whether clinical trial designs warrant (or would be justified in) the inclusion of typical drugs as standard active comparators. Workshop participants-including clinical researchers, patient advocates, bioethicists, and NIMH staff-discussed the conclusions drawn from current data, ethical issues for subjects in clinical trials, funding for ongoing studies using typical agents, and appropriate comparators for trials using atypical agents. C1 Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. NIMH, Adult Geriatr Treatment & Prevent Intervent Res B, Rockville, MD 20857 USA. NIMH, Schizophrenia Bulletin, Rockville, MD 20857 USA. RP Dawkins, K (reprint author), Univ N Carolina, Dept Psychiat, Campus Box 7160, Chapel Hill, NC 27599 USA. NR 60 TC 22 Z9 25 U1 2 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1999 VL 25 IS 2 BP 395 EP 404 PG 10 WC Psychiatry SC Psychiatry GA 203QQ UT WOS:000080718700017 PM 10416740 ER PT J AU Elkashef, AM Wyatt, RJ AF Elkashef, AM Wyatt, RJ TI Tardive dyskinesia: Possible involvement of free radicals and treatment with vitamin E SO SCHIZOPHRENIA BULLETIN LA English DT Article DE tardive dyskinesia; free radicals; neurodegeneration; vitamin E; antioxidants; neuroleptic ID NEUROTOXIC PYRIDINIUM METABOLITE; BASAL GANGLIA; NEUROLEPTIC MEDICATIONS; OXIDATIVE STRESS; CEREBROSPINAL-FLUID; LIPID-PEROXIDATION; ALPHA-TOCOPHEROL; BRAIN IRON; SCHIZOPHRENIA; HALOPERIDOL AB A decade ago a hypothesis introduced to explain tardive dyskinesia (TD) implicated free radicals generated secondary to neuroleptic treatment. Since then many preclinical and clinical studies have investigated this possibility. These studies suggest that free radicals are probably involved in the pathogenesis of TD and that vitamin E could be efficacious in its treatment. C1 NIDA, Medicat Dev Div, Bethesda, MD 20892 USA. NIDA, Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. RP NIDA, Medicat Dev Div, 6001 Execut Blvd,Rm 4123,MSC 9551, Bethesda, MD 20892 USA. EM ae8a@nih.gov NR 69 TC 61 Z9 71 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1999 VL 25 IS 4 BP 731 EP 740 PG 10 WC Psychiatry SC Psychiatry GA 266WV UT WOS:000084324000008 PM 10667743 ER EF