FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Vonakis, BM Chen, HX HaleemSmith, H Metzger, H AF Vonakis, BM Chen, HX HaleemSmith, H Metzger, H TI The unique domain as the site on Lyn kinase for its constitutive association with the high affinity receptor for IgE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; BASOPHILIC LEUKEMIA-CELLS; ACTIVATION MOTIF ITAM; IMMUNOGLOBULIN-E; MAST-CELLS; 2-HYBRID SYSTEM; 2 FORMS; BINDING; HISTAMINE; SUBUNITS AB Aggregation of the high affinity receptor for IgE (Fc epsilon RI) leads to the phosphorylation of tyrosines on the beta and gamma chains of the receptor by the Src family kinase Lyn. We have studied the interaction between Lyn and the Fc epsilon RI in vivo using a transfection-based approach. Fc epsilon RI were stably transfected into Chinese hamster ovary cells. The small amount of endogenous Src family kinase was sufficient to phosphorylate receptor tyrosines upon extensive aggregation of Fc epsilon RI but not after addition of dimers of IgE. Upon stable co-transfection of Lyn kinase into the cells, dimers were now able to stimulate receptor phosphorylation and the response to more extensive aggregation was enhanced. In contrast, co-transfection with catalytically inactive Lyn inhibited the aggregation-induced phosphorylation by the endogenous kinase, and a quantitatively similar inhibition was observed in cells transfected with the SH4-containing unique domain of Lyn. Consistent with the results of others using alternative approaches, our additional studies using a yeast two-hybrid system detected a direct interaction between intact Lyn or its unique domain and the C-terminal cytoplasmic domain of the beta chain but not with the receptor's other cytoplasmic domains. RP Vonakis, BM (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BLDG 10-RM 9N-258,10 CTR DR MSC 1520,BETHESDA,MD 20892, USA. NR 39 TC 97 Z9 100 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 19 PY 1997 VL 272 IS 38 BP 24072 EP 24080 DI 10.1074/jbc.272.38.24072 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX381 UT WOS:A1997XX38100086 PM 9295361 ER PT J AU Moody, TW Leyton, J Coelho, T Jakowlew, S Takahashi, K Jameison, F Koh, M Fridkin, M Gozes, I Knight, M AF Moody, TW Leyton, J Coelho, T Jakowlew, S Takahashi, K Jameison, F Koh, M Fridkin, M Gozes, I Knight, M TI (Stearyl, Norleucine(17))VIP hybrid antagonizes VIP receptors on non-small cell lung cancer cells SO LIFE SCIENCES LA English DT Article DE VIP receptor antagonists; non-small cell lung cancer; cAMP; (S,N) VIPhybrid; cell proliferation ID VASOACTIVE-INTESTINAL-PEPTIDE; FUNCTIONAL EXPRESSION; GROWTH; PACAP; POLYPEPTIDE; SURVIVAL AB The effects of VIP receptor antagonists were investigated using non-small cell lung cancer (NSCLC) cells. By Northern blot and RT-PCR, VIP, receptors were detected on NSCLC cell line NCI-H1299. VIPhybrid,(N-Stearyl-Norleucine(17)) VIPhybrid ((SN)VIPhybrid) and PTC4495 inhibited I-125-VIP binding to NCI-H1299 cells with IC50 values of 500, 30 and 5000 nM respectively. (SN)VIPhybrid (1 mu M) had no effect on basal cAMP but strongly inhibited the increase in cAMP caused by 10 nM VIP. The order of peptide potency to inhibit cAMP was (SN)VIPhybrid > VIPhybrid > PTC4495. (SN)VIPhybrid was more potent than VIPhybrid at inhibiting NCI-H1299 colony formation. Also, (SN)VIPhybrid was more potent than VIPhybrid at inhibiting NCI-H1299 xenograft formation in nude mice. These data suggest that (SN)VIPhybrid antagonizes VIP, receptors on NSCLC cells. C1 PEPTIDE TECHNOL, GAITHERSBURG, MD 20877 USA. UNIV MARYLAND, SCH MED, DEPT OPHTHALMOL, BALTIMORE, MD 21201 USA. WEIZMANN INST SCI, DEPT ORGAN CHEM, IL-76100 REHOVOT, ISRAEL. SACKLER SCH MED, DEPT CLIN BIOCHEM, TEL AVIV, ISRAEL. RP NCI, MED BRANCH, ROCKVILLE, MD 20850 USA. NR 27 TC 32 Z9 32 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 EI 1879-0631 J9 LIFE SCI JI Life Sci. PD SEP 19 PY 1997 VL 61 IS 17 BP 1657 EP 1666 DI 10.1016/S0024-3205(97)00771-6 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XY555 UT WOS:A1997XY55500004 PM 9363981 ER PT J AU Elman, I Breier, A AF Elman, I Breier, A TI Effects of acute metabolic stress on plasma progesterone and testosterone in male subjects: Relationship to pituitary-adrenocortical axis activation SO LIFE SCIENCES LA English DT Article DE progesterone; testosterone; 2-deoxy-D-glucose; HPA axis; stress; glucose deprivation ID CORTICOTROPIN-RELEASING HORMONE; ADIPOSE-TISSUE INVIVO; MALE RHESUS MACAQUES; LUTEINIZING-HORMONE; INDUCED SUPPRESSION; MALE-RATS; SECRETION; CORTISOL; BINDING; MEN AB Stress effects on progesterone and testosterone as well as the relationship of these effects to the hypothalamic-pituitary-adrenal (HPA) axis activation have been extensively investigated in laboratory animals. There is less information about the impact of stress on sex steroids in humans. The purpose of the present study was to examine the influence of acute metabolic stress on arterial levels of progesterone, testosterone, adrenocorticotropic hormone (ACTH), cortisol, gonadotropins and sex hormone binding globulin (SHBG) in healthy male subjects. The stressor used was glucoprivation induced by pharmacological doses of 2-deoxy-D-glucose (2DG) (40mg/kg). This stress resulted in increases in progesterone, decreases in testosterone and no significant change in gonadotropins or SHBG. ACTH and cortisol were robustly elevated and these elevations related significantly to changes in progesterone but not testosterone. The implications of these data for the understanding of the role of sex steroids in the stress response is discussed. RP Elman, I (reprint author), NIMH,ETB,IRP,NIH,BLDG 10,ROOM 4N212,10 CTR DR,BETHESDA,MD 20892, USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 42 TC 29 Z9 29 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD SEP 19 PY 1997 VL 61 IS 17 BP 1705 EP 1712 DI 10.1016/S0024-3205(97)00776-5 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XY555 UT WOS:A1997XY55500009 PM 9363986 ER PT J AU Schaaf, L Leiprecht, A Saji, M Hubner, U Usadel, KH Kohn, LD AF Schaaf, L Leiprecht, A Saji, M Hubner, U Usadel, KH Kohn, LD TI Glycosylation variants of human TSH selectively activate signal transduction pathways SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE glycosylation variants (hTSH); signal transduction; CHO-cells; Cos-7-cells ID FOLLICLE-STIMULATING-HORMONE; ASPARAGINE-LINKED OLIGOSACCHARIDES; LECTIN AFFINITY-CHROMATOGRAPHY; 3RD CYTOPLASMIC LOOP; HAMSTER OVARY CELLS; HUMAN THYROTROPIN; CYCLIC-AMP; BIOLOGICAL-ACTIVITY; RECEPTOR; BIOACTIVITY AB The oligosaccharide chains of pituitary glycoprotein hormones such as human thyroid-stimulating hormone (hTSH) have been shown to be important in biosynthesis, subunit association, secretion and bioactivity. However, the exact biological significance of these glycosylation variants (isoforms) remains controversial, The aim of this paper is to investigate the role of hTSH glycosylation variants in signal transduction. Human pituitary standard TSH (2nd International Reference Preparation 80/558; IRP-hTSH) was treated with neuraminidase, fractionated by isoelectric focusing (IEF) and affinity chromatography using the lectins concanavalin A (Con A) and lentil. To determine the in vitro bioactivity of these hTSH isoforms, simultaneous measurement of cAMP formation and inositol phosphates release was applied in two different cell systems (CHO cells stably and Cos-7 cells transiently transfected with hTSHR cDNA). Desialylated TSH variants showed a significantly increased ratio of bioactivity to immunoreactivity for cAMP production in CHO-R cells (B/I ratio desialylated variants: 3.54 +/- 0.005; B/I ratio sialylated variants: 2.84 +/- 0.01; P < 0.05), Testing the bioactivity of hTSH glycosylation variants isolated by IEF, we found basic variants to be significantly more active than acidic ones in stimulating the cAMP formation in CHO-R cells (B/I ratio basic variants: 9.92 +/- 0.64; neutral variants: 5.98 +/- 0.07; acidic variants: 2.80 +/- 0.12; P < 0.01). There were no differences in stimulation of IF-release. High-mannose TSH variants (firmly bound to Con A) showed greater potency to stimulate cAMP formation and IF-release in both CHO-R and Cos-7 cells than biantennary TSH variants (weakly bound to Con A). Both core-fucosylated (lentil-bound) and core-unfucosylated (lentil-unbound) TSH variants proved to be strong stimulators of cAMP release in CHO and Cos-7 cells. In CHO-R (Cos-7) cells, 400 mu U/ml core-fucosylated TSH stimulated cAMP formation 14(2.6)-fold, core-unfucosylated TSH 7.3(2.3)-fold over control values. In contrast to our findings of cAMP activation by both core-fucosylated and core-unfucosylated TSH variants, release of IPs was stimulated only by, core-fucosylated (lentil-bound) TSH variants and not by TSH variants lacking core-fucose residues (lentil-unbound TSH). This was true for both CHO-R and Cos-7 cells. The lentil-unbound TSH therefore showed an identical differential activation of signal transduction pathways in two different cell systems: strong stimulation of the cAMP-cascade without activation of IPs release (P < 0.05). In conclusion, we showed for the first time for TSH that the two dominant intracellular signal transduction systems (cAMP formation and IPs release) are activated to different degrees by hTSH glycosylation variants. (C) 1997 Elsevier Science Ireland Ltd. C1 NIDDKD, SECT CELL REGULAT, LAB BIOCHEM & METAB, SECT CELL REGULAT, BETHESDA, MD 20892 USA. UNIV FRANKFURT, SCH MED, CTR INTERNAL MED, MED CLIN 1, D-60590 FRANKFURT, GERMANY. RP Schaaf, L (reprint author), MAX PLANCK INST PSYCHIAT, INST CLIN, KRAEPELINSTR 10, D-80804 MUNICH, GERMANY. RI Saji, Motoyasu/E-4007-2011 NR 45 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD SEP 19 PY 1997 VL 132 IS 1-2 BP 185 EP 194 DI 10.1016/S0303-7207(97)00136-6 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA XV852 UT WOS:A1997XV85200021 PM 9324060 ER PT J AU Mehlman, PT Higley, JD Fernald, BJ Sallee, FR Suomi, SJ Linnoila, M AF Mehlman, PT Higley, JD Fernald, BJ Sallee, FR Suomi, SJ Linnoila, M TI CSF 5-HIAA, testosterone, and sociosexual behaviors in free-ranging male rhesus macaques in the mating season SO PSYCHIATRY RESEARCH LA English DT Article DE serotonin; sexual behavior; monkeys; Macaca mulatta ID FLUID 5-HYDROXYINDOLEACETIC ACID; CEREBROSPINAL-FLUID; MONOAMINE METABOLITES; AMINE METABOLITES; SOCIAL-BEHAVIOR; NONHUMAN-PRIMATES; HOMOVANILLIC-ACID; SEVERE AGGRESSION; PLASMA-CORTISOL; MACACA-MULATTA AB This study examines sexual behavior, serotonin turnover in the central nervous system, and testosterone in free-ranging non-human primates. Study subjects were 33 young adult male rhesus macaques (Macaca mulatta) living in naturalistic social groups on a 375-acre South Carolina barrier island. Blood and cerebrospinal fluid (CSF) samples were obtained during random trappings, and the subjects were located for observation by radio telemetry. Quantitative behavioral samples totaling 203 observation hours were taken during two mating seasons (September through January) in 1994 and 1995. Control observations (65 h) on 13 subjects were also taken during the non-mating seasons in 1994 and 1995. The results indicate that CSF 5-hydroxyindoleacetic acid (5-HIAA), CSF testosterone, and plasma testosterone concentrations increase significantly during the mating season. During the mating season, there were significant increases in high intensity aggression, law intensity aggression, grooming behavior, and heterosexual mounting. In the mating season, CSF 5-HIAA was significantly correlated with several sociosexual behaviors. consorts per hour, heterosexual mounts per hour, and inseminations per hour. In contrast to previous findings from the non-mating season, CSF 5-HIAA was not correlated with any measures of aggression or sociality, although during consorting, CSF 5-HIAA was positively correlated with grooming. From these findings, we conclude that the lack of correlation between intense and severe aggression and CSF 5-HIAA in the mating season may reflect the use of high intensity aggression in 'normative' male-male competition over access to reproductively active females. We also conclude that CNS serotonin turnover is positively correlated with sexual competence, i.e. males with low CSF 5-HIAA concentrations are less sexually competent than males with higher concentrations. (C) 1997 Elsevier Science Ireland Ltd. C1 NIAAA,CLIN STUDIES LAB,PRIMATE UNIT,NIH,ANIM CTR,POOLESVILLE,MD 20837. DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. NICHHD,COMPARAT ETHOL LAB,NIH,ANIM CTR,POOLESVILLE,MD 20837. NIAAA,CLIN STUDIES LAB,DICBR,BETHESDA,MD 20892. RP Mehlman, PT (reprint author), LABS VIRGINIA INC,POB 557,YEMASSEE,SC 29945, USA. FU PHS HHS [223-92-1101] NR 42 TC 54 Z9 55 U1 0 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD SEP 19 PY 1997 VL 72 IS 2 BP 89 EP 102 DI 10.1016/S0165-1781(97)00084-X PG 14 WC Psychiatry SC Psychiatry GA XZ733 UT WOS:A1997XZ73300003 PM 9335200 ER PT J AU Allikmets, R Shroyer, NF Singh, N Seddon, JM Lewis, RA Bernstein, PS Peiffer, A Zabriskie, NA Li, YX Hutchinson, A Dean, M Lupski, JR Leppert, M AF Allikmets, R Shroyer, NF Singh, N Seddon, JM Lewis, RA Bernstein, PS Peiffer, A Zabriskie, NA Li, YX Hutchinson, A Dean, M Lupski, JR Leppert, M TI Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration SO SCIENCE LA English DT Article ID BEAVER DAM EYE; FUNDUS FLAVIMACULATUS; MACULOPATHY; DYSTROPHY; FROG AB Age-related macular degeneration (AMD) is the leading cause of severe central visual impairment among the elderly and is associated both with environmental factors such as smoking and with genetic factors. Here, 167 unrelated AMD patients were screened for alterations in ABCR, a gene that encodes a retinal rod photoreceptor protein and is defective in Stargardt disease, a common hereditary form of macular dystrophy. Thirteen different AMD-associated alterations, both deletions and amino acid substitutions, were found in one allele of ABCR in 26 patients (16%). Identification of ABCR alterations will permit presymptomatic testing of high-risk individuals and may lead to earlier diagnosis of AMD and to new strategies for prevention and therapy. C1 NCI,LAB GENOM DIVERS,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. UNIV UTAH,DEPT HUMAN GENET,ECCLED INST HUMAN GENET,SALT LAKE CITY,UT 84112. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. UNIV UTAH,MORAN EYE CTR,DEPT OPHTHALMOL,SALT LAKE CITY,UT 84132. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Shroyer, Noah/0000-0002-5934-2852 NR 25 TC 602 Z9 618 U1 0 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 19 PY 1997 VL 277 IS 5333 BP 1805 EP 1807 DI 10.1126/science.277.5333.1805 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX298 UT WOS:A1997XX29800042 PM 9295268 ER PT J AU Sipowicz, MA Anderson, LM Utermahlen, WE Issaq, HJ Kasprzak, KS AF Sipowicz, MA Anderson, LM Utermahlen, WE Issaq, HJ Kasprzak, KS TI Uptake acid tissue distribution of chromium(III) in mice after a single intraperitoneal or subcutaneous administration SO TOXICOLOGY LETTERS LA English DT Article DE chromium(III) chloride; trivalent chromium; organ distribution AB The tissue levels of chromium were followed after single intraperitoneal or subcutaneous injection of 1 mmol CrCl3/kg body wt. in Swiss male mice. Blood levels were similar after both treatment modes, with half-lives of 31-41 h. Organs not directly exposed by i.p. treatment contained similar amounts in the two groups, with kidneys > lungs, heart > brain. However, after i.p. treatment peritoneal organs (liver, spleen, pancreas and testis) had 40- to 200-fold more chromium compared with s.c. Assay of subsurface liver tissue and of testes removed via the scrotum indicated infiltration of the organs, rather than surface adsorption, of peritoneal chromium. Relative chromium concentrations after i.p. treatment were liver > pancreas = spleen > testis and after s.c. liver > spleen > testis > pancreas. Thus, s.c. treatment with CrCl3 is as effective as i.p. in terms of absorption into the blood. Treatment i.p., leading to direct uptake into peritoneal organs, is an effective way to deliver high chromium doses to these organs, but does not model likely human exposure. (C) 1997 Elsevier Science Ireland Ltd. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. NR 12 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 19 PY 1997 VL 93 IS 1 BP 9 EP 14 DI 10.1016/S0378-4274(97)00064-7 PG 6 WC Toxicology SC Toxicology GA YC273 UT WOS:A1997YC27300002 PM 9381486 ER PT J AU Lin, KH Chen, SL Zhu, XG Shieh, HY McPhie, P Cheng, SY AF Lin, KH Chen, SL Zhu, XG Shieh, HY McPhie, P Cheng, SY TI The gene regulating activity of thyroid hormone nuclear receptors is modulated by cell-type specific factors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BETA-1 RECEPTORS; EXPRESSION; MUTANTS; ELEMENT; BINDING; DNA AB To understand whether the transcriptional activity of thyroid hormone nuclear receptors (TRs) is modulated by cell-type specific factors, full length TR subtype alpha 1 (TR alpha 1) and beta 1 (TR beta 1) cDNAs were cloned from human hepatoma cell lines: HA22T, SK-Hep-1 and HepG2. The cloned receptor bound to the thyroid hormone 3,3',5-triiodo-L-thyronine (T-3) and the thyroid hormone response elements (TREs) similarly to those cloned from other tissues. They exhibited T-3- and TRE-dependent transactivation activities, indicating these TRs were transcriptionally active. The lipogenic malic enzyme (ME), a T-3-target gene in Liver, was stimulated similar to 3- and 1.5-fold by T-3 in HA22T and SR-Hep-l, respectively. The T-3-stimulated ME gene expression was inhibited in HA22T, but stimulated in SH-Hep-l cells by insulin. These results suggest that the gene regulating activity of TRs was modulated by cell-type specific factors. Furthermore, these cell-type specific factors could modulate the cross talk between TR-and insulin receptor-mediated pathways. (C) 1997 Academic Press. C1 NCI,GENE REGULAT SECT,MOL BIOL LAB,DBS,NIH,BETHESDA,MD 20892. CHANG GUNG COLL MED & TECHNOL,GRAD INST CLIN MED,TAYUAN,TAIWAN. NIDDKD,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 17 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 18 PY 1997 VL 238 IS 2 BP 280 EP 284 DI 10.1006/bbrc.1997.7285 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XZ137 UT WOS:A1997XZ13700003 PM 9299494 ER PT J AU Zhou, J Egan, JM AF Zhou, J Egan, JM TI SNAP-25 is phosphorylated by glucose and GLP-1 in RIN 1046-38 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SYNAPTIC VESICLES; BETA-CELLS; PROTEIN; IDENTIFICATION; EXPRESSION; SECRETION; SYNTAXIN; RELEASE; ISLETS AB We investigated the possibility that tyrosine phosphorylation might play a role in insulin secretion in the insulinoma. cell line, RIN 1046-38 cells. At least 4 proteins of 18, 25, 35, and 46 kDa size were found to be tyrosine phosphorylated in the presence of glucose and an insulin secretagogue, glucagon-like peptide-1 (GLP-1). The addition of glucose and GLP-1 to cells that were exposed to the tyrosine kinase inhibitor genistein resulted in a decrease in the extent of phosphorylation of the 18, 25, and 35 kDa proteins and a concomitant reduction in insulin secretion, whereas treatment with vanadate, a tyrosine phosphatase inhibit;or, led to enhanced responses. Immunoprecipitation of cellular proteins with an antiphosphotyrosine antibody followed by immunoblotting with a specific monoclonal antibody to SNAP-25 (synaptosome-associated protein of 25 kDa) revealed that the 25 kDa protein is SNAP-25, These results suggest that tyrosine phosphorylation of SNAP-25 may be involved in the regulation of insulin secretion in RIN 1046-38 cells. (C) 1997 Academic Press. RP Zhou, J (reprint author), NIA,GERONTOL RES CTR,DIABET SECT,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 19 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 18 PY 1997 VL 238 IS 2 BP 297 EP 300 DI 10.1006/bbrc.1997.7286 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XZ137 UT WOS:A1997XZ13700007 PM 9299498 ER PT J AU Hu, X Xia, H Srivastava, SK Herzog, C Awasthi, YC Ji, XH Zimniak, P Singh, SV AF Hu, X Xia, H Srivastava, SK Herzog, C Awasthi, YC Ji, XH Zimniak, P Singh, SV TI Activity of four allelic forms of glutathione S-transferase hGSTP1-1 for diol epoxides of polycyclic aromatic hydrocarbons SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ENZYMATIC-PROPERTIES; EXPRESSION; PI; CANCER; GENE; CDNA AB Allelic forms of hGSTP1-1 which differ from each other by their catalytic properties and, structurally, by the amino ac:id(s) in position(s) 104 or (and) 113 are known to exist in human populations. The four possible isoforms of hGSTP1-1 with isoleucine or valine in position 104 and with alanine or valine in position 113 were produced by site-directed mutagenesis of the cDNA followed by bacterial expression and purification of the proteins. Glutathione-conjugating activity was measured with the diol epoxides of benzo(a)pyrene and chrysene, as well as with the model substrate 1-chloro-2,4-dinitrobenzene. Isoenzymes with valine in position 104 were more effective with the diol epoxides of polycyclic aromatic hydrocarbons but less effective with 1-chloro-2,4-dinitrobenzene than the iso forms with isoleucine 104. In addition, the transition A113V in the presence of V104 caused a pronounced increase in catalytic efficiency for the benzo(a)pyrene but not the chrysene diol epoxide. It is proposed that amino acid 113 functions as part of a clamp that lines the mouth of the water channel leading to the active sites of the hGSTP1-1 dimer and controls the access to substrates. Therefore, the hydrophobicity and the size of residue 113 are important in co-determining the substrate specificity of the isoenzymes. The widely different activities of the allelic isoforms toward carcinogenic diol epoxides of polycyclic aromatic hydrocarbons may help to explain the correlation between cancer susceptibility and genotype at the hGSTP1 locus that has been found by others. (C) 1997 Academic Press. C1 MERCY HOSP PITTSBURGH,MERCY CANC INST,CANC RES LAB,PITTSBURGH,PA 15219. UNIV ARKANSAS MED SCI,DEPT MED,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77555. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [CA 55589]; NIEHS NIH HHS [ES 07804]; NIGMS NIH HHS [GM 32304] NR 25 TC 135 Z9 137 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 18 PY 1997 VL 238 IS 2 BP 397 EP 402 DI 10.1006/bbrc.1997.7311 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XZ137 UT WOS:A1997XZ13700029 PM 9299520 ER PT J AU Kwon, TK Nordin, AA AF Kwon, TK Nordin, AA TI Overexpression of cyclin E and cyclin-dependent kinase inhibitor (p27(Kip1)): Effect on cell cycle regulation in HeLa cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE; PHASE; G(1); FIBROBLASTS; EXPRESSION; ARREST; ROLES AB Transfection of the epithelioid cell line HeLa with p27(Kip1) resulted in an accumulation of cells in the G(1) phase of the cell cycle. Although the cellular level of cdk2 was not decreased as a result of this transfection, there was a significant decline in the cdk2 associated kinase activity. Restoration of the cdk2 kinase activity was proportional to the amount of cotransfected cyclin E plasmid DNA. Overexpression of cyclin E also reversed the p27(Kip1) mediated G(1) growth arrest. These findings suggest that the overexpression of cyclin E reverses the p27(Kip1) mediated G(1) growth arrest by binding the inhibitor restoring the cdk2 associated kinase activity necessary for the G(1)/S transition. (C) 1997 Academic Press. C1 NIA,GERONTOL RES CTR,IMMUNOL LAB,NIH,BALTIMORE,MD 21224. NR 28 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 18 PY 1997 VL 238 IS 2 BP 534 EP 538 DI 10.1006/bbrc.1997.7335 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XZ137 UT WOS:A1997XZ13700055 PM 9299546 ER PT J AU Lei, XD Woodworth, CD Johnen, G Kaufman, S AF Lei, XD Woodworth, CD Johnen, G Kaufman, S TI Expression of 4 alpha-carbinolamine dehydratase in human epidermal keratinocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AMINO-ACID HYDROXYLASES; 4A-CARBINOLAMINE DEHYDRATASE; PHENYLALANINE-HYDROXYLASE; 4A-HYDROXYTETRAHYDROPTERIN DEHYDRATASE; 7-SUBSTITUTED PTERINS; PROTEIN; COFACTOR; RAT; HYPERPHENYLALANINEMIA; TETRAHYDROBIOPTERIN AB 4 alpha-Carbinolamine dehydratase is a bifunctional protein involved in the regeneration of tetrahydrobiopterin during the hydroxylation of the aromatic amino acids. It is also a dimerization cofactor of HNF1 and therefore is believed to function as part of the hepatic gene transcription system. In view of the recent discoveries that the distribution and developmental pattern of the dehydratase do not correlate strictly with those of the aromatic amino acid hydroxylases and HNF1, the hypothesis that the dehydratase may have other unknown functions has been put forward. In the present paper, we demonstrate unambiguously that human epidermal keratinocytes express detectable levels of this protein as indicated by enzyme assay, immunoprecipitation, Western blot, and RT-PCR. Its complete coding sequence has been cloned and was found to be identical with the human liver counterpart. The possible function of the dehydratase in skin is discussed. (C) 1997 Academic Press. C1 NCI,BIOL LAB,NIH,BETHESDA,MD 20892. RP Lei, XD (reprint author), NIMH,NEUROCHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 29 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 18 PY 1997 VL 238 IS 2 BP 556 EP 559 DI 10.1006/bbrc.1997.7336 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XZ137 UT WOS:A1997XZ13700059 PM 9299550 ER PT J AU Masson, GS Busettini, C Miles, FA AF Masson, GS Busettini, C Miles, FA TI Vergence eye movements in response to binocular disparity without depth perception SO NATURE LA English DT Article ID VIEWING DISTANCE; VISUAL-CORTEX; MONKEY; DEPENDENCE; MECHANISMS; STEREOPSIS; MOTION AB Primates use vergence eye movements to align their two eyes on the same object and can correct misalignments by sensing the difference in the positions of the two retinal images of the object (binocular disparity). When large random-dot patterns are viewed dichoptically and small binocular misalignments are suddenly imposed (disparity steps), corrective vergence eye movements are elicited at ultrashort latencies(1,2). Here we show that the same steps applied to dense anticorrelated patterns, in which each black dot in one eye is matched to a white dot in the other eye, initiate vergence responses that are very similar, except that they are in the opposite direction. This sensitivity to the disparity of anticorrelated patterns is shared by many disparity-selective neurons in cortical area V1 (ref. 3), despite the fact that human subjects fail to perceive depth in such stimuli(4,5). These data indicate that the vergence eye movements initiated at ultrashort latencies result solely from locally matched binocular features, and derive their visual input from an early stage of cortical processing before the level at which depth percepts are elaborated. C1 NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. CNRS,CTR RECH NEUROSCI COGNIT,F-13402 MARSEILLE,FRANCE. RI MASSON, Guillaume/G-4615-2012 NR 21 TC 145 Z9 148 U1 0 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 18 PY 1997 VL 389 IS 6648 BP 283 EP 286 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XW772 UT WOS:A1997XW77200047 PM 9305842 ER PT J AU Newton, R Ferlay, J Beral, V Devesa, SS AF Newton, R Ferlay, J Beral, V Devesa, SS TI The epidemiology of non-Hodgkin's lymphoma: Comparison of nodal and extra-nodal sites SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID B-CELL LYMPHOMA; MALIGNANT-LYMPHOMA; GASTRIC LYMPHOMA; CLINICOPATHOLOGICAL FEATURES; MYOEPITHELIAL SIALADENITIS; HELICOBACTER-PYLORI; CELIAC-DISEASE; TISSUE AB International population-based cancer incidence data, coded according to the International Classification of Diseases for Oncology (WHO, 1990), were used to describe geographical patterns of incidence of extra-nodal non-Hodgkin's lymphomas. Incidence data from the USA were also used to describe age and sex distribution of lymphomas at different extranodal sites. The percentage of all non-Hodgkin's lymphomas coded as being of extra-nodal origin is between 25% and 35% in most countries, with the stomach, skin and small intestine being the most common extra-nodal sites. In general, the pattern of incidence rates for extra-nodal lymphomas tends to reflect that of other lymphomas. For example, the age incidence curve of each site-specific extra-nodal lymphoma is similar to that of nodal lymphomas, and in countries where total lymphoma incidence is high the incidence of lymphomas at each extra-nodal site also tends to be relatively high. Although specific factors are known to increase the risk of lymphomas at certain anatomical sites, these data suggest that the aetiology of extra-nodal lymphomas is not entirely independent from that of nodal lymphomas. (C) 1997 Wiley-Liss, Inc. C1 INT AGCY RES CANC,F-69372 LYON,FRANCE. NCI,DEPT HLTH & HUMAN SERV,DESCRIPT STUDIES SECT,BIOSTAT BRANCH,BETHESDA,MD 20892. RP Newton, R (reprint author), RADCLIFFE INFIRM,IMPERIAL CANC RES FUND,CANC EPIDEMIOL UNIT,GIBSON BLDG,OXFORD OX2 6HE,ENGLAND. RI Beral, Valerie/B-2979-2013 NR 28 TC 78 Z9 80 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 17 PY 1997 VL 72 IS 6 BP 923 EP 930 DI 10.1002/(SICI)1097-0215(19970917)72:6<923::AID-IJC1>3.0.CO;2-R PG 8 WC Oncology SC Oncology GA XY833 UT WOS:A1997XY83300001 PM 9378552 ER PT J AU Guadagni, F Roselli, M Cosimelli, M Spila, A Cavaliere, F Arcuri, R DAlessandro, R Fracasso, PL Casale, V Vecchione, A Casciani, CU Greiner, JW Schlom, J AF Guadagni, F Roselli, M Cosimelli, M Spila, A Cavaliere, F Arcuri, R DAlessandro, R Fracasso, PL Casale, V Vecchione, A Casciani, CU Greiner, JW Schlom, J TI Quantitative analysis of CEA expression in colorectal adenocarcinoma and serum: Lack of correlation SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CARCINOEMBRYONIC ANTIGEN GENE; CARCINOMA-ASSOCIATED ANTIGENS; VACCINIA VIRUS-VACCINE; MONOCLONAL-ANTIBODY; CANCER; FAMILY; CELLS AB Tissues and sera from 110 patients diagnosed with colorectal primary carcinoma, 20 patients with benign colorectal diseases and 31 healthy donors were subjected to quantitative CEA analysis. Multiple samples from tumor lesions and autologous histologically normal mucosa (10 cm from the tumor) were obtained at the time of surgery (cancer patients) or endoscopy (benign patients and healthy volunteers). CEA content was measured in protein extracts obtained from these tissues using a quantitative RIA method. A limit of normality for CEA content was established as 300 ng/mg of protein. When this was taken as cut-off, 104 of 110 (94.5%) tumor lesions and 51 of 110 (46.4%) autologous histologically normal colonic mucosa from cancer patients had elevated CEA levels. No correlation with stage of disease was found, while a correlation was observed with degree of tumor differentiation. A statistically significant difference between CEA content in tumor lesions and in histologically normal mucosa from cancer patients was observed (p = -0.001). Moreover, CEA content was statistically higher in the normal mucosa from cancer patients than in that from healthy donors (p = 0.005). CEA content in tissue specimens from benign lesions differed significantly from that in tissue from healthy donors (p = 0.005) and in carcinoma lesions (p < 0.001). The highest CEA content was observed in benign lesions with severe dysplasia. No statistical correlation between CEA content in carcinoma tissues and serum CEA levels (r = 0.195, p = .13) was found. Therefore, in considering diagnosis or therapy with anti-CEA MAbs for colorectal-carcinoma patients, or potential therapies with anti-CEA recombinant vaccines, serum CEA levels should not be taken as indicating CEA expression in tumor lesions. (C) 1997 Wiley-Liss Inc. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. UNIV ROMA LA SAPIENZA,DEPT EXPT MED & PATHOL,ROME,ITALY. REGINA ELENA INST CANC RES,DEPT DIGEST ENDOSCOPY,ROME,ITALY. REGINA ELENA INST CANC RES,DEPT SURG,ROME,ITALY. UNIV ROMA TOR VERGATA,SCH MED,DEPT SURG,ROME,ITALY. REGINA ELENA INST CANC RES,CLIN PATHOL LAB,ROME,ITALY. RI Guadagni, Fiorella/J-4432-2013; Cavaliere, Francesco/J-7635-2016 OI Guadagni, Fiorella/0000-0003-3652-0457; Cavaliere, Francesco/0000-0001-6501-8648 NR 31 TC 47 Z9 47 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 17 PY 1997 VL 72 IS 6 BP 949 EP 954 PG 6 WC Oncology SC Oncology GA XY833 UT WOS:A1997XY83300005 PM 9378556 ER PT J AU Laurencot, CM Scheffer, GL Scheper, RJ Shoemaker, RH AF Laurencot, CM Scheffer, GL Scheper, RJ Shoemaker, RH TI Increased LRP mRNA expression is associated with the MDR phenotype in intrinsically resistant human cancer cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MAJOR VAULT PROTEIN; DRUG-RESISTANCE; MULTIDRUG-RESISTANCE; CROSS-RESISTANCE; GENE; MRP; TRANSPORTER AB Multidrug resistance (MDR) in human cancer cells is multifactorial. Previously, we reported on the association between expression of P-glycoprotein (Pgp), the multidrug resistance-associated protein (MRP), and the lung resistance protein (LRP) with the MDR phenotype in the NCI panel of 60 human cancer cell lines used for in vitro anticancer drug screening. Eight cell lines from this panel, manifesting widely divergent levels of in vitro drug resistance were chosen to investigate the role of MRP and LRP expression at the molecular level. LRP mRNA levels, as determined by ribonuclease protection assay, varied significantly among the 8 cell lines, and correlated closely with in vitro drug resistance to both MDR and non-MDR related drugs. LRP mRNA expression was determined to be a stronger correlate of drug sensitivity than protein expression. In contrast, MRP mRNA levels were not significantly correlated with drug sensitivity. The rates of newly transcribed LRP or MRP mRNA did not correlate with mRNA levels, indicating that mRNA stability or other features of processing may be important in regulation of LRP and MRP mRNA levels. Using Southern blot analysis, LRP gene amplification was shown not to be associated with LRP overexpression. These data suggest that LRP expression may be an important determinant of the MDR phenotype in cell lines intrinsically resistant to cancer chemotherapeutic agents. (C) 1997 Wiley-Liss, Inc. C1 NCI, FREDERICK CANC RES & DEV CTR, DIV CANC TREATMENT DIAG & CTR, LAB DRUG DISCOVERY RES & DEV, FREDERICK, MD 21702 USA. FREE UNIV AMSTERDAM HOSP, DEPT PATHOL, AMSTERDAM, NETHERLANDS. NR 26 TC 60 Z9 66 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 17 PY 1997 VL 72 IS 6 BP 1021 EP 1026 PG 6 WC Oncology SC Oncology GA XY833 UT WOS:A1997XY83300017 PM 9378536 ER PT J AU Fassina, G Aluigi, MG Gentleman, S Wong, P Cai, TN Albini, A Noonan, DM AF Fassina, G Aluigi, MG Gentleman, S Wong, P Cai, TN Albini, A Noonan, DM TI The cAMP analog 8-Cl-cAMP inhibits growth and induces differentiation and apoptosis in retinoblastoma cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID DEPENDENT PROTEIN-KINASE; CYCLIC-AMP; 8-CHLORO-CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; GENE-EXPRESSION; RI SUBUNIT; CANCER; MODULATION; DEATH; CARCINOMA; LAMININ AB Retinoblastomas appear to be derived from a multipotential stem cell of the retina, due to alterations of the Rb I gene. These tumors arise only within a discrete time frame during childhood, prior to terminal differentiation of the retinal precursor cells. Treatment of retinoblastoma cells with certain agents can induce a partial differentiation of cell types resembling those of the mature retina, such as rod and cone photoreceptors, glia, conventional neurons and pigment epititelia. We have tested the effects of 8-CI-cAMP, a synthetic analog of cAMP which preferentially binds to and activates the RII subunit of protein kinase A on the Y-79 retinoblastoma cell line in vitro. Y-79 cells treated with 8-CI-cAMP produced short, branching processes and showed a substantial increase in staining for neuron-specific enolase, a marker for conventional neuronal differentiation. In contrast, dibutyryl-cAMP gives a strong increase in the glial marker glial acidic fibrillary protein. Y-79 cell proliferation was strongly inhibited by 8-CI-cAMP at concentrations as low as 5-25 mu M. 8-CI-cAMP significantly increased the rate of apoptosis of Y-79 cells in a dose-dependent manner. It also modulated expression of the RI regulatory subunit of intracellular cAMP-dependent protein kinase A, which is produced in abnormal quantities by Y-79 cells. A decrease in protein production was observed, with no clear effect on the RI subunit mRNA expression, suggesting that RI regulation occurs posttranscriptionally. (C) 1997 Wiley-Liss, Inc. C1 CNR,CTR STUDIO NEUROFISIOL CEREBRALE,GENOA,ITALY. NEI,NIH,BETHESDA,MD 20892. RP Fassina, G (reprint author), IST NAZL RIC CANC,LARGO ROSANNA BENZI 10,I-16132 GENOA,ITALY. RI Noonan, Douglas/A-8620-2010 OI Noonan, Douglas/0000-0001-8058-0719 NR 28 TC 25 Z9 27 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 17 PY 1997 VL 72 IS 6 BP 1088 EP 1094 PG 7 WC Oncology SC Oncology GA XY833 UT WOS:A1997XY83300025 PM 9378544 ER PT J AU Sugarman, J Kaalund, V Kodish, E Marshall, MF Reisner, EG Wilfond, BS Wolpe, PR Hage, ML Kurtzberg, J Olson, J Capron, AM Faden, RR Powers, M Harvath, L Howe, CWS AF Sugarman, J Kaalund, V Kodish, E Marshall, MF Reisner, EG Wilfond, BS Wolpe, PR Hage, ML Kurtzberg, J Olson, J Capron, AM Faden, RR Powers, M Harvath, L Howe, CWS TI Ethical issues in umbilical cord blood banking SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEMATOPOIETIC STEM-CELLS; PLACENTAL BLOOD; TRANSPLANTATION; CHILDREN; DISEASE AB Objective.-Banking umbilical cord blood (UCB) to be used as a source of stem cells for transplantation is associated with a set of ethical issues. An examination of these issues is needed to inform public policy and to raise the awareness of prospective parents, clinicians, and investigators. Participants.-Individuals with expertise in anthropology, blood banking, bone marrow transplantation, ethics, law, obstetrics, pediatrics, and the social sciences were invited to join the Working Group on Ethical Issues in Umbilical Cord Blood Banking. Evidence.-Members were assigned topics to present to the Working Group. Following independent reviews, background materials were sent to the Working Group. Consensus Process.-Individual presentations of topics at a 2-day meeting were followed by extensive group discussions in which consensus emerged. A writing committee then drafted a document that was circulated to the entire Working Group. After 3 rounds of comments over several months, all but 1 member of the Working Group agreed with the presentation of our conclusions. Conclusions.-(1) Umbilical cord blood technology is promising although it has several investigational aspects; (2) during this investigational phase, secure linkage should be maintained of stored UCB to the identity of the donor; (3) UCB banking for autologous use is associated with even greater uncertainty than banking for allogeneic use; (4) marketing practices for UCB banking in the private sector need close attention; (5) more data are needed to ensure that recruitment for banking and use of UCB are equitable; and (6) the process of obtaining informed consent for collection of UCB should begin before labor and delivery. C1 UNIV N CAROLINA, AFRICAN & AFROAMER STUDIES, CHAPEL HILL, NC USA. CASE WESTERN RESERVE UNIV, SCH MED, CTR BIOMED ETH, CLEVELAND, OH 44106 USA. MED UNIV S CAROLINA, PROGRAM BIOETH, CHARLESTON, SC 29425 USA. UNIV ARIZONA, DEPT PEDIAT, TUCSON, AZ 85721 USA. UNIV PENN, CTR BIOETH, PHILADELPHIA, PA 19104 USA. UNIV SO CALIF, LOS ANGELES, CA 90089 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD 21218 USA. GEORGETOWN UNIV, WASHINGTON, DC 20057 USA. US FDA, BETHESDA, MD 20014 USA. NATL MARROW DONOR PROGRAM, MINNEAPOLIS, MN USA. JOHNS HOPKINS SCH PUBL HLTH, BETHESDA, MD USA. PENN STATE UNIV, COLL MED, HERSHEY, PA USA. ALBERT EINSTEIN COLL MED, NEW YORK, NY USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. NHLBI, NIH, BETHESDA, MD 20892 USA. AMER RED CROSS, CHARLOTTE, NC USA. RP Sugarman, J (reprint author), DUKE UNIV, MED CTR, DIV GEN INTERNAL MED, CTR HLTH POLICY RES & EDUC, CTR STUDY AGING & HUMAN DEV, DURHAM, NC 27710 USA. RI Wolpe, Paul/A-1032-2007 NR 30 TC 69 Z9 69 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 17 PY 1997 VL 278 IS 11 BP 938 EP 943 DI 10.1001/jama.278.11.938 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XV640 UT WOS:A1997XV64000034 PM 9302248 ER PT J AU Brinton, LA Brown, SL AF Brinton, LA Brown, SL TI Breast implants and cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID CONNECTIVE-TISSUE DISEASES; SILICONE GEL IMPLANTS; GENETICALLY SUSCEPTIBLE STRAINS; AUGMENTATION MAMMAPLASTY; MULTIPLE-MYELOMA; MONOCLONAL GAMMOPATHY; UNITED-STATES; RISK FACTOR; FOLLOW-UP; WOMEN AB Background: Although silicone breast implants have been linked to various short-term complications, less is known about their long-range effects, Most attention has focused on connective tissue disorders, but the range of immunologic disturbances observed in women with implants suggests that consideration also be given to other chronic diseases, including cancer, The greatest attention has focused on breast cancer, given clinical reports suggesting an association and observations that mammographic visualization is deterred by implants, Findings from epidemiologic studies, however, actually suggest that breast cancer risk might be reduced among women with implants, although the biologic mechanism remains undefined, In addition, most studies do not suggest that women with breast implants have more advanced breast cancer at diagnosis or a worse prognosis than those without implants, The majority of studies have focused on women who received implants for cosmetic reasons, with little previous investigation of women who received implants for breast reconstruction following cancer surgery, In terms of other cancers, animal as well as clinical data suggest potential risks of sarcomas and hematologic cancers, including multiple myeloma, The risk of these cancers has not yet been adequately addressed by epidemiologic studies, although several ongoing studies should provide insights, It will be important for studies to consider effects of other lifestyle factors as well as to analyze relationships according to duration of implantation, a demonstrated determinant of implant deterioration, In addition, consideration should be given to type of implant, including implants with polyurethane foam covers, which can leak toluene diamine, a demonstrated carcinogen in animals. C1 US FDA,OFF SURVEILLANCE & BIOMETR,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. RP Brinton, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,RM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 118 TC 47 Z9 49 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 17 PY 1997 VL 89 IS 18 BP 1341 EP 1349 DI 10.1093/jnci/89.18.1341 PG 9 WC Oncology SC Oncology GA XW477 UT WOS:A1997XW47700007 PM 9308703 ER PT J AU Wideroff, L Gridley, G Mellemkjaer, L Chow, WH Linet, M Keehn, S BorchJohnsen, K Olsen, JH AF Wideroff, L Gridley, G Mellemkjaer, L Chow, WH Linet, M Keehn, S BorchJohnsen, K Olsen, JH TI Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RENAL-CELL CARCINOMA; PRIMARY LIVER-CANCER; BREAST-CANCER; RISK-FACTORS; PANCREATIC-CANCER; GLUCOSE TOLERANT; MEDICAL HISTORY; BODY-SIZE; DISEASE; MEN AB Background: Diabetes has been associated with an increased risk of several cancers, notably cancers of the pancreas, liver, endometrium, and kidney, Since most previous studies have involved a limited sample size or focused on specific cancer sites, we conducted a comprehensive assessment of the risk of cancer in a nationwide cohort of diabetics in Denmark, Methods: Discharge records of 109581 individuals hospitalized with a diagnosis of diabetes from 1977 through 1989 were linked with national cancer registry records through 1993, Standardized incidence ratios (SIRs) were calculated for specific cancer sites, Results: The SIRs for primary liver cancer were 4.0 (95% confidence interval [CI] = 3.5-4.6) in males and 2.1 (95% CI = 1.6-2.7) in females, These SIRs remained elevated with increasing years of follow-up and after exclusion of patients with reported risk factors (e.g., cirrhosis and hepatitis) or patients whose cancers were diagnosed at autopsy. Kidney cancer risk was also elevated, with SIRs of 1.4 (95% CI = 1.2-1.6) in males and 1.7 (95% CI = 1.4-1.9) in females, For both sexes combined, the SIR for pancreatic cancer was 2.1 (95% CI = 1.9-2.4), with a follow-up time of 1-4 years; this SIR declined to 1.3 (95% CI = 1.1-1.6) after 5-9 years of follow-up, Excess risks were also observed for biliary tract and endometrial cancers, The SIRs for kidney and endometrial cancers declined somewhat after exclusion of diabetics with reported obesity, Conclusions: Patients hospitalized with a diagnosis of diabetes appear to be at higher risk of developing cancers of the liver, biliary tract, pancreas, endometrium, and kidney, The elevated risks of endometrial and kidney cancers, however, may be confounded by obesity. C1 DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. GLOSTRUP UNIV HOSP,COPENHAGEN CTY CTR PREVENT MED,GLOSTRUP,DENMARK. RP Wideroff, L (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,RM 443,BETHESDA,MD 20892, USA. RI Hernandez, Jessica/G-6527-2011 NR 44 TC 418 Z9 437 U1 0 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 17 PY 1997 VL 89 IS 18 BP 1360 EP 1365 DI 10.1093/jnci/89.18.1360 PG 6 WC Oncology SC Oncology GA XW477 UT WOS:A1997XW47700010 PM 9308706 ER PT J AU Wistuba, II Lam, S Behrens, C Virmani, AK Fong, KM LeRiche, J Samet, JM Srivastava, S Minna, JD Gazdar, AF AF Wistuba, II Lam, S Behrens, C Virmani, AK Fong, KM LeRiche, J Samet, JM Srivastava, S Minna, JD Gazdar, AF TI Molecular damage in the bronchial epithelium of current and former smokers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; MICROSATELLITE INSTABILITY; MUTATOR PHENOTYPE; CARCINOMA; LESIONS; GENE; TUMORS; P53; ABNORMALITIES; PATHOGENESIS AB Background: Most lung cancers are attributed to smoking, These cancers have been associated with multiple genetic alterations and with the presence of preneoplastic bronchial lesions, In view of such associations, we evaluated the status of specific chromosomal loci in histologically normal and abnormal bronchial biopsy specimens from current and former smokers and specimens from nonsmokers, Methods: Multiple biopsy specimens were obtained from 18 current smokers, 24 former smokers, and 21 nonsmokers, Polymerase chain reaction-based assays involving 15 polymorphic microsatellite DNA markers were used to examine eight chromosomal regions for genetic changes (loss of heterozygosity [LOH] and microsatellite alterations), Results: LOH and microsatellite alterations were observed in biopsy specimens from both current and former smokers, but no statistically significant differences were observed between the two groups. Among individuals with a history of smoking, 86% demonstrated LOH in one or more biopsy specimens, and 24% showed LOH in all biopsy specimens, About half of the histologically normal specimens from smokers showed LOH, but the frequency of LOH and the severity of histologic change did not correspond until the carcinoma in situ stage, A subset of biopsy specimens from smokers that exhibited either normal or preneoplastic histology showed LOH at multiple chromosomal sites, a phenomenon frequently observed in carcinoma in situ and invasive cancer, LOH on chromosomes 3p and 9p was more frequent than LOH on chromosomes 5q, 17p (17p13; TP53 gene), and 13q (13q14; retinoblastoma gene), Microsatellite alterations were detected in 64% of the smokers, No genetic alterations were detected in nonsmokers, Conclusions: Genetic changes similar to those found in lung cancers can be detected in the nonmalignant bronchial epithelium of current and former smokers and may persist for many years after smoking cessation. C1 UNIV TEXAS,SW MED CTR,HAMON CTR THERAPEUT ONCOL RES,NB8 106,DALLAS,TX 75235. PONTIFICIA UNIV CATOLICA CHILE,DEPT PATHOL,SANTIAGO,CHILE. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75235. BRITISH COLUMBIA CANC AGCY,VANCOUVER,BC V5Z 4E6,CANADA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,HAMON CTR THERAPEUT ONCOL RES,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. NCI,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DEPT INTERNAL MED,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235. RI Fong, Kwun/G-6369-2010 FU NCI NIH HHS [1P50CA70907-01, N01CN45580-01, P50 CA070907] NR 46 TC 327 Z9 333 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 17 PY 1997 VL 89 IS 18 BP 1366 EP 1373 DI 10.1093/jnci/89.18.1366 PG 8 WC Oncology SC Oncology GA XW477 UT WOS:A1997XW47700011 PM 9308707 ER PT J AU Schwartz, JL Rice, JS Luxon, BA Sayer, JM Xie, G Yeh, HJC Liu, X Jerina, DM Gorenstein, DG AF Schwartz, JL Rice, JS Luxon, BA Sayer, JM Xie, G Yeh, HJC Liu, X Jerina, DM Gorenstein, DG TI Solution structure of the minor conformer of a DNA duplex containing a dG mismatch opposite a benzo[a]pyrene diol epoxide/dA adduct: Glycosidic rotation from syn to anti at the modified deoxyadenosine SO BIOCHEMISTRY LA English DT Article ID NMR SOLUTION STRUCTURE; NONANUCLEOTIDE DUPLEX; N-6-AMINO GROUP; TRANS ADDITION; INTERCALATION; SPECTROSCOPY; FRAME; SITE; DT AB Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants whose metabolism in mammals results in deleterious cell transformation. Covalent modification of DNA by diol epoxides metabolically formed from PAHs such as benzo[a]pyrene (BaP) provides a mechanism for the genotoxicity, mutagenicity, and carcinogenicity of PAHs. We had previously reported NMR evidence for a minor conformer of the duplex d(G(1)G(2)T(3)C(4)A(5)*C(6)G(7)A(8)C(9)).d(C(10)T(11)C(12)G(13)G(14)G(15)A(16)C(17)C(18)) containing a dG(14) mismatch opposite a dA(5)* residue modified at the exocyclic amino group by trans addition to (+)-(7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [Yeh, H. J. C., Sayer, J. M., Liu, X., Altieri, A. S., Byrd, R. A., Lashman, M. K., Yagi, H., Schurter, E. J., Gorenstein, D. G., & Jerina, D. M. (1995) Biochemistry 34, 13570-13581]. In the present work, we describe the structure of this minor conformer (ca. 17% of the total conformer population). This represents the first structural determination of a minor conformer of a carcinogen-lesion DNA adduct. Two-dimensional NOESY, ROESY, TOCSY, and exchange-only spectra at 750 MHz allowed nearly complete sequential assignment of both conformers. In the minor conformer, the adducted base assumes an anti-glycosidic torsion angle whereas in the major conformer it assumes an unusual syn-glycosidic torsion angle. The aromatic hydrocarbon in the minor conformer is intercalated between dG(13) and dG(14), preserving the energetically favorable stacking interactions found in the major conformer. The major structural differences between the two conformers appear to be near the lesion site as evidenced by the large chemical shift differences between major and minor conformer protons near the lesion site; away from this site, the chemical shifts of the major and minor conformer protons are nearly identical. Because any of the conformations of benzo[a]pyrene diol epoxide-modified DNA may contribute to tumorigenic activity, structural determination of all conformations is essential for the elucidation of the mechanism of cell transformation initiated by covalent modification of DNA by PAHs. C1 UNIV TEXAS,MED BRANCH,SEALY CTR STRUCT BIOL,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77555. NIDDKD,NIH,BETHESDA,MD 20892. RI Luxon, Bruce/C-9140-2012 FU NIAID NIH HHS [AI27744]; NIEHS NIH HHS [ES06676, R01 ES06839] NR 24 TC 46 Z9 46 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 16 PY 1997 VL 36 IS 37 BP 11069 EP 11076 DI 10.1021/bi971306u PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW733 UT WOS:A1997XW73300004 PM 9333324 ER PT J AU Paalman, SR Sung, C Clarke, ND AF Paalman, SR Sung, C Clarke, ND TI Specificity of DNA repair methyltransferases determined by competitive inactivation with oligonucleotide substrates: Evidence that Escherichia coli Ada repairs O-6-methylguanine and O-4-methylthymine with similar efficiency SO BIOCHEMISTRY LA English DT Article ID 3 O-6-SUBSTITUTED GUANINES; POLYMERASE-I; UNIQUE SITE; O6-METHYLGUANINE; O4-METHYLTHYMINE; MUTAGENESIS; PROTEIN; O-6-ALKYLGUANINE; PURIFICATION; ALKYLATION AB DNA repair methyltransferases (MTases) are stoichiometric acceptor molecules that are irreversibly inactivated in the course of removing a methyl group from O-6-methylguanine (meG)-DNA or O-4-methylthymine (meT)-DNA. A new assay has been developed to determine the relative efficiency of repair of meG and meT. The assay is based on the deprotection of methylated restriction sites in synthetic oligonucleotides and can be used to measure meG repair or meT repair directly. More importantly, relative repair efficiencies can be measured in competition experiments, using each of the methylated oligomers in turn as an inhibitor of repair for the other. Relative repair rates are determined by numerical solution of the coupled rate equations that describe this competition to the experimental data. We find that the human MTase repairs meT about 35-fold less well than meG, qualitatively similar to earlier studies. Contrary to previous reports, however, we find that Escherichia coli Ada repairs meG and meT with nearly equal efficiency. This finding, in conjunction with other recent reports, may indicate that low meT repair is a relatively unusual characteristic of the human homolog. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOPHYS & BIOPHYS CHEM,BALTIMORE,MD 21205. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Clarke, Neil/D-9613-2014 FU NCI NIH HHS [CA59492] NR 32 TC 14 Z9 14 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 16 PY 1997 VL 36 IS 37 BP 11118 EP 11124 DI 10.1021/bi970740t PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW733 UT WOS:A1997XW73300009 PM 9287154 ER PT J AU Sawaya, MR Prasad, R Wilson, SH Kraut, J Pelletier, H AF Sawaya, MR Prasad, R Wilson, SH Kraut, J Pelletier, H TI Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: Evidence for an induced fit mechanism SO BIOCHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; ADENOSINE 5'-TRIPHOSPHATE; ESCHERICHIA-COLI; CATALYTIC DOMAIN; NUCLEIC-ACIDS; BINDING; FIDELITY; ENZYME; REPLICATION; TRIPHOSPHATE AB DNA polymerase beta (pol beta) fills single nucleotide (nt) gaps in DNA produced by the base excision repair pathway of mammalian cells. Crystal structures have been determined representing intermediates in the 1 nt gap-filling reaction of pol beta: the binary complex with a gapped DNA substrate (2.4 Angstrom resolution), the ternary complex including ddCTP (2.2 Angstrom), and the binary product complex containing only nicked DNA (2.6 Angstrom). Upon binding ddCTP to the binary gap complex, the thumb subdomain rotates into the closed conformation to contact the otherwise solvent-exposed ddCTP-template base pair. Thumb movement triggers further conformational changes which poise catalytic residue Asp192, dNTP, and template for nucleotidyl transfer, effectively assembling the active site. In the product nicked DNA complex, the thumb returns to the open conformation as in the gapped binary DNA complex, facilitating dissociation of the product. These findings suggest that pol beta may enhance fidelity by an induced fit mechanism in which correct base pairing between template and incoming dNTP induces alignment of catalytic groups for catalysis (via thumb closure), but incorrect base pairing will not. The structures also reveal that pol beta binds both gapped and nicked DNA with a 90 degrees kink occurring precisely at the 5'-phosphodiester linkage of the templating residue. If the DNA were not kinked in this way, contact between the thumb and dNTP-template base pair, presumably important for the checking mechanism, would be impossible, especially when the gap is but a single nucleotide. Such a 90 degrees kink may be a mechanistic feature employed by any polymerase involved in filling gaps to completion. C1 NIEHS,RES TRIANGLE PK,NC 27709. BAYLOR COLL MED,VERNA & MARRS MCLEAN DEPT BIOCHEM,HOUSTON,TX 77030. RP Sawaya, MR (reprint author), UNIV CALIF SAN DIEGO,DEPT CHEM & BIOCHEM,9500 GILMAN DR,LA JOLLA,CA 92093, USA. OI Sawaya, Michael/0000-0003-0874-9043 FU NHGRI NIH HHS [HG00005]; NIDDK NIH HHS [DK07233]; NIGMS NIH HHS [GM52860] NR 57 TC 496 Z9 501 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 16 PY 1997 VL 36 IS 37 BP 11205 EP 11215 DI 10.1021/bi9703812 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW733 UT WOS:A1997XW73300018 PM 9287163 ER PT J AU Watson, KE Abrolat, ML Malone, LL Hoeg, JM Doherty, T Detrano, R Demer, LL AF Watson, KE Abrolat, ML Malone, LL Hoeg, JM Doherty, T Detrano, R Demer, LL TI Active serum vitamin D levels are inversely correlated with coronary calcification SO CIRCULATION LA English DT Article DE calcium; coronary disease; hypercholesterolemia ID OSTEOPONTIN MESSENGER-RNA; BEAM COMPUTED-TOMOGRAPHY; HUMAN ATHEROSCLEROTIC LESIONS; INTRAVASCULAR ULTRASOUND; AORTIC CALCIFICATION; PARATHYROID-HORMONE; ARTERY CALCIUM; BONE-DENSITY; CELLS; EXPRESSION AB Background Arterial calcification is a common feature of atherosclerosis, occurring in >90% of angiographically significant lesions. Recent evidence from this and other studies suggests that development of atherosclerotic calcification is similar to osteogenesis; thus, we undertook the current investigation on the potential role of osteoregulatory factors in arterial calcification. Methods and Results We studied two human populations (173 subjects) at high and moderate risk for coronary heart disease and assessed them for associations between vascular calcification and serum levels of the osteoregulatory molecules osteocalcin, parathyroid hormone, and 1 alpha,25-dihydroxyvitamin D-3 (1,25-vitamin D). Our results revealed that 1,25-vitamin D levels are inversely correlated with the extent of vascular calcification in both groups. No correlations were found between extent of calcification and levels of osteocalcin or parathyroid hormone. Conclusions These data suggest a possible role for vitamin D in the development of vascular calcification. Vitamin D is also known to be important in bone mineralization; thus, 1,25-vitamin D may be one factor to explain the long observed association between osteoporosis and vascular calcification. C1 UNIV CALIF LOS ANGELES,SCH MED,CTR HLTH SCI 47 123,DEPT MED,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,CTR HLTH SCI 47 123,DEPT PHYSIOL,LOS ANGELES,CA 90095. NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,HARBOR MED CTR,LOS ANGELES,CA 90024. RP Watson, KE (reprint author), UNIV CALIF LOS ANGELES,SCH MED,CTR HLTH SCI 47 123,DIV CARDIOL,LOS ANGELES,CA 90095, USA. RI Demer, Linda/I-5770-2013 OI Demer, Linda/0000-0002-9618-6895 FU NCRR NIH HHS [MO1-RR-00865]; NHLBI NIH HHS [HL-30568] NR 43 TC 313 Z9 329 U1 1 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 16 PY 1997 VL 96 IS 6 BP 1755 EP 1760 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XW901 UT WOS:A1997XW90100013 PM 9323058 ER PT J AU Alderman, E Bourassa, M Brooks, MM Califf, R Chaitman, B Detre, K Faxon, DP Feit, F Frye, RL Hardison, RM Holmes, D Holubkov, R Kouchoukos, N Krone, R Rogers, W Rosen, AD Schaff, H Schwartz, L Siewers, AS Sopko, G SuttonTyrrell, K Whitlow, P AF Alderman, E Bourassa, M Brooks, MM Califf, R Chaitman, B Detre, K Faxon, DP Feit, F Frye, RL Hardison, RM Holmes, D Holubkov, R Kouchoukos, N Krone, R Rogers, W Rosen, AD Schaff, H Schwartz, L Siewers, AS Sopko, G SuttonTyrrell, K Whitlow, P TI Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease - The bypass angioplasty revascularization investigation (BARI) SO CIRCULATION LA English DT Article DE angioplasty; bypass; coronary disease; diabetes mellitus; trials ID ACUTE MYOCARDIAL-INFARCTION; CORONARY HEART-DISEASE; LEFT-VENTRICULAR DYSFUNCTION; FOLLOW-UP; NONDIABETIC PATIENTS; BALLOON ANGIOPLASTY; ARTERY DISEASE; RISK-FACTORS; MELLITUS; PROGNOSIS AB Background Patients with diabetes mellitus have increased morbidity and mortality after coronary revascularization. The Bypass Angioplasty Revascularization Investigation (BARI), a trial of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG) in patients with multivessel disease, reported a 5-year survival advantage of CABG over PTCA in patients with treated diabetes mellitus (TDM). This report examines these findings in more detail. Methods and Results Eighteen clinical centers randomly assigned 1829 patients with multivessel coronary disease to undergo initial CABG or PTCA. Patients were followed an average of 5.4 years. TDM was defined as a history of diabetes with use of oral hypoglycemic agents or insulin at study entry. Nineteen percent of the randomized population (353 patients) met these criteria. TDM patients had more unfavorable baseline characteristics than other patients, but among TDM patients, these characteristics were similar between the CABG and PTCA groups. Better average 5.4-year survival with CABG was due to reduced cardiac mortality (5.8% versus 20.6%, P=.0003), which was confined to those receiving at least one internal mammary artery graft. Conclusions Patients with TDM assigned to an initial strategy of CABG have a striking reduction in cardiac mortality compared with PTCA. Long-term internal mammary artery graft patency may contribute to this improved outcome by reducing the fatality of follow-up myocardial infarction. C1 UNIV PITTSBURGH,PITTSBURGH,PA 15261. NHLBI,BETHESDA,MD 20892. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15260. NR 53 TC 368 Z9 387 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 16 PY 1997 VL 96 IS 6 BP 1761 EP 1769 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XW901 UT WOS:A1997XW90100014 ER PT J AU Vasan, RS Larson, MG Levy, D Evans, JC Benjamin, EJ AF Vasan, RS Larson, MG Levy, D Evans, JC Benjamin, EJ TI Distribution and categorization of echocardiographic measurements in relation to reference limits - The Framingham Heart Study: Formulation of a height- and sex-specific classification and its prospective validation SO CIRCULATION LA English DT Article DE echocardiography; cardiovascular diseases; ventricles; atrium; follow-up studies ID LEFT-VENTRICULAR MASS; BODY-SURFACE AREA; ATRIAL-FIBRILLATION; REFERENCE VALUES; CARDIAC CHAMBER; POPULATION; AGE; HYPERTROPHY; DISEASE; HYPERTENSION AB Background Despite widespread categorization of echocardiographic measurements, there are no standardized guidelines for partitioning values exceeding reference limits. Methods and Results We used regression analyses to develop sex- and height-specific reference limits for cardiac M-mode measurements (left ventricular [LV] mass, LV wall thickness, and LV and left atrial dimensions) in a healthy reference sample (n=1099) from the Framingham Heart Study. We then examined the distribution of measurements in a broad sample (n=4957) and classified the measurements according to increasing deviation from the height-and sex-specific reference limits and the 95th, 98th, and 99th percentile values for the broad sample (categories 0 through 4, respectively). To validate the categorization scheme, we used multi variable proportional-hazards regression to assess the relations of LV mass and LV wall thickness categories to risk of cardiovascular events and the relations of left atrial size to risk of atrial fibrillation. During a mean follow-up period of 7.7 years, 587 subjects developed new cardiovascular disease events, and 166 subjects developed new-onset atrial fibrillation. After adjustment for known risk factors, there was a 1.2- and 1.3-fold risk of cardiovascular disease events per category of LV wall thickness and LV mass, respectively, and a 1.6-fold risk of atrial fibrillation per category of left atrial size. Conclusions Using a large community-based study sample, we propose a classification scheme that provides a standardized and validated framework for partitioning echocardiographic measurements. If adopted, the categorization scheme should promote uniformity in describing measurements among echocardiographic laboratories and enhance the comprehensibility of measurements to clinicians. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, NHLBI, FRAMINGHAM, MA 01701 USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DIV CARDIOL, BOSTON, MA 02215 USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DIV CLIN EPIDEMIOL, BOSTON, MA 02215 USA. BOSTON UNIV, SCH MED, DEPT PREVENT MED & EPIDEMIOL, BOSTON, MA 02118 USA. BOSTON UNIV, SCH MED, CARDIOL SECT, BOSTON, MA 02118 USA. NHLBI, BETHESDA, MD 20892 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N0I-HC-38038]; NINDS NIH HHS [2-ROI-NS-17950-11] NR 54 TC 138 Z9 142 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 16 PY 1997 VL 96 IS 6 BP 1863 EP 1873 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XW901 UT WOS:A1997XW90100029 PM 9323074 ER PT J AU Ishii, M Jones, M Shiota, T Yamada, I Heinrich, RS Holcomb, SR Yoganathan, AP Sahn, DJ AF Ishii, M Jones, M Shiota, T Yamada, I Heinrich, RS Holcomb, SR Yoganathan, AP Sahn, DJ TI Quantifying aortic regurgitation by using the color Doppler-imaged vena contracta - A chronic animal model study SO CIRCULATION LA English DT Article DE echocardiography; hemodynamics; imaging; valves ID MITRAL REGURGITATION; ORIFICE AREA; QUANTITATIVE ASSESSMENT; VALVULAR REGURGITATION; CONVERGENCE METHOD; JET WIDTH; IN-VITRO; FLOW; ECHOCARDIOGRAPHY; LIMITATIONS AB Background The aim of the present study was to evaluate the accuracy of determining aortic effective regurgitant orifice area (EROA) and aortic regurgitant volume by using the color Doppler-imaged vena contracta (CDVC). Methods and Results Twenty-nine hemodynamically different states were obtained pharmacologically in eight sheep with surgically induced aortic regurgitation. Instantaneous regurgitant flow rates (RFRs) were obtained with aortic and pulmonary electromagnetic flowmeters (EFMs), and aortic EROAs were determined from EFM RFRs divided by continuous wave Doppler velocities. Color Doppler-derived EROAs were estimated by measuring the maximal diameters of the CDVC. Peak and mean RFRs and regurgitant volumes per beat were calculated from vena contracta area continuous wave diastolic Doppler velocity curves. Peak EFM-derived RFRs varied from 1.8 to 13.6 (6.3 +/- 3.2) L/min (range [mean +/- SD]), mean RFRs varied from 0.7 to 4.9 (2.7 +/- 1.3) L/min, regurgitant volumes per beat varied from 7.0 to 48.0 (26.9 +/- 12.2) mL/beat, and the regurgitant fractions varied from 23% to 78% (55 +/- 16%). EROAs determined by using CDVC measurements correlated well with reference EROAs obtained by using the EFM method (r = .91, SEE = 0.07 cm(2)). Excellent correlations and agreements between peak and mean RFR and regurgitant volumes per beat as determined by Doppler echocardiography and EFM were also demonstrated (r = .95 to .96). Conclusions Our study indicates that the CDVC method can be used to quantify both aortic EROAs and regurgitant flow rates. C1 NHLBI,NIH,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. GEORGIA INST TECHNOL,ATLANTA,GA 30332. FU NHLBI NIH HHS [HL-43287] NR 42 TC 29 Z9 30 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 16 PY 1997 VL 96 IS 6 BP 2009 EP 2015 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XW901 UT WOS:A1997XW90100048 PM 9323093 ER PT J AU Wickner, RB AF Wickner, RB TI A new prion controls fungal cell fusion incompatibility SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID VEGETATIVE INCOMPATIBILITY; PODOSPORA-ANSERINA; PROPAGATION; PROTEIN; SCRAPIE; PSI(+); PRP RP Wickner, RB (reprint author), NIDDKD,LAB BIOCHEM & GENET,NIH,BLDG 8,ROOM 225,8 CTR DR MSC 0830,BETHESDA,MD 20892, USA. NR 21 TC 46 Z9 46 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 16 PY 1997 VL 94 IS 19 BP 10012 EP 10014 DI 10.1073/pnas.94.19.10012 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX399 UT WOS:A1997XX39900003 PM 9294153 ER PT J AU Fromm, C Coso, OA Montaner, S Xu, NZ Gutkind, JS AF Fromm, C Coso, OA Montaner, S Xu, NZ Gutkind, JS TI The small GTP-binding protein Rho links G protein-coupled receptors and G alpha(12) to the serum response element and to cellular transformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE G proteins; transcription factors; signal transduction; c-fos ID NIH 3T3 CELLS; C-FOS PROMOTER; HETEROTRIMERIC G-PROTEINS; BETA-GAMMA-SUBUNITS; TERNARY COMPLEX; ALPHA-SUBUNIT; TRANSCRIPTIONAL ACTIVATION; MALIGNANT TRANSFORMATION; DEPENDENT ACTIVATION; SIGNALING PATHWAY AB Receptors coupled to heterotrimeric G proteins can effectively stimulate growth promoting pathways in a large variety of cell types, and if persistently activated, these receptors can also behave as dominant-acting oncoproteins, Consistently, activating mutations for G proteins of the G alpha(s) and G alpha(i2) families were found in human tumors; and members of the G alpha(q) and G alpha(12) families are fully transforming when expressed in murine fibroblasts. In an effort aimed to elucidate the molecular events involved in proliferative signaling through heterotrimeric G proteins we have focused recently on gene expression regulation, Using NIH 3T3 fibroblasts expressing mi muscarinic acetylcholine receptors as a model system, we have observed that activation of this transforming G protein-coupled receptors induces the rapid expression of a variety of early responsive genes, including the c-fos protooncogene, One of the c-fos promoter elements, the serum response element (SRE), plays a central regulatory role, and activation of SRE-dependent transcription has been found to be regulated by several proteins, including the serum response factor and the ternary complex factor, With the aid of reporter plasmids for gene expression, we observed here that stimulation of m1 muscarinic acetylcholine receptors potently induced SRE-driven reporter gene activity in NIH 3T3 cells, In these cells, only the G alpha(12) family of heterotrimeric G protein alpha subunits strongly induced the SRE, while G beta(1) gamma(2) dimers activated SRE to a more limited extent, Furthermore, our study provides strong evidence that m1, G alpha(12) and the small GTP-binding protein RhoA are components of a novel signal transduction pathway that leads to the ternary complex factor-independent transcriptional activation of the SRE and to cellular transformation. C1 NIDR,ORAL & PHARYNGEAL CANC BRANCH,NIH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 40 TC 177 Z9 179 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 16 PY 1997 VL 94 IS 19 BP 10098 EP 10103 DI 10.1073/pnas.94.19.10098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX399 UT WOS:A1997XX39900019 PM 9294169 ER PT J AU Yurchenco, PD Quan, Y Colognato, H Mathus, T Harrison, D Yamada, Y ORear, JJ AF Yurchenco, PD Quan, Y Colognato, H Mathus, T Harrison, D Yamada, Y ORear, JJ TI The alpha chain of laminin-1 is independently secreted and drives secretion of its beta- and gamma-chain partners SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE basement membrane; recombinant protein; coiled-coil ID MULTIDOMAIN PROTEIN; HEPARIN-BINDING; SHORT-ARM; B-CHAINS; A-CHAIN; EXPRESSION; SUBUNITS; DOMAINS; SITES; GLYCOPROTEIN AB A mammalian recombinant strategy,vas established to dissect rules of basement membrane laminin assembly and secretion, The alpha-, beta-, and gamma-chain subunits of laminin-1 were expressed in all combinations, transiently and/or stably, in a near-null background. In the absence of its normal partners, the alpha chain was secreted as intact protein and protein that had been cleaved in the coiled-coil domain. In contrast, the beta and gamma chains, expressed separately or together, remained intracellular with formation of beta beta or beta gamma, but not gamma gamma, disulfide-linked dimers, Secretion of the beta and gamma chains required simultaneous expression of all three chains and their assembly into alpha beta gamma heterotrimers. Epitope-tagged recombinant alpha subunit and recombinant laminin were affinity-purified from the conditioned medium of alpha gamma and alpha beta gamma clones, Rotary-shadow electron microscopy revealed that the free alpha subunit is a linear structure containing N-terminal and included globules with a foreshortened long arm, while the trimeric species has the typical four-arm morphology of native laminin, We conclude that the alpha chain can be delivered to the extracellular environment as a single subunit, whereas the beta and gamma chains cannot, and that the alpha chain drives the secretion of the trimeric molecule, Such an alpha-chain-dependent mechanism could allow for the regulation of laminin export into a nascent basement membrane, and might serve an important role in controlling basement membrane formation. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MOL GENET & MICROBIOL,PISCATAWAY,NJ 08854. NIDR,NIH,BETHESDA,MD 20892. RP Yurchenco, PD (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PATHOL & LAB MED,675 HOES LANE,PISCATAWAY,NJ 08854, USA. FU NIDDK NIH HHS [R01-DK36425, R01 DK036425] NR 28 TC 101 Z9 102 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 16 PY 1997 VL 94 IS 19 BP 10189 EP 10194 DI 10.1073/pnas.94.19.10189 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX399 UT WOS:A1997XX39900035 PM 9294185 ER PT J AU DeMaria, A Ferraris, A Guastella, M Pilia, S Cantoni, C Polero, L Mingari, MC Bassetti, D Fauci, AS Moretta, L AF DeMaria, A Ferraris, A Guastella, M Pilia, S Cantoni, C Polero, L Mingari, MC Bassetti, D Fauci, AS Moretta, L TI Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: Impairment of specific cytolytic functions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MHC CLASS-I; RECOGNITION; CLONES; AIDS; MOLECULES; INFECTION; SUBSETS; P58; EXPANSION; ANTIGENS AB Human T lymphocytes have been shown to express inhibitory natural killer cell receptors (NKR), which can down-regulate T cell antigen receptor-mediated T cell function, including cytolytic activity, In the present study, we demonstrate that CD3+NKR+ cells can be identified in HIV-infected patients, HIV-specific cytolytic activity was analyzed in five patients in whom autologous lymphoblastoid B cell lines could be derived as a source of autologous target cells, Phytohemagglutinin-activated T cell populations that had been cultured in interleukin 2 displayed HIV-specific cytotoxic T lymphocyte (CTL) activity against HIV env, gag, pol, and nef in 3 of 5 patients, Addition of anti-NKR mAb of IgM isotype could increase the specific CTL activity, Moreover, in one additional patient, HIV-specific CTL activity was undetectable; however, after addition of anti-NKR mAb such CTL activity appeared ne novo. Similar results were obtained by analysis of CD3+NKR+ clones derived from two patients, These data provide direct evidence that CD3+NKR+ cells may include antigen (HIV)-specific CTLs and that mAb-mediated masking of inhibitory NKR may revert the down-regulation of CTL function. C1 ADV BIOTECHNOL CTR,IMMUNOPATHOL LAB,IST NAZL RIC CANC,I-16132 GENOA,ITALY. UNIV GENOA,DIPARTIMENTO ONCOL CLIN & SPERIMENTALE,I-16132 GENOA,ITALY. UNIV GENOA,CLIN MALATTIE INFETT 1,I-16132 GENOA,ITALY. UNIV GENOA,IST PATOL GEN,I-16132 GENOA,ITALY. NIH,BETHESDA,MD 20892. RI de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X NR 25 TC 94 Z9 95 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 16 PY 1997 VL 94 IS 19 BP 10285 EP 10288 DI 10.1073/pnas.94.19.10285 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XX399 UT WOS:A1997XX39900052 PM 9294202 ER PT J AU Curiel, RV Laurienzo, JM Unger, EF Panza, JA AF Curiel, RV Laurienzo, JM Unger, EF Panza, JA TI The magnitude of inotropic reserve is unrelated to basal systolic function or wall thickness in patients with chronic ischemic left ventricular dysfunction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; POSITRON EMISSION TOMOGRAPHY; HIBERNATING MYOCARDIUM; PREDICTING RECOVERY; REVASCULARIZATION; TL-201; IMPROVEMENT AB Forty-four patients with coronary artery disease and left ventricular dysfunction underwent transesophageal echocardiography with dobutamine infusion to investigate the relation between basal contractile function and inotropic reserve. No significant relation was observed between basal percent systolic thickening or diastolic thickness and the maximum increase in contractile function in response to dobutamine, thus emphasizing the heterogneity of the mechanisms by which coronary stenoses may affect contraction at rest and inotropic reserve in these patients. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NR 20 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 1997 VL 80 IS 6 BP 783 EP & PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XW491 UT WOS:A1997XW49100023 PM 9315591 ER PT J AU Troisi, R Potischman, N Hoover, RN Siiteri, P Brinton, LA AF Troisi, R Potischman, N Hoover, RN Siiteri, P Brinton, LA TI Insulin and endometrical cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body mass index; C-peptide; endometrial neoplasms; hyperinsulinism; sex hormones ID BODY-FAT DISTRIBUTION; HORMONE-BINDING GLOBULIN; POSTMENOPAUSAL WOMEN; STEROID-HORMONES; RISK-FACTORS; OBESITY; METABOLISM; HYPERINSULINEMIA AB Elevated insulin levels may explain part of the increased risk of endometrial cancer observed in obese postmenopausal women, Circulating sex hormones and fasting C-peptide levels were measured in sera obtained from 165 postmenopausal endometrial cancer cases accrued between June 1, 1987, and May 15, 1990, from hospitals in Chicago, Illinois; Hershey, Pennsylvania; irvine and Long Beach, California; Minneapolis, Minnesota; and Winston-Salem, North Carolina, and 180 community and hysterectomy controls. Women with a personal history of diabetes were excluded. Among controls, C-peptide was positively correlated with body mass index (BMI) ((r = 0,44), waist-to-thigh circumference ratio ((r = 0.24), estrone ((r = 0.18), and estradiol ((r = 0.28) (albumin-bound (r = 0,45), and free (r = 0.37)) and negatively correlated with sex hormone-binding globulin (r = -0,48). In age-adjusted analyses, the odds ratios and 95% confidence intervals for tertiles of C-peptide and endometrial cancer were, from lowest to highest: 1,0 (reference), 0.78 (95% confidence interval (CI) 0,43-1.4), and 2.2 (95% CI 1.3-3.7). Further adjustment for BMI substantially attenuated the odds ratios for the highest tertile of C-peptide (odds ratio = 1.2, 95% CI 0.63-2.1), and adjustment for body mass index and other risk factors for endometrial cancer eliminated the association (odds ratio = 1,0, 95% CI 0.55-2.0). In contrast, adjustment for C-peptide had little influence on the magnitude of the positive associations between body mass index (odds ratio for highest vs, lowest tertile, without and with adjustment far C-peptide = 4.1 (95% CI 2.3-7.5) and 3.7 (95% CI 1,9-7.1), respectively) or several steroid hormones and endometrial cancer. These data are not consistent with the hypothesis that the effect of obesity on endometrial cancer risk is mediated through high insulin levels. RP Troisi, R (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN ROOM 443,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 22 TC 57 Z9 62 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1997 VL 146 IS 6 BP 476 EP 482 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XV263 UT WOS:A1997XV26300003 PM 9290508 ER PT J AU Chambless, LE Heiss, G Folsom, AR Rosamond, W Szklo, M Sharrett, AR Clegg, LX AF Chambless, LE Heiss, G Folsom, AR Rosamond, W Szklo, M Sharrett, AR Clegg, LX TI Association of Coronary Heart Disease incidence with carotid arterial wall thickness and major risk factors: The Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carotid arteries; coronary disease; incidence; risk factors; ultrasonography ID INTIMA-MEDIA THICKNESS; B-MODE ULTRASOUND; PREVALENT CARDIOVASCULAR-DISEASE; HYPERCHOLESTEROLEMIC MEN; PHYSICAL-ACTIVITY; SHORT-TERM; VARIABILITY; SMOKING; LIPIDS; ULTRASONOGRAPHY AB Few studies have determined whether greater carotid artery intima-media thickness (IMT) in asymptomatic individuals is associated prospectively with increased risk of coronary heart disease (CHD). In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measurements at six sites of the carotid arteries using B-mode ultrasound. The authors assessed its relation to CHD incidence over 4-7 years of follow-up (1987-1993) in four US communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland) from samples of 7,289 women and 5,552 men aged 45-64 years who were free of clinical CHD at baseline. There were 96 incident events for women and 194 for men. In sex-specific Cox proportional hazards models adjusted only for age, race, and center, the hazard rate ratio comparing extreme mean IMT(greater than or equal to 1 mm) to not extreme (<1 mm) was 5.07 for women (95% confidence interval 3.08-8.36) and 1.85 for men (95% confidence interval 1.28-2.69). The relation was graded (monotonic), and models with cubic splines indicated significant nonlinearity. The strength of the association was reduced by including major CHD risk factors, but remained elevated at higher IMT. Up to 1 mm mean IMT, women had lower adjusted annual event rates than did men, but above 1 mm their event rate was closer to that of men. Thus, mean carotid IMT is a noninvasive predictor of future CHD incidence. C1 UNIV N CAROLINA, SCH PUBL HLTH, DEPT EPIDEMIOL, CHAPEL HILL, NC 27514 USA. UNIV MINNESOTA, SCH PUBL HLTH, DIV EPIDEMIOL, MINNEAPOLIS, MN 55455 USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, BALTIMORE, MD USA. NHLBI, BETHESDA, MD 20892 USA. RP Chambless, LE (reprint author), UNIV N CAROLINA, SCH PUBL HLTH, DEPT BIOSTAT, CHAPEL HILL, NC 27514 USA. FU NHLBI NIH HHS [N01-HC-55016, N01-HC-55015, N01-HC-55018] NR 66 TC 1207 Z9 1256 U1 2 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1997 VL 146 IS 6 BP 483 EP 494 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XV263 UT WOS:A1997XV26300004 PM 9290509 ER PT J AU Borkowf, CB Gail, MH AF Borkowf, CB Gail, MH TI On measures of agreement calculated from contingency tables with categories defined by the empirical quantiles of the marginal distributions SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE epidemiologic methods; nutrition surveys; questionnaires; statistics ID DIETARY ASSESSMENT INSTRUMENTS; FOOD FREQUENCY QUESTIONNAIRE; REPRODUCIBILITY; VALIDITY; KAPPA AB Epidemiologists sometimes collect bivariate continuous data on a number of subjects, compute the empirical (sample) quantiles of the marginal data, and then use these values to partition the original data into two-way contingency tables, Tables created in this manner have row and column categories defined by the random empirical marginal quantiles rather than by preset cutpoints, so these tables have fixed marginal totals. Hence, instead of the conventional multinomial distribution, these tables have the empirical bivariate quantile-partitioned (EBQP) distribution, In this paper, the authors demonstrate how to use empirical methods appropriate for EBQP tables to make inferences and construct confidence intervals for three commonly used measures of agreement: kappa, weighted kappa, and another class of measures derived from conditional proportions in the extreme rows of the table. They also show that if one incorrectly applies conventional methods appropriate for multinomial tables to statistics calculated from EBQP tables, one can obtain substantially misleading results. In addition, the authors present alternative parametric methods for estimating these measures of agreement and illustrate corresponding methods of inference and confidence interval construction, Finally, they show that these empirical (EBQP) methods can have low efficiency compared with parametric methods for some of these measures of agreement. C1 NCI,DIV CANC EPIDEMIOL & GENET,BIOSTAT BRANCH,BETHESDA,MD 20892. NR 17 TC 4 Z9 4 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1997 VL 146 IS 6 BP 520 EP 526 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XV263 UT WOS:A1997XV26300008 PM 9290513 ER PT J AU Korn, EL Graubard, BI Midthune, D AF Korn, EL Graubard, BI Midthune, D TI Time-to-event analysis of longitudinal follow-up of a survey: Choice of the time-scale - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 NCI,BIOMETRY BRANCH,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. RP Korn, EL (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 1 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1997 VL 146 IS 6 BP 529 EP 529 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XV263 UT WOS:A1997XV26300012 ER PT J AU DeChristoforo, R Minor, JR AF DeChristoforo, R Minor, JR TI AIDs buyers' clubs SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 GLAXO WELLCOME INC,ANTIVIRALS STRATEG INFORMAT DEPT,US MED AFFAIRS,RES TRIANGLE PK,NC 27709. RP DeChristoforo, R (reprint author), NIH,CLIN PHARM SECT,DEPT PHARM,WARREN G MAGNUSON CLIN CTR,BLDG 10,ROOM 1N257,10 CTR DR,MSC-1196,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD SEP 15 PY 1997 VL 54 IS 18 BP 2122 EP 2124 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XZ322 UT WOS:A1997XZ32200015 PM 9377212 ER PT J AU Colley, WC Altshuller, YM SueLing, CK Copeland, NG Gilbert, DJ Jenkins, NA Branch, KD Tsirka, SE Bollag, RJ Bollag, WB Frohman, MA AF Colley, WC Altshuller, YM SueLing, CK Copeland, NG Gilbert, DJ Jenkins, NA Branch, KD Tsirka, SE Bollag, RJ Bollag, WB Frohman, MA TI Cloning and expression analysis of murine phospholipase D1 SO BIOCHEMICAL JOURNAL LA English DT Article ID PHOSPHATIDIC-ACID; LYSOPHOSPHATIDIC ACID; MOUSE; RIBOSYLATION; CELLS; GENE; STIMULATION; ACTIVATION; FAMILY; SITE AB Activation of phosphatidylcholine-specific phospholipase D (PLD) occurs as part of the complex signal-transduction cascade initiated by agonist stimulation of tyrosine kinase and G-protein-coupled receptors. A variety of mammalian PLD activities have been described, and cDNAs for two PLDs recently reported (human PLD 1 and murine PLD2). We describe here the cloning and chromosomal localization of murine PLD1. Northern-blot hybridization and RNase protection analyses were used to examine the expression of murine PLD1 and PLD2 in a variety of cell lines and tissues. PLD1 and PLD2 were expressed in all RNA samples examined, although the absolute expression of each isoform varied, as well as the ratio of PLD1 to PLD2. Moreover, in situ hybridization of adult brain and murine embryo sections revealed high levels of expression of individual PLDs in some cell types and no detectable expression in others. Thus the two PLDs probably carry out distinct roles in restricted subsets of cells rather than ubiquitous roles in all cells. C1 SUNY STONY BROOK,DEPT PHARMACOL SCI,GENET PROGRAM,STONY BROOK,NY 11794. MED COLL GEORGIA,INST MOL & MED GENET,AUGUSTA,GA 30912. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. SUNY STONY BROOK,INST CELL & DEV BIOL,STONY BROOK,NY 11794. FU NICHD NIH HHS [HD29758]; NINDS NIH HHS [NS35843] NR 41 TC 108 Z9 111 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 15 PY 1997 VL 326 BP 745 EP 753 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX017 UT WOS:A1997XX01700017 PM 9307024 ER PT J AU Stahl, SJ Wingfield, PT Kaufman, JD Pannell, LK Cioce, V Sakata, H Taylor, WG Rubin, JS Bottaro, DP AF Stahl, SJ Wingfield, PT Kaufman, JD Pannell, LK Cioce, V Sakata, H Taylor, WG Rubin, JS Bottaro, DP TI Functional and biophysical characterization of recombinant human hepatocyte growth factor isoforms produced in Escherichia coli SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN SECONDARY STRUCTURE; C-MET RECEPTOR; FACTOR SCATTER FACTOR; CIRCULAR-DICHROISM; MOLECULAR-CLONING; PROTOONCOGENE PRODUCT; HUMAN-PLASMINOGEN; EPITHELIAL-CELLS; IDENTIFICATION; DOMAIN AB Hepatocyte growth factor (HGF) is a pluripotent secreted protein that stimulates a wide array of cellular targets, including hepatocytes and other epithelial cells, melanocytes, endothelial and haematopoietic cells. Multiple mRNA species transcribed from a single HGF gene encode at least three distinct proteins: the full-length HGF protein and two truncated HGF isoforms that encompass the N-terminal(Nf domain through kringle 1 (NK1) or through kringle 2 (NK2), We report the high-level expression in Escherichia call of NK1 and NK2, as well as the individual kringle 1 (K1) and N domains of HGF. All proteins accumulated as insoluble aggregates that were solubilized, folded and purified in high yield using a simple procedure that included two gelfiltration steps. Characterization of the purified proteins indicated chemical and physical homogeneity, and analysis by CD suggested native conformations, Although the K1 and N-terminal domains of HGF have limited biological activity, spectroscopic evidence indicated that the conformation of each matched that observed when the domains were components of biologically active NK1. Both NK1 and NK2 produced in bacteria were functionally equivalent to proteins generated by eukaryotic systems, as indicated by mitogenicity, cell scatter, and receptor binding and activation assays. These data indicate that all four bacterially produced HGF derivatives are well suited for detailed structural analysis. C1 NIAMSD, PROT EXPRESS LAB, NIH, BETHESDA, MD 20892 USA. NIDDKD, STRUCT MASS SPECTROMETRY GRP, LAC, BETHESDA, MD 20892 USA. NCI, CELLULAR & MOL BIOL LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 58 TC 44 Z9 46 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 15 PY 1997 VL 326 BP 763 EP 772 PN 3 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XX017 UT WOS:A1997XX01700019 PM 9307026 ER PT J AU Lieberman, J Skolnik, PR Parkerson, GR Fabry, JA Landry, B Bethel, J Kagan, J Atkins, MB Gradon, J Stein, D ViraniKetter, N Banach, M Scott, M Meyers, J Lee, E Standiford, H Fong, DM Wang, A Beyer, D AF Lieberman, J Skolnik, PR Parkerson, GR Fabry, JA Landry, B Bethel, J Kagan, J Atkins, MB Gradon, J Stein, D ViraniKetter, N Banach, M Scott, M Meyers, J Lee, E Standiford, H Fong, DM Wang, A Beyer, D TI Safety of autologous, ex vivo expanded human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients SO BLOOD LA English DT Article ID PERIPHERAL-BLOOD; CELL CLONES; SEROPOSITIVE INDIVIDUALS; ADOPTIVE IMMUNOTHERAPY; DISEASE PROGRESSION; TYPE-1 INFECTION; AIDS VIRUS; RESPONSES; MICE; INTERLEUKIN-2 AB We infused six human immunodeficiency virus (HIV)-seropositive subjects with autologous CD8(+) cytotoxic T cells (CTLs) enriched for HIV-specific cytotoxicity targeted against a diversity of HIV epitopes in gp120, gag p17 and p24, and nef. There was no toxicity and no subject deteriorated clinically, In the first 2 weeks, CD4 counts increased for all subjects and plasma viremia decreased in five of six subjects. Twenty-four weeks later, the mean values of all measures of viral burden and surrogate markers of HIV infection were either unchanged or improved, but none of the changes was statistically significant. Two subjects continued to have decreased cell-associated viral burden and another subject had more than doubled CD4 cell count, HIV-specific CTL activity increased in most subjects, The increase in CD4 T-cell counts in the first weeks after the infusion suggests that antiviral CTLs of diverse specificities do not play a significant role in CD4 T-cell decline. The lack of any acute toxicity or adverse effect on viral burden suggests that therapy with antiviral CTLs deserves further study. (C) 1997 by The American Society of Hematology. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,DIV HEMATOL & ONCOL,BOSTON,MA 02111. WESTAT CORP,ROCKVILLE,MD. NIAID,ROCKVILLE,MD. RP Lieberman, J (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Lieberman, Judy/A-2717-2015 FU NCI NIH HHS [K08-CA01449]; NIAID NIH HHS [U19-AI36611]; PHS HHS [N01-A115123] NR 48 TC 52 Z9 57 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1997 VL 90 IS 6 BP 2196 EP 2206 PG 11 WC Hematology SC Hematology GA XW306 UT WOS:A1997XW30600008 PM 9310470 ER PT J AU Marcantonio, D Panasci, LC Hollingshead, MG Alley, MC Camalier, RF Sausville, EA Dykes, DJ Carter, CA Malspeis, L AF Marcantonio, D Panasci, LC Hollingshead, MG Alley, MC Camalier, RF Sausville, EA Dykes, DJ Carter, CA Malspeis, L TI 2-chloroethyl-3-sarcosinamide-1-nitrosourea novel chloroethylnitrosourea analogue with enhanced antitumor activity against human glioma xenografts SO CANCER RESEARCH LA English DT Article ID AMINO-ACID AMIDES; CLINICAL-TRIAL; (2-CHLOROETHYL)-3-SARCOSINAMIDE-1-NITROSOUREA; RADIOTHERAPY; CYTOTOXICITY; CONGENERS; TRANSPORT; SK-MG-1; CARRIER; SYSTEM AB Nitrosoureas are among the most widely used agents used in the treatment of malignant gliomas, Here, the activity of 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) was compared with that of 1,3-bis-(2-chloroethyl) -1-nitrosourea (BCNU), in vivo against s.c. implanted SF-295 and U-251 central nervous system (CNS) tumor xenografts. When given i.v., q4d for 3 doses, to athymic mice bearing s.c. SF-295 tumors, SarCNU, at an optimum of 167 mg/kg/dose, produced 9 tumor-free animals of 10 total animals, 1 regression, and no evidence of overt toxicity (greater than or equal to 20% body weight loss). With a similar dosing schedule, BCNU produced no tumor-free animals, six regressions, and one drug-related death at its optimum of 30 mg/kg/dose. Furthermore, SarCNU retained high antitumor activity at two lower dose levels, 66 and 45% of the optimal dose, whereas BCNU demonstrated a progressive loss of antitumor activity at lower doses. Following p.o. administration, SarCNU similarly demonstrated antitumor activity that was superior to that of BCNU, In the U-251 CNS tumor model, SarCNU yielded six of six tumor-free animals at 80 mg/kg/dose with i.p. administration q.d. for 5 days, starting on day 14, whereas BCNU, at 9 mg/kg/dose, yielded three of six tumor-free mice and one drug-related death. Again, SarCNU resulted in tumor-free animals at 66 and 45% of its optimal dose and was relatively nontoxic, in contrast to BCNU. Results of testing to date indicate that SarCNU is clearly more effective than BCNU against the human CNS tumors SF-295 and U-251 lit vivo. These results encourage the initiation of clinical trials for SarCNU, in an effort to improve therapeutic approaches to glioma, but clinical trials must determine whether superiority of SarCNU in preclinical models can be extrapolated to patients. C1 SIR MORTIMER B DAVIS JEWISH HOSP,LADY DAVIS INST MED RES,MONTREAL,PQ H3T 1E2,CANADA. FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT DIAG & CTR,DEV THERAPEUT PROGRAM,FREDERICK,MD 21701. SO RES INST,BIRMINGHAM,AL 35205. FU NCI NIH HHS [N01-CM-57207, N01-CM-47000] NR 18 TC 19 Z9 20 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1997 VL 57 IS 18 BP 3895 EP 3898 PG 4 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900005 PM 9307267 ER PT J AU Yoshiji, H Harris, SR Thorgeirsson, UP AF Yoshiji, H Harris, SR Thorgeirsson, UP TI Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells SO CANCER RESEARCH LA English DT Article ID TUMOR-GROWTH; PERMEABILITY FACTOR; PROGNOSTIC INDICATOR; MAMMALIAN-CELLS; ANGIOGENESIS; EXPRESSION; CANCER; INHIBITION; METASTASIS; RECEPTOR AB In this study, we used a self-contained tetracycline-regulated retroviral vector system to elucidate the role of vascular endothelial growth factor (VEGF) in controlling s.c. growth of human T-47D breast carcinoma cells. VEGF expression was tightly regulated by this system, both in vitro and in nude mouse xenografts. A 2.4-fold increase in tumor volume was associated with VEGF overexpression. Tumor growth was almost completely inhibited when VEGF was suppressed from the time of T-47D cell inoculation, and a 6-fold reduction in tumor volume was observed when VEGF suppression was started in 175-mm(3) tumors, However, no growth inhibition was observed when VEGF suppression was started in 820-mm(3) tumors, In these tumors, basic fibroblast growth factor and transforming growth factor alpha RNA expression was detected after VEGF was switched off. These findings demonstrate that VEGF is critical for the initial ss. growth of T-47D breast carcinoma cells, whereas other angiogenic factors can compensate for the loss of VEGF after the tumors have reached a certain size. C1 NCI,DIV BASIC SCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,TUMOR BIOL & CARCINOGENESIS SECT,BETHESDA,MD 20892. NR 21 TC 169 Z9 172 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1997 VL 57 IS 18 BP 3924 EP 3928 PG 5 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900011 PM 9307273 ER PT J AU Umar, A Koi, M Risinger, JI Glaab, WE Tindall, KR Kolodner, RD Boland, CR Barrett, JC Kunkel, TA AF Umar, A Koi, M Risinger, JI Glaab, WE Tindall, KR Kolodner, RD Boland, CR Barrett, JC Kunkel, TA TI Correction of hypermutability, N-methyl-N'-nitro-N-nitrosoguanidine resistance, and defective DNA mismatch repair by introducing chromosome 2 into human tumor cells with mutations in MSH2 and MSH6 SO CANCER RESEARCH LA English DT Article ID COLON-CARCINOMA-CELLS; MICROSATELLITE INSTABILITY; SACCHAROMYCES-CEREVISIAE; 3'-5' EXONUCLEASE; GENOME INSTABILITY; MUTATOR PHENOTYPES; DAMAGE TOLERANCE; POLYMERASE-DELTA; ACTIVE-SITE; LINES AB The human DNA mismatch repair genes hMSH2 and hMSH6 encode the proteins that, together, bind to mismatches to initiate repair of replication errors, Human tumor cells containing mutations in these genes have strongly elevated mutation rates in selectable genes and at microsatellite loci, although mutations in these genes cause somewhat different mutator phenotypes. These cells are also resistant to killing by certain drugs and are defective in mismatch repair, Because the elevated mutation rates in these cells may lead to mutations in additional genes that are causally related to the other defects, here we attempt to establish a cause-effect relationship between the hMSH2 and hMSH6 gene mutations and the observed phenotypes. The endometrial tumor cell line HEC59 contains mutations in both alleles of hMSH2. The colon tumor cell line HCT15 contains mutations in hMSH6 and also has a sequence change in a conserved region of the coding sequence for DNA polymerase delta, a replicative DNA polymerase, We introduced human chromosome 2 containing the wild-type hMSH2 and hMSH6 genes into HEC59 and HCT15 cells, Introduction of chromosome 2 to HEC59 cells restored microsatellite stability, sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine treatment, and mismatch repair activity, Transfer of chromosome 2 to HCT15 cells also reduced the mutation rate at the HPRT locus and restored sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine treatment and mismatch repair activity, The results demonstrate that the observed defects are causally related to mutations in genes on chromosome 2, probably hMSH2 or hMSH6, but are not related to sequence changes in other genes, including the gene encoding DNA polymerase delta. C1 NIEHS,GENET MOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULA GENET & MOL BIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULA TOXICOL,CHAPEL HILL,NC 27599. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. DANA FARBER CANC INST,CHARLES A DANA DIV HUMAN CANC GENET,BOSTON,MA 02115. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014 FU NCI NIH HHS [CA72851] NR 48 TC 148 Z9 148 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1997 VL 57 IS 18 BP 3949 EP 3955 PG 7 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900016 PM 9307278 ER PT J AU Fay, MP Freedman, LS Clifford, CK Midthune, DN AF Fay, MP Freedman, LS Clifford, CK Midthune, DN TI Effect of different types and amounts of fat on the development of mammary tumors in rodents: A review SO CANCER RESEARCH LA English DT Review ID SPRAGUE-DAWLEY RATS; 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED BREAST-CANCER; DIFFERENT DIETARY FATS; POLY-UNSATURATED FAT; FEMALE SD-RATS; N-NITROSOMETHYLUREA; CALORIC RESTRICTION; EICOSANOID SYNTHESIS; GLAND TUMORIGENESIS; SYNTHESIS INHIBITORS AB We performed a meta-analysis on data extracted from 97 reports of experiments, involving a total of 12,803 mice or rats, studying the effect on mammary tumor incidence of different types of dietary fatty acids, Fatty acids were categorized into saturated, monounsaturated, n-6 polyunsaturated, and n-3 polyunsaturated. We modeled the relation between tumor incidence and percentage of total calories from these fatty acids using conditional logistic regression and allowing for varying effects between experiments, and for each fatty acid we estimated the effect of substituting the fatty acid calories far nonfat calories. our results show that n-6 polyunsaturated fatty acids (PUFAs) have a strong tumor-enhancing effect and that saturated fats have a weaker tumor-enhancing effect, The n-3 PUFAs have a small protective effect that is not statistically significant. There is no significant effect of monounsaturated fats, n-6 PUFAs have a stronger tumor-enhancing effect at levels under 4% of total calories, but an effect is still present at intake levels greater than 4% of calories. In addition, when the intake of n-6 PUFAs is at least 4% of calories, the n-6 PUFA effect remains stronger than the saturated fat effect. C1 NCI, DIV CANC PREVENT & CONTROL, DIET & CANC BRANCH, BETHESDA, MD 20892 USA. INFORMAT MANAGEMENT SERV INC, SILVER SPRING, MD 20902 USA. RP Fay, MP (reprint author), NCI, DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH, EXECUT PLAZA N,SUITE 344, 6130 EXECUT BLVD MSC 735, BETHESDA, MD 20892 USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 137 TC 145 Z9 146 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1997 VL 57 IS 18 BP 3979 EP 3988 PG 10 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900020 PM 9307282 ER PT J AU Bjorge, T Hakulinen, T Engeland, A Jellum, E Koskela, P Lehtinen, M Luostarinen, T Paavonen, J Sapp, M Schiller, J Thoresen, S Wang, ZH Youngman, L Dillner, J AF Bjorge, T Hakulinen, T Engeland, A Jellum, E Koskela, P Lehtinen, M Luostarinen, T Paavonen, J Sapp, M Schiller, J Thoresen, S Wang, ZH Youngman, L Dillner, J TI A prospective, seroepidemiological study of the role of human papillomavirus in esophageal cancer in Norway SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; CERVICAL INTRAEPITHELIAL NEOPLASIA; 18 MAJOR CANCERS; SERUM ANTIBODIES; TYPE-16 INFECTION; HPV DNA; ASSOCIATION; COTININE; CAPSIDS; RISK AB Infection with the human papillomavirus (HPV), notably HPV type 16, has been associated with esophageal cancer in seroepidemiological studies. To evaluate the consistency of the association, we performed a nested case-control study of HPV seropositivity and risk of esophageal cancer within a prospectively followed cohort of 300,000 Norwegian men and women who had donated blood samples to a serum bank. The data file of the serum bank was linked with the nationwide Cancer Registry of Norway to identify esophageal cancers diagnosed after donation of the serum sample. Fifty-seven cases and 171 matched controls were analyzed for antibodies to specific microorganisms, and odds ratios for developing esophageal cancer were calculated. There was an increased risk of developing esophageal cancer among HPV 16-seropositive subjects (odds ratio = 6.6; 95% confidence interval, 1.1-71) but not among Chlamydia trachomatis-seropositive subjects. Adjustment for the presence of serum cotinine, a marker of smoking habits, did not affect the estimates substantially. The seroepidemiological association between HPV 16 and esophageal cancer seems to be consistent in different countries. C1 NORWEGIAN RADIUM HOSP,DEPT GYNECOL ONCOL,N-0310 OSLO,NORWAY. KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. NATL PUBL HLTH INST,DEPT INFECT DIS & EPIDEMIOL,SF-00300 HELSINKI,FINLAND. NATL PUBL HLTH INST,OULU 90101,FINLAND. UNIV HELSINKI,DEPT PUBL HLTH,HELSINKI 00014,FINLAND. NORWEGIAN CANC SOC,JANUS COMM,N-0369 OSLO,NORWAY. FINNISH CANC REGISTRY,INST STAT & EPIDEMIOL CANC RES,FIN-00170 HELSINKI,FINLAND. UNIV HELSINKI HOSP,DEPT OBSTET & GYNECOL,HELSINKI 00290,FINLAND. UNIV MAINZ,DEPT MED MICROBIOL,D-55101 MAINZ,GERMANY. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. UNIV OXFORD,CLIN TRIAL SERV UNIT,OXFORD OX2 6HE,ENGLAND. RP Bjorge, T (reprint author), CANC REGISTRY NORWAY,INST EPIDEMIOL CANC RES,MONTEBELLO,N-0310 OSLO,NORWAY. NR 31 TC 57 Z9 59 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1997 VL 57 IS 18 BP 3989 EP 3992 PG 4 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900021 PM 9307283 ER PT J AU Shao, RG Cao, CX Shimizu, T OConnor, PM Kohn, KW Pommier, Y AF Shao, RG Cao, CX Shimizu, T OConnor, PM Kohn, KW Pommier, Y TI Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-O1) in human cancer cell lines, possibly influenced by p53 function SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; CYCLIN-DEPENDENT KINASES; DNA CLEAVABLE COMPLEXES; SELECTIVE INHIBITOR; TOPOISOMERASE-I; ANTITUMOR-ACTIVITY; REPLICATION FORKS; CARCINOMA CELLS; G2 ARREST; DAMAGE AB 7-Hydroxystaurosporine (UCN-01) is a selective protein kinase C inhibitor in clinical trial for cancer treatment, In this study, we found that nanomolar concentrations of camptothecin (CPT), a topoisomerase I inhibitor, arrest or delay cell cycle progression during the S and G(2) phases in p53 mutant human colon carcinoma HT29 cells and that UCN-01 abrogates the S-phase arrest or delay induced by CPT, Under these conditions, CPT increased cyclin A levels and cyclin A/cyclin-dependent kinase 2 activity, UCN-01 prevented the increase of cyclin A/cyclin-dependent kinase 2 activity induced by CPT and enhanced Cdc2 kinase activity. Replication protein A (RPA2) was hyperphosphorylated after CPT treatment, and this effect was also abrogated by UCN-01, UCN-01 potentiated the cytotoxicity of CPT and reduced by 6-fold the concentration of CPT required to kill 50% of the HT-29 cells, as determined by clonogenic assays, This effect was observed at concentrations of UCN-01 that alone were not cytotoxic and had no detectable effect on cell cycle progression, UCN-01 markedly potentiated the cytotoxicity of CPT also in HCT116/E6 and MCF-7/ADR cells defective for p53 function, whereas significantly less potentiation was observed in p53-wild-type HCT116 and MCF-7 cells, These results suggest the existence of an S-phase checkpoint that delays replication and that may extend the time available for DNA repair, Thus, pharmacological abrogation of CPT-induced S-and G,phase checkpoints by UCN-01 may provide an effective strategy for enhancing the chemotherapeutic activity of CPT, particularly against p53-defective tumors. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 40 TC 243 Z9 252 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1997 VL 57 IS 18 BP 4029 EP 4035 PG 7 WC Oncology SC Oncology GA XV559 UT WOS:A1997XV55900027 PM 9307289 ER PT J AU Alimandi, M Wang, LM Bottaro, D Lee, CC Kuo, A Frankel, M Fedi, P Tang, C Lippman, M Pierce, JH AF Alimandi, M Wang, LM Bottaro, D Lee, CC Kuo, A Frankel, M Fedi, P Tang, C Lippman, M Pierce, JH TI Epidermal growth factor and betacellulin mediate signal transduction through co-expressed ErbB2 and ErbB3 receptors SO EMBO JOURNAL LA English DT Article DE betacellulin; epidermal growth factor; ErbB2 receptor; ErbB3 receptor; signal transduction ID NEU DIFFERENTIATION FACTOR; MAMMARY EPITHELIAL-CELLS; EGF-RECEPTOR; FACTOR-ALPHA; BREAST-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; EXTRACELLULAR DOMAIN; HEMATOPOIETIC-CELLS; CELLULAR-RESPONSE; CARCINOMA-CELLS AB Interleukin-3 (IL-3)-dependent murine 32D cells do not detectably express epidermal growth factor receptors (EGFRs) and do not proliferate in response to EGF, heregulin (HRG) or other known EGF-like ligands, Here, we report that EGF specifically binds to and can be crosslinked to 32D transfectants co-expressing ErbB2 and ErbB3 (32D.E2/E3), but not to transfectants expressing either ErbB2 or ErbB3 individually. [I-125]EGF-crosslinked species detected in 32D.E2/E3 cells were displaced by HRG and betacellulin (ETC) but not by other EGF-like ligands that were analyzed. EGF, ETC and HRG also induced receptor tyrosine phosphorylation, activation of downstream signaling molecules and proliferation of 32D.E2/E3 cells. 32D transfectants were also generated which expressed an ErbB3-EGFR chimera alone (32D.E3-E1) or in combination with ErbB2 (32D.E2/E3-E1). While HRG stimulation of 32D.E3-E1 cells resulted in DNA synthesis and receptor phosphorylation, EGF and ETC were inactive. However, EGF and ETC were as effective as HRG in mediating signaling when ErbB2 was co-expressed with the chimera in the 32D.E2/E3-E1 transfectant. These results provide evidence that ErbB2/ErbB3 binding sites for EGF and ETC are formed by a previously undescribed mechanism that requires co-expression of two distinct receptors. Additional data utilizing MDA MB134 human breast carcinoma cells, which naturally express ErbB2 and ErbB3 in the absence of EGFRs, supported the results obtained employing 32D cells and suggest that EGF and ETC may contribute to the progression of carcinomas that co-express ErbB2 and ErbB3. C1 NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 64 TC 103 Z9 106 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 15 PY 1997 VL 16 IS 18 BP 5608 EP 5617 DI 10.1093/emboj/16.18.5608 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XY112 UT WOS:A1997XY11200014 PM 9312020 ER PT J AU Kang, JS Lee, HB Rhee, SG Park, K Yoo, OJ AF Kang, JS Lee, HB Rhee, SG Park, K Yoo, OJ TI The 5'-upstream region of the rat phospholipase C-beta 3 gene contains two critical Sp1 sites and an HIV Inr-like element SO GENE LA English DT Article DE promoter; TATA-less; transcription factor; housekeeping gene ID BOX-BINDING-PROTEINS; RNA POLYMERASE-II; C BETA-3 GENE; TRANSCRIPTION FACTORS; INITIATOR SEQUENCE; PROMOTER ACTIVITY; RECEPTOR GENE; CLONING; EXPRESSION; FAMILY AB The 5'-upstream region of the rat phospholipase C-beta 3 gene (PLC-beta 3) has been cloned and characterized. Sequence analysis of the 5'-upstream region showed that it contains a GC-rich region (-166 to +1:79%) and multiple binding sites for the transcription factors Sp1, AP-1 and AP-2, but does not contain a canonical TATA box. Primer extension analysis of total RNA isolated from rat glial cell C6Bu1 revealed that single transcription start point (tsp) is located at an initiator (Inr) element similar to that found in the HIV promoter. Gel mobility shift and competitive mobility shift assays indicated that this Inr element forms a DNA-protein complex with the HIV Inr-binding protein, LBP-1/CP2 or a homologue. In order to localize functional elements of the 5'-upstream region of the rat PLC-beta 3 gene, 5'-deletion fragments were cloned into a chloramphenicol acetyltransferase (CAT) reporter vector. Transient transfection analyses of the 5'-deletion mutants identified a crucial promoter element located at -128 to -14. Supershift mobility assays, site-directed mutagenesis and DNase I footprints indicated that Spl binds to three GC boxes within the sequence between -128 and -14 of the PLC-beta 3 promoter. Transient transfection analyses of promoter constructs containing site-specific mutation(s) of these three GC boxes demonstrated that two GC boxes, located proximal to the tsp, are important elements for normal promoter activity. (C) 1997 Elsevier Science B.V. C1 KOREA ADV INST SCI & TECHNOL,DEPT BIOL SCI,TAEJON 305701,SOUTH KOREA. CHONNAM NATL UNIV,COLL NAT SCI,DEPT BIOL,KWANGJU 500757,SOUTH KOREA. NHLBI,LAB CELL SIGNALING,BETHESDA,MD 20892. RI Yoo, Ook Joon/C-1860-2011 NR 35 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 15 PY 1997 VL 197 IS 1-2 BP 19 EP 28 DI 10.1016/S0378-1119(97)00213-8 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA XX866 UT WOS:A1997XX86600003 PM 9332346 ER PT J AU Park, JB Levine, M AF Park, JB Levine, M TI The human glutaredoxin gene: determination of its organization, transcription start point, and promoter analysis SO GENE LA English DT Article DE thioltransferase; dehydroascorbic acid; ascorbic acid ID RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE; HYDROGEN DONOR SYSTEM; HUMAN NEUTROPHILS; ASCORBIC-ACID; GLUTATHIONE; THIOLTRANSFERASE; PURIFICATION; THIOREDOXIN; CALF AB A genomic clone for the human glutaredoxin gene was isolated and sequenced. An intron was located within the coding region and began 211 nt downstream of the initiator codon. Except for this intron, the genomic sequence shares 100% identity to the published glutaredoxin cDNA sequence. A second intron was located in the 3' UTR 6 bp downstream of the terminator codon. The tsp of the glutaredoxin gene was determined by primer extension and confirmed by S1 mapping analysis. Analysis of the 5'-flanking region of the gene revealed that the promoter sequences TATA and CCAAT were 30 and 160 bp upstream, respectively, from the tsp. Other potential transcription factor binding sites included NF-E1, HNF-5, P2II and AP-1. Glutaredoxin promoter constructs inserted into a reporter plasmid for firefly luciferase were transfected into fibroblasts, and luciferase activity was 8-10-fold higher compared with controls lacking glutaredoxin promoter. These data indicate that the promoter region of the isolated glutaredoxin gene is functional. (C) 1997 Elsevier Science B.V. C1 NIDDKD,MOL & CLIN NUTR SECT,NIH,BETHESDA,MD 20892. NR 17 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 15 PY 1997 VL 197 IS 1-2 BP 189 EP 193 DI 10.1016/S0378-1119(97)00262-X PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XX866 UT WOS:A1997XX86600023 PM 9332366 ER PT J AU Kouprina, N Graves, J Cancilla, MR Resnick, MA Larionov, V AF Kouprina, N Graves, J Cancilla, MR Resnick, MA Larionov, V TI Specific isolation of human rDNA genes by TAR cloning SO GENE LA English DT Article DE human rDNA; YACs; transformation; TAR cloning ID YEAST ARTIFICIAL CHROMOSOMES; TRANSFORMATION-ASSOCIATED RECOMBINATION; TANDEMLY REPEATED DNA; HUMAN RIBOSOMAL DNA; MAMMALIAN GENOMES; SEQUENCE; FAMILY; CELLS; AMPLIFICATION; FRAGMENTS AB Selective cloning of human DNA in YACs from monochromosomal human/rodent hybrid cells lines and radiation hybrids can be accomplished by transformation-associated recombination (TAR) between Alu-containing vector(s) and human DNA in yeast. We have expanded this approach to the specific isolation of repetitive genes from the human genome. Highly selective isolation of human rDNA was accomplished using total human DNA and a pair of differentially marked linear TAR cloning vectors where one contained a small fragment of a human rDNA repeat and the other had an Alu repeat as targeting sequences. About half the transformants that acquired both vectors markers had YACs with human rDNA inserts. These results suggest that TAR can be applied to the general isolation of gene families and amplified region from genomic DNAs. (C) 1997 Elsevier Science B.V. RP Kouprina, N (reprint author), NIEHS,MOL GENET LAB,BOX 12233,RES TRIANGLE PK,NC 27709, USA. FU NHGRI NIH HHS [1-YO2-HG-60021-01] NR 35 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 15 PY 1997 VL 197 IS 1-2 BP 269 EP 276 DI 10.1016/S0378-1119(97)00271-0 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA XX866 UT WOS:A1997XX86600032 PM 9332375 ER PT J AU Balow, JE Shelton, DA Orsborn, A Mangelsdorf, M Aksentijevich, I Blake, T Sood, R Gardner, D Liu, R Pras, E Levy, EN Centola, M Deng, ZM Zaks, N Wood, G Chen, XG Richards, N Shohat, M Livneh, A Pras, M Doggett, NA Collins, FS Liu, PP Rotter, JI FischelGhodsian, N Gumucio, D Richards, RI Kastner, DL AF Balow, JE Shelton, DA Orsborn, A Mangelsdorf, M Aksentijevich, I Blake, T Sood, R Gardner, D Liu, R Pras, E Levy, EN Centola, M Deng, ZM Zaks, N Wood, G Chen, XG Richards, N Shohat, M Livneh, A Pras, M Doggett, NA Collins, FS Liu, PP Rotter, JI FischelGhodsian, N Gumucio, D Richards, RI Kastner, DL TI A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups SO GENOMICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; COLCHICINE THERAPY; ASHKENAZI JEWS; DOUBLE-BLIND; SHORT ARM; CHROMOSOME-16; AMYLOIDOSIS; POPULATIONS; INHERITANCE; FREQUENCY AB Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3, We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the similar to 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (similar to 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that same of these mutations arose before the affected Middle Eastern populations diverged from one another. (C) 1997 Academic Press. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,GRAD PROGRAM GENET,WASHINGTON,DC 20052. UNIV MICHIGAN,DEPT ANAT & CELL BIOL,ANN ARBOR,MI 48109. ADELAIDE WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOL GENET,ADELAIDE,SA 5006,AUSTRALIA. NATL HUMAN GENOME RES INST,LAB GENE TRANSFER,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,DEPT MED C,IL-52621 TEL HASHOMER,ISRAEL. CEDARS SINAI MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90048. CEDARS SINAI MED CTR,DEPT MED GENET,LOS ANGELES,CA 90048. BEILINSON MED CTR,DEPT MED GENET,IL-49100 PETAH TIQWA,ISRAEL. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. LOS ALAMOS NATL LAB,CTR HUMAN GENOME STUDIES,LOS ALAMOS,NM 87545. RI Liu, Paul/A-7976-2012; Mangelsdorf, Marie/A-2318-2013 OI Liu, Paul/0000-0002-6779-025X; Mangelsdorf, Marie/0000-0002-7855-7701 FU NIAMS NIH HHS [P60 AR20557] NR 30 TC 34 Z9 35 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 15 PY 1997 VL 44 IS 3 BP 280 EP 291 DI 10.1006/geno.1997.4860 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XY274 UT WOS:A1997XY27400004 PM 9325049 ER PT J AU Kostyu, DD Hannick, LI Traweek, JL Ghanayem, M Heilpern, D Dawson, DV AF Kostyu, DD Hannick, LI Traweek, JL Ghanayem, M Heilpern, D Dawson, DV TI HLA class I polymorphism: Structure and function and still questions SO HUMAN IMMUNOLOGY LA English DT Article DE HLA-A; HLA-B; HLA-C MHC class I; polymorphism ID T-CELL RECEPTOR; PEPTIDE BINDING; ALPHA-3 DOMAIN; HISTOCOMPATIBILITY ANTIGENS; INHIBITORY RECEPTOR; LYMPHOCYTES-T; B ALLELES; MOLECULES; SPECIFICITY; SURFACES AB The HLA-A, HLA-B and HLA-C molecules have turned out to be highly polymorphic and functionally complex. They not only serve as peptide receptors, but also interact with beta(2)-microglobulin, an alpha beta T cell receptor, CD8 and NK inhibitory molecules, all at different sites. The fact that more than 300 class I alleles have now been defined prompted us to ask the question of where polymorphism really occurs in a class I molecule. We have used a database of 275 HLA-A, HLA-B and HLA-C alleles to illustrate how extensive the polymorphism is. The data is presented here for comparison of alleles and allele families and to facilitate studies of class I structure and function. (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc. C1 Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. NIAID, Mol Struct Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Biostat & Epidemiol, Cleveland, OH 44106 USA. RP Kostyu, DD (reprint author), Duke Univ, Med Ctr, Dept Immunol, Box 3010, Durham, NC 27710 USA. FU NCRR NIH HHS [NCRR-RR03655]; NIDA NIH HHS [DAMD17-94-J-4467] NR 55 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP 15 PY 1997 VL 57 IS 1 BP 1 EP 18 DI 10.1016/S0198-8859(97)00175-4 PG 18 WC Immunology SC Immunology GA YN914 UT WOS:000071221400001 PM 9438190 ER PT J AU Deulofeut, H Robinson, MA AF Deulofeut, H Robinson, MA TI The human T cell receptor repertoire utilized in response to HBsAg SO HUMAN IMMUNOLOGY LA English DT Article ID HEPATITIS-B VACCINE; IMMUNE-RESPONSE; ALPHA-BETA; PEPTIDE; DIVERSITY; PATTERNS; CHAIN; COMPLEX; HLA-A2; REGION AB The complexity of the T cell receptor beta (TCRB) chain repertoire utilized in the recognition of recombinant hepatitis B surface antigen (HBsAg) was investigated. T cell lines were derived from two individuals vaccinated with Recombivax-HB and the TCRB repertoire was characterized by spectratype analysis, a molecular technology based on the differential size display of the complementarily determining region 3 (CDR3) of the TCRB chain. In contrast to the Gaussian distribution of CDR3 lengths observed for peripheral blood mononuclear cells (PBMCs), highly restricted patterns of CDR3 lengths were observed for most TCRB variable gene families in HBsAg-specific T cell lines (TCL). Although similarities in the repertoire of TCL derived from the two donors were noted, each TCL presented an unique profile of CDR3 length diversity. Among the TCR used by the two donors, no CDR3 sequence identity within or between TCRBV families was observed. Additionally, conservation of specific amino acids at homologous positions of the CDR3s was not evident. The T cell repertoire in response to HBsAg is oligoclonal, involves multiple TCRBV families and is individually specific. Human Immunology 57, 54-61 (1997). American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc. C1 NIAID, Human Immunogenet Res Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Robinson, MA (reprint author), NIAID, Human Immunogenet Res Sect, Immunogenet Lab, NIH, Room 217,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP 15 PY 1997 VL 57 IS 1 BP 54 EP 61 DI 10.1016/S0198-8859(97)00181-X PG 8 WC Immunology SC Immunology GA YN914 UT WOS:000071221400007 PM 9438196 ER PT J AU Wang, JW Niu, W Nikiforov, Y Naito, S Chernausek, S Witte, D LeRoith, D Strauch, A Fagin, JA AF Wang, JW Niu, W Nikiforov, Y Naito, S Chernausek, S Witte, D LeRoith, D Strauch, A Fagin, JA TI Targeted overexpression of IGF-I evokes distinct patterns of organ remodeling in smooth muscle cell tissue beds of transgenic mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE alpha actin; IGF binding proteins; hyperplasia; small-intestine; bladder ID GROWTH-FACTOR-I; ALPHA-ACTIN GENE; REGULATORY ELEMENTS; FUNCTIONAL PROMOTER; BALLOON DENUDATION; BINDING PROTEINS; ELEVATED LEVELS; FUSION GENES; SMALL-BOWEL; RAT AORTA AB Smooth muscle cells (SMC) of the vascular wall, bladder, myometrium, and gastrointestinal and respiratory tracts retain the ability to proliferate postnatally, which enables adaptive responses to injury, hormonal, or mechanical stimulation. SMC growth is regulated by a number of mesenchymal growth factors, including insulin-like growth factor I (IGF-I). To explore the function of IGF-I on SMC in vivo, the mouse SMC alpha-actin promoter fragment SMPS (-1074 bp, 63 bp of 5'UT and 2.5 kb of intron 1) was cloned upstream of rat IGF-I cDNA, and the fusion gene microinjected to fertilized eggs of the FVB-N mouse strain. Mating of hemizygous mice with controls produced about 50% transgenic offspring, with equal sex distribution. Transgenic IGF-I mRNA expression was confined to SMC-containing tissues, with the following hierarchy: bladder > stomach > aorta = uterus > intestine. There was no transgene expression in skeletal muscle, heart, or liver. Radioimmunoassayable IGF-I content was increased by 3.5- to 4-fold in aorta, and by almost 10-fold in bladder of transgenic mice at 5 and 10 wk, with no change in plasma IGF-I levels. Wet weight of bladder, stomach, intestine, uterus, and aorta was selectively increased, with no change in total body or carcass weight of transgenic animals. In situ hybridization showed that transgene expression was exquisitely targeted to the smooth muscle layers of the arteries, veins, bladder, ureter, stomach, intestine, and uterus. Paracrine overproduction of IGF-I resulted in hyperplasia of the muscular layers of these tissues, manifesting in remarkably different phenotypes in the various SMC beds. Whereas the muscular layer of the bladder and stomach exhibited a concentric thickening, the SMC of the intestine and uterus grew in a longitudinal fashion, resulting in a marked lengthening of the small bowel and of the uterine horns. This report describes the first successful targeting of expression of any functional protein capable of modifying the phenotype of SMC in transgenic mice. IGF-I stimulates SMC hyperplasia, Ieading to distinct patterns of organ remodeling in the different tissue environments. C1 UNIV CINCINNATI,COLL MED,DIV ENDOCRINOL & METAB,CINCINNATI,OH 45267. UNIV CINCINNATI,DIV PEDIAT ENDOCRINOL,CINCINNATI,OH 45267. UNIV CINCINNATI,DIV PEDIAT PATHOL,CINCINNATI,OH 45267. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. OHIO STATE UNIV,DEPT CELL BIOL NEUROBIOL & ANAT,COLUMBUS,OH 43210. FU NHLBI NIH HHS [HL43802] NR 56 TC 148 Z9 148 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1997 VL 100 IS 6 BP 1425 EP 1439 DI 10.1172/JCI119663 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XY730 UT WOS:A1997XY73000013 PM 9294108 ER PT J AU Schoneberg, T Sandig, V Wess, J Gudermann, T Schultz, G AF Schoneberg, T Sandig, V Wess, J Gudermann, T Schultz, G TI Reconstitution of mutant V2 vasopressin receptors by adenovirus-mediated gene transfer - Molecular basis and clinical implication SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE nephrogenic diabetes insipidus; vasopressin receptor; gene therapy; receptor mutagenesis; receptor folding ID NEPHROGENIC DIABETES-INSIPIDUS; LUTEINIZING-HORMONE RECEPTOR; FUNCTIONAL RESCUE; ADENYLYL-CYCLASE; IN-VIVO; EXPRESSION; BINDING; MUTATIONS; EFFICIENT; INVIVO AB Recent studies with transfected COS-7 cells have shown that functionally inactive mutant V2 vasopressin receptors (occurring in patients with nephrogenic diabetes insipidus) can be functionally rescued by coexpression of a carboxyterminal V2 receptor fragment (V2-tail) spanning the region where various mutations occur [Schoneberg, T., J. Yun, D, Wenkert, and J, Wess, 1996. EMBO (fur, Mel. Biol. Organ.) J, 15:1283-1291]. In this study, we set out to characterize the underlying molecular mechanism, Using a coimmunoprecipitation strategy and a newly developed sandwich ELISA system, a direct and highly specific interaction between the mutant V2 vasopressin receptor proteins and the V2-tail polypeptide was demonstrated. To study the potential therapeutic usefulness of these findings, Chinese hamster ovary (CHO) cell lines stably expressing low levels of functionally inactive mutant V2 vasopressin receptors were created and infected with a recombinant adenovirus carrying the V2-tail gene fragment, After adenovirus infection, vasopressin gained the ability to stimulate cAMP formation with high potency and efficacy in all CHO cell clones studied. Moreover, adenovirus-mediated gene transfer also proved to be a highly efficient method for achieving expression of the V2-tail fragment (as well as the wild-type V2 receptor) in Madin-Darby canine kidney tubular cells, Taken together, these studies clarify the molecular mechanisms by which receptor fragments can restore function of mutationally inactivated G protein-coupled receptors and suggest that adenovirus-mediated expression of receptor fragments may lead to novel strategies for the treatment of a variety of human diseases. C1 MAX DELBRUCK CTR MOL MED, D-13122 BERLIN, GERMANY. NIDDK, BIOORGAN CHEM LAB, NIH, BETHESDA, MD 20892 USA. RP FREE UNIV BERLIN, INST PHARMAKOL, FACHBEREICH HUMANMED, THIELALLEE 69-73, D-14195 BERLIN, GERMANY. NR 41 TC 49 Z9 49 U1 1 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1997 VL 100 IS 6 BP 1547 EP 1556 DI 10.1172/JCI119678 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XY730 UT WOS:A1997XY73000028 PM 9294123 ER PT J AU Cohen, OJ Vaccarezza, N Lam, GK Baird, BF Wildt, K Murphy, PM Zimmerman, PA Nutman, TB Fox, CH Hoover, S Adelsberger, J Baseler, M Arthos, J Davey, RT Dewar, RL Metcalf, J Schwartzentruber, DJ Orenstein, JM Buchbinder, S Saah, AJ Detels, R Phair, J Rinaldo, C Margolick, JB Pantaleo, G Fauci, AS AF Cohen, OJ Vaccarezza, N Lam, GK Baird, BF Wildt, K Murphy, PM Zimmerman, PA Nutman, TB Fox, CH Hoover, S Adelsberger, J Baseler, M Arthos, J Davey, RT Dewar, RL Metcalf, J Schwartzentruber, DJ Orenstein, JM Buchbinder, S Saah, AJ Detels, R Phair, J Rinaldo, C Margolick, JB Pantaleo, G Fauci, AS TI Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HIV-1; disease progression; CC chemokine receptor 5; polymorphism; lymph nodes ID HUMAN-IMMUNODEFICIENCY-VIRUS; 7-TRANSMEMBRANE DOMAIN RECEPTOR; TYPE-1 INFECTION; LYMPHOID-TISSUE; NEF SEQUENCES; DISEASE; PROGRESSION; INDIVIDUALS; ENTRY; FUSION AB HIV-l-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HTV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HTV-1-infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCRS gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-l-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCRS wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1-infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. MOL HISTOL INC,GAITHERSBURG,MD 20879. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LAB VIRUS ISOLAT & SEROL,FREDERICK,MD 21701. NCI,SURG BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. SAN FRANCISCO AIDS OFF,CLIN STUDIES SECT,SAN FRANCISCO,CA 94102. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90095. NORTHWESTERN UNIV,SCH MED,COMPREHENS AIDS CTR,CHICAGO,IL 60611. UNIV PITTSBURGH,SCH PUBL HLTH,DEPT PATHOL,PITTSBURGH,PA 15261. HOP BEAUMONT,DIV INFECT DIS,CH-1011 LAUSANNE,SWITZERLAND. RP Cohen, OJ (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,10 CTR DR,MSC 1876,ROOM 11B13,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 61 TC 38 Z9 38 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1997 VL 100 IS 6 BP 1581 EP 1589 DI 10.1172/JCI119682 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XY730 UT WOS:A1997XY73000032 PM 9294127 ER PT J AU Mahata, SK OConnor, DT Mahata, M Yoo, SH Taupenot, L Wu, HJ Gill, BM Parmer, RJ AF Mahata, SK OConnor, DT Mahata, M Yoo, SH Taupenot, L Wu, HJ Gill, BM Parmer, RJ TI Novel autocrine feedback control of catecholamine release - A discrete chromogranin A fragment is a noncompetitive nicotinic cholinergic antagonist SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE chromogranin A; catestatin; acetylcholine; catecholamine; PC12 ID PARATHYROID CELL SECRETION; ADRENAL CHROMAFFIN CELLS; NERVE GROWTH-FACTOR; A-DERIVED PEPTIDE; PHEOCHROMOCYTOMA CELLS; MESSENGER-RNA; SUBSTANCE-P; PROHORMONE CONVERTASES; MOLECULAR-CLONING; CALCIUM AB Catecholamine secretory vesicle core proteins (chromogranins) contain an activity that inhibits catecholamine release, but the identity of the responsible peptide has been elusive. Size-fractionated chromogranins antagonized nicotinic cholinergic-stimulated catecholamine secretion; the inhibitor was enriched in processed chromogranin fragments, and was liberated from purified chromogranin A. Of 15 synthetic peptides spanning similar to 80% of chromogranin A, one (bovine chromogranin A(344-364) [RSMRLSFRARGYGFRGPGLQL], or catestatin) was a potent, dose-dependent (IC50 similar to 200 nM), reversible secretory inhibitor on pheochromocytoma and adrenal chromaffin cells, as well as noradrenergic neurites. An antibody directed against this peptide blocked the inhibitory effect of chromogranin A proteolytic fragments on nicotinic-stimulated catecholamine secretion. This region of chromogranin A is extensively processed within chromaffin vesicles in vivo. The inhibitory effect was specific for nicotinic cholinergic stimulation of catecholamine release, and was shared by this chromogranin A region from several species. Nicotinic cationic (Na+, Ca2+) signal transduction was specifically disrupted by catestatin. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. This small domain within chromogranin A may contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release from chromaffin cells and neurons. C1 UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,CTR GENET MOL,SAN DIEGO,CA 92161. DEPT VET AFFAIRS MED CTR,LA JOLLA,CA 92161. NATL INST DEAFNESS & COMMUNICAT DISORDERS,NIH,BETHESDA,MD 20892. NR 67 TC 252 Z9 262 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1997 VL 100 IS 6 BP 1623 EP 1633 DI 10.1172/JCI119686 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XY730 UT WOS:A1997XY73000036 PM 9294131 ER PT J AU Castelli, JC Hassel, BA Wood, KA Li, XL Amemiya, K Dalakas, MC Torrence, PF Youle, RJ AF Castelli, JC Hassel, BA Wood, KA Li, XL Amemiya, K Dalakas, MC Torrence, PF Youle, RJ TI A study of the interferon antiviral mechanism: Apoptosis activation by the 2-5A system SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID 28S RIBOSOMAL-RNA; 2-5A-DEPENDENT RNASE; DNA FRAGMENTATION; CELLS; INFECTION; DEATH AB The 2-5A system contributes to the antiviral effect of interferons through the synthesis of 2-5A and its activation of the ribonuclease, RNase L. RNase L degrades viral and cellular RNA after activation by unique, 2'-5' phosphodiester-linked, oligoadenylates [2-5A, (pp)p5'A2'(P5'A2')](n), n greater than or equal to 2. Because both the 2-5A system and apoptosis can serve as viral defense mechanisms and RNA degradation occurs during both processes, we investigated the potential role of RNase L in apoptosis. Overexpression of human RNase L by an inducible promoter in NIH3T3 fibroblasts decreased cell viability and triggered apoptosis. Activation of endogenous RNase L, ape specifically with 2-5A or with dsRNA, induced apoptosis. Inhibition of RNase L with a dominant negative mutant suppressed poly (I)poly (C)-induced apoptosis in interferon-primed fibroblasts. Moreover, inhibition of RNase L suppressed apoptosis induced by poliovirus. Thus, increased RNase L levels induced apoptosis and inhibition of RNase L activity blocked viral-induced apoptosis. Apoptosis may be one of the antiviral mechanisms regulated by the 2-5A system. C1 NINCDS,BIOCHEM SECT,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. UNIV MARYLAND,CTR CANC,DEPT MICROBIOL & IMMUNOL,BALTIMORE,MD 21201. NINCDS,NEUROMUSCULAR DIS SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 25 TC 185 Z9 189 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 15 PY 1997 VL 186 IS 6 BP 967 EP 972 DI 10.1084/jem.186.6.967 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XX678 UT WOS:A1997XX67800017 PM 9294150 ER PT J AU Pericle, F Kirken, RA Bronte, V Sconocchia, G DaSilva, L Segal, DM AF Pericle, F Kirken, RA Bronte, V Sconocchia, G DaSilva, L Segal, DM TI Immunocompromised tumor-bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION MOLECULES; TARGETED DISRUPTION; CELLS; RESPONSES; GENE; MACROPHAGES; P56(LCK); PATHWAY; COMPLEX; STAT6 AB Progression of tumor growth in experimental animals and in patients is frequently associated with a decline in immune function (1, 2). In the advanced stages of tumor growth, loss of immune reactivity has been attributed to the secretion of suppressive cytokines and to tumor-stimulated host immune suppressor T cells or monocytes (3-5). Recently, efforts to explain the decrease in immune responsiveness during tumor growth have focused on molecular defects in T cells isolated from tumor-bearing hosts (6, 7). These studies suggested that the loss of zeta-chain within the TCR-CDS complex contributed to the loss of immune function (6, 7). However, such abnormalities were detectable only at the very end stages of disease and could not account for the immunologic alterations observed during progressive tumor growth (8). Therefore, although a number of mechanisms have been proposed to explain immunosuppression in tumor-bearing hosts, the cause of this phenomenon is still poorly understood. Tumor growth frequently results in the abnormal production of cytokines by the immune system and/or by the tumor itself (9). Cytokines modulate immune cellular responses by transducing biological signals from cell surface receptors to the nucleus through the JAK-STAT signaling pathway (10-12). Ligation of specific cytokine receptors leads to the activation of one or more members of the JAK tyrosine kinase family that constitutively associate with the intracellular domains of the receptor. The activated receptor-kinase complex recruits members of the STAT family of transcription factors to the receptor and phosphorylates them on tyrosine residues. The phosphorylated STAT molecules detach from the receptor, dimerize, translocate into the nucleus, and promote transcriptional activation of cytokine-inducible genes, ultimately controlling cell growth, differentiation, and maintenance of cellular homeostasis. Therefore, STAT proteins are essential components of the cytokine signaling apparatus, contributing to the specificity and diversity of cellular responses to growth factors, peptide hormones, ILs, and cytokines. To date, seven STAT genes (STAT1, 2, 3, 4, 5a, 5b, and 6) have been identified (10-12). STAT5a and STAT5b are two closely related genes that presumably arose by gene duplication (13). The purpose of the current report was to investigate molecular changes in lymphoid cells that could explain the loss of immune functions observed in tumor-bearing mice. In this study, we first showed that mice bearing a syngeneic mammary adenocarcinoma (TS/A) displayed loss of Ag-specific T cell responsiveness and Ab production. Lymphocytes from tumor-bearing mice were then screened for abnormalities in STAT expression because of their central role in regulating immune function. We present evidence here that STAT5a and STAT5b protein and message are strongly depressed in tumor-bearing mice. In contrast, no changes were observed in the expression of the remaining STATs. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NR 28 TC 39 Z9 42 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2580 EP 2585 PG 6 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000007 PM 9300676 ER PT J AU Chang, EY Szallasi, Z Acs, P Raizada, V Wolfe, PC Fewtrell, C Blumberg, PM Rivera, J AF Chang, EY Szallasi, Z Acs, P Raizada, V Wolfe, PC Fewtrell, C Blumberg, PM Rivera, J TI Functional effects of overexpression of protein kinase C-alpha, -beta, -delta, -epsilon, and -eta in the mast cell line RBL-2H3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIGH-AFFINITY RECEPTOR; HISTAMINE-RELEASE; IMMUNOGLOBULIN-E; PHOSPHOLIPASE-C; MESSENGER-RNAS; IFN-GAMMA; EXPRESSION; CALCIUM; IGE; ISOZYMES AB Protein kinase C (PKC)(3) is comprised of a family of closely related serine/threonine protein kinases for which at least 12 isotypes have been described. They are grouped according to their sensitivities to Ca2+ and whether they are activated by diacylglycerol and the tumor-promoting analogue, PMA (reviewed in Ref. 1). A role for PKC activity in mast cell function has long been suggested by the synergistic activation of effector function by PMA and calcium ionophore (reviewed in Ref. 2). At least five PKC isozymes are present in the RBL-2H3 cell line (3). They include the Ca2+-dependent alpha and beta and the Ca2+-independent delta, epsilon, and zeta isoforms. All the isozymes, except zeta, were found to translocate to the particulate fraction after Ag or PMA stimulation (3, 4), suggesting the activation of each of these PKC isozymes in receptor-mediated mast cell responses and the possibility that the activation is mimicked by PMA treatment. Understanding the role of each PKC isoform in generating specific molecular signals and responses in RBL-2H3 cells, as in other cell systems, presents a major challenge. Reconstitution studies on permeabilized and washed RBL-2H3 cells suggested that PKC-beta and -delta mediate positive signals for secretion (3), while the a and epsilon isoforms mediate inhibitory signals for phospholipase C gamma (PLC-gamma) activity (5). Another study using this permeabilized cell model provided evidence for a receptor-dependent role of PKC-beta and -epsilon in the regulation of transcription factor mRNA synthesis, suggesting a link between receptors and the nucleus (6). The weak; nesses of the reconstitution approach with permeablized cells are that small signaling molecules and cofactors may be removed by this procedure, and the direct reconstitution of the PKC isozymes may target these proteins to membranes where they may not normally reside. Other approaches, such as the use of phorbol esters to mimic receptor-induced generation of diacylglycerol, may be misleading, in that nonphysiologic concentrations of activator may simultaneously activate multiple PKC isoforms, resulting in a nonregulated phosphorylation of specific and spurious substrates. Interpretation of PMA-induced effects is further complicated by the ability of this agent to act on non-PKC proteins, such as Unc-13 and the chimaerins (7, 8). The present study investigates the roles of the four PKC isozymes that are endogenously expressed in RBL-2H3 cells (alpha, beta, delta, and epsilon) as well as that of the PKC-eta isozyme. The latter was examined because of its homology to PKC-E coupled to unusual characteristics for its activation and diverse intracellular localiza tion (9-16). The focus of this study was on PKC-mediated responses to the physiologic stimulus of Ag-induced aggregation of the Fc epsilon RI. The approach we chose was to overexpress each individual PKC isozyme in intact cells and analyze the effect of each isozyme's activity on mast cell responses. We report on the functional effects of each studied PKC isozyme with regard to Fc epsilon RI-stimulated secretion, PI hydrolysis, cPLA(2) activity, Ca2+ response, cytokine mRNA production, and cell proliferation. C1 NIAMSD,SECT CHEM IMMUNOL,NIH,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. CORNELL UNIV,DEPT PHARMACOL,ITHACA,NY 14853. NR 47 TC 80 Z9 85 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2624 EP 2632 PG 9 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000012 PM 9300681 ER PT J AU Jakob, T Saitoh, A Udey, MC AF Jakob, T Saitoh, A Udey, MC TI E-cadherin-mediated adhesion involving Langerhans cell-like dendritic cells expanded from murine fetal skin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; EPITHELIAL-CELLS; T-LYMPHOCYTES; PROTEIN ANTIGENS; LYMPH-NODE; EXPRESSION; MOUSE; GENERATION; EPIDERMIS; CULTURES AB Langerhans cells (LC), the epidermal contingent of the dendritic cell (DC) lineage, migrate from skin to regional lymph nodes to initiate primary immune responses against Ag encountered in skin. Because E-cadherin mediates LC-keratinocyte adhesion, E-cadherin expression and/or function must be modulated during LC migration. To facilitate studies of LC/DC cadherin biology, we defined culture conditions that allowed expansion of LC-like cells from fetal murine skin. Fetal skin-derived dendritic cells (FSDDC) were propagated from C57BL/6 day 16 fetal skin in CM-CSF-and CSF-l-supplemented media. After 14 days, aggregates of E-cadherin(+) FSDDC (FSDDC-A) that resembled freshly-obtained LC with regard to phenotype and function were isolated. Nonadherent FSDDC (FSDDC-NA) with dendritic morphology, surface phenotype identical to that of interdigitating DC and potent allostimulatory capacity were released from FSDDC-A with continued incubation. A Survey of cytokine mRNAs expressed by FSDDC revealed that FSDDC-A expressed predominantly TNF-alpha; TGF-beta 1,and MIF mRNA. In contrast, FSDDC-NA exhibited de novo expression of IL-1 beta, IL-12 (p40), increased levels of TNF-alpha and decreased MIF mRNA. Neutralizing anti-E-cadherin mAb dissociated FSDDC-A into single cells, whereas functionally inactive anti-E-cadherin mAb and mAb reactive with other adhesion molecules did not, demonstrating that adhesion within FSDDC-A was E-cadherin-mediated. FSDDC-A also preferentially adhered to E-cadherin-transfected fibroblasts. Spontaneous dissociation of FSDDC-A was accompanied by a reduction in cell surface E-cadherin expression. The availability of large numbers of cells with characteristics of LC in situ that spontaneously mature into interdigitating DC will permit detailed studies of LC/DC cadherin biology and LC/DC differentiation. C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Jakob, Thilo/J-1621-2012 NR 53 TC 33 Z9 33 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2693 EP 2701 PG 9 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000020 PM 9300689 ER PT J AU Kojima, H Eshima, K Takayama, H Sitkovsky, MV AF Kojima, H Eshima, K Takayama, H Sitkovsky, MV TI Leukocyte function-associated antigen-1-dependent lysis of Fas(+) (CD95(+)/Apo-1(+)) innocent bystanders by antigen-specific CD8(+) CTL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-MEDIATED CYTOTOXICITY; LYMPHOCYTE-T CLONES; PERFORIN; PATHWAYS; MICE; IONOPHORES; RECEPTORS; INFECTION; LIGAND AB Exquisite specificity toward Ag-bearing cells (cognate targets) is one of the most important properties of CD8(+) CTL-mediated cytotoxicity. Using highly Ag-specific CD8(+) CTL lines and clones, which spare noncognate, Ag-free targets, we found that in the presence of Ag-bearing targets the CTL acquire the ability to lyse noncognate target cells (bystanders), It is shown that the unexpectedly rapid and efficient lysis of bystanders by Ag-activated CTL is mediated by a Fas ligand (FasL)/Fas-based mechanism and does not depend on perforin, The CTL lysed Fas-expressing bystanders, but spared the Fas-negative or anti-fas mAb-resistant bystander cells. Accordingly, the FasL-deficient gld/gld CTL did not kill bystanders, while perforin-deficient CTL did, Unlike anti-fas mAb-induced cell death, the lysis of bystanders was not only FasL/Fas dependent but also required adhesion molecule LFA-1 on the surface of the activated CTL. Lysis of bystanders is viewed as acceptable ''collateral'' damage, but the persistent presence of activated CTL could result in immunopathologies involving functional Fas-expressing tissues. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. MITSUBISHI KASEI INST LIFE SCI,TOKYO,JAPAN. NR 29 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2728 EP 2734 PG 7 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000024 PM 9300693 ER PT J AU Kanaitsuka, T Bortell, R Stevens, LA Moss, J Sardinha, D Rajan, TV Zipris, D Mordes, JP Greiner, DL Rossini, AA AF Kanaitsuka, T Bortell, R Stevens, LA Moss, J Sardinha, D Rajan, TV Zipris, D Mordes, JP Greiner, DL Rossini, AA TI Expression in BALB/c and C57BL/6 mice of Rt6-1 and Rt6-2 ADP-ribosyltransferases that differ in enzymatic activity - C57BL/6 Rt6-1 is a natural transferase knockout SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DIFFERENTIATION MARKER RT6; LYMPHOCYTE ALLOANTIGEN RT6.1; AMINO-ACID-SEQUENCE; CYTOTOXIC T-CELLS; BB RATS; MOLECULAR CHARACTERIZATION; BACTERIAL TOXINS; MOUSE HOMOLOG; MESSENGER-RNA; RIBOSYLATION AB Several proteins with NAD(+) :arginine ADP-ribosyltransferase (ART) activity are expressed in T cells and affect their function. Rat T cells that express the ART designated RT6 are determinants of the expression of autoimmune diabetes. In the mouse, a 35-kDa ecto-ART modulates the proliferation and functional activity of CTL. Here we report on mouse ARTs designated Rt6-1 and Rt6-2 in BALB/c and C57BL/6 mice. mRNAs for Rt6-1 and Rt6-2 were found in spleen, thymus, and intestinal tissue of both strains, but Rt6-1 mRNA in C57BL/6 mice was detected only at low levels, Rt6-1 and Rt6-2 cDNAs from both strains were cloned and sequenced. Predicted amino acid sequences of Rt6-2 were identical in both strains, but there was an in-frame stop codon in the sequence of Rt6-1 in C57BL/6 mice not present in BALB/c mice, Recombinant C57BL/6 Rt6-2 and BALB/c Rt6-1 proteins expressed in COS1 cells exhibited ART activity and were documented to be glycosylphosphatidylinositol-linked membrane proteins, COS-1 cells transfected with a C57BL/6 Rt6-1 cDNA construct expressed a truncated protein consistent in size with that predicted by the presence of the stop codon. This similar to 21-kDa protein appeared not to be glycosylphosphatidylinositol linked to the cell surface and lacked ART activity, C57BL/6 Rt6-1 therefore appears to be a naturally occurring ART knockout. The expression of Rt6-1 and Rt6-2 mRNAs in lymphoid tissues suggests that these ARTs may regulate immune system functions. Expression of Rt6-2 or another redundant ART may compensate for the lack of enzymatically active Rt6-1 in C57BL/6 mice. C1 UNIV MASSACHUSETTS,SCH MED,DIABET DIV,DEPT MED,WORCESTER,MA 01605. NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. UNIV CONNECTICUT,HLTH SCI CTR,DEPT PATHOL,FARMINGTON,CT 06032. FU NIDDK NIH HHS [DK41235, DK25306, DK36024] NR 40 TC 19 Z9 21 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2741 EP 2749 PG 9 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000026 PM 9300695 ER PT J AU Rumsaeng, V Cruikshank, WW Foster, B Prussin, C Kirshenbaum, AS Davis, TA Kornfeld, H Center, DM Metcalfe, DD AF Rumsaeng, V Cruikshank, WW Foster, B Prussin, C Kirshenbaum, AS Davis, TA Kornfeld, H Center, DM Metcalfe, DD TI Human mast cells produce the CD4(+) T lymphocyte chemoattractant factor, IL-16 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BRONCHOALVEOLAR LAVAGE FLUID; MARROW PROGENITOR CELLS; PHENOTYPIC CHARACTERIZATION; ATOPIC ASTHMA; IN-VITRO; IDENTIFICATION; EXPRESSION; RELEASE; INTERLEUKIN-16; CYTOKINES AB CD4(+) T cell infiltration is known to occur in tissues at sites of mast cell activation. The molecules produced and released by mast cells that account for this lymphocyte accumulation are poorly characterized. Here we report that a CD4(+) T cell chemoattractant cytokine, IL-16, is stored preformed in bone marrow-cultured human mast cells and a human mast cell line, HMC-1, as demonstrated by intracytoplasmic cytokine staining and flow cytometry, and in human lung mast cells, as detected by immunohistochemistry. In response to the anaphylatoxin, C5a, or to PMA treatment, IL-16 mRNA transcripts detected by Northern blot analysis in HMC-1 cells increased 6- to 10-fold. HMC-1 cell lysates and activated supernatants contained IL-16 protein, as demonstrated by both ELISA and in vitro lymphocyte chemotaxis assays, the latter of which was blocked 59 to 88% by the addition of neutralizing Ab to recombinant human IL-16. IL-16 bioactivity was detected in the supernatants 2 to 4 h after PMA or C5a activation, and this activity remained elevated through 24 h. The capacity of human mast cells to synthesize and release biologically active IL-16 provides a possible link between mast cell activation and the accumulation of T cells in mast cell-dependent inflammation, thus amplifying the immune response and perpetuating the pathologic process. C1 NIAID,LAB ALLERG DIS,NIH,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,CTR PULM,BOSTON,MA 02118. USN,MED RES INST,STEM CELL BIOL BRANCH,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. OI Prussin, Calman/0000-0002-3917-3326 FU NIAID NIH HHS [AI35680] NR 30 TC 115 Z9 119 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2904 EP 2910 PG 7 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000045 PM 9300714 ER PT J AU Xia, HZ Du, ZM Craig, S Klisch, G NobenTrauth, N Kochan, JP Huff, TH Irani, AMA Schwartz, LB AF Xia, HZ Du, ZM Craig, S Klisch, G NobenTrauth, N Kochan, JP Huff, TH Irani, AMA Schwartz, LB TI Effect of recombinant human IL-4 on tryptase, chymase, and Fc epsilon receptor type I expression in recombinant human stem cell factor-dependent fetal liver-derived human mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID C-KIT LIGAND; EPIDERMAL LANGERHANS CELLS; HIGH-AFFINITY RECEPTOR; NON-T CELLS; IMMUNOGLOBULIN-E; BONE-MARROW; HUMAN BASOPHILS; MESSENGER-RNA; IGE RECEPTOR; B-CELLS AB The effect of recombinant human IL-4 (rhIL-4) on the development of recombinant human stem cell factor-dependent fetal liver-derived mast cells was examined. RhIL-4 attenuates the number of mast cells that develop, preferentially affecting the MC, type of mast cell. Cellular levels of tryptase and chymase mRNA normalized to that of glyceraldehyde-3-phosphate dehydrogenase were not appreciably affected. Tryptase mRNA levels peaked at least 2 wk before tryptase protein and before chymase mRNA and protein, indicating that tryptase mRNA expression is an early marker of commitment to a mast cell lineage. in contrast, alpha-tryptase and beta-tryptase mRNA levels increased and decreased in parallel. The most dramatic effect of rhIL-4 was to induce expression of functional surface Fc epsilon RI. Expression was maximal by 21 days with 20 ng/ml of rhIL-4 and reached a plateau by 2 ng/ml of rhIL-4 at 4 wk. Fc epsilon RI+ cells increased modestly when myeloma IgE was added to the developing mast cells, but increased synergistically when both myeloma IgE and rhIL-4 were present together. Delayed addition of rhIL-4 progressively diminished Fc epsilon RI expression, as did withdrawal of rhIL-4 during the first 2 wk of culture. RhIL-4 selectively increased Fc epsilon RI alpha mRNA levels at least 10-fold. Mast cells developed in the presence of rhIL-4 released tryptase when exposed to anti-fc epsilon RI alpha. In conclusion, induction of functional Fc epsilon RI on recombinant human stem cell factor-dependent human fetal liver-derived mast cells by rhIL-4 harmonizes with the well-accepted ability of this cytokine to enhance IgE production by B cells. C1 VIRGINIA COMMONWEALTH UNIV,DEPT INTERNAL MED,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,DEPT IMMUNOL & MICROBIOL,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,DEPT PEDIAT,RICHMOND,VA 23298. NIAID,NIH,ROCKVILLE,MD 20852. HOFFMANN LA ROCHE INC,DEPT METAB DIS,NUTLEY,NJ 07110. FU NIAID NIH HHS [AI20487, AI27517] NR 74 TC 109 Z9 111 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2911 EP 2921 PG 11 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000046 PM 9300715 ER PT J AU Bosco, MC EspinozaDelgado, I Rowe, TK Malabarba, MG Longo, DL Varesio, L AF Bosco, MC EspinozaDelgado, I Rowe, TK Malabarba, MG Longo, DL Varesio, L TI Functional role for the myeloid differentiation antigen CD14 in the activation of human monocytes by IL-2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LPS BINDING-PROTEIN; NECROSIS-FACTOR-ALPHA; INTERLEUKIN-2 RECEPTOR; INTERFERON-GAMMA; GENE-EXPRESSION; LIPOPOLYSACCHARIDE LPS; MONONUCLEAR PHAGOCYTES; ALVEOLAR MACROPHAGES; BETA-CHAIN; IFN-GAMMA AB Human monocytes express functional IL-2Rs and are directly activated by IL-2 to exert effector and secretory functions. In this study, we demonstrate that the myeloid differentiation Ag CD14 participates in monocyte activation by IL-2. Engagement of CD14 by specific mAbs resulted in the selective and dose-dependent suppression of IL-2-induced, but not of IFN-gamma-induced, monocyte tumoricidal activity. Furthermore, anti-CD14 mAbs effectively inhibited the secretion of IL-8 and IL-1 beta in response to IL-2. Preincubation of monocytes with mAbs directed to selected epitopes on CD14 blocked the binding of IL-2 to the cell surface, providing a possible explanation for the inhibition of IL-2-triggered responses. A critical role for CD14 in IL-2-mediated monocyte activation was further demonstrated by experiments with the human U937 promonocytic cell line. These cells are negative for CD14 and unresponsive to IL-2 despite the expression of the beta and gamma subunits of the IL-2R. U937 cells acquired the capacity to respond to IL-2 following transfection with the human CD14 cDNA (U937/CD14). Stimulation of U937/CD14 cells with IL-2 up-regulated the constitutive levels of IL-8 mRNA, whereas no change in IL-8 mRNA basal expression was observed in control cells transfected with the vector alone (U937/Neo). Accordingly, increased secretion of IL-8 by U937/CD14, but not by U937/Neo cells, was detected following exposure to IL-2, Expression of IL-1 beta was also augmented by IL-2 in U937/CD14 cells. These data provide the first evidence that CD14 expression is required for the response of monocytic cells to IL-2. C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MACROPHAGE CELL BIOL SECT,EXPT IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CYTOKINE MOL MECHANISMS SECT,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA 70112. RP Bosco, MC (reprint author), IST GIANNINA GASLINI,MOL BIOL LAB,LGO G GASLINI 5,I-16147 GENOA,ITALY. RI Malabarba, Maria Grazia/L-4805-2015; Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Malabarba, Maria Grazia/0000-0002-9457-2047; Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 FU Telethon [A.075] NR 58 TC 25 Z9 27 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2922 EP 2931 PG 10 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000047 PM 9300716 ER PT J AU Mittleman, BB Castellanos, FX Jacobsen, LK Rapoport, JL Swedo, SE Shearer, GM AF Mittleman, BB Castellanos, FX Jacobsen, LK Rapoport, JL Swedo, SE Shearer, GM TI Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; PYROGENIC EXOTOXIN-A; MULTIPLE-SCLEROSIS; T-CELLS; SCHIZOPHRENIA; INDUCTION; INTERLEUKIN-2; PREVALENCE AB This study examines cerebrospinal fluid from patients with three neuropsychiatric diseases of childhood for the presence and levels of several cytokines relevant to cell-mediated (type 1) and humoral (type 2) immunity. The patient groups include childhood-onset schizophrenia (n = 22), obsessive-compulsive disorder (OCD) (n = 24), and attention deficit hyperactivity disorder (n = 42). The cytokines examined include IL-2, IFN-gamma, TNF-beta/LT, IL-4, IL-5, IL-10, and TNF-alpha, Patients with OCD had a preponderance of type 1 cytokines. IL-4 was detectable only in samples from patients with schizophrenia. IL-10 was rarely detected and never in patients with OCD. Few patients with schizophrenia had detectable amounts of IFN-gamma in CSFL. We conclude that there is a relative skewing of CSFL profiles toward type 1 cytokines in patients with OCD, whereas in schizophrenia the relative preponderance is toward type 2 mediators. Patients with attention deficit hyperactivity disorder exhibited profiles intermediate between OCD and schizophrenia. We infer that cell-mediated immunity may be involved in the etiopathogenesis of OCD, whereas a relative lack of cell-mediated immunity and involvement of humoral immunity may be present in schizophrenia. These data provide a rationale for immune-based strategies of study and therapeutics in childhood neuropsychiatric disease. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NIMH,BEHAV PEDIAT SECT,CHILD PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. NR 32 TC 127 Z9 131 U1 3 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 2994 EP 2999 PG 6 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000055 PM 9300724 ER PT J AU Kolenko, V Wang, Q Riedy, MC OShea, J Ritz, J Cathcart, MK Rayman, P Tubbs, R Edinger, M Novick, A Bukowski, R Finke, J AF Kolenko, V Wang, Q Riedy, MC OShea, J Ritz, J Cathcart, MK Rayman, P Tubbs, R Edinger, M Novick, A Bukowski, R Finke, J TI Tumor-induced suppression of T lymphocyte proliferation coincides with inhibition of Jak3 expression and IL-2 receptor signaling - Role of soluble products from human renal cell carcinomas SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MICE LACKING JAK3; ZETA-CHAIN; C-MYC; JANUS KINASE; BETA-CHAIN; TYROSINE PHOSPHORYLATION; TRANSDUCTION MOLECULES; DECREASED EXPRESSION; CYTOPLASMIC DOMAINS AB The proliferative capacity of T cells infiltrating human tumors is known to be impaired, possibly through their interaction with tumor. Here we demonstrate that soluble products derived from renal cell carcinoma (RCC-S) explants but not normal kidney can inhibit an IL-2-dependent signaling pathway that is critical to T cell proliferation. A major target of the immunosuppression was the IL-2R-associated protein tyrosine kinase, Janus kinase 3 (Jak3). RCC-S suppressed basal expression of Jak3 and its increase following stimulation with anti-CD3/IL-2. Jak3 was most sensitive to suppression by RCC-S; however, reduction in expression of p56(lck), p59(fyn), and ZAP-70 was observed in some experiments. Expression of other signaling elements linked to the IL-2R (Jak1) and the TCR (TCR-zeta, CD3-epsilon, and phospholipase C-gamma) were minimally affected. In naive T cells, RCC-S also partially blocked induction of IL-2R alpha-, beta- and gamma-chain expression when stimulating via the TCR/CD3 complex with anti-CD3 Ab. To determine whether RCC-S suppressed IL-2-dependent signaling, primed T cells were employed since RCC-S had no effect on IL-2R expression but did down-regulate Jak3 expression and, to a lesser degree, p56(lck) and p59(fyn). Reduction in Jak3 correlated with impaired IL-2-dependent proliferation and signal transduction. This included loss of Jak1 kinase tyrosine phosphorylation and no induction of the proto-oncogene, c-Myc. These findings suggest that soluble products from tumors may suppress T cell proliferation through a mechanism that involves down-regulation of Jak3 expression and inhibition of IL-2-dependent signaling pathways. C1 CLEVELAND CLIN FDN,DEPT UROL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT CELL BIOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT CLIN PATHOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT HEMATOL ONCOL,CLEVELAND,OH 44195. NIAMSD,LYMPHOCYTE CELL BIOL SECT,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20814. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES & TUMOR IMMUNOL,BOSTON,MA 02115. RP Kolenko, V (reprint author), CLEVELAND CLIN FDN,DEPT IMMUNOL NN10,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA56937] NR 57 TC 65 Z9 67 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1997 VL 159 IS 6 BP 3057 EP 3067 PG 11 WC Immunology SC Immunology GA XV750 UT WOS:A1997XV75000062 PM 9300731 ER PT J AU Xu, RH Kim, JB Taira, M Sredni, D Kung, HF AF Xu, RH Kim, JB Taira, M Sredni, D Kung, HF TI Studies on the role of fibroblast growth factor signaling in neurogenesis using conjugated/aged animal caps and dorsal ectoderm-grafted embryos SO JOURNAL OF NEUROSCIENCE LA English DT Article DE FGF; BMP; neurogenesis; anteroposterior patterning; Xenopus; embryo ID EARLY XENOPUS DEVELOPMENT; NEURAL INDUCTION; MESODERM INDUCTION; VENTRAL MESODERM; EARLY RESPONSE; HOMEOBOX GENE; MAP KINASE; EXPRESSION; FGF; GASTRULATION AB Basic fibroblast growth factor (bFGF) has been shown to induce neural fate in dissociated animal cap (AC) cells or in AC explants cultured in low calcium and magnesium concentrations. However, long-term disclosure of the cap may cause diffusion of the secreted molecule bone morphogenetic protein 4 (BMP-4), a neural inhibitor present in the AC. This may contribute to the subsequent neurogenesis induced by bFGF. Here we used conjugated and aged blastula AC to avoid diffusion of endogenous molecules from the AC. Unlike noggin, bFGF failed to induce neural tissue in this system. However, it enhanced neuralization elicited by a dominant negative BMP receptor (DN-BR) that inhibits the BMP-4 signaling. Posterior neural markers were turned on by bFGF in AC expressing DN-BR or chordin. Blocking the endogenous FGF signal with dominant negative FGF receptor (XFD) mainly inhibited development of posterior neural tissue in neuralized ACs. These in vitro studies were confirmed in vivo in embryos grafted with XFD-expressing ACs in the place of neuroectoderm. Expression of some regional neural markers was inhibited, although markers for muscle and posterior notochord were still detectable in the grafted embryos, suggesting that XFD specifically affected neurogenesis but not the dorsal mesoderm. The use of these in vitro and in vivo model systems provides new evidence that FGF, although unable to initiate neurogenesis on its own, is required for neural induction as well as for posteriorization. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,DIV BASIC SCI,FREDERICK,MD 21702. SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. UNIV TOKYO,GRAD SCH SCI,DEPT SCI BIOL,MOL EMBRYOL LAB,TOKYO 113,JAPAN. BAR ILAN UNIV,INTERDISCIPLINARY DEPT,IL-52900 RAMAT GAN,ISRAEL. RI TAIRA, MASANORI/G-4923-2014; Xu, Ren-He/M-3125-2016 NR 50 TC 19 Z9 20 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1997 VL 17 IS 18 BP 6892 EP 6898 PG 7 WC Neurosciences SC Neurosciences & Neurology GA XY896 UT WOS:A1997XY89600006 PM 9278524 ER PT J AU Nirenberg, MJ Chan, J Pohorille, A Vaughan, RA Uhl, GR Kuhar, MJ Pickel, VM AF Nirenberg, MJ Chan, J Pohorille, A Vaughan, RA Uhl, GR Kuhar, MJ Pickel, VM TI The dopamine transporter: Comparative ultrastructure of dopaminergic axons in limbic and motor compartments of the nucleus accumbens SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine transporter; dopamine reuptake; immunogold; accumbens; striatum; cocaine; amphetamine ID PARKINSONISM-INDUCING NEUROTOXIN; EXTRACELLULAR DOPAMINE; MESSENGER-RNA; RAT-BRAIN; VENTRAL STRIATUM; TYROSINE-HYDROXYLASE; PROJECTION PATTERNS; MIDBRAIN NEURONS; REPEATED COCAINE; D-2 RECEPTOR AB The dopamine transporter (DAT) regulates extracellular dopamine concentrations, transports neurotoxins, and acts as a substrate for cocaine reinforcement. These functions are known to differ in the limbic-associated shell and motor-associated core compartments of the nucleus accumbens (NAc). Previous studies have shown differential expression of DAT in the NAc shell and core but were limited in resolution to the regional level, Thus, it is not known whether there are differences in the amount, subcellular localization, or plasmalemmal targeting of DAT within individual dopaminergic axons in the two regions. We used high-resolution electron microscopic immunocytochemistry to investigate these possibilities, We show that in both the shell and core, DAT immunogold labeling is present in tyrosine hydroxylase-immunoreactive varicose axons that form symmetric synapses. Within these labeled axons, most DAT gold particles are located on extrasynaptic plasma membranes, but some are associated with intracellular membranes, Dopaminergic axons in the shell contain lower mean densities of both total DAT gold particles (per square micron) and plasmalemmal DAT gold particles (per micron) than those in the core. Within labeled axons in the NAc shell and core, however, there are no detectable differences in the subcellullar distribution of DAT or the percentage of total DAT gold particles that are located on plasma membranes. These studies are the first to examine and compare the subcellular localization of DAT in the NAc shell and core, As a result, they identify intrinsic, cell-specific differences in the expression of DAT within dopaminergic axons in these functionally distinct striatal compartments. C1 NIDA,MOL NEUROBIOL BRANCH,BALTIMORE,MD 21224. NIDA,NEUROSCI BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. EMORY UNIV,YERKES REG PRIMATE RES CTR,DIV NEUROSCI,ATLANTA,GA 30322. RP Nirenberg, MJ (reprint author), CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,411 E 69TH ST,ROOM KB-410,NEW YORK,NY 10021, USA. FU NIDA NIH HHS [DA04600]; NIMH NIH HHS [MH00078, MH40342] NR 69 TC 143 Z9 144 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1997 VL 17 IS 18 BP 6899 EP 6907 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XY896 UT WOS:A1997XY89600007 PM 9278525 ER PT J AU Sugita, Y Becerra, SP Chader, GJ Schwartz, JP AF Sugita, Y Becerra, SP Chader, GJ Schwartz, JP TI Pigment epithelium-derived factor (PEDF) has direct effects on the metabolism and proliferation of microglia and indirect effects on astrocytes SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neurotrophic factor; granulocyte-macrophage stimulating factor; co-culture; MTS assay; pigment epithelium-derived factor ID GROWTH-FACTOR-BETA; COLONY-STIMULATING FACTORS; NEUROTROPHIC ACTIVITY; COLORIMETRIC ASSAY; RAT-BRAIN; CELLS; CULTURE; FACTOR-BETA-1; SURVIVAL; ALPHA-1-ANTICHYMOTRYPSIN AB Pigment epithelium-derived factor (PEDF), a neurotrophic agent first identified in conditioned medium from cultured human retinal pigment epithelial cells, induces neuronal differentiation with neurite outgrowth in Y-79 retinoblastoma cells and has a neurotrophic survival effect on cerebellar granule cells in culture, In the present study, we investigated the effects of human recombinant PEDF (rPEDF) on proliferation and activation of microglia and astrocytes isolated from newborn rat brain. rPEDF treatment caused microglia to round up morphologically, increased their metabolic activity (measured by both MTS conversion and acid phosphatase activity), but blocked proliferation (mitosis), This blocking effect could be demonstrated in cultures stimulated to proliferate by addition of granulocyte-macrophage colony stimulating factor. The effect of rPEDF on microglial metabolic activity showed a dose-response relationship both in serum-containing medium and in chemically defined medium and was blocked with anti-PEDF antibody rPEDF had no direct effect on the metabolic activity or proliferation of cultured astrocytes but blocked their proliferation in astrocytemicroglia co-cultures. Proliferation of isolated astrocytes was also blocked by conditioned medium from microglia treated with PEDF (PMCM), The effect of PMCM on astrocytes was not blocked by an antibody to transforming growth factor-beta. These results demonstrate that PEDF activates microglial metabolism while blocking proliferation and suggest that a soluble factor(s) released by rPEDF-stimulated microglia blocks the proliferation of astrocytes, Thus, PEDF could play an important role in regulation of glial function and proliferation in the central nervous system. (C) 1997 Wiley-Liss, Inc. C1 NINCDS,MOL GENET SECT,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NEI,RETINAL CELL & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 37 TC 54 Z9 56 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 15 PY 1997 VL 49 IS 6 BP 710 EP 718 DI 10.1002/(SICI)1097-4547(19970915)49:6<710::AID-JNR5>3.0.CO;2-A PG 9 WC Neurosciences SC Neurosciences & Neurology GA XY944 UT WOS:A1997XY94400005 PM 9335258 ER PT J AU Lipman, DJ AF Lipman, DJ TI Making (anti)sense of non-coding sequence conservation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MESSENGER-RNA DEGRADATION; FIBROBLAST GROWTH-FACTOR; 3' UNTRANSLATED REGION; DOUBLE-STRANDED-RNA; ANTISENSE TRANSCRIPTION; GENE-EXPRESSION; PROTEIN; MYC; STABILITY; LOCUS AB A substantial fraction of vertebrate mRNAs contain long conserved blocks in their untranslated regions as well as long blocks without silent changes in their protein coding regions. These conserved blocks are largely comprised of unique sequence within the genome, leaving us with an important puzzle regarding their function. A large body of experimental data shows that these regions are associated with regulation of mRNA stability. Combining this information with the rapidly accumulating data on endogenous antisense transcripts, we propose that the conserved sequences form long perfect duplexes with antisense transcripts. The formation of such duplexes may be essential for recognition by post-transcriptional regulatory systems. The conservation may then be explained by selection against the dominant negative effect of allelic divergence. RP Lipman, DJ (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BLDG 38A 8N803,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 54 TC 72 Z9 73 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 15 PY 1997 VL 25 IS 18 BP 3580 EP 3583 DI 10.1093/nar/25.18.3580 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW788 UT WOS:A1997XW78800004 PM 9278476 ER PT J AU Esposito, D Scocca, JJ AF Esposito, D Scocca, JJ TI The integrase family of tyrosine recombinases: evolution of a conserved active site domain SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FLP RECOMBINASE; IDENTIFYING DETERMINANTS; BACTERIOPHAGE INTEGRASES; BINDING-SITES; IN-VITRO; DNA; GENE; CONSTRUCTION; SPECIFICITY; MECHANISM AB The integrases are a diverse family of tyrosine recombinases which rearrange DNA duplexes by means of conservative site-specific recombination reactions. Members of this family, of which the well-studied lambda Int protein is the prototype, were previously found to share four strongly conserved residues, including an active site tyrosine directly involved in transesterification. However, few additional sequence similarities were found in the original group of 27 proteins. We have now identified a total of 81 members of the integrase family deposited in the databases, Alignment and comparisons of these sequences combined with an evolutionary analysis aided in identifying broader sequence similarities and clarifying the possible functions of these conserved residues, This analysis showed that members of the family aggregate into subfamilies which are consistent with their biological roles; these subfamilies have significant levels of sequence similarity beyond the four residues previously identified. It was also possible to map the location of conserved residues onto the available crystal structures; most of the conserved residues cluster in the predicted active site cleft. In addition, these results offer clues into an apparent discrepancy between the mechanisms of different subfamilies of integrases. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOCHEM,BALTIMORE,MD 21205. RP Esposito, D (reprint author), NIDDK,MOL BIOL LAB,NIH,5 CTR DR MSC0560,BETHESDA,MD 20782, USA. NR 36 TC 224 Z9 230 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 15 PY 1997 VL 25 IS 18 BP 3605 EP 3614 DI 10.1093/nar/25.18.3605 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW788 UT WOS:A1997XW78800008 PM 9278480 ER PT J AU Dianov, GL Houle, JF Iyer, N Bohr, VA Friedberg, EC AF Dianov, GL Houle, JF Iyer, N Bohr, VA Friedberg, EC TI Reduced RNA polymerase II transcription in extracts of Cockayne syndrome and xeroderma pigmentosum/Cockayne syndrome cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEOTIDE-EXCISION-REPAIR; DNA-REPAIR; ACTIVE GENES; PREFERENTIAL REPAIR; COUPLED REPAIR; FACTOR TFIIH; COMPLEX; DEFECT; COMPLEMENTATION; INITIATION AB The hereditary disease Cockayne syndrome (CS) is a complex clinical syndrome characterized by arrested post-natal growth as well as neurological and other defects, The CSA and CSB genes are implicated in this disease, The clinical features of CS can also accompany the excision repair-defective hereditary disorder xeroderma pigmentosum (XP) from genetic complementation groups B, D or G. The XPB and XPD proteins are subunits of RNA polymerase II (RNAP II) transcription factor IIH (TFIIH), We show here that extracts of CS-A and CS-B cells, as well as those from XP-B/CS cells, support reduced levels of RNAP II transcription in vitro and that this feature is dependent on the state or quality of the template. C1 UNIV TEXAS,SW MED CTR,LAB MOL PATHOL,DEPT PATHOL,DALLAS,TX 75235. NIA,GENET MOL LAB,NIH,BALTIMORE,MD 21224. NR 43 TC 55 Z9 55 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 15 PY 1997 VL 25 IS 18 BP 3636 EP 3642 DI 10.1093/nar/25.18.3636 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW788 UT WOS:A1997XW78800012 PM 9278484 ER PT J AU Leipe, DD Landsman, D AF Leipe, DD Landsman, D TI Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR; YEAST; ACETYLATION; RPD3; REGULATOR; TOOL; POLYAMINES; SEARCH; HDA1 AB Searches of several sequence databases reveal that human HD1, yeast HDA1, yeast RPD3 and other eukaryotic histone deacetylases share nine motifs with archaeal and eubacterial enzymes, including acetoin utilization protein (acuC) and acetylpolyamine amidohydrolase. Histone deacetylase and acetylpolyamine amidohydrolase also share profound functional similarities in that both: (i) recognize an acetylated aminoalkyl group; (ii) catalyze the removal of the acetyl group by cleaving an amide bond; (iii) increase the positive charge of the substrate. Stabilization of nucleosomal DNA-histone interaction brought about by the change in charge has been implicated as the underlying cause for histone deacetylase-mediated transcriptional repression, We speculate that the eukaryotic histone deacetylases originated from a prokaryotic enzyme similar to the acetylpolyamine amidohydrolases that relied on reversible acetylation and deacetylation of the aminoalkyl group of a DNA binding molecule to achieve a gene regulatory effect. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20984. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 32 TC 90 Z9 91 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 15 PY 1997 VL 25 IS 18 BP 3693 EP 3697 DI 10.1093/nar/25.18.3693 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XW788 UT WOS:A1997XW78800020 PM 9278492 ER PT J AU Wang, XQ Wang, CS Tang, J Dyda, F Zhang, XJC AF Wang, XQ Wang, CS Tang, J Dyda, F Zhang, XJC TI The crystal structure of bovine bile salt activated lipase: insights into the bile salt activation mechanism SO STRUCTURE LA English DT Article DE alpha/beta hydrolase; bile salt activated lipase; crystal structure; dimerization; enzyme activation; heparin-binding site ID CANDIDA-RUGOSA LIPASE; CHOLESTEROL ESTERASE; 3-DIMENSIONAL STRUCTURE; INTERFACIAL ACTIVATION; PROTEIN STRUCTURES; HUMAN-MILK; SEQUENCE; PROGRAM; REFINEMENT; HYDROLASE AB Background: The intestinally located pancreatic enzyme, bile salt activated lipase (BAL), possesses unique activities for digesting different kinds of lipids. It also differs from other lipases in a requirement of bile salts for activity. A structure-based explanation for these unique properties has not been reached so far due to the absence of a three-dimensional structure. Results: The crystal structures of bovine BAL and its complex with taurocholate have been determined at 2.8 Angstrom resolution. The overall structure of BAL belongs to the alpha/beta hydrolase fold family. Two bile salt binding sites were found in each BAL molecule within the BAL-taurocholate complex structure. One of these sites is located close to a hairpin loop near the active site. Upon the binding of taurocholate, this loop becomes less mobile and assumes a different conformation. The other bile salt binding site is located remote from the active site. In both structures, BAL forms similar dimers with the active sites facing each other. Conclusions: Bile salts activate BAL by binding to a relatively short ten-residue loop near the active site, and stabilize the loop in an open conformation. Presumably, this conformational change leads to the formation of the substrate-binding site, as suggested from kinetic data. The BAL dimer observed in the crystal structure may also play a functional role under physiological conditions. C1 OKLAHOMA MED RES FDN,CRYSTALLOG PROGRAM,OKLAHOMA CITY,OK 73104. OKLAHOMA MED RES FDN,PROT STUDY PROGRAM,OKLAHOMA CITY,OK 73104. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73104. NIDDKD,NIH,BETHESDA,MD 20892. NR 43 TC 78 Z9 80 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD SEP 15 PY 1997 VL 5 IS 9 BP 1209 EP 1218 DI 10.1016/S0969-2126(97)00271-2 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YA414 UT WOS:A1997YA41400009 PM 9331420 ER PT J AU Wonderling, RS Kyostio, SRM Walker, SL Owens, RA AF Wonderling, RS Kyostio, SRM Walker, SL Owens, RA TI The Rep68 protein of adeno-associated virus type 2 increases RNA levels from the human cytomegalovirus major immediate early promoter SO VIROLOGY LA English DT Article ID SITE-SPECIFIC INTEGRATION; LONG TERMINAL REPEAT; ADENOASSOCIATED VIRUS; EARLY GENE; REGULATORY REGION; CELLULAR-TRANSFORMATION; CLINICAL MANIFESTATIONS; TRANSCRIPTION FACTORS; MEDIATED INHIBITION; NEGATIVE REGULATION AB The Rep68 and Rep78 proteins of adeno-associated virus type-2 (AAV) are multifunctional DNA binding proteins which are involved in the positive and negative regulation of AAV genes, as well as various cellular and heterologous viral genes. In this study we report that Rep68 enhances expression from the major immediate early promoter (MIEP) or human cytomegalovirus (HCMV). This Rep-mediated enhancement of RNA levels is abrogated by the introduction of a Rep recognition sequence (RRS) at either position -18 or -244 in the HCMV-M[EP. However, a mutant RRS (mRRS), which is not bound by Rep68 is unable to negate the effect of Rep68. Sequence analysis and electrophoretic mobility shift assays showed no Rep68 binding sites within the wild-type HCMV-MIEP. Rep68 may therefore be enhancing expression from the HCMV-MIEP by interacting with other regulatory proteins that have an effect on the expression from this promoter or by altering the expression of a cellular gene whose product influences the HCMV-MIEP. Our results may also help to explain the previous observation that coinfection with AAV enhances the cytopathic effect of HCMV. (C) 1997 Academic Press. C1 NIDDK,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. NR 72 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 1997 VL 236 IS 1 BP 167 EP 176 DI 10.1006/viro.1997.8724 PG 10 WC Virology SC Virology GA XX860 UT WOS:A1997XX86000019 PM 9299629 ER PT J AU Katsafanas, GC Grem, JL Blough, HA Moss, B AF Katsafanas, GC Grem, JL Blough, HA Moss, B TI Inhibition of vaccinia virus replication by N-(phosphonoacetyl)-L-aspartate: Differential effects on viral gene expression result from a reduced pyrimidine nucleotide pool SO VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; ASPARTATE-TRANSCARBAMYLASE; COLORIMETRIC ASSAY; ANTIVIRAL ACTIVITY; N-(PHOSPHONACETYL)-L-ASPARTATE; GENOME; PROLIFERATION; CELLS; RIBONUCLEOTIDE; TRANSCRIPTION AB The replication of vaccinia virus was reduced by 3 logs in cells that had been treated before and during infection with a concentration of N-(phosphonoacetyl)-L-aspartate (PALA) which lowered the UTP and CTP to 5 and 20% of controls, respectively, without affecting cell viability. The antiviral activity of PALA was reversed with uridine, indicating that it was entirely due to the diminution in pyrimidine nucleotides. Analysis of Viral proteins revealed prolonged synthesis of some early stage species but a drastic reduction in late stage species, even though the nucleotide concentrations remained relatively constant throughout the infection. Although the gene expression pattern resembled that caused by a potent inhibitor of DNA synthesis, viral DNA accumulation was reduced by only 60%. Very little of the DNA made in the presence of PALA was converted to genome length molecules. The effect of PALA on transcription of early genes was complex: there was a twofold increase in the amount of a relatively short mRNA of 500 nucleotides but a two-to threefold decrease in the amount of a 4300-nucleotide mRNA encoding the largest subunit of RNA polymerase. In contrast, PALA severely inhibited the accumulation of viral intermediate and late stage mRNAs. The extreme sensitivity of vaccinia virus to PALA and the differential effects of the drug on viral gene expression result from the cascade mechanism of viral gene regulation. (C) 1997 Academic Press. C1 NIAID, VIRAL DIS LAB, NIH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, MED BRANCH, NCI, BETHESDA, MD 20889 USA. US BIOSCI INC, W CONSHOHOCKEN, PA 19428 USA. NR 40 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 1997 VL 236 IS 1 BP 177 EP 187 DI 10.1006/viro.1997.8735 PG 11 WC Virology SC Virology GA XX860 UT WOS:A1997XX86000020 PM 9299630 ER PT J AU Fearns, R Peeples, ME Collins, PL AF Fearns, R Peeples, ME Collins, PL TI Increased expression of the N protein of respiratory syncytial virus stimulates minigenome replication but does not alter the balance between the synthesis of mRNA and antigenome SO VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; CASEIN KINASE-II; NUCLEOCAPSID PROTEIN; RNA-SYNTHESIS; GENOME REPLICATION; LEADER RNA; TRANSCRIPTIONAL ACTIVITY; REGULATES TRANSCRIPTION; INVITRO REPLICATION; PHOSPHOPROTEIN-P AB A popular model for RNA synthesis by nonsegmented negative-strand RNA viruses is that transcription and RNA replication are executed by the same polymerase complex and that there is a dynamic balance between the two processes that is mediated by the nucleocapsid N protein. According to this model, transcription occurs until sufficient soluble N protein accumulates to initiate encapsidation of the nascent RNA product, which somehow switches the polymerase into a readthrough replicative mode. This model was examined for respiratory syncytial virus (RSV) using a reconstituted transcription and RNA replication system that involves a minireplicon and viral proteins that are expressed intracellularly from transfected plasmids. Preliminary experiments showed that reconstituted RNA replication was highly productive, such that on average each molecule of plasmid-supplied minigenome that became encapsidated was amplified 10- to 50-fold. N protein was increased on its own or in concert with the phosphoprotein P and in the presence or absence of the M2 ORF1 transcription elongation factor. The maximum level of N and P protein expression achieved from plasmids equalled or exceeded that obtained in RSV-infected cells. Increased levels of N protein stimulated RNA replication. This is consistent with the idea that RNA replication is dependent on the availability of N protein for encapsidation, which is one postulate of the model. The M2 ORF1 protein had no detectable effect on RNA replication under the various conditions of expression of N and P, which confirmed and extended previous results. However, there was no evidence of a significant switch in positive-sense RNA synthesis from transcription (synthesis of mRNAs) to RNA replication (synthesis of antigenome). The synthesis of positive-sense antigenome and mRNA appeared to occur at a fixed ratio, with mRNA being by far the more abundant product. (C) 1997 Academic Press. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT MICROBIOL & IMMUNOL,CHICAGO,IL 60612. NR 46 TC 68 Z9 71 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 1997 VL 236 IS 1 BP 188 EP 201 DI 10.1006/viro.1997.8734 PG 14 WC Virology SC Virology GA XX860 UT WOS:A1997XX86000021 PM 9299631 ER PT J AU Lauermann, V Hughes, SH Peden, KWC AF Lauermann, V Hughes, SH Peden, KWC TI Maintenance of an unusual polypurine tract in HIV-2: Stability to passage in culture SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEQUENCE FEATURES IMPORTANT; MURINE LEUKEMIA-VIRUS; REVERSE TRANSCRIPTION; NUCLEOTIDE-SEQUENCE; CIRCLE JUNCTION; RNASE-H; DNA-SYNTHESIS; CIRCULAR DNA; LINEAR DNA AB A stretch of purine residues, the polypurine tract (PPT), is found in all retroviruses and is used to initiate plus-strand DNA synthesis. While the PPT of most lentiviruses is a homogeneous sequence of purine residues, the PPT of some isolates of the human and simian immunodeficiency viruses is interrupted with a single pyrimidine residue. The ROD strain of human immunodeficiency virus type 2 (HIV-2) has such a pyrimidine-containing variant PPT. Virus generated from an infectious molecular clone, pROD10, was used to infect two CD4-positive T-cell lines, H9 and CEM. The sequence of the PPT was determined after two passages. From both cell lines, the variant PPT was retained, demonstrating that the presence of a pyrimidine in the PPT was fully functional and that there was no strong selection for an all-purine PPT. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,BETHESDA,MD 20892. NR 41 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 1997 VL 236 IS 1 BP 208 EP 212 DI 10.1006/viro.1997.8721 PG 5 WC Virology SC Virology GA XX860 UT WOS:A1997XX86000023 PM 9299633 ER PT J AU Strickler, HD Schiffman, MH AF Strickler, HD Schiffman, MH TI Is human papillomavirus an infectious cause of non-cervical anogenital tract cancers? SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID CARCINOMA; PREVALENCE; TYPE-16; WOMEN C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP Strickler, HD (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD SEP 13 PY 1997 VL 315 IS 7109 BP 620 EP 621 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XW694 UT WOS:A1997XW69400003 PM 9310555 ER PT J AU Bjorge, T Dillner, J Anttila, T Engeland, A Hakulinen, T Jellum, E Lehtinen, M Luostarinen, T Paavonen, J Pukkala, E Sapp, M Schiller, J Youngman, L Thoresen, S AF Bjorge, T Dillner, J Anttila, T Engeland, A Hakulinen, T Jellum, E Lehtinen, M Luostarinen, T Paavonen, J Pukkala, E Sapp, M Schiller, J Youngman, L Thoresen, S TI Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers SO BRITISH MEDICAL JOURNAL LA English DT Article ID ANAL EPIDERMOID CARCINOMA; SQUAMOUS-CELL CARCINOMA; INTRAEPITHELIAL NEOPLASIA; SERUM ANTIBODIES; UTERINE CERVIX; HPV DNA; TYPE-16; VULVA; INFECTION; EXPERIENCE AB Objective: To evaluate the association between infection with the major oncogenic types of human papillomavirus and the risk of developing non-cervical anogenital cancers in a cohort followed up prospectively. Design: Data from two large serum banks to which about 700 000 people had donated serum samples were followed up for a mean of 8 years. People who developed non-cervical anogenital cancers during follow up were identified by registry linkage with the nationwide cancer registries in Finland and Norway Within this cohort a nested case-control study was conducted based on the serological diagnosis of infection with human papillomavirus types 16, 18, and 33. Subjects: 81 cases and 240 controls matched for sex, age, and storage time of serum samples. Main outcome measures: Odds ratios of developing non-cervical anogenital cancers in presence of IgG antibodies to specific micro-organisms. Results: Subjects seropositive far human. papillomavirus type 16 had an increased risk of developing non-cervical anogenital cancers (odds ratio 3.1 (95% confidence interval 1.4 to 6.9)). Subjects seropositive for type 33 also had an increased risk (odds ratio 2.8 (1.0 to 8.3)) but not significantly after adjustment for infection with type 16. Seropositivity for human papillomavirus type 16 was associated with an increased risk of developing vulvar and vaginal. cancers (odds ratio 4.5 (1.1 to 22)) and a strongly increased risk of developing preinvasive vulvar and vaginal lesions (odds ratio infinity (3.8 to infinity)). Seropositivity for human papillomavirus type 18 increased the risk of developing preinvasive lesions (odds ratio 12 (1.2 to 590)). High, but non-significant odds ratios for types 16 and 33 were seen for penile cancers. Conclusions: This study provides prospective seroepidemiological evidence that infection with human papillomavirus type 16 confers an increased risk of developing non-cervical genital cancers, particularly vulvar and vaginal cancers. C1 KAROLINSKA INST,MICROBIOL & TUMORBIOL CTR,S-17177 STOCKHOLM,SWEDEN. NATL PUBL HLTH INST,FIN-90101 OULU,FINLAND. KAROLINSKA INST,DEPT CANC EPIDEMIOL,S-17177 STOCKHOLM,SWEDEN. NORWEGIAN CANC SOC,JANUS COMM,N-0369 OSLO,NORWAY. NATL PUBL HLTH INST,DEPT INFECT DIS EPIDEMIOL,FIN-00300 HELSINKI,FINLAND. FINNISH CANC REGISTRY,INST STAT & EPIDEMIOL CANC RES,FIN-00170 HELSINKI,FINLAND. UNIV HELSINKI HOSP,DEPT OBSTET & GYNECOL,FIN-00290 HELSINKI,FINLAND. UNIV TAMPERE,TAMPERE SCH PUBL HLTH,FIN-33101 TAMPERE,FINLAND. UNIV MAINZ,DEPT MED MICROBIOL,D-55101 MAINZ,GERMANY. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. UNIV OXFORD,CLIN TRIALS SERV UNIT,OXFORD OX2 6HE,ENGLAND. RP Bjorge, T (reprint author), CANC REGISTRY NORWAY,INST EPIDEMIOL CANC RES,N-0310 OSLO,NORWAY. NR 35 TC 47 Z9 49 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD SEP 13 PY 1997 VL 315 IS 7109 BP 646 EP 649 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XW694 UT WOS:A1997XW69400019 PM 9310566 ER PT J AU Garcia, MC Kim, HY AF Garcia, MC Kim, HY TI Mobilization of arachidonate and docosahexaenoate by stimulation of the 5-HT2A receptor in rat C6 glioma cells SO BRAIN RESEARCH LA English DT Article DE arachidonate; docosahexaenoate; serotonin-2 receptor; phospholipase A(2); phospholipase C; C6 glioma cell ID SEROTONIN RECEPTORS; PHOSPHOINOSITIDE HYDROLYSIS; INOSITOL PHOSPHATE; PHOSPHOLIPASE A(2); ACID; ASTROCYTES; BINDING; NEURONS; BRAIN; METABOLISM AB In this study, we demonstrate that astroglial 5-HT2A receptors are linked to the mobilization of polyunsaturated fatty acids (PUFA). Stimulation of C6 glioma cells, prelabeled with [(3)Hlarachidonate (AA, 20:4n6) and [C-14]docosahexaenoate (DHA, 22:6n3), with serotonin and the 5-HT2A/2C receptor agonist(+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) resulted in the mobilization of both [H-3] and [C-14] into the supernatant of the cell monolayers. The increased radioactivity in the supernatant was mainly associated with free fatty acids. Experiments using inhibitors of phosphoinositide-specific phospholipase C and PLA(2), inhibited the DOI-stimulated mobilization of AA and DHA, suggesting the involvement of both phospholipases. Ketanserin (1 mu M), a 5-HT2A/2C receptor antagonist, and MDL 100,907 (R(+)-alpha-(2,3-dimethoxyphenyl)]-1-[2-(4-fluophenylethyl)]-4-piperidine-methanol) (1 mu M), a highly selective antagonist for 5-HT2A receptors, significantly decreased the DOI-stimulated release of AA and DHA. These results indicate that the 5-HT2A receptor is coupled to the mobilization of PUFA. The release of AA and DHA in response to serotonin may represent a mechanism through which astroglia provide these polyunsaturated fatty acids to neurons. (C) 1997 Elsevier Science B.V. C1 NIAAA, SECT MASS SPECTROMETRY, LAB MEMBRANE BIOCHEM & BIOPHYS, NIH, ROCKVILLE, MD 20852 USA. NR 34 TC 80 Z9 83 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 12 PY 1997 VL 768 IS 1-2 BP 43 EP 48 DI 10.1016/S0006-8993(97)00583-0 PG 6 WC Neurosciences SC Neurosciences & Neurology GA YB442 UT WOS:A1997YB44200006 PM 9369299 ER PT J AU Wang, ZX Toloczko, D Young, LJ Moody, K Newman, JD Insel, TR AF Wang, ZX Toloczko, D Young, LJ Moody, K Newman, JD Insel, TR TI Vasopressin in the forebrain of common marmosets (Callithrix jacchus): studies with in situ hybridization, immunocytochemistry and receptor autoradiography SO BRAIN RESEARCH LA English DT Article DE stria terminalis; amygdala; lateral septum; hypothalamus ID AFFINITY BINDING-SITES; RAT-BRAIN; STRIA TERMINALIS; GOLDEN-HAMSTERS; LATERAL SEPTUM; PRAIRIE VOLES; MESSENGER-RNA; BED NUCLEUS; SUPRACHIASMATIC NUCLEUS; MICROTUS-OCHROGASTER AB The distribution of vasopressin (AVP) producing cells, their projections and AVP receptors was examined in the brain of common marmosets (Callithrix jacchus) using in situ hybridization, immunocytochemistry and receptor autoradiography. Clusters of cells labeled for AVP mRNA or stained for AVP immunoreactivity (AVP-ir) were found in the paraventricular (PVN), supraoptic (SON) and suprachiasmatic nuclei (SCN) of the hypothalamus. Scattered AVP producing cells were also found in the lateral hypothalamus and the bed nucleus of the stria terminalis (BST). Neither AVP mRNA-labeled nor AVP-ir cells were detected in the amygdala. Although AVP-ir fibers were evident outside of the hypothalamic-neurohypophyseal tract, a plexus of fibers in the lateral septum, as observed in the rat brain, was not detected. Receptor autoradiography using I-125-linear-AVP revealed specific binding for AVP receptors in the nucleus accumbens, diagonal band, lateral septum, the BST, SCN, PVN, amygdala, anterodorsal and ventromedial nucleus of the hypothalamus, indicating sites for central AVP action in the marmoset brain. Together, these data provide a comprehensive picture of AVP pathways in the marmoset brain, demonstrating differences from rodents in the distribution of cell bodies, fibers and receptors. (C) 1997 Elsevier Science B.V. C1 EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. NICHHD,COMPARAT ETHOL LAB,NIH,POOLESVILLE,MD 20837. RP Wang, ZX (reprint author), EMORY UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,ATLANTA,GA 30322, USA. FU NIMH NIH HHS [NIMH 54554, NIMH 56538] NR 49 TC 44 Z9 45 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 12 PY 1997 VL 768 IS 1-2 BP 147 EP 156 DI 10.1016/S0006-8993(97)00636-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA YB442 UT WOS:A1997YB44200018 PM 9369311 ER PT J AU Hirata, H Cadet, JL AF Hirata, H Cadet, JL TI Methamphetamine-induced serotonin neurotoxicity is attenuated in p53-knockout mice SO BRAIN RESEARCH LA English DT Article DE knockout mouse; methamphetamine; neurotoxicity; p53; serotonin transporter ID DISMUTASE TRANSGENIC MICE; DNA-DAMAGING AGENTS; WILD-TYPE P53; RAT-BRAIN; APOPTOSIS; DOPAMINE; 5-HYDROXYTRYPTAMINE; INDUCTION; RADICALS; PROTEIN AB Methamphetamine (METH) is a drug of abuse that causes deleterious effects to brain monoaminergic systems. The tumor suppressor gene, p53, is thought to play an important role in cell death. In the present study, we have assessed the participation of p53 in METH-induced serotonergic neurotoxicity, by using the mice lacking the gene for p53 protein. Three dosages (2.5, 5.0 and 10.0 mg/kg x 4) of METH were administered to wild-type (p53(+/+)), heterozygous (p53(-/-)) and homozygous (p53 -/-) p53-knockout mice. The two lower doses caused no significant changes in serotonin (5-HT) transporters in any of the groups. The highest dose (10.0 mg/kg) caused significant decreases in striatal 5-HT transporters in wild-type (-31%) and heterozygous (-18%) mice. In contrast, 5-HT transporters were not significantly decreased in homozygous mice. These results suggest that the tumor suppressor, p53, plays an important role in METH-induced serotonergic neurotoxicity in mice brain. These data provide further evidence for a role of p53 in the neurotoxic effects of METH. (C) 1997 Elsevier Science B.V. C1 NIDA,MOL NEUROPSYCHIAT SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. NR 22 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 12 PY 1997 VL 768 IS 1-2 BP 345 EP 348 DI 10.1016/S0006-8993(97)00798-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YB442 UT WOS:A1997YB44200043 PM 9369336 ER PT J AU Vance, BA Wu, WY Ribaudo, RK Segal, DM Kearse, KP AF Vance, BA Wu, WY Ribaudo, RK Segal, DM Kearse, KP TI Multiple dimeric forms of human CD69 result from differential addition of N-glycans to typical (Asn-X-Ser/Thr) and atypical (Asn-X-Cys) glycosylation motifs SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATION ANTIGEN CD69; ASPARAGINE-LINKED OLIGOSACCHARIDES; NATURAL-KILLER-CELLS; LYMPHOCYTE-ACTIVATION; AMINO-ACID; ENDOPLASMIC-RETICULUM; PROTEIN-C; RECEPTOR; EXPRESSION; SEQUENCE AB CD69 is expressed on the surface of all hematopoietically derived leukocytes and is suggested to function as a multipurpose cell-surface trigger molecule important in the development and activation of many different cell types. Human CD69 contains only a single consensus sequence for N-linked oligosaccharide addition within its extracellular domain (Asn-Val-Thr), yet exists as two distinct glycoforms that are assembled together into disulfide-linked homodimers and heterodimers. The molecular basis for human CD69 heterogeneity has remained elusive. In the current report we show that human CD69 glycoforms are generated before the egress of CD69 proteins from the endoplasmic reticulum to the Golgi and are synthesized under conditions where Golgi processing is inhibited, effectively ruling out the possibility that CD69 heterogeneity results from the differential processing of a single glycosylation site in the Golgi complex. Importantly, these data demonstrate that contrary to current belief, not one but two sites for N-glycan addition exist within the human CD69 extracellular do main and identify the second, ''cryptic'' CD69 N-glycan attachment site as the atypical Cys-containing glycosylation motif, Asn-Ala-Cys. The results in this study provide a molecular basis for human CD69 heterogeneity and show that multiple dimeric forms of human CD69 result from the variable addition of N-glycans to atypical and typical glycosylation motifs within the CD69 extracellular domain. C1 E CAROLINA UNIV, SCH MED, DEPT MICROBIOL & IMMUNOL, GREENVILLE, NC 27858 USA. NCI, EXPT IMMUNOL BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, LAB IMMUNE CELL BIOL, NIH, BETHESDA, MD 20892 USA. NR 34 TC 53 Z9 55 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 12 PY 1997 VL 272 IS 37 BP 23117 EP 23122 DI 10.1074/jbc.272.37.23117 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV744 UT WOS:A1997XV74400024 PM 9287313 ER PT J AU Chen, K Kuo, SC Hsieh, MC Mauger, A Lin, CM Hamel, E Lee, KH AF Chen, K Kuo, SC Hsieh, MC Mauger, A Lin, CM Hamel, E Lee, KH TI Antitumor agents .178. Synthesis and biological evaluation of substituted 2-aryl-1,8-naphthyridin-4(1H)-ones as antitumor agents that inhibit tubulin polymerization SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID COLCHICINE; PODOPHYLLOTOXIN; BINDING; SITE AB As part of our continuing search for potential anticancer drug candidates:in the 2-aryl-1,8-naphthyridin-4(1H)-one series, we have synthesized two series of 3'-substituted 2-phenyl-1,8-naphthyridin-4(1H)-ones and 2-naphthyl-1,8-naphthyridin-4(1H)-ones. All compounds showed significant cytotoxic effects (log GI(50) < -4.0; log molar drug concentration required to cause 50% growth inhibition) against a variety of human tumor cell lines of the National Cancer Institute's in vitro screen, including cells derived from solid tumors such as non-small cell lung, colon, central nervous system, melanoma, ovarian, prostate, and breast cancers. All 3'-substituted compounds demonstrated strong cytotoxic effects in almost all tumor cell lines. Introduction of an aromatic ring at the 2'- and 3'-positions also generated compounds with potent antitumor activity. Incorporation of an aromatic ring at the 3'- and 4'-positions produced compounds with reduced activity. Interestingly, introduction of a halogen at the 3'-position yielded compounds with different selectivity. for the tumor cell lines tested. All 3'-halogenated compounds (29-36) and compounds 38 and 42-44 were potent inhibitors of tubulin polymerization with activities nearly comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. Active agents also inhibited the binding of [H-3]colchicine to tubulin. C1 UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. CHINA MED COLL,GRAD INST PHARMACEUT CHEM,TAICHUNG 400,TAIWAN. NCI,DIV BASIC SCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG SYNTH & CHEM BRANCH,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-17625] NR 16 TC 91 Z9 91 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 12 PY 1997 VL 40 IS 19 BP 3049 EP 3056 DI 10.1021/jm970146h PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XV769 UT WOS:A1997XV76900010 PM 9301667 ER PT J AU Mazumder, A Neamati, N Sunder, S Schulz, J Pertz, H Eich, E Pommier, Y AF Mazumder, A Neamati, N Sunder, S Schulz, J Pertz, H Eich, E Pommier, Y TI Curcumin analogs with altered potencies against HIV-1 integrase as probes for biochemical mechanisms of drug action SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INTEGRASE; CATALYTIC DOMAIN; INHIBITION; RESIDUES; BINDING; PROTEIN; INVITRO; SITE AB We have previously reported the inhibitory activity of curcumin against human immunodeficiency virus type one (HIV-1) integrase. In the present study, we have synthesized and tested analogs of curcumin to explore the structure-activity relationships and mechanism of action of this family of compounds in more detail. We found that two curcumin analogs, dicaffeoyl-methane (6) and rosmarinic acid (9), inhibited both activities of integrase with IC50 values below 10 mu M. We have previously demonstrated that lysine 136 may play a role in viral DNA binding. We demonstrated equivalent potencies of two curcumin analogs against both this integrase mutant and wild-type integrase, suggesting that the curcumin-binding site and the substrate-binding site may not overlap. Combining one curcumin analog with the recently described integrase inhibitor NSC 158393 resulted in integrase inhibition which was synergistic, reflective of drug-binding sites which may not overlap. We have also determined that these analogs can inhibit binding of the enzyme to the viral DNA but that this inhibition is independent of divalent metal ion. Furthermore, kinetic studies of these analogs suggest that they bind to the enzyme at a slow rate. These studies can provide mechanistic and structural information which may guide the future design of integrase inhibitors. C1 NCI,DIV BASIC SCI,MOL PHARMACOL LAB,BETHESDA,MD 20892. FREE UNIV BERLIN,INST PHARM 3,D-14195 BERLIN,GERMANY. NR 23 TC 175 Z9 194 U1 2 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 12 PY 1997 VL 40 IS 19 BP 3057 EP 3063 DI 10.1021/jm970190x PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XV769 UT WOS:A1997XV76900011 PM 9301668 ER PT J AU Salvadori, S Balboni, G Guerrini, R Tomatis, R Bianchi, C Bryant, SD Cooper, PS Lazarus, LH AF Salvadori, S Balboni, G Guerrini, R Tomatis, R Bianchi, C Bryant, SD Cooper, PS Lazarus, LH TI Evolution of the Dmt-Tic pharmacophore: N-terminal methylated derivatives with extraordinary delta opioid antagonist activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TETRAPEPTIDE TYR-COH JOM-13; SELECTIVE PEPTIDE ANTAGONISTS; RECEPTOR SELECTIVITY; DELTORPHIN ANALOGS; TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID; ALKYLATED DERIVATIVES; ENKEPHALIN ANALOGS; MORPHINE-TOLERANCE; ACTIVITY PROFILE; SINGLE RESIDUE AB The delta opioid antagonist H-Dmt-Tic-OH (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) exhibits extraordinary delta receptor binding characteristics [K-i(delta) = 0.022 nM; K-i(u)/K-i(delta) = 150 000] and delta antagonism (pA(2) = 8.2; K-e = 5.7 nM). A change in chirality of Dmt at C alpha (1, 2, 6, 8, 10, 13) curtailed delta receptor parameters, while replacement of its alpha-amino function by a methyl group (3) led to inactivity; Tyr-Tic analogues 4 and 11 weakly interacted with delta receptors. N-Alkylation of H-Dmt-Tic-OH and H-Dmt-Tic-Ala-OH with methyl groups produced potent delta-opioid ligands with high delta receptor binding capabilities and enhanced delta antagonism: (i) N-Me-Dmt-Tic-OH 5 had high delta opioid binding (K-i(delta) = 0.2 nM), elevated delta antagonism on mouse vas deferens (MVD) (pA(2) = 8.5; K-e = 2.8 nM), and nondetectable mu activity with guinea pig ileum (GPI). (ii) N,N-Me-2-Dmt-Tic-OH (12) was equally efficacious in delta receptor binding (K-i(delta) = 0.12 nM; K-i(mu)/K-i(delta) = 20 000), but delta antagonism rose considerably (pA(2) = 9.4; K-e = 0.28 nM) with weak mu antagonism (pA(2) = 5.8; K-e = 1.58 mu M; GPI/MVD = 1:5640). N-Me-(9) and N,N-Me-2-Dmt-Tic-Ala-OH (15) also augmented delta opioid receptor binding, such that 15 demonstrated high affinity (K-i(delta) = 0.0755 nM) and selectivity (K-i(mu)/K-i(delta) = 20 132) with exceptional antagonist activity on MVD (pA(2) = 9.6; K-e = 0.22 nM) and weak antagonism on GPI (pA(2) = 5.8; K-e = 1.58 mu M; GPI/MVD = 1:7180). Although the amidated dimethylated dipeptide analogue 14 had high K-i(delta) (0.31 nM) and excellent antagonist activity (pA(2) = 9.9; K-e = 0.12 nM), the increased activity toward mu receptors in the absence of a free acid function at the C-terminus revealed modest delta selectivity (K-i(mu)/K-i(delta) = 1 655) and somewhat comparable bioactivity (GPI/MVD = 4500). Thus, the data demonstrate that N,N-(Me)(2)-Dmt-Tic-OH (12) and N,N-Me-2-Dmt-Tic-Ala-OH (15) retained high delta receptor affinities and delta selectivities and acquired enhanced potency in pharmacological bioassays on MVD greater than that of other peptide or non-peptide delta antagonists. C1 NIEHS,LCBRA,RES TRIANGLE PK,NC 27709. UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. UNIV FERRARA,CTR BIOTECHNOL,I-44100 FERRARA,ITALY. UNIV FERRARA,INST PHARMACOL,I-44100 FERRARA,ITALY. OI Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 NR 94 TC 82 Z9 83 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 12 PY 1997 VL 40 IS 19 BP 3100 EP 3108 DI 10.1021/jm9607663 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XV769 UT WOS:A1997XV76900017 PM 9301674 ER PT J AU Garcia, LJ Rosado, JA Tsuda, T Jensen, RT AF Garcia, LJ Rosado, JA Tsuda, T Jensen, RT TI CCK causes rapid tyrosine phosphorylation of p125(FAK) focal adhesion kinase and paxillin in rat pancreatic acini SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE tyrosine phosphorylation; pancreatic acini; cholecystokinin ID SWISS 3T3 CELLS; AFFINITY CHOLECYSTOKININ RECEPTORS; B GASTRIN RECEPTORS; GUINEA-PIG PANCREAS; AMYLASE RELEASE; BOMBESIN STIMULATION; ENZYME-SECRETION; DISPERSED ACINI; PROTEIN-KINASE; GROWTH-FACTOR AB Recent studies show CCK stimulates tyrosine phosphorylation (TYR PHOSP) of a number of proteins and evidence from the pancreas and other cellular systems suggest this could be important in mediating some of CCK's growth and secretory effects. In other tissues various neuropeptides such as bombesin can cause tyrosine phosphorylation of p125 focal adhesion kinase (p125(FAK)) and paxillin which are important in mediating their growth effects. The purpose of the present study was to determine the effects of CCK in rat pancreatic acini on the TYR PHOSP of these latter proteins, In dispersed rat pancreatic acini, cell lysates were incubated with an anti-phosphotyrosine mAb (PY20) which was immunoprecipitated and then analyzed by Western blotting with anti phosphotyrosine mAb (4G10), anti-p125(FAK) mAb or anti-paxillin mAb. CCK-8 at 5 min increased TYR PHOSP of five proteins of molecular weight > 60 000 including a broad M-r 110-130 000 and M-r 70-80 000, An increase in TYR PHOSP of both p125(FAK) and paxillin was detected within 1 min of adding CCK and reached a maximum at 2.5 min with a 9.1 +/- 1.9-fold increase for p125(FAK) and 3.6 +/- 0.6-fold for paxillin. CCK-8 caused a half-maximal increase in TYR PHOSP of p125(FAK) at 0.1 nM and paxillin at 0.03 nM. CCK-JMV also stimulated an increase in TYR PHOSP of both proteins, but was only 50% as efficacious as CCK-8, CCK-JMV caused a half-maximal increase at 10 nM and maximal at 1 mu M for both proteins. To investigate whether the low affinity CCK receptor state also caused TYR PHOSP of both proteins, increasing concentrations of CCK-JMV were added to a maximally effective CCK-8 concentration (1 nM). Detectable inhibition of CCK-8-stimulated TYR PHOSP occurred with 1 mu M CCK-JMV and with 3 mu M CCK-JMV the CCK-8-stimulated response was inhibited 50% and was the same as that seen with CCK-JMV alone. These studies demonstrate that in rat pancreatic acini, CCK causes rapid TYR PHOSP of both p125(FAK) and paxillin. This stimulation is mediated by both the high affinity and low affinity CCK receptor states. This phosphorylation of these proteins could be important in mediating CCK's effect on the cytoskeleton or growth effects as shown for a number of other agents (oncogenes, neuropeptides, integrins). (C) 1997 Elsevier Science B.V. C1 NIDDKD,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV EXTREMADURA,DEPT PHYSIOL,E-10080 CACERES,SPAIN. RI Garcia-Marin, Luis /L-4680-2014; rosado, juan/H-3488-2015 OI Garcia-Marin, Luis /0000-0002-1795-7381; rosado, juan/0000-0002-9749-2325 NR 53 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD SEP 11 PY 1997 VL 1358 IS 2 BP 189 EP 199 DI 10.1016/S0167-4889(97)00056-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XX785 UT WOS:A1997XX78500008 PM 9332455 ER PT J AU Cohen, LG Celnik, P PascualLeone, A Corwell, B Faiz, L Dambrosia, J Honda, M Sadato, N Gerloff, C Catala, MD Hallett, M AF Cohen, LG Celnik, P PascualLeone, A Corwell, B Faiz, L Dambrosia, J Honda, M Sadato, N Gerloff, C Catala, MD Hallett, M TI Functional relevance of cross-modal plasticity in blind humans SO NATURE LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; VISUAL-CORTEX; OCCIPITAL CORTEX; COIL SUPPRESSION; PERCEPTION; DISCRIMINATION; ACTIVATION AB Functional imaging studies of people who were blind from an early age have revealed that their primary visual cortex can be activated by Braille reading and other tactile discrimination task(1). Other studies have also shown that visual cortical areas can be activated by somatosensory input in blind subjects but not those with sight(2-7). The significance of this cross-modal plasticity is unclear, however, as it is not known whether the visual cortex can process somatosensory information in a functionally relevant way. To address this issue, we used transcranial magnetic stimulation to disrupt the function of different cortical areas in people who were blind from an early age as they identified Braille or embossed Roman letters, Transient stimulation of the occipital (visual) cortex induced errors in both tasks and distorted the tactile perceptions of blind subjects, In contrast, occipital stimu lation had no effect on tactile performance in normal-sighted subjects, whereas similar stimulation is known to disrupt their visual performance. We conclude that blindness from an early age can cause the visual cortex to be recruited to a role in somatosensory processing. We propose that this cross-modal plasticity may account in part for the superior tactile perceptual abilities of blind subjects. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. UNIV BUENOS AIRES,DEPT NEUROL REHABIL,FDN LUCHA ENFERMEDADES NEUROL INFANTILES,RA-1053 BUENOS AIRES,DF,ARGENTINA. BETH ISRAEL DEACONESS MED CTR,LAB MAGNET BRAIN STIMULAT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV VALENCIA,INST CAJAL,VALENCIA,SPAIN. FUKUI MED SCH,BIOMED IMAGING RES CTR,MATUOKA,FUKUI 91011,JAPAN. RP Cohen, LG (reprint author), NINCDS,HUMAN CORT PHYSIOL UNIT,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 30 TC 536 Z9 547 U1 4 U2 46 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 11 PY 1997 VL 389 IS 6647 BP 180 EP 183 DI 10.1038/38278 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XV757 UT WOS:A1997XV75700048 PM 9296495 ER PT J AU Hammer, SM Squires, KE Hughes, MD Grimes, JM Demeter, LM Currier, JS Eron, JJ Feinberg, JE Balfour, HH Dayton, LR Chodakewitz, JA Fischl, MA AF Hammer, SM Squires, KE Hughes, MD Grimes, JM Demeter, LM Currier, JS Eron, JJ Feinberg, JE Balfour, HH Dayton, LR Chodakewitz, JA Fischl, MA TI A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ZIDOVUDINE COMBINATION THERAPY; HIV-1 INFECTION; VIRAL INFECTIVITY; CLINICAL-TRIALS; TYPE-1 RNA; PLASMA; PROTEASE; LAMIVUDINE; EFFICACY; MONOTHERAPY AB Background The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. Methods A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. Stavudine could be substituted for zidovudine. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. Results The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine (or stavudine), and lamivudine (6 percent) than with zidovudine (or stavudine) and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P = 0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P = 0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results. Conclusions Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine. (C) 1997, Massachusetts Medical Society. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV ALABAMA, BIRMINGHAM, AL USA. LONDON SCH HYG & TROP MED, LONDON WC1, ENGLAND. HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. UNIV ROCHESTER, ROCHESTER, NY USA. UNIV SO CALIF, LOS ANGELES, CA USA. UNIV N CAROLINA, CHAPEL HILL, NC USA. UNIV MINNESOTA, MINNEAPOLIS, MN USA. UNIV CINCINNATI, CINCINNATI, OH USA. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. MERCK & CO INC, W POINT, PA USA. UNIV MIAMI, MIAMI, FL 33152 USA. NORTHWESTERN UNIV, EVANSTON, IL 60208 USA. GLAXO WELLCOME INC, RES TRIANGLE PK, NC 27709 USA. BRISTOL MYERS SQUIBB, NEW BRUNSWICK, NJ 08903 USA. NR 47 TC 2036 Z9 2063 U1 2 U2 46 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 11 PY 1997 VL 337 IS 11 BP 725 EP 733 DI 10.1056/NEJM199709113371101 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA XV174 UT WOS:A1997XV17400001 PM 9287227 ER PT J AU Su, YA Lee, MM Hutter, CM Meltzer, PS AF Su, YA Lee, MM Hutter, CM Meltzer, PS TI Characterization of a highly conserved gene (OS4) amplified with CDK4 in human sarcomas SO ONCOGENE LA English DT Article DE neoplasm; genetics; chromosome 12q; homogeneously staining region ID HUMAN-MALIGNANT GLIOMAS; SOFT-TISSUE SARCOMAS; HUMAN CANCERS; AMPLIFICATION; MDM2; REGION; DNA; SAS; MICRODISSECTION; AMPLICONS AB Amplification and overexpression of genes involved in growth control occur frequently in human Here, we report characterization of the fun length OS4 cDNA derived from 12q13-q15 (Su et al., Proc. Natl. Acad. Sci. USA, 91: 9121-9125, 1994), a region frequently amplified in sarcomas and brain tumors. This cDNA consists of 4833 base pairs (bp) encoding an open reading frame (ORF) of 283 amino acids, The ORF predicts a water-soluble acidic (pi 5.50) polypeptide with a molecular weight of 31 759. Database searches revealed highly significant similarity between OS4 and eight proteins predicted from genomic sequences of Caenorhabditis elegans, Schizosaccaharomyces pombe, and Saccharomyces cerevisiae. Thus, OS4 defines a novel evolutionarily conserved gene superfamily. Northern and database analyses revealed OS4 transcripts in numerous human tissues demonstrating its ubiquitous expression. We also observed overexpression of OS4 in three cancer cell lines with amplification of this gene. Furthermore, we detected OS4 amplification in 5/5 primary sarcomas with known amplification of the closely linked marker CDK4. These results demonstrate that the highly conserved OS4 gene is frequently included in the 22q13-q15 amplicon and may contribute to the development of a subset of sarcomas. C1 NATL HUMAN GENOME RES INST, NIH, CANC GENET LAB, BETHESDA, MD 20892 USA. NR 23 TC 31 Z9 33 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD SEP 11 PY 1997 VL 15 IS 11 BP 1289 EP 1294 DI 10.1038/sj.onc.1201294 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XV845 UT WOS:A1997XV84500006 PM 9315096 ER PT J AU Fukasawa, K Wiener, F VandeWoude, GF Mai, SB AF Fukasawa, K Wiener, F VandeWoude, GF Mai, SB TI Genomic instability and apoptosis are frequent in p53 deficient young mice SO ONCOGENE LA English DT Article DE p53; genomic instability; gene amplification; centrosome; Myc; apoptosis ID CELL-CYCLE CONTROL; WILD-TYPE P53; DIHYDROFOLATE-REDUCTASE GENE; C-MYC; CANCER-CELLS; AMPLIFICATION; OVEREXPRESSION; CHECKPOINT; ONCOGENES; MOUSE AB The loss of p53 tumor suppressor functions results in genetic instability, characteristically associated with changes in chromosome ploidy and gene amplification. In vivo, we find that cells from various organs of 4 to 6-week old p53-nullizygous (p53 (-/-)) mice display aneuploidy and frequent gene amplification as well as evidence for apoptosis. Regardless of tissue types, many p53 (-/-) cells contain multiple centrosomes and abnormally formed mitotic spindles. Thus, chromosome vivo may be associated with abnormal Moreover, we observed a significant increase in the number of cells overexpressing c-Myc in p53 (-/-) mice. Consistent with previous studies showing that c-Myc overexpression is associated with gene amplification in vitro, many of the p53 (-/-) cells exhibited, in the same cell, c-Myc overexpression and amplified c-myc, dihydrofolate reductase (DHFR), and carbamoyl-phosphate synthetase-aspartate transcarbamoyl-dihydroorotase (CAD) genes. Furthermore, apoptosis was frequently observed in cells isolated from p53 (-/-) mice. The apoptotic cells contained abnormally amplified centrosomes, displayed aneuploidy, high levels of c-Myc expression, as web as gene amplification. These results indicate that a high number of aberrant cells is eliminated by p53-independent pathways in vivo. C1 MANITOBA CANC TREATMENT & RES FDN,MANITOBA INST CELL BIOL,WINNIPEG,MB R3E 0V9,CANADA. UNIV MANITOBA,DEPT PHYSIOL,WINNIPEG,MB R3E 0V9,CANADA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV CINCINNATI,COLL MED,DEPT CELL BIOL NEUROBIOL & ANAT,CINCINNATI,OH. KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. RI Mai, Sabine/E-5667-2017 OI Mai, Sabine/0000-0002-5797-2201 NR 49 TC 117 Z9 118 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 11 PY 1997 VL 15 IS 11 BP 1295 EP 1302 DI 10.1038/sj.onc.1201482 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XV845 UT WOS:A1997XV84500007 PM 9315097 ER PT J AU Cao, WS BritosBray, M Claxton, DF Kelley, CA Speck, NA Liu, PP Friedman, AD AF Cao, WS BritosBray, M Claxton, DF Kelley, CA Speck, NA Liu, PP Friedman, AD TI CBF beta-SMMHC, expressed in M4Eo AML, reduced CBF DNA-binding and inhibited the G1 to S cell cycle transition at the restriction point in myeloid and lymphoid cells SO ONCOGENE LA English DT Article DE CBF beta-SMMHC; inv(16); CBF; leukemia; myeloid; cell cycle ID MYOSIN HEAVY-CHAIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; ACUTE MYELOMONOCYTIC LEUKEMIA; FACTOR-RECEPTOR PROMOTER; TRANSCRIPTION FACTOR; FUSION TRANSCRIPT; CHIMERIC PROTEIN; NUCLEAR FACTOR AB CBF beta-SMMHC is expressed from the inv(16) chromosome in M4Eo AML. Mice lacking CBF subunits or expressing the CBF beta-SMMHC or AML1-ETO onco-proteins failed to develop definitive hematopoiesis. To investigate these effects on hematopoiesis, we expressed CBF beta-SMMHC from the metallothionein promoter, in both 32D c13 myeloid cells and Ba/F3 B-lymphoid cells. Addition of zinc increased CBF beta-SMMHC levels more than tenfold, with higher levels evident in Ba/F3 lines. Levels obtained in 32D c13 cells were similar to those of endogenous CBF beta. Indirect immunofluorescence revealed zinc-inducible speckled, nuclear staining in Ba/F3 cells and diffuse nuclear staining in 32D c13 cells. CBF beta-SMMHC reduced endogenous CBF DNA-binding fivefold in both cell types, increased cell generation time 1.9-fold, on average, in 32D c13 cells and 1.5-fold in Ba/ F3 cells and decreased tritiated thymidine incorporation into DNA correspondingly. CBFP beta-SMMHC increased the proportion of cells in G1 1.7-fold, on average, in 32D c13 and Ba/F3 cells, and decreased the proportion of cells in S phase by a similar degree. CBF beta-SMMHC induced a marked increase in hypophosphorylated Rb, but did not alter IL-3 Receptor alpha or beta subunit levels. Neither apoptosis nor 32D differentiation was induced by zinc in IL-3 in these lines. Induction of CBF beta-SMMHC WC in 32D c13 cells did not inhibit their differentiation to neutrophils or their expression of myeloperoxidase mRNA in GCSF, and did not produce an eosinophilic phenotype. Additional, proliferative genetic changes in M4eo AMLs might potentiate inhibition of differentiation by CBF beta-SMMHC by allowing its increased expression. C1 JOHNS HOPKINS UNIV,CTR ONCOL,DIV PEDIAT ONCOL,BALTIMORE,MD 21287. UNIV TEXAS,DEPT HEMATOL,HOUSTON,TX 77030. NHLBI,NIH,BETHESDA,MD 20892. DARTMOUTH COLL,SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NHLBI NIH HHS [R01 HL51388] NR 67 TC 68 Z9 68 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 11 PY 1997 VL 15 IS 11 BP 1315 EP 1327 DI 10.1038/sj.onc.1201305 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XV845 UT WOS:A1997XV84500010 PM 9315100 ER PT J AU Rutberg, SE Saez, E Lo, S Jang, SI Markova, N Spiegelman, BM Yuspa, SH AF Rutberg, SE Saez, E Lo, S Jang, SI Markova, N Spiegelman, BM Yuspa, SH TI Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters SO ONCOGENE LA English DT Article DE c-Fos; Fra-2; mouse keratinocytes; differentiation; calcium; phorbol ester ID PROTEIN-KINASE-C; HUMAN INVOLUCRIN GENE; HUMAN EPIDERMAL-KERATINOCYTES; CROSS-LINKED ENVELOPE; HUMAN KERATIN-1 GENE; SKIN CARCINOGENESIS; PROXIMAL PROMOTER; RETINOIC ACID; CELL-ENVELOPE; EXPRESSION AB The major differentiation products of maturing keratinocytes contain AP-I regulatory motifs, and AP-1 DNA binding activity increases in cultured keratinocytes induced to differentiate by calcium. Here, we have analysed AP-I transcriptional activity in mouse keratinocytes treated with calcium and 12-O-tetradecanoyl phorbol-13-acetate (TPA), two agents that induce terminal differentiation of keratinocytes with different phenotypic consequences. Reporter constructs representing multimers of AP-I sequences found in keratinocyte marker genes demonstrated that the calcium-induced AP-I DNA binding activity does not correlate with transcriptional activation. Moreover, expression from active subunits of the profilaggrin and spr 1 promoters increased in calcium-treated keratinocytes when the AP-1 sites were disrupted, indicating that AP-I may negatively regulate certain promoters in these cells. In contrast, AP-1 reporter activity was increased in keratinocytes treated with TPA. This induction was dependent upon the expression of c-Fos since AP-I transcriptional activity was not increased in TPA-treated keratinocytes derived from c-fos null mice. Analysis of AP-1 protein expression in calcium-and TPA-treated keratinocytes demonstrated that only TPA increased the expression of c-Jun, while Jun B and Jun D were induced by both of these agents. c-Fos was expressed only in TPA treated keratinocytes, Fra-2 was expressed only in calcium-treated cells, and Fra-1 was expressed in both. Exogenous expression of Fra-2 repressed AP-1 transcriptional activity in TPA-treated keratinocytes, while c-Fos expression activated the AP-I sequence in calcium-treated keratinocytes. These data indicate that Fra-2 and c-Fos play opposing roles in regulating AP-1 activity in keratinocytes and that multiple inducer-dependent regulatory pathways may exist for the expression of keratinocyte differentiation markers. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NIAMSD,SKIN BIOL LAB,BETHESDA,MD. NR 64 TC 58 Z9 59 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 11 PY 1997 VL 15 IS 11 BP 1337 EP 1346 DI 10.1038/sj.onc.1201293 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XV845 UT WOS:A1997XV84500012 PM 9315102 ER PT J AU Cook, LS Daling, JR Voigt, LF deHart, MP Malone, KE Weiss, NS Stanford, JS Brinton, LA Gammon, MD Brogan, D AF Cook, LS Daling, JR Voigt, LF deHart, MP Malone, KE Weiss, NS Stanford, JS Brinton, LA Gammon, MD Brogan, D TI Characteristics of women with and without breast implants - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 UNIV UTAH,SALT LAKE CITY,UT. NATL CANC INST,BETHESDA,MD. COLUMBIA UNIV,NEW YORK,NY. EMORY UNIV,ATLANTA,GA 30322. RP Cook, LS (reprint author), FRED HUTCHINSON CANC RES CTR,1124 COLUMBIA ST,SEATTLE,WA 98104, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 10 PY 1997 VL 278 IS 10 BP 818 EP 819 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XU552 UT WOS:A1997XU55200024 ER PT J AU Huang, XL Barchi, JJ Lung, EDT Roller, PP Nara, PL Muschik, J Garrity, RR AF Huang, XL Barchi, JJ Lung, EDT Roller, PP Nara, PL Muschik, J Garrity, RR TI Glycosylation affects both the three-dimensional structure and antibody binding properties of the HIV-1(IIIB) GP120 peptide RP135 SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRINCIPAL NEUTRALIZING DETERMINANT; TYPE-1 ENVELOPE GLYCOPROTEIN; V3 LOOP; HIV ENVELOPE; CONFORMATIONAL PREFERENCES; MONOCLONAL-ANTIBODIES; SYNCYTIUM FORMATION; SECONDARY STRUCTURE; CIRCULAR-DICHROISM AB We have prepared glycosylated analogues of the principal neutralizing determinant of gp120 and studied their conformations by NMR and circular dichroism spectroscopies. The 24-residue peptide from the HIV-1(IIIB) isolate (residues 308-331) designated RP135, which contains the immunodominant tip of the V3 loop, was glycosylated with both N- and O-linked sugars. The structures of two glycopeptides, one with an N-linked beta-glucosamine (RP135(NG)) and. the other with two O-linked alpha-galactosamine units (RP135(digal)), were studied by NMR and circular dichroism spectroscopies. Molecular dynamics calculations based on the NMR data obtained in water solutions were performed to explore the conformational substates sampled by the glycopeptides. The data showed that covalently linking a carbohydrate to the peptide has a major effect on the local conformation and imparts additional minor changes at more distant sites of partially defined secondary structure. In particular, the transient beta-type turn comprised of the -Gly-Pro-Gly-Arg- segment at the ''tip'' of the V3 loop is more highly populated in RP135(digal) than in the native peptide and N-linked analogue. Binding data for the glycopeptides with 0.5 beta, a monoclonal antibody mapped to the RP135 sequence, revealed a significant enhancement in binding for RP135(digal) as compared with the native peptide, whereas binding was reduced for the N-linked glycopeptide. These data show that glycosylation of V3 loop peptides can affect their conformations as well as their interactions with antibodies, The design of more ordered and biologically relevant conformations of immunogenic regions from gp120 may aid in the design of more effective immunogens for HIV-1 vaccine development. C1 NCI, MED CHEM LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. NCI, VACCINE RESISTANT DIS SECT, DIV BASIC SCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 72 TC 80 Z9 81 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 9 PY 1997 VL 36 IS 36 BP 10846 EP 10856 DI 10.1021/bi9703655 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV538 UT WOS:A1997XV53800008 PM 9312273 ER PT J AU Banerjee, S Shigematsu, N Pannell, LK Ruvinov, S Orban, J Schwarz, F Herzberg, O AF Banerjee, S Shigematsu, N Pannell, LK Ruvinov, S Orban, J Schwarz, F Herzberg, O TI Probing the non-proline cis peptide bond in beta-lactamase from Staphylococcus aureus PC1 by the replacement Asn136->Ala SO BIOCHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; ACYL-ENZYME INTERMEDIATE; BACILLUS-LICHENIFORMIS 749/C; REFINED CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; 6-BETA-BROMOPENICILLANIC ACID; FOLDING PATHWAY; ACTIVE-SITE; RESOLUTION; MECHANISM AB A non-proline cis peptide is present between Glu166 and Ile167 in the active site of beta-lactamase from Staphylococcus nul eus PC1. To examine the role of the interaction between the side chain of Asn136 and the main chain of Glu166, the site-directed mutant N136A was produced. The enzyme shows no measurable hydrolytic activity toward a variety of penicillins or cephalosporins except for the chromogenic cephalosporin, nitrocefin. For nitrocefin, the progress curve exhibits a fast burst with a stoichiometry of 1 mol of degraded substrate per mole of enzyme followed by a slow phase with a hydrolysis rate that is reduced by approximately 700-fold compared with that of the wild-type enzyme. Thus, the mutant enzyme is deacylation defective. Monitoring the hydrolysis of nitrocefin after preincubation with a number of beta-lactam compounds shows that cephalosporins form stable acyl complexes with the enzyme, whereas penicillins do not. The molecular weight of the mutant was determined by electrospray mass spectrometry, and the presence of the stable acyl enzyme adducts with cephaloridine and cefotaxime was confirmed by both electrospray and MALDI mass spectrometry. Therefore, in addition to impairing deacylation, the acylation machinery has been altered compared with the wild-type enzyme to act on cephalosporins and not on penicillins. Urea denaturation and thermal unfolding studies show that the N136A mutant enzyme is less stable than the wild-type enzyme. However, stability against chemical denaturation of the mutant enzyme is enhanced in the presence of cephaloridine beyond the stability of the wild-type protein. This is attributed to accumulation of favorable interactions between the cephaloridine and the protein, which play a role in the folded state and not in the unfolded state. C1 UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. NIST,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RI Shigematsu, Naoyuki/B-9374-2014 FU NIAID NIH HHS [R01-AI27175] NR 49 TC 8 Z9 8 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 9 PY 1997 VL 36 IS 36 BP 10857 EP 10866 DI 10.1021/bi970352r PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV538 UT WOS:A1997XV53800009 PM 9283075 ER PT J AU Stevens, DA Lee, JY AF Stevens, DA Lee, JY TI Analysis of compassionate use itraconazole therapy for invasive aspergillosis by the NIAID Mycoses Study Group criteria SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ANTIFUNGAL AB Background: Successful therapy of invasive aspergillosis is difficult, and the place of new drugs is evolving. Earlier studies, with fewer patients, suggest itraconazole, an oral azole, is effective for some patients. Methods: Compassionate use data were analyzed by criteria applied previously in a multicenter trial as a reference point. The course of 125 patients was evaluated and their clinical settings and responses were categorized. Results: Overall, 34 (27%) had a complete response, 45 (36%) improved, 20 (16%) were unchanged, and 26 (21%) worsened. The subset receiving less than 2 weeks of itraconazole therapy had a worse outcome than the remainder of the group as did patients with sinus, central nervous system, or widely disseminated disease. Prior therapy, age, underlying disease, other sites of aspergillosis, dose, or Aspergillus species did not correlate closely with outcome. Inpatients who responded, a period of months was commonly required before objective improvement was documented. Patients who underwent bone marrow transplantation fared better than in previous reports. Conclusions: Itraconazole is effective in many patients with aspergillosis. This large series supports earlier conclusions that response rates are similar to those reported for amphotericin B. C1 CALIF INST MED RES,SAN JOSE,CA 95128. STANFORD UNIV,SCH MED,DEPT MED,DIV INFECT DIS & GEOG MED,STANFORD,CA 94305. NIAID,MYCOSES STUDY GRP,BETHESDA,MD 20892. UNIV ALABAMA,CTR COMPREHENS CANC,BIOSTAT UNIT,BIRMINGHAM,AL 35294. RP Stevens, DA (reprint author), SANTA CLARA VALLEY MED CTR,DEPT MED,DIV INFECT DIS,751 S BASCOM AVE,SAN JOSE,CA 95128, USA. NR 13 TC 84 Z9 87 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 8 PY 1997 VL 157 IS 16 BP 1857 EP 1862 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XV086 UT WOS:A1997XV08600009 PM 9290545 ER PT J AU Murata, T Obiri, NI Debinski, W Puri, RK AF Murata, T Obiri, NI Debinski, W Puri, RK TI Structure of IL-13 receptor: Analysis of subunit composition in cancer and immune cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE interleukin-13; interleukin-4; cytokine receptor; RT-PCR; immunoprecipitation ID COMMON GAMMA-CHAIN; INTERLEUKIN-4 RECEPTOR; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CARCINOMA-CELLS; ALPHA CHAIN; B-CELLS; CYTOKINE; COMPONENT; CLONING AB The structure of IL-13 receptor (IL-13R) is currently under investigation. Recently, two different human IL-13R chains, termed here IL-13R alpha and -alpha' have been cloned. We have examined various cancer and normal cell lines for the presence of mRNA for IL-13R alpha and alpha', as well as IL-4R p140 (termed beta chain) and IL-2R gamma(c), chains. In renal cell carcinoma, glioblastoma and ovarian carcinoma (IGROV-1) cell lines, both IL-13R alpha and alpha' chains were expressed (type I IL-13R). In epidermoid, colon, ovarian adenocarcinoma (PA-I) and normal mouse fibroblast (COS7) cell lines, only IL-13R alpha' was expressed (type II IL-13R), In hematopoietic TF-1 and EBV-immortalized normal B cell lines only IL-13R alpha' but not cu chain was expressed along with gamma(c) (type III or type IV IL-13R). IL-13R alpha' chain was faintly detected in human T cells. All cells expressed the IL-4Rp140 beta chain, These data provide a direct support for our model of IL-13R which consists of three different forms composed of different subunits. (C) 1997 Academic Press. C1 US FDA,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,NIH,BETHESDA,MD 20892. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT SURG,NEUROSURG SECT,HERSHEY,PA 17033. NR 24 TC 85 Z9 90 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 8 PY 1997 VL 238 IS 1 BP 90 EP 94 DI 10.1006/bbrc.1997.7248 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XX890 UT WOS:A1997XX89000019 PM 9299458 ER PT J AU Mori, T Shoemaker, RH Gulakowski, RJ Krepps, BL McMahon, JB Gustafson, KR Pannell, LK Boyd, MR AF Mori, T Shoemaker, RH Gulakowski, RJ Krepps, BL McMahon, JB Gustafson, KR Pannell, LK Boyd, MR TI Analysis of sequence requirements for biological activity of cyanovirin-N, a potent HIV (human immunodeficiency virus)-inactivating protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SOLUBLE CD4; BINDING AB Site-directed mutagenesis of DNA constructs coding for the novel, HIV-inactivating proteins cyanovirin-N (CV-N) and FLAG-cyanovirin-N (F-CV-N) was performed using mutagenic oligonucleotide primers in the polymerase chain reaction or by a restriction site elimination maneuver. The mutant constructs were expressed in Escherichia coli and the recombinant protein products were tested for binding to the HIV surface envelope glycoprotein gp120 and for antiviral activity against infectious HIV. Results showed an overall very high correlation (r(2) > 0.9) between the relative gp120 binding affinities and the anti-HIV activities of CV-N, F-CV-N, and the various mutants. An outlier, however, was a mutant which lacked one of the internal disulfide linkages normally present in CV-N and which showed modest gp120 binding but no antiviral activity against HIV. These findings are consistent with the view that gp120 binding is a necessary but not sufficient requirement for the HIV-inactivating activity of CV-N and related proteins; the sequence specificities for gp120 binding and anti-HIV activity are not identical. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892. NR 9 TC 37 Z9 39 U1 3 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 8 PY 1997 VL 238 IS 1 BP 218 EP 222 DI 10.1006/bbrc.1997.7202 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XX890 UT WOS:A1997XX89000043 PM 9299482 ER PT J AU Gustafson, KR Sowder, RC Henderson, LE Cardellina, JH McMahon, JB Rajamani, U Pannell, LK Boyd, MR AF Gustafson, KR Sowder, RC Henderson, LE Cardellina, JH McMahon, JB Rajamani, U Pannell, LK Boyd, MR TI Isolation, primary sequence determination, and disulfide bond structure of cyanovirin-N, an anti-HIV (human immunodeficiency virus) protein from the cyanobacterium Nostoc ellipsosporum SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ALGA MICROCYSTIS-AERUGINOSA; BLUE-GREEN-ALGAE; VACUUM LIQUID-CHROMATOGRAPHY; INHIBITORY NATURAL-PRODUCTS; CALOPHYLLUM-LANIGERUM; ANTIVIRAL ACTIVITY; CYCLIC-PEPTIDES; CALANOLIDE-A; SCYTONEMA; SCYTOPHYCINS AB A novel anti-HIV protein, cyanovirin-N (CV-N), was isolated from an aqueous cellular extract of the cultured cyanobacterium (blue-green alga) Nostoc ellipsosporum, purified by reverse-phase HPLC, and sequenced by N-terminal Edman degradation of the intact protein and peptide fragments produced by endoproteinase digestions. CV-N consists of a single 101 amino acid chain which exhibits significant internal sequence duplication, but no significant homology to previously described proteins or to the transcription products of known nucleotide sequences. Alignment of residues 1-50 with residues 51-101 reveals 13 conservative amino acid changes as well as direct homology between 16 amino acid residues. CV-N contains four cysteines which form two intrachain disulfide bonds, The positions of the disulfide linkages were established by fast atom bombardment mass spectral studies of peptide fragments generated by a tryptic digestion of the native protein, Reductive cleavage of these crosslinks resulted in loss of anti-HIV activity. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892. NR 49 TC 65 Z9 76 U1 1 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 8 PY 1997 VL 238 IS 1 BP 223 EP 228 DI 10.1006/bbrc.1997.7203 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XX890 UT WOS:A1997XX89000044 PM 9299483 ER PT J AU Alexandrov, I Shlyakhova, L Vartanian, A Zajac-Kaye, M Alexandrova, N AF Alexandrov, I Shlyakhova, L Vartanian, A Zajac-Kaye, M Alexandrova, N TI c-Raf kinase binds to N-terminal domain of c-Myc SO FEBS LETTERS LA English DT Article DE c-Raf; c-Myc; protein phosphorylation; protein-protein interaction ID PROTEIN-KINASE; IN-VIVO; V-RAF; TRANSCRIPTIONAL ACTIVATION; SIGNAL-TRANSDUCTION; DNA-BINDING; PHOSPHORYLATION; CELLS; ASSOCIATION; MEMBRANE AB We have demonstrated that the 50 N-terminal amino acids of c-Myc bind a kinase activity, which phosphorylates Myc in vitro predominantly on Thr(8). We also have shown that c-Raf, a widely known Ser/Thr kinase, involved in the Ras signaling pathway, binds to the same portion of c-Myc in vitro, In addition we were able to precipitate native c-Myc/Raf complex from various cell lysates. Physical interaction of Myc and Raf may potentially be a part of their well-known functional cooperation. (C) 1997 Federation of European Biochemical Societies. C1 RUSSIAN ACAD SCI, ENGELGARDT INST MOL BIOL, MOSCOW 117984, RUSSIA. RUSSIAN ACAD MED SCI, MENTAL HLTH RES CTR, MOSCOW 113152, RUSSIA. NCI, NAVY ONCOL BRANCH, BETHESDA, MD 20889 USA. NR 43 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 8 PY 1997 VL 414 IS 2 BP 465 EP 470 DI 10.1016/S0014-5793(97)00992-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XW759 UT WOS:A1997XW75900062 PM 9315742 ER PT J AU Caston, JR Trus, BL Booy, FP Wickner, RB Wall, JS Steven, AC AF Caston, JR Trus, BL Booy, FP Wickner, RB Wall, JS Steven, AC TI Structure of L-A virus: A specialized compartment for the transcription and replication of double-stranded RNA SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; CRYO-ELECTRON-MICROSCOPY; POL FUSION PROTEIN; SACCHAROMYCES-CEREVISIAE; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL RECONSTRUCTION; BLUETONGUE VIRUS; SIMIAN VIRUS-40; CORE PARTICLE; CAPSIDS AB The genomes of double-stranded (ds)RNA viruses are never exposed to the cytoplasm but are confined to and replicated from a specialized protein-bound compartment-the viral capsid, We have used cryoelectron microscopy and three-dimensional image reconstruction to study this compartment in the case of L-A, a yeast virus whose capsid consists of 60 asymmetric dimers of Gag protein (76 kD). At 16-Angstrom resolution, we distinguish multiple domains in the elongated Gag subunits, whose nonequivalent packing is reflected in subtly different morphologies of the two protomers. Small holes, 10-15 Angstrom across, perforate the capsid wall, which functions as a molecular sieve, allowing the exit of transcripts and the influx of metabolites, while retaining dsRNA and excluding degradative enzymes. Scanning transmission electron microscope measurements of mass-per-unit length suggest that L-A RNA is an A-form duplex, and that RNA filaments emanating from disrupted virions often consist of two or more closely associated duplexes. Nuclease protection experiments confirm that the genome is entirely sequestered inside full capsids, but it is packed relatively loosely; in L-A, the center-to-center spacing between duplexes is 40-45 Angstrom, compared with 25-30 Angstrom in other double-stranded viruses. The looser packing of L-A RNA allows for maneuverability in the crowded capsid interior, in which the genome (in both replication and transcription) must be translocated sequentially past the polymerase immobilized on the inner capsid wall. C1 NIAMSD,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,COMPUTAT BIOSCI & ENGN LAB,DIV COMP RES & TECHNOL,NIH,BETHESDA,MD 20892. NIDDKD,LAB BIOCHEM & GENET,NIH,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. RI Caston, Jose/L-5896-2014 OI Caston, Jose/0000-0003-2350-9048 NR 58 TC 78 Z9 81 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 8 PY 1997 VL 138 IS 5 BP 975 EP 985 DI 10.1083/jcb.138.5.975 PG 11 WC Cell Biology SC Cell Biology GA XW463 UT WOS:A1997XW46300004 PM 9281577 ER PT J AU Mattay, VS Callicott, JH Bertolino, A Santha, AKS Tallent, KA Goldberg, TE Frank, JA Weinberger, DR AF Mattay, VS Callicott, JH Bertolino, A Santha, AKS Tallent, KA Goldberg, TE Frank, JA Weinberger, DR TI Abnormal functional lateralization of the sensorimotor cortex in patients with schizophrenia SO NEUROREPORT LA English DT Article DE cortex; fMRI; functional imaging; lateralization; motor function; schizophrenia ID POTENTIALS; INHIBITION; MOVEMENTS; FLUENCY AB PREVIOUS neuroimaging studies have suggested that patients with schizophrenia fail to recruit appropriate focal patterns of cortical responses to cognitive tasks. We investigated whether patients with schizophrenia show a normal focal response to a simple motor task. Seven strongly right-handed patients with schizophrenia and seven strongly right-handed normal subjects performed motor tasks of increasing complexity. Patients were unable to recruit as focal a response even to a simple, automatic sequential finger movement task. They showed greater ipsilateral activation in the primary sensorimotor and lateral premotor regions and had a significantly lower laterality quotient than normal subjects. These phenomena increased with the complexity of the task. These results demonstrate a functional disturbance in the cortical motor circuitry of patients with schizophrenia. C1 ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,CLIN DISORDERS BRANCH,NIH,WASHINGTON,DC 20032. NIH,OIR,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. RI Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380 NR 29 TC 60 Z9 61 U1 2 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 8 PY 1997 VL 8 IS 13 BP 2977 EP 2984 DI 10.1097/00001756-199709080-00034 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XV844 UT WOS:A1997XV84400034 PM 9376542 ER PT J AU Rapaka, RS AF Rapaka, RS TI Molecular pharmacology biochemistry and chemical toxicology of drugs of abuse. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 4 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85701441 ER PT J AU Rhee, SG AF Rhee, SG TI Interaction between phospholipase C and other lipid signaling pathways. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 13 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85700479 ER PT J AU Porter, DW Yakushiji, H Nakabeppu, Y Sekiguchi, M Fivash, MJ Kasprzak, KS AF Porter, DW Yakushiji, H Nakabeppu, Y Sekiguchi, M Fivash, MJ Kasprzak, KS TI 8-oxo-dGTPases, the deoxynucleotide pool-purifying enzymes, are inhibited by carcinogenic metal ions Ni(II), Cu(II), Co(II), and Cd(II). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. KYUSHU UNIV,DEPT BIOCHEM,FUKUOKA 812,JAPAN. FUKUOKA DENT COLL,DEPT BIOL,FUKUOKA,JAPAN. DATA MANAGEMENT SERV INC,FCRDC,FREDERICK,MD 21702. RI Nakabeppu, Yusaku/A-8902-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 32 EP TOXI PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85701469 ER PT J AU Barlow, T Dipple, A AF Barlow, T Dipple, A TI Mechanisms of guanosine aralkylation probed with para-substituted styrene oxides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 43 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85701480 ER PT J AU Milne, GWA Wang, SM Nicklaus, MC AF Milne, GWA Wang, SM Nicklaus, MC TI Pharmacophores in drug discovery. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 47 EP CINF PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85700914 ER PT J AU Shears, SB AF Shears, SB TI Versatility in inositide signaling. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,INOSITIDE SIGNALING GRP,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 53 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85700519 ER PT J AU Erickson, JW AF Erickson, JW TI Structural mechanisms of drug resistance for HIV-1 protease mutants. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 56 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85701255 ER PT J AU Brooks, BR AF Brooks, BR TI Techniques in QM/MM modeling of macromolecular systems. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 72 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85701271 ER PT J AU Tycko, R Bennett, AE Long, HW Weliky, DP AF Tycko, R Bennett, AE Long, HW Weliky, DP TI Structures of structured and unstructured peptides from solid state NMR. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 92 EP PHYS PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ859 UT WOS:A1997XQ85900609 ER PT J AU Kozikowski, AP Qiao, LX Wang, SM George, C Lewin, NE Blumberg, PM AF Kozikowski, AP Qiao, LX Wang, SM George, C Lewin, NE Blumberg, PM TI Synthesis, modeling and bioactivity of a new class of PKC modulators SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,DRUG DISCOVERY LAB,WASHINGTON,DC 20007. USN,RES LAB,WASHINGTON,DC 20375. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 130 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85702589 ER PT J AU Antonucci, JM Fowler, BO Stansbury, JW AF Antonucci, JM Fowler, BO Stansbury, JW TI Facile syntheses of acrylic organosilsesquioxanes for dental applications SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIST,GAITHERSBURG,MD 20899. NIDR,NIH,BETHESDA,MD 20982. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 143 EP POLY PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ859 UT WOS:A1997XQ85901077 ER PT J AU Burke, TR Yao, ZJ Ye, B Wang, SM Zhang, ZY Barford, D AF Burke, TR Yao, ZJ Ye, B Wang, SM Zhang, ZY Barford, D TI Structure-based design of protein-tyrosine phosphatase inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RI Yao, Zhu-Jun/E-7635-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 160 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85701359 ER PT J AU Pan, WX Eissenstat, M Majer, P Gulnik, SV Yu, B Lee, A Bhat, TN Collins, JR Erickson, JW AF Pan, WX Eissenstat, M Majer, P Gulnik, SV Yu, B Lee, A Bhat, TN Collins, JR Erickson, JW TI Design and parallel synthesis of inhibitor library of human cathepsin D. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,SAIC,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 170 EP MEDI PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85702629 ER PT J AU Chatfield, DC Brooks, BR Szabo, A AF Chatfield, DC Brooks, BR Szabo, A TI Molecular dynamics of staphyloccocal nuclease SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 FLORIDA INT UNIV,DEPT CHEM,MIAMI,FL 33199. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 190 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85701389 ER PT J AU Benzaria, S Marquez, VE Lewin, NE Blumberg, PM AF Benzaria, S Marquez, VE Lewin, NE Blumberg, PM TI Strategies for the design of conformationally restricted diacylglyerols (dag) as protein kinase C (PK-C) ligands based on a receptor-guided approach .1. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 191 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85702649 ER PT J AU Nacro, K Marquez, VE Lewin, NE AF Nacro, K Marquez, VE Lewin, NE TI Strategies for the design of conformationally restricted diacylglyerols (DAG) as protein kinase C (PK-C) ligands based on a receptor-guided approach .2. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 192 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85702650 ER PT J AU Ananthan, S Kezar, HS Porreca, F Davis, P Xu, H Rothman, RB AF Ananthan, S Kezar, HS Porreca, F Davis, P Xu, H Rothman, RB TI Opioid receptor ligands: Synthesis and structure-activity relationships of 4'-phenyl pyrido- and pyrimidoepoxymorphinans. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SO RES INST,BIRMINGHAM,AL 35255. UNIV ARIZONA,DEPT PHARMACOL,TUCSON,AZ 85724. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 236 EP MEDI PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85702692 ER PT J AU Jackson, CL Chanzy, HD Booy, FP Tomalia, DA Amis, EJ AF Jackson, CL Chanzy, HD Booy, FP Tomalia, DA Amis, EJ TI Characterization of dendrimer molecules by staining and cryoelectron microscopy techniques. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899. CNRS,CERMAV,GRENOBLE,FRANCE. NIH,BETHESDA,MD 20892. MICHIGAN MOL INST,MIDLAND,MI 48640. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 259 EP PMSE PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ859 UT WOS:A1997XQ85901521 ER PT J AU Durell, SR Guy, HR AF Durell, SR Guy, HR TI Structural models of the transmembrane portion of voltage-gated K+ channels in closed, open, and inactivated conformations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,LECB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 276 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ857 UT WOS:A1997XQ85702727 ER PT J AU Tjandra, N Ottiger, M Bax, A AF Tjandra, N Ottiger, M Bax, A TI Measurement of H-1, C-13 and N-15 chemical shift anisotropy in proteins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 7 PY 1997 VL 214 BP 403 EP PHYS PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA XQ859 UT WOS:A1997XQ85900917 ER PT J AU Smith, MW Dean, M Carrington, M Huttley, GA OBrien, SJ AF Smith, MW Dean, M Carrington, M Huttley, GA OBrien, SJ TI CCR5-Delta 32 gene deletion in HIV-1 infected patients SO LANCET LA English DT Letter ID PROGRESSION; ALLELE C1 NCI,LAB GENOM DIVERS,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RI Smith, Michael/B-5341-2012; Dean, Michael/G-8172-2012; Huttley, Gavin/G-5169-2015 OI Dean, Michael/0000-0003-2234-0631; Huttley, Gavin/0000-0001-7224-2074 NR 4 TC 23 Z9 25 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 6 PY 1997 VL 350 IS 9079 BP 741 EP 741 DI 10.1016/S0140-6736(05)63551-9 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XU977 UT WOS:A1997XU97700059 PM 9291930 ER PT J AU Pozsgay, V Dubois, EP Lotter, H Neszmelyi, A AF Pozsgay, V Dubois, EP Lotter, H Neszmelyi, A TI Synthesis and X-ray crystallographic study of cyclobis-(1->2)-alpha-D-glucopyranosyl peracetate SO CARBOHYDRATE RESEARCH LA English DT Article DE cyclic disaccharide; cyclobisglucosyl; internal glycosylation; Kojibiose; X-ray analysis ID DIHETEROLEVULOSAN-IV; HYDROGEN-FLUORIDE; FACILE SYNTHESIS; OLIGOSACCHARIDES; POLYCONDENSATION; CYCLODEXTRINS; DIANHYDRIDES; DERIVATIVES; REACTIVITY; GLYCOSYL AB Treatment of O-(3,4,6-tri-O-acetyl-2-O-benzyl-alpha-D-glucopyranosyl)-( 1 --> 2)-3,4,6-tri-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate with BF3 . Et2O gave a high yield of the peracetate of cyclobis-(1 --> 2)-alpha-D-glucopyranosyl (6). Compound 6 crystallizes in the space group P2(1) [a = 6.888(2), b = 24.771(5), c = 9.105(2) Angstrom, beta = 111.49(2)degrees, Z= 2] and shows a high degree of symmetry. In 6 the two alpha-D-glucopyranosyl residues are in a slightly distorted chair conformation. The glucose moieties are interconnected by a 1,4-dioxane moiety which is ina boat conformation, with the anomeric carbon atoms in the bow positions. (C) 1997 Elsevier Science Ltd. C1 UNIV MUNICH,INST PHARMAZEUT BIOL,D-80333 MUNICH,GERMANY. HUNGARIAN ACAD SCI,CENT RES INST CHEM,H-1025 BUDAPEST,HUNGARY. RP Pozsgay, V (reprint author), NICHHD,LAB DEV & MOL IMMUN,NIH,BETHESDA,MD 20892, USA. RI Neszmelyi, Andras/C-3104-2009; Neszmelyi, Andras/A-6323-2010 NR 34 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 5 PY 1997 VL 303 IS 2 BP 165 EP 173 DI 10.1016/S0008-6215(97)00153-5 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA YB563 UT WOS:A1997YB56300005 ER PT J AU Hodosi, G Kovac, P AF Hodosi, G Kovac, P TI Manipulation of free carbohydrates via stannylene acetals. Preparation of beta-per-O-acyl derivatives of D-mannose, L-rhamnose, 6-O-trityl-D-talose, and D-lyxose SO CARBOHYDRATE RESEARCH LA English DT Article DE stannylene complexes; 1,2-O-cis-stannylene acetals; beta-mannose; beta-rhamnose; beta-talose; beta-lyxose ID OLIGOSACCHARIDES; GLYCOSYLATION AB A simple and high-yielding method for the preparation of 1-O-beta-acyl derivatives of carbohydrates with an axial OH group at C-2 is described. It utilizes the property of unprotected carbohydrates to preferentially form 1,2-O-cis stannylene acetals, when treated with dibutyltin oxide. These acetals can be acylated with retention of configuration at the anomeric position. (C) 1997 Elsevier Science Ltd. C1 NIDDK,NIH,BETHESDA,MD 20892. NR 21 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 5 PY 1997 VL 303 IS 2 BP 239 EP 243 DI 10.1016/S0008-6215(97)00155-9 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA YB563 UT WOS:A1997YB56300014 ER PT J AU Lijam, N Paylor, R McDonald, MP Crawley, JN Deng, CX Herrup, K Stevens, KE Maccaferri, G McBain, CJ Sussman, DJ WynshawBoris, A AF Lijam, N Paylor, R McDonald, MP Crawley, JN Deng, CX Herrup, K Stevens, KE Maccaferri, G McBain, CJ Sussman, DJ WynshawBoris, A TI Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1 SO CELL LA English DT Article ID SEGMENT-POLARITY GENE; PREPULSE INHIBITION; ACOUSTIC STARTLE; SCHIZOPHRENIC-PATIENTS; INBRED STRAINS; ANIMAL-MODEL; DROSOPHILA; STIMULATION; DEFICITS; HABITUATION AB Mice completely deficient for Dvl1, one of three mouse homologs of the Drosophila segment polarity gene Dishevelled, were created by gene targeting. Dv1-deficient mice are viable, fertile, and structurally normal. Surprisingly, these mice exhibited reduced social interaction, including differences in whisker trimming, deficits in nest-building, less huddling contact during home cage sleeping, and subordinate responses in a social dominance test. Sensorimotor gating was abnormal, as measured by deficits in prepulse inhibition of acoustic and tactile startle. Thus, Dv1 mutants may provide a model for aspects of several human psychiatric disorders. These results are consistent with an interpretation that common genetic mechanisms underlie abnormal social behavior and sensorimotor gating deficits and implicate Dvl1 in processes underlying complex behaviors. C1 NIMH,SECT BEHAV NEUROPHARMACOL,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NATL INST HLTH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH 44106. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. UNIV MARYLAND,SCH MED,DIV HUMAN GENET,BALTIMORE,MD 21201. RP Lijam, N (reprint author), NATL HUMAN GENOME RES INST,LAB GENET DIS RES,BETHESDA,MD 20892, USA. RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [CA63929] NR 51 TC 313 Z9 325 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 5 PY 1997 VL 90 IS 5 BP 895 EP 905 DI 10.1016/S0092-8674(00)80354-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XV563 UT WOS:A1997XV56300010 PM 9298901 ER PT J AU Skinner, J Sinclair, C Romeo, C Armstrong, D Charbonneau, H Rossie, S AF Skinner, J Sinclair, C Romeo, C Armstrong, D Charbonneau, H Rossie, S TI Purification of a fatty acid-stimulated protein-serine/threonine phosphatase from bovine brain and its identification as a homolog of protein phosphatase 5 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TETRATRICOPEPTIDE REPEAT DOMAIN; SERINE THREONINE PHOSPHATASES; LIGHT-CHAIN-PHOSPHATASE; SMOOTH-MUSCLE CELLS; ARACHIDONIC-ACID; ACTIVATING PROTEIN; CATALYTIC SUBUNIT; ESCHERICHIA-COLI; RAT-BRAIN; CALCIUM AB An arachidonic acid-stimulated Ser/Thr phosphatase activity was detected in soluble extracts prepared from rat pituitary clonal GH(4)C(1) cells, rat or bovine brain, and bovine heart. The enzyme activity was purified to homogeneity from bovine brain as a monomer with a M-r of 63,000 and a specific activity of 32 nmol of P-i released per min/mg of protein when assayed in the presence of 10 mu M phosphocasein in the absence of lipid. Arachidonic acid stimulated activity 4-14-fold, with half-maximal stimulation at 50-100 mu M, when assayed in the presence of a variety of phosphosubstrates including casein, reduced carboxamidomethylated and maleylated lysozyme, myelin basic protein, and histone. Oleic acid, linoleic acid, and palmitoleic acid also stimulated activity; however, saturated fatty acids and alcohol or methyl ester derivatives of fatty acids did not significantly affect activity. The lipid-stimulated phosphatase was identified as the bovine equivalent of protein phosphatase 5 or a closely related homolog by sequence analysis of proteolytic fragments generated from the purified enzyme, When recombinant rat protein phosphatase 5 was expressed as a cleavable glutathione S-transferase fusion protein, the affinity-purified thrombin-cleaved enzyme exhibited a specific activity and sensitivity to arachidonic acid similar to those of the purified bovine brain enzyme. These results suggest that protein phosphatase 5 may be regulated in vivo by a lipid second messenger or another endogenous activator. C1 PURDUE UNIV,DEPT BIOCHEM,W LAFAYETTE,IN 47907. NIEHS,LAB SIGNAL TRANSDUCT,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA59935]; NIDDK NIH HHS [DK20542]; NINDS NIH HHS [NS31221] NR 51 TC 88 Z9 89 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1997 VL 272 IS 36 BP 22464 EP 22471 DI 10.1074/jbc.272.36.22464 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV492 UT WOS:A1997XV49200017 PM 9278397 ER PT J AU Michelotti, EF Sanford, S Freije, JMP MacDonald, NJ Steeg, PS Levens, D AF Michelotti, EF Sanford, S Freije, JMP MacDonald, NJ Steeg, PS Levens, D TI Nm23/PuF does not directly stimulate transcription through the CT element in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSIDE-DIPHOSPHATE KINASE; NUCLEAR RIBONUCLEOPROTEIN-K; BREAST-CARCINOMA CELLS; TUMOR-METASTASIS; MYC PROMOTER; DROSOPHILA DEVELOPMENT; MYXOCOCCUS-XANTHUS; ESCHERICHIA-COLI; MELANOMA-CELLS; DNA-BINDING AB Decreased levels of the nm23 gene product have been correlated with increased tumor metastatic potential in a variety of malignancies. At least a subset of the regulatory properties of Nm23 has been proposed to be due to transactivation of the human c-myc oncogene through binding to a homopyrimidine tract 140 base pairs upstream of the transcription start site (termed the CT element or the PuF site). Conventional transcription factors possess DNA binding and transactivation domains; Nm23 fusion proteins were used to address two questions. First, if provided with a well characterized DNA binding domain, does Nm23 possess a transactivation domain capable of stimulating transcription of an appropriate reporter? Second, if provided with a potent transactivation domain, is the DNA binding of Nm23 of sufficient specificity and affinity to direct the fusion protein to a CT-dependent reporter? Since reporter gene expression was not stimulated in either case, we conclude that Nm23 does not directly stimulate transcription through binding to the CT element and that its antimetastatic and other reported functions are likely due to other biochemical activities. C1 NCI,WOMENS CANC SECT,PATHOL LAB,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NCI,GENE REGULAT SECT,NIH,BETHESDA,MD 20892. RI Levens, David/C-9216-2009; Freije, Jose M.P./A-6535-2008 OI Levens, David/0000-0002-7616-922X; Freije, Jose M.P./0000-0002-4688-8266 NR 41 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1997 VL 272 IS 36 BP 22526 EP 22530 DI 10.1074/jbc.272.36.22526 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV492 UT WOS:A1997XV49200025 PM 9278405 ER PT J AU Simpson, PB Mehotra, S Lange, GD Russell, JT AF Simpson, PB Mehotra, S Lange, GD Russell, JT TI High density distribution of endoplasmic reticulum proteins and mitochondria at specialized Ca2+ release sites in oligodendrocyte processes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; CALCIUM WAVES; SARCOPLASMIC-RETICULUM; CELLS; RAT; CALRETICULIN; ASTROCYTES; STORES; LOCALIZATION; EXPRESSION AB In oligodendrocyte processes, methacholine-evoked Ca2+ waves propagate via regions of specialized Ca2+ release kinetics (wave amplification sites) at which the amplitude and rate of rise of local Ca2+ signals are markedly higher than in surrounding areas (Simpson, P. B., and Russell, J. T. (1996) J. Biol. Chem. 271, 33493-33501). In the present study we have examined the effects of other phosphoinositide-coupled agonists on Ca2+ in these cells, and the structural specializations underlying regenerative wave amplification sites, Both bradykinin and norepinephrine evoke Ca2+ waves, which initiate at the same loci and propagate through the cell body and multiple processes via identical wave amplification sites, Antibodies against type 2 inositol 1,4,5-trisphosphate receptors (InsP(3)R2) and calreticulin identify expression of these proteins in oligodendrocyte membranes in Western blots, Immunocytochemistry followed by high resolution fluorescence microscopy revealed that both InsP(3)R2 and calreticulin are expressed in high intensity patches along processes. Cross-correlation analysis of the profiles of local Ca2+ release kinetics during a Ca2+ wave and immunofluorescence for these proteins along cellular processes showed that the domains of high endoplasmic reticulum protein expression correspond closely to wave amplification sites, Staining cells with the mitochondrial dye, MitoTracker(R), showed that mitochondria are only found in intimate association with these sites possessing high density endoplasmic reticulum proteins, and they remain in the same locations over relatively long periods of time. It appears, therefore, that multiple specializations are found at domains of elevated Ca2+ release in oligodendrocyte processes, including high levels of calreticulin, InsP(3)R2 Ca2+ release channels, and mitochondria. C1 NICHHD,LCMN,NIH,BETHESDA,MD 20892. NINCDS,NIH,BETHESDA,MD 20892. NR 40 TC 133 Z9 133 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1997 VL 272 IS 36 BP 22654 EP 22661 DI 10.1074/jbc.272.36.22654 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV492 UT WOS:A1997XV49200043 PM 9278423 ER PT J AU Watson, JT AF Watson, JT TI NIH Biomaterials and Medical Implant Science Coordinating Committee SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Editorial Material RP Watson, JT (reprint author), NHLBI,BIOENGN RES GRP,6701 ROCKLEDGE DR,RM 9178,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD SEP 5 PY 1997 VL 36 IS 3 BP 283 EP 283 PG 1 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA XP501 UT WOS:A1997XP50100001 ER PT J AU Caffrey, M Cai, ML Kaufman, J Stahl, SJ Wingfield, PT Gronenborn, AM Clore, GM AF Caffrey, M Cai, ML Kaufman, J Stahl, SJ Wingfield, PT Gronenborn, AM Clore, GM TI Determination of the secondary structure and global topology of the 44 kDa ectodomain of gp41 of the simian immunodeficiency virus by multidimensional nuclear magnetic resonance spectroscopy SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE gp41; SIV; HIV; NMR; global topology ID NMR CHEMICAL-SHIFTS; PERDEUTERATED PROTEINS; TRANSMEMBRANE PROTEIN; HIGH-SENSITIVITY; FUSION PEPTIDE; C-13; GLYCOPROTEIN; RECEPTOR; ALPHA; N-15 AB The gp41 protein of the human (HIV) and simian (SIV) immunodeficiency viruses is part of the envelope glycoprotein complex gp41/gp120 which plays an essential role in viral infection. We present a multidimensional NMR study on the trimeric 44 kDa soluble ectodomain of SIV gp41 (e-gp41), comprising residues 27 to 149. Despite the large molecular weight and very limited spectral dispersion, complete backbone H-1, C-13, (CO)-C-13 and N-15 assignments have been made using a combination of triple resonance experiments on uniformly C-13/N-15 and H-2/C-13/N-15-labeled samples. The secondary structure of SIV e-gp41, derived on the basis of C-13 chemical shifts, NH exchange rates, medium range nuclear Overhauser enhancements (NOE), and (3)J(HN alpha) coupling constants, consists of a 49 residue helix at the N terminus (residues 29 to 77) and a 40 residue helix at the C terminus (residues 108 to 147), connected by a 30 residue loop which does not display any of the characteristics of regular secondary structure. The cross-peak intensities of the loop region in scalar correlation experiments suggests that it is more mobile than the core helical regions. The presence, however, of numerous long range NOEs, both intra and inter-subunit, within the loop indicates that it adopts a well-defined structure in which the loops from the three subunits interact with each other. Based on a number of long range intra and inter-subunit NOEs, a topological model is presented for the symmetric SIV e-gp41 trimer in which the N-terminal helices are packed within the protein interior in a parallel trimeric coiled-coil arrangement, while the C-terminal helices are located on the protein exterior, oriented antiparallel to the N-terminal helices. (C) 1997 Academic Press Limited. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NIAMSD,PROT EXPRESS LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 37 TC 37 Z9 37 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 5 PY 1997 VL 271 IS 5 BP 819 EP 826 DI 10.1006/jmbi.1997.1217 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU907 UT WOS:A1997XU90700012 PM 9299329 ER PT J AU Lin, SL Xu, D Li, AJ Rosen, M Wolfson, HJ Nussinov, R AF Lin, SL Xu, D Li, AJ Rosen, M Wolfson, HJ Nussinov, R TI Investigation of the enzymatic mechanism of the yeast chorismate mutase by docking a transition state analog SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE chorismate; mutase; structure; docking; modeling ID MOLECULAR-SURFACE; PROGRAM; SPARSE; POINTS AB The structure of the complex of the chorismate mutase from the yeast Saccharomyces cerevisiae with a transition state analog is constructed using a suite of docking tools. The construction finds the best location for the active site in the enzyme, and the best orientation of the analog compound in the active site. The resulting complex shows extensive salt links and hydrogen bonds between the enzyme and the compound, including those mediated by water molecules. A network of polar interactions between amino acid residues is found to solidify the active site of the enzyme. The enzymatic mechanism suggested for a bacterial chorismate mutase, that the active site is by design capable of selecting an active conformer of the substrate, and of stabilizing the transition state, is apparently intact in the yeast enzyme. No direct evidence is found to support an alternative mechanism which involves specific catalytic groups, although the possibility is not eliminated. This finding reinforces the notion elf a function being evolutionarily conserved via a common mechanism, rather than via sequential or structural homology. (C) 1997 Academic Press Limited. C1 TEL AVIV UNIV,DEPT COMP SCI,SCH MATH SCI,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. RP Lin, SL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB EXPT & COMPUTAT BIOL,SAIC,BLDG 469,RM 151,FREDERICK,MD 21702, USA. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 20 TC 10 Z9 10 U1 1 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 5 PY 1997 VL 271 IS 5 BP 838 EP 845 DI 10.1006/jmbi.1997.1168 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU907 UT WOS:A1997XU90700014 PM 9299331 ER PT J AU Shelby, MD AF Shelby, MD TI Selecting chemicals and assays for assessing mammalian germ cell mutagenicity - Response SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Letter RP Shelby, MD (reprint author), NIEHS,TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 5 PY 1997 VL 379 IS 1 BP 107 EP 107 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA YC145 UT WOS:A1997YC14500013 ER PT J AU Siarey, RJ Coan, EJ Rapoport, SI Galdzicki, Z AF Siarey, RJ Coan, EJ Rapoport, SI Galdzicki, Z TI Responses to NMDA in cultured hippocampal neurons from trisomy 16 embryonic mice SO NEUROSCIENCE LETTERS LA English DT Article DE Down syndrome; trisomy 16; glutamate; N-methyl-D-aspartate; whole-cell patch-clamp; hippocampus ID DORSAL-ROOT GANGLION; ELECTRICAL MEMBRANE-PROPERTIES; AMYOTROPHIC-LATERAL-SCLEROSIS; SPINAL-CORD NEURONS; MOUSE FETUS; DOWNS-SYNDROME; GLUTAMATE; MODEL; ABNORMALITIES; CURRENTS AB The trisomy 16 (Ts16) mouse is regarded as a model of human trisomy 21 (Ts21), or Down syndrome. The ionic current evoked by the glutamate receptor agonist N-methyl-D-aspartate (NMDA) was investigated in cultured hippocampal neurons from embryonic Ts16 and control diploid mice, In both Ts16 and control neurons, NMDA-(6-150 mu M) evoked a similar inward current. The reversal potential, the minimum current, the dose response plot of the conductance, the effect of Mg2+ on the current-voltage plot and the inhibition by D-2-amino-5-phosphonovaleric acid (AP5; 50 mu M) showed no significant difference between Ts16 and control neurons. These data suggest that, although voltage-dependent ion channels are reported to have altered active properties in Ts16 neurons, NMDA-evoked currents are not altered. (C) 1997 Elsevier Science Ireland Ltd. C1 NIA, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. UNIV BRISTOL, SCH MED, DEPT ANAT, BRISTOL BS8 1TD, AVON, ENGLAND. NR 27 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 5 PY 1997 VL 232 IS 3 BP 131 EP 134 DI 10.1016/S0304-3940(97)00581-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA XV841 UT WOS:A1997XV84100003 PM 9310297 ER PT J AU Redegeld, FA Smith, P Apasov, S Sitkovsky, MV AF Redegeld, FA Smith, P Apasov, S Sitkovsky, MV TI Phosphorylation of T-lymphocyte plasma membrane-associated proteins by ectoprotein kinases: implications for a possible role for ectophosphorylation in T-cell effector functions SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE cell mediated cytotoxicity; extracellular ATP; ectoprotein kinase K-252b; ectophosphorylation; T lymphocyte ID FIBROBLAST GROWTH-FACTOR; EXTRACELLULAR ATP; SURFACE-PROTEINS; CASEIN KINASE-2; RECEPTOR; DEPHOSPHORYLATION; ACTIVATION; INHIBITION; SUBSTRATE; HEPARIN AB Extracellular adenosine triphosphate (ATPo) has been suggested to play a role in lymphocyte effector functions. Recently, it has been suggested that MgATP(2-) may be the molecular species which is involved in modulating the lytic interaction between cytotoxic T-lymphocytes (CTL) and their target cells. In this study, we provide evidence that ATPo mediates the phosphorylation of extracellular proteins on T-lymphocytes through the action of ectoprotein kinases. The ectophosphorylation is temperature-dependent, supported by Mg2+ and Mn2+, and both ATP and GTP, whereas kinase activity and/or substrates were removed by pretreatment of intact lymphocytes with trypsin. We show the presence of extracellular ATP/GTP-binding sites, indicating the presence of ectoenzymes on intact lymphocytes. The major ectoprotein kinase was identified as a casein kinase II-like protein kinase and could be inhibited by heparin, whereas its activity was enhanced by spermine. The ectoprotein kinase showed remarkable substrate specificity, phosphorylating the serum protein vitronectin, but not fibronectin. In experiments with the cell-impermeable protein kinase inhibitor K-252b, we demonstrate the possible functional importance of ectoprotein kinase in CTL-mediated cytotoxicity, i.e., target cell death was completely blocked by K-252b without affecting intracellular phosphorylation. These results suggest that ectoprotein phosphorylation may possibly be an important event in immunologically relevant cell-cell interactions. (C) 1997 Elsevier Science B.V. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Redegeld, Frank/O-6534-2016 OI Redegeld, Frank/0000-0001-8830-7960 NR 35 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD SEP 4 PY 1997 VL 1328 IS 2 BP 151 EP 165 DI 10.1016/S0005-2736(97)00082-5 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XV202 UT WOS:A1997XV20200007 PM 9315612 ER PT J AU Liaw, KL Adami, J Gridley, G Nyren, O Linet, MS AF Liaw, KL Adami, J Gridley, G Nyren, O Linet, MS TI Risk of Hodgkin's disease subsequent to tonsillectomy: A population-based cohort study in Sweden SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article AB Although some studies have linked excess of Hodgkin's disease (HD) to tonsillectomy, the findings have not been consistent. In particular, risk of HD by age at tonsillectomy has not been fully evaluated, despite the notable change in immunologic function of the tonsils between childhood and adulthood. To evaluate the risk of HD and other lymphomas, associated with tonsillectomy according to age at surgery, a population-based cohort study was conducted. Using nationwide Swedish hospitalization records, 55,169 patients undergoing tonsillectomy with/without adenoidectomy (T/A) were identified during the period 1964-1983. By linkage with the nationwide Total Population, Migration, Cancer and Causes-of-Death registries, these patients were followed up for as long as 25 years. After exclusion of the first post-operative year, a total of 533 first primary-cancer cases was identified between 1965 and 1989. Small excess risk was observed for HD (20 cases, SIR = 1.4, 95% CI 0.9-2.2). HD risk was more pronounced among patients tonsillectomized before age 12 (7 observed vs. 1.7 expected, SIR = 4.1, 95% CI 1.6-8.4), but declined significantly with older ages at TIA. While our data suggest a small increase in HD among all patients undergoing TIA and a significant excess for those under age 12 at surgery, we cannot exclude the possibility that the excess may be due to factors underlying the disorders that led to surgery. (C) 1997 Wiley-Liss, Inc. C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. RP Liaw, KL (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EPN 443,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 22 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 4 PY 1997 VL 72 IS 5 BP 711 EP 713 DI 10.1002/(SICI)1097-0215(19970904)72:5<711::AID-IJC1>3.0.CO;2-V PG 3 WC Oncology SC Oncology GA XU745 UT WOS:A1997XU74500001 PM 9311582 ER PT J AU Pumphrey, JG Hausner, P Rudikoff, S AF Pumphrey, JG Hausner, P Rudikoff, S TI Characterization of C57BL/6 plasmacytomas lacking a C-MYC translocation SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MULTIPLE-MYELOMA MODEL; GENE; EXPRESSION; CELLS AB BALB/c peritoneal plasmacytomas induced by a variety of agents are invariably associated with a c-myc translocation. In contrast, naturally arising bone marrow plasma cell tumors in C57BL/KaLwRij mice lack this translocation. This difference has led to the suggestion that these are 2 fundamentally different plasma cell diseases. Herein, we have analyzed 2 rare C57BL/6 peritoneal plasmacytomas in terms of characteristics associated with the bone marrow-derived lines. Like the bone marrow lines, these peritoneal plasmacytomas do not exhibit c-myc translocations, indicating that c-myc translocation is not an obligatory event in the development of all murine extramedullary plasmacytomas, However, myc is dysregulated at the mRNA level, indicating that myc overexpression may be fundamental to most plasma cell diseases but that dysregulation can occur by alternative. (C) 1997 Wiley-Liss, Inc. C1 NIH,NCI,GENET LAB,BETHESDA,MD 20892. NR 18 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 4 PY 1997 VL 72 IS 5 BP 892 EP 897 DI 10.1002/(SICI)1097-0215(19970904)72:5<892::AID-IJC29>3.0.CO;2-9 PG 6 WC Oncology SC Oncology GA XU745 UT WOS:A1997XU74500029 PM 9311610 ER PT J AU Basso, MA Wurtz, RH AF Basso, MA Wurtz, RH TI Modulation of neuronal activity by target uncertainty SO NATURE LA English DT Article ID FRONTAL EYE FIELD; SUPERIOR COLLICULUS; VISUAL-SEARCH; ATTENTION; SELECTION; MONKEY; CORTEX AB Visual scenes are composed of many elements and although we can appreciate a scene as a whole, we can only move our eyes to one element of the scene at a time. As visual scenes become more complex, the number of potential targets in the scene increases, and the uncertainty that any particular one will be selected for an eye movement also increases. How motor systems accommodate this target uncertainty remains unknown. The activities of neurons in both the cerebral cortex(1-5) and superior colliculus(6-8) are modulated by this selection process. We reasoned that activity associated with target uncertainty should be evident in the saccadic motor system at the final stages of neural processing, in the superior colliculus(9,10). By systematically changing the number of stimuli from which a selection must be made and recording from superior colliculus neurons, we found that as the target uncertainty increased,the neural activity preceding target selection decreased. These results indicate that neurons within the final common pathway for movement generation are active well in advance of the selection of a particular movement. This early activity varies with the probability that a particular movement will be selected. RP Basso, MA (reprint author), NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892, USA. NR 16 TC 210 Z9 212 U1 1 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 4 PY 1997 VL 389 IS 6646 BP 66 EP 69 DI 10.1038/37975 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU596 UT WOS:A1997XU59600045 PM 9288967 ER PT J AU Presley, JF Cole, NB Schroer, TA Hirschberg, K Zaal, KJM LippincottSchwartz, J AF Presley, JF Cole, NB Schroer, TA Hirschberg, K Zaal, KJM LippincottSchwartz, J TI ER-to-Golgi transport visualized in living cells SO NATURE LA English DT Article ID GREEN-FLUORESCENT PROTEIN; ENDOPLASMIC-RETICULUM; VIRAL GLYCOPROTEIN; BETA-COP; COMPLEX; COMPARTMENT; VIRUS; ORGANIZATION; MEMBRANES; SURFACE AB Newly synthesized proteins that leave the endoplasmic reticulum (ER) are funnelled through the Golgi complex before being sorted for transport to their different final destinations. Traditional approaches have elucidated the biochemical requirements for such transport(1-3) and have established a role for transport intermediates(4-8). New techniques for tagging proteins fluorescently(9,10) have made it possible to follow the complete life history of single transport intermediates in living cells, including their formation, path and velocity en route to the Golgi complex. We have now visualized ER-to-Golgi transport using the viral. glycoprotein ts045 VSVG tagged with green fluorescent protein (VSVG-GFP). Upon export from the ER, VSVG-GFP became concentrated in many differently shaped, rapidly forming pre-Golgi structures, which translocated inwards towards the Golgi complex along microtubules by using the microtubule minus-end-directed motor complex of dynein/dynactin. No loss of fluorescent material from pre-Golgi structures occurred during their translocation to the Golgi complex and they frequently stretched into tubular shapes. Together, our results indicate that these pre-Golgi carrier structures moving unidirectionally along microtubule tracks are responsible for transporting VSVG-GFP through the cytoplasm to the Golgi complex. This contrasts with the traditional focus on small vesicles as the primary vehicles for ER-to-Golgi transport. C1 NICHHD,CELL BIOL & METAB BRANCH,NICHHD,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. OI Schroer, Trina/0000-0002-5065-1835 NR 31 TC 806 Z9 816 U1 9 U2 60 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 4 PY 1997 VL 389 IS 6646 BP 81 EP 85 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU596 UT WOS:A1997XU59600049 PM 9288971 ER PT J AU Fan, QR Mosyak, L Winter, CC Wagtmann, N Long, EO Wiley, DC AF Fan, QR Mosyak, L Winter, CC Wagtmann, N Long, EO Wiley, DC TI Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors SO NATURE LA English DT Article ID IMMUNOGLOBULIN-LIKE DOMAINS; HUMAN GROWTH-HORMONE; HUMAN TISSUE FACTOR; CRYSTAL-STRUCTURE; EXTRACELLULAR DOMAIN; HUMAN CD4; COMPLEX; BINDING; 2.8-ANGSTROM; MOLECULE AB Abnormal cells deficient in class I major histocompatibility complex (MHC) expression are lysed by a class of lymphocytes called natural killer (NK) cells(1). This lysis provides a defence against pathogens and tumour cells that downregulate MHC expression to avoid an MHC-restricted, T-cell immune response. Normal cells escape lysis because their MHC molecules are recognized by NK-cell inhibitory receptors, which inhibit lysis(2). Several such inhibitory receptor families have been described in humans and mice (reviewed in Ief. 2). In the human killer-cell inhibitory receptor family, individual p58 members are specific for a subset of class I human leukocyte antigen (HLA)-C molecules. The human p58 natural killer-cell inhibitory receptor done 42 recognizes HLA-Cw4, -Cw2 and -Cw6, but not HLA-Cw3, -Cw2, -Cw7 or -Cw8, which are recognized by p58 killer-cell inhibitor receptor clone 43 (ref. 3). We have determined the X-ray structure of the p58 NK-cell inhibitory receptor clone 42 at 1.7-Angstrom resolution. The structure has tandem immunoglobulin-like domains positioned at an acute, 60-degree angle. Loops on the outside of the elbow between the domains form a binding site projected away from the NK-cell surface. The topology of the domains and their arrangement relative to each other reveal a relationship to the haematopoietic receptor family, with implications for the signalling mechanism in NK cells. C1 NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. HARVARD UNIV,HOWARD HUGHES MED INST,DEPT MOL & CELLULAR BIOL,CAMBRIDGE,MA 02138. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 31 TC 142 Z9 145 U1 1 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 4 PY 1997 VL 389 IS 6646 BP 96 EP 100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU596 UT WOS:A1997XU59600053 PM 9288975 ER PT J AU Gammon, MD Schoenberg, JB Ahsan, H Risch, HA Vaughan, TL Chow, WH Rotterdam, H West, AB Dubrow, R Stanford, JL Mayne, ST Farrow, DC Niwa, S Blot, WJ Fraumeni, JF AF Gammon, MD Schoenberg, JB Ahsan, H Risch, HA Vaughan, TL Chow, WH Rotterdam, H West, AB Dubrow, R Stanford, JL Mayne, ST Farrow, DC Niwa, S Blot, WJ Fraumeni, JF TI Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MEDICAL CONDITIONS; CIGARETTE-SMOKING; HISTOLOGIC TYPE; UNITED-STATES; LIFE-STYLE; CANCER; RISK; CONSUMPTION; CARCINOMA; STOMACH AB Background: Incidence rates for adenocarcinomas of the esophagus and gastric cardia have risen steeply over the last few decades, To determine risk factors for these tumors, we conducted a multicenter, population-based, case-control study, Methods: The study included 554 subjects newly diagnosed with esophageal or gastric cardia adenocarcinomas, 589 subjects newly diagnosed with esophageal squamous cell carcinoma or other gastric adenocarcinomas, and 695 control subjects. Estimates of risk (odds ratios [ORs] and corresponding 95% confidence intervals [CIs]) were calculated for the four tumor types separately and for esophageal and gastric cardia adenocarcinomas combined. Results: Risk of esophageal and gastric cardia adenocarcinomas combined was increased among current cigarette smokers (OR = 2.4; 95% = 1.7-3.4), with little reduction observed until 30 years after smoking cessation; this risk rose with increasing intensity and duration of smoking. Risk of these tumors was not related to beer (OR = 0.8; 95% CI = 0.6-1.1) or liquor (OR = 1.1; 95% CI = 0.8-1.4) consumption, but it was reduced for drinking wine (OR = 0.6; 95% CI = 0.5-0.8), Similar ORs were obtained for the development of noncardia gastric adenocarcinomas in relation to tobacco and alcohol use, but higher ORs were obtained for the development of esophageal squamous cell carcinomas, For all four tumor types, risks were higher among those with low income or education, Conclusions: Smoking is a major risk factor for esophageal and gastric cardia adenocarcinomas, accounting for approximately 40% of cases, Implications: Because of the long lag time before risk of these tumors is reduced among exsmokers, smoking may affect early stage carcinogenesis, The increase in smoking prevalence during the first two thirds of this century may be reflected in the rising incidence of these tumors in the past few decades among older individuals, The recent decrease in smoking may not yet have had an impact. C1 COLUMBIA SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. NEW JERSEY DEPT HLTH & SENIOR SERV,APPL CANC EPIDEMIOL PROGRAM,TRENTON,NJ. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. FRED HUTCHINSON CANC RES CTR,PROGRAM EPIDEMIOL,SEATTLE,WA 98104. UNIV WASHINGTON,SCH PUBL HLTH,DEPT EPIDEMIOL,SEATTLE,WA 98195. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY. WESTAT CORP,ROCKVILLE,MD. INT EPIDEMIOL INST,ROCKVILLE,MD. FU NCI NIH HHS [U01-CA57983, U01-CA57923, U01-CA57949] NR 29 TC 382 Z9 392 U1 1 U2 10 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 3 PY 1997 VL 89 IS 17 BP 1277 EP 1284 DI 10.1093/jnci/89.17.1277 PG 8 WC Oncology SC Oncology GA XU080 UT WOS:A1997XU08000010 PM 9293918 ER PT J AU Dillner, J Lehtinen, M Bjorge, T Luostarinen, T Youngman, L Jellum, E Koskela, P Gislefoss, RE Hallmans, G Paavonen, J Sapp, M Schiller, JT Hakulinen, T Thoresen, S Hakama, M AF Dillner, J Lehtinen, M Bjorge, T Luostarinen, T Youngman, L Jellum, E Koskela, P Gislefoss, RE Hallmans, G Paavonen, J Sapp, M Schiller, JT Hakulinen, T Thoresen, S Hakama, M TI Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID VIRUS-LIKE PARTICLES; HERPES-SIMPLEX VIRUS; INTRAEPITHELIAL NEOPLASIA; SERUM ANTIBODIES; TYPE-16; CARCINOMA; WOMEN; COLOMBIA; COHORT; DNA AB Background: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. Methods: A nested case-control study within a joint cohort of 700 000 Nordic subjects was performed, The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 538 control women on the basis of age and time of enrollment. Serum samples taken at enrollment were analyzed for evidence of tobacco use (i.e., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis. Relative risks (RRs) were estimated by use of conditional logistic regression, Results: Presence of antibodies against HPV in serum (seropositivity) was associated with an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2.4; 95% confidence interval [CI] = 1.6-3.7), HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antibodies against C trachomatis, the HPV16-associated risk of cervical cancer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in populations with a high prevalence of antibodies against C. trachomatis, no excess risk was found, Conclusion: Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases. C1 NATL PUBL HLTH INST,DEPT INFECT DIS EPIDEMIOL,HELSINKI,FINLAND. CANC REGISTRY NORWAY,INST EPIDEMIOL CANC RES,OSLO,NORWAY. NORWEGIAN RADIUM HOSP,DEPT GYNECOL ONCOL,OSLO,NORWAY. FINNISH CANC REGISTRY,INST STAT & EPIDEMIOL CANC RES,FIN-00170 HELSINKI,FINLAND. UNIV OXFORD,CLIN TRIAL SERV UNIT,OXFORD,ENGLAND. NORWEGIAN CANC SOC,JANUS COMMITTEE,OSLO,NORWAY. NATL PUBL HLTH INST,OULU,FINLAND. UMEA UNIV,DEPT NUTR RES & PATHOL,UMEA,SWEDEN. UNIV HELSINKI,DEPT OBSTET & GYNECOL,HELSINKI,FINLAND. UNIV MAINZ,DEPT MED MICROBIOL,D-6500 MAINZ,GERMANY. NATL CANC INST,BETHESDA,MD. KAROLINSKA INST,CANC EPIDEMIOL UNIT,S-10401 STOCKHOLM,SWEDEN. SCH PUBL HLTH,TAMPERE,FINLAND. RP Dillner, J (reprint author), KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,BOX 280,S-17177 STOCKHOLM,SWEDEN. NR 37 TC 104 Z9 108 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 3 PY 1997 VL 89 IS 17 BP 1293 EP 1299 DI 10.1093/jnci/89.17.1293 PG 7 WC Oncology SC Oncology GA XU080 UT WOS:A1997XU08000012 PM 9293920 ER PT J AU Podgornik, R AF Podgornik, R TI Supporting membrane shape instability in the presence of strongly adsorbed flexible polymers SO LANGMUIR LA English DT Letter ID DNA; SURFACE; MICROSCOPY; LIPOSOMES AB Strongly adsorbed polymers are shown to undergo an isotropic-nematic surface-ordering transition as a consequence of interactions mediated by the supporting elastic membrane. Depending on the elastic coupling ratio between the membrane and polymer elasticity, the supporting membrane can concurrently undergo a transition into either preferred saddle or tubular shapes. It is argued that this scenario is relevant for the initial stages of the DNA-cationic liposome interactions. RP Podgornik, R (reprint author), NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892, USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 17 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0743-7463 J9 LANGMUIR JI Langmuir PD SEP 3 PY 1997 VL 13 IS 18 BP 4791 EP 4794 DI 10.1021/la960956g PG 4 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA XU706 UT WOS:A1997XU70600005 ER PT J AU Laco, GS SchalkHihi, C Lubkowski, J Morris, G Zdanov, A Olson, A Elder, JH Wlodawer, A Gustchina, A AF Laco, GS SchalkHihi, C Lubkowski, J Morris, G Zdanov, A Olson, A Elder, JH Wlodawer, A Gustchina, A TI Crystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor SO BIOCHEMISTRY LA English DT Article ID HIV-1 PROTEASE; CRYSTALLOGRAPHIC ANALYSIS; ASPARTIC PROTEINASES; 3-DIMENSIONAL STRUCTURE; TYPE-1 PROTEASE; RETROVIRAL PROTEASES; CATALYTIC MECHANISM; RHIZOPUS-CHINENSIS; ESCHERICHIA-COLI; RNA-POLYMERASE AB Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as with a substrate based on a modification of this inhibitor (LP-149S): have been solved and refined at resolutions of 2.0 and 1.85 Angstrom, respectively, Both the inhibitor and the substrate are bound in the active site of the mutant protease in a similar mode, which also resembles the mode of binding of LP-149 to the native protease. the carbonyl oxygen of the scissile bond in the substrate is not hydrated and is located within the distance of a hydrogen bond to an amido nitrogen atom from one of the two asparagines in the active site of the enzyme. The nitrogen atom of the scissile bond is 3.25 Angstrom from the conserved water molecule (Wat301). A: model of a tetrahedral intermediate bound to the active site of the native enzyme was built by considering the interactions observed in all three crystal structures of FIV PR. Molecular dynamics simulations of this model bound to native wild-type FIV PR were carried out, to investigate the final stages of the catalytic mechanism of aspartic proteases. C1 Scripps Res Inst, DEPT MOL BIOL, LA JOLLA, CA 92037 USA. RP Laco, GS (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MACROMOL STRUCT LAB, FREDERICK, MD 21702 USA. OI Morris, Garrett/0000-0003-1731-8405 FU NIGMS NIH HHS [P01GM48870] NR 65 TC 37 Z9 39 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 2 PY 1997 VL 36 IS 35 BP 10696 EP 10708 DI 10.1021/bi9707436 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV689 UT WOS:A1997XV68900011 PM 9271500 ER PT J AU FagotCampagna, A Hanson, RL Narayan, KMV Sievers, ML Pettitt, DJ Nelson, RG Knowler, WC AF FagotCampagna, A Hanson, RL Narayan, KMV Sievers, ML Pettitt, DJ Nelson, RG Knowler, WC TI Serum cholesterol and mortality rates in a native American population with low cholesterol concentrations - A U-shaped association SO CIRCULATION LA English DT Article DE cholesterol; risk factors; mortality ID FACTOR INTERVENTION TRIAL; CORONARY HEART-DISEASE; LOW BLOOD CHOLESTEROL; CANCER MORTALITY; PIMA-INDIANS; CARDIOVASCULAR-DISEASE; PLASMA-CHOLESTEROL; SHORT-TERM; FOLLOW-UP; MEN AB Background Low serum cholesterol concentrations are associated with high death rates from cancer, trauma, and infectious diseases, but the meaning of these associations remains controversial. The present report evaluates whether low cholesterol is likely to be a causal factor for mortality from all causes or from specific causes. Methods and Results Among 4553 Pima Indians greater than or equal to 20 pears old, a population with low serum cholesterol (median, 4.50 mmol/L), 1077 deaths occurred during a mean follow-up of 12.8 years. Trauma was the most common cause. The relationship between serum cholesterol measured at 2-year intervals and age-and sex-standardized mortality rates was U-shaped. Cholesterol was related positively to mortality from cardiovascular diseases and diabetes (including nephropathy) and negatively to mortality from cancer and alcohol-related diseases. The relationship was U-shaped for mortality from infectious diseases, and cholesterol was not related to mortality from trauma. Change in cholesterol from one examination to the next was positively related to mortality from diabetes. In proportional-hazards models adjusted for potential confounders, the relationship between baseline cholesterol and mortality was U-shaped for all causes and diabetes and positive for cardiovascular diseases. Other relationships were nonsignificant. Among 3358 subjects followed greater than or equal to 5 years, the relationship was significant and positive only for mortality from cardiovascular diseases. Conclusions Despite a high exposure risk for Pima Indians, If low cholesterol level is a causal factor, the relationships between low serum cholesterol and high mortality rates probably result from diseases lowering cholesterol rather than from a low cholesterol causing the diseases. RP FagotCampagna, A (reprint author), NATL INST DIABETES & DIGEST & KIDNEY DIS,1550 E INDINA SCH RD,PHOENIX,AZ 85014, USA. RI Nelson, Robert/B-1470-2012; Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068 NR 58 TC 16 Z9 18 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 2 PY 1997 VL 96 IS 5 BP 1408 EP 1415 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XU856 UT WOS:A1997XU85600011 PM 9315525 ER PT J AU Devereux, RB Roman, MJ deSimone, G OGrady, MJ Paranicas, M Yeh, JL Fabsitz, RR Howard, BV AF Devereux, RB Roman, MJ deSimone, G OGrady, MJ Paranicas, M Yeh, JL Fabsitz, RR Howard, BV TI Relations of left ventricular mass to demographic and hemodynamic variables in American Indians - The Strong Heart Study SO CIRCULATION LA English DT Article DE blood pressure; contractility; ventricles; echocardiography ID END-SYSTOLIC STRESS; PRESSURE-OVERLOAD HYPERTROPHY; BLOOD-PRESSURE; SHORTENING RELATIONS; RENOVASCULAR HYPERTENSION; DILATED CARDIOMYOPATHY; ARTERIAL-HYPERTENSION; VOLUME RATIO; RISK-FACTORS; ADULTS AB Background Previous studies have identified associations of left ventricular (LV) mass with demographic (body habitus and sex) and hemodynamic variables (blood pressure, stroke volume [SV], and myocardial contractility), but the relative strength and independence of these associations remain unknown. Methods and Results We examined the relations of echocardiographically determined LV mass to demographic variables, blood pressure, Doppler SV, and measures of contractility (end-systolic stress [ESS]/end-systolic volume index and mid-wall fractional shortening [MFS] as a percentage of predicted for circumferential end-systolic stress [stress-independent shortening]) in 1935 American Indian participants in the Strong Heart Study phase 2 examination without mitral regurgitation or segmental wail motion abnormalities. Weak positive relations of LV mass with systolic and diastolic pressures (r=.22, and r=.20) were exceeded by positive relations with height (r=.30), weight (r=.47), body mass index (r=.31), body surface area (r=.49), and Doppler SV (r=.50) and negative relations with ESS/volume index ratios (r=-.33 and -.29) and stress-independent MFS (r=-.26, all P<.0001). In multivariate analyses that included blood pressure, SV, and a different contractility measure in each model, systolic pressure, stroke volume, and the contractility measure were independent correlates of LV mass (multiple R=.60 to .66, all P<.0001). When demographic variables were added. LV mass was more strongly predicted by higher SV and lower afterload-independent MFS than by greater systolic pressure, height, and body mass index (each P<.00001, multiple R=.71). Conclusions Additional characterization of Volume load and contractile efficiency improves hemodynamic prediction of LV mass (R-2=.30 to .44) over the use of systolic blood pressure alone (R-2=.05), with a further increase in R-2 to .51 when demographic variables are also considered. However, nearly half of the ventricular mass variability remains unexplained. C1 MEDLANT RES INST,WASHINGTON,DC. UNIV OKLAHOMA,SCH PUBL HLTH SCI,OKLAHOMA CITY,OK. NHLBI,DIV EPIDEMIOL & DIS CONTROL,BETHESDA,MD 20892. RP Devereux, RB (reprint author), CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV CARDIOL,DEPT MED,BOX 222,525 E 68TH ST,NEW YORK,NY 10021, USA. RI de Simone, Giovanni/D-1767-2011 OI de Simone, Giovanni/0000-0001-8567-9881 FU NHLBI NIH HHS [U01-HL-41652, U01-HL-41654, U01-HL-41642] NR 38 TC 158 Z9 167 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 2 PY 1997 VL 96 IS 5 BP 1416 EP 1423 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XU856 UT WOS:A1997XU85600012 PM 9315526 ER PT J AU Zlotnick, A Cheng, N Stahl, SJ Conway, JF Steven, AC Wingfield, PT AF Zlotnick, A Cheng, N Stahl, SJ Conway, JF Steven, AC Wingfield, PT TI Localization of the C terminus of the assembly domain of hepatitis B virus capsid protein: Implications for morphogenesis and organization of encapsidated RNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-BINDING ACTIVITY; ELECTRON-MICROSCOPY; CORE-PROTEIN; ESCHERICHIA-COLI; CRYOELECTRON MICROSCOPY; PARTICLES; ANTIGEN; REPLICATION; ENVELOPMENT; POLYMERASE AB The capsid protein of hepatitis B virus, consisting of an ''assembly'' domain (residues 1-149) and an RNA-binding ''protamine'' domain (residues 150-183), assembles from dimers into icosahedral capsids of two different sizes, The C terminus of the assembly domain (residues 140-149) functions as a morphogenetic switch, longer C termini favoring a higher proportion of the larger capsids, it also connects the protamine domain to the capsid shell, We now have defined the location of this peptide in capsids assembled in vitro by engineering a mutant assembly domain with a single cysteine at its C terminus (residue 150), labeling it with a gold cluster and visualizing the cluster by cryo-electron microscopy, The labeled protein is unimpaired in its ability to form capsids, Our density map reveals a single undecagold cluster under each fivefold and quasi-sixfold vertex, connected to sites at either end of the undersides of the dimers, Considering the geometry of the vertices, the C termini must be more crowded at the fivefolds. Thus, a bulky C terminus would be expected to favor formation of the larger (T = 4) capsids, which have a greater proportion of quasi-sixfolds. Capsids assembled by expressing the full-length protein in Escherichia coli package bacterial RNAs in amounts equivalent to the viral pregenome, Our density map of these capsids reveals a distinct inner shell of density-the RNA, The RNA is connected to the protein shell via the C-terminal linkers and also makes contact around the dimer axes. C1 NIAMSD, PROT EXPRESS LAB, NIH, BETHESDA, MD 20892 USA. NIAMSD, STRUCT BIOL LAB, NIH, BETHESDA, MD 20892 USA. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 45 TC 110 Z9 120 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9556 EP 9561 DI 10.1073/pnas.94.18.9556 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500009 PM 9275161 ER PT J AU Moskovitz, J Berlett, BS Poston, JM Stadtman, ER AF Moskovitz, J Berlett, BS Poston, JM Stadtman, ER TI The yeast peptide methionine sulfoxide reductase functions as an antioxidant in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RESIDUES; PROTEINS AB A gene homologous to methionine sulfoxide reductase (msrA) was identified as the predicted ORF (cosmid 9379) in chromosome V of Saccharomyces cerevisiae encoding a protein of 184 amino acids. The corresponding protein has been expressed in Escherichia coli and purified to homogeneity. The recombinant yeast MsrA possessed the same substrate specificity as the other known MsrA enzymes from mammalian and bacterial cells. Interruption of the yeast gene resulted in a null mutant, Delta msrA::URA3 strain, which totally lost its cellular MsrA activity and was shown to be more sensitive to oxidative stress in comparison to its wild-type parent strain. Furthermore, high levels of free and protein-bound methionine sulfoxide were detected in extracts of msrA mutant cells relative to their wild-type parent cells, under various oxidative stresses. These findings show that MsrA is responsible for the reduction of methionine sulfoxide in vivo as well as in vitro in eukaryotic cells. Also, the results support the proposition that MsrA possess an antioxidant function. The ability of MsrA to repair oxidative damage in vivo may be of singular importance if methionine residues serve as antioxidants. RP Moskovitz, J (reprint author), NHLBI, BIOCHEM LAB, NIH, BETHESDA, MD 20892 USA. NR 13 TC 247 Z9 255 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9585 EP 9589 DI 10.1073/pnas.94.18.9585 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500014 PM 9275166 ER PT J AU Cavallaro, S Meiri, N Yi, CL Musco, S Ma, W Goldberg, J Alkon, DL AF Cavallaro, S Meiri, N Yi, CL Musco, S Ma, W Goldberg, J Alkon, DL TI Late memory-related genes in the hippocampus revealed by RNA fingerprinting SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MORRIS WATER MAZE; FREELY-MOVING RAT; RYANODINE RECEPTORS; MESSENGER-RNA; C-FOS; DIFFERENTIAL DISPLAY; CALCIUM CHANNELS; APLYSIA LEADS; EXPRESSION; BRAIN AB Although long-term memory is thought to require a cellular program of gene expression and increased protein synthesis, the identity of proteins critical for associative memory is largely unknown. We used RNA fingerprinting to identify candidate memory-related genes (MRGs), which were up-regulated in the hippocampus of water maze-trained rats, a brain area that is critically involved in spatial learning. Two of the original 10 candidate genes implicated by RNA fingerprinting, the rat homolog of the ryanodine receptor type-2 and glutamate dehydrogenase (EC 1.4.1.3), were further investigated by Northern blot analysis, reverse transcription-PCR, and in situ hybridization and confirmed as MRGs with distinct temporal and regional expression. Successive RNA screening as illustrated here may help to reveal a spectrum of MRGs as they appear in distinct domains of memory storage. C1 NINCDS, LAB ADAPT SYST, NIH, BETHESDA, MD 20892 USA. CNR, INST BIOIMMAGINI & FISIOPATOL SISTEMA NERVOSO CEN, CATANIA, ITALY. SCI APPLICAT INT CORP, BIOTECHNOL RES & APPLICAT DIV, ROCKVILLE, MD 20850 USA. RI Cavallaro, Sebastiano/F-3104-2010 OI Cavallaro, Sebastiano/0000-0001-7590-1792 NR 45 TC 79 Z9 82 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9669 EP 9673 DI 10.1073/pnas.94.18.9669 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500029 PM 9275181 ER PT J AU Rebbert, ML Dawid, IB AF Rebbert, ML Dawid, IB TI Transcriptional regulation of the Xlim-1 gene by activin is mediated by an element in intron I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; XENOPUS MESODERM INDUCTION; SPEMANN ORGANIZER; AXIAL MESODERM; RETINOIC ACID; BETA-CATENIN; VENTRALIZING FACTOR; DORSAL MESODERM; MAD PROTEINS; VG1 PROTEIN AB The Xlim-1 gene is activated in the late blastula stage of Xenopus embryogenesis in the mesoderm, and its RNA product becomes concentrated in the Spemann organizer at early gastrula stage. A major regulator of early expression of Xlim-1 is activin or an activin-like signal. We report experiments aiming to identify the activin response element in the Xlim-1 gene. The 5' flanking region of the gene contains a constitutive promoter that is not activin responsive, whereas sequences in the first intron mediate repression of basal promoter activity and stimulation by activin. An intron-derived fragment of 212 nt is the smallest element that could mediate activin responsiveness. Nodal and act-Vg1, factors with signaling properties similar to activin, also stimulated Xlim-1 reporter constructs, whereas BMP-4 did not stimulate or repress the constructs. The mechanism of activin regulation of Xlim-1 and the sequence of the response element are distinct from activin response elements of other genes studied so far. C1 NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. NR 66 TC 34 Z9 35 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9717 EP 9722 DI 10.1073/pnas.94.18.9717 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500038 PM 9275190 ER PT J AU Nelson, GW Kaslow, R Mann, DL AF Nelson, GW Kaslow, R Mann, DL TI Frequency of HLA allele-specific peptide motifs in HIV-1 proteins correlates with the allele's association with relative rates of disease progression after HIV-1 infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLASS-I MOLECULES; T-CELL EPITOPES; LONGITUDINAL ANALYSIS; LYMPHOCYTE RESPONSE; CONSERVED REGIONS; FINE SPECIFICITY; IMMUNE-RESPONSE; ANCHOR RESIDUES; NEF PROTEIN AB An HLA allele-specific cytotoxic T lymphocyte response is thought to influence the rate of disease progression in HIV-1-infected individuals, In a prior study of 139 HIV-1-infected homosexual men, we identified HLA class I alleles and observed an association of specific alleles with different relative hazards for progression to AIDS, Seeking an explanation for this association, we searched HIV-1 protein sequences to determine the number of peptides matching motifs defined by combinations of specific amino acids reported to bind 16 class I alleles, Analyzing complete sequences of 12 clade B HIV isolates, we determined the number of allele motifs that were conserved (occurring in all 12 isolates) and nonconserved (occurring in only one isolate), as well as the average number of allele motifs per isolate, We found significant correlations with an allele's association with disease progression for counts of conserved motifs in gag (R = 0.73; P = 0.002), pol (R = 0.58, P = 0.024), gp120 (R = 0.78, P = 0.00056), and total viral protein sequences (R = 0.67, P = 0.0058) and also for counts of nonconserved motifs in gag (R = 0.62, P = 0.013), pol (R = 0.74, P = 0.0017), gp41 (R = 0.52, P = 0.016), and total viral protein (R = 0.71, P = 0.0033). We also found significant correlations for the average number of motifs per isolate for gag, pol, gp120, and total viral protein, This study provides a plausible functional explanation for the observed association of different HLA alleles with variable rates of disease progression. C1 UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35294. NR 61 TC 50 Z9 51 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9802 EP 9807 DI 10.1073/pnas.94.18.9802 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500054 PM 9275206 ER PT J AU Pantaleo, G Soudeyns, H Demarest, JF Vaccarezza, M Graziosi, C Paolucci, S Daucher, M Cohen, OJ Denis, F Biddison, WE Sekaly, RP Fauci, AS AF Pantaleo, G Soudeyns, H Demarest, JF Vaccarezza, M Graziosi, C Paolucci, S Daucher, M Cohen, OJ Denis, F Biddison, WE Sekaly, RP Fauci, AS TI Evidence for rapid disappearance of initially expanded HIV-specific CD8(+) T cell clones during primary HIV infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VARIABLE REGION GENES; CD8+ LYMPHOCYTES-T; V-BETA REPERTOIRE; VACCINIA VIRUS; EXPRESSION VECTOR; TYPE-1 INFECTION; IN-VIVO; IMMUNOLOGY; POPULATION AB Down-regulation of the initial burst of viremia during primary HIV infection is thought to be mediated predominantly by HIV-specific cytotoxic T lymphocytes, and the appearance of this response is associated with major perturbations of the T cell receptor repertoire. Changes in the T cell receptor repertoire of virus-specific cytotoxic T lymphocytes were analyzed in patients with primary infection to understand the failure of the cellular immune response to control viral spread and replication. This analysis demonstrated that a significant number of HIV-specific T cell clones involved in the primary immune response rapidly disappeared. The disappearance was not the result of mutations in the virus epitopes recognized by these clones. Evidence is provided that phenomena such as high-dose tolerance or clonal exhaustion might be involved in the disappearance of these monoclonally expanded HIV-specific cytotoxic T cell clones, These findings should provide insights into how HIV, and possibly other viruses, elude the host immune response during primary infection. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. INST RECH CLIN MONTREAL,IMMUNOL LAB,MONTREAL,PQ H2W 1R7,CANADA. UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,MONTREAL,PQ H3C 3J7,CANADA. MCGILL UNIV,DEPT MICROBIOL & IMMUNOL,MONTREAL,PQ H3A 2B4,CANADA. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 49 TC 171 Z9 171 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9848 EP 9853 DI 10.1073/pnas.94.18.9848 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500062 PM 9275214 ER PT J AU Meng, XJ Purcell, RH Halbur, PG Lehman, JR Webb, DM Tsareva, TS Haynes, JS Thacker, BJ Emerson, SU AF Meng, XJ Purcell, RH Halbur, PG Lehman, JR Webb, DM Tsareva, TS Haynes, JS Thacker, BJ Emerson, SU TI A novel virus in swine is closely related to the human hepatitis E virus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOLECULAR-CLONING; HEV; ANTIBODIES; SEQUENCE; INFECTION; EPIDEMIC; ETIOLOGY; MONKEYS; ISOLATE; DISEASE AB A novel virus, designated swine hepatitis E virus (swine HEV), was identified in pigs, Swine HEV crossreacts with antibody to the human HEV capsid antigen, Swine HEV is a ubiquitous agent and the majority of swine greater than or equal to 3 months of age in herds from the midwestern United States were seropositive. Young pigs naturally infected by swine HEV were clinically normal but had microscopic evidence of hepatitis, and developed viremia prior to seroconversion, The entire ORFs 2 and 3 were amplified by reverse transcription-PCR from sera of naturally infected pigs, The putative capsid gene (ORF2) of swine HEV shared about 79-80% sequence identity at the nucleotide level and 90-92% identity at the amino acid level with human HEV strains, The small ORF3 of swine HEV had 83-85% nucleotide sequence identity and 77-82% amino acid identity with human HEV strains, Phylogenetic analyses showed that swine HEV is closely related to, but distinct from, human HEV strains, The discovery of swine HEV not only has implications for HEV vaccine development, diagnosis, and biology, but also raises a potential public health concern for zoonosis or xenozoonosis following xenotransplantation with pig organs. C1 IOWA STATE UNIV SCI & TECHNOL,COLL VET MED,AMES,IA 50011. ILLINOIS DEPT AGR,ANIM DIS LAB,GALESBURG,IL 61401. RP Meng, XJ (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,NIH,7 CTR DR,MSC 0740,BETHESDA,MD 20892, USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 24 TC 670 Z9 747 U1 4 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9860 EP 9865 DI 10.1073/pnas.94.18.9860 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500064 PM 9275216 ER PT J AU Sun, H Gilbert, DJ Copeland, NG Jenkins, NA Nathans, J AF Sun, H Gilbert, DJ Copeland, NG Jenkins, NA Nathans, J TI Peropsin, a novel visual pigment-like protein located in the apical microvilli of the retinal pigment epithelium SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OUTER SEGMENT; OPSIN; RHODOPSIN; GENE; ROD; PHOTORECEPTOR; LOCALIZATION; RETINOCHROME; SEQUENCE; HOMOLOG AB A visual pigment-like protein, referred to as peropsin, has been identified by large-scale sequencing of cDNAs derived from human ocular tissues, The corresponding mRNA was found only in the eye, where it is localized to the retinal pigment epithelium (RPE), Peropsin immunoreactivity, visualized by light and electron microscopy, localizes the protein to the apical face of the RPE, and most prominently to the microvilli that surround the photoreceptor outer segments, These observations suggest that peropsin may play a role in RPE physiology either by detecting light directly or by monitoring the concentration of retinoids or other photoreceptor-derived compounds. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 30 TC 87 Z9 91 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9893 EP 9898 DI 10.1073/pnas.94.18.9893 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500070 PM 9275222 ER PT J AU Takahashi, N Miner, LL Sora, I Ujike, H Revay, RS Kostic, V JacksonLewis, V Przedborski, S Uhl, GR AF Takahashi, N Miner, LL Sora, I Ujike, H Revay, RS Kostic, V JacksonLewis, V Przedborski, S Uhl, GR TI VMAT2 knockout mice: Heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VESICULAR MONOAMINE TRANSPORTER; DOPAMINE TRANSPORTER; CHROMAFFIN GRANULES; RAT-BRAIN; EXPRESSION CLONING; PARKINSONS-DISEASE; AMINE TRANSPORTER; RECEPTOR-BINDING; MESSENGER-RNA; COCAINE AB The brain vesicular monoamine transporter (VMAT2) pumps monoamine neurotransmitters and Parkinsonism-inducing dopamine neurotoxins such as 1-methyl-4-phenyl-phenypyridinium (MPP+) from neuronal cytoplasm into synaptic vesicles, from which amphetamines cause their release. Amphetamines and MPP+ each also act at nonvesicular sites, providing current uncertainties about the contributions of vesicular actions to their in vivo effects. To assess vesicular contributions to amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and resistance to dopaminergic neurotoxins, we have constructed transgenic VMAT2 knockout mice. Heterozygous VMAT2 knockouts are viable into adult life and display VMAT2 levels one-half that of wild-type values, accompanied by smaller changes in monoaminergic markers, heart rate, and blood pressure. Weight gain, fertility, habituation, passive avoidance, and locomotor activities are similar to wild-type littermates. In these heterozygotes, amphetamine produces enhanced locomotion but diminished behavioral reward, as measured by conditioned place preference. Administration of the MPP+ precursor N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to heterozygotes produces more than twice the dopamine cell losses found in wild-type mice. These mice provide novel information about the contributions of synaptic vesicular actions of monoaminergic drugs and neurotoxins and suggest that intact synaptic vesicle function may contribute more to amphetamine-conditioned reward than to amphetamine-induced locomotion. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL & NEUROSCI,BALTIMORE,MD 21224. NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. COLUMBIA UNIV,DEPT NEUROL,MOVEMENT DISORDERS DIV,NEW YORK,NY 10032. FU NINDS NIH HHS [NS01724] NR 42 TC 276 Z9 279 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 2 PY 1997 VL 94 IS 18 BP 9938 EP 9943 DI 10.1073/pnas.94.18.9938 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XU455 UT WOS:A1997XU45500078 PM 9275230 ER PT J AU Skirboll, LR AF Skirboll, LR TI The impact of managed care on research: The changing face of medicine SO ACADEMIC MEDICINE LA English DT Article RP Skirboll, LR (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 1997 VL 72 IS 9 BP 778 EP 779 DI 10.1097/00001888-199709000-00012 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA XY228 UT WOS:A1997XY22800019 PM 9311319 ER PT J AU Rundqvist, B Eisenhofer, G Emanuelsson, H Albertsson, P Friberg, P AF Rundqvist, B Eisenhofer, G Emanuelsson, H Albertsson, P Friberg, P TI Intracoronary blockade of angiotensin-converting enzyme in humans: Interaction with cardiac sympathetic neurotransmission? SO ACTA PHYSIOLOGICA SCANDINAVICA LA English DT Article DE enalaprilat; heart; human; noradrenaline; renin-angiotensin; system; sympathetic nervous system ID SPONTANEOUSLY HYPERTENSIVE RATS; LEFT-VENTRICULAR HYPERTROPHY; IMPROVES DIASTOLIC FUNCTION; CONGESTIVE-HEART-FAILURE; MUSCLE INVIVO; HUMAN FOREARM; II RECEPTORS; NOREPINEPHRINE; INHIBITION; PLASMA AB The present study was designed to identify an interaction between the renin-angiotensin system and noradrenergic transmission in the human heart. It is still under debate whether angiotensin ii facilitates noradrenaline release in the heart. Clinical studies of congestive heart failure, involving systemic angiotensin-converting enzyme (ACE) inhibitor administration, have indicated anti-adrenergic effects, without giving a clear mechanistic picture. The influence on cardiac sympathetic transmission by local intracardiac administration of an ACE inhibitor has not been determined. Seven angina patients with normal left ventricular function, who underwent control coronary angiography after successful percutaneous transluminal coronary angioplasty were studied. Baseline measurements of haemodynamics and total and cardiac noradrenaline spillover were followed by handgrip exercise in the absence and presence of intracoronary enalaprilat infusion (0.05 mg min(-1), 1 mL min(-1)). Baseline total body and cardiac noradrenaline spillover remained unchanged following intracoronary enalaprilat infusion, being 3745 +/- 349 and 3896 +/- 257 pmol min(-1), and 148 +/- 56 and 149 +/- 55 pmol min(-1), before and after drug administration, respectively. Mean arterial pressure, peripheral plasma renin activity and angiotensin II levels were also unaffected by enalaprilat infusion. During handgrip exercise procedures, both total body and cardiac noradrenaline spillover increased substantially, showing no reduction in the presence of intracardiac enalaprilat. Direct administration of the ACE inhibitor enalaprilat to the human heart failed to attenuate cardiac sympathetic drive during baseline conditions or following cardiac adrenergic activation by handgrip exercise. Thus, in the non-failing heart, without chronic adrenergic activation, no angiotensin II-facilitated effect on cardiac noradrenaline spillover could be detected. C1 SAHLGRENS UNIV HOSP,DEPT CLIN PHYSIOL,HEART & LUNG INST,S-41345 GOTHENBURG,SWEDEN. SAHLGRENS UNIV HOSP,DEPT CARDIOL,HEART & LUNG INST,S-41345 GOTHENBURG,SWEDEN. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 36 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0001-6772 J9 ACTA PHYSIOL SCAND JI Acta Physiol. Scand. PD SEP PY 1997 VL 161 IS 1 BP 15 EP 22 DI 10.1046/j.1365-201X.1997.00199.x PG 8 WC Physiology SC Physiology GA XX621 UT WOS:A1997XX62100003 PM 9381945 ER PT J AU Biggar, RJ Mtimavalye, L Justesen, A Broadhead, R Miley, W Waters, D Goedert, JJ Chiphangwi, JD Taha, TE Miotti, PG AF Biggar, RJ Mtimavalye, L Justesen, A Broadhead, R Miley, W Waters, D Goedert, JJ Chiphangwi, JD Taha, TE Miotti, PG TI Does umbilical cord blood polymerase chain reaction positivity indicate in utero (pre-labor) HIV infection? SO AIDS LA English DT Article DE AIDS; HIV; infants; cord blood; perinatal transmission; vertical transmission; viruses ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOTHER-TO-CHILD; VIRAL LOAD; VERTICAL TRANSMISSION; TYPE-1; INTRAUTERINE; RISK; INTERVENTION; SPECIMENS; HEPATITIS AB Objective: To compare risk factors for infants whose cord blood was positive for HIV DNA with those who were cord blood-negative but found to be HIV DNA-positive in early infancy. Methods: In 1994, infants born to HIV-infected women were enrolled in a study in Blantyre, Malawi. Birth weight and transmission risk factors from cord blood-positive infants were compared with cord blood-negative/HIV-positive infants on their first postnatal visit (4-7 weeks of age). Testing for HIV DNA on cord and peripheral blood was performed by polymerase chain reaction. Results: Of 249 HIV-infected infants (overall transmission rate, 26%), 83 (33%) were cord blood-positive and 166 were initially cord blood-negative. The mean birth weight was 2.1% (59 g) lighter in cord blood-positive infants than initially cord blood-negative infants; initially cord blood-negative infants were 2.8% (80 g) lighter than uninfected infants born to HIV-infected women. There were no significant differences in the risk factors for infection between HIV-infected cord blood-positive and -negative infants; when transmission was increased, both HIV-infected cord blood-positive and -negative infants contributed to the increase in a similar proportion. Interpretation: It was concluded that umbilical cord blood positivity for HIV DNA did not identify a subset of in utero HIV-infected infants and suggested that HIV-infected cord blood-positive and -negative infants have similar timing and routes of HIV infection. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. QUEEN ELIZABETH CENT HOSP,DEPT PEDIAT,BLANTYRE,MALAWI. QUEEN ELIZABETH CENT HOSP,DEPT OBSTET & GYNECOL,BLANTYRE,MALAWI. FREDERICK CANC RES CTR,SCI APPLICAT INT CORP,FREDERICK,MD. JOHNS HOPKINS UNIV,MINIST HLTH RES PROJECT,BLANTYRE,MALAWI. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. FU NCI NIH HHS [N01-CP-33005] NR 29 TC 11 Z9 12 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1997 VL 11 IS 11 BP 1375 EP 1382 DI 10.1097/00002030-199711000-00012 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XU629 UT WOS:A1997XU62900013 PM 9302448 ER PT J AU Lori, F Gallo, RC Malykh, A Cara, A Romano, J Markham, P Franchini, G AF Lori, F Gallo, RC Malykh, A Cara, A Romano, J Markham, P Franchini, G TI Didanosine but not high doses of hydroxyurea rescue pigtail macaque from a lethal dose of SIVsmmpbj14 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID AIDS-RELATED COMPLEX; IMMUNODEFICIENCY-VIRUS; SOOTY MANGABEYS; 2',3'-DIDEOXYINOSINE; INFECTION; REPLICATION; LYMPHOCYTES; PROFILE; RHESUS; TRIAL AB It has been previously reported that hydroxyurea (HU) displays anti-HIV-1 activity and potentiates the antiviral effects of didanosine (ddI) in vitro, To assess the antiviral efficacy of HU in an animal model, the effects of HU and ddI, either individually or as combination therapy, were tested in a model using infection of pigtail macaque with the acutely fatal variant SIVsmmpbj14. At the high dosage used (100 mg/kg/day), HU monotherapy failed to protect the exposed animals from viral infection and death, which occurred within 10 days postinoculation, However, both of the ddI-treated animals (5 mg/kg/day) survived the SIVsmmpbj14 lethal dose and displayed a reduction in viral load (undetectable SIV RNA or p27(gag)) in the primary phase of infection, Of the animals treated with the combination of drugs, one died at day 18 after infection and failed to seroconvert to viral antigens, These data suggest that a high dose of HU monotherapy does not protect against death induced by SIVsmmpbj14. However, lower doses of HU as monotherapy or combination therapy deserve further evaluation for their therapeutic effects. C1 NCI,BASIC RES LAB,NIH,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 22 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 1 PY 1997 VL 13 IS 13 BP 1083 EP 1088 DI 10.1089/aid.1997.13.1083 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XU901 UT WOS:A1997XU90100002 PM 9282812 ER PT J AU Brooks, PJ AF Brooks, PJ TI DNA damage, DNA repair, and alcohol toxicity - A review SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE liver pathology; carcinogenesis; fetal alcohol syndrome; oxidative damage; lipid peroxidation ID LIPID-PEROXIDATION PRODUCTS; ETHANOL WITHDRAWAL SEIZURES; CEREBELLAR PURKINJE-CELLS; SIMIAN KIDNEY-CELLS; LIVER-DISEASE; CYTOCHROME P4502E1; INDUCIBLE CYTOCHROME-P-450; POSSIBLE MECHANISM; OXIDATIVE STRESS; RAT-LIVER AB Alcohol (ethanol) is clearly a toxic substance when consumed in excess. Chronic alcohol abuse results in a variety of pathological effects, including damage to the liver and brain; as well as other organs, and is associated with an increased risk of certain types of cancers. Alcohol consumption by pregnant women can result in fetal alcohol effects and fetal alcohol syndrome. All of these toxic effects are well documented. What is needed at present is a complete understanding of the molecular mechanisms by which alcohol causes these toxic effects. Such an understanding may lead to better treatments of some of these toxic effects. This review, focuses on the possibility that toxic effects of ethanol are mediated, at least in part, by damage to DNA. In particular, I emphasize data on the production of endogenous DNA-damaging molecules as a result of alcohol consumption and metabolism. Specific examples of DNA-damaging molecules to be considered are reactive oxygen species, including oxygen radicals, lipid peroxidation products, and acetaldehyde. The relevant DNA repair pathways that protect cells against DNA damage produced by these molecules will also be reviewed. The goal of this review is to integrate recent results from the fields of mutagenesis and DNA repair with the alcohol toxicity literature, with the aim of stimulating research into the role of DNA damage in different types of alcohol toxicity and the role of DNA repair in protecting cells from alcohol-related damage. RP Brooks, PJ (reprint author), NIAAA,NEUROGENET LAB,MOL NEUROBIOL SECT,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 124 TC 123 Z9 126 U1 1 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 1997 VL 21 IS 6 BP 1073 EP 1082 DI 10.1097/00000374-199709000-00021 PG 10 WC Substance Abuse SC Substance Abuse GA XX192 UT WOS:A1997XX19200021 PM 9309320 ER PT J AU Cohen, SG AF Cohen, SG TI Edward VII (1841-1910) - King of Great Britain SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Item About an Individual RP Cohen, SG (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1997 VL 18 IS 5 BP 328 EP 330 PG 3 WC Allergy SC Allergy GA YA588 UT WOS:A1997YA58800009 PM 9337429 ER PT J AU Cohen, SG AF Cohen, SG TI Ambrose Bierce (1842-1914) - American journalist and author SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Item About an Individual RP Cohen, SG (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1997 VL 18 IS 5 BP 331 EP 339 PG 9 WC Allergy SC Allergy GA YA588 UT WOS:A1997YA58800010 PM 9337430 ER PT J AU Cohen, SG AF Cohen, SG TI Marie-Bernarde Soubirous (1844-1879) - French canonized Catholic Nun; St. Bernadette SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Item About an Individual RP Cohen, SG (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1997 VL 18 IS 5 BP 340 EP 342 PG 3 WC Allergy SC Allergy GA YA588 UT WOS:A1997YA58800011 PM 9337431 ER PT J AU Cohen, SG AF Cohen, SG TI Joseph Pulitzer (1847-1911) - American journalist and publisher SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Item About an Individual RP Cohen, SG (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1997 VL 18 IS 5 BP 343 EP 346 PG 4 WC Allergy SC Allergy GA YA588 UT WOS:A1997YA58800012 PM 9337432 ER PT J AU Cohen, SG AF Cohen, SG TI The Jewish physician in the post Columbus era: The 15th century Spanish inquisition and expulsion revisited in 20th century Germany and Austria SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,NIH,BETHESDA,MD 20892, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1997 VL 18 IS 5 BP 347 EP 352 DI 10.2500/108854197778590524 PG 6 WC Allergy SC Allergy GA YA588 UT WOS:A1997YA58800013 PM 9337433 ER PT J AU Ciraulo, AM Alpert, N Franko, KJ AF Ciraulo, AM Alpert, N Franko, KJ TI Naltrexone for the treatment of alcoholism SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID ABUSE; DEPENDENCE; PSYCHOPATHOLOGY; MANAGEMENT; DEPRESSION; CARE AB Naltrexone is a pure opioid antagonist that is an effective nonaversive pharmacologic treatment for alcohol dependence. The usual dosage is 50 mg per day. Side effects may include nausea, headache, dizziness and arthralgia. Naltrexone appears to exert its effect by decreasing the craving for alcohol. It has also been useful in allowing some patients to decrease their need for other medications, such as benzodiazepines and antihypertensives. Naltrexone should be used as an adjunct to a comprehensive alcohol treatment program that addresses concomitant medical problems and psychosocial concerns. RP Ciraulo, AM (reprint author), BOSTON VA OPC PSYCHIAT RES 116A,VA MEDICAT DEV CTR,BOSTON NIDA,SUITE 314,251 CAUSEWAY ST,BOSTON,MA 02111, USA. NR 29 TC 3 Z9 4 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD SEP 1 PY 1997 VL 56 IS 3 BP 803 EP 806 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA XW905 UT WOS:A1997XW90500016 PM 9301573 ER PT J AU Klein, S Kinney, J Jeejeebhoy, K Alpers, D Hellerstein, M Murray, M Twomey, P Bistrian, B Bothe, A Heitkemper, M Hubbard, V Schnackenberg, D Bernstein, E Hambidge, M Heymsfield, S IretonJones, C Wolfson, M Jacobs, D Keithley, J Meguid, M Pingleton, S Kopple, J Koretz, R Shulman, R Wilmore, D Driscoll, D Fleming, CR Greene, H Sitrin, M Herrmann, V Lipman, T Mock, D Borum, P Shronts, E AF Klein, S Kinney, J Jeejeebhoy, K Alpers, D Hellerstein, M Murray, M Twomey, P Bistrian, B Bothe, A Heitkemper, M Hubbard, V Schnackenberg, D Bernstein, E Hambidge, M Heymsfield, S IretonJones, C Wolfson, M Jacobs, D Keithley, J Meguid, M Pingleton, S Kopple, J Koretz, R Shulman, R Wilmore, D Driscoll, D Fleming, CR Greene, H Sitrin, M Herrmann, V Lipman, T Mock, D Borum, P Shronts, E TI Nutrition support in clinical practice: Review of published data and recommendations for future research directions SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review ID TOTAL PARENTERAL-NUTRITION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SHORT BOWEL SYNDROME; CHAIN AMINO-ACIDS; BONE-MARROW TRANSPLANTATION; SEVERE ACUTE-PANCREATITIS; ACUTE-RENAL-FAILURE; DOUBLE-BLIND TRIAL; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; SUBJECTIVE GLOBAL ASSESSMENT AB In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being heated, clinical expertise in nutritional therapy, and input from the patient and his/her family. C1 HARVARD UNIV,MED CTR,BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. UNIV WASHINGTON,SEATTLE,WA 98195. NIDDKD,BETHESDA,MD 20892. ASCN,BETHESDA,MD. ASPEN,SILVER SPRING,MD. ROCKEFELLER UNIV,NEW YORK,NY 10021. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. ST MICHAELS HOSP,TORONTO,ON M5B 1W8,CANADA. UNIV COLORADO,MED CTR,DENVER,CO 80202. ST LUKES ROOSEVELT HOSP,NEW YORK,NY 10025. CORAM HEALTHCARE,CARROLLTON,TX. BAXTER HEALTHCARE CORP,MCGAW PK,IL. VET ADM MED CTR,SAN FRANCISCO,CA 94121. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL. SUNY HLTH SCI CTR,SYRACUSE,NY 13210. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. MAYO CLIN,ROCHESTER,MN. UNIV CALIF LOS ANGELES,HARBOR MED CTR,TORRANCE,CA 90509. OLIVE VIEW UCLA MED CTR,SYLMAR,CA 91342. BAYLOR COLL MED,HOUSTON,TX 77030. MAYO CLIN JACKSONVILLE,JACKSONVILLE,FL 32224. SLIM FAST FOOD CO,W PALM BEACH,FL. UNIV CALIF BERKELEY,BERKELEY,CA 94720. ST LOUIS UNIV,SCH MED,ST LOUIS,MO. DEPT VET AFFAIRS MED CTR,WASHINGTON,DC. UNIV ARKANSAS MED SCI,LITTLE ROCK,AR 72205. UNIV MINNESOTA,MINNEAPOLIS,MN. UNIV FLORIDA,GAINESVILLE,FL. RP Klein, S (reprint author), WASHINGTON UNIV,SCH MED,660 S EUCLID AVE,BOX 8127,ST LOUIS,MO 63110, USA. RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 256 TC 160 Z9 173 U1 1 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 1997 VL 66 IS 3 BP 683 EP 706 PG 24 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XT049 UT WOS:A1997XT04900026 PM 9280194 ER PT J AU Abruzzo, LV Griffith, LM Nandedkar, M Aguilera, NS Taubenberger, K Raffeld, M Stass, SA Abbondanzo, SL Jaffe, ES AF Abruzzo, LV Griffith, LM Nandedkar, M Aguilera, NS Taubenberger, K Raffeld, M Stass, SA Abbondanzo, SL Jaffe, ES TI Histologically discordant lymphomas with B-cell and T-cell components SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE discordant lymphoma; B-cell lymphoma; T-cell lymphoma; Epstein-Barr virus; immuno-phenotype ID POLYMERASE CHAIN-REACTION; EPSTEIN-BARR-VIRUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; COMPOSITE LYMPHOMA; MALIGNANT-LYMPHOMA; GENE REARRANGEMENT; CLONAL ORIGIN; IMMUNOPHENOTYPE AB We describe the clinical, histologic, immunophenotypic, and genotypic features of five cases of histologically discordant lymphomas with B-cell and T-cell components, Three patients presented with B-cell lymphoma;T-cell lymphoma subsequently developed. One patient presented with T-cell lymphoma; B-cell lymphoma subsequently developed. One patient presented with synchronous B-cell and T-cell lymphomas. There were three men and two women. The median age at the initial diagnosis of lymphoma was 66 years. The mean interval between the development of the two lymphomas was 83 months. All patients died of disease. The mean survival was 96 months after the initial diagnosis of lymphoma and 14 months after the diagnosis of the histologically discordant lymphoma. Epstein-Barr virus was found in two cases-the B-cell lymphoma in the patient who presented with synchronous lymphomas, and the subsequent T-cell lymphoma in one of the patients who presented with B-cell lymphoma, Based on the results of immunophenotypic and genotypic analyses, these cases likely represent the occurrence of two distinct lymphoid neoplasms rather than histologic progression of the same neoplastic clone. Furthermore, a subset of these cases are Epstein-Barr virus-associated. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,MARLENE & STEWART GREENEBAUM CANC CTR,BALTIMORE,MD 21201. ARMED FORCES INST PATHOL,DEPT HEMATOL & LYMPHAT PATHOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. NR 34 TC 40 Z9 41 U1 0 U2 1 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 1997 VL 108 IS 3 BP 316 EP 323 PG 8 WC Pathology SC Pathology GA XT308 UT WOS:A1997XT30800012 PM 9291461 ER PT J AU Harris, HW Lebowitz, BD AF Harris, HW Lebowitz, BD TI Clinically oriented basic science - Emerging opportunities for research in late-life mental disorders SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material RP Harris, HW (reprint author), NIMH,MENTAL DISORDERS AGING RES BRANCH,5600 FISHERS LANE,ROOM 18-101,ROCKVILLE,MD 20857, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FAL PY 1997 VL 5 IS 4 BP 284 EP 286 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA YE227 UT WOS:A1997YE22700003 PM 9363285 ER PT J AU Shapria, SK McCaskill, C Northrup, H Spikes, AS Elder, FFB Sutton, VR Korenberg, JR Greenberg, F Shaffer, LG AF Shapria, SK McCaskill, C Northrup, H Spikes, AS Elder, FFB Sutton, VR Korenberg, JR Greenberg, F Shaffer, LG TI Chromosome 1p36 deletions: The clinical phenotype and molecular characterization of a common newly delineated syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TERMINAL DELETION; DIAGNOSIS; CONFIRMATION; CONSEQUENCES; MONOSOMY; FEATURES; DISTAL; REGION; DNA; 5P AB Deletions of the distal short arm of chromosome 1 (1p36) represent a common, newly delineated deletion syndrome, characterized by moderate to severe psychomotor retardation, seizures, growth delay, and dysmorphic features. Previous cytogenetic underascertainment of this chromosomal deletion has made it difficult to characterize the clinical and molecular aspects of the syndrome. Recent advances in cytogenetic technology, particularly FISH, have greatly improved the ability to identify 1p36 deletions and have allowed a clearer definition of the clinical phenotype and molecular characteristics of this syndrome. We have identified 14 patients with chromosome 1p36 deletions and have assessed the frequency of each phenotypic feature and clinical manifestation in the 13 patients with pure 1p36 deletions. The physical extent and parental origin of each deletion were determined by use of FISH probes an cytogenetic preparations and by analysis of polymorphic DNA markers in the patients and their available parents. Clinical examinations revealed that the most common features and medical problems in patients with this deletion syndrome include large anterior fontanelle (100%), motor delay/hypotonia (32%), moderate to severe mental retardation (92%), growth delay (85%), pointed chin (80%), eye/vision problems (75%), seizures (72%), flat nasal bridge (65%), clinodactyly and/or short fifth finger(s) (64%), low-set ear(s) (53%), ear asymmetry (57%), hearing deficits (56%), abusive behavior (56%), thickened ear helices (53%), and deep-set eyes (50%). FISH and DNA polymorphism analysis showed that there is no uniform region of deletion but, rather, a spectrum of different deletion sizes with a common minimal region of deletion overlap. C1 BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV TEXAS,SCH MED,DEPT PATHOL,HOUSTON,TX 77030. UNIV TEXAS,SCH MED,DEPT PEDIAT,HOUSTON,TX 77030. CEDARS SINAI MED CTR,DIV MED GENET,LOS ANGELES,CA 90048. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Shapria, SK (reprint author), BAYLOR COLL MED,DEPT MOL & HUMAN GENET,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. NR 32 TC 153 Z9 155 U1 0 U2 9 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1997 VL 61 IS 3 BP 642 EP 650 DI 10.1086/515520 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA XY523 UT WOS:A1997XY52300022 PM 9326330 ER PT J AU Kaplan, NL Martin, ER Weir, BS AF Kaplan, NL Martin, ER Weir, BS TI Transmission/disequilibrium tests for multiallelic loci - Reply SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 N CAROLINA STATE UNIV,DEPT STAT,PROGRAM STAT GENET,RALEIGH,NC 27695. RP Kaplan, NL (reprint author), NIEHS,BIOSTAT BRANCH,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 1 TC 3 Z9 3 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1997 VL 61 IS 3 BP 778 EP 778 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA XY523 UT WOS:A1997XY52300038 ER PT J AU Zahm, SH Blair, A Alvarado, A Butterfield, P Cooper, S DeStefano, F Egan, J Engel, L Garcia, D Hendrikson, E Heppel, M Heyer, N Hunt, L Keifer, MC Krauska, M McDonnell, C Mills, P Mountain, K Mull, LD Nordstrom, D Outterson, B Rottenberg, L Ryder, R Slesinger, DP Smith, MA Stallones, L Stephens, C Stevens, D Sweeney, A Torres, LR Vernon, S Wilk, V AF Zahm, SH Blair, A Alvarado, A Butterfield, P Cooper, S DeStefano, F Egan, J Engel, L Garcia, D Hendrikson, E Heppel, M Heyer, N Hunt, L Keifer, MC Krauska, M McDonnell, C Mills, P Mountain, K Mull, LD Nordstrom, D Outterson, B Rottenberg, L Ryder, R Slesinger, DP Smith, MA Stallones, L Stephens, C Stevens, D Sweeney, A Torres, LR Vernon, S Wilk, V TI Cancer feasibility studies among migrant farmworkers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article C1 MONTANA STATE UNIV,BOZEMAN,MT. UNIV WASHINGTON,SEATTLE,WA 98195. BOSTON UNIV,BOSTON,MA 02215. UNIV WISCONSIN,MADISON,WI 53706. COLORADO STATE UNIV,FT COLLINS,CO 80523. BUR PRIMARY HLTH CARE,BETHESDA,MD. RP Zahm, SH (reprint author), NATL CANC INST,OCCUPAT EPIDEMIOL BRANCH,EPN 418,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 1 TC 9 Z9 9 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD SEP PY 1997 VL 32 IS 3 BP 301 EP 302 DI 10.1002/(SICI)1097-0274(199709)32:3<301::AID-AJIM17>3.0.CO;2-Z PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XJ147 UT WOS:A1997XJ14700017 PM 9219661 ER PT J AU Wheat, J MaWhinney, S Hafner, R McKinsey, D Chen, DF Korzun, A Shakan, KJ Johnson, P Hamill, R Bamberger, D Pappas, P Stansell, J Koletar, S Squires, K Larsen, RA Cheung, T Hyslop, N Lai, KK Schneider, D Kauffman, C Saag, M Dismukes, W Powderly, W AF Wheat, J MaWhinney, S Hafner, R McKinsey, D Chen, DF Korzun, A Shakan, KJ Johnson, P Hamill, R Bamberger, D Pappas, P Stansell, J Koletar, S Squires, K Larsen, RA Cheung, T Hyslop, N Lai, KK Schneider, D Kauffman, C Saag, M Dismukes, W Powderly, W TI Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID AMPHOTERICIN-B THERAPY; CAPSULATUM ANTIGEN; SYNDROME AIDS; ITRACONAZOLE; RELAPSE; PREVENTION; ANTIFUNGAL; DIAGNOSIS AB PURPOSE: This study assesses the efficacy and safety of fluconazole therapy in patients with acquired immunodeficiency syndrome (AIDS) and mild to moderately severe manifestations of disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial. All patients had AIDS and disseminated histoplasmosis. Patients were treated with 1,200 mg of fluconazole given by mouth once on the first day, then 600 mg once daily for 8 weeks, and those patients who improved clinically were then assigned fluconazole maintenance therapy 200 mg once daily for at least 1 year. Interim analysis revealed a high failure rate (10 of 20, 50%), causing revision of the protocol to increase the fluconazole dose to 1,600 mg given once on the first day, then 800 mg once daily, and the duration to 12 weeks for induction therapy and then 400 mg daily for 1 year for maintenance therapy. MEASUREMENTS AND MAIN RESULTS: Thirty-six of 49 patients (74%; 95% confidence interval [CI]: 59% to 85%) with mild to moderately severe clinical manifestations who entered into the revised study responded to 800 mg of fluconazole daily for 12 weeks as induction therapy. Of the seven patients who failed induction therapy because of progression of histoplasmosis, one died of the infection. Of 36 patients who entered into the maintenance phase of the study receiving 400 mg of fluconazole daily for 1 year, 11 (30.5%) relapsed, including one who died (2.8%). Two of the 49 patients (4.1%) were removed because of grade 4 adverse events, alkaline phosphatase elevation for one and aspartate aminotransferase elevation in the other. The relapse-free rate at 1 year was 53% (95% CI: 32% to 89%), prompting closure of the study. CONCLUSIONS: Fluconazole 800 mg daily is a safe and moderately effective induction therapy for mild or moderately severe disseminated histoplasmosis in patients with AIDS. On the basis of historic comparison, fluconazole 400 mg daily is less effective than itraconazole 200 to 400 mg daily or amphotericin B 50 mg given weekly as maintenance therapy to prevent relapse. (C) 1997 by Excerpta Medica, Inc. C1 INDIANA UNIV,INDIANAPOLIS,IN 46204. ROUDEBUSH DEPT VET AFFAIRS MED CTR,INDIANAPOLIS,IN. SDAC AIDS CLIN TRIALS GRP,BOSTON,MA. NIAID,DIV AIDS,ROCKVILLE,MD. INFECT DIS ASSOCIATES KANSAS CITY,KANSAS CITY,MO. UNIV CINCINNATI,CINCINNATI,OH. UNIV TEXAS,SCH MED,HOUSTON,TX. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV MISSOURI,KANSAS CITY,MO 64110. UNIV ALABAMA,BIRMINGHAM,AL. SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. OHIO STATE UNIV,COLUMBUS,OH 43210. CORNELL UNIV,NEW YORK,NY. UNIV SO CALIF,LOS ANGELES,CA. MT SINAI SCH MED,NEW YORK,NY. TULANE UNIV,NEW ORLEANS,LA 70118. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. FRONTIER SCI TECH & RES FDN,AMHERST,NY. VET AFFAIRS MED CTR,ANN ARBOR,MI. WASHINGTON UNIV,ST LOUIS,MO. FU NCRR NIH HHS [MO1-RR00750]; NIAID NIH HHS [N01-AI-15082, N01-AI-65296] NR 19 TC 81 Z9 88 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1997 VL 103 IS 3 BP 223 EP 232 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA XX322 UT WOS:A1997XX32200007 PM 9316555 ER PT J AU Hendrix, MJC Muschel, RJ Padarathsingh, M AF Hendrix, MJC Muschel, RJ Padarathsingh, M TI Recent advances in breast cancer research: From genes to management SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material C1 UNIV IOWA,IOWA CANC CTR,IOWA CITY,IA 52242. UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. NIH,DIV RES GRANTS,BETHESDA,MD 20892. RP Hendrix, MJC (reprint author), UNIV IOWA,COLL MED,DEPT ANAT & CELL BIOL,ROOM 1-402,BSB,IOWA CITY,IA 52242, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1997 VL 151 IS 3 BP 883 EP 888 PG 6 WC Pathology SC Pathology GA XU378 UT WOS:A1997XU37800028 PM 9284837 ER PT J AU Egidy, G Friedman, J Viswanathan, M Wahl, LM Saavedra, JM AF Egidy, G Friedman, J Viswanathan, M Wahl, LM Saavedra, JM TI CGP-42112 partially activates human monocytes and reduces their stimulation by lipopolysaccharides SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE anti-inflammatory agent; proinflammatory cytokines; matrix metallaproteinase-9; adenosine 3',5'-cyclic monophosphate; orphan receptor ID ANGIOTENSIN-II AT(2); BINDING-SITE; COLLAGENASE PRODUCTION; EXPRESSION; MACROPHAGES; INHIBITION; RECEPTORS; BRAIN; METALLOPROTEINASES; AUTORADIOGRAPHY AB CGP 42112, a high-affinity Ligand for angiotensin II AT(2) receptors, binds to rat macrophage/microglia lacking AT(2) receptors. Here we report that CGP-42112 binds to human monocytes and exerts specific effects. Binding studies revealed a single site, highly specific for CGP-42112, not displaceable by angiotensin II, angiotensin fragments, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, IL-IO, transforming growth factor-beta, or lipopolysaccharide (LPS). Incubation of purified human monocytes in serum-free medium with CGP-42112 enhanced, in a dose-dependent manner, cell attachment to fibronectin and collagen-coated dishes as well as matrix metalloproteinase-9 secretion. CGP-42112 did not promote cytokine secretion. In contrast, when added in the presence of low doses of LPS, CGP-42112 reduced the LPS-stimulated secretion of TNF-alpha, IL-1 alpha, IL-1 beta, and. IL-6 without affecting IL-10 and decreased the LPS-stimulated matrix metalloproteinase-9 activity. Additionally, CGP-42112 inhibited the increase in protein kinase A activity produced by LPS. Our results indicate that CGP-42112 may modulate monocyte activation through binding to a novel receptor. C1 NIMH, PHARMACOL SECT, CLIN SCI LAB, NIH, BETHESDA, MD 20892 USA. NIDR, IMMUNOL LAB, CELLULAR IMMUNOL SECT, NIH, BETHESDA, MD 20892 USA. NR 28 TC 13 Z9 14 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 1997 VL 273 IS 3 BP C826 EP C833 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XV710 UT WOS:A1997XV71000007 PM 9316402 ER PT J AU Pratley, RE Nicolson, M Bogardus, C Ravussin, E AF Pratley, RE Nicolson, M Bogardus, C Ravussin, E TI Plasma leptin responses to fasting in Pima Indians SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE obesity; food intake; insulin ID OBESE GENE-PRODUCT; OB GENE; INSULIN; WEIGHT; HUMANS; EXPRESSION; PROTEIN; ABSENCE; MICE; RNA AB Leptin is believed to play a role in the regulation of energy balance, but little is known about factors influencing plasma leptin concentrations. To determine the effect of short-term changes in energy balance, we measured plasma leptin concentrations as well as plasma glucose, insulin, triglyceride, nonesterified fatty acid concentrations, and metabolic rate in response to a standard test meal followed by a 24-h fast in 21 healthy Pima Indians. Plasma leptin concentrations decreased by 8% (P < 0.05) 2-4 h after the test meal. They returned to baseline 6-12 h after the subjects ate, then subsequently decreased, and, by the, end of the fast, were an average of 37% below baseline (P < 0.0001). Changes in plasma leptin concentrations did not correlate with changes in plasma glucose, insulin, triglyceride, or nonesterified fatty acid concentrations or with changes in metabolic rate. The re suits of this study indicate that plasma leptin concentrations decrease in response to short-term energy restriction. These changes were not due to changes in glucose, insulin, triglycerides, or nonesterified fatty acids, nor did they relate to changes in metabolic rate. The decrease in plasma leptin concentrations with fasting map be an important homeostatic response to an energy deficit, stimulating food intake and thus restoring energy balance. C1 NIDDKD, CLIN DIABET & NUTR SECT, PHOENIX EPIDEMIOL & CLIN RES BRANCH, PHOENIX, AZ 85016 USA. AMGEN INC, THOUSAND OAKS, CA 91330 USA. NR 27 TC 30 Z9 30 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 1997 VL 273 IS 3 BP E644 EP E649 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA XV094 UT WOS:A1997XV09400025 PM 9316457 ER PT J AU Yoshigi, M Ettel, JM Keller, BB AF Yoshigi, M Ettel, JM Keller, BB TI Developmental changes in flow-wave propagation velocity in embryonic chick vascular system SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE chick embryo; cardiovascular development; phase velocity; Fourier transform; arterial elasticity ID BLOOD-FLOW; SMALL VESSELS; HYPERTENSION; URBAN AB We analyzed flow-wave propagation velocity in the early embryonic vascular system and its responses to acute alterations in circulating blood volume. Two 20-MHz pulsed Doppler velocimeters were positioned along the arterial system in stage 18 (n = 12), 21 (n = 10), and 24 (n = II) chick embryos. Distance between the two measurement sites was measured by video-microscopy. Phase velocity was calculated using Fourier transform up to the fourth harmonics. Wave-front velocity was also calculated by threshold technique. In a subset of embryos at stage 24 (n = 10), circulating blood volume was acutely altered to change stroke volume. Mean phase velocity increased from 42.9 +/- 3.3 to 95.8 +/- 7.5 cm/s from stage 18 to 24 (P < 0.05 by analysis of variance), whereas wave-front velocity increased from 52.8 +/- 2.4 to 72.2 +/- 5.2 cm/s. Stroke volume and mean aortic pressure paralleled the changes in mean phase velocity and wave-front velocity in normal development and in response to changes in circulating blood volume. Thus developmental changes in wave-propagation velocity were consistent with changes in the size of the vascular system, pressure range, and elastic properties of the arterial wall during systemic vasculogenesis in the embryo. C1 Univ Rochester, Sch Med & Dent,Strong Childrens Res Ctr, NIH,Specialized Ctr Res Pediat Cardiovasc Dis, Dept Pediat,Div Pediat Cardiol, Rochester, NY 14642 USA. RP Yoshigi, M (reprint author), Univ Rochester, Sch Med & Dent,Strong Childrens Res Ctr, NIH,Specialized Ctr Res Pediat Cardiovasc Dis, Dept Pediat,Div Pediat Cardiol, 601 Elmwood Ave,Box 631, Rochester, NY 14642 USA. FU NHLBI NIH HHS [P50-HL-51498] NR 37 TC 9 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1997 VL 273 IS 3 BP H1523 EP H1529 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA XV709 UT WOS:A1997XV70900058 PM 9321845 ER PT J AU Zhou, YY Cheng, HP Bogdanov, KY Hohl, C Altschuld, R Lakatta, EG Xiao, RP AF Zhou, YY Cheng, HP Bogdanov, KY Hohl, C Altschuld, R Lakatta, EG Xiao, RP TI Localized cAMP-dependent signaling mediates beta(2)-adrenergic modulation of cardiac excitation-contraction coupling SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE beta(2)-adrenergic receptor; adenosine 3 ',5 '-cylic monophosphate compartmentation; pertussis toxin-sensitive G proteins; calcium current; intracellular calcium ID BETA-ADRENERGIC STIMULATION; GUINEA-PIG HEARTS; CYCLIC-AMP; PROTEIN-KINASE; VENTRICULAR MYOCYTES; PHOSPHOLAMBAN PHOSPHORYLATION; SARCOPLASMIC-RETICULUM; INOTROPIC RESPONSES; CALCIUM CURRENT; CA2+ CHANNELS AB Recent studies have shown that beta(2)-adrenergic receptor (beta(2)-AR)-stimulated increases in the intracellular Ca2+ (Ca-i) transient and contraction in cardiac myocytes are dissociated from the increase in adenosine 3',5'-cyclic monophosphate (cAMP) level and are not accompanied by an increase in phospholamban phosphorylation, an acceleration in relaxation, or a reduction in myofilament Ca2+ response. Thus we hypothesized that the beta(2)-AR modulation of cardiac excitation-contraction (EC) coupling may be mediated by either a cAMP-independent mechanism or a compartmentalized cAMP pathway. To directly distinguish between these two possibilities, the responses of the L-type Ca2+ current (I-Ca), Ca-i transient, and contraction to beta(2)-AR as well as to beta(1)-AR stimulation were examined in rat ventricular myocytes in the presence or absence of specific inhibitory cAMP analogs, Rp diastereomers of adenosine 3',5'-cyclic monophasphothioate (Rp-cAMPS) and 8-(4-chlorophenylthio)-cAMP (Rp-CPT-cAMPS). As expected, the positive inotropic effect induced by an adenylyl cyclase activator, forskolin (2 x 10(-7) M), or a beta(1)-AR agonist, norepinephrine (5 x 10(-8) M) plus prazosin (10(-6) M), was completely blocked by Rp-CPT-cAMPS. More importantly, the responses of I-Ca, Ca-i transient, and contraction to beta(2)-AR stimulation by zinterol (10(-5) M) or isoproterenol plus a selective beta(1)-AR antagonist, CGP-20712A, were also entirely abolished by Rp-cAMPS (in the patch-pipette solution) or Rp-CPT-cAMPS (in the bath solution). in pertussis toxin-treated cells, although the response of cAMP was not altered, the beta(2)-AR-stimulated increase in contraction amplitude was markedly enhanced and accompanied by a hastened relaxation, resulting in a tight association between cAMP and contraction. These results indicate that beta(2)-AR modulation of cardiac excitation-contraction coupling requires cAMP. The dissociation of beta(2)-AR-stimulated cAMP production and regulation of myofilament and sarcoplasmic reticulum functions is attributable to a functional compartmentation of the cAMP-dependent signaling due to an activation of beta(2)-AR-coupled G(i) and/or G(o). C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Inst Expt Cardiol, Heart Electrophysiol Lab, Moscow 121552, RUSSIA. Ohio State Univ, Dept Med Biochem, Columbus, OH 43210 USA. RP Xiao, RP (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 38 TC 79 Z9 80 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1997 VL 273 IS 3 BP H1611 EP H1618 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA XV709 UT WOS:A1997XV70900069 ER PT J AU White, AM Yoshimura, T Smith, AW Westwick, J Watson, ML AF White, AM Yoshimura, T Smith, AW Westwick, J Watson, ML TI Airway inflammation induced by recombinant guinea pig tumor necrosis factor-alpha SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE lung inflammation; eosinophil; cytokine ID MESSENGER-RNA EXPRESSION; ESCHERICHIA-COLI; EOSINOPHIL ACCUMULATION; MOLECULAR-CLONING; CYTOKINES; PULMONARY; CDNA; RATS; TNF; INTERLEUKIN-1 AB We have cloned and expressed recombinant guinea pig tumor necrosis factor-alpha (gpTNF-alpha) and examined its inflammatory activities after tracheal instillation in guinea pigs. A 1,071-bp cDNA, including the region encoding the full-length 234-amino acid gpTNF-alpha protein, was cloned from concanavalin A-stimulated guinea pig splenocytes. The 154-amino acid protein corresponding to secreted gpTNF-alpha was expressed as a fusion protein in Escherichia coli, purified by affinity chromatography, and cleaved to yield a 17-kDa protein. gpTNF-alpha had a cytotoxic effect on WEHI 164 cells and was detected by goat anti-murine tumor necrosis factor-alpha (TNF-alpha) antibody in Western blots. Intratracheal instillation of gpTNF-alpha (50-150 ng) caused pronounced and dose-dependent airway eosinophilia. Incubation of gpTNF-alpha with rabbit anti-murine TNF-alpha sera or heating the gpTNF-alpha before instillation reduced bronchoalveolar lavage (BAL) eosinophils to near control levels. Maximum BAL eosinophilia was observed at 24 h, but eosinophil numbers remained significantly above vehicle-treated animals for 72 h. Hence, gpTNF-alpha elicits a pronounced and protracted eosinophil accumulation in the guinea pig lung. C1 UNIV BATH, SCH PHARM & PHARMACOL, BATH BA2 7AY, AVON, ENGLAND. NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NR 31 TC 17 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 1997 VL 273 IS 3 BP L524 EP L530 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA XU863 UT WOS:A1997XU86300004 PM 9316485 ER PT J AU Coe, JE Cieplak, W Hadlow, WJ Ross, MJ AF Coe, JE Cieplak, W Hadlow, WJ Ross, MJ TI Female protein, amyloidosis, and hormonal carcinogenesis in Turkish hamster: differences from Syrian hamster SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE pentraxin structure and regulation; hamster serum amyloid P component; estrogen-induced renal and hepatic tumors ID C-REACTIVE PROTEIN; P-COMPONENT; ARMENIAN HAMSTER; GENE STRUCTURE; PENTRAXIN; EXPRESSION; EVOLUTION; SAP AB The Syrian hamster (Mesocricetus auratus) has been widely used as an experimental animal and is a unique model for three sex hormone-regulated events: 1) estrogen-initiated renal carcinogenesis, 2) sex-limited expression of amyloidosis, a ubiquitous disease, and 3) sex hormone control of a serum amyloid P component (SAP) called female protein (FP). In this study, we evaluated the closely related Turkish hamster (Mesocricetus brandti) for these three events and found some very different responses: 1) estrogen-initiated renal carcinogenesis was not found in Turkish hamster, 2) amyloidosis was not sex limited and actually was a rare disease in the Turkish hamster, and 3) Turkish hamsters did express a sex-limited SAP-FP in serum that was antigenically identical and structurally very similar (97.5%) to Syrian hamster SAP-FP. However, acute phase regulation of SAP-FP synthesis was different, and serum levels of this pentraxin were much lower than those found in the Syrian hamster. On the other hand, in contrast to findings in the Syrian hamster, hepatic tumors were relatively common in normal and especially in estrogen-treated Turkish hamsters. Therefore, although they are closely related, these two Mesocricetus hamster species have markedly dissimilar responses to sex hormones. RP Coe, JE (reprint author), NIAID, ROCKY MT LABS, PERSISTENT VIRAL DIS LAB, 903 S 4TH ST, HAMILTON, MT 59840 USA. NR 30 TC 7 Z9 7 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 1997 VL 273 IS 3 BP R934 EP R941 PG 8 WC Physiology SC Physiology GA XV805 UT WOS:A1997XV80500013 PM 9321870 ER PT J AU Martin, SL Kim, H Kupper, LL Meyer, RE Hays, M AF Martin, SL Kim, H Kupper, LL Meyer, RE Hays, M TI Is incarceration during pregnancy associated with infant birthweight? SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article; Proceedings Paper CT Reproductive Epidemiology Conference of the ADELF-Congress CY JUN 03, 1996 CL BRUSSELS, BELGIUM SP ADELF Congress ID PHYSICAL ABUSE; DRUG-ABUSE; WEIGHT; WOMEN AB Objectives. This study examined whether incarceration during pregnancy is associated with infant birthweight. Methods. Multivariable analyses compared infant birthweight outcomes among three groups of women: 168 women incarcerated during pregnancy, 630 women incarcerated at a time other than during pregnancy, and 3910 women never incarcerated. Results. After confounders were controlled for, infant birthweights among women incarcerated during pregnancy were not significantly different from women never incarcerated; however, infant birthweights were significantly worse among women incarcerated at a time other than during pregnancy than among never-incarcerated women and women incarcerated during pregnancy. Conclusions. Certain aspects of the prison environment (shelter, food, etc.) may be health-promoting for high-risk pregnant women. C1 UNIV N CAROLINA,DEPT BIOSTAT,CHAPEL HILL,NC 27599. NICHHD,NIH,ROCKVILLE,MD. NC STATE CTR HLTH & STAT,DEPT ENVIRONM HLTH & NAT RESOURCES,RALEIGH,NC. RP Martin, SL (reprint author), UNIV N CAROLINA,SCH PUBL HLTH,DEPT MATERNAL & CHILD HLTH,CB 7400,CHAPEL HILL,NC 27599, USA. FU PHS HHS [MCJ-107] NR 33 TC 21 Z9 21 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 1997 VL 87 IS 9 BP 1526 EP 1531 DI 10.2105/AJPH.87.9.1526 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XY235 UT WOS:A1997XY23500024 PM 9314809 ER PT J AU Issaragrisil, S Chansung, K Kaufman, DW Sirijirachai, J Thamprasit, T Young, NS Anderson, T Leaverton, PE Piankijagum, A Porapakkham, Y Shapiro, S Vannasaeng, S Sompradeekul, S Vuthivatanakul, T Sriratanasatavorn, C Yamcharoen, C Laewsiri, P Kittimongcolporn, S Tepmongcol, K Wongkongdej, R Vejjapinand, R Kiatvirakul, V Kareng, K Suvatte, V Intaragumthornchai, T Chancharunee, S Prayoonwiwat, V Seksan, P Chuansumrit, A Chinarat, V Angkuravorakul, S Atichartkarn, V Chutipong, S Fucharoen, S Hathirat, P Isarankura, P Jetsrisuparb, A Jootar, S Kiatkachorntada, N Kitkornpan, S Laohavinij, S Laosombat, V Lekhakul, A Mahasandana, C Makornkaewkayoon, V Nitiyanont, P Pootrakul, P Singhapan, K Siritanaratanakul, N Sonakul, D Srichaikul, T Sripaisal, T Sucharitchan, P Sukpanichnand, S Sukpanichnand, SY Supradit, P Suwanwela, N Tanphaichitr, VS Tantechanurak, C Tanyavudh, K Vatanavicharn, S Visudhiphan, S Wanachiwanawin, W Watananukul, P AF Issaragrisil, S Chansung, K Kaufman, DW Sirijirachai, J Thamprasit, T Young, NS Anderson, T Leaverton, PE Piankijagum, A Porapakkham, Y Shapiro, S Vannasaeng, S Sompradeekul, S Vuthivatanakul, T Sriratanasatavorn, C Yamcharoen, C Laewsiri, P Kittimongcolporn, S Tepmongcol, K Wongkongdej, R Vejjapinand, R Kiatvirakul, V Kareng, K Suvatte, V Intaragumthornchai, T Chancharunee, S Prayoonwiwat, V Seksan, P Chuansumrit, A Chinarat, V Angkuravorakul, S Atichartkarn, V Chutipong, S Fucharoen, S Hathirat, P Isarankura, P Jetsrisuparb, A Jootar, S Kiatkachorntada, N Kitkornpan, S Laohavinij, S Laosombat, V Lekhakul, A Mahasandana, C Makornkaewkayoon, V Nitiyanont, P Pootrakul, P Singhapan, K Siritanaratanakul, N Sonakul, D Srichaikul, T Sripaisal, T Sucharitchan, P Sukpanichnand, S Sukpanichnand, SY Supradit, P Suwanwela, N Tanphaichitr, VS Tantechanurak, C Tanyavudh, K Vatanavicharn, S Visudhiphan, S Wanachiwanawin, W Watananukul, P TI Aplastic anemia in rural Thailand: Its association with grain farming and agricultural pesticide exposure SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Objectives. A population-based cage-control study was conducted to elucidate the incidence and etiology of aplastic anemia in Thailand. Methods. Case patients and hospital control patients:were enrolled in three regions from 1989 to 1994; data were collected by interview. Results. Forty-six percent of 81 case patients and 19% of 295 control patients from Khonkaen were grain farmers (estimated relative risk [RR] = 2.7, 95% confidence interval [CI] = 1.4, 5.2). Sixteen percent of case patients and 6% of control patients used agricultural pesticides (estimated RR = 2.7, 95% CI = 1.1, 6.6). The association with grain farming remained among those not exposed to pesticides. In Songkla, 16% of 43 case patients and 2% of 181 control patients were grain farmers (crude RR estimate = 11, 95% CI = 3.4, 35). Conclusions. The relation. of aplastic anemia to grain farming may partly explain the high incidence of aplastic anemia in Thailand. C1 KHON KAEN UNIV,FAC MED,DEPT MED,KHON KAEN 40002,THAILAND. BOSTON UNIV,SCH MED,SCH PUBL HLTH,SLOAN EPIDEMIOL UNIT,BROOKLINE,MA. PRINCE SONGKLA UNIV,FAC MED,DEPT MED,SONGKHLA,THAILAND. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RP Issaragrisil, S (reprint author), MAHIDOL UNIV,SIRIRAJ HOSP,DEPT MED,DIV HEMATOL,BANGKOK 10700,THAILAND. OI Issaragrisil, Surapol/0000-0002-8924-0646 FU NHLBI NIH HHS [HL35068] NR 9 TC 23 Z9 27 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 1997 VL 87 IS 9 BP 1551 EP 1554 DI 10.2105/AJPH.87.9.1551 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XY235 UT WOS:A1997XY23500030 PM 9314815 ER PT J AU Hafner, R Cohn, JA Wright, DJ Dunlap, NE Egorin, MJ Enama, ME Muth, K Peloquin, CA Mor, N Heifets, LB Dunlap, N Phillips, P Campo, R James, P Sension, M Bourie, M Witt, M Kruger, S Mushatt, D Greenspan, D AF Hafner, R Cohn, JA Wright, DJ Dunlap, NE Egorin, MJ Enama, ME Muth, K Peloquin, CA Mor, N Heifets, LB Dunlap, N Phillips, P Campo, R James, P Sension, M Bourie, M Witt, M Kruger, S Mushatt, D Greenspan, D TI Early bactericidal activity of isoniazid in pulmonary tuberculosis - Optimization of methodology SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID SPUTUM VIABLE COUNTS; CIPROFLOXACIN; RIFABUTIN AB Early bactericidal activity (EBA) of antituberculosis drugs is the rate of decrease in the concentration of tubercle bacilli sputum during the initial days of therapy. The study reported here was designed to optimize the methodology for obtaining precise EBA measurements. The study compared the results with two versus five treatment days; overnight sputum collections with early morning collections; and quantitative smears for acid-fast bacilli (AFB) with quantitative cultures. Isoniazid (INH) was used as a model drug. Among 28 smear-positive patients enrolled in the study in five cities in the United States, 16 were evaluable (INH-susceptible tuberculosis [TB] and adequate sputum collections). The mean baseline bacterial load was 6.69 log(10) cfu/ml (SE = 0.24). Quantitative culture of 10- or 12-h sputum collections obtained on two baseline days and treatment Day 5 was the optimal method for EBA measurement. The mean 5-d EBA was 0.21 log(10) cfu/ml/d (SE = 0.03; p < 0.001), and the EBA appeared to be constant during the first five treatment days. On the basis of these data, multiarm studies of investigational drugs will require 25 evaluable subjects per arm to detect (80% power and two-tailed alpha of 0.05) an EBA at least 50% as large as the EBA of INH. In countries with a low incidence of TB, the usefulness of this methodology for rapidly assessing new antituberculosis agents may be limited by the relatively large number of subjects required to compare EBA values across treatment arms. C1 UNIV MARYLAND,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT MED,DIV HEMATOL ONCOL,CTR CANC,BALTIMORE,MD 21201. WESTAT CORP,ROCKVILLE,MD. SOCIAL & SCI SYST INC,ROCKVILLE,MD. UNIV ALABAMA,DIV PULM & CRIT CARE MED,BIRMINGHAM,AL. NATL JEWISH MED & RES CTR,DENVER,CO. UNIV ALABAMA,BIRMINGHAM,AL. UNIV MIAMI,MIAMI,FL 33152. N BROWARD HOSP DIST,FT LAUDERDALE,FL. UNIV CALIF LOS ANGELES,HARBOR MED CTR,TORRANCE,CA 90509. TULANE UNIV,SCH MED,NEW ORLEANS,LA 70112. RP Hafner, R (reprint author), NIAID,DIV AIDS,NIH,SOLAR 2C25,6003 EXECUT BLVD,ROCKVILLE,MD 20852, USA. FU NIAID NIH HHS [N01-AI-15123] NR 11 TC 25 Z9 25 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP PY 1997 VL 156 IS 3 BP 918 EP 923 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XX177 UT WOS:A1997XX17700036 PM 9310014 ER PT J AU Manolio, TA Weinmann, GG Buist, AS Furberg, CD Pinsky, JL Hurd, SH AF Manolio, TA Weinmann, GG Buist, AS Furberg, CD Pinsky, JL Hurd, SH TI Pulmonary function testing in population-based studies SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID JAPANESE-AMERICAN MEN; LEFT-VENTRICULAR HYPERTROPHY; CORONARY-HEART-DISEASE; LUNG HEALTH; REFERENCE VALUES; CARDIOVASCULAR HEALTH; CIGARETTE-SMOKING; FISH CONSUMPTION; VITAL CAPACITY; INTERVENTION C1 NHLBI,DIV LUNG DIS,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,DIV PULM & CRIT CARE MED,PORTLAND,OR 97201. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. RP Manolio, TA (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,DIV EPIDEMIOL & CLIN APPLICAT,6701 ROCKLEDGE DR,ROOM 8160,BETHESDA,MD 20892, USA. NR 41 TC 6 Z9 6 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP PY 1997 VL 156 IS 3 BP 1004 EP 1010 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XX177 UT WOS:A1997XX17700049 PM 9310027 ER PT J AU Fanucchi, MV Murphy, ME Buckpitt, AR Philpot, RM Plopper, CG AF Fanucchi, MV Murphy, ME Buckpitt, AR Philpot, RM Plopper, CG TI Pulmonary cytochrome P450 monooxygenase and Clara cell differentiation in mice SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID FUNCTION OXIDASE ACTIVITY; NAPHTHALENE EPOXIDATION; MICRODISSECTED AIRWAYS; BRONCHIOLAR EPITHELIUM; RABBIT LUNG; EXPRESSION; CYTOTOXICITY; METABOLISM; HAMSTERS; MOUSE AB Various studies indicate that cytodifferentiation of Clara cells and development of pulmonary cytochrome P450 (CYP) monooxygenases occur postnatally. The timing of these events is species-specific. Neonatal mice are more susceptible than adult mice are to Clara cell injury by naphthalene, but little is known about the postnatal development of Clara cells and CYP in mice. This study war; designed to determine the developmental pattern of Clara cell differentiation and CYP expression in mice. Lungs from mice aged 16 days gestation to 63 days postnatal (DPN) were studied. Clara cell secretory protein (CC10) expression in nonciliated cells was detected earlier in proximal airways than in distal airways, but reached adult levels at 14 DPN in all airway levels, Cilia-associated tubulin expression closely followed the onset of CC10 expression, as did expression of CYP reductase. CYP2B protein expression appeared and differentiated earlier in bronchi than in bronchioles and reached adult levels at 14 and 28 DPN, respectively. CYP2F2 expression appeared earlier in proximal airways, but did not reach adult levels of expression until after 28 DPN. CYP activity, measured by naphthalene metabolism, increased with age and corresponded to CYP2F2 protein expression. We conclude that: in the mouse. (I) Clara cell maturation is a postnatal event, (2) Clara cell differentiation is complete at the same age in proximal and distal airways, (3) CYP reductase protein expression occurs at the same time as CC10 expression, but CYP2B and CYP2F2 lag behind, and (4) stereoselective naphthalene monooxygenase activity corresponds with CYP2F2 protein expression. C1 UNIV CALIF DAVIS,VM APC,SCH VET MED,DEPT VET ANAT,DAVIS,CA 95616. UNIV CALIF DAVIS,VM APC,SCH VET MED,DEPT PHYSIOL & CELL BIOL,DAVIS,CA 95616. UNIV CALIF DAVIS,VM APC,SCH VET MED,DEPT MOL BIOSCI,DAVIS,CA 95616. NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. FU PHS HHS [04311, 05707, 06700] NR 39 TC 43 Z9 44 U1 1 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 1997 VL 17 IS 3 BP 302 EP 314 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA XW107 UT WOS:A1997XW10700007 PM 9308917 ER PT J AU Andrade, ZA Andrade, SG Sadigursky, M Wenthold, RJ Hilbert, SL Ferrans, VJ AF Andrade, ZA Andrade, SG Sadigursky, M Wenthold, RJ Hilbert, SL Ferrans, VJ TI The indeterminate phase of Chagas' disease: Ultrastructural characterization of cardiac changes in the canine model SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID TRYPANOSOMA-CRUZI; CELL-DEATH; MYOCARDITIS; CYCLOPHOSPHAMIDE; TISSUE; MICROSCOPY; INFECTION; DAMAGE; HEART; MICE AB The indeterminate phase of Chagas' disease is defined as the prolonged period of clinically silent infection that follows the phase of acute primary infection with Trypanosoma cruzi. The dog is the only experimental animal model in which the indeterminate phase progresses to the late phase of severs, chronic myocarditis. This report describes the cardiac histologic and ultrastructural findings in dogs that survived the acute phase of infection with T. cruzi, becoming clinically and electrocardiographically normal for up to 3.5 years, while maintaining positive serologic test results during this period of time. Most of the myocardium appeared morphologically normal; however, small foci of mild, chronic myocarditis were present, with interstitial edema, mild fibrosis, and infiltration by lymphocytes, macrophages, and plasma cells. No microvascular lesions and no areas of close contact between immune effector cells and endothelial cells or cardiac myocytes were present. These findings were in sharp contrast to those observed in the canine model during the acute infection with T, cruzi. In this model, acute myocyte damage and lesions in the microcirculation, including fibrin microthrombi, were associated with close contacts between immune effector cells and myocytes or endothelial cells. Focally inflamed interstitial tissue showed increased deposition of amorphous and collagenous extracellular matrix as well as evidence of breakdown of collagen. The features of the inflammatory cells in the indeterminate phase of Chagas' disease were interpreted as indicating a self-limited cycle of focal inflammatory changes, with modulation and suppression of cell-mediated immune responses, Thus, we consider the indeterminate phase of Chagas' disease to be a stage of host-parasite equilibrium rather than a process of progressive damage. C1 NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,ROCKVILLE,MD 20852. RP Andrade, ZA (reprint author), MINIST SAUDE,FUNDACAO OSWALDO CRUZ,CTR PESQUISAS GONCALO MUNIZ,RUE VALDEMAR FALCAO 121 BROTAS,BR-41945 SALVADOR,BA,BRAZIL. NR 29 TC 34 Z9 37 U1 1 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 1997 VL 57 IS 3 BP 328 EP 336 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA XZ010 UT WOS:A1997XZ01000016 PM 9311645 ER PT J AU Hevener, W Almond, GW Armstrong, JD Richards, RG AF Hevener, W Almond, GW Armstrong, JD Richards, RG TI Effects of acute endotoxemia on serum somatotropin and insulin-like growth factor I concentrations in prepubertal gilts SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID HORMONE-RELEASING FACTOR; IGF-BINDING PROTEINS; METABOLIC HORMONES; BEEF HEIFERS; PIGS; CORTISOL; PLASMA; STRESS; SWINE; INFECTION AB Objective-To evaluate effects of endotoxemia on serum somatotropin (ST) and insulin-like growth-factor I (IGF-I) concentrations in finishing pigs. Animals-Eight female pigs (98 +/- 2 kg) randomly assigned to IV administration (time 0) of saline solution (n = 4) or Escherichia coli lipopolysaccharide (LPS; 5 mu g/kg of body weight; n = 4). Procedure-Serum ST concentration was determined in serum samples obtained at 20-minute intervals for 6 hours after treatment. Serum IGF-I concentration was determined in samples collected at 1-hour intervals for 6 hours and at 12, 15, 18, 24, 48, 72, and 96 hours after treatment. Results-One distinct pulse of ST (peak 10.5 +/- 0.5 ng/ml) was observed at 40 minutes in each pig after administration of LPS. Control pigs had 2.25 +/- 0.48 ST pulses during the 6 hours of frequent sample collection; however, magnitude of the ST pulses was similar between gilts given LPS and control gilts. A temporal association between ST pulses and saline administration was not evident. Serum IGF-I concentration was similar between gilts of the LPS and control groups prior to treatment. The IGF-I concentration was lower (P < 0.01) in gilts of the LPS group (44 +/- 5 ng/ml) than in gilts of the control group (157 +/- 4 ng/ml) at 24 hours. The difference in IGF-I concentrations between groups was evident for 96 hours. Conclusions-Immediate release of ST was attributed to stress associated with acute endotoxemia and stimulation of the pituitary gland; immune stimulation by LPS may have contributed to the changes in IGF-I concentration. Because feed consumption was similar between the 2 groups of pigs, suppression of IGF-I concentration for 96 hours after administration of LPS was attributable to factors in addition to transient feed restriction. Thus, acute endotoxemia altered the positive association between ST and IGF-I, and provided evidence for a potential mechanism of impaired growth in endotoxemic animals. C1 N CAROLINA STATE UNIV,DEPT ANIM SCI,RALEIGH,NC 27606. NIEHS,RES TRIANGLE PK,NC 27709. RP Hevener, W (reprint author), N CAROLINA STATE UNIV,DEPT FOOD ANIM & EQUINE MED,RALEIGH,NC 27606, USA. NR 26 TC 15 Z9 15 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD SEP PY 1997 VL 58 IS 9 BP 1010 EP 1013 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA XU029 UT WOS:A1997XU02900016 PM 9285006 ER PT J AU Choi, BT Moon, DY Choi, YH Jo, UB AF Choi, BT Moon, DY Choi, YH Jo, UB TI Seasonal variations in integumental glycoconjugates of Rana rugosa SO ANATOMICAL RECORD LA English DT Article DE integument; glycoconjugates; Rana rugosa; lectin; hibernation ID NOTOPHTHALMUS-VIRIDESCENS; FROG-SKIN; MORPHOLOGY; GLANDS; HISTOCHEMISTRY; EPIDERMIS; NEWT AB Background: Although environmental conditions can influence the expression of glycoconjugates (GCs) in the epidermis and cutaneous gland of amphibians, seasonal features regarding GCs in frogs have rarely been studied. In the present study, we report the seasonal variations of the integumental GCs in Rana rugosa. Methods: GCs were investigated at the light microscopic level using conventional and lectin histochemistry. Results: During the pre-through posthibernating periods, stronger periodic acid-Schiff (PAS)-positive GCs were observed in the stratum corneum and transitional layer of the epidermis. At the same time, alcian blue and PAS-positive GCs filled the lumen of the mucous gland. The affinity for PNA in the transitional layer, UEA-1 in stratum germinativum, and SBA in the mucous glands increased significantly during the same periods. In addition, new GCs, which are specific for SEA in the stratum corneum, BSL-1, RCA-1, sWGA, and LCA in some cells of the transitional layer, were detected. Conclusions: Elevated GCs and a diversity of lectin affinities may be a result of seasonal adaptations related to hibernation. An affinity for PNA, UEA-1, and SEA in the frog shin may be useful as a marker of seasonal changes. (C) 1997 Wiley-Liss, Inc. C1 NATL FISHERIES RES & DEV AGCY,PUSAN,SOUTH KOREA. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. PUSAN NATL UNIV,COLL EDUC,DEPT BIOL EDUC,PUSAN 609735,SOUTH KOREA. RP Choi, BT (reprint author), DONG EUI UNIV,COLL ORIENTAL MED,DEPT ORIENTAL MED,PUSAN 614054,SOUTH KOREA. NR 36 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD SEP PY 1997 VL 249 IS 1 BP 24 EP 31 PG 8 WC Anatomy & Morphology SC Anatomy & Morphology GA XU625 UT WOS:A1997XU62500004 PM 9294646 ER PT J AU Moody, E Knauer, S Skolnick, P AF Moody, E Knauer, S Skolnick, P TI Etomidate action is dependent on a specific amino acid in the beta subunit of the GABA(A) receptor complex SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DEPT ANES CRIT CARE MED,BALTIMORE,MD 21205. NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1997 VL 87 IS 3 SU S BP A705 EP A705 DI 10.1097/00000542-199709001-00705 PG 1 WC Anesthesiology SC Anesthesiology GA XV636 UT WOS:A1997XV63600705 ER PT J AU Audrain, J Schwartz, MD Lerman, C Hughes, C Peshkin, BN Biesecker, B AF Audrain, J Schwartz, MD Lerman, C Hughes, C Peshkin, BN Biesecker, B TI Psychological distress in women seeking genetic counseling for breast-ovarian cancer risk: The contributions of personality and appraisal SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID RANDOMIZED TRIAL; FAMILY HISTORY; COPING STYLES; ADJUSTMENT; OPTIMISM; SUSCEPTIBILITY; ADHERENCE; SYMPTOMS; BEHAVIOR; ILLNESS AB The purpose of the present study was two-fold: (a) to characterize the psychological status of women with a family history of breast or ovarian cancer who self-refer for genetic counseling and BRCA1 testing; and (b) to identify specific demographic, personality and appraisal factors that contribute to cancer-specific distress and general distress in this group of women. Participants were 256 women ages 18 and older who had at least one first-degree relative (FDR) with breast and/or ovarian cancer: Participants were recruited through breast cancer clinics and obstetrics/gynecology departments at two medical centers by responding to program information described in a brochure. The results revealed moderate distress levels in this population. The results of a hierarchical regression of general distress indicated that women with higher levels of general distress were less likely to be married, less optimistic, and had heightened breast cancer risk perceptions accompanied by feelings of low perceptions of control over the development of breast cancer (R-2 = .44, p = .0001). Women with higher levels of cancer-specific distress tended to be younger and non-White and had low perceptions of control over developing breast cancer (R-2 = .15, p = .0002). These findings suggest that self-referred genetic counseling participants may be psychologically vulnerable and may benefit from interventions designed to decrease distress and the perceived absence of control over developing breast cancer. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NIH, Ctr Human Genome Res, Bethesda, MD USA. RP Audrain, J (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, 2233 Wisconsin Ave NW,Suite 535, Washington, DC 20007 USA. FU NIMH NIH HHS [MH/HG#54435] NR 45 TC 86 Z9 87 U1 0 U2 2 PU SOC BEHAVIORAL MEDICINE PI MIDDLETON PA 7611 ELMWOOD AVE, STE 201, MIDDLETON, WI 53562-3161 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD FAL PY 1997 VL 19 IS 4 BP 370 EP 377 DI 10.1007/BF02895156 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 107PD UT WOS:000075216900009 PM 9706364 ER PT J AU Adami, J Nyren, O Bergstrom, R Ekbom, A McLaughlin, JK Hogman, C Fraumeni, JF Glimelius, B AF Adami, J Nyren, O Bergstrom, R Ekbom, A McLaughlin, JK Hogman, C Fraumeni, JF Glimelius, B TI Blood transfusion and non-Hodgkin lymphoma: Lack of association SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE blood transfusion; lymphoma, non-Hodgkin's; case-control studies; leukemia, lymphocytic, chronic; immunosuppression ID C VIRUS-INFECTION; POSTOPERATIVE INFECTIONS; CANCER RISK; SELECTION; INCREASE; SURGERY; SWEDEN; WOMEN AB Background: Non-Hodgkin lymphoma is the seventh most commonly diagnosed malignant condition worldwide, and its incidence has increased markedly in recent decades. Blood transfusions have been implicated as a possible risk factor for non-Hodgkin lymphoma. Objective: To determine whether blood transfusions are associated with an elevated risk for non-Hodgkin lymphoma. Design: Population-based, nested case-control study. Setting: Nationwide cohort in Sweden. Patients: 361 patients with non-Hodgkin lymphoma and 705 matched controls, nested within a population-based cohort of 96 795 patients at risk for blood transfusion between 1970 and 1983. Prospectively collected information on exposure was retrieved from computerized transfusion registries. Measurements: Odds ratios obtained from conditional logistic regression models were used as measures of relative risks. Results: No association was found between blood transfusions and the risk for non-Hodgkin lymphoma when patients who had received transfusions were compared with patients who had not received transfusions (odds ratio, 0.93 [95% Cf, 0.71 to 1.23]). A reduction in risk was seen among persons who received transfusion of blood without leukocyte depletion (odds ratio, 0.72 [CI, 0.53 to 0.97]). Risk was not related to number of transfusions, and no interaction was seen with latency after transfusion. Conclusion: The findings in this study do not support previous observations of an association between blood transfusions and the risk for non-Hodgkin lymphoma. C1 INT EPIDEMIOL INST LTD,ROCKVILLE,MD 20850. UPPSALA UNIV,UPPSALA,SWEDEN. NCI,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP Adami, J (reprint author), KAROLINSKA INST,DEPT MED EPIDEMIOL,BOX 281,S-17177 STOCKHOLM,SWEDEN. NR 41 TC 30 Z9 31 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1997 VL 127 IS 5 BP 365 EP & PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XU100 UT WOS:A1997XU10000004 PM 9273827 ER PT J AU Advani, S Pai, S Adde, M Vaidya, S Vats, T Naresh, K Kurkure, PA Nair, CN Venzon, D Magrath, I AF Advani, S Pai, S Adde, M Vaidya, S Vats, T Naresh, K Kurkure, PA Nair, CN Venzon, D Magrath, I TI Preliminary report of an intensified, short duration chemotherapy protocol for the treatment of pediatric non-Hodgkin's lymphoma in India SO ANNALS OF ONCOLOGY LA English DT Article DE childhood; India; lymphoblastic; non-Hodgkin's lymphoma; small non-cleaved; treatment ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ONCOLOGY-SOCIETY; RANDOMIZED TRIAL; SURVIVAL RATE; STAGE-III; CHILDREN; CHILDHOOD; REGIMEN; LSA2-L2; THERAPY AB Background: In the past, the results of the treatment of nonHodgkin's lymphomas (NHL) in Indian children have been poor, due to inadequate chemotherapy and poor supportive care. In an attempt to overcome these problems, we conducted a clinical trial in Bombay with a new protocol, MCP842. Patients and methods: Seventy-four previously untreated patients <25 years were entered on study at the Tata Memorial Hospital, Bombay. Patients with lymphoblastic lymphoma (LL) (38) without bone marrow involvement and all patients with small noncleaved cell lymphoma (SNCL) (18) and large cell lymphoma (LCL) (18) were eligible. Treatment consisted of alternating cycles of two regimens, A and B. Patients with SI. Jude stages I and II received six cycles, and those with stages III or IV received eight cycles. A cycles included cyclophosphamide, adriamycin, vincristine and ara-C, and B cycles, etoposide, vincristine, methotrexate, ifosfamide and mesna. Results: Complete response was achieved in 67 (91%) of patients. Event free survival (EFS) for all patients was 58%; 68% for patients with SNCL and LCL combined, and 48% for patients with LL. There was no significant difference in EFS by histology (LL ver sus non-LL), or stage. There were nine (12%) toxic deaths, two during induction and seven in patients in remission; six occurred in patients with LL. Conclusions. These results are better than past results in Bombay. Unlike earlier CCG protocols, in which the outcome between patients with LL and non-LL differed, this was not so in MCP842. Even patients with extensive LL without bone marrow disease received only eight cycles of therapy, suggesting that short duration therapy is curative in as many as half of such patients - an important observation in a country with limited resources. C1 NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. TATA MEM HOSP,BOMBAY 400012,MAHARASHTRA,INDIA. TEXAS TECH UNIV,AMARILLO,TX. RI Venzon, David/B-3078-2008 NR 20 TC 9 Z9 9 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1997 VL 8 IS 9 BP 893 EP 897 DI 10.1023/A:1008228529397 PG 5 WC Oncology SC Oncology GA YD478 UT WOS:A1997YD47800014 PM 9358941 ER PT J AU Bolling, SF Tramontini, NL Kilgore, KS Su, TP Oeltgen, PR Harlow, HH AF Bolling, SF Tramontini, NL Kilgore, KS Su, TP Oeltgen, PR Harlow, HH TI Use of ''natural'' hibernation induction triggers for myocardial protection SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Thoracic-Surgeons CY FEB 03-05, 1997 CL SAN DIEGO, CA SP Soc Thorac Surgeons ID OPIOID RECEPTORS; PRESERVATION; METABOLISM; NALOXONE; MYOCYTES; CA2+ AB Background. Hypothermic cardioplegia provides adequate myocellular protection, yet stunning and dysfunction remain significant problems. Interestingly, the subcellular changes of hibernation parallel the altered biology of induced cardiac ischemia, but are well tolerated by hibernating mammalian myocardium. Hibernation induction trigger (HIT) from winter-hibernating animal serum induces hibernation in active animals. Hibernation induction trigger is opiate in nature and is similar to the delta 2 opioids. Methods. To determine whether HIT could improve myocardial recovery following global ischemia, we gave 37 isolated rabbit hearts either standard cardioplegia or cardioplegia containing summer-active woodchuck, hibernating woodchuck, or black bear HIT serum or a delta 2 opioid, D-Ala2-Leu5-enkephalin, before 2 hours of global ischemia. Results. Hibernation induction trigger appeared not to have an active mechanism during ischemia, as all hearts had equal recovery. In contrast, when examining for a preischemia mechanism, 23 additional rabbits received 3 days pretreatment with summer-active woodchuck or HIT hibernating woodchuck or black bear serum, or were preperfused with D-Ala2-Leu5-enkephalin or D-pen2,5-enkephalin, a delta 1 opioid, again before 2 hours of global ischemia. Postischemic ventricular function, coronary flows, myocardial oxygen consumption, and ultrastructural preservation were all significantly improved with HIT and D-Ala2-Leu5-enkephalin pretreatment. Conclusion. ''Natural'' HIT protection is superior to standard cardioplegia alone and may have clinical application. (C) 1997 by The Society of Thoracic Surgeons. C1 UNIV MICHIGAN,MED CTR,THORAC SURG SECT,ANN ARBOR,MI. NIDA,BALTIMORE,MD. UNIV KENTUCKY,DEPT PATHOL,LEXINGTON,KY. RI Jansen, Heiko/A-5770-2008 NR 30 TC 63 Z9 63 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 1997 VL 64 IS 3 BP 623 EP 627 DI 10.1016/S0003-4975(97)00631-0 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA XX184 UT WOS:A1997XX18400008 PM 9307448 ER PT J AU Walsh, TJ Whitcomb, P Piscitelli, S Figg, WD Hill, S Chanock, SJ Jarosinski, P Gupta, R Pizzo, PA AF Walsh, TJ Whitcomb, P Piscitelli, S Figg, WD Hill, S Chanock, SJ Jarosinski, P Gupta, R Pizzo, PA TI Safety, tolerance, and pharmacokinetics of amphotericin B lipid complex in children with hepatosplenic candidiasis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HEPATIC CANDIDIASIS; FLUCONAZOLE; LEUKEMIA; TOXICITY; CHEMOTHERAPY; NEUTROPENIA; INFECTIONS; THERAPY; INFANTS AB The safety, tolerance, and pharmacokinetics of amphotericin B lipid complex (ABLC) were studied in a cohort of pediatric cancer patients. Six children with hepatosplenic candidiasis (HSC) received 2.5 mg of ABLC/kg of body weight/day for 6 weeks for a total dosage of 105 mg/kg. Mean serum creatinine (0.85 +/- 0.12 mg/dl at baseline) was stable at the end of therapy at 0.85 +/- 0.18 mg/dl and at 1-month follow-up at 0.72 +/- 0.12 mg/dl. There was no increase in hepatic transaminases. Mean plasma concentrations over the dosing interval (C-ave) and area under the curve from 0 to 24 h (AUC(0-24h)) increased between the first and seventh doses but were similar between doses 7 and 42, suggesting that steady state was achieved by day 7 of therapy. Following the final (42nd) dose of ABLC, mean AUC(0-24h) was 11.9 +/- 2.6 mu g.h/ml, C-nve was 0.50 +/- 0.11 mu g/ml, maximum concentration of the drug in whole blood was 1.69 +/- 0.75 mu g/ml, and clearance was 3.64 +/- 0.78 ml/min/kg. Response of hepatic and splenic lesions was monitored by serial computerized tomographic and magnetic resonance imaging scans. The five evaluable patients responded to ABLC,vith complete or partial resolution of physical findings and of lesions of HSC. During the course of ABLC infusions and follow-up, there was no progression of HSC, breakthrough fungemia, or posttherapy recurrence. Hepatic lesions continued to resolve after the completion of administration of ABLC. Thus, ABLC administered in multiple doses to children was safe, was characterized by a steady state attainable within 1 week of therapy, and was effective in treatment of HSC. C1 NCI,MED BRANCH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT NURSING,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB,PRINCETON,NJ. RP Walsh, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 28 TC 79 Z9 83 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1997 VL 41 IS 9 BP 1944 EP 1948 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XV701 UT WOS:A1997XV70100019 PM 9303390 ER PT J AU Hu, X Ji, XH Srivastava, SK Xia, H Awasthi, S Nanduri, B Awasthi, YC Zimniak, P Singh, SV AF Hu, X Ji, XH Srivastava, SK Xia, H Awasthi, S Nanduri, B Awasthi, YC Zimniak, P Singh, SV TI Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE chrysene; carcinogenesis; glutathione S-transferase P1-1; polymorphism; detoxification ID RAT-LIVER ENZYMES; ENZYMATIC-PROPERTIES; OPTICAL ENANTIOMERS; NEWBORN MICE; BAY; 7,8-DIOL-9,10-EPOXIDES; BENZOPYRENE; TUMORIGENICITY; DIASTEREOMERS; PURIFICATION AB The kinetics of the conjugation of glutathione (GSH) with anti-1,2-dihydroxy-3,4-oxy-1,2,3,4-tetrahydrochrysene (anti-CDE), the activated form of the widespread environmental pollutant chrysene, catalyzed by two naturally occurring polymorphic forms of the pi class human GSH S-transferase (hGSTP1-1), has been investigated, The polymorphic forms of hGSTP1-1, which differ in their primary structure by a single amino acid in position 104, exhibited preference for the GSH conjugation of (+)-anti-CDE, which is a far more potent carcinogen than (-)-anti-CDE. When concentration of anti-CDE was varied (5-200 mu M) and the GSH concentration was kept constant at 2 mM, both hGSTP1-1(I104) and hGSTP1-1(V104) obeyed Michaelis-Menten kinetics, However, the V-max of GSH conjugation of anti-CDE was approximately 5.3-fold higher for the V104 variant than for the I104 form, Calculation of catalytic efficiency (k(cat)/K-m) thus resulted in a value for hGSTP1-1(V1O4), 28 nm(-1) s(-1), that was 7.0-fold higher than that for hGSTP1-1(I104), 4 mM(-1) s(-1). The mechanism of the differences in the kinetic properties of hGSTP1-1 isoforms toward anti-CDE was investigated by molecular modeling of the two proteins with GSH conjugation products in their active sites, These studies revealed that the enantioselectivity of hGSTP1-1 for (+)-anti-CDE and the differential catalytic efficiencies of the V104 and I104 forms of hGSTP1-1 in the GSH conjugation of (+)-anti-CDE were due to the differences in the active-site architecture of the two proteins, The results of the present study, for the first time, provide evidence for the toxicological relevance of GSTP1-1 polymorphism in humans and suggest that the population polymorphism of hGSTP1-1 variants with disparate enzyme activities may, at least in part, account for the differential susceptibility of individuals to environmental carcinogens such as anti-CDE and possibly other similar carcinogens. (C) 1997 Academic Press. C1 NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. MERCY HOSP,CANC RES LAB,PITTSBURGH,PA 15219. UNIV TEXAS,MED BRANCH,DEPT INTERNAL MED,GALVESTON,TX 77555. UNIV ARKANSAS MED SCI,DEPT MED,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. MCCLELLAN VET ADM HOSP MED RES,LITTLE ROCK,AR 72205. UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77555. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [CA 55589, CA 63660]; NIEHS NIH HHS [ES 07804] NR 32 TC 65 Z9 66 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1997 VL 345 IS 1 BP 32 EP 38 DI 10.1006/abbi.1997.0269 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XV706 UT WOS:A1997XV70600004 PM 9281308 ER PT J AU Tabacova, S Balabaeva, L Little, RE AF Tabacova, S Balabaeva, L Little, RE TI Maternal exposure to exogenous nitrogen compounds and complications of pregnancy SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID LIPID PEROXIDES; HUMAN PLACENTA; PREECLAMPSIA; THROMBOXANE AB Increased lipid peroxidation and reduced antioxidant activity have been reported with pregnancy complications. Given that exogenous oxidants stimulate formation of lipid peroxides, the authors investigated the relationship between exposure to nitrogen-oxidizing species and pregnancy complications and took into account markers of antioxidant and oxidant status. The study sample included pregnant women who were from an area polluted by oxidized nitrogen compounds. Methemoglobin, a biomarker of individual; exposure, was determined, as were measures of oxidant/antioxidant status, including glutathione balance and lipid peroxide levels. Only 10 women experienced normal pregnancies. The most common complications were anemia (67%), threatened abortion/premature labor (33%), and signs of preeclampsia (23%). Methemoglobin was elevated significantly in all three conditions, compared with normal pregnancies. Reduced:total glutathione decreased, whereas lipid peroxide levels increased. These results suggest that maternal exposure to environmental oxidants can increase the risk of pregnancy complications through stimulation of the formation of cell-damaging lipid peroxides and from a decrease in maternal antioxidant reserves. C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. Natl Ctr Hyg Ecol & Nutr, Sofia, Bulgaria. RP Little, RE (reprint author), NIEHS, Epidemiol Branch, NIH, A3-05, Res Triangle Pk, NC 27709 USA. NR 23 TC 32 Z9 33 U1 0 U2 4 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD SEP-OCT PY 1997 VL 52 IS 5 BP 341 EP 347 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA YN285 UT WOS:000071151600003 PM 9546756 ER PT J AU Vitiello, B Jensen, PS AF Vitiello, B Jensen, PS TI Medication development and testing in children and adolescents - Current problems, future directions SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID PEDIATRIC PSYCHOPHARMACOLOGY; ETHICAL ISSUES; CHILDHOOD; PERSPECTIVES; DEPRESSION; BLOOD AB Progress in pediatric psychopharmacological research has suffered notable delay, especially compared with the achievements in adult psychopharmacology Although safety and efficacy of the use of many psychotropic agents in children remain largely unproved, their pediatric use has been increasing and their widespread off-label prescribing by practitioners has raised some important concerns. The National Institute of Mental Health, in cooperation with the Food and Drug Administration and leading researchers, has coordinated systematic efforts to identify the major obstacles to research in pediatric psychopharmacology and to propose feasible solutions. In 1995, a conference cosponsored by the National Institute of Mental Health and the Food and Drug Administration gathered more than 100 research experts, family and patient advocates, and representatives of mental health professional associations. Participants met in working groups focused on specific aspects of child research and reached consensus on various recommendations. Each of the various aspects relevant to conducting research in this area (methodological, ethical, legal, regulatory, financial, and family or community context) presents specific challenges, which are herein outlined. Recommendations for possible solutions are presented, some of which are being implemented. Because data about drug safety and efficacy in adults can rarely be extrapolated to children, there is no substitute for pediatric psychopharmacological research. Successful strategies for overcoming the many obstacles with which this research has to contend must enlist the concerted efforts of all the relevant parties (investigators, clinicians, industry, federal agencies, ethicists, families, and community representatives). C1 NIMH, CHILD & ADOLESCENT DISORDERS RES BRANCH, ROCKVILLE, MD 20857 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 44 TC 65 Z9 66 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1997 VL 54 IS 9 BP 871 EP 876 PG 6 WC Psychiatry SC Psychiatry GA XU909 UT WOS:A1997XU90900013 PM 9294379 ER PT J AU Chase, TN AF Chase, TN TI A gene for Parkinson disease SO ARCHIVES OF NEUROLOGY LA English DT Review ID A-BETA COMPONENT; CENTRAL-NERVOUS-SYSTEM; PRECURSOR PROTEIN; SYNUCLEINS; BRAIN RP Chase, TN (reprint author), NINCDS,EXPT THERAPEUT BRANCH,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 15 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 1997 VL 54 IS 9 BP 1156 EP 1157 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA XV731 UT WOS:A1997XV73100014 PM 9311360 ER PT J AU Hiller, R Sperduto, RD Podgor, MJ Wilson, PWF Ferris, FL Colton, T DAgostino, RB Roseman, MJ Stockman, ME Milton, RC AF Hiller, R Sperduto, RD Podgor, MJ Wilson, PWF Ferris, FL Colton, T DAgostino, RB Roseman, MJ Stockman, ME Milton, RC TI Cigarette smoking and the risk of development of lens opacities - The Framingham studies SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; EPIDEMIOLOGIC ASSOCIATIONS; VITAMIN-C; CATARACT; NUCLEAR; CADMIUM AB Objective: To examine the association between cigarette smoking and the incidence of nuclear and nonnuclear lens opacities in members of the Framingham Eye Study Cohort. Participants and Methods: Eye examinations were conducted on surviving members of the Framingham Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986 to 1989 (Framingham Eye Study II). Smoking data, collected biennially since 1948 in the Heart Study, were used to examine the relationship between cigarette smoking and the incidence of lens opacities. Two thousand six hundred seventy-five persons were examined in the Framingham Eye Study I. Our analysis included 660 persons, aged 52 to 80 years, who were free of lens opacities at the first eye examination. Results: During the approximately 12.5 years between eye examinations, lens opacities developed in a total of 381 persons, with nuclear opacities constituting the most frequent type. In logistic regression analyses that controlled for age, sex, education, and diabetes, a significant positive association with increasing duration of smoking and number of cigarettes smoked daily was found for nuclear lens opacities, alone or in combination (test for trend, P less than or equal to.002), but not for nonnuclear opacities (test for trend, P=.62). Among the heavier smokers (persons who smoked greater than or equal to 20 cigarettes per day according to 6 or more biennial Framingham Heart Study examinations), 77% were still smoking at the time of the first eye examination. Persons who smoked 20 or more cigarettes per day at the time of the first eye examination were at substantially increased risk for the development of nuclear opacities than nonsmokers (odds ratio, 2.84; 95% confidence interval, 1.46-5.51). There was no apparent excess risk for persons with nonnuclear lens opacities (odds ratio, 1.42; 95% confidence interval, 0.65-3.07). Conclusion: This study provides further evidence that cigarette smokers have an increased risk of developing nuclear lens opacities. The risk was greatest for heavier smokers, who tended to be current smokers and who smoked more cigarettes and for a longer duration. C1 NHLBI,FRAMINGHAM,MA. BOSTON UNIV,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA 02215. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. EMMES CORP,POTOMAC,MD. RP Hiller, R (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,BLDG 31,ROOM 6A52,31 CTR DR,MSC 2510,BETHESDA,MD 20892, USA. FU NEI NIH HHS [N01-EY-2-2112, N01-EY-6-2105] NR 24 TC 62 Z9 65 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1997 VL 115 IS 9 BP 1113 EP 1118 PG 6 WC Ophthalmology SC Ophthalmology GA XV759 UT WOS:A1997XV75900003 PM 9298050 ER PT J AU Whitcup, SM StarkVancs, V Wittes, RE Solomon, D Podgor, MJ Nussenblatt, RB Chan, CC AF Whitcup, SM StarkVancs, V Wittes, RE Solomon, D Podgor, MJ Nussenblatt, RB Chan, CC TI Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RETICULUM-CELL SARCOMA; INTRAOCULAR LYMPHOMA; UVEITIS; EXPRESSION; LINES; IL-10 AB Background: Diagnosis of primary central nervous system lymphoma (PCNSL) is usually made by identifying malignant lymphocytes in the brain, cerebrospinal fluid (CSF), or vitreous. However, these cells are few and friable, and misdiagnosis can occur, even in properly prepared specimens. Recent data Suggest that levels of interleukin 10 (IL-10) are elevated in the serum and vitreous of patients with non-Hodgkin lymphoma; levels of interleukin 6 (IL-6) are elevated in the vitreous of patients with intraocular inflammation unrelated to a malignant neoplasm. We investigated whether PCNSL involving the vitreous or CSF is associated with elevated ratios of IL-10 to IL-6. Patients: Vitreous specimens were obtained from 5 patients with PCNSL involving the eye and from 13 control patients with intraocular inflammation not related to a malignant neoplasm; CSF specimens were obtained from 11 patients with PCNSL. Results: Levels of IL-10 exceeded those of IL-6 in all 5 patients with intraocular lymphoma but in none of the 13 patients with uveitis (P<.001). In patients with PCNSL, levels of IL-10 exceeded those of IL-6 in 6 of 11 CSF samples with malignant cells compared with 7 of 53 samples without malignant cells (P=.01). The calculated odds ratio (OR) suggests that the risk for malignant involvement of the CSF is about 8 times higher when IL-10 levels exceed IL-6 levels. Methods: Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay in both vitreous and CSF specimens. Conclusions: The occurrence of PCNSL in the eye was strongly associated with elevated vitreous levels of IL-10 relative to levels of IL-6. Moreover, among patients with diagnosed PCNSL, malignant cells were significantly more likely to be present in CSF when levels of IL-10 exceeded those of IL-6. C1 NCI,NIH,BETHESDA,MD 20892. RP Whitcup, SM (reprint author), NEI,NIH,10 CTR DR,BLDG 10,ROOM 10N 202,BETHESDA,MD 20892, USA. NR 24 TC 89 Z9 97 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1997 VL 115 IS 9 BP 1157 EP 1160 PG 4 WC Ophthalmology SC Ophthalmology GA XV759 UT WOS:A1997XV75900010 PM 9298057 ER PT J AU Hayashi, T Rush, WL Travis, WD Liotta, LA StetlerStevenson, WG Ferrans, VJ AF Hayashi, T Rush, WL Travis, WD Liotta, LA StetlerStevenson, WG Ferrans, VJ TI Immunohistochemical study of matrix metalloproteinases and their tissue inhibitors in pulmonary Langerhans' cell granulomatosis SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID HISTIOCYTOSIS-X; IV COLLAGENASE; INTERSTITIAL COLLAGENASE; INTRALUMINAL FIBROSIS; EXTRACELLULAR-MATRIX; MESSENGER-RNA; EXPRESSION; GELATINASE; DIAGNOSIS; EOSINOPHILS AB Objective.-To evaluate the role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis of the lesions of pulmonary Langerhans' cell granulomatosis. Design.-Immunohistochemical and confocal microscopic studies were made of lung biopsy specimens from five patients with pulmonary Langerhans' cell granulomatosis. Results.-The reactivity of Langerhans' cells was moderate to intense for MMP-2, weaker for MMP-9, and faint for TIMP-1 and TIMP-2. Type IV collagen colocalized with MMP-2 in areas of damage to epithelial basement membranes, a finding that emphasizes the potential importance of this enzyme in the pathogenesis of the destructive lesions of pulmonary Langerhans' cell granulomatosis. In the more advanced fibrotic lesions, TIMP-2 colocalized with basement membranes and with fibrillar collagen, suggesting that it contributes to the permanence of the fibrosis. Conclusion.-These results indicate an important role for MMPs and TIMPs in pulmonary Langerhans' cell granulomatosis. C1 NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC 20306. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 28 TC 34 Z9 34 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1997 VL 121 IS 9 BP 930 EP 937 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA XW175 UT WOS:A1997XW17500005 PM 9302924 ER PT J AU Zweig, MH Kroll, MH AF Zweig, MH Kroll, MH TI Linear regression estimation of minimal detectable concentration - Thyrotropin as an example SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PERFORMANCE CRITERIA; IMMUNOMETRIC ASSAYS; TSH; SENSITIVITY AB Background.-Minimal detectable concentration is an important analytic feature of certain clinical immunoassays. We believe that accuracy is an important component of the minimal detectable concentration; for a given observed concentration to be meaningful, it should reflect a consistent linear relationship with the amount of analyte actually present. Methods.-To evaluate the minimal detectable concentration, we developed a linearity regression protocol based on accuracy and also accounting for between-run variability. Using serial twofold dilutions of serum samples, we regressed the log of concentration (x) and of dilution (y) with linear, second-, and third-order polynomials. Initially, we evaluated two elements to find the linear region of the dataset, establishing the statistical significance of the beta coefficients with a t test and the reduction of the sum of square of the residuals between the linear regression and the higher-order regressions by means of an F test. As needed, we successively eliminated the lowest point until the linear regression was the best fit. Once we found the best fit, we added the most recently removed point back and calculated the difference between the value predicted by the first-order regression and the observed value. If the difference was not analytically significant, then we considered the point to be part of the linear set; otherwise, it was not included. In either case, the lowest included point was considered to be the minimal detectable concentration. Results.-We applied the technique in evaluating two automated systems for serum thyrotropin. One system appeared linear and accurate down to 0.02 mU/L, or better, approximately 77% of the time, and to 0.01 mU/L 68% of the time. The second system was linear infrequently and appeared to be useful down to 0.02 mU/L, or better, only about 20% of the time. Conclusions.-This accuracy-based approach to determining the minimal detectable concentration is an attractive alternative to current empiric approaches, which are based only on interassay variability. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21287. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 13 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1997 VL 121 IS 9 BP 948 EP 955 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA XW175 UT WOS:A1997XW17500007 PM 9302926 ER PT J AU Nieto, FJ Sorlie, P Comstock, GW Wu, K Adam, E Melnick, JL Szklo, M AF Nieto, FJ Sorlie, P Comstock, GW Wu, K Adam, E Melnick, JL Szklo, M TI Cytomegalovirus infection, lipoprotein(a), and hypercoagulability: An atherogenic link? SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; cytomegalovirus; fibrinogen; hemostasis; lipoprotein(a) ID CORONARY-ARTERY DISEASE; SOLID-PHASE RADIOIMMUNOASSAY; SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; MYOCARDIAL-INFARCTION; RISK FACTOR; ATHEROSCLEROSIS RISK; VONWILLEBRAND-FACTOR; HEMOSTATIC FUNCTION; VIRUS AB A link between cytomegalovirus (CMV) infection and atherosclerosis has been suggested by experimental, clinical, and epidemiologic studies. We investigated the association between CMV antibody titers in serum collected in 1974 in 300 adult residents in Washington County, Md, and hemostatic parameters in plasma collected in 1987 through 1989, when these individuals participated in the baseline examination of the Atherosclerosis Risk in Communities Study. The cross-sectional association of CMV serum antibodies and hemostatic parameters was also explored in another set of Atherosclerosis Risk in Communities cases and controls. In the longitudinal analyses, CMV titers in 1974 were directly associated with 1987 through 1989 plasma levels of von Willebrand factor, factor VIII, and protein C and negatively associated with activated partial thromboplastin time. In the cross-sectional analyses, CMV titers were directly related to antithrombin III and fibrinogen levels. When the association between CMV antibodies and atherosclerosis was examined in stratified analyses, a significant association was restricted to individuals with high levels of lipoprotein(a) and fibrinogen. These results are compatible with previous evidence suggesting that CMV virus might have procoagulant properties. The possible synergism of CMV infection and resulting hypercoagulability with reduced fibrinolysis due to increased lipoprotein(a) levels deserves further investigation. C1 NHLBI,NIH,BETHESDA,MD 20892. UNIV TEXAS,SCH MED,DIV HEMATOL,HOUSTON,TX. BAYLOR COLL MED,DIV MOL VIROL,HOUSTON,TX 77030. RP Nieto, FJ (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55018, N01-HC-55016] NR 54 TC 35 Z9 36 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 1997 VL 17 IS 9 BP 1780 EP 1785 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YA612 UT WOS:A1997YA61200024 PM 9327777 ER PT J AU Remaley, AT Schumacher, UK Stonik, JA Farsi, BD Nazih, H Brewer, HB AF Remaley, AT Schumacher, UK Stonik, JA Farsi, BD Nazih, H Brewer, HB TI Decreased reverse cholesterol transport from Tangier disease fibroblasts - Acceptor specificity and effect of brefeldin on lipid efflux SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE Tangier disease; high-density lipoprotein; cholesterol; atherosclerosis; brefeldin ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; CELLULAR CHOLESTEROL; INTRACELLULAR CHOLESTEROL; HDL; CELLS; MEMBRANE; MACROPHAGES; REMOVAL; PHOSPHOLIPIDS AB Tangier disease is characterized by HDL hypercatabolism and increased deposition of cholesterol in tissues. Tangier disease skin fibroblasts have decreased apoA-I-meidated cholesterol and phospholipid efflux, which may lead to the excess accumulation of cellular cholesterol. The mechanism of apolipoprotein-mediated cholesterol efflux and the apolipoprotein acceptor specificity for cholesterol efflux from normal and Tangier disease fibroblasts was investigated. Normal cells readily effluxed cholesterol and phospholipid to apoA-I and to all of the other apolipoproteins tested (apoA-II, AIV, C-I, C-II, C-III). In contrast, Tangier cells were almost completely defective in cholesterol efflux to apoA-I and to all of the other apolipoproteins tested. HDL was also less effective, by approximately 50%, in stimulating cholesterol efflux from Tangier cells compared with normal cells. In addition, Tangier cells also showed significantly reduced phospholipid efflux to both apolipoproteins and HDL. A similar rate of cholesterol efflux, however, was observed from normal and Tangier cells when phospholipid vesicles or cyclodextrin were used as accepters. In contrast to normal cells, only phospholipid vesicles and cyclodextrin and not apoA-I or HDL depleted intracellular cholesteryl esters from Tangier cells. Brefeldin, an inhibitor of intracellular vesicular trafficking, decreased HDL-mediated cholesterol efflux by approximately 40% but almost completely blocked both cholesterol and phospholipid efflux to apoA-I from normal cells. Brefeldin also inhibited cholesteryl ester depletion by apoA-I and HDL from normal cells. Brefeldin, however, had no significant effect on cholesterol efflux from Tangier cells to HDL. In summary, Tangier cells were found to be defective in both cholesterol and phospholipid efflux to HDL and apoA-I. The defect in apolipoprotein-mediated lipid efflux was not specific for apoA-I but also occurred for other apolipoproteins, and brefeldin blocked HDL-mediated lipid efflux from normal but not Tangier disease cells. On the basis of these results, a model is proposed whereby decreased cholesterol efflux by apolipoproteins in Tangier cells is the result of a defect in a brefeldin-sensitive pathway of lipid efflux. C1 NHLBI,NIH,BETHESDA,MD 20892. RP Remaley, AT (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,BLDG 10-2C-431,BETHESDA,MD 20892, USA. NR 50 TC 170 Z9 170 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 1997 VL 17 IS 9 BP 1813 EP 1821 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YA612 UT WOS:A1997YA61200029 PM 9327782 ER PT J AU Chu, CC Paul, WE AF Chu, CC Paul, WE TI E4BP4, a transcription factor induced by IL-4 in mouse B cells. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 N SHORE UNIV HOSP,MANHASSET,NY 11030. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 47 EP 47 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400047 ER PT J AU Pillemer, SR Torpy, DJ Papanicolaou, DA Wilder, RL Chrousos, GP AF Pillemer, SR Torpy, DJ Papanicolaou, DA Wilder, RL Chrousos, GP TI Interleukin-6 evokes a hypersecretory adrenocorticotropin (ACTH) response in fibromyalgia patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 92 EP 92 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400092 ER PT J AU Chen, WJ Jin, WW Song, XY Wahl, SM AF Chen, WJ Jin, WW Song, XY Wahl, SM TI Oral administration of streptococcal cell walls (SCW) induces mucosal cytokines and suppresses SCW arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIDR,OIIB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 150 EP 150 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400150 ER PT J AU Davis, JC Manzi, S Yarboro, C Rairie, J Sinicropi, D Hale, VG Boumpas, DT Klippel, JH AF Davis, JC Manzi, S Yarboro, C Rairie, J Sinicropi, D Hale, VG Boumpas, DT Klippel, JH TI Phase Ib study of recombinant human DNase I (rhDNase) in lupus nephritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. GENENTECH INC,S SAN FRANCISCO,CA 94080. UNIV PITTSBURGH,PITTSBURGH,PA 15213. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 172 EP 172 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400171 ER PT J AU Tassiulas, IO Aksentijevich, I Salmon, JE Gourley, MF Boumpas, DT AF Tassiulas, IO Aksentijevich, I Salmon, JE Gourley, MF Boumpas, DT TI Decreased prevalence of DD genotype of the angiotensin I converting enzyme gene in African American patients with systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HOSP SPECIAL SURG,NEW YORK,NY 10021. NIAMS,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 182 EP 182 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400181 ER PT J AU Davis, JC Fessler, BJ Tassiulas, I Yarboro, CH McInnes, I Lee, J Pillemer, S Klippel, JH Boumpas, DT AF Davis, JC Fessler, BJ Tassiulas, I Yarboro, CH McInnes, I Lee, J Pillemer, S Klippel, JH Boumpas, DT TI High dose versus low dose fludarabine in the treatment of patients with refractory rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 381 EP 381 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400380 ER PT J AU Illei, G Aravssi, T Yarboro, C Davis, J Gulko, P Klippel, J Schumacher, HR AF Illei, G Aravssi, T Yarboro, C Davis, J Gulko, P Klippel, J Schumacher, HR TI Treatment patterns of early rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 395 EP 395 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400394 ER PT J AU Ling, SM Morris, C Fried, L Hirsch, R Hochberg, M AF Ling, SM Morris, C Fried, L Hirsch, R Hochberg, M TI Accuracy of self-reported physician diagnosis of rheumatoid arthritis in a cohort of disabled elderly women. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD 21224. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 495 EP 495 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400494 ER PT J AU Alarcon, GS Tilley, B Li, SH Pillemer, S Mikhail, IS AF Alarcon, GS Tilley, B Li, SH Pillemer, S Mikhail, IS TI Self-administered (SA) joint counts (SA-JCs) correlate with standard JCs in RA. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL 35294. HENRY FORD SYST HLTH SCI,DETROIT,MI 48202. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 498 EP 498 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400497 ER PT J AU Hicks, J Drinkard, B Jain, M Danoff, J Gerber, L Rider, L AF Hicks, J Drinkard, B Jain, M Danoff, J Gerber, L Rider, L TI Aerobic capacity in juvenile dermatomyositis (JDM) and normal juvenile subjects. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 657 EP 657 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400655 ER PT J AU Powell, MJ Steere, AC Dorward, D Anderson, PH vanVollenhoven, RF AF Powell, MJ Steere, AC Dorward, D Anderson, PH vanVollenhoven, RF TI Prevalence of Borrelia burgdorferi specific antibodies in the Pacific Northwest: Immune complex western blot reveals unexpected OspA reactivity in patients from a nonendemic region. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 PROVIDENCE ST VINCENT MED CTR,DEPT INTERNAL MED,PORTLAND,OR 97225. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. NIH,ROCKY MT LAB,HAMILTON,MT 59340. STANFORD DIV RHEUMATOL,PALO ALTO,CA 94305. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 668 EP 668 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400666 ER PT J AU Kotake, S Schumacher, HR Arayssi, TK Gerard, HC Branigan, PJ Hudson, AP Yarboro, CH Klippel, JH Wilder, RL AF Kotake, S Schumacher, HR Arayssi, TK Gerard, HC Branigan, PJ Hudson, AP Yarboro, CH Klippel, JH Wilder, RL TI IFN-gamma, IL-10 and IL-12p40 gene expression in synovial tissues from patients with recent-onset chlamydia-associated arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 673 EP 673 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400671 ER PT J AU McCartneyFrancis, NL Song, XY Mizel, DE Wahl, SM AF McCartneyFrancis, NL Song, XY Mizel, DE Wahl, SM TI Modulation of bacterial cell wall-induced arthritis by hemoglobin. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 692 EP 692 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400690 ER PT J AU Gulko, PS Griffiths, MM Kawahito, Y McCall, S Cannon, GW Reese, VR Remmers, EF Wilder, RL AF Gulko, PS Griffiths, MM Kawahito, Y McCall, S Cannon, GW Reese, VR Remmers, EF Wilder, RL TI Genome-wide scan identifies a non-MHC rat chromosome 2 locus controlling collagen-induced arthritis (CIA) severity. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. UNIV UTAH,VAMC,SALT LAKE CITY,UT 84132. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 768 EP 768 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400766 ER PT J AU Kawahito, Y Cannon, GW Gulko, PS Remmers, EF Longman, RE Griffiths, MM Wilder, RL AF Kawahito, Y Cannon, GW Gulko, PS Remmers, EF Longman, RE Griffiths, MM Wilder, RL TI MHC and non-MHC genetic loci regulating adjuvant induced arthritis in rats: A comparative study with collagen induced arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. VET ADM MED CTR,SALT LAKE CITY,UT 84148. UNIV UTAH,SALT LAKE CITY,UT 84148. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 770 EP 770 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400768 ER PT J AU Griffiths, MM Cannon, GW Remmers, EF Wilder, RL Carter, R McOmber, L Elliot, C AF Griffiths, MM Cannon, GW Remmers, EF Wilder, RL Carter, R McOmber, L Elliot, C TI Multiple gene control of collagen induced arthritis (CIA) analyzed in DA, BB and BN rats. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV UTAH,VAMC,SALT LAKE CITY,UT 84132. NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 773 EP 773 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400771 ER PT J AU Cooper, GS Karlson, EW Willett, WC Speizer, FE AF Cooper, GS Karlson, EW Willett, WC Speizer, FE TI Dietary risk factors for systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 789 EP 789 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400787 ER PT J AU Erlacher, L Ng, CK tenDijke, P Luyten, FP AF Erlacher, L Ng, CK tenDijke, P Luyten, FP TI Cartilage-derived morphogenetic proteins: Activities in vivo and in vitro and receptor binding studies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. LUDWIG INST CANC RES,S-75124 UPPSALA,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 912 EP 912 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63400910 ER PT J AU Pillemer, SR Pando, J Magno, B Kurrasch, R Atkinson, J Macynski, A Fox, P AF Pillemer, SR Pando, J Magno, B Kurrasch, R Atkinson, J Macynski, A Fox, P TI Hydroxychloroquine for Sjogren's syndrome: A double-blind placebo controlled pilot trial SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1035 EP 1035 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401033 ER PT J AU Martens, PB Pillemer, SR Jacobsson, LTH Fox, PC OFallon, WM Matteson, EL AF Martens, PB Pillemer, SR Jacobsson, LTH Fox, PC OFallon, WM Matteson, EL TI Survivorship in a population based cohort of patients with Sjogren's syndrome, 1976-1992. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MAYO CLIN,ROCHESTER,MN. NIAMS,NIH,BETHESDA,MD. LUND UNIV,MALMO,SWEDEN. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1101 EP 1101 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401099 ER PT J AU Sakata, KM Nakabayashi, T Sakata, A Kong, LP Letterio, JJ Talal, N Dang, H AF Sakata, KM Nakabayashi, T Sakata, A Kong, LP Letterio, JJ Talal, N Dang, H TI TGF-beta 1 knockout mice spontaneously overexpress CD40L mRNA in salivary gland and other tissues. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NCI,NIH,BETHESDA,MD 20892. COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY 10019. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1151 EP 1151 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401149 ER PT J AU Gerard, H Hudson, A Williams, W Yarboro, C Klippel, J Branigan, P Sieck, M Clayburne, G Arayssi, T Schumacher, HR AF Gerard, H Hudson, A Williams, W Yarboro, C Klippel, J Branigan, P Sieck, M Clayburne, G Arayssi, T Schumacher, HR TI Screening synovial fluid (SF) and tissue using PCR for pan bacterial 16S rRNA. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. ALLEGHENY UNIV HLTH SCI,PHILADELPHIA,PA 19104. VET ADM MED CTR,PHILADELPHIA,PA 19104. NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1176 EP 1176 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401174 ER PT J AU Thronton, B Hicks, J McGarvey, C Danoff, J Adams, E AF Thronton, B Hicks, J McGarvey, C Danoff, J Adams, E TI Measuring motor and process skills in people with myositis: Performance measures in research drug trials SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1199 EP 1199 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401196 ER PT J AU Hirsch, R Guralnik, JM Leveille, S Simonsick, E Ling, SM BandeenRoche, K Fried, LP Hochberg, MC AF Hirsch, R Guralnik, JM Leveille, S Simonsick, E Ling, SM BandeenRoche, K Fried, LP Hochberg, MC TI Assessing the impact of hand osteoarthritis: New indices to measure severity independent of function. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1230 EP 1230 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401227 ER PT J AU Hirsch, R Guralnik, JM Leveille, S Simonsick, E BandeenRoche, K Rantanen, T Fried, LP Hochberg, MC AF Hirsch, R Guralnik, JM Leveille, S Simonsick, E BandeenRoche, K Rantanen, T Fried, LP Hochberg, MC TI Development of a disease severity index for knee osteoarthritis with validation against physical performance measures. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1231 EP 1231 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401228 ER PT J AU Arayssi, T Duray, P Gulko, P Davis, J Yarboro, C Lee, J Wilder, R Klippel, J Schumacher, HR AF Arayssi, T Duray, P Gulko, P Davis, J Yarboro, C Lee, J Wilder, R Klippel, J Schumacher, HR TI Synovial tissue macrophages do not predict one year clinical outcome of synovitis in patients with early rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1319 EP 1319 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401316 ER PT J AU Aravssi, T Duray, P Crane, M Lee, J Klippel, J Schumacher, HR AF Aravssi, T Duray, P Crane, M Lee, J Klippel, J Schumacher, HR TI The spectrum of normal synovial histology. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20815. UNIV PENN,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1320 EP 1320 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401317 ER PT J AU Tasslulas, IO Duncan, SR Centola, M Theofilopoulos, AN Boumpas, DT AF Tasslulas, IO Duncan, SR Centola, M Theofilopoulos, AN Boumpas, DT TI Concordant T cell receptor V beta expansions in synovial tissue and skin of patents with psoriatic arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS, ARTRIT & RHEUMALISM BRANCH, NIH, BETHESDA, MD USA. SCRIPPS RES INST, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1375 EP 1375 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401372 ER PT J AU Reginato, AJ Eid, H Shanahan, J Kastner, DL Ansentijevich, I Benson, MD Gallo, G AF Reginato, AJ Eid, H Shanahan, J Kastner, DL Ansentijevich, I Benson, MD Gallo, G TI Familial recurrent fever (FRF) and liver amyloidosis in a Puerto Rican (PR) kindred (K). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,COOPER HOSP,RHEUMATOL SECT,CAMDEN,NJ 08103. NIH,WASHINGTON,DC. VAMC,INDIANAPOLIS,IN. NYU,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1409 EP 1409 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401406 ER PT J AU Gentiletti, A PonsEstel, B Miguel, R Battagliotti, C Rosario, SP Ansentijevich, I Kastner, D Reginato, AJ AF Gentiletti, A PonsEstel, B Miguel, R Battagliotti, C Rosario, SP Ansentijevich, I Kastner, D Reginato, AJ TI Familial Mediterranean fever (FMF) in a kindred with uncommon manifestations. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,WASHINGTON,DC. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,CAMDEN,NJ 08103. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1410 EP 1410 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401407 ER PT J AU Schumacher, HR Arayssi, T Branigan, P Crane, M Lee, J Hudson, A Gerard, H Klippel, J AF Schumacher, HR Arayssi, T Branigan, P Crane, M Lee, J Hudson, A Gerard, H Klippel, J TI PCR study for bacterial DNA in normal synovium. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. ALLEGHENY UNIV HLTH SCI,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1431 EP 1431 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401428 ER PT J AU Schumacher, HR Arayssi, T Branigan, P Gerard, H Klippel, J Pando, J Getsy, J Bulbul, R Yarboro, C Rothfuss, S Hudson, A AF Schumacher, HR Arayssi, T Branigan, P Gerard, H Klippel, J Pando, J Getsy, J Bulbul, R Yarboro, C Rothfuss, S Hudson, A TI Surveying for evidence of synovial chlamydia trachomatis by polymerase chain reaction (PCR). A study of 411 synovial biopsies and synovial fluids (SF). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. ALLEGHENY UNIV HLTH SCI,PHILADELPHIA,PA 19104. NIAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1432 EP 1432 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401429 ER PT J AU Branigan, P Rao, J Rao, J Gerard, H Hudson, A Williams, W Arayssi, T Pando, J Bayer, M Rothfuss, S Clayburne, G Sieck, M Schumacher, HR AF Branigan, P Rao, J Rao, J Gerard, H Hudson, A Williams, W Arayssi, T Pando, J Bayer, M Rothfuss, S Clayburne, G Sieck, M Schumacher, HR TI PCR evidence for Borrelia burgdorferi DNA in synovium in absence of positive serology. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. ALLEGHENY UNIV HLTH SCI,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1435 EP 1435 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401432 ER PT J AU Ascherman, DP Migone, TS Friedmann, MC Leonard, WJ AF Ascherman, DP Migone, TS Friedmann, MC Leonard, WJ TI IL-2-mediated IL-2R alpha gene induction. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1454 EP 1454 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401451 ER PT J AU Leung, BP Chaudhuri, K Forsey, RJ Liew, FY McInnes, IB AF Leung, BP Chaudhuri, K Forsey, RJ Liew, FY McInnes, IB TI Interleukin-15 (IL-15) induces cytokine production by rheumatoid arthritis (RA) synovial neutrophils. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV GLASGOW,DEPT IMMUNOL,GLASGOW G12,LANARK,SCOTLAND. UNIV GLASGOW,CTR RHEUMAT DIS,GLASGOW G12,LANARK,SCOTLAND. ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1457 EP 1457 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401454 ER PT J AU LethbridgeCeiku, M Hochberg, MC Roy, TA Plato, CC Tobin, JD AF LethbridgeCeiku, M Hochberg, MC Roy, TA Plato, CC Tobin, JD TI Hand osteoarthritis (OA), but not knee OA, is associated with greater rates of radial bone loss: Data from the Baltimore longitudinal study of aging (BLSA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1481 EP 1481 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401478 ER PT J AU Gerber, L Furst, G Hicks, J Greenberg, J Arayssi, T Yarboro, C Schumacher, R AF Gerber, L Furst, G Hicks, J Greenberg, J Arayssi, T Yarboro, C Schumacher, R TI Signs and symptoms of early synovitis as predictors of physical and functional outcomes at one year. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1491 EP 1491 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401488 ER PT J AU Chen, AL Chen, M Zhou, YJ Candotti, F Notorangelo, LD OShea, JJ AF Chen, AL Chen, M Zhou, YJ Candotti, F Notorangelo, LD OShea, JJ TI JAK3-deficient severe combined immunodeficiency in a patient expressing JAK3: Functional implications of the JH2 pseudokinase domain. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,ARB,NIH,BETHESDA,MD 20892. UNIV BRESCIA,DEPT PEDIAT,BRESCIA,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1513 EP 1513 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401510 ER PT J AU Gulko, PS Aravssi, TK Furst, G Lee, J Yarboro, C Klippel, JH Wilder, RL Schumacher, HR Gerber, L AF Gulko, PS Aravssi, TK Furst, G Lee, J Yarboro, C Klippel, JH Wilder, RL Schumacher, HR Gerber, L TI Can shared epitope (SE) typing predict disease activity and biopsychological (BioP) status changes at one year in patients with recent-onset rheumatoid arthritis (RA)? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. NIH,CC,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1553 EP 1553 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401550 ER PT J AU Csako, G Pucino, F Yarboro, CH Nagy, B Wesley, R Gourley, M Eggerman, TL Hoeg, JM Scott, D Costello, R Balow, JE Klippel, JH AF Csako, G Pucino, F Yarboro, CH Nagy, B Wesley, R Gourley, M Eggerman, TL Hoeg, JM Scott, D Costello, R Balow, JE Klippel, JH TI Apolipoprotein(a) isoforms and anti-cardiolipin antibodies as predictors of premature thromboembolic events in SLE patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Nagy, Balint/F-6943-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1643 EP 1643 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401640 ER PT J AU Wu, J Bansal, V Arnett, F Reveille, J Ginzler, E Gourley, M RamseyGoldman, R Salmon, J Edberg, J Kimberly, R AF Wu, J Bansal, V Arnett, F Reveille, J Ginzler, E Gourley, M RamseyGoldman, R Salmon, J Edberg, J Kimberly, R TI The Fc gamma RIIIA 176F/V polymorphism associates with the SLE phenotype in Caucasians and African Americans (AA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HOUSTON,TX. SUNY DOWNSTATE,BROOKLYN,NY. NIAMS,ARB,NIH,BETHESDA,MD. NORTHWESTERN UNIV,CHICAGO,IL 60611. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. UNIV ALABAMA,BIRMINGHAM,AL 35294. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1709 EP 1709 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401706 ER PT J AU Thornton, B Shrader, J AF Thornton, B Shrader, J TI Evaluation and treatment of the rheumatoid hand and foot: A joint venture. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,DEPT REHABIL MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1997 VL 40 IS 9 SU S BP 1775 EP 1775 PG 1 WC Rheumatology SC Rheumatology GA XY634 UT WOS:A1997XY63401772 ER PT J AU Gallaher, WR Garry, RF Lambert, DM Lewis, DE Maurer, BA Meier, GW AF Gallaher, WR Garry, RF Lambert, DM Lewis, DE Maurer, BA Meier, GW TI Marcel Pons - Deceased member SO ASM NEWS LA English DT Item About an Individual C1 LOUISIANA STATE UNIV,SCH MED,NEW ORLEANS,LA. TULANE MED SCH,NEW ORLEANS,LA. TRIMERIS INC,DURHAM,NC 27707. BAYLOR COLL MED,HOUSTON,TX 77030. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0044-7897 J9 ASM NEWS JI ASM News PD SEP PY 1997 VL 63 IS 9 BP 504 EP 505 PG 2 WC Microbiology SC Microbiology GA XW125 UT WOS:A1997XW12500014 ER PT J AU Berg, DE Strausbaugh, L Shaw, KJ Zhang, JH AF Berg, DE Strausbaugh, L Shaw, KJ Zhang, JH TI Claire M. Berg - Deceased member SO ASM NEWS LA English DT Item About an Individual C1 WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63130. UNIV CONNECTICUT,STORRS,CT 06269. SCHERING PLOUGH RES INST,KENILWORTH,NJ. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0044-7897 J9 ASM NEWS JI ASM News PD SEP PY 1997 VL 63 IS 9 BP 505 EP 506 PG 2 WC Microbiology SC Microbiology GA XW125 UT WOS:A1997XW12500015 ER PT J AU Gracely, RH AF Gracely, RH TI Persistent pain: Trim the branches or fell the tree? SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB In patients with pain characterized by a painful focus and allodynia, the painful symptoms arise from altered central processing that is initiated and subsequently maintained by persistent input from nociceptive afferents. Treatments directed at this normal consequence of persistent input are inherently limited. The most efficacious treatments with target the pathology, the various sources of ongoing nociceptor input. C1 NIDR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Gracely, RH (reprint author), NIDR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1997 VL 20 IS 3 BP 449 EP + PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA YW127 UT WOS:000071900600020 ER PT J AU Goel, V Nichelli, P Grafman, J AF Goel, V Nichelli, P Grafman, J TI What is the locality assumption and how is it violated? SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB We respond to Farah (1994) by making some general remarks about information encapsulation and locality and asking how these are violated in her computational models. Our point is not that we disagree, but rather that Farah's treatment of the issues is not sufficiently rigorous to allow an evaluation of her claims. C1 York Univ, Dept Psychol, N York, ON M3J 1P3, Canada. Neurol Clin, Modena, Italy. NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Goel, V (reprint author), York Univ, Dept Psychol, 4700 Keele St, N York, ON M3J 1P3, Canada. RI Nichelli, Paolo/F-7336-2015 OI Nichelli, Paolo/0000-0001-9756-6796 NR 12 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1997 VL 20 IS 3 BP 519 EP + PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA YW127 UT WOS:000071900600055 ER PT J AU Hayes, LM AF Hayes, LM TI From chaos to calm: One jail system's struggle with suicide prevention SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID URBAN JAIL AB This article profiles the suicide prevention practices at a large metropolitan jail, a facility that experienced nine inmate suicides in a recent 24-month period. The suicide rate in this facility was found to far exceed the rate for jails of comparable size as well as the national rate of jail suicides. The nine suicides are summarized and common features (including the issue of protective custody) of the deaths and systemic jail deficiencies are discussed. The process by which the jail system developed a suicide prevention program based upon the principles of staff training, identification/screening, communication, levels of supervision, housing, and intervention is offered. (C) 1997 John Wiley & Sons, Ltd. C1 Natl Ctr Inst & Alternat, Mansfield, MA 02048 USA. RP Hayes, LM (reprint author), Natl Ctr Inst & Alternat, 40 Lantern Lane, Mansfield, MA 02048 USA. NR 21 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PD FAL PY 1997 VL 15 IS 4 BP 399 EP 413 DI 10.1002/(SICI)1099-0798(199723/09)15:4<399::AID-BSL284>3.0.CO;2-O PG 15 WC Psychology, Applied; Law SC Psychology; Government & Law GA YP618 UT WOS:000071296400003 PM 9433745 ER PT J AU Heyes, MP Chen, CY Major, EO Saito, K AF Heyes, MP Chen, CY Major, EO Saito, K TI Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types SO BIOCHEMICAL JOURNAL LA English DT Article ID CONVERT L-TRYPTOPHAN; INDOLEAMINE 2,3-DIOXYGENASE; NEUROLOGICAL DISEASE; IMMUNE ACTIVATION; CEREBRAL-ISCHEMIA; BRAIN; 4-CHLORO-3-HYDROXYANTHRANILATE; 6-CHLOROTRYPTOPHAN; METABOLISM; MECHANISM AB Substantial increases in the tryptophan-kynurenine pathway metabolites, L-kynurenine and the neurotoxin quinolinic acid, occur in human brain, blood and systemic tissues during immune activation. Studies br vitro have shown that not all human cells are capable of synthesizing quinolinate. To investigate further the mechanisms that limit L-kynurenine and quinolinate production, the activities of kynurenine pathway enzymes and the ability of different human cells to convert pathway intermediates into quinolinate were compared. Stimulation with interferon gamma substantially increased indoleamine 2,3-dioxygenase activity and L-kynurenine production in primary peripheral blood macrophages and fetal brains (astrocytes and neurons), as well as cell. lines derived from macrophage/monocytes (THP-1), U373MG astrocytoma, SKHEP1 liver and lung (MRC-9). High activities of kynurenine 3-hydroxylase, kynureninase or 3-hydroxyanthranilate 3,4-dioxygenase were found in interferon-gamma-stimulated macrophages, THP-1 cells and SKHEP1 cells, and these cells made large amounts of quinolinate when supplied with L-tryptophan, L-kynurenine, 3-hydroxykynurenine or 3-hydroxyanthranilate. Quinolinate production by human fetal brain cultures and U373MG cells was restricted by the low activities of kynurenine 3-hydroxylase, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase, and only small amounts of quinolinate were synthesized when cultures were supplied with L-tryptophan or 3-hydroxyanthranilate. In MRC-9 cells, quinolinate was produced only from 3-hydroxykynurenine and 3-hydroxyanthranilate, consistent with their low kynurenine 3-hydroxylase activity. The results are consistent with the notion that indoleamine 2,3-dioxygenase is an important regulatory enzyme in the production of L-kynurenine and quinolinate. Kynurenine 3-hydroxylase and, in some cells, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase are important determinants of whether a cell can make quinolinate. C1 NINCDS,VIRAL & MOL PATHOGENESIS LAB,BETHESDA,MD 20892. RP Heyes, MP (reprint author), NIMH,LAB NEUROTOXICOL,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 125 Z9 129 U1 2 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1997 VL 326 BP 351 EP 356 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU411 UT WOS:A1997XU41100010 PM 9291104 ER PT J AU Roberts, SJ Chung, KN Nachmanoff, K Elwood, PC AF Roberts, SJ Chung, KN Nachmanoff, K Elwood, PC TI Tissue-specific promoters of the alpha human folate receptor gene yield transcripts with divergent 5' leader sequences and different translational efficiencies SO BIOCHEMICAL JOURNAL LA English DT Article ID MESSENGER-RNA STABILITY; BINDING-PROTEIN; KB CELLS; SECONDARY STRUCTURE; INITIATION; REGION; CDNA; EXPRESSION; PLACENTA; MEMBRANE AB The ct human folate receptor (alpha hFR), or KB cell folate receptor, gene contains two major promoters that produce transcripts, KB1 and KB4, varying only in the length and sequence of their 5' untranslated regions (UTRs). Using RNase protection assays specific for each isoform, we show that the level of expression of these two transcripts is tissue-specific, indicating that promoter usage is regulated, not constitutive. RNA stabilities and translational efficiencies of the KB1 and KB4 transcripts were compared to determine the functional significance of the different 5' UTRs. Analyses of RNA turnover in vivo with actinomycin D to block new transcription and in vitro with a cytoplasmic extract indicate no discernible differences in the stabilities of the two transcripts. However, the KB4 transcript is 2-3-fold mon efficiently translated in wheat germ extracts in vitro and transfected CHO cells in vivo. Also, high ionic strength, which favours the formation of RNA secondary structure, differentially affects the translational efficiencies of the two transcripts. Translation of the longer KB1 mRNA is 2-5-fold more inhibited by hypertonic conditions than translation of the KB4 mRNA. Because the 5' UTR of KB1 is approximately four times longer than the 5' UTR of KB4, 149 bp (75%) of the KB1 5' UTR were deleted to determine whether the long leader sequence inhibited translation. The resulting derivative, dKB1, has a 5' UTR similar in length, but not sequence, to the 5' UTR of KB4. dKB1 is translated at a level approaching that of KB4 in wheat germ extracts, indicating that the upstream portion of the 5' leader sequence contributes to the relative translational inefficiency of KB1. Hence, one consequence of tissue-specific promoter usage is the production of alpha hFR transcripts with different 5' non-coding regions that affect translational efficiency. RP Roberts, SJ (reprint author), NCI,MED BRANCH,DIV CLIN SCI,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 21 Z9 21 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1997 VL 326 BP 439 EP 447 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU411 UT WOS:A1997XU41100022 PM 9291116 ER PT J AU ElAni, D Jacobson, KA Shainberg, A AF ElAni, D Jacobson, KA Shainberg, A TI Regulation of A(1) adenosine receptors by amiodarone and electrical stimulation in rat myocardial cells in vitro SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE adenosine receptor; heart rate; amiodarone; electrical stimulation; temperature; cardiocytes ID CULTURED HEART-CELLS; ANTIARRHYTHMIC DRUGS; BETA-ADRENOCEPTORS; MUSCLE CULTURES; CARDIOMYOCYTES; MANAGEMENT; CHANNELS; FIELDS AB The effects of conditions that either increase or decrease heart rate on the pharmacological properties of adenosine receptors in cultured rat myocytes were examined. Levels of A(1) adenosine receptors, following prolonged treatment with electrical stimulation (ES) or the antiarrhythmic drug amiodarone, were determined using radioligand binding with the specific A(1) receptor antagonist [H-3]1,3-dipropyl-8-cyclopentylxanthine (CPX). The effects of lowering temperature were also explored. Exposure to amiodarone for 4 days reduced the density of A(1) receptors by 19% (from 24.7 +/- 0.4 to 20.09 +/- 0.3 fmol/dish) and inhibited the rate of contraction by 60% (from 188 +/- 16 to 76 +/- 30 beats/min), without changing the receptor affinity, protein content, creatine kinase (CK) activity or cell number. Electrical stimulation at 25 degrees C elevated the density of A(1) adenosine receptors by 185% (from 4.1 +/- 0.4 to 11.69 +/- 2.1 fmol/dish). Four days of reduced temperature (from 37 degrees C to either 30 or 25 degrees C) lowered the density of A(1) adenosine receptors by 69 or 86%, respectively (from 24.1 +/- 1.2 to 7.4 +/- 0.4 or 3.4 +/- 0.3 fmol/dish), with no significant change in the receptor affinity, activity of CK, or lactate dehydrogenase (LDH), protein content or cell number. The observed up-and down-regulation of A(1) adenosine receptors in primary myocyte cultures in response to conditions that exogenously alter the rate of contraction, is indicative of the role of adenosine receptors in adaptation of heart cells to stress. (C) 1997 Elsevier Science Inc. C1 BAR ILAN UNIV, DEPT LIFE SCI, OTTO MEYERHOFF DRUG RECEPTOR CTR, IL-52900 RAMAT GAN, ISRAEL. NIDDK, MOL RECOGNIT SECT, BIOORGAN CHEM LAB, NIH, BETHESDA, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031117-20] NR 31 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 1997 VL 54 IS 5 BP 583 EP 587 DI 10.1016/S0006-2952(97)00177-9 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XW098 UT WOS:A1997XW09800007 PM 9337074 ER PT J AU Samokhvalov, I Hendrikx, J Visser, J Belyavsky, A Sotiropolous, D Gu, H AF Samokhvalov, I Hendrikx, J Visser, J Belyavsky, A Sotiropolous, D Gu, H TI Mice lacking a functional CHK gene have no apparent defects in the hematopoietic system. SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE Chk; non-receptor protein tyrosine kinase; gene targeting; flow cytometry; CAFC assay ID PROTEIN-TYROSINE KINASE; CELL; CSK; CTK; FAMILY; BRAIN; ASSAY; MOUSE AB Non-receptor tyrosine kinase Chk has been implicated in hematopoietic development. To study the function of Chk lit vivo, we have generated chk-deficient mice using gene targeting. Overall development of mice homozygous for this mutation was apparently normal. Blood counts, FAGS analysis of hematopoietic cell populations, CFU-C and CAFC assays shelved no significant difference between wild type and mutant animals. Thus, the dispensability of Chk for mouse development and hematopoiesis suggests that its function may be redundant iii vivo, and most likely be compensated by activity of a closely related protein tyrosine kinase Csk. C1 VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. NIAID, NIH, Rockville, MD 20852 USA. New York Blood Ctr, New York, NY 10021 USA. RP Samokhvalov, I (reprint author), VA Engelhardt Mol Biol Inst, Vavilov Str 32,B-334, Moscow 117984, Russia. NR 18 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE, NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD SEP PY 1997 VL 43 IS 1 BP 115 EP 122 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ213 UT WOS:000073190800014 PM 9315289 ER PT J AU Katz, BZ Yamada, KM AF Katz, BZ Yamada, KM TI Integrins in morphogenesis and signaling SO BIOCHIMIE LA English DT Review DE integrin; morphogenesis; cytoskeleton tyrosine phosphorylation; signal transduction; focal adhesion; Rho ID FOCAL ADHESION KINASE; PROTEIN-TYROSINE KINASES; CELL-MATRIX ADHESIONS; EXTRACELLULAR-MATRIX; FIBRONECTIN RECEPTOR; CYTOPLASMIC DOMAIN; GROWTH-FACTOR; SYNTHETIC PEPTIDES; BINDING PROTEIN; ALPHA-ACTININ AB Integrins are a family of heterodimeric transmembrane receptors that provide a physical and biochemical bridge between components of the extracellular matrix and the intracellular physiological environment. Binding of integrins to their ligands results in the formation of cytoplasmic multi-protein assemblies composed of both cytoskeletal and signaling molecules. The composition and activity of these assemblies is regulated by the nature of integrin-ligand interactions, as well as by intracellular regulators that include tyrosine kinases and phosphatases, PKC, and small GTPases. Integrin-mediated cellular physiological responses include the activation of signal transduction, cytoskeletal rearrangements, and co-regulation of growth factor activities. These responses, combined with integrin-mediated cell adhesion, play a major role in tissue morphogenesis and developmental processes. C1 NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Katz, BZ (reprint author), NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 80 TC 32 Z9 33 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD SEP PY 1997 VL 79 IS 8 BP 467 EP 476 DI 10.1016/S0300-9084(97)82738-1 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YR470 UT WOS:000071498500001 PM 9451447 ER PT J AU Ma, SL Hu, HZ Thompson, J Stavrou, S Scharff, J Neville, DM AF Ma, SL Hu, HZ Thompson, J Stavrou, S Scharff, J Neville, DM TI Genetic construction and characterization of an anti-monkey CD3 single-chain immunotoxin with a truncated diphtheria toxin SO BIOCONJUGATE CHEMISTRY LA English DT Article ID T-CELL RECEPTOR; BINDING DOMAIN SUBSTITUTION; FUSION PROTEIN; PSEUDOMONAS EXOTOXIN; BACTERIAL EXPRESSION AB We have previously developed a chemically conjugated anti-rhesus monkey CD3 immunotoxin FN18-CRM9 that can deplete in vivo T cells and induce long term tolerance of mismatched renal allograft in rhesus monkeys. This immunotoxin is a monkey analogue of anti-human CD3 immunotoxin UCHT1-CRM9. In this study, we cloned the light and heavy chain variable regions of anti-monkey CD3 monoclonal antibody FN18 and constructed a single-chain Fv (sFv) by linking variable light and variable heavy regions with a (Gly(4)Ser)(3) linker. The single-chain immunotoxin DT390-FN18sFv was constructed by ligating the sFv to the carboxyl terminus of DT390, a truncated form of diphtheria toxin. The DT390-FN18sFv fusion protein was expressed in Escherichia coli and purified with Ni-RTA affinity and anion exchange columns. Similar to the chemically conjugated immunotoxin FN18-CRM9, DT390-FN18sFv can also specifically inhibit protein synthesis in primary monkey T cells in a dose-dependent manner. DT390-FN18sFv at 10(-7) mol/L or FN18-CRM9 at 10(-8) mol/L is sufficient to reduce protein synthesis of monkey primary T cells to less than 5% of the control. The 50% inhibition dosage (IC50) of FN18-CRM9 is 1 x 10(-10) mol/L, while the IC50 Of DT390-FN18sFv is 1 x 10(-8) mol/L, reflecting the lowered affinity of monovalent Fab' FN18 to its parental divalent antibody. The availability of functional FN18sFv will provide the basis for the construction of divalent anti-CDS immunotoxins for preclinical studies on the induction of tolerance in organ transplantation and experimental autoimmune diseases. C1 NIMH,MOL BIOL LAB,SECT BIOPHYS CHEM,NIH,BETHESDA,MD 20892. NR 29 TC 15 Z9 17 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 1997 VL 8 IS 5 BP 695 EP 701 DI 10.1021/bc9701398 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA XY705 UT WOS:A1997XY70500011 PM 9327133 ER PT J AU Parascandola, M AF Parascandola, M TI Scientific reasoning in an imperfect world SO BIOESSAYS LA English DT Editorial Material RP Parascandola, M (reprint author), NIH,HISTOR OFF,BETHESDA,MD 20892, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD SEP PY 1997 VL 19 IS 9 BP 745 EP 746 DI 10.1002/bies.950190902 PG 2 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA XV531 UT WOS:A1997XV53100001 PM 9297963 ER PT J AU Miller, FG Rosenstein, DL AF Miller, FG Rosenstein, DL TI Psychiatric symptom-provoking studies: An ethical appraisal SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material DE bioethics; biological psychiatry; challenge studies; institutional review board; informed consent ID OBSESSIVE-COMPULSIVE DISORDER; ANTIDEPRESSANT ACTION; BEHAVIORAL-RESPONSE; METHYLPHENIDATE; SCHIZOPHRENIA; MECHANISM; CHALLENGE; DEPLETION C1 NIMH,PSYCHIAT CONSULTAT LIAS SERV,BETHESDA,MD 20892. UNIV VIRGINIA,CTR BIOMED ETH,CHARLOTTESVILLE,VA. NR 30 TC 24 Z9 24 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 1997 VL 42 IS 5 BP 403 EP 409 DI 10.1016/S0006-3223(97)00189-3 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XR874 UT WOS:A1997XR87400011 PM 9276080 ER PT J AU Bowman, ED Rothman, N Hackl, C Santella, RM Weston, A AF Bowman, ED Rothman, N Hackl, C Santella, RM Weston, A TI Interindividual variation in the levels of certain urinary polycyclic aromatic hydrocarbon metabolites following medicinal exposure to coal tar ointment SO BIOMARKERS LA English DT Article DE benzo[a]pyrene; biomonitoring; carcinogen; metabolism; pyrene ID TREATED PSORIASIS PATIENTS; WHITE BLOOD-CELLS; DNA-ADDUCTS; SKIN-CANCER; GOECKERMAN REGIMEN; 1-HYDROXYPYRENE; MUTAGENICITY; CARCINOGENESIS; BENZOPYRENE; SUSCEPTIBILITY AB Determination of human exposure to polycyclic aromatic hydrocarbons (PAHs) is challenging because they are so broadly distributed in the environment and often difficult to quantitate using questionnaire methods. To enhance the ability to non-invasively evaluate markers of both internal dose and biologically effective dose we have developed methods for the identification and quantitation of l-hydroxypyrene-glucuronide and r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,1O-tetrahydrobenzo[a] (BP-7,10/8,9-tetrol) in human urine. In the current study we applied these assays to urine samples collected from 43 hospitalized psoriasis patients treated with coal tar medication and 39 non-treated volunteer controls, BP-7,10/8,9-tetrol was detected in 20 of 43 (47%) patients, ranging from less than or equal to 1 (not detected) to 124 fmol mu mol(-1) creatinine. In contrast, BP-7,10/8,9-tetrol was detected in only 4 of 39 (10%) controls, range less than or equal to 1 to 20.6 fmol mu mol(-1) creatinine (p = 0.0006, Wilcoxon rank sum test). A second, more polar PAH metabolite, identified as 1-hydroxypyrene-glucuronide, was present in all urine samples, Mean 1-hydroxypyrene-glucuronide levels were 40.96+/-72.62 pmol mu mol(-1) creatinine in patients and 0.38+/-0.32 pmol mu mol(-1) creatinine in control subjects (p less than or equal to 0.0001). The ratio of urinary levels of BP-7,10/8,9-tetrol to l-hydroxypyrene-glucuronide was examined in the coal tar-treated patients, This ratio was found to vary by approximately 6000-fold, This parameter cannot be explained by measurement error because the coefficients of variation for these assays are only 12 and 10% respectively, nor can it be explained by use of different coal tar products. These results provide further evidence that substantial interindividual variation in activation of benzo[a]pyrene and other PAHs exists, which may have implications for disease risk. C1 NCI,MOL EPIDEMIOL SECT,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NCI,OCCUPAT STUDIES SECT,ENVIRONM EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. GSF FORSCHUNGSZENTRUM UMWELT & GESUNDHEIT GMBH,INST OEKOL CHEM,D-85758 OBERSCHLEISSHEIM,GERMANY. COLUMBIA UNIV,SCH PUBL HLTH,DIV ENVIRONM SCI,NEW YORK,NY 10032. NR 46 TC 13 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 1354-750X J9 BIOMARKERS JI Biomarkers PD SEP-OCT PY 1997 VL 2 IS 5 BP 321 EP 327 PG 7 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA YA059 UT WOS:A1997YA05900007 ER PT J AU Park, SI Park, JM Chittum, HS Yang, ES Carlson, BA Lee, BJ Hatfield, DL AF Park, SI Park, JM Chittum, HS Yang, ES Carlson, BA Lee, BJ Hatfield, DL TI Selenocysteine tRNAs as central components of selenoprotein biosynthesis in eukaryotes SO BIOMEDICAL AND ENVIRONMENTAL SCIENCES LA English DT Proceedings Paper CT 6th International Symposium on Selenium in Biology and Medicine CY AUG 18-22, 1996 CL BEIJING, PEOPLES R CHINA ID TRANSFER-RNA GENE; SERINE TRANSFER-RNA; TRANSFER RNA(SER)SEC GENE; SUPPRESSOR TRANSFER-RNA; HUMAN CHROMOSOME-19; MAMMALIAN-CELLS; TRANSCRIPTION; UGA; ELEMENTS; PHOSPHOSERINE AB Selenocysteine (Sec) tRNAs serve as carrier molecules for the biosynthesis oi Sec from serine and to donate Sec to protein in response to specific UGA codons. In this study, we describe the current status oi Sec tRNAs in higher animals and further we examine: (i) the Sec tRNA population in Drosophila; (ii) transcription of the Sec tRNA in vivo (in Xenopus oocytes) and in vitro (in Xenopus oocyte extracts); () the effect oi selenium on the Sec tRNA population in various rat tissues following replenishment of extremely selenium deficient rats with this element; and (iv) the biosynthesis oi the modified bases on See tRNA in Xenopus oocytes. C1 NCI,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Hatfield, DL (reprint author), NCI,EXPT CARCINOGENESIS LAB,NIH,BLDG 27 ROOM 3C23,BETHESDA,MD 20892, USA. NR 47 TC 6 Z9 6 U1 0 U2 0 PU CHINESE ACAD PREVENTIVE MEDICINE PI ORLANDO PA C/O ACADEMIC PRESS INC, 6277 SEA HARBOR DR, ORLANDO, FL 32887-4900 SN 0895-3988 J9 BIOMED ENVIRON SCI JI Biomed. Environ. Sci. PD SEP PY 1997 VL 10 IS 2-3 BP 116 EP 124 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA XX838 UT WOS:A1997XX83800002 PM 9315302 ER PT J AU Borkowf, CB Gail, MH Carroll, RJ Gill, RD AF Borkowf, CB Gail, MH Carroll, RJ Gill, RD TI Analyzing bivariate continuous data grouped into categories defined by empirical quantiles of marginal distributions SO BIOMETRICS LA English DT Article DE agreement; contingency table; empirical bivariate quantile-partitioned distribution; kappa statistic; quantile ID FOOD FREQUENCY QUESTIONNAIRE; REPRODUCIBILITY; AGREEMENT; VALIDITY AB Epidemiologists sometimes study the association between two measurements of exposure on the same subjects by grouping the original bivariate continuous data into categories that are defined by the empirical quantiles of the two marginal distributions. Although such grouped data are presented in a two-way contingency table, the cell counts in this table do not have a multinomial distribution. We describe the joint distribution of counts in such a table by the term empirical bivariate quantile-partitioned (EBQP) distribution. Blomqvist (1950, Annals of Mathematical Statistics 21, 539-600) gave an asymptotic EBQP theory for bivariate data partitioned by the sample medians. We demonstrate that his asymptotic theory is not correct, however, except in special cases. We present a general asymptotic theory for tables of arbitrary dimensions and apply this theory to construct confidence intervals for the kappa statistic. We show by simulations that the confidence interval procedures we propose have near nominal coverage for sample sizes exceeding 60 for both 2 x 2 and 3 x 3 tables. These simulations also illustrate that the asymptotic theory of Blomqvist (1950) and the methods that Fleiss, Cohen, and Everitt (1969, Psychological Bulletin 72, 323-327) give for multinomial tables can yield subnominal coverage for kappa calculated from EBQP tables, although in some cases the coverage for these procedures is near nominal levels. C1 NCI,DIV CANC EPIDEMIOL & GENET,BIOSTAT BRANCH,BETHESDA,MD 20892. TEXAS A&M UNIV,DEPT STAT,COLLEGE STN,TX 77843. UNIV UTRECHT,DEPT MATH,NL-3508 TA UTRECHT,NETHERLANDS. RI Gill, Richard/B-2863-2014 OI Gill, Richard/0000-0001-5821-9986 FU NCI NIH HHS [CA-57030] NR 23 TC 14 Z9 14 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1997 VL 53 IS 3 BP 1054 EP 1069 DI 10.2307/2533563 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XV523 UT WOS:A1997XV52300022 PM 9290229 ER PT J AU Albert, PS Follmann, DA Barnhart, HX AF Albert, PS Follmann, DA Barnhart, HX TI A generalized estimating equation approach for modeling random length binary vector data SO BIOMETRICS LA English DT Article DE correlated binary data; GEE estimation; modeling frequency data; shared parameter models ID MISSING DATA; LINEAR-MODELS; REGRESSION AB A common measure in clinical trials and epidemiologic studies is the number of events such as seizures, hospitalizations, or bouts of disease. Frequently, a binary measure of severity for each event is available but is not incorporated in the analysis. This paper proposes methodology for jointly modeling the number of events and the vector of correlated binary severity measures. Our formulation exploits the notion that a given covariate may affect both outcomes in a similar way. We functionally link the regression parameters for the counts and binary means and discuss a generalized estimating equation (GEE) approach for parameter estimation. We discuss conditions under which the proposed joint modeling approach provides marked gains in efficiency relative to the common procedure of simply modeling the counts, and we illustrate the methodology with epilepsy clinical trial data. C1 EMORY UNIV,SCH PUBL HLTH,DEPT BIOSTAT,ATLANTA,GA 30322. RP Albert, PS (reprint author), NHLBI,OFF BIOSTAT RES,BLDG 10,BETHESDA,MD 20892, USA. NR 18 TC 10 Z9 11 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1997 VL 53 IS 3 BP 1116 EP 1124 DI 10.2307/2533568 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XV523 UT WOS:A1997XV52300027 PM 9290230 ER PT J AU Burgess, K Li, W Linthicum, DS Ni, Q Pledger, D Rothman, RB Shitangkoon, A AF Burgess, K Li, W Linthicum, DS Ni, Q Pledger, D Rothman, RB Shitangkoon, A TI Libraries of opiate and anti-opiate peptidomimetics containing 2,3-methanoleucine SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ENHANCED ANTIOPIATE ACTIVITY; SOLID-PHASE SYNTHESIS; ENZYME RESISTANCE; PEPTIDES; FMRFAMIDE; RECEPTORS AB A library of 96 peptides/peptidomimetics was prepared, in which half was based on the YGGFL-NH2 sequence, while the remainder were derivatives of a presumed anti-opiate peptide, YGGFLRF-NH2. Of the 48 compounds in each half of the library, 32 contained a stereoisomer of 2,3-methanoleucine substituted for Leu(5). Binding of the YGGFL-NH2 derivatives to the mu- and delta-opioid receptors, and to the anti-beta-endorphin monoclonal antibody (clone 3E7), indicated any change at the Leu(5) had little effect on the binding when compared with modifications to the YGGF-sequence. Conversely, cyclo-Leu residues did alter the binding of YGGFLRF-NH2 derivatives when substituted for Leu(5). Of these 32 peptidomimetics, three derivatives of 2S,3S-cyclo-Leu had relatively low K-i values for binding to an NPFF receptor. Differences between the outcome of the screens were interpreted in terms of the position of the cyclo-Leu residue in the two sequences. (C) 1997 Elsevier Science Ltd. C1 TEXAS A&M UNIV,DEPT VET PATHOBIOL,COLLEGE STN,TX 77843. NIDA,CLIN PSYCHOPHARMACOL SECT,DIR,NIH,BALTIMORE,MD 21224. RP Burgess, K (reprint author), TEXAS A&M UNIV,DEPT CHEM,COLLEGE STN,TX 77843, USA. RI Burgess, Kevin/B-5372-2015 OI Burgess, Kevin/0000-0001-6597-1842 FU NIDA NIH HHS [DA 06554]; NIGMS NIH HHS [GM 50772] NR 27 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP PY 1997 VL 5 IS 9 BP 1867 EP 1871 DI 10.1016/S0968-0896(97)00117-X PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA YB459 UT WOS:A1997YB45900014 PM 9354243 ER PT J AU Candeias, LP Wardman, P Mason, RP AF Candeias, LP Wardman, P Mason, RP TI The reaction of oxygen with radicals from oxidation of tryptophan and indole-3-acetic acid SO BIOPHYSICAL CHEMISTRY LA English DT Article DE tryptophan; indole-3-acetic acid; superoxide; peroxidase; radiolysis; EPR; spin-trapping ID ELECTRON-TRANSFER REACTIONS; PULSE-RADIOLYSIS; HORSERADISH-PEROXIDASE; HYDROXYL RADICALS; INDOLYL RADICALS; SUPEROXIDE; INVOLVEMENT; MECHANISM; PRODUCTS; KINETICS AB The oxidation of tryptophan and indole-3-acetic acid (IAA) by the dibromine radical anion or peroxidase from horseradish in aqueous solution was investigated and compared, especially with respect to the involvement of oxygen and superoxide. Using EPR with spin-trapping, the tryptophanyl radical, generated by either method was found to react with oxygen, although this reaction is too slow to be observed by pulse radiolysis (k < 5 x 10(6) dm(3) mol(-1) s(-1)). No superoxide results from this reaction, thus excluding an electron-transfer mechanism and suggesting the formation of a tryptophan peroxyl radical, possibly in a reversible process. These observations imply that in proteins when the tryptophanyl radical exists as a stable species it must either have its reactivity modified by the protein environment or be inaccessible to oxygen. The related molecule IAA is oxidized by either peroxidase or Br2(.-) to a radical cation that decarboxylates to yield a skatolyl radical. The latter reacts with oxygen to give a peroxyl radical that does not release superoxide. However, O-2(.-) is formed during the peroxidase-catalyzed oxidation of indoleacetic acid. This supports the hypothesis that the peroxidase can act in an oxidase cycle involving ferrous enzyme and compound III, with superoxide as a product. (C) 1997 Elsevier Science B.V. C1 NIEHS,LAB PHARMACOL & CHEM,RES TRIANGLE PK,NC 27709. RP Candeias, LP (reprint author), MT VERNON HOSP,GRAY LAB,CANC RES TRUST,POB 100,NORTHWOOD HA6 2JR,MIDDX,ENGLAND. NR 38 TC 41 Z9 41 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD SEP 1 PY 1997 VL 67 IS 1-3 BP 229 EP 237 DI 10.1016/S0301-4622(97)00052-5 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA YH206 UT WOS:A1997YH20600023 PM 9397527 ER PT J AU Ehrenstein, G Galdzicki, Z Lange, GD AF Ehrenstein, G Galdzicki, Z Lange, GD TI The choline-leakage hypothesis for the loss of acetylcholine in Alzheimer's disease SO BIOPHYSICAL JOURNAL LA English DT Article ID AMYLOID BETA-PROTEIN; CEREBROSPINAL-FLUID; POSSIBLE MECHANISM; APOLIPOPROTEIN-E; PC12 CELLS; PRECURSOR; BRAIN; MEMBRANES; TOXICITY; DEMENTIA AB We present a hypothesis for the loss of acetylcholine in Alzheimer's disease that is based on two recent experimental results: that beta-amyloid causes leakage of choline across cell membranes and that decreased production of acetylcholine increases the production of beta-amyloid. According to the hypothesis, an increase in beta-amyloid concentration caused by proteolysis of the amyloid precursor protein results in an increase in the leakage of choline out of cells. This leads to a reduction in intracellular choline concentration and hence a reduction in acetylcholine production. The reduction in acetylcholine production, in turn, causes an increase in the concentration of beta-amyloid. The resultant positive feedback between decreased acetylcholine and increased beta-amyloid accelerates the loss of acetylcholine. We compare the predictions of the choline-leakage hypothesis with a number of experimental observations. We also approximate it with a pair of ordinary differential equations. The solutions of these equations indicate that the loss of acetylcholine is very sensitive to the initial rate of beta-amyloid production. C1 NINCDS,NIH,INSTRUMENTAT & COMP SECT,BETHESDA,MD 20892. NINCDS,BIOPHYS SECT,BETHESDA,MD. NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 30 TC 20 Z9 20 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1997 VL 73 IS 3 BP 1276 EP 1280 PG 5 WC Biophysics SC Biophysics GA XT261 UT WOS:A1997XT26100015 PM 9284295 ER PT J AU Frolenkov, GI Kalinec, F Tavartkiladze, GA Kachar, B AF Frolenkov, GI Kalinec, F Tavartkiladze, GA Kachar, B TI Cochlear outer hair cell bending in am external electric field SO BIOPHYSICAL JOURNAL LA English DT Article ID GUINEA-PIG; MECHANICAL RESPONSES; SHAPE CHANGES; MOTILITY; ELECTROMOTILITY; AMPLIFIER; SENSITIVITY; MOVEMENTS; PHASE AB We have used a high-resolution motion analysis system to reinvestigate shape changes in isolated guinea pig cochlear outer hair cells (OHCs) evoked by low-frequency (2-3 Hz) external electric stimulation. This phenomenon of electromotility is presumed to result from voltage-dependent structural changes in the lateral plasma membrane of the OHC. in addition to well-known longitudinal movements, OHCs were found to display bending movements when the alternating external electric field gradients were oriented perpendicular to the cylindrical cell body. The peak-to-peak amplitude of the bending movement was found to be as large as 0.7 mu m. The specific sulfhydryl reagents, p-chloromercuriphenylsulfonic acid and p-hydroxymercuriphenylsulfonic acid, that suppress electrically evoked longitudinal OHCs movements, also inhibit the bending movements, indicating that these two movements share the same underlying mechanism. The OHC bending is likely to result from an electrical charge separation that produces depolarization of the lateral plasma membrane on one side of the cell and hyperpolarization on the other side. In the cochlea, OHC bending could produce radial distortions in the sensory epithelium and influence the micromechanics of the organ of Corti. C1 NIDCD,SECT STRUCT CELL BIOL,NIH,BETHESDA,MD 20892. RES CTR AUDIOL & HEARING REHABIL,DEPT EXPT & CLIN AUDIOL,MOSCOW,RUSSIA. NR 32 TC 22 Z9 22 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1997 VL 73 IS 3 BP 1665 EP 1672 PG 8 WC Biophysics SC Biophysics GA XT261 UT WOS:A1997XT26100053 PM 9284333 ER PT J AU Feldman, GM Rosenthal, LA Liu, XW Hayes, MP WynshawBoris, A Leonard, WJ Hennighausen, L Finbloom, DS AF Feldman, GM Rosenthal, LA Liu, XW Hayes, MP WynshawBoris, A Leonard, WJ Hennighausen, L Finbloom, DS TI STAT5A-deficient mice demonstrate a defect in granulocyte-macrophage colony-stimulating factor-induced proliferation and gene expression SO BLOOD LA English DT Article ID DNA-BINDING ACTIVITY; TYROSINE PHOSPHORYLATION; GAMMA RECEPTOR; STAT5; ERYTHROPOIETIN; INTERLEUKIN-3; ACTIVATION; INTERFERON; PROLACTIN; PROMOTER AB Responses of cells to cytokines typically involve the activation of a family of latent DNA binding proteins, referred to as signal transducers and activators of transcription (STAT) proteins, which are critical for the expression of early response genes, Of the seven known STAT proteins, STAT5 (originally called mammary gland factor) has been shown to be activated by several cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5, which are known to play important roles in growth and differentiation of hematopoietic precursors. In this report we have used mice that are deficient in STAT5A (one of two homologues of STATS) to study the role of STAT5A in GM-CSF stimulation of cells. When bone marrow-derived macrophages were generated by differentiation with macrophage-CSF (M-CSF), exposure of cells from wild-type mice to GM-CSF resulted in a typical pattern of assembly of DNA binding proteins specific for the gamma activation sequence (GAS) element within the beta-casein promoter. However, in cells from the STAT5A null moose one of the shifted bands was absent, Immunoblotting analysis in the null mice showed that lack of STAT5A protein resulted in no alteration in activation of STAT5B by tyrosine phosphorylation. Proliferation experiments revealed that, when exposed to increasing concentrations of GM-CSF, cells derived from the null mice grew considerably more slowly than cells derived from the wild-type mice. Moreover, expression of GM-CSF-dependent genes, CIS and Al, was markedly inhibited in cells derived from null mice as compared with those of wild-type mice. The decreased expression observed with A1, a bcl-2 like gene, may account in part for the suppression of growth in cells from the null mice. These data suggest that the presence of STAT5A during the GM-CSF-induced assembly of STAT5 dimers is critical for the formation of competent transcription factors that are required for both gene expression and cell proliferation. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. NIH,LAB GENET DIS RES,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. RI Rosenthal, Louis/A-8868-2008 NR 34 TC 140 Z9 140 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1997 VL 90 IS 5 BP 1768 EP 1776 PG 9 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600005 PM 9292509 ER PT J AU Mansfield, E Amlot, P Pastan, I Fitzgerald, DJ AF Mansfield, E Amlot, P Pastan, I Fitzgerald, DJ TI Recombinant RFB4 immunotoxins exhibit potent cytotoxic activity for CD22-bearing cells and tumors SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; CONSERVED FRAMEWORK REGIONS; INTERCHAIN DISULFIDE BONDS; SINGLE-CHAIN IMMUNOTOXINS; FV FRAGMENTS; PHASE-I; ANTI-B4-BLOCKED RICIN; CONTINUOUS-INFUSION; ANTITUMOR-ACTIVITY; STABILIZED FV AB Many B-cell malignancies express the CD22 antigen on their cell surface, To kill cells expressing this antigen, the RFB4 monoclonal antibody (MoAb) has been linked chemically with either deglycosylated ricin A chain or truncated versions of Pseudomonas exotoxin, These immuno toxins exhibited selective cytotoxic activity for CD22(+) cells and antitumor activity in nude moose models bearing human B-cell lymphomas. To construct a recombinant immunotoxin targeted to CD22, we first cloned the variable portions of the heavy and light chains of RFB4. The cloned Fv fragments were joined by a newly created disulfide bond to form a disulfide stabilized (ds) construct. The RFB4 construct was combined by gene fusion with PE38, a truncated version of PE. The recombinant immunotoxin was then expressed in Escherichia coli, purified by column chromatography and tested for cytotoxicity activity. RFB4(dsFv)PE38 retained its binding activity for CD22, was very stable at 37 degrees C and exhibited selective cytotoxic activity for CD22(+)-cultured cell lines, Because of its favorable binding characteristics and potency for CD22-positive cell lines, RFB4(dsFv)PE38 was tested for antitumor activity in a nude mouse model of human lymphoma, CA46 cells were injected subcutaneously and then treated with the RFB4(dsFv)PE38 immunotoxin. Antitumor activity was dose responsive and was not evident when an irrelevant immunotoxin was administered on the same schedule. C1 NCI,MOL BIOL LAB,DBS,DCBDC,NIH,BETHESDA,MD 20892. ROYAL FREE HOSP,DEPT IMMUNOL,LONDON NW3 2QG,ENGLAND. NR 21 TC 97 Z9 101 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1997 VL 90 IS 5 BP 2020 EP 2026 PG 7 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600034 PM 9292538 ER PT J AU Bloom, ML SimonStoos, KL AF Bloom, ML SimonStoos, KL TI The hemoglobin-deficit mouse: Analysis of phenotype and hematopoiesis in the transplant model SO BLOOD LA English DT Article ID STEM-CELLS; COMPETITIVE REPOPULATION; MICE; ANEMIA; ASSAY AB The mouse mutant hemoglobin deficit (gene symbol hbd) is characterized by a severe microcytic anemia that is inherited in an autosomal-recessive manner. To assess the mutation's effect on hematopoiesis, unfractionated bone marrow (BM) from either a mutant: C57BL6/J-hbd/hbd, Gpi1(b)/Gpi1(b) (phenotype symbol HBD), or normal C57BL6/J -+(hbd)/+(hbd), Gpi1(b)/Gpi1(b) mouse was injected intravenously into irradiated congenic C57BL6/J-+(hbd)/+(hbd), Gpi1(a)/Gpi1(a), Igh(a)/Igh(a), Thy1(a)/Thy1(a) mice, The congenic recipients of mutant or normal marrow obtained complete red blood cell (RBC) and leukocyte reconstitution, with the exception of one recipient of HBD marrow, After 24 weeks posttransplantation, the normal recipients of HBD marrow obtained a microcytic anemia similar to the donor, These results suggest that the HBD phenotype is caused by ii SM defect, We observed that. the erythroid lineage derived from donor HBD marrow repopulated more slowly than the normal marrow at 4 weeks posttransplantation. To determine if this difference was a result of an erythropoietic defect, competitive repopulation was performed using either mutant or normal marrow competed against normal congenic marrow. For the erythroid lineage, no significant contribution from HBD marrow was observed, To assess if the RBC block was based on a deficiency of myeloid progenitors, both in vitro and in vivo assays were performed: absolute numbers of bone progenitors were increased, suggesting that the defect results in a late block to erythroid differentiation. RP Bloom, ML (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7C 118,BETHESDA,MD 20892, USA. NR 21 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1997 VL 90 IS 5 BP 2062 EP 2067 PG 6 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600040 PM 9292544 ER PT J AU McCaffrey, PG Newsome, DA Fibach, E Yoshida, M Su, MSS AF McCaffrey, PG Newsome, DA Fibach, E Yoshida, M Su, MSS TI Induction of gamma-globin by histone deacetylase inhibitors SO BLOOD LA English DT Article ID SICKLE-CELL-ANEMIA; FETAL HEMOGLOBIN; SODIUM-BUTYRATE; GENE-EXPRESSION; BETA-THALASSEMIA; TRANSGENIC MICE; TRICHOSTATIN-A; ACETYLATION; PROMOTER; BINDING AB The short-chain fatty acid butyrate has been shown to elevate fetal hemoglobin (HbF) by inducing expression of the gamma-globin gene, Regulation of gene expression by butyrate is thought to proceed via inhibition of the enzyme histone deacetylase, leading to elevated levels of core histone acetylation which affect chromatin structure and transcription rates. To determine whether changes in histone acetylation are critical for the regulation of the gamma-globin gene, we tested three potent and specific inhibitors of histone deacetylase, the cyclic tetrapeptides trapoxin and Helminthsporium carbonum toxin (HC toxin), and the antifungal antibiotic trichostatin A for their ability to induce fetal hemoglobin expression in erythroid cells. These compounds induced fetal hemoglobin in both primary erythroid cell cultures and human erythroleukemia (K562) cells, A butyrate-responsive element spanning the duplicated CCAAT box region of the gamma-globin promoter has been identified in transient transfection assays using a reporter construct in K562 cells, and we show that the same promoter region is required for response to trapoxin and trichostatin. Mutational analysis of the gamma-globin promoter indicates that the distal CCAAT box and 3' flanking sequence (CCAATAGCC) is critical for activation by butyrate, trapoxin, and trichostatin, whereas the proximal element (CCAATAGTC) plays a less important role, These results show that inhibition of histone deacetylase can lead to transcriptional activation of gamma-globin promoter reporter gene constructs through proximal promoter elements, and suggest that butyrate induces gamma-globin expression via such changes in histone acetylation. (C) 1997 by The American Society of Hematology. C1 HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. UNIV TOKYO,DEPT BIOTECHNOL,TOKYO,JAPAN. RP McCaffrey, PG (reprint author), VERTEX PHARMACEUT INC,DEPT BIOL MOL,130 WAVERLY ST,CAMBRIDGE,MA 02139, USA. RI Yoshida, Minoru/C-8049-2014 NR 41 TC 107 Z9 107 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1997 VL 90 IS 5 BP 2075 EP 2083 PG 9 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600042 PM 9292546 ER PT J AU Halverson, DC Schwartz, GN Carter, C Gress, RE Fowler, DH AF Halverson, DC Schwartz, GN Carter, C Gress, RE Fowler, DH TI In vitro generation of allospecific human CD8(+) T cells of Tc1 and Tc2 phenotype SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; MEDIATED CYTOTOXICITY; IN-VIVO; LYMPHOKINE PRODUCTION; EFFECTOR POPULATIONS; CYTOKINE PROFILES; GROWTH-FACTOR; FAS; INTERLEUKIN-7; LYMPHOCYTES AB We have previously shown that allospecific murine CD8(+) T cells of the Tc1 and Tc2 phenotype could be generated in vitro, and that such functionally defined T-cell subsets mediated a graft-versus-leukemia (GVL) effect with reduced graft-versus-host disease (GVHD). To evaluate whether analogous Tcl and Tc2 subsets might be generated in humans, Ca8(+) T cells were allostimulated in the presence of either interleukin-12 (IL-12) and transforming growth factor-beta (TGF-P) (Tcl culture) or IL-4 (Tc2 culture). Tc1-type CD8 cells secreted the type I cytokines IL-2 and interferon gamma (IFN-gamma), whereas Tc2-type cells primarily secreted the type II cytokines IL-4, IL-5, and IL-10, Both cytokine-secreting populations effectively lysed tumor targets when stimulated with anti-T-cell receptor (TCR) antibody; allospecificity of Tc1- and Tc2-mediated cytolytic function was demonstrated using bone marrow-derived stimulator cells as targets. In addition, both Tcl and Tc2 subsets were capable of mediating cytolysis through the fas pathway. We therefore conclude that allospecific human CD8(+) T cells of Tcl and Tc2 phenotype can be generated in vitro, and that these T-cell populations may be important for the mediation and regulation of allogeneic transplantation responses. C1 NCI,TRANSPLANTAT THERAPY SECT,MED BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 36 TC 41 Z9 46 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1997 VL 90 IS 5 BP 2089 EP 2096 PG 8 WC Hematology SC Hematology GA XX166 UT WOS:A1997XX16600044 PM 9292548 ER PT J AU Tedeschi, G Litvan, I Bonavita, S Bertolino, A Lundbom, N Patronas, NJ Hallett, M AF Tedeschi, G Litvan, I Bonavita, S Bertolino, A Lundbom, N Patronas, NJ Hallett, M TI Proton magnetic resonance spectroscopic imaging in progressive supranuclear palsy, Parkinson's disease and corticobasal degeneration SO BRAIN LA English DT Article DE proton magnetic resonance spectroscopy; progressive supranuclear palsy; Parkinson's disease; corticobasal degeneration ID STEELE-RICHARDSON-OLSZEWSKI; BASAL GANGLIONIC DEGENERATION; POSITRON EMISSION TOMOGRAPHY; ALZHEIMERS-DISEASE; IN-VIVO; H-1-NMR SPECTROSCOPY; CLINICAL-DIAGNOSIS; N-ACETYLASPARTATE; MR SPECTROSCOPY; RAT-BRAIN AB We used proton magnetic resonance spectroscopic imaging (H-1-MRSI) to assess the in vivo cortical and subcortical neuronal involvement in progressive supranuclear palsy, Parkinson's disease and corticobasal degeneration. This technique permitted the simultaneous measurement of compounds containing N-acetylaspartate (NA), choline (Cho), creatine-phosphocreatine (Cre) and lactate, from four 15-mm slices divided into 0.84-ml single-volume elements. The study included 12 patients with progressive supranuclear palsy, 10 with Parkinson's disease, nine with corticobasal degeneration and 11 age-matched normal control subjects. Regions of interest were selected from the brainstem, caudate, thalamus, lentiform nucleus, centrum semiovale, and from frontal, parietal, precentral, temporal and occipital cortices. Progressive supranuclear palsy patients, compared with the control subjects, had significantly reduced NA/Cre in the brainstem, centrum semiovale, frontal and precentral cortex, and significantly reduced NA/Cho in the lentiform nucleus. Corticobasal degeneration patients, compared with control subjects, had significantly reduced NA/Cre in the centrum semiovale, and significantly reduced NA/Cho in the lentiform nucleus and parietal cortex. There were no significant differences between Parkinson's disease patients and control subjects, or between patient groups in any individual region of interest. In the parietal cortex of corticobasal degeneration patients, NA/Cho was significantly reduced contralateral to the most affected side. There were statistically significant group differences in the regional pattern of NA/Cre and NA/Cho reduction, comparing normal control subjects with all patient groups. Parkinson's disease with corticobasal degeneration, and Parkinson's disease with progressive supranuclear palsy. Although the occurrence of significant groups differences does not imply that it is possible to differentiate between individual patients using H-1-MRSI in progressive supranuclear palsy and corticobasal degeneration, detection of specific cortical and subcortical patterns of neuronal involvement is possible with this technique. We suggest that this regional pattern of neuronal involvement found in progressive supranuclear palsy and corticobasal degeneration may help in the diagnostic evaluation of affected individuals. C1 NINCDS,NEUROIMAGING BRANCH,NIH,BETHESDA,MD 20892. NINCDS,NEUROEPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. NIMH,CTR CLIN,DEPT DIAGNOST RADIOL,NIH,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BETHESDA,MD 20892. RI Bertolino, Alessandro/O-6352-2016; OI Bertolino, Alessandro/0000-0002-1251-1380; Litvan, Irene/0000-0002-3485-3445 NR 56 TC 102 Z9 109 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 1997 VL 120 BP 1541 EP 1552 DI 10.1093/brain/120.9.1541 PN 9 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XX509 UT WOS:A1997XX50900003 PM 9313638 ER PT J AU Gerloff, C Corwell, B Chen, R Hallett, M Cohen, LG AF Gerloff, C Corwell, B Chen, R Hallett, M Cohen, LG TI Stimulation over the human supplementary motor area interferes with the organization of future elements in complex motor sequences SO BRAIN LA English DT Article; Proceedings Paper CT 4th International Congress of Movement Disorders CY JUN 17-21, 1996 CL VIENNA, AUSTRIA DE supplementary motor areal finger movements; motor sequences; motor control ID TRANSCRANIAL MAGNETIC STIMULATION; MOVEMENT-RELATED POTENTIALS; CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; PRECEDING VOLUNTARY MOVEMENT; SEQUENTIAL FINGER MOVEMENTS; HUMAN VISUAL-CORTEX; PARKINSONS-DISEASE; PREMOTOR CORTEX; NEURONAL-ACTIVITY AB We used high-frequency repetitive transcranial magnetic stimulation (rTMS) to study the role of the mesial frontocentral cortex (including the supplementary motor area) in the organization of sequential finger movements of different complexity in humans. In 15 subjects, rTMS was randomly applied to the scalp overlying the region of the supplementary motor area and over other positions, including the contralateral primary motor cortex (hand area) during the performance of three overlearned finger sequences on an electronic piano. In all trials, rTMS (frequency 15-20 Hz) started 2 s after the first key press and lasted for similar to 2 s. All sequences were metronome-paced at 2 Hz and retrieved from memory. The 'simple' sequence consisted of 16 repeated index finger key presses, the 'scale' sequence of four times four sequential key presses of the little, ring, middle and index fingers, and the 'complex' sequence of a much less systematic and, therefore, more difficult series of 16 key presses. To measure the effects of rTMS interference with regional cortical function, we analysed rTMS-induced accuracy errors in the movement sequences. Stimulation over the supplementary motor area induced accuracy errors only in the complex sequence, while stimulation over the primary motor cortex induced errors in both the complex and scale sequences, and stimulation over other positions (e.g. F3, F4, FCz, P3, P4) did nor interfere with sequence performance at all. Stimulation over the supplementary motor area interfered with the organization of subsequent elements in the complex sequence of movements, with error induction occurring similar to 1 s later than with stimulation over the primary motor cortex. Our findings are in keeping with recent results in non-human primates (Tanji J, Shima K. Nature, 1994; 371: 413-6) indicating a critical role of the supplementary motor area in the organization of forthcoming movements in complex motor sequences that are rehearsed from memory and fit into a precise timing plan. C1 NINCDS, HUMAN CORT PHYSIOL UNIT,HUMAN MOTOR CONTROL SECT, MED NEUROL BRANCH,NIH, BETHESDA, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 89 TC 199 Z9 202 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD SEP PY 1997 VL 120 BP 1587 EP 1602 DI 10.1093/brain/120.9.1587 PN 9 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XX509 UT WOS:A1997XX50900007 PM 9313642 ER PT J AU Suzuki, K Fiu, YJ Sango, K Yamanaka, S Taniike, M Proia, R AF Suzuki, K Fiu, YJ Sango, K Yamanaka, S Taniike, M Proia, R TI Marine models of GM2 gangliosidoses generated by targeted gene disruption SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC. NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 1997 VL 7 IS 4 BP 1062 EP 1062 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XQ527 UT WOS:A1997XQ52700028 ER PT J AU Kok, CC Martins, R Askanas, V Dalakas, MC Mastaglia, FL Garlepp, MJ AF Kok, CC Martins, R Askanas, V Dalakas, MC Mastaglia, FL Garlepp, MJ TI An investigation of mitochondrial DNA point mutation in inclusion body myositis and Alzheimer's disease SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 UNIV WESTERN AUSTRALIA,HOLLYWOOD PRIVATE HOSP,DEPT SURG,NEDLANDS,WA 6009,AUSTRALIA. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 1997 VL 7 IS 4 BP 1222 EP 1222 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XQ527 UT WOS:A1997XQ52700348 ER PT J AU Brown, P AF Brown, P TI Host and invader in environmentally acquired CJD SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 NINCDS,LAB ONS STUDIES,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 1997 VL 7 IS 4 BP 1267 EP 1267 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XQ527 UT WOS:A1997XQ52700386 ER PT J AU Rao, GN Ney, E Herbert, RA AF Rao, GN Ney, E Herbert, RA TI Influence of diet on mammary cancer in transgenic mice bearing an oncogene expressed in mammary tissue SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; c-neu/erbB2 oncogene; diet; dietary fiber; transgenic mice ID BREAST-CANCER; BODY-WEIGHT; LONG-TERM; FIBER; RATS; GROWTH; TOXICOLOGY; TUMORS; GENES AB Breast cancer is one of the most common cancers in women. The laboratory rat treated with strong carcinogen is the most commonly used animal model for study of breast cancer. Transgenic mouse lines with homologues of human breast cancer oncogenes have been developed. The transgenic mouse line TG.NK with c-neu the human breast cancer oncogene homologue of erbB2, was evaluated to determine its suitability for study of intervention strategies to delay/prevent the development of breast cancer. There were no palpable mammary tumor masses up to 22-weeks of age, and almost all mice fed a purified diet developed palpable mammary tumors by 28-weeks of age. Nonpurified diets decreased the incidence and multiplicity, and delayed the development of mammary tumors as compared to a purified diet. Increasing the fiber content of nonpurified diet decreased the tumor incidence further. There is approximately a 19-week interval between weaning and development of palpable mammary masses to evaluate intervention strategies to delay or prevent the development of mammary cancer in the TG.NK mouse model. Fiber from nonpurified cereal ingredients appears to be highly beneficial in delaying the development of mammary cancer in TG.NK mice, and this observation is in agreement with human epidemiological findings. Therefore, the TG.NK transgenic mouse with oncogene c-neu (erbB2), appears to be a useful animal model for evaluation of dietary intervention strategies. RP Rao, GN (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,NIH,B3-08,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 22 Z9 22 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 1997 VL 45 IS 2 BP 149 EP 158 DI 10.1023/A:1005822318256 PG 10 WC Oncology SC Oncology GA XZ642 UT WOS:A1997XZ64200006 PM 9342440 ER PT J AU Rozemuller, H Rombouts, EJC Touw, IP FitzGerald, DJP Kreitman, RJ Pastan, I Hagenbeek, A Martens, ACM AF Rozemuller, H Rombouts, EJC Touw, IP FitzGerald, DJP Kreitman, RJ Pastan, I Hagenbeek, A Martens, ACM TI Sensitivity of human acute myeloid leukaemia to diphtheria toxin-GM-CSF fusion protein SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE diphtheria toxin GM-CSF; GM-CSF receptor; AML; leukaemia treatment ID COLONY-STIMULATING FACTOR; ACUTE MYELOBLASTIC-LEUKEMIA; NONHEMATOPOIETIC TUMOR-CELLS; HEMATOPOIETIC GROWTH-FACTORS; BINDING DOMAIN SUBSTITUTION; ACUTE MYELOCYTIC-LEUKEMIA; MARROW PROGENITOR CELLS; SERUM-FREE CULTURE; GENETIC CONSTRUCTION; GRANULOCYTE-COLONY AB The potential to selectively eliminate acute myeloid leukaemia (AML) cells with the GM-CSF-diphtheria toxin fusion protein (DT-GM-CSF) was studied under conditions of autonomous proliferation in vitro with no growth factors (GFs) added and after growth stimulation with a mixture of human (hu)G-CSF, huIL-3 and huSCF. DNA synthesis was maximally inhibited after 48 h exposure to DT-GM-CSF. Cell viability and AML colony forming ability in vitro were reduced. 18/22 samples were found to be sensitive to DT-GM-CSF, with 50% inhibition of DNA synthesis (ID50) at concentrations ranging from 0.1 to 16 ng/ml, and four samples were minimally or not sensitive to DT-GM-CSF (ID50 greater than or equal to 99 ng/ml). From the 15 samples which showed autonomous proliferation, 13 were sensitive to inhibition of proliferation by DT-GM-CSF. The level of GM-CSF receptor (GM-CSFR) expression was determined by flow cytometry after labelling with specific antibodies for the alpha and beta subunits. Although the toxicity to DT-GM-CSF was specifically mediated by the GM-CSFR alpha or beta subunit and sensitivity for DT-GM-CSF. These in vitro studies show that the DT-GM-CSF fusion protein can be used for specifically targeting and eliminating leukaemic cells in the majority of AML cases. C1 ERASMUS UNIV ROTTERDAM,INST HAEMATOL,ROTTERDAM,NETHERLANDS. DR DANIEL DEN HOED CANC CTR,NL-3008 AE ROTTERDAM,NETHERLANDS. NCI,DIV CANC BIOL DIAG & CTR,MOL BIOL LAB,BETHESDA,MD 20892. NR 40 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1997 VL 98 IS 4 BP 952 EP 959 DI 10.1046/j.1365-2141.1997.2893106.x PG 8 WC Hematology SC Hematology GA XZ111 UT WOS:A1997XZ11100026 PM 9326195 ER PT J AU Paolini, M Pozzetti, L Sapone, A Biagi, GL CantelliForti, G AF Paolini, M Pozzetti, L Sapone, A Biagi, GL CantelliForti, G TI Development of basal and induced testosterone hydroxylase activity in the chicken embryo in ovo SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE cytochrome P450; chicken embryo liver; testosterone hydroxylase; phenobarbitone induction ID ADULT HEN LIVER; CYTOCHROME-P-450 ISOZYMES; INDUCTION; PURIFICATION; EXPRESSION; EVOLUTION; ENZYME; FORMS; ACID; RAT AB 1 The sensitivity of the developing embryo to xenobiotics is highly dependent on the expression of metabolizing enzymes including cytochromes P450 (CYP). In the present study, therefore, the ontogeny of the CYP-dependent system in the chick was investigated with testosterone hydroxylase activity as a marker of CYP expression. 2 Chicken embryo livers were assayed for basal and phenobarbitone (PB)-induced regio-and stereoselective testosterone hydroxylase activity, from the first appearance of the liver as a discrete organ at 5 days of incubation through day 10 posthatching. In addition, whole embryo preparations were assayed at 3 and 4 days of incubation. 3 Whereas testosterone 16 beta-hydroxylase and androst-4-ene-3,17-dione-linked activities were expressed during all stages of embryonic development, testosterone 6 alpha-, 6 beta-, 7 alpha- and 16 alpha-hydroxylase activities were observed only in basal embryos from 8 days of incubation. Furthermore, testosterone 2 alpha- and 2 beta-hydroxylase activities were detected exclusively from 10 days of incubation onward. All activities increased steadily throughout development as did the responsiveness of the embryonic liver to PB induction. 4 A typical pattern of development with a higher activity from 10 to 14 days of incubation (testosterone 16 alpha-, 7 alpha-, 6 alpha- and 2 beta-hydroxylase activities; up to 4.1 +/- 0.3 pmol mg(-1) protein min(-1) at 13 days of incubation for testosterone 7 alpha-hydroxylase) or shifted to 14 to 18 days of incubation (testosterone 6 beta-, 2 alpha- and 16 beta-hydroxylase activities: up to 56.6 +/- 1.4 pmol mg(-1) protein min(-1) at 16 days of incubation for testosterone 6 beta-hydroxylase) was observed. There was a tendency towards an increased activity for all activities around hatching, specifically from 19 days of incubation to 4 days posthatching (up to 1,759.3 +/- 179.4 pmol mg(-1) protein min(-1) at 1 day posthatching for androst-4-ene-3,17-dione-linked activity). 5 The highest level of PB-induced enzyme activity was observed for testosterone 2 alpha-hydroxylase activity (95.14 +/- 7.35 and 660.19 +/- 45.27 pmol mg(-1) protein min(-1)) at 12 days of incubation and day 3 posthatching, respectively. Except for testosterone 2 alpha- and 2 beta-hydroxylase activities at 3 to 4 days of incubation, all metabolites were detectable during the first period of organogenesis in the presence of PB. 6 The use of highly specific substrates, studies on the immunoinhibition of metabolism by polyclonal antibodies raised against highly purified rat CYPs, and the use of selective inhibitors seemed to reveal a wide pleiotropic response with the posssible presence in liver of PB-treated chickens of CYP1A together with CYP2H1/H2, CYP2E and CYP3A. C1 NCI,NIH,LAB METAB,BETHESDA,MD 20892. UNIV TEXAS,MED BRANCH,DEPT PREVENT MED & COMMUNITY HLTH,DIV ENVIRONM TOXICOL,GALVESTON,TX 77550. RP Paolini, M (reprint author), UNIV BOLOGNA,DEPT PHARMACOL,BIOCHEM TOXICOL UNIT,VIA IRNERIO 48,I-40126 BOLOGNA,ITALY. RI Sapone, Andrea/E-6704-2013; OI paolini, moreno/0000-0002-2338-8859; Sapone, Andrea/0000-0001-8496-6977 NR 53 TC 21 Z9 21 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 1997 VL 122 IS 2 BP 344 EP 350 DI 10.1038/sj.bjp.0701352 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XW039 UT WOS:A1997XW03900022 PM 9313945 ER PT J AU Fenton, WS Blyler, CR Wyatt, RJ McGlashan, TH AF Fenton, WS Blyler, CR Wyatt, RJ McGlashan, TH TI Prevalence of spontaneous dyskinesia in schizophrenic and non-schizophrenic psychiatric patients SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID NEUROLEPTIC-NAIVE; TARDIVE-DYSKINESIA; NATURAL-HISTORY; MOVEMENTS; DISORDERS; SUBTYPES; DRUGS; SIGNS; NEVER AB Background Although movement disorders have been noted among patients never exposed to neuroleptic medications, the specificity of spontaneous dyskinesia to schizophrenia has rarely been examined. Method By abstracting detailed case records, we compared the prevalence of dyskinetic movements between 94 neuroleptic-naive schizophrenic patients and 179 patients with other psychiatric disorders. Results Dyskinetic movements were more common among patients with schizophrenia than among those with all other diagnoses, and were most often noted in the body areas typically associated with tardive dyskinesia. Conclusions Spontaneous dyskinesia appears to be relatively specific to schizophrenia and may be intrinsic to the pathophysiology of the disorder. C1 NIMH,NEUROPSYCHIAT BRANCH,BETHESDA,MD 20892. YALE UNIV,INST PSYCHIAT,NEW HAVEN,CT 06520. RP Fenton, WS (reprint author), CHESTNUT LODGE RES INST,500 W MONTGOMERY AVE,ROCKVILLE,MD 20850, USA. NR 23 TC 38 Z9 39 U1 0 U2 1 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 1997 VL 171 BP 265 EP 268 DI 10.1192/bjp.171.3.265 PG 4 WC Psychiatry SC Psychiatry GA XV692 UT WOS:A1997XV69200017 PM 9337982 ER PT J AU Bellahcene, A Maloujahmoum, N Fisher, LW Pastorino, H Tagliabue, E Menard, S Castronovo, V AF Bellahcene, A Maloujahmoum, N Fisher, LW Pastorino, H Tagliabue, E Menard, S Castronovo, V TI Expression of bone sialoprotein in human lung cancer SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE bone sialoprotein; lung cancer; bone metastasis; microcalcifications ID CELL-ADHESION; LOCALIZATION; TISSUES; MODULATION; INTEGRINS; SEQUENCE; PROTEIN; BREAST; BSP AB Lung cancer belongs to the group of malignant lesions that specifically select bone as secondary implantation site. The molecular bases for this property, defined as osteotropism, is still largely unknown. The recent demonstration that human breast cancer cells express and attach to bone sialoprotein (BSP), a sulfated phosphoprotein rich in bone and other mineralized tissues, could provide a clue to elucidating bone metastases formation. BSP contains the integrin binding peptide Arg-Gly-Asp (RGD), as well as non-RGD cell attachment domain. Using an immunoperoxidase technique and a specific polyclonal antibody directed against a BSP synthetic peptide, we examined the expression of BSP in 48 lung lesions including 25 squamous carcinoma, 21 adenocarcinoma, and 2 bronchioloalveolar cancers, as well as 38 human ovarian carcinoma that constitute a group of generally nonosteotropic cancers. BSP was not specifically detected in normal lung tissue with the exception of cartilage associated with bronchi. Most of the adenocarcinoma (74%) and all squamous carcinoma of the lung examined exhibited detectable levels of BSP. Staining was mainly cytoplasmic and membrane associated. The two bronchioloalveolar lung cancers examined did not show detectable amounts of BSP. When microcalcifications were observed in pulmonary malignant lesions, they were usually associated with cancer cells expressing BSP. Only 21% of the ovarian cancers examined contained malignant cells with 2+ or 3+ positivity for BSP. We further demonstrated that in 8 of 10 additional lung cancers, BSP was detected at the mRNA level. Our observation is the first demonstration that BSP is expressed in non-small cell lung carcinoma. Lung cancer cells are now the second type of osteotropic malignant cells described to express BSP. Added to the observation that BSP expression is not frequent in ovarian carcinoma, a low osteotropic cancer, our study supports our hypothesis that BSP could play a role in determining the affinity of cancer cells to bone. C1 UNIV LIEGE,METASTASIS RES LAB,TOUR PATHOL 1,B-4000 LIEGE,BELGIUM. NIDR,NIH,BETHESDA,MD 20892. INST TUMORI,MILAN,ITALY. RI Tagliabue, Elda/B-9377-2017 OI Tagliabue, Elda/0000-0001-9877-2903 NR 29 TC 55 Z9 57 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD SEP PY 1997 VL 61 IS 3 BP 183 EP 188 DI 10.1007/s002239900320 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XR504 UT WOS:A1997XR50400003 PM 9262507 ER PT J AU Medeiros, LJ Jones, EC Aizawa, S Aldape, HC Cheville, JC Goldstein, NS Lubensky, IA Ro, J Shanks, J Pacelli, A Jung, SH AF Medeiros, LJ Jones, EC Aizawa, S Aldape, HC Cheville, JC Goldstein, NS Lubensky, IA Ro, J Shanks, J Pacelli, A Jung, SH TI Grading of renal cell carcinoma - Workgroup no 2 SO CANCER LA English DT Article; Proceedings Paper CT 1997 Workshop on Diagnosis and Prognosis of Renal Cell Carcinoma CY MAR 21-22, 1997 CL ROCHESTER, MN C1 VANCOUVER HOSP & HLTH SCI CTR,VANCOUVER,BC V5Z 1M9,CANADA. JIKEI UNIV,SCH MED,TOKYO,JAPAN. NW HOSP,SEATTLE,WA. MAYO CLIN,ROCHESTER,MN. WILLIAM BEAUMONT HOSP,ROYAL OAK,MI 48072. NCI,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. RP Medeiros, LJ (reprint author), CITY HOPE NATL MED CTR,DIV PATHOL,1500 E DUARTE RD,DUARTE,CA 91010, USA. NR 0 TC 82 Z9 85 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1997 VL 80 IS 5 BP 990 EP 991 DI 10.1002/(SICI)1097-0142(19970901)80:5<990::AID-CNCR25>3.0.CO;2-Q PG 2 WC Oncology SC Oncology GA XR860 UT WOS:A1997XR86000025 PM 9307204 ER PT J AU Srigley, JR Hutter, RVP Gelb, AB Henson, DE Kenney, G King, BF Raziuddin, S Pisansky, TM AF Srigley, JR Hutter, RVP Gelb, AB Henson, DE Kenney, G King, BF Raziuddin, S Pisansky, TM TI Current prognostic factors - Renal cell carcinoma - Workgroup no 4 SO CANCER LA English DT Article; Proceedings Paper CT 1997 Workshop on Diagnosis and Prognosis of Renal Cell Carcinoma CY MAR 21-22, 1997 CL ROCHESTER, MN ID MORPHOLOGIC PARAMETERS; SURVIVAL; STAGE; CLASSIFICATION; STRATIFICATION; CANCER; TUMOR; NODES C1 ST BARNABAS HOSP,LIVINGSTON,NJ. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NCI,BETHESDA,MD 20892. PACIFIC NW CANC FDN,SEATTLE,WA. MAYO CLIN,ROCHESTER,MN. KING FAISAL SPECIALIST HOSP & RES CTR,RIYADH 11211,SAUDI ARABIA. RP Srigley, JR (reprint author), CREDIT VALLEY HOSP,2200 EGLINTON AVE W,MISSISSAUGA,ON L5M 2N1,CANADA. NR 29 TC 66 Z9 68 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1997 VL 80 IS 5 BP 994 EP 996 DI 10.1002/(SICI)1097-0142(19970901)80:5<994::AID-CNCR27>3.0.CO;2-Q PG 3 WC Oncology SC Oncology GA XR860 UT WOS:A1997XR86000027 PM 9307206 ER PT J AU Hanash, KA Aquilina, JW Barrett, DM Blute, ML Cockett, ATK Corica, FA Hillman, GG Zbar, B Zhuang, ZP AF Hanash, KA Aquilina, JW Barrett, DM Blute, ML Cockett, ATK Corica, FA Hillman, GG Zbar, B Zhuang, ZP TI Clinical research priorities in renal cell carcinoma - Renal cell carcinoma chemoprevention strategies including target populations, proposed agents, and clinical trial designs - Workgroup no 6 SO CANCER LA English DT Article; Proceedings Paper CT 1997 Workshop on Diagnosis and Prognosis of Renal Cell Carcinoma CY MAR 21-22, 1997 CL ROCHESTER, MN ID CANCER; IDENTIFICATION; INTERLEUKIN-2; THERAPY; GENE C1 MAYO CLIN, ROCHESTER, MN USA. UNIV ROCHESTER, STRONG MEM HOSP, ROCHESTER, NY 14642 USA. NCI, FREDERICK, MD 21701 USA. NCI, BETHESDA, MD 20892 USA. RP Hanash, KA (reprint author), KING FAISAL SPECIALIST HOSP & RES CTR, DEPT UROL, MBC 83, POB 3354, RIYADH 11211, SAUDI ARABIA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 1997 VL 80 IS 5 BP 999 EP 1001 DI 10.1002/(SICI)1097-0142(19970901)80:5<999::AID-CNCR29>3.0.CO;2-Q PG 3 WC Oncology SC Oncology GA XR860 UT WOS:A1997XR86000029 PM 9307208 ER PT J AU Schatzkin, A AF Schatzkin, A TI Dietary change as a strategy for preventing cancer SO CANCER AND METASTASIS REVIEWS LA English DT Review DE malignant neoplasm; neoplasm-lung; breast; prostate; colorectum; epidemiology; clinical trials; diet; nutrition; susceptibility genes ID LARGE-BOWEL CANCER; IOWA WOMENS HEALTH; BREAST-CANCER; COLON-CANCER; BETA-CAROTENE; COLORECTAL-CANCER; CARDIOVASCULAR-DISEASE; ANTIOXIDANT VITAMINS; HETEROCYCLIC AMINES; PLASMA CAROTENOIDS AB The idea that dietary change can alter risk of malignant disease arose historically from animal experiments and observations of human cancer rates. Diet and cancer hypotheses correspond to one of two conceptual approaches to 'diet': 1) the decomposition approach, focusing on specific nutrients and other chemical constituents of food; and 2) the integrative approach, emphasizing the action of whole foods or food patterns (cuisines). Four types of scientific investigation are available for advancing our understanding of diet and cancer: animal experiments, human metabolic (clinical nutrition) studies, observational epidemiologic studies, and randomized, controlled trials (intervention studies). Each of these study types has its strengths and limitations. Observational epidemiologic studies and trials have the advantage of examining explicit cancer end points in humans. Positive findings from large, randomized dietary intervention studies would be particularly compelling. Results from animal and metabolic research, however, can complement findings from epidemiologic studies and trials. Considerable attention is now being paid to the joint action of dietary factors and 'susceptibility' genes. Finally, the author considers the extent to which dietary change can be considered a realistic strategy for preventing major cancers - those of the lung, breast, prostate, and colorectum. C1 NCI, Bethesda, MD 20892 USA. RP Schatzkin, A (reprint author), NCI, 9000 Rockville Pike,EPN 211, Bethesda, MD 20892 USA. NR 89 TC 8 Z9 9 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD SEP-DEC PY 1997 VL 16 IS 3-4 BP 377 EP 392 DI 10.1023/A:1005812514155 PG 16 WC Oncology SC Oncology GA YL635 UT WOS:000070976200009 PM 9433646 ER PT J AU Taylor, PR Albanes, D Tangrea, JA AF Taylor, PR Albanes, D Tangrea, JA TI To supplement or not to supplement, that is the question SO CANCER CAUSES & CONTROL LA English DT Editorial Material ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; BETA-CAROTENE; CARDIOVASCULAR-DISEASE; CANCER PREVENTION; ESOPHAGEAL; LINXIAN; CHINA; VEGETABLES; CARCINOMA RP Taylor, PR (reprint author), NCI,CANC PREVENT STUDIES BRANCH,ROCKVILLE,MD, USA. RI Albanes, Demetrius/B-9749-2015 NR 13 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1997 VL 8 IS 5 BP 685 EP 687 DI 10.1023/A:1018452026110 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XX825 UT WOS:A1997XX82500001 PM 9328189 ER PT J AU Potischman, N Swanson, CA Coates, RJ Weiss, HA Brogan, DR Stanford, JL Schoenberg, JB Gammon, MD Brinton, LA AF Potischman, N Swanson, CA Coates, RJ Weiss, HA Brogan, DR Stanford, JL Schoenberg, JB Gammon, MD Brinton, LA TI Dietary relationships with early onset (under age 45) breast cancer in a case-control study in the United States: influence of chemotherapy treatment SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; chemotherapy; diet; United States; women ID ADJUVANT CHEMOTHERAPY; WEIGHT-GAIN; WOMEN; RISK; TAMOXIFEN; FAT; QUESTIONNAIRE; MORTALITY AB Methodologic investigations have addressed selection and recall bias in case-control studies of diet and breast cancer, whereas the effect of disease progression and medical treatment on estimates of dietary intake has been largely overlooked. In a multicenter, population-based case-control study of breast cancer in the United States, 1,588 newly diagnosed cases and 1,451 controls completed a self-administered food-frequency questionnaire. Initial evaluation suggested increased risk related to high intakes of calories, carbohydrates, fat, and protein. All nutrient associations were diminished after adjustment for calories. Evaluation by stage of disease revealed no relation of calories to risk among women with in situ disease, but elevated risks among women with localized (odds ratio [OR] = 1.33, 95 percent confidence interval [CI] = 1.0-1.7 highest cf lowest quartile) or regional and distant disease (OR = 1.79, CI = 13-2.4). Further evaluation showed that the increased risk associated with calories was restricted to cases who reported having been treated with chemotherapy (OR = 1.66, CI = 1.3-2.1). A gradient of increasing risk with time interval from diagnosis to interview suggested the chemotherapy regimen itself and not necessarily characteristics of tumors requiring this treatment was responsible for the observed increased risk. These results indicate that epidemiologic studies of diet and breast cancer, particularly among young women, should evaluate possible bias related to post-diagnosis influences. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. CTR DIS CONTROL,DIV CANC PREVENT & CONTROL,ATLANTA,GA 30333. EMORY UNIV,ROLLINS SCH PUBL HLTH,ATLANTA,GA 30322. UTAH CANC REGISTRY,SALT LAKE CITY,UT. NEW JERSEY DEPT HLTH & SENIOR SERV,TRENTON,NJ. COLUMBIA SCH PUBL HLTH,NEW YORK,NY. RP Potischman, N (reprint author), NCI,NUTR EPIDEMIOL BRANCH,EPN 430,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 33 TC 30 Z9 30 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1997 VL 8 IS 5 BP 713 EP 721 DI 10.1023/A:1018475203820 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XX825 UT WOS:A1997XX82500005 PM 9328193 ER PT J AU Dosemeci, M Gokmen, I Unsal, H Hayes, RB Blair, A AF Dosemeci, M Gokmen, I Unsal, H Hayes, RB Blair, A TI Tobacco, alcohol use, and risks of laryngeal and lung cancer by subsite and histologic type in Turkey SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; histologic type; laryngeal cancer; lung cancer; men; smoking; Turkey ID SQUAMOUS-CELL CARCINOMA; CIGARETTE-SMOKING; OCCUPATIONAL FACTORS; ORAL CAVITY; ETIOLOGY; PHARYNX; CHINA; CONSUMPTION; ASBESTOS; MALES AB Effects of tobacco smoking and alcohol use on risks of cancers of the larynx and lung have been evaluated extensively in industrialized countries, Few studies on the effect of these risk factors have been reported from developing countries. We conducted a case-control study to evaluate risks of laryngeal and lung cancers in men by subsite and cell type in relation to smoking and alcohol drinking in Turkey, a country where smoking and alcohol consumption patterns are different from those in industrialized countries. We identified 832 laryngeal and 1,210 lung cancer cases and 829 controls with information on smoking and alcohol use (amount and duration) and histologic cell type from an oncology treatment center of a Social Security Agency hospital in Istanbul, Turkey, admitted between 1979 and 1984. Both laryngeal and lung cancer showed significant associations with smoking and alcohol drinking, but no monotonic dose-response was obtained for alcohol drinking. Among smokers, the highest risks were observed in the supraglottis region of the larynx (odds ratio COR] = 4.1) after adjustment for age and alcohol use. Among alcohol drinkers, the highest risks were observed in the glottis region of the larynx (OR = 1.7) after adjustment for age and smoking, In the analysis by the cell type of lung cancer among ever-smokers, small cell type showed the highest risk (OR = 5.4), while it showed no association with alcohol drinking. Cumulative cigarette use (pack-years) and number of cigarettes per day showed stronger associations than years smoked for both cancer sites. The relative risks of joint exposure to smoking and alcohol were 12.2 for laryngeal cancer and 14.1 for lung cancer among heavy smokers and heavy alcohol drinkers. This study provides epidemiologic evidence from Turkey that smoking and alcohol use are associated with risks of cancers of the larynx and lung. C1 MIDDLE E TECH UNIV, FAC ARTS & SCI, DEPT CHEM, TR-06531 ANKARA, TURKEY. SOCIAL SECUR AGCY HOSP, ONCOL CLIN, ISTANBUL, TURKEY. RP Dosemeci, M (reprint author), NCI, DIV CANC EPIDEMIOL & GENET, OCCUPAT EPIDEMIOL BRANCH, EXECUT PLAZA N, ROOM 418, ROCKVILLE, MD 20892 USA. NR 63 TC 67 Z9 67 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1997 VL 8 IS 5 BP 729 EP 737 DI 10.1023/A:1018479304728 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XX825 UT WOS:A1997XX82500007 PM 9328195 ER PT J AU Freedman, DM Cantor, KP Lee, NL Chen, LS Lei, HH Ruhl, CE Wang, SS AF Freedman, DM Cantor, KP Lee, NL Chen, LS Lei, HH Ruhl, CE Wang, SS TI Bladder cancer and drinking water: a population-based case-control study in Washington County, Maryland (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE bladder cancer; chlorine; United States; water supply ID CHLORINATION BY-PRODUCTS; CIGARETTE-SMOKING; MORTALITY; EPIDEMIOLOGY; RATES; RISK AB A population-based case-control study was conducted in Washington County Maryland (United States) to explore the association between incident bladder cancer and exposure to drinking water from chlorinated surface sources. Cancer cases were White residents, enumerated in a 1975 county census and reported to the Washington County Cancer Registry (n = 294) between 1975 and 1992. White controls, frequency matched by age (+/-5 years) and gender, were selected randomly from the census (n = 2,326). Households receiving municipal water, which generally derived from chlorinated surface waters, were treated as having 'high exposure' and all others, as 'low exposure.' Duration of exposure to type of drinking water was based on length of residence in the census household prior to 1975. Odds ratios (OR) were calculated using logistic regression methods, adjusting for age, gender, tobacco use, and urbanicity. Bladder cancer risk was associated weakly in the general population with duration of exposure to municipal water The association was limited to those who had smoked cigarettes. In ever-smokers compared with never-smokers with low exposure, the adjusted ORs for bladder cancer risk with increasing exposure were 1.3, 1.4, 1.4, 1.7, 2.2, 2.8, respectively, for 0, 1-10, 11-20, 21-30, 31-40, > 40 years' exposure duration. The ORs in smokers were not diminished after adjusting for smoking history and intensity. C1 JOHNS HOPKINS SCH HYG & PUBL HLTH,BALTIMORE,MD. RP Freedman, DM (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EPN 418,6130 EXECUT BLVD MSC 7332,BETHESDA,MD 20892, USA. NR 40 TC 36 Z9 36 U1 1 U2 5 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1997 VL 8 IS 5 BP 738 EP 744 DI 10.1023/A:1018431421567 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XX825 UT WOS:A1997XX82500008 PM 9328196 ER PT J AU Herman, EH Zhang, J Hasinoff, BB Chadwick, DP Clark, JR Ferrans, VJ AF Herman, EH Zhang, J Hasinoff, BB Chadwick, DP Clark, JR Ferrans, VJ TI Comparison of the protective effects against chronic doxorubicin cardiotoxicity and the rates of iron (III) displacement reactions of ICRF-187 and other bisdiketopiperazines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE doxorubicin cardiotoxicity; iron((III)) displacement; bisdiketopiperazines ID SPONTANEOUSLY HYPERTENSIVE RATS; SYRIAN GOLDEN-HAMSTERS; DNA TOPOISOMERASE-II; BIS(2,6-DIOXOPIPERAZINE) DERIVATIVES; HYDROLYSIS; (+)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE; DEXRAZOXANE; COMPLEXES; REDUCTION; TOXICITY AB Histologic and biochemical studies were carried out to compare the protective activity of various bisdiketopiperazines against the cardiac and renal toxicity induced by doxorubicin in spontaneously hypertensive rats (SHR), a well-established animal model of this disorder, with: (1) the rates of hydrolysis of these agents to form the iron-chelating derivatives (which are considered to cause a decrease in the formation of reactive oxygen intermediates) and (2) the ability of these derivatives to bind iron. SHR were given 12 weekly injections of doxorubicin. 1 mg/kg i.v, either alone or 30 min after the administration of ICRF-154, ICRF-187. ICRF-192. ICRF-197. ICRF-198. ICRF-239 and ADR-559. Semiquantitative grading of the severity of the resulting cardiac and renal lesions showed that ICRF-187. ICRF-154 and ADR-559 were the most protective, whereas lCRF-197 and ICRF-339 provided intermediate degrees of protection, and ICRF-192 and ICRF-198 were not protective. Quantitative measurements in vitro revealed only relatively small differences in the rates of opening of the two diketopiperazine rings of the various agents to form the corresponding iron-chelating diacid diamide derivatives. and in the ability of these various derivatives to remove iron from the iron-doxorubicin complex. Such differences showed no relationship with cardioprotective activity. Some bisdiketopiperazines (including ICRF-154 and ICRF-187) with cardioprotective activity also are inhibitors of DNA topoisomerase II: however. the significance of this relationship remains uncertain, since ADR-925, the open-ring derivative of ICRF-187, does not inhibit DNA topoisomerase II. C1 UNIV MANITOBA,FAC PHARM,WINNIPEG,MB R3T 2N2,CANADA. NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. RP Herman, EH (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING HFD 910,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 35 TC 23 Z9 23 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1997 VL 40 IS 5 BP 400 EP 408 DI 10.1007/s002800050677 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XQ320 UT WOS:A1997XQ32000005 PM 9272116 ER PT J AU Hoki, Y Fujimori, A Pommier, Y AF Hoki, Y Fujimori, A Pommier, Y TI Differential cytotoxicity of clinically important camptothecin derivatives in P-glycoprotein overexpressing cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE topoisomerase I; camptothecin; multidrug resistance; P-glycoprotein(MDR); cancer chemotherapy ID DNA TOPOISOMERASE-I; CROSS-RESISTANCE; INHIBITORS; CANCER; CPT-11; TOPOTECAN; ANALOGS; IDENTIFICATION; ESTABLISHMENT; DETERMINANTS AB Camptothecin and its derivatives are specific inhibitors of eukaryotic topoisomerase I (top1) and are active in cancer patients against a variety of refractory solid tumors and leukemia. Purpose: The present study further investigated the relationship between multidrug resistance (MDR) mediated by P-glycoprotein(MDR) and potential resistance to camptothecin derivatives using two experimental systems: (1) MDR KB-V1 cells selected for vinblastine resistance, and (2) NIH3T3 cells transfected with a plasmid expressing wildtype P-glycoprotein(MDR) multidrug transporter (NIH-MDR-G185). Results: We found that both KBV-1 and NIH-MDR-G185 cells were resistant to topotecan, and that topotecan-induced cleavable complexes were reduced in KB-V1 cells, consistent with a role of P-glycoprotein(MDR) in cellular resistance to topotecan. By contrast, no significant resistance to camptothecin, 9-aminocamptothecin, 10, 11-methylenedioxycamptothecin, or SN-38 (the active metabolite of CPT-I1) was observed in NIH-MDR-G185 cells, while KB-V1 cells were cross-resistant to these compounds but produced cleavable complexes similar to those produced by parental KB-3-1 cells. Conclusions: These results suggest that topotecan is the only camptothecin tested with significant susceptibility to MDR in cell culture, and that multidrug resistant cells such as KBV1 probably exhibit additional resistance mechanisms to camptothecins besides P-glycoprotein(MDR) overexpression. C1 NIH,MOL PHARMACOL LAB,BETHESDA,MD 20892. NCI,DIV BASIC SCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 48 TC 53 Z9 53 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1997 VL 40 IS 5 BP 433 EP 438 DI 10.1007/s002800050682 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XQ320 UT WOS:A1997XQ32000010 PM 9272121 ER PT J AU Walther, W Stein, U Fichtner, I Naundorf, H Alexander, M Shoemaker, RH Schlag, PM AF Walther, W Stein, U Fichtner, I Naundorf, H Alexander, M Shoemaker, RH Schlag, PM TI In vivo evaluation of a drug-inducible vector system for the combined gene- and chemotherapy of cancer SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 MAX DELBRUCK CTR MOL MED,D-13122 BERLIN,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,LDDRD,FREDERICK,MD 21702. FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,ROBERT ROSSLE KLIN,D-13122 BERLIN,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP-OCT PY 1997 VL 4 IS 5 BP 305 EP 306 PG 2 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YA978 UT WOS:A1997YA97800040 ER PT J AU Stein, U Walther, W Shoemaker, RH Schlag, PM AF Stein, U Walther, W Shoemaker, RH Schlag, PM TI IL-2 gene transfer for chemosensitization of multidrug resistant human colon carcinoma cells SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 MAX DELBRUCK CTR MOL MED,D-13122 BERLIN,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,LDDRD,FREDERICK,MD 21702. FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,ROBERT ROSSLE KLIN,D-13122 BERLIN,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP-OCT PY 1997 VL 4 IS 5 BP 306 EP 306 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YA978 UT WOS:A1997YA97800042 ER PT J AU Loimas, S Wahlfors, J Janne, J AF Loimas, S Wahlfors, J Janne, J TI Thymidine kinase - Green fluorescent protein fusion gene; a versatile tool for gene transfer studies SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 UNIV KUOPIO,AI VIRTANEN INST,FIN-70211 KUOPIO,FINLAND. NIH,CLIN GENE THERAPY BRANCH,NCHGR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP-OCT PY 1997 VL 4 IS 5 BP 327 EP 327 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YA978 UT WOS:A1997YA97800120 ER PT J AU ColonOtero, G Marschke, R Camoriano, JK Sorensen, JM Sloan, JA Richardson, RL AF ColonOtero, G Marschke, R Camoriano, JK Sorensen, JM Sloan, JA Richardson, RL TI A dose-seeking trial of edatrexate in combination with vinblastine, adriamycin, cisplatin, and filgrastim (EVAC/G-CSF) in patients with advanced malignancies: Promising antineoplastic activity against non-small cell lung carcinomas SO CANCER JOURNAL LA English DT Article DE edatrexate; non-small cell lung carcinoma; phase I trial ID PHASE-II; CANCER; 10-ETHYL-10-DEAZA-AMINOPTERIN; CHEMOTHERAPY AB PURPOSE To determine the maximum tolerated dose, toxicities, and potential antitumor activity of edatrexate (E), an antifolate agent with enhanced in vitro antitumor activity as compared with methotrexate (M), when given in combination with vinblastine, doxorubicin, cisplatin, and filgrastim (G-CSF) to patients with advanced malignancies. PATIENTS AND METHODS Thirty-seven patients with advanced malignancies were treated with escalating doses of edatrexate in combination with vinblastine (V), doxorubicin (A), cisplatin (C), and filgrastim (EVAC/G-CSF) following three different subsequently developed schedules. Schedule 1 was patterned after the MVAC regimen, a combination chemotherapy program with activity against different epithelial malignancies, and consisted of E, 40 mg/m(2)/day, days 1/15/22; V,3 mg/m(2)/day, days 2/15/22; A, 30 mg/m(2)/day, day 2; C, 70 mg/m(2)/day, day 2; repeated every 28 days. Schedules 2 and 3 were designed to avoid observed dose-limiting toxicity on schedule 1 consisting of transient elevation of serum creatinine levels and delayed myelosuppression. Schedule 2 consisted of E, 40 or 60 mg/m(2)/day, days 1 and 15; V, 3 mg/m(2)/day, days 2 and 15; A, 30 mg/m(2)/day, day 2; C, 30 mg/m(2)/day, days 1 and 2; cycled every 28 days. Schedule 3 consisted of E, 60) to 120 mg/m(2)/day, day 1; V, 3 mg/m(2)/day, day 2; A, 30 mg/m(2)/day, day 2; C, 30 mg/m(2)/day, days 1 and 2; cycled every 21 days. Filgrastim 5 mu g/kg/day was given to all patients subcutaneously until the absolute neutrophil count was greater than 10,000/mu L postnadir. Three patients were treated on schedule 1, 10 on schedule 2 (four at an E dose of 40 mg/m(2)/day and six at an E dose of 60 mg/m(2)/day), and 24 on schedule 3 (six at each of the following E dosages: 60, 80, 100, and 120 mg/m(2)/day). RESULTS Dose-limiting toxicities of grade 3 to 4 leukopenia and transient elevation of serum creatinine values were observed in two of three patients treated on schedule 1. A dose-limiting toxicity of grade 3 to 4 leukopenia was noted. in two of six patients treated on schedule 2 at an edatrexate dose of 60 mg/m(2)/day. Two of six patients treated on schedule 3 at an edatrexate dose of 120 mg/m(2)/day had a dose-limiting toxicity of grade 3 stomatitis (one patient) and grade 3 cytopenia (one patient). Nineteen of 37 patients with evaluable or measurable disease had a response to treatment (response rate 51%, 95% confidence intervals = 35%-67%). Nine of 15 patients with metastatic non-small cell lung cancer responded, including one complete remission (response rate 60%, confidence intervals = 35%-85%). A median survival of 517 days (confidence interval = 163-808 days) and a 1-year survival rate of 60% (confidence interval = 35%-85%) was seen in patients with advanced non-small cell lung cancer. CONCLUSIONS The maximum tolerated dose and the recommended phase II dose of edatrexate is 100 mg/m(2)/day when administered as part of the EVAC/G-CSF program following schedule 3. Promising antineoplastic activity against non-small cell lung carcinomas was observed, and a phase II study is planned. C1 MAYO CLIN & MAYO FDN, SCOTTSDALE, AZ USA. NCI, CANC TREATMENT & EVALUAT PROGRAM, BETHESDA, MD 20892 USA. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. RP ColonOtero, G (reprint author), MAYO CLIN JACKSONVILLE, DIV HEMATOL ONCOL, 4500 SAN PABLO RD, JACKSONVILLE, FL 32224 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 1997 VL 3 IS 5 BP 297 EP 302 PG 6 WC Oncology SC Oncology GA XX755 UT WOS:A1997XX75500010 PM 9327154 ER PT J AU DeanClower, E Vortmeyer, AO Bonner, RF EmmertBuck, M Zhuang, ZP Liotta, LA AF DeanClower, E Vortmeyer, AO Bonner, RF EmmertBuck, M Zhuang, ZP Liotta, LA TI Microdissection-based genetic discovery and analysis applied to cancer progression SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; POLYMERASE CHAIN-REACTION; VONHIPPEL-LINDAU DISEASE; ALLELIC LOSS; CHROMOSOME 8P12-21; RENAL PATHOLOGY; HETEROZYGOSITY; CARCINOMAS; TISSUE C1 NICHHD,NIH,BETHESDA,MD. NATL CTR RES RESOURCES,NIH,BETHESDA,MD. RP DeanClower, E (reprint author), NCI,PATHOL LAB,DIV CLIN SCI,BLDG 31,ROOM 10A10,31 CTR DR-MCS 2580,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 34 TC 10 Z9 10 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD SEP-OCT PY 1997 VL 3 IS 5 BP 259 EP 265 PG 7 WC Oncology SC Oncology GA XX755 UT WOS:A1997XX75500002 PM 9327146 ER PT J AU Yarchoan, R Little, R AF Yarchoan, R Little, R TI Optimizing combination chemotherapy for Kaposi's sarcoma SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; RANDOMIZED TRIAL; DOXORUBICIN; BLEOMYCIN; VINBLASTINE; VINCRISTINE; REPLICATION; INTERFERON; CYTOKINES RP Yarchoan, R (reprint author), NCI,HIV & AIDS MALIGNANCY BRANCH,DIV CLIN SCI,NIH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD SEP-OCT PY 1997 VL 3 IS 5 BP 268 EP 270 PG 3 WC Oncology SC Oncology GA XX755 UT WOS:A1997XX75500004 PM 9327148 ER PT J AU Lee, CO AF Lee, CO TI Quality of life and breast cancer survivors - Psychosocial and treatment issues SO CANCER PRACTICE LA English DT Article DE breast cancer; cancer survival; psychosocial considerations; quality of life; social support ID SOCIAL SUPPORT; OF-LIFE; WOMEN; MASTECTOMY; ADJUSTMENT AB PURPOSE: This study aas conducted to determine the relationship between social support, extent of breast cancer surgery, length of time since surgery, geographic location, and overall quality of life (QOL) in breast cancer survivors, Additionally, the motivational factors for survivors to volunteer in a community rehabilitation program were assessed. DESCRIPTIONS OF STUDY: A convenience sample of 134 survivors who had undergone mastectomies were invited to participate, Study packets including an information letter, a demographic sheet, and Ferrans and Powers Quality of Life-Cancer Version questionnaire were mailed. The return of completed forms was considered consent. RESULTS: The sample (N = 100) consisted mostly of married women (75%) who had surgery a mean of 14 years previously. Findings indicated that there is no correlation between marital status and the number or type of support persons and overall QOL. Interestingly, unmarried women were found to have a better perceived QOL than married women, although the difference was not statistically significant. There was no significant difference between extent of surgery, length of time since surgery, and geographic location with overall QOL. Thematic analysis of motivation to volunteer revealed an under-lying theme of helping with sharing knowledge/providing information and giving emotional support for all age groups. Other themes were personal gain; giving back to the program, others, and God; and assisting others in avoiding a negative experience. CLINICAL IMPLICATIONS: Quality of life is a dynamic, multifaceted process through which perceptions, viewpoints, and behaviors change as a result of the various experiences throughout the survival period. These findings demonstrate that social support plays a vital role in promoting overall QOL in breast cancer survivors. The development of supportive behaviors by healthcare providers and Reach for Recovery volunteers is essential in providing this social support for breast cancer survivors. Growth in understanding and relieving the psychological stress that new cancer survivors endure is an area that warrants particular attention. Additionally, these participants indicated their need and willingness to share their experiences. Support is needed to provide survivors with the opportunity to function as volunteers. Program developers and evaluators must work together to ensure this support on a consistent basis. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Lee, CO (reprint author), Rt 1,Box 94-14, Shenandoah Jct, WV 25442 USA. NR 37 TC 40 Z9 40 U1 0 U2 5 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD SEP-OCT PY 1997 VL 5 IS 5 BP 309 EP 316 PG 8 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA ZG092 UT WOS:000072964800007 PM 9341354 ER PT J AU Rao, CV Wang, CX Simi, B Lubet, R Kelloff, G Steele, V Reddy, BS AF Rao, CV Wang, CX Simi, B Lubet, R Kelloff, G Steele, V Reddy, BS TI Enhancement of experimental colon cancer by genistein SO CANCER RESEARCH LA English DT Article ID SUPPRESSES MAMMARY-CANCER; OXIDATIVE DNA-DAMAGE; MALE F344 RATS; CHEMOPREVENTIVE AGENTS; SIGNAL TRANSDUCTION; COLORECTAL-CANCER; TOPOISOMERASE-II; NIH-3T3 CELLS; CARCINOGENESIS; AZOXYMETHANE AB Several phytochemicals and micronutrients that are present in fruits and vegetables are known to exert cancer chemopreventive effects in several organs, including the colon. Among them, the soybean isoflavonoid genistein received much attention due to its potential anticarcinogenic, antiproliferative effects and its potential role in several signal transduction pathways. The present study was designed to investigate the effect of genistein on azoxymethane (AOM)-induced colon carcinogenesis and to study its modulatory role on the levels of activity of 8-isoprostane, cyclooxygenase (COX), and 15-hydroxyprostaglandin F-2 alpha dehydrogenase (15-PGDH) in the colonic mucosa and colon tumors of male F344 rats. At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A) diet or a diet containing 250 ppm genistein. Beginning 2 weeks later, all animals except those in the vehicle-treated groups were given weekly s.c. injections of AOM (15 mg/kg body weight) for 2 successive weeks. All rats were continued on their respective dietary regimen for 52 weeks after AOM treatment and were then sacrificed. Colon tumors mere evaluated histopathologically. Colonic mucosae and tumors were analyzed for COX, 15-PGDH, and 8-isoprostane levels. Administration of genistein significantly increased noninvasive and total adenocarcinoma multiplicity (P < 0.01) in the colon, compared to the control diet, but it had no effect on the colon adenocarcinoma incidence nor on the multiplicity of invasive adenocarcinoma (P > 0.05). Also, genistein significantly inhibited the 15-PGDH activity (>35%) and levels of 8-iosoprostane (50%) in colonic mucosa and in tumors. In contrast, genistein had no significant effect on the COX synthetic activity, as measured by the rate of formation of prostaglandins and thromboxane B-2 from [C-14]arachidonic acid. The results of this investigation emphasize that the biological effects of genistein mag be organ specific, inhibiting cancer development in some sites get showing no effect or an enhancing effect on the tumorigenesis at other sites, such as the colon. The inhibition of 8-isoprostane levels by genistein indicates its possible antioxidant potential, which is independent of the observed colon tumor enhancement, Set this agent may also possess several biological effects that overshadow its antioxidant potential. The exact mechanism(s) of colon tumor enhancement by genistein remain to be elucidated; it is likely that its colon tumor-enhancing effects map, at least in part, be related to inhibition of prostaglandin catabolic enzyme activities. C1 AMER HLTH FDN, DIV PATHOL, VALHALLA, NY 10595 USA. NATL CANC INST, DIV CANC PREVENT & CONTROL, CHEMOPREVENT BRANCH, BETHESDA, MD 20892 USA. RP Rao, CV (reprint author), AMER HLTH FDN, DIV NUTR CARCINOGENESIS, 1 DANA RD, VALHALLA, NY 10595 USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CA17613, N01CN-25450-01] NR 48 TC 152 Z9 164 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1997 VL 57 IS 17 BP 3717 EP 3722 PG 6 WC Oncology SC Oncology GA XU396 UT WOS:A1997XU39600020 PM 9288778 ER PT J AU LopezCarrillo, L Blair, A LopezCervantes, M Cebrian, M Rueda, C Reyes, R Mohar, A Bravo, J AF LopezCarrillo, L Blair, A LopezCervantes, M Cebrian, M Rueda, C Reyes, R Mohar, A Bravo, J TI Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: A case-control study from Mexico SO CANCER RESEARCH LA English DT Article ID ASIAN WOMEN; RESIDUES; ORGANOCHLORINES; WHITE; BLACK AB Some, but not all, epidemiological studies have suggested that dichlorodiphenyltrichloroethane (DDT) may play a role in the development of breast cancer. These investigations have been conducted in countries where this substance has been banned for at least 20 years. We conducted a study in Mexico, a country in which DDT is still being used to control malaria. In a hospital-based case-control study, we compared 141 histologically confirmed cases of breast cancer with 141 age-matched controls (+/-3 years). All subjects were identified at three referral hospitals of Mexico City between March 1994 and April 1996. Reproductive histories and other variables were obtained by structured interviews, DDT/DDE levels were determined in serum by gas-liquid chromatography. The arithmetic mean of serum DDE in lipid basis was 562.48 +/- 676.18 ppb (range, 10.24-4661.44) for the cases and 505.46 +/- 567.22 ppb (range, 0.004 to 4361.75) for the controls, but this difference was not statistically significant. The age-adjusted odds ratios for breast cancer regarding the serum level of DDE were 0.69 (95% confidence interval, 0.38-1.24) and 0.97 (confidence interval, 0.55-1.70) for the contrasts between tertile 1 (lowest level) and tertiles 2 and 3, respectively. These estimates were unaffected by adjustment for body mass, accumulated time of breastfeeding and menopause, and other breast cancer risk factors. These results do not lend support to the hypothesis that DDT is causally related to breast cancer at the body-burden levels found in our study population but do not exclude the possibility that higher levels of exposure could still play a role in the etiology of this tumor. C1 JOHN D & CATHERINE T MACARTHUR FDN,MEXICO CITY,DF,MEXICO. NATL CANC INST,OCCUPAT EPIDEMIOL BRANCH,NIH,ROCKVILLE,MD 20892. NATL POLYTECH INST,CTR RES & ADV STUDIES,MEXICO CITY,DF,MEXICO. MEXICO SECRETARIAT HLTH,NATL CANC INST,MEXICO CITY,DF,MEXICO. RP LopezCarrillo, L (reprint author), MEXICO SECRETARIAT HLTH,NATL PUBL HLTH INST,AVENIDA UNIV 655,CP 62508,CUERNAVACA,MORELOS,MEXICO. NR 14 TC 127 Z9 130 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1997 VL 57 IS 17 BP 3728 EP 3732 PG 5 WC Oncology SC Oncology GA XU396 UT WOS:A1997XU39600022 PM 9288780 ER PT J AU Devereux, TR Anna, CH Patel, AC White, CM Festing, MFW You, M AF Devereux, TR Anna, CH Patel, AC White, CM Festing, MFW You, M TI Smad4 (homolog of human DPC4) and Smad2 (homolog of human JV18-1): candidates for murine lung tumor resistance and suppressor genes SO CARCINOGENESIS LA English DT Article ID FREQUENT ALLELIC LOSSES; IN-VIVO ALTERATIONS; HOMOZYGOUS DELETIONS; MOUSE CHROMOSOME-18; COLORECTAL-CANCER; RAS ACTIVATION; SUSCEPTIBILITY; CELL; MICE; MUTATIONS AB In this study we investigated the mouse mad-related genes, Smad4/Dpc4 and Smad2 (homolog of JV18-1), as candidates for involvement in lung tumor resistance and suppression, These genes are located in a region of mouse chromosome 18 that is syntenic with human 18q21.1, where several genes that are mutated in various cancers have been mapped. A newly identified murine lung tumor resistance locus, Par2 has also been mapped to this region of chromosome 18, We found no mutations in the coding regions of either gene in 11 lung tumors from B6CF1 (C57BL/6xBALB/c) mice by RT-PCR and SSCP/RFLP, suggesting that these genes are not mutated in lung carcinogenesis in this strain, Moreover, loss of heterozygosity in this region of chromosome 18 was not detected in 28 lung adenocarcinomas from B6CF1 mice, 17 lung adenocarcinomas from B6C3F1 mice or 18 lung adenocarcinomas from AB6F1 mice, These data provide evidence that a 'classical' tumor suppressor gene for mouse lung carcinogenesis in these strains does not reside in this region, In order to investigate Smad4/Dpc4 and Smad2 as candidates for the Par2 resistance locus mapped to this region, we also sequenced the coding regions of both genes in cDNA from normal lungs of A/J, BALB/c and C57BL/6 inbred strains of mice, No polymorphisms were detected in the coding region of Smad4. In Smad2, two sequence polymorphisms were identified that are not in the conserved regions of the gene, Northern blot analysis revealed no differential expression in normal lung tissue among the three strains for either gene, Thus, in this study we found no evidence that either Smad4 or Smad2 represents the Par2 lung tumor resistance locus or is a lung tumor suppressor gene in the B6CF1 mice. C1 UNIV LEICESTER,MRC,TOXICOL UNIT,LEICESTER LE1 9HN,LEICS,ENGLAND. MED COLL OHIO,TOLEDO,OH 43614. RP Devereux, TR (reprint author), NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 19 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1997 VL 18 IS 9 BP 1751 EP 1755 DI 10.1093/carcin/18.9.1751 PG 5 WC Oncology SC Oncology GA XX926 UT WOS:A1997XX92600010 PM 9328171 ER PT J AU Diwan, BA Kasprzak, KS Anderson, LM AF Diwan, BA Kasprzak, KS Anderson, LM TI Promotion of dimethylbenz[a]anthracene-initiated mammary carcinogenesis by iron in female Sprague-Dawley rats SO CARCINOGENESIS LA English DT Article ID CELL-SURFACE GLYCOPROTEIN; BREAST-CANCER; DIETARY IRON; TRANSFERRIN; RISK; RECEPTOR; PROLIFERATION; DEFEROXAMINE; RADICALS; EXCESS AB Iron body-stores and iron dietary intake have been sporadically reported to increase the risk of cancer in humans, To investigate the effect of iron on the development of mammary tumors, female Sprague-Dawley rats were given dimethylbenz[a]anthracene (DMBA) (5 mg/kg, i.g., 1x) at 55 days of age. Eight days later, rats received iron(II) sulfate s.c. (50 mu mol/kg, 2 x /week) for 53 weeks. Mammary tumors started to appear 6-8 weeks after DMBA initiation, At 20 weeks after DMBA treatment, iron(II) increased mammary tumor frequency twofold (11/30 versus 5/30 with DMBA alone), Tumor frequency increased with time and was significantly higher in iron-promoted rats after 40 weeks of treatment (24/30 versus 11/30, P = 0.001), Also, mammary tumors in iron-promoted rats were significantly larger than in DMBA-only rats at 20 weeks after initiation (P = 0.04) and this difference remained significant through the observation time point at 40 weeks, Iron could be detected histochemically in the stromal connective tissue, but not in the epithelial cells of mammary carcinomas, Mammary tumors in the DMBA-only group were mostly adenomas and adenocarcinomas, while those promoted by iron sulfate included fibroadenomas, adenomas and adenocarcinomas. Thus, iron(II) administered s.c. subsequent to DMBA initiation, greatly accelerated mammary carcinogenesis, implying its promoting activity for mammary tissue of female rats. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Diwan, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702, USA. NR 46 TC 30 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1997 VL 18 IS 9 BP 1757 EP 1762 DI 10.1093/carcin/18.9.1757 PG 6 WC Oncology SC Oncology GA XX926 UT WOS:A1997XX92600011 PM 9328172 ER PT J AU Porter, DW Yakushiji, H Nakabeppu, Y Sekiguchi, M Fivash, MJ Kasprzak, KS AF Porter, DW Yakushiji, H Nakabeppu, Y Sekiguchi, M Fivash, MJ Kasprzak, KS TI Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II) SO CARCINOGENESIS LA English DT Article ID GENERATES G.C->T.A TRANSVERSIONS; C-G TRANSVERSION; DNA-BASE DAMAGE; MUTAGENIC SUBSTRATE; HUMAN-CELLS; NUCLEOSIDE TRIPHOSPHATASE; MOLECULAR-CLONING; TERNARY COMPLEXES; MUTATOR LOCUS; A-T AB The toxicity of Ni(II), Co(II) and Cu(II) in animals, and that of Cd(II) in cultured cells, has been associated with generation of the promutagenic lesion 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA, among other effects. One possible source of this base may be 8-oxo-7,8-dihydro-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool, from which it is incorporated into DNA. To promote such incorporation, the metals would have to inhibit specific cellular 8-oxo-dGTPases that eliminate 8-oxo-dGTP from the nucleotide pool. The present study was designed to test such inhibition in vitro on 8-oxo-dGTPases from two different species, the human MTH1 protein and Escherichia coli MutT protein. In the presence of Mg(II), the natural activator of 8-oxo-dGTPases, all four metals were found to inhibit both enzymes. For MTH1, the IC50 values (+/- SE; n = 3-4) were 17 +/- 2 mu M for Cu(II), 30 +/- 8 mu M for Cd(II), 376 +/- 71 mu M for Co(II) and 801 +/- 97 mu M for Ni(II). For MutT, they were 60 +/- 6 mu M for Cd(II), 102 +/- 8 mu M for Cu(II), 1461 +/- 96 mu M for Ni(II) and 8788 +/- 1003 mu M for Co(II). Thus, Cu(II) and Cd(II) emerged as much stronger inhibitors than Ni(II) and Co(II), and MTH1 appeared to be generally more sensitive to metal inhibition than MutT. Interestingly, in the absence of Mg(II), the activity of the enzymes could be restored by Co(II) to 73% of that with Mg(II) alone for MutT, and 34% for MTH1, the other metals being much less or non-effective. The difference in sensitivity to metal inhibition between the two enzymes may reflect the differences in the amino acid ligands, especially the cysteine ligand, outside their evolutionarily conserved Mg(II)-binding active sites, which might indicate predominantly non-competitive or uncompetitive mechanism of the inhibition. The overall results suggest that inhibition of 8-oxo-dGTPases may be involved in the mechanisms of induction of the 8-oxoguanine lesion in DNA by the metal ions studied, especially the non-redoxactive Cd(II) cation. C1 NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. KYUSHU UNIV 69, DEPT BIOCHEM, MED INST BIOREGULAT, HIGASHI KU, FUKUOKA 81282, JAPAN. FUKUOKA DENT COLL, DEPT BIOL, FUKUOKA 81401, JAPAN. NCI, FREDERICK CANC RES & DEV CTR, DATA MANAGEMENT SERV INC, FREDERICK, MD 21702 USA. RI Nakabeppu, Yusaku/A-8902-2011 NR 64 TC 30 Z9 34 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1997 VL 18 IS 9 BP 1785 EP 1791 DI 10.1093/carcin/18.9.1785 PG 7 WC Oncology SC Oncology GA XX926 UT WOS:A1997XX92600015 PM 9328176 ER PT J AU Melillo, G Scoccianti, M Kovesdi, I Safi, J Riccioni, T Capogrossi, MC AF Melillo, G Scoccianti, M Kovesdi, I Safi, J Riccioni, T Capogrossi, MC TI Gene therapy for collateral vessel development SO CARDIOVASCULAR RESEARCH LA English DT Review DE gene therapy; angiogenesis; ischemia; FGF; VEGF; heparin; adenovirus ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; RECOMBINANT ADENOVIRUS VECTORS; MOLECULAR-WEIGHT HEPARIN; ANGIOGENESIS IN-VIVO; FACTOR MESSENGER-RNA; FACTOR FAMILY; BLOOD-FLOW; CELL-LINE; SIGNAL-TRANSDUCTION AB Transfer of the cDNA coding for angiogenic factors represents a novel and promising approach to induce therapeutic angiogenesis and enhance blood flow to ischemic tissues which cannot be revascularized otherwise. This review will focus on therapeutic angiogenesis based on gene transfer techniques for the treatment of myocardial and limb ischemia. The experimental studies demonstrating the angiogenic effect of recombinant growth factors in animal models and in humans, as well as the most promising methods for gene transfer, will be described. Further, gene transfer studies to induce therapeutic angiogenesis will be reviewed to identify critical questions that still need to be answered before gene therapy with angiogenic factors may be considered for routine clinical application. (C) 1997 Elsevier Science B.V. C1 IST DERMOPAT IMMACOLATA,LAB PATOL VASCOLARE,I-00167 ROME,ITALY. GENVEC INC,ROCKVILLE,MD. NIA,GENE THERAPY UNIT,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. RI Melillo, Guido/K-6341-2016 OI Melillo, Guido/0000-0002-2379-9471 NR 135 TC 27 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP PY 1997 VL 35 IS 3 BP 480 EP 489 DI 10.1016/S0008-6363(97)00167-3 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YD940 UT WOS:A1997YD94000011 PM 9415292 ER PT J AU Zhang, ZH Poirier, MC AF Zhang, ZH Poirier, MC TI Cisplatin-DNA adduct determination in the hepatic albumin gene as compared to whole genomic DNA SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID REPAIR; DAMAGE; CELLS; OVARIAN; CANCER; CIS-DIAMMINEDICHLOROPLATINUM(II); QUANTITATION AB A quantitative time-resolved fluorometric PCR-stop assay has been used to determine cisplatin-DNA adducts in a 1.612 kb region and a polymorphic 1.85 kb region of the rat liver albumin gene containing parts of exons B and C and all of the BC intron. The values were compared to adducts in the whole rat liver genome determined by atomic absorbance spectrometry(AAS). Initial validation of the PCR-stop assay involved modification of purified rat liver DNA in vitro to desired levels by incubation with different concentrations of cisplatin. In these DNA samples, cisplatin-DNA adduct levels determined in the 1612 base pair fragment by PCR-stop assay were shown to be similar to those determined in the whole genomic DNA by AAS. In freshly isolated primary rat hepatocytes cultured for 2 h with 50, 75, 100, and 150 mu M cisplatin, adduct levels determined by the PCR-stop assay were similar to those measured by AAS. Cultured MH1C1 rat hepatoma cells, which express albumin, had a polymorphism in the rat albumin gene such that the fragment amplified with the same primers was about 1.85 kb (13% larger). When MH1C1 cells were exposed to 5, 15, 25, 50, and 75 mu M cisplatin for 24 h, 50% cell kill was at 21.0 +/- 5.5 mu M cisplatin. For doses of 15-75 mu M cisplatin, the cisplatin-DNA adduct levels in this fragment, measured by PCR-stop assay, were about one-half of those in the whole genomic DNA measured by AAS. In addition, MH1C1 cells exposed to 150 mu M cisplatin for 4 h and subsequently incubated with fresh medium for 24 h showed no change in adduct level in whole genomic DNA during this time but showed a 29% adduct removal in the 1.85 kb fragment. The data demonstrate that this 1.85 kb region containing expressed regions of the albumin gene has undergone both less adduction and more rapid adduct removal, as compared to the MH1C1 genome as a whole. RP Zhang, ZH (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BLDG 37,RM 3B12,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 21 TC 7 Z9 7 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 1997 VL 10 IS 9 BP 971 EP 977 DI 10.1021/tx970051i PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA XW897 UT WOS:A1997XW89700006 PM 9305578 ER PT J AU Smolich, JJ Cox, HS Berger, PJ Walker, AM Eisenhofer, G Eisler, MD AF Smolich, JJ Cox, HS Berger, PJ Walker, AM Eisenhofer, G Eisler, MD TI Left ventricular norepinephrine and epinephrine kinetics at birth in lambs SO CIRCULATION RESEARCH LA English DT Article DE fetus; newborn; norepinephrine; epinephrine; spillover ID CATECHOLAMINE-CONTAINING CELLS; GUINEA-PIG HEART; SYMPATHETIC INNERVATION; CHEMICAL SYMPATHECTOMY; FETAL; BLOOD; NORADRENALINE; CIRCULATION; EXTRACTION; RESPONSES AB Little is known about the changes in the left ventricular (LV) kinetics of the catecholamines norepinephrine and epinephrine occurring at birth and their relationship to perinatal alterations in LV function and whole-body catecholamine kinetics. To address this issue, whole-body and LV catecholamine kinetics (radiotracer dilution methodology) and fetal LV output and myocardial blood flow (radioactive microspheres) were measured in chronically instrumented near-term fetuses and in the same animals 1 and 4 hours after birth. Between fetal and 1-hour lambs, LV external work increased 115% (P<.005); carotid arterial plasma norepinephrine concentration, 148% (P<.01); carotid arterial plasma epinephrine concentration, 546% (P<.005); LV norepinephrine spillover, a measure of LV sympathetic activity, 4.1-fold (P<.005); LV epinephrine spillover, 3-fold (P<.05); total-body spillover of norepinephrine, 52% (P<.025); and total-body spillover of epinephrine, 460% (P<.005). Arterial catecholamine concentrations and total-body catecholamine spillovers were unchanged between 1- and 4-hour lambs, but LV external work fell (P<.05) to a level still 77% greater than in fetal lambs (P<.005); LV norepinephrine spillover returned to near-fetal levels, and LV epinephrine spillover became undetectable. These results suggest that (1) a transient increase in LV sympathetic activity occurs at birth and may contribute to the immediate postnatal augmentation of LV performance, (2) organ differences in the pattern of sympathetic activation occur at birth, and (3) birth-related increases in LV sympathetic activity are accompanied by release of epinephrine from the heart. C1 BAKER MED RES INST, PRAHRAN, VIC 3181, AUSTRALIA. NINCDS, CLIN NEUROSCI BRANCH, NIH, BETHESDA, MD 20892 USA. RP Smolich, JJ (reprint author), MONASH UNIV, MONASH MED CTR, INST REPROD & DEV, LEVEL 5, 246 CLAYTON RD, CLAYTON, VIC 3168, AUSTRALIA. NR 53 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD SEP PY 1997 VL 81 IS 3 BP 438 EP 447 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA XT851 UT WOS:A1997XT85100018 PM 9285646 ER PT J AU Beaty, TH Maestri, NE Hetmanski, JB Wyszynski, DF Vanderkolk, CA Simpson, JC McIntosh, I Smith, EA Zeiger, JS Raymond, GV Panny, SR Tifft, CJ Lewanda, AF Cristion, CA Wulfsberg, EA AF Beaty, TH Maestri, NE Hetmanski, JB Wyszynski, DF Vanderkolk, CA Simpson, JC McIntosh, I Smith, EA Zeiger, JS Raymond, GV Panny, SR Tifft, CJ Lewanda, AF Cristion, CA Wulfsberg, EA TI Testing for interaction between maternal smoking and TGFA genotype among oral cleft cases born in Maryland 1992-1996 SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article DE birth defects; cleft lip; cleft palate; gene-environment interaction; smoking; TGFA ID GROWTH-FACTOR-ALPHA; GENE-ENVIRONMENT INTERACTION; CIGARETTE-SMOKING; PALATE; LIP; ASSOCIATION; LOCUS; POPULATION; PREGNANCY; POLYMORPHISM AB Objective: Infants born in Maryland between June 1992 and June 1996 were used in a case-control study of nonsyndromic oral clefts to test for effects of maternal smoking and a polymorphic genetic marker at the transforming growth factor alpha (TGFA) locus, both of which have been reported to be risk factors for these common birth defects. Design and Setting: Cases were infants with an oral cleft ascertained through three comprehensive treatment centers, with additional ascertainment through a registry of birth defects maintained by the Maryland Hearth Department. Controls were healthy infants. Medical history information on infants and mothers were collected, along with DNA samples. Patients, Participants: Among 286 cases contacted (72% ascertainment), there were 192 nonsyndromic isolated oral clefts (Ins M; 86 F) available for this case-control study. Main Outcome Measures: The largest group of 149 Caucasian nonsyndromic cases and 86 controls was used to test for association with maternal smoking and genotype at the Taq1 polymorphism in TGFA. Results: While this modest sample had limited statistical power to detect gene-environment interaction, there was a significant marginal increase in risk of having an oral cleft if the mother smoked (odds ratio = 1.75, 95%Cl = 1.01 to 3.02). We could not demonstrate statistical interaction between maternal smoking and TGFA genotype in this study, however, and the observed increase in the C2 allele among cases was not statistically significant. Conclusions:We could not confirm either the reported association between oral clefts and TGFA genotype or its interaction with maternal smoking. However, these data do show an increased risk if the mother smoked during pregnancy, and this effect was greatest among infants with a bilateral cleft and no close family history of clefts. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,KENNEDY KRIEGER INST,BALTIMORE,MD 21205. MARYLAND DEPT HLTH & MENTAL HYG,BALTIMORE,MD. CHILDRENS NATL MED CTR,DEPT MED GENET,WASHINGTON,DC 20010. UNIV MARYLAND,DIV HUMAN GENET,BALTIMORE,MD 21201. NIH,NATL HUMAN GENOME RES INST,MED GENET BRANCH,BETHESDA,MD 20892. RP Beaty, TH (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NIDCR NIH HHS [R01-DE-10293] NR 34 TC 59 Z9 65 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD SEP PY 1997 VL 34 IS 5 BP 447 EP 454 DI 10.1597/1545-1569(1997)034<0447:TFIBMS>2.3.CO;2 PG 8 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA YB085 UT WOS:A1997YB08500015 PM 9345615 ER PT J AU Eastman, RC AF Eastman, RC TI Is intensive glycemic control worth the expense? SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article RP Eastman, RC (reprint author), NIDDKD,NIH,DIV DIABET ENDOCRINOL & METAB DIS,BLDG 31 RM 9A16,31 CTR DR MSC 2560,BETHESDA,MD 20892, USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD SEP PY 1997 VL 64 IS 8 BP 410 EP 413 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XV561 UT WOS:A1997XV56100003 PM 9308216 ER PT J AU Ghedin, E Zhang, WW Charest, H Sundar, S Kenney, RT Matlashewski, G AF Ghedin, E Zhang, WW Charest, H Sundar, S Kenney, RT Matlashewski, G TI Antibody response against a Leishmania donovani amastigote-stage-specific protein in patients with visceral leishmaniasis SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID INDIAN KALA-AZAR; MONOCLONAL-ANTIBODIES; SERODIAGNOSIS; IDENTIFICATION; PURIFICATION; EXPRESSION; INFECTION; ANTIGEN; CHAGASI; TROPICA AB The antibody response against an amastigote-specific protein (A2) from Leishmania donovani was investigated. Sera from patients with trypanosomiasis and various forms of leishmaniasis were screened for anti-A2 antibodies, Sera from patients infected only with L. donovani or Leishmania mexicana specifically recognized the A2 recombinant protein, These results were consistent with karyotype analyses which revealed that the A2 gene is conserved in L. donovani and L. mexicana strains. The potential of this antigen in diagnosis was further explored by screening a series of sera obtained from patients in regions of the Sudan and India where L. donovani is endemic, The prevalence of anti-A2 antibodies was determined by Western blotting for all samples. Enzyme-linked immunosorbent assay (ELISA) and an immunoprecipitation assay were also performed on some of the samples. Anti-A2 antibodies were detected bg ELISA in 82 and 60% of the samples from individuals with active visceral leishmaniasis (kala-azar) from the Sudan and India, respectively, while the immunoprecipitation assay defected the antibodies in 92% of the samples from India, These data suggest that the A2 protein mag be a useful diagnostic antigen for visceral leishmaniasis. C1 MCGILL UNIV,INST PARASITOL,ST ANNE BELLEVUE,PQ H9X 3V9,CANADA. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. BANARAS HINDU UNIV,INST MED SCI,VARANASI 221005,UTTAR PRADESH,INDIA. US FDA,ROCKVILLE,MD 20852. NR 23 TC 56 Z9 57 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 1997 VL 4 IS 5 BP 530 EP 535 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XU923 UT WOS:A1997XU92300007 PM 9302200 ER PT J AU Holden, JP Chou, G Stanhope, SJ AF Holden, JP Chou, G Stanhope, SJ TI Changes in knee joint function over a wide range of walking speeds SO CLINICAL BIOMECHANICS LA English DT Article DE gait; walking; kinematics; kinetics; speed; knee; moment; power ID GROUND REACTION FORCES; HUMAN GAIT; LOWER-LIMB; PATTERNS; PARAMETERS; ARTHROPLASTY AB Objective. Changes in patterns of knee joint flexion-extension rotations, moments and powers were investigated during the stance phase across a wide range of walking speeds that includes the very slow speeds used by many patients referred for gait analysis. Design. Each subject walked at 25, 50, 75, 100, and 125% of a scaled natural speed of 0.785 statures.s(-1). Background. The results of earlier studies suggest that control subjects, as they walk at progressively slower speeds, increasingly use a large internal knee flexor moment in the early stance phase. Methods. Eighteen healthy adult subjects (nine male and nine female) were tested. Results. The shapes of the mean patterns were similar for the three fastest, most natural walking speeds. At the two slowest speeds, however, subjects used little knee flexion and small knee moments through mid-stance, resulting in negligible joint power through the first 80% of the stance phase. At these speeds, most subjects had moment patterns that could not be classified with confidence as 'normal' or as predominantly flexor or extensor. Only four subjects had knee flexor moment patterns at the slowest speeds, and these included much smaller flexor moments in the early stance phase than in some previous reports. C1 NIAMSD,BETHESDA,MD 20892. PENN COLL PODIAT MED,PHILADELPHIA,PA 19107. WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,BETHESDA,MD. NIH,BIOMECH LAB,BETHESDA,MD 20892. NR 48 TC 36 Z9 36 U1 2 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD SEP PY 1997 VL 12 IS 6 BP 375 EP 382 DI 10.1016/S0268-0033(97)00020-X PG 8 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA YG757 UT WOS:A1997YG75700003 ER PT J AU Macey, DJ Grant, EJ Kasi, L Rosenblum, MG Zhang, HZ Katz, RL Rieger, PT LeBherz, D South, M Greiner, JW Schlom, J Podoloff, DA Murray, JL AF Macey, DJ Grant, EJ Kasi, L Rosenblum, MG Zhang, HZ Katz, RL Rieger, PT LeBherz, D South, M Greiner, JW Schlom, J Podoloff, DA Murray, JL TI Effect of recombinant alpha-interferon on pharmacokinetics, biodistribution, toxicity, and efficacy of I-131-labeled monoclonal antibody CC49 in breast cancer: A phase II trial SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-ASSOCIATED GLYCOPROTEIN-72; HUMAN-MELANOMA CELLS; CARCINOEMBRYONIC ANTIGEN; GAMMA-INTERFERON; RADIOIMMUNOTHERAPY TRIAL; ENHANCES EXPRESSION; COLORECTAL-CANCER; LEUKOCYTE ALPHA; COLON-CARCINOMA; BONE-MARROW AB Preclinical studies have demonstrated that recombinant IFN-alpha (rIFN-alpha) can enhance the tumor associated glycoprotein 72 (TAG-72) on tumors, To determine whether rIFN-alpha could enhance TAG-72 expression iii vivo in patients, 15 women with breast cancer were randomized to receive daily injections of rIFN-alpha (3 x 10(6) units/m(2) for 13 days) beginning on day 1 (group I = 7 patients) or on day 6 (group 2 = 8 patients), On day 3, all patients received a 10-20-mCi tracer dose of I-131-CC49, a high-affinity murine monoclonal antibody reactive against TAG-72, followed by a therapy dose of 60-75 mCi/m(2) of I-131-CC49 on day 6. Whole body and single-photon emission computed tomography scans along with whole blood pharmacokinetics were performed following tracer and treatment phases, Hematological toxicity was considerable; reversible grade 3-4 neutropenia and thrombocytopenia was observed in 12 of 15 patients, Twelve of 14 patients tested developed human antimouse antibodies 3-6 weeks after treatment, For group 1 patients, whole blood residence time increased significantly between that predicted from the tracer doses and therapy doses (42.6 +/- 4.7 versus 51.5 +/- 4.8 h, respectively; P < 0.01). The calculated radiation absorbed dose to red marrow from therapy compared to tracer activity was also significantly higher for this group (1.25 +/- 0.35 versus 1.07 +/- 0.26 cGy/mCi; P < 0.05). Treatment with rIFN-alpha was found to enhance TAG-72 expression in tumors from patients receiving rIFN-alpha (group 1) by 46 +/- 19% (P < 0.05) compared to only 1.3 +/- 0.95% in patients not initially receiving IFN (group 2). The uptake of CC49 in tumors was also significantly increased in rIFN-alpha-treated patients, One partial and two minor tumor responses were seen, In summary, rIFN-alpha treatment altered the pharmacokinetics and tumor uptake of I-131-CC49 in patients at the expense of increased toxicity. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. NCI,BETHESDA,MD 20815. FU NCI NIH HHS [CM97610] NR 38 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1997 VL 3 IS 9 BP 1547 EP 1555 PG 9 WC Oncology SC Oncology GA XU660 UT WOS:A1997XU66000013 PM 9815842 ER PT J AU Gupta, M Fan, SJ Zhan, QM Kohn, KW OConnor, PM Pommier, Y AF Gupta, M Fan, SJ Zhan, QM Kohn, KW OConnor, PM Pommier, Y TI Inactivation of p53 increases the cytotoxicity of camptothecin in human colon HCT116 and breast MCF-7 cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA-DAMAGING AGENTS; WILD-TYPE P53; TOPOISOMERASE-I; GROWTH ARREST; STRAND BREAKS; SENSITIVITY; EXPRESSION; APOPTOSIS; FIBROBLASTS; CHECKPOINT AB Camptothecin (CPT) derivatives are topoisomerase I (top1) inhibitors recently introduced as clinical agents, To explore the role of p53 in CPT-induced cytotoxicity, me examined CPT effects in two isogenic pairs of human cancer cell lines, MCF-7 breast carcinoma and HCT116 colon carcinoma cells, in which p53 function had been disrupted by transfection with the human papillomavirus type-16 E6 gene. Clonogenic survival assays showed that both MCF-7/E6 and HCT116/E6 cells were more sensitive to CPT. No differences in top1 protein levels and activity analyzed by a novel in vitro oligonucleotide assay were observed in the E6 transfectants, Also, CPT showed comparable top1 cleavable complex formation in vivo, as determined by DNA single-strand breaks and DNA protein cross-links, These results suggest that p53 can protect against CPT-induced cytotoxicity and that this protection is mediated downstream of CPT-induced DNA damage, Flow cytometry analyses showed that CPT can induce G(1) arrest in cells with normal p53, This G(1) arrest was markedly reduced in the p53-deficient cells, These results demonstrate a critical role of p53 as a G(1) checkpoint regulator after CPT-induced DNA damage and suggest a rationale for the selectivity of CPT toward tumors with p53 mutations. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 43 TC 68 Z9 72 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1997 VL 3 IS 9 BP 1653 EP 1660 PG 8 WC Oncology SC Oncology GA XU660 UT WOS:A1997XU66000027 PM 9815856 ER PT J AU Rehak, NN Cecco, SA Niemela, JE Elin, RJ AF Rehak, NN Cecco, SA Niemela, JE Elin, RJ TI Thiocyanate in smokers interferes with the Nova magnesium ion-selective electrode SO CLINICAL CHEMISTRY LA English DT Article ID IONIZED MAGNESIUM; SERUM THIOCYANATE; SMOKING; ANALYZER; EXPOSURE; CALCIUM; AVL AB Thiocyanate found in serum ordinarily is the metabolite of cyanide that is inhaled with tobacco smoke and ingested with cyanogenic foods. We investigated the effect of the thiocyanate ion (SCN-) on the ionized magnesium (iMg) and ionized calcium (iCa) results determined with the AVL and Nova magnesium and calcium ion-selective electrodes (ISEs). We analyzed saline and pooled serum with added SCN-, and serum from apparently healthy nonsmokers (n = 20) and smokers (n = 20). The mean (and range) of the measured serum SCN- concentration was 0.019 (0.008-0.046) mmol/L for nonsmokers and 0.077 (0.020-0.138) mmol/L for smokers. Only the Nova iMg results decreased with increasing SCN- concentration, and the change was dependent on the baseline iMg concentration. In the absence of Mg, SCN- decreased the voltage response of the Nova Mg ISE to calcium ions. At apparently normal serum iMg and iCa concentrations, the interference by SCN- appeared to be equimolar (iMg = -1.04 x SCN- + 0.52). Thus, the serum SCN- commonly found in smokers causes a significant (P <0.0001) decrease in the Nova iMg results. RP Rehak, NN (reprint author), NIH,CLIN CHEM SERV,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,RM 2C-306,10 CTR DR,BETHESDA,MD 20892, USA. OI Niemela, Julie/0000-0003-4197-3792 NR 26 TC 24 Z9 24 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 1997 VL 43 IS 9 BP 1595 EP 1600 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XV897 UT WOS:A1997XV89700007 PM 9299939 ER PT J AU Chen, Z Smith, CW Kiel, D VanWaes, C AF Chen, Z Smith, CW Kiel, D VanWaes, C TI Metastastic variants derived following in vivo tumor progression of an in vitro transformed squamous cell carcinoma line acquire a differential growth advantage requiring tumor-host interaction SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE metastasis; squamous cell carcinoma; tumor progression ID ANTIGENS; TRANSFECTION; EXPRESSION; INHIBITION; MOUSE AB The purpose of this study was to develop an experimental model of squamous cell carcinoma that can be used to identify molecular and immunologic changes associated with primary events in malignant transformation, and those associated with metastatic tumor progression in the presence of host homeostatic and immunologic factors, Metastatic variants were derived following in vivo tumor progression of the in vitro transformed squamous cell carcinoma line Pam 212, The parental and metastatic cell lines exhibited similar morphologic features and molecular markers of an epithelial lineage, including an epithelial morphology in culture, cell surface expression of integrin alpha 6 beta 4, and expression of mRNA of cytokeratins K6 and K14, When the growth and metastatic phenotype of the parental and reisolate cell lines was compared, the reisolate cell lines were found to exhibit a greater rate of growth and incidence of metastasis than the parental cell line when reimplanted in vivo, The difference in the growth rate of the parental cell line and the variants observed in vivo was not detected when growth of these lines was compared in vitro, suggesting that the growth advantage and selection of these variants requires tumor-host interaction, The metastatic variants exhibited a similar growth advantage in normal immunocompetent and SCID Balb/c mice, indicating that the growth advantage in vivo is not due to T or B lymphocyte-dependent immune factor(s), We conclude that metastatic variants derived following in vivo tumor progression of an in vitro transformed squamous cell carcinoma line exhibit a differential growth advantage in vivo that requires the host environment, Comparison of these in vitro transformed and in vivo derived metastatic variant cell lines with phenotypic differences in growth and metastasis should prove useful for dissecting the role of tumor and host factor(s) in malignant transformation and metastatic tumor progression of squamous cell carcinoma. C1 NIDCD,TUMOR BIOL SECT,HEAD & NECK SURG BRANCH,NIH,BETHESDA,MD. FU NIDCD NIH HHS [Z01-DC-00016] NR 23 TC 30 Z9 31 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD SEP PY 1997 VL 15 IS 5 BP 527 EP 537 DI 10.1023/A:1018474910432 PG 11 WC Oncology SC Oncology GA XN251 UT WOS:A1997XN25100006 PM 9247255 ER PT J AU Letterio, JJ Roberts, AB AF Letterio, JJ Roberts, AB TI TGF-beta: A critical modulator of immune cell function SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; ORAL TOLERANCE; T-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSGENIC MICE; HOST-DEFENSE; FACTOR-BETA-1; PROGRESSION RP Letterio, JJ (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 61 TC 104 Z9 109 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD SEP PY 1997 VL 84 IS 3 BP 244 EP 250 DI 10.1006/clin.1997.4409 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA XV882 UT WOS:A1997XV88200002 PM 9281382 ER PT J AU Villano, SA Nelson, KE Vlahov, D Purcell, RH Saah, AJ Thomas, DL AF Villano, SA Nelson, KE Vlahov, D Purcell, RH Saah, AJ Thomas, DL TI Hepatitis A among homosexual men and injection drug users: More evidence for vaccination SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INFECTION AB As agencies develop guidelines for administering the newly developed hepatitis A virus (HAV) vaccine, information is needed regarding the occurrence of HAV infection in groups putatively at risk for the infection, We tested serum samples from 300 injection drug users (IDUs), 300 homosexual males, and 300 blood donors for the presence of total antibody to HAV (anti-HAV). Anti-HAV tvas detected in 66% of IDUs, 32% of homosexual males, and 14% of blood donors. Anti-HAV was not significantly associated (P > .10) with high-risk drug-using behaviors but was more prevalent among IDUs with annual incomes of <$5,000 (P = .018). The occurrence of anti-HAV increased among homosexual males as the number of sexual partners increased (P < .001) but was similar to the age-adjusted prevalence (30.6%) estimated for the general United States population. IDUs are at increased risk for HAV infection; however, our data suggest that factors related to low socioeconomic status contribute more to the occurrence of HAV infection among IDUs than does injection drug use, IDUs and persons at risk for injection drug use should receive HAV vaccine. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [U01-AI-35042]; NIDA NIH HHS [DA-04334, DA-05911] NR 14 TC 62 Z9 64 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1997 VL 25 IS 3 BP 726 EP 728 DI 10.1086/513757 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XW375 UT WOS:A1997XW37500028 PM 9314468 ER PT J AU Richters, JE AF Richters, JE TI Psychiatry's turbid solution SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE mental disorder; psychopathology; DSM-IV; treatment; psychiatry ID HARMFUL DYSFUNCTION; CONDUCT DISORDER; MENTAL DISORDER AB Psychiatry's generic concept of disorder has long served an important legitimizing function for the broad array of conditions for which individuals seek mental health treatment, regardless of their presumed causes. Wakefield's proposal to restrict the mental disorder concept to only a subset of these conditions has given rise to concerns about the uncertain consequences of classifying others as nondisorders. In Bergner's recent counter-proposal, this concern is masked in the form of a conspicuously overinclusive definition of mental disorder. Bergner's resistance to Wakefield's classification objective underscores an important, unmet, and often unacknowledged need within the clinical treatment community, The challenge ahead lies in finding ways to address this need without compromising the integrity of efforts to develop a more coherent concept of mental disorder. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. RP Richters, JE (reprint author), NIMH,5600 FISHERS LANE,ROOM 18C-17,ROCKVILLE,MD 20857, USA. OI Richters, John/0000-0002-6780-1828 NR 11 TC 3 Z9 3 U1 3 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD FAL PY 1997 VL 4 IS 3 BP 276 EP 280 PG 5 WC Psychology, Clinical SC Psychology GA YB768 UT WOS:A1997YB76800011 ER PT J AU Gotlib, IH Kurtzman, HS Blehar, MC AF Gotlib, IH Kurtzman, HS Blehar, MC TI The cognitive psychology of depression: Introduction to the special issue SO COGNITION & EMOTION LA English DT Editorial Material ID AFFECTIVE-DISORDERS C1 NIMH,BETHESDA,MD 20892. RP Gotlib, IH (reprint author), STANFORD UNIV,DEPT PSYCHOL,BLDG 420,JORDAN HALL,STANFORD,CA 94305, USA. NR 14 TC 1 Z9 1 U1 2 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PD SEP-NOV PY 1997 VL 11 IS 5-6 BP 497 EP 500 PG 4 WC Psychology, Experimental SC Psychology GA YG513 UT WOS:A1997YG51300001 ER PT J AU Gotlib, IH Kurtzman, HS Blehar, MC AF Gotlib, IH Kurtzman, HS Blehar, MC TI Cognition and depression: Issues and future directions SO COGNITION & EMOTION LA English DT Article ID FOLLOW-UP; MEMORY; PSYCHOPATHOLOGY; SYMPTOMATOLOGY; SPECIFICITY; PREDICTION; ADJUSTMENT; ATTITUDES; SYMPTOMS; PATTERNS AB As we noted in the Introduction, the papers in this Special Issue represent a wide range of approaches to examining the relation between cognition and depression. They also raise a number of important specific issues. In this epilogue, we will identify and discuss two major issues in some detail that were touched on by almost all of the papers in this Special Issue: the assessment of cognition in depression and the definition and assessment of vulnerability to depression. We will then offer some concluding comments concerning fruitful directions for future research and the need to integrate cognitive paradigms with more biological approaches to the study of depression. C1 NIMH,ROCKVILLE,MD 20857. RP Gotlib, IH (reprint author), STANFORD UNIV,DEPT PSYCHOL,BLDG 420,JORDAN HALL,STANFORD,CA 94305, USA. NR 45 TC 14 Z9 14 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PD SEP-NOV PY 1997 VL 11 IS 5-6 BP 663 EP 673 PG 11 WC Psychology, Experimental SC Psychology GA YG513 UT WOS:A1997YG51300010 ER PT J AU Slonim, AD Magnuson, WG Pollack, MM AF Slonim, AD Magnuson, WG Pollack, MM TI Lessons from international comparisons of pediatric critical care SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE pediatric critical care; severity-adjusted scoring systems; outcome; PRISM; mortality ID MORTALITY PRISM SCORE; INTENSIVE-CARE; RISK; UNIT; MULTICENTER; INFECTION C1 GEORGE WASHINGTON UNIV,SCH MED,CHILDRENS NATL MED CTR,WASHINGTON,DC. RP Slonim, AD (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1997 VL 25 IS 9 BP 1445 EP 1446 DI 10.1097/00003246-199709000-00001 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA XV557 UT WOS:A1997XV55700001 PM 9295808 ER PT J AU Susla, GM AF Susla, GM TI Weight-based heparin dosing: Maybe it's just a matter of time SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE heparin dosing, weight-based; thromboembolism; nomogram; pharmacokinetics ID NOMOGRAM RP Susla, GM (reprint author), NIH,CTR CLIN,DEPT PHARM,10 CTR DR,MSC 1196,BETHESDA,MD 20878, USA. NR 7 TC 0 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1997 VL 25 IS 9 BP 1451 EP 1452 DI 10.1097/00003246-199709000-00005 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA XV557 UT WOS:A1997XV55700005 PM 9295812 ER PT J AU Saavedra, C Felber, B Izaurralde, E AF Saavedra, C Felber, B Izaurralde, E TI The simian retrovirus-1 constitutive transport element, unlike the HIV-1 RRE, uses factors required for cellular mRNA export SO CURRENT BIOLOGY LA English DT Article ID PRE-MESSENGER-RNA; NUCLEAR-PROTEIN IMPORT; BINDING-PROTEIN; TYPE-1; CYTOPLASM; PATHWAY; COMPLEX; MUTANTS; SIGNAL; SNRNAS AB Background: A hallmark of retroviral gene expression is that unspliced retroviral genomic RNA is exported to the cytoplasm, whereas endogenous intron containing cellular RNAs are usually retained in the nucleus. In complex retroviruses, such as human immunodeficiency virus-1 (HIV-1), nuclear export is accomplished by the interaction of a virally encoded protein, Rev, with a cis-acting RNA element, the Rev-responsive element (RRE), In type D retroviruses, such as the simian retrovirus type 1 (SRV-1), however, genomic RNA is exported by cellular factor(s) that interact with a conserved cis-acting RNA element, the constitutive transport element (CTE), Results: We found that the CTE was exported in a specific and saturable fashion from Xenopus oocyte nuclei, When inserted into the intron of an adenovirus-derived pre-mRNA, the CTE did not affect splicing efficiency but promoted the nuclear export of the excised intron lariat that is normally retained within the nucleus, Export of CTE-containing RNAs to the cytoplasm was not affected by the heterogeneous nuclear ribonucleoprotein Al or an excess of peptides corresponding to the Rev nuclear export signal, Microinjection of saturating amounts of CTE RNA did not affect tRNA export or Rev-mediated export but did inhibit mRNA export, CTE-mediated export was found to be dependent on Ran-mediated GTP hydrolysis. Conclusion: The Rev-RRE system and the CTE direct intron-containing RNAs to distinct export pathways, Although previous data have suggested that Rev uses the same export pathway as uracil-rich small nuclear RNAs and 5S ribosomal RNA, the CTE seems to interact with evolutionarily conserved factors that are essential for cellular mRNA export. C1 UNIV GENEVA,DEPT MOL BIOL,CH-1211 GENEVA 4,SWITZERLAND. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. RI Izaurralde, Elisa/G-3239-2012; OI Izaurralde, Elisa/0000-0001-7365-2649 NR 49 TC 138 Z9 139 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 1 PY 1997 VL 7 IS 9 BP 619 EP 628 DI 10.1016/S0960-9822(06)00288-0 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XW889 UT WOS:A1997XW88900023 PM 9285715 ER PT J AU Imhof, A Yang, XJ Ogryzko, VV Nakatani, Y Wolffe, AP Ge, H AF Imhof, A Yang, XJ Ogryzko, VV Nakatani, Y Wolffe, AP Ge, H TI Acetylation of general transcription factors by histone acetyltransferases SO CURRENT BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; BASAL TRANSCRIPTION; NUCLEOSOMAL DNA; CHROMATIN; DOMAIN; TFIIH; H4 AB The acetylation of histones increases the accessibility of nucleosomal DNA to transcription factors [1,2], relieving transcriptional repression [3] and correlating with the potential for transcriptional activity in vivo [4-7]. The characterization of several novel histone acetyltransferases - including the human GCN5, homolog PCAF (p300/CBP-associated factor) [8], the transcription coactivator p300/CBP [9], and TAF(II)250 [in] - has provided a potential explanation for the relationship between histone acetylation and transcriptional activation, In addition to histones, however, other components of the basal transcription machinery might be acetylated by these enzymes and directly affect transcription, Here, we examine the acetylation of the basal transcriptional machinery for RNA polymerase II by PCAF, p300 and TAF(II)250, We find that all three acetyltransferases can direct the acetylation of TFIIE beta and TFIIF, and we identify a preferred site of acetylation in TFIIE beta. Human TFIIE consists of two subunits, alpha (p56) and beta (p34), which form a heterotetramer (alpha(2) beta(2)) in solution ([11], reviewed in [12]), TFIIE enters the preinitiation complex after RNA polymerase II and TFIIF, suggesting that TFIIE may interact directly with RNA polymerase II and/or TFIIF [13,14], In addition, TFIIE can facilitate promoter melting either in the presence or absence of TFIIH and can stimulate TFIIH dependent phosphorylation of the carboxy-terminal domain of RNA polymerase 11 [15-18]. TFIIF has an essential role in both transcription initiation and elongation ([19,20], for review see [21]). We discuss the implications of the acetylation of TFIIE beta and TFIIF for transcriptional control by PCAF, p300 and TAF(II)250. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. RI Ogryzko, Vasily/M-6665-2015; OI Ogryzko, Vasily/0000-0002-8548-1389; Imhof, Axel/0000-0003-2993-8249 NR 25 TC 495 Z9 500 U1 1 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 1 PY 1997 VL 7 IS 9 BP 689 EP 692 DI 10.1016/S0960-9822(06)00296-X PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XW889 UT WOS:A1997XW88900031 PM 9285713 ER PT J AU Bettelheim, FA Churchill, AC Zigler, JS AF Bettelheim, FA Churchill, AC Zigler, JS TI On the nature of hereditary cataract in strain 13/N guinea pigs SO CURRENT EYE RESEARCH LA English DT Article DE congenital cataract; guinea pig; hereditary cataract; hydration; light scattering; morphology ID ZETA-CRYSTALLIN; LENS; GENE; PROTEIN; NADPH AB Purpose. Congenital nuclear cataracts in strain 13/N guinea pigs are caused by a single splice-site mutation in the zeta-crystallin gene. Very little is known of the physical factors involved in lens opacification of this system. The aim of this study is to elucidate the biophysical processes causing the nuclear turbidity. Methods. Normal, homozygous and heterozygous mutant guinea pig lenses were studied. Polarized light scattering measurements were performed on thin sections of lenses as a function of scattering angle. Scattering intensities were collected in two modes, I'' and I+. The total water content of lenses was determined by thermogravimetric analysis. The nonfreezable (bound) water content was obtained by differential scanning calorimetry. The morphology of lenses was investigated by scanning electron microscopy. Results. Normal lenses scatter 5- to 10-fold less light than cataractous lenses at wide angles in both modes. The intensity ratios of the two modes imply that most of the scattering comes from density fluctuations; 10-20% of the turbidity may be contributed by orientation fluctuations. The nucleus of heterozygous cataractous lenses contain less total water than normal lenses, whereas the cortex has the same hydration as the normal lens. The nonfreezable water content of the cataractous nucleus is higher than that of the normal lens. Scanning electron microscopy showed frequent truncation of the fiber cells, cavitations and occasional longitudinal splitting resulting in hollow cylinder formation in the nucleus of the cataractous lens. Conclusion. Mutation of zeta-crystallin in guinea pigs causes a congenital cataract. A number of supramolecular events contribute to the turbidity. The mobile water leaves the nuclear fiber cells, causing a collapse of supramolecular structures. Both the size of the aggregates and their refractive index increase by this dehydration process, contributing to the turbidity. The truncation and hollowing of fiber cells causes the orientation fluctuations that also increase turbidity. C1 ADELPHI UNIV,DEPT BIOL,GARDEN CITY,NY 11530. NEI,NIH,BETHESDA,MD 20892. RP Bettelheim, FA (reprint author), ADELPHI UNIV,DEPT CHEM,GARDEN CITY,NY 11530, USA. FU NEI NIH HHS [EY-02571] NR 12 TC 10 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 1997 VL 16 IS 9 BP 917 EP 924 DI 10.1076/ceyr.16.9.917.5047 PG 8 WC Ophthalmology SC Ophthalmology GA XU017 UT WOS:A1997XU01700008 PM 9288453 ER PT J AU Burg, MB AF Burg, MB TI Renal osmoregulatory transport of compatible organic osmolytes SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID NA+/MYO-INOSITOL COTRANSPORTER; MESSENGER-RNA; RAT-KIDNEY; RAPID REGULATION; LOCALIZATION; MYOINOSITOL; TONICITY; TAURINE; CELLS; GENE AB Cells in renal medullas are exposed to a high concentration of salt during antidiuresis. They adapt in part by accumulating myo-inositol, glycine betaine, taurine, and other amino acids by transporting them from the interstitial fluid. This transport is osmotically regulated by changes in transcription of the transporters and by post-translational modifications. Most of the original studies were in vitro, but these processes are increasingly being examined in vivo. RP Burg, MB (reprint author), NHLBI,NIH,BLDG 10,ROOM 6N260,BETHESDA,MD 20892, USA. NR 38 TC 29 Z9 30 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 1997 VL 6 IS 5 BP 430 EP 433 DI 10.1097/00041552-199709000-00004 PG 4 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA XX756 UT WOS:A1997XX75600004 PM 9327200 ER PT J AU Kayama, F Yoshida, T Kodama, Y Matsui, T Matheson, JM Luster, MI AF Kayama, F Yoshida, T Kodama, Y Matsui, T Matheson, JM Luster, MI TI Pro-inflammatory cytokines and interleukin 6 in the renal response to bacterial endotoxin SO CYTOKINE LA English DT Article DE kidney cytokines; renal sepsis; urinary IL-6 ID TUMOR-NECROSIS-FACTOR; MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS; FACTOR-ALPHA; GENE-EXPRESSION; URINARY INTERLEUKIN-6; EPITHELIAL-CELLS; IGA NEPHROPATHY; DISEASE; IL-6; PATHOGENESIS AB Pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1 and IL-6 are thought to play important roles in the pathophysiology of chronic kidney disorders, including glomerulonephritis, In particular, IL-6 has received considerable attention as it appears at high concentrations to promote the progression of renal disease while at lower levels may be involved in regulating repair mechanisms, As such, cytokine profiles have been examined in the kidney by either examining secretion from isolated kidney cells or quantitating plasma and urinary levels in experimental models of glomerulonephritis. To examine the cytokine responses within the kidney, without the contribution of other organ systems, we used semi-quantitive polymerase chain reaction (RT-PCR) analysis and a recently developed kidney slice culture model from tissues of mice treated with combinations of endotoxin and neutralizing antibodies against TNF-alpha. The expression of IL-6, in addition to other pro-inflammatory cytokine genes, was increased by endotoxin treatment and reduced by pretreatment with neutralizing antibodies to TNF-alpha. Immunohistochemical staining revealed that IL-6 was expressed primarily in mesangial cells, Urinary IL-6 was also increased in endotoxin-treated mice and was inhibited by treatment with neutralizing TNF-alpha antibodies, Kinetics of the kidney-specific cytokine responses indicated that increase in TNF-alpha occurred initially, followed by IL-1 beta and finally IL-6, Furthermore, addition of TNF-alpha to glomerular mesangial cells induces IL-6 secretion, Taken together, these studies indicate that, like in the liver, a cytokine response occurs in the kidney from bacterial endotoxin and that TNF-alpha acts as a primary cytokine capable of stimulating additional cytokines, including IL-6. (C) 1997 Academic Press Limited. C1 NIOSH,HLTH EFFECTS LAB DIV,TOXICOL & MOL BIOL BRANCH,MORGANTOWN,WV 26505. NIEHS,RES TRIANGLE PK,NC 27709. UNIV OCCUPAT & ENVIRONM HLTH,DEPT MOL BIOL,KITAKYUSHU,FUKUOKA 807,JAPAN. UNIV OCCUPAT & ENVIRONM HLTH,DEPT ENVIRONM HLTH,KITAKYUSHU,FUKUOKA 807,JAPAN. TOKAI UNIV,SCH MED,DEPT ENVIRONM HLTH,ISCHERA,JAPAN. NR 31 TC 22 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 1997 VL 9 IS 9 BP 688 EP 695 DI 10.1006/cyto.1997.0214 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA XX046 UT WOS:A1997XX04600008 PM 9325018 ER PT J AU Gollop, R Kimmel, AR AF Gollop, R Kimmel, AR TI Control of cell-type specific gene expression in Dictyostelium by the general transcription factor GBF SO DEVELOPMENT LA English DT Article DE promoters; gene regulation; cAMP; receptors; development ID PRESPORE-SPECIFIC GENE; DROSOPHILA EMBRYO; CAMP; DISCOIDEUM; ELEMENT; DIFFERENTIATION; REPRESSION; SUFFICIENT; SEQUENCES; ENHANCER AB To understand how positional information within an organism specifies patterning during development, we are analyzing spatially regulated gene expression in Dictyostelium. CAR3 is a member of the cAMP, 7-span receptor family which directs the transition from unicellular to multicellular organism and regulates cellular differentiation and pattern formation. CAR3 mRNA is expressed maximally at 8-10 hours of development, as individual cells aggregate and differentiate, and is accumulated to equivalent levels in all cells. CAR3 is also induced in shaking cultures by response to extracellular cAMP. We now show, by extensive mutagenesis, that the maximum length of contiguous sequences required for accurate spatiotemporal regulation of CAR3 is approx, 350 bp. These sequences include three significant elements located in upstream and transcribed regions. Arrays of G-boxes (GBF regulatory sites) are centered near positions -165 and +50 and, although either is sufficient for induction by cAMP and expression in prespore cells, both are required for expression in prestalk cells. Another GC-rich element near position -80 is required for maximal expression of prespore-specific constructs, although full-length promoters carrying clustered mutations through the -80 region are still expressed in all cells, but with slightly reduced expression. Spatiotemporal expression of CAR3 during development, thus, requires cell-specific combinatorial interactions of multiple but redundant regulatory components. These essential elements are located in upstream and transcribed regions. However, most surprisingly, a primary control for spatial patterning of CAR3 expression appears to be mediated by GBF, a general transcription factor expressed ubiquitously during Dictyostelium development following early aggregation. C1 NIDDK,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 29 TC 13 Z9 13 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 1997 VL 124 IS 17 BP 3395 EP 3405 PG 11 WC Developmental Biology SC Developmental Biology GA XY460 UT WOS:A1997XY46000018 PM 9310334 ER PT J AU Post, RM Weiss, SRB AF Post, RM Weiss, SRB TI Emergent properties of neural systems: How focal molecular neurobiological alterations can affect behavior SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID CORTICOTROPIN-RELEASING FACTOR; AMYGDALA-KINDLED SEIZURES; POSTTRAUMATIC-STRESS-DISORDER; RECURRENT AFFECTIVE-DISORDER; TRINUCLEOTIDE REPEAT; HUNTINGTONS-DISEASE; RECOGNITION MEMORY; NONHUMAN-PRIMATES; PREFRONTAL CORTEX; NEURONAL-ACTIVITY AB Whereas the basic wiring diagram of the mammalian central nervous system (CNS) is genetically preprogramed, its fine tuning throughout different phases of infancy, childhood, and adulthood are highly experience dependent. The potential neurobiological mechanisms and behavioral effects of such experience-dependent neuroplasticity as a function of stage of development are outlined. A basic thesis of this paper is that mechanisms involved in neuronal learning and memory, such as long-term potentiation (LTP) and long-term depression (LTD), are used and reused not only in the sculpting of the CNS in the initial establishment of connections, but also again in the molding of personality and behavior based on experience. It is postulated that for higher order processes such as emotional memory, such neuroplasticity is occurring at increasingly larger numbers of synapses and cell assemblies with increasing mechanistic complexity and self-organization. Just as overexcitation or deprivation can profoundly affect the development of the visual system, it is postulated that similar phenomena exist in the neural substrates of emotional and cognitive development. In addition, a secondary and potentially more widespread series of ramifications are likely to occur in the higher order and integrative systems, such as secondary and tertiary cortical association areas and prefrontal cortex that become the ultimate integrators of emotion and experience, leading to subsequent actions and plans for the future. This process is, by definition, plastic, and such remodeling is likely to take place not only at the level of the single synapse, but also at higher levels of network integration of which we currently have only the barest glimpse. Nonetheless, beginning to discuss the neurobiology of such self-organizing plastic systems may begin to change our conceptual approaches to psychopathology and open new avenues of therapeutics for the major psychiatric illnesses that are critically dependent on such higher order learning and memory mechanisms. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 104 TC 36 Z9 38 U1 1 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 1997 VL 9 IS 4 BP 907 EP 929 PG 23 WC Psychology, Developmental SC Psychology GA YQ119 UT WOS:000071350400014 PM 9449011 ER PT J AU Louvi, A Accili, D Efstratiadis, A AF Louvi, A Accili, D Efstratiadis, A TI Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development SO DEVELOPMENTAL BIOLOGY LA English DT Article ID HOMOZYGOUS NONSENSE MUTATION; ENDOCRINE PANCREAS; DIABETES-MELLITUS; PERINATAL LETHALITY; CONGENITAL ABSENCE; POSTNATAL-GROWTH; CELL-POPULATIONS; FETAL GROWTH; NULL ALLELE; EFE PYGMIES AB Genetic analyses of dwarfing phenotypes resulting from targeted mutagenesis of the genes encoding the insulin-like growth factors (IGF-I and IGF-II) and their cognate type 1 IGF receptor (IGF1R) have demonstrated that this signaling system is a major determinant of mouse embryonic growth. Of the two IGE ligands, IGF-I interacts exclusively with IGF1R, whereas IGF-II recognizes an additional receptor (XR), because the growth retardation of embryos lacking both IGR1R and IGF-II (30% of normal birthweight) is more severe than that manifested in either class of single Igf1r or Igf2 null mutants (45 and 60% of normal, respectively). To determine whether XR is the insulin receptor (IR), we examined embryos nullizygons for both Igf1r and Insr. While the growth of embryos lacking solely IR is affected very mildly and only at the end of gestation, concomitant absence of IGF1R results in a severe growth-deficiency phenotype (30% of normal size at birth) that is first detected at Embryonic Day 13.5 and is also characterized by transient edema, curly tail, generalized organ hypoplasia, including the muscles, developmental delays in ossification, and thin epidermis. The Igf1r/Insr double nullizygotes are phenotypically indistinguishable from double mutants lacking IGF1R and IGF-II and from other double and triple mutants in which all of the IGF ligand/receptor interactions have been eliminated. Therefore, these results provide genetic evidence that the growth-promoting function of IGF-II during mouse embryogenesis is mediated in part by signaling through the insulin receptor. (C) 1997 Academic Press. C1 COLUMBIA UNIV, DEPT GENET & DEV, NEW YORK, NY 10032 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RI Gu, tianwei/K-2146-2012 FU NICHD NIH HHS [HD34526]; NIMH NIH HHS [MH50733] NR 91 TC 247 Z9 253 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 1997 VL 189 IS 1 BP 33 EP 48 DI 10.1006/dbio.1997.8666 PG 16 WC Developmental Biology SC Developmental Biology GA XV824 UT WOS:A1997XV82400004 PM 9281335 ER PT J AU Levin, M Pagan, S Roberts, DJ Cooke, J Kuehn, MR Tabin, CJ AF Levin, M Pagan, S Roberts, DJ Cooke, J Kuehn, MR Tabin, CJ TI Left/right patterning signals and the independent regulation of different aspects of Situs in the chick embryo SO DEVELOPMENTAL BIOLOGY LA English DT Article ID LEFT-RIGHT ASYMMETRY; NODAL EXPRESSION; ACTIN BUNDLES; INDUCTION; HEART; HANDEDNESS; LATERALITY; MUTATION; INVERSUS; CELLS AB Recently, a pathway of genes which are part of a cascade regulating the side on which the heart forms during chick development was characterized (M. Levin ct al., 1995, Cell 82, 1-20). Here we extend these previous studies, showing that manipulation of at least one member of the cascade, Sonic hedgehog (Shh), can affect the situs of embryonic rotation and of the gut, in addition to the heart. Bilateral expression of Shh, which is normally found exclusively can the left, does not result in left isomerism (a bilaterally symmetrical embryo having two left sides) nor in a complete situs inversus phenotype. Instead, misexpression of Shh on the right side of the node, which in turn leads to bilateral nodal expression, produces a heterotaxia-like condition, where different aspects of laterality are determined independently. Heart situs has previously been shown to be altered by ectopic Shh and activin. However, the most downstream gene identified in the LR pathway, nodal, had not been functionally linked to heart laterality. We show that ectopic (right-sided) nodal expression is able to affect heart situs, suggesting that the randomization of heart laterality observed in Shh and activin misexpression experiments is a result of changes in nodal expression and that nodal is likely to regulate heart situs endogenously. The first defined asymmetric signal in the left-right patterning pathway is Shh, which is initially expressed throughout Hensen's node but becomes restricted to the left side at stage 4(+). It has been hypothesized that the restriction of Shh expression may be due to repression by an upstream activin-like factor. The involvement of such an activin-like factor on the right side of Hensen's node was suggested because ectopic activin protein is able to repress Shh on the left side of the node, as well as to induce ectopic expression of a normally right-sided marker, the activin receptor cAct-RIIa. Here we provide further evidence in favor of this model. We find that a member of this family, Activin PB, is indeed expressed asymmetrically, only on the right side of Hensen's node, at the correct time for it to be the endogenous asymmetric activin signal. Furthermore, we show that application of follistatin-loaded beads eliminates the asymmetry in Shh expression, consistent with an inhibition of an endogenous member of the activin-BMP superfamily. This combined with the previous data on exogenous activin supports the model that Activin beta B functions in the chick embryo to initiate Shh asymmetry. While these data extend our understanding of the early signals which establish left-right asymmetry, they leave unanswered the interesting question of how the bilateral symmetry of the embryo is initially broken to define a consistent left-right axis. Analysis of spontaneous chick twins suggests that, whatever the molecular mechanism, left-right patterning is unlikely to be due to a blastodermal prepattern but rather is initiated in a streak-autonomous manner. (C) 1997 Academic Press. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV WOMENS & PERINATAL PATHOL,BOSTON,MA 02115. NATL INST MED RES,DEV NEUROBIOL LAB,LONDON NW7 1AA,ENGLAND. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 51 TC 161 Z9 163 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 1997 VL 189 IS 1 BP 57 EP 67 DI 10.1006/dbio.1997.8662 PG 11 WC Developmental Biology SC Developmental Biology GA XV824 UT WOS:A1997XV82400006 PM 9281337 ER PT J AU Ohshima, T Gilmore, EC Herrup, K Brady, RO Kulkarni, A AF Ohshima, T Gilmore, EC Herrup, K Brady, RO Kulkarni, A TI Ontogeny of abnormal brain development in Cdk5(-/-) mice SO DEVELOPMENTAL BRAIN DYSFUNCTION LA English DT Article DE corticogenesis; embryo; gene targeting; cyclin-dependent kinase; cerebral cortex; cerebellum; thalamus; olfactory bulb ID CYCLIN-DEPENDENT KINASE-5; NEURONAL CDC2-LIKE KINASE; DIRECTED PROTEIN-KINASE; REGULATORY SUBUNIT; MOLECULAR-CLONING; PERINATAL DEATH; NERVOUS-SYSTEM; CORTICAL PLATE; VISUAL-SYSTEM; REELER MICE AB Cyclin-dependent kinase 5 (Cdk5) was originally identified by its homology to other Cdks. Its expression is predominant in the central nervous system where Cdk5 expression and kinase activity are correlated with the extent of differentiation of neuronal cells and corticogenesis in the developing brain. Cdk5 purified from nervous tissue phosphorylates neuronal cytoskeletal proteins including neurofilament proteins and microtubule-associated protein tau in vitro. These findings indicate that Cdk5 may have unique functions in neuronal cells, especially in the regulation of phosphorylation of cytoskeletal molecules. We reported earlier the generation of Cdk5(-/-) mouse line by gene targeting. Cdk5(-/-) mice exhibit a lack of cortical laminar structure in cerebrum and cerebellum with perinatal mortality. In this study, we analyzed embryonic brains at different ages to define the ontogeny of formation of abnormal brain structure in Cdk5(-/-) mouse embryos. Abnormal lamination patterns are apparent at E16.5 in cerebral and cerebellar cortex, although normal neurogenesis is observed in ventricular zone in Cdk5(-/-) mice. At E18.5 the olfactory bulb also lacks the characteristic structure of cortical lamination. Additionally, the thalamus of Cdk5(-/-) embryos is decreased in size by E18.5. The ontogeny of formation of abnormal brain structures in these mice parallels Cdk5 expression pattern indicating the importance of Cdk5 in corticogenesis. C1 NIDR, Gene Targeting Res & Core Facil, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Alzheimers Res Lab, Cleveland, OH 44106 USA. OI Herrup, Karl/0000-0001-7786-5844 NR 46 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-5815 J9 DEV BRAIN DYSFUNCT JI Dev. Brain Dysfunct. PD SEP-OCT PY 1997 VL 10 IS 5 BP 271 EP 281 PG 11 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 195TF UT WOS:000080266900002 ER PT J AU Suzuki, K Parker, CC Pentchev, PG AF Suzuki, K Parker, CC Pentchev, PG TI Niemann-Pick disease type C: Neuropathology revisited SO DEVELOPMENTAL BRAIN DYSFUNCTION LA English DT Article DE neuronal storage disease; cholesterol transport; neurofibrillary tangles; tau ID ALZHEIMER NEUROFIBRILLARY TANGLES; JUVENILE DYSTONIC LIPIDOSIS; STORAGE-DISEASE; FETAL ASCITES; ADULT; CHOLESTEROL; HETEROGENEITY; DYSTROPHY; SPECTRUM; DEMENTIA AB Niemann-Pick disease type C (NPC) is a neurodegenerative disease characterized by lysosomal accumulation of low-density-lipoprotein (LDL)-derived cholesterol due to defective intracellular transport. The disease-causing gene has been recently identified. The clinical spectrum of NPC is heterogeneous; in general, those who have earlier onset are thought to have a rapidly progressive course with hepatosplenomegaly, while those with later onset show slowly progressive neurological symptoms without significant visceromegaly. However, there are still others with early onset who develop neurological symptoms slowly. In all NPC cases with heterogeneous clinical courses that we examined, the cardinal pathology was neuronal storage and a variable degree of storage in cells of the reticuloendothelial system. In a case with rapid progression, numerous neuroaxonal dystrophies (axonal spheroids) were noted throughout the brain in addition to extensive neuronal storage, while in cases with slow progression, regardless the age of onset, the presence of neurofibrillary tangles was a conspicuous feature in association with variable degrees of neuroaxonal dystrophies. The neurofibrillary tangles in these NPC patients may be somewhat different histologically from those of Alzheimer disease, but ultrastructurally and biochemically they are identical. Thus, there appear to be some differences in the neuropathological features of NPC cases with rapid clinical progression versus slow progression. The underlying mechanism(s) causing such differences in cellular responses is yet to be investigated. C1 Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NR 53 TC 9 Z9 9 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-5815 J9 DEV BRAIN DYSFUNCT JI Dev. Brain Dysfunct. PD SEP-OCT PY 1997 VL 10 IS 5 BP 306 EP 320 PG 15 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 195TF UT WOS:000080266900005 ER PT J AU Mansouri, A Yokota, Y Wehr, R Copeland, NG Jenkins, NA Gruss, P AF Mansouri, A Yokota, Y Wehr, R Copeland, NG Jenkins, NA Gruss, P TI Paired-related murine homeobox gene expressed in the developing sclerotome, kidney, and nervous system SO DEVELOPMENTAL DYNAMICS LA English DT Article DE homeobox; sclerotome; nervous system; mouse; C-elegans ID NEURAL CREST CELLS; C-ELEGANS UNC-4; DEVELOPMENTAL EXPRESSION; CAENORHABDITIS-ELEGANS; HOMEODOMAIN PROTEIN; MOTOR-NEURONS; MOUSE DEVELOPMENT; SYNAPTIC INPUT; FOREBRAIN; PATTERN AB We isolated a murine homeobox containing gene, Uncx4.1. The homeodomain sequence exhibits 88% identity to the unc-4 protein at the amino acid level. In situ hybridization analysis revealed that Uncx4.1 is expressed in the paraxial mesoderm, in the developing kidney, and central nervous system. The most intriguing expression domain is the somite, where it is confined to the caudal part of the newly formed somite and subsequently restricted to the caudal domain of the developing sclerotome. In the central nervous system, Uncx4.1 is detected in the developing spinal cord, hindbrain, mesencephalon, and telencephalon. The temporal and spatial expression pattern suggests that Uncx4.1 may play an important role in kidney development and in the differentiation of the sclerotome and the nervous system. (C) 1997 Wiley-Liss, Inc. C1 MAX PLANCK INST BIOPHYS CHEM,DEPT MOL CELL BIOL,D-37077 GOTTINGEN,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD. NR 72 TC 97 Z9 100 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 1997 VL 210 IS 1 BP 53 EP 65 DI 10.1002/(SICI)1097-0177(199709)210:1<53::AID-AJA6>3.3.CO;2-4 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA XT756 UT WOS:A1997XT75600006 PM 9286595 ER PT J AU Westergaard, GC Suomi, SJ AF Westergaard, GC Suomi, SJ TI Lateral bias in capuchin monkeys (Cebus apella): Concordance between parents and offspring SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE Cebus; handedness; heritability; laterality; monkey ID HAND PREFERENCES; RHESUS-MONKEYS; MACACA-MULATTA; BIMANUAL TASK; HANDEDNESS; BEHAVIOR AB We examined lateral bias for looking, reaching, and turning in 33 tufted capuchin monkeys (Cebus apella) comprising 29 parent-offspring dyads (13 mother-offspring dyads and 16 father-offspring dyads). We found evidence for maternal and paternal contributions to the direction of looking bias but no evidence for contribution from either parent to the direction of reaching bias. Further, we found evidence of differential maternal and paternal influences on the direction of offspring turning bias. Finally, we found no evidence of parental contribution to the strength of lateral bias for any of our measures. Our results indicate that parental contributions to lateral bias in humans and apes may not correspond to those in monkeys. (C) 1997 John Wiley & Sons, Inc. RP Westergaard, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD 20837, USA. NR 22 TC 15 Z9 15 U1 0 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD SEP PY 1997 VL 31 IS 2 BP 143 EP 147 PG 5 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA XU699 UT WOS:A1997XU69900006 PM 9298640 ER PT J AU Elias, PK Elias, MF DAgostino, RB Cupples, LA Wilson, PW Silbershatz, H Wolf, PA AF Elias, PK Elias, MF DAgostino, RB Cupples, LA Wilson, PW Silbershatz, H Wolf, PA TI NIDDM and blood pressure as risk factors for poor cognitive performance - The Framingham Study SO DIABETES CARE LA English DT Article ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; DEPENDENT DIABETES-MELLITUS; OLDER SUBJECTS; HYPERTENSION; MEMORY; POPULATION; STROKE; MEN; AGE; HYPERINSULINEMIA AB OBJECTIVE - To determine if NIDDM and blood pressure are risk factors for poor cognitive performance and if history and duration of NIDDM and blood pressure interact such that the risk of poor performance is greater for subjects with both NIDDM and hypertension. RESEARCH DESIGN AND METHODS - We used a large prospective cohort sample with 187 NIDDM subjects and 1,624 nondiabetic subjects who were followed for 28-30 years. Cognitive function was assessed using eight tests of learning, memory, visual organization, verbal fluency, attention, concept formation, and abstract reasoning. A composite score was also calculated. Odds ratios were used to estimate the relative risk of performing below the lower 25th percentile of z scores on these tests. RESULTS - NIDDM and blood pressure interacted such that diagnosis and duration of NIDDM were associated with greater risk of poor performance on tests of visual memory and on the composite score for hypertensive subjects. Duration of NIDDM was associated with increased risk for poor performance on tests of verbal memory and concept formation. Insulin-treated NIDDM subjects were at higher risk for poor cognitive performance than those NIDDM subjects treated with oral agents or diet. Blood pressure level was associated independently with a measure of verbal fluency. CONCLUSIONS - History and duration of NIDDM and high blood pressure are significant risk factors for poor cognitive performance. Hypertensive people with NIDDM are at greatest risk for poor performance on tests measuring visual organization and memory. C1 BOSTON UNIV, DEPT MATH, STAT & CONSULTING UNIT, BOSTON, MA 02215 USA. BOSTON UNIV, SCH PUBL HLTH, DEPT BIOSTAT & EPIDEMIOL, BOSTON, MA 02215 USA. BOSTON UNIV, SCH PUBL HLTH, DEPT NEUROL, BOSTON, MA 02215 USA. NHLBI, FRAMINGHAM HEART DIS EPIDEMIOL STUDY, BETHESDA, MD 20892 USA. UNIV MAINE, DEPT PSYCHOL, ORONO, ME 04469 USA. FU NIA NIH HHS [R01-AG0646-02, 2-R01-AG08122-07, 5-R37-AG03055-14] NR 57 TC 234 Z9 242 U1 2 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 1997 VL 20 IS 9 BP 1388 EP 1395 DI 10.2337/diacare.20.9.1388 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT091 UT WOS:A1997XT09100010 PM 9283785 ER PT J AU Shi, D Padgett, WL Hutchinson, KD Moore, SP Daly, JW AF Shi, D Padgett, WL Hutchinson, KD Moore, SP Daly, JW TI Pyrazolopyridines: Effect of structural alterations on activity at adenosine- and GABA(A)-receptors SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE adenosine receptors; GABA receptors; benzodiazepines; anxiolytics ID GAMMA-AMINOBUTYRIC-ACID; BARBITURATE RECEPTOR-SITES; RAT-BRAIN MEMBRANES; BINDING-SITES; ANXIOLYTIC AGENTS; HIGH-AFFINITY; GABA BINDING; BENZODIAZEPINE; ENHANCEMENT; MODULATION AB A series of 4-substituted 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid derivatives related in structure to the putative anxiolytics cartazolate, tracazolate, and etazolate were assessed for affinity at A(1)- and A(2A)-adenosine receptors and at GABA-, benzodiazepine-, and picrotoxin in-binding sites of the GABA(A)-receptor-channel. None of the derivatives had markedly greater affinity al Al-receptors than cartazolate (K-i-0.5 mu M), but many had markedly lower affinity than cartazolate (K-i-1.5 mu M) at A(2A)-receptors. At the benzodiazepine-binding site of GABA(A)-receptors some of the derivatives enhanced [H-3]diazepam binding, as did cartazolate and GABA, some had no effect and some inhibited binding. Most of the derivatives inhibited binding of the benzodiazepine-antagonist [H-3]Ro 15-1788. At the GABA-binding site, only a few of the derivatives inhibited binding of the antagonist [H-3]SR-95531, as did GABA. Al the picrotoxinin-binding sire, many inhibited binding of [S-35]TBPS, but none were as potent as cartazolate or GABA. Analysis of the interactions indicates that stimulation of [H-3]diazepam binding is allosteric and results from binding of the pyrazolopyridine at the GABA site or a subdomain of that site, while inhibition of [H-3]Ro 15-1788 binding is competitive and due to binding at the benzodiazepine site. Inhibition of [S-35]TBPS binding at the picrotoxinin-channel site appears to be allosteric through the GABA site and/or by direct competition at the channel site. Alterations in structure markedly alter the affinities of pyrazolopyridines at such sites on the GABA(A)-receptor-channel. (C) 1997 Wiley-Liss, Inc.dagger. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bldg 8,Rm 1A17, Bethesda, MD 20892 USA. NR 30 TC 10 Z9 10 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD SEP PY 1997 VL 42 IS 1 BP 41 EP 56 DI 10.1002/(SICI)1098-2299(199709)42:1<41::AID-DDR4>3.0.CO;2-R PG 16 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YU879 UT WOS:000071765200004 ER PT J AU Griffin, RJ Godfrey, VB Kim, YC Burka, LT AF Griffin, RJ Godfrey, VB Kim, YC Burka, LT TI Sex-dependent differences in the disposition of 2,4-dichlorophenoxyacetic acid in Sprague-Dawley rats, B6C3F1 mice, and Syrian Hamsters SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HERBICIDES PARAQUAT; 2,4-D; METABOLISM; EXCRETION; EXPOSURE; AMINE; HEPATOCYTES; ABSORPTION; TOXICITY; DINOSEB AB 2,4-Dichlorophenoxyacetic acid (2,4-D), a widely used broadleaf herbicide, is under investigation in a study of peroxisome proliferators. To supplement that study, male and female rats, mice, and hamsters were dosed with C-14-2,4-D orally at 5 and 200 mg/kg and tissue distributions were determined. Blood, liver, kidney, muscle, skin, fat, brain, testes, and ovaries were examined. At early time points tissues from female rats consistently contained higher amounts of radioactivity than did corresponding tissues from males (up to 9 times). By 72 hr, tissue levels were equivalent and males and females had excreted equal amounts of radioactivity. This sex difference was absent in mice, In hamsters, males had higher tissue levels than females. Taurine, glycine, and glucuronide conjugates of 2,4-D were excreted along with parent, Metabolite profiles differed between species qualitatively and quantitatively; however, differences between sexes were minimal. Plasma elimination curves were generated in male and female rats after iv and oral administration. Kinetic analysis revealed significant differences in elimination and exposure parameters consistent with a greater ability to clear 2,4-D by male rats relative to females. This suggests that at equivalent doses, female rats are exposed to higher concentrations of 2,4-D for a longer time than males and may be more susceptible to 2,4-D-induced toxicity. These sex-dependent variations in the clearance of 2,4-D in rats and hamsters may indicate a need for sex-specific models to accurately assess human health risks. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. SEOUL NATL UNIV,COLL PHARM,SEOUL 151,SOUTH KOREA. NR 33 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP PY 1997 VL 25 IS 9 BP 1065 EP 1071 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XV521 UT WOS:A1997XV52100008 PM 9311622 ER PT J AU Yu, AE Hewitt, RE Connor, EW StetlerStevenson, WG AF Yu, AE Hewitt, RE Connor, EW StetlerStevenson, WG TI Matrix metalloproteinases - Novel targets for directed cancer therapy SO DRUGS & AGING LA English DT Review ID TUMOR-CELL INVASION; C-TERMINAL DOMAIN; IN-SITU HYBRIDIZATION; COLLAGENASE GENE-EXPRESSION; INHIBITOR BATIMASTAT BB-94; CONSERVED PEPTIDE SEQUENCE; GELATINASE-A EXPRESSION; B16-F10 MELANOMA-CELLS; HUMAN TISSUE INHIBITOR; HEMOPEXIN-LIKE DOMAIN AB Matrix metalloproteinases (MMPs), or matrixins, are a family of zinc endopeptidases that play a key role in both physiological and pathological tissue degradation. Normally, there is a careful balance between cell division, matrix synthesis and matrix degradation, which is under the control of cytokines, growth factors and cell matrix interactions. The MMPs are involved in remodelling during tissue morphogenesis and wound healing. Under pathological conditions, this balance is altered: in arthritis, there is uncontrolled destruction of cartilage; in cancer, increased matrix turnover is thought to promote tumour cell invasion. The demonstration of a functional role of MMPs in arthritis and tumour metastasis raises the possibility of therapeutic intervention using synthetic MMP inhibitors with appropriate selectivity and pharmacokinetics. As the process of drug discovery focuses on structure-based design, efforts to resolve the 3-dimensional structures of the MMP family have intensified. Several novel MMP inhibitors have been identified and are currently being investigated in clinical trials. The structural information that is rapidly accumulating will be useful in refining the available inhibitors to selectively target specific MMP family members. In this review, we focus on the role of MMPs and their inhibitors in tumour metastasis and angiogenesis, and examine how MMPs may be targeted to prevent cancer progression. C1 NCI,EXTRACELLULAR MATRIX PATHOL SECT,PATHOL LAB,DCS,NIH,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 144 TC 116 Z9 118 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD SEP PY 1997 VL 11 IS 3 BP 229 EP 244 DI 10.2165/00002512-199711030-00006 PG 16 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA XW172 UT WOS:A1997XW17200006 PM 9303281 ER PT J AU Martinez, V Cuttitta, F Tache, Y AF Martinez, V Cuttitta, F Tache, Y TI Central action of adrenomedullin to inhibit gastric emptying in rats SO ENDOCRINOLOGY LA English DT Article ID GENE-RELATED PEPTIDE; CORTICOTROPIN-RELEASING FACTOR; PROADRENOMEDULLIN N-TERMINAL-20 PEPTIDE; HYPOTENSIVE PEPTIDE; CONSCIOUS RATS; NERVOUS-SYSTEM; MOTOR FUNCTION; CALCITONIN; RECEPTOR; NUCLEUS AB The central action of human adrenomedullin (AM) to influence gastric emptying and the peripheral mechanisms involved were studied in conscious rats. The 20-min rate of gastric emptying of a methylcellulose solution was assessed after intracisternal (ic) injection of AM or rat alpha-calcitonin gene-related peptide (alpha CGRP). AM and alpha CGRP dose-dependently inhibited gastric emptying with ic ED50 values of 120 and 100 pmol, respectively. Human proadrenomedullin N-terminal 20 peptide (150-600 pmol, ic) and AM (150 pmol, iv) had no effect. The inhibitory actions of AM and alpha CGRP (150 pmol, ic) were completely blocked by the CGRP antagonist, human CGRP-(8-37) injected ic at 30 mu g, but not at 15 mu g. The CRF antagonist, [D-Phe(12),Nle(21,38),C(alpha)MeLeu(37)]CRF-(12-41)(10 mu g/rat) injected in prevented ic rat/human CRF (150 pmol)-induced 53% inhibition of gastric emptying while not modifying the effect of AM. The action of AM (150 pmol, ic) was abolished by bilateral adrenalectomy or the beta-adrenergic blocker, propranolol (1 mg/kg, ip), but was not altered by indomethacin (5 mg/kg, ip) or subdiaphragmatic vagotomy. These results indicate that ic AM and alpha CGRP equipotently inhibit gastric emptying through mechanisms similarly antagonized by a high dose of CGRP(8-37). The central AM action is mediated through adrenal-dependent, beta-adrenergic pathways independently from activation of central CRF receptors. C1 UNIV CALIF LOS ANGELES, SCH MED, INST BRAIN RES, LOS ANGELES, CA 90073 USA. NCI, DIV CANC PREVENT & CONTROL, BIOMARKERS & PREVENT RES BRANCH, NIH, ROCKVILLE, MD 20850 USA. RP Martinez, V (reprint author), UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET AFFAIRS MED CTR, CURE DIGEST DIS RES CTR, LOS ANGELES, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 NR 51 TC 46 Z9 46 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1997 VL 138 IS 9 BP 3749 EP 3755 DI 10.1210/en.138.9.3749 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XR907 UT WOS:A1997XR90700025 PM 9275061 ER PT J AU Adashi, EY Resnick, CE Payne, DW Rosenfeld, RG Matsumoto, T Hunter, MK Gargosky, SE Zhou, J Bondy, CA AF Adashi, EY Resnick, CE Payne, DW Rosenfeld, RG Matsumoto, T Hunter, MK Gargosky, SE Zhou, J Bondy, CA TI The mouse intraovarian insulin-like growth factor I system: Departures from the rat paradigm SO ENDOCRINOLOGY LA English DT Article ID FACTOR-BINDING-PROTEINS; FOLLICLE-STIMULATING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; GONADOTROPIN-RELEASING-HORMONE; RECEPTOR GENE-EXPRESSION; OVARIAN GRANULOSA-CELLS; IGF-I; INDUCED DIFFERENTIATION; INVIVO REGULATION; ADULT-RAT AB Although the rat intraovarian insulin-like growth factor I (IGF-I) system is well documented, the increasing availability of null mouse mutants for components of the IGF system necessitates characterization of the mouse model as well. Therefore, we undertook to define the components of the mouse intraovarian IGF-I system and to examine its operational characteristics. The cellular pattern of ovarian gene expression was comparable in the immature rat and mouse for IGF-I and the type I IGF receptor. In both species, IGF-I messenger RNA (mRNA) is selectively expressed by granulosa cells in growing, healthy appearing follicles. Type I IGF receptor mRNA was also concentrated in granulosa cells, but was uniformly expressed in all follicles large and small, healthy and atretic appearing alike. Cellular patterns of IGF-binding protein (IGFBP) gene expression were similar in mouse and rat, except in the case of IGFBP-2. IGFBP-2 mRNA was localized to the mouse granulosa cell, in contrast to its concentration in the rat thecal-interstitial compartment. This difference in IGFBP expression pattern was also noted in cultured mouse and rat granulosa cells. Although immunoreactive IGFBP-4 (24 and 28 kDa) and IGFBP-5 (29 kDa) were shared by both species, the cultured mouse granulosa cell also featured immunoreactive IGFBP-2 (30 kDa). The mouse paradigm further differed from its rat counterpart in that a maximal dose of FSH, previously shown to suppress the elaboration of rat granulosa cell-derived IGFBPs, was without effect. The addition of IGF-I proved stimulatory to the accumulation of the 28- to 29-kDa IGFBPs, as previously reported for the rat. However, IGF-I proved inhibitory to the accumulation of the 24-kDa IGFBP (presumptive nonglycosylated IGFBP-4); no consistent effect was reported for the rat model. Functional comparisons of mouse and rat ovarian cell cultures revealed qualitatively comparable FSH-stimulated steroidogenesis, disposition of radiolabeled pregnenolone, IGF-I-amplified FSH action, and IGFBP-mediated antigonadotropic activity. These findings indicate that the mouse intrafollicular IGF-I system differs from the rat paradigm in both the makeup and regulation of granulosa cell-derived IGFBPs as well as in the intensity and character of the steroidogenic process. Studies employing the mouse model must take into account these important distinctions relative to the more established rat paradigm. C1 UNIV MARYLAND, SCH MED, DEPT OBSTET GYNECOL, DIV REPROD ENDOCRINOL, BALTIMORE, MD 21201 USA. UNIV OREGON, HLTH SCI CTR, DEPT PEDIAT, PORTLAND, OR 97201 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-19998] NR 69 TC 58 Z9 60 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1997 VL 138 IS 9 BP 3881 EP 3890 DI 10.1210/en.138.9.3881 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XR907 UT WOS:A1997XR90700043 PM 9275078 ER PT J AU Roman, SH Harris, MI AF Roman, SH Harris, MI TI Management of diabetes mellitus from a public health perspective SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID UNITED-STATES POPULATION; NON-HISPANIC WHITES; GLYCOSYLATED HEMOGLOBIN; COMPLICATIONS TRIAL; GENERAL-PRACTICE; US POPULATION; BLOOD-GLUCOSE; RISK-FACTORS; CARE; NIDDM AB This article details the score and the impact of diabetes in the United States including the prevalence, demographics, morbidity and mortality, and costs. The current status of medical care for diabetes is used to illustrate why diabetes should be approached from a proactive public health perspective, rather than a reactive, traditional medical perspective. The importance of early diagnosis and secondary intervention programs for prevention and early detection of diabetes complications are emphasized. The specialty-based intensive management model, the primary care-based co-management model, the systems management model, and the mini-clinic models are presented as potential paradigms for approaching diabetes care from a public health perspective. Requirements for implementing a public health approach to diabetes care including long-term planning, targeting patients for improved care, and goal setting for outcomes of care, are discussed. C1 MT SINAI MED CTR,ADULT DIABET PROGRAM,NEW YORK,NY 10029. NIDDK,NATL DIABET DATA GRP,BETHESDA,MD. RP Roman, SH (reprint author), MT SINAI MED CTR,DIV ENDOCRINOL & METAB,MT SINAI SCH MED,BOX 1055,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. NR 85 TC 52 Z9 57 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1997 VL 26 IS 3 BP 443 EP & DI 10.1016/S0889-8529(05)70260-7 PG 33 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XX368 UT WOS:A1997XX36800002 PM 9314008 ER PT J AU Herman, WH Dasbach, EJ Songer, TJ Eastman, RC AF Herman, WH Dasbach, EJ Songer, TJ Eastman, RC TI The cost-effectiveness of intensive therapy for diabetes mellitus SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID ROCHESTER; CARE; RETINOPATHY; PREVALENCE; MINNESOTA; REFORM AB Although patients with diabetes constitute only 3.1% of the United States population, costs for their care account for 11.9% of total United States health care expenditures. Approximately half of the expenditures for medical care for diabetes are for treatment of the metabolic condition and half for the treatment of chronic complications. Intensive therapy for patients with diabetes uses more resources and is more expensive than conventional therapy. On the other hand, intensive therapy is associated with a lower incidence of costly chronic complications. Formal economic analyses have demonstrated that intensive therapy is cost-effective for the treatment of diabetes. C1 UNIV MICHIGAN, DEPT INTERNAL MED, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, DEPT EPIDEMIOL, ANN ARBOR, MI 48109 USA. MERCK RES LABS, BLUE BELL, PA USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, DEPT EPIDEMIOL, PITTSBURGH, PA USA. NIDDK, DIV DIABET ENDOCRINOL & METAB DIS, NIH, BETHESDA, MD USA. OI Songer, Thomas/0000-0002-5253-2514 NR 37 TC 30 Z9 30 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 EI 1558-4410 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1997 VL 26 IS 3 BP 679 EP + DI 10.1016/S0889-8529(05)70274-7 PG 0 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XX368 UT WOS:A1997XX36800016 PM 9314022 ER PT J AU Melnick, RL Kohn, MC Huff, J AF Melnick, RL Kohn, MC Huff, J TI Weight of evidence versus weight of speculation to evaluate the alpha 2u-globulin hypothesis SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID ALTERNATIVE HYPOTHESIS; RENAL CARCINOGENESIS; FISCHER-344 RATS; NEPHROPATHY; EXPOSURE; LINDANE RP Melnick, RL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 18 TC 17 Z9 17 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1997 VL 105 IS 9 BP 904 EP 906 DI 10.2307/3433864 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA YG652 UT WOS:A1997YG65200005 PM 9341100 ER PT J AU Lechner, JF Tesfaigzi, J Gerwin, BI AF Lechner, JF Tesfaigzi, J Gerwin, BI TI Oncogenes and tumor-suppressor genes in mesothelioma - A synopsis SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 6th International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles CY SEP 15-18, 1996 CL LAKE PLACID, NY DE oncogenes; tumor-suppressor genes; PDGF; p16(INK4a); SV40 T-antigen; NF2; mesothelioma; human; fibers; cancer ID HUMAN-MALIGNANT MESOTHELIOMA; GROWTH-FACTOR-A; CELL-LINES; PLEURAL MESOTHELIOMA; ASBESTOS FIBERS; NEOPLASTIC TRANSFORMATION; TRANSCRIPTIONAL CONTROL; RECEPTOR EXPRESSION; GENOMIC INSTABILITY; KINASE INHIBITORS AB Invariably mesothelioma is diagnosed late in the development of the disease when treatment is no longer effective. Therefore, a key to reducing the mortality rate of this neoplasm is knowledge of the general sequence of genetic events between initiation of mesothelial cells and the emergence of the metastatic tumor cells. Unfortunately, relatively little is known about the early changes in the genesis of this disease. Of the known changes, the most frequent are in the tumor-suppressor genes p16(INK4a) and NF2 and possibly that SV40 virus large T-antigen oncogene. The molecular nature of the changes in these genes as well as other alterations are addressed in this overview. C1 LOVELACE BIOMED & ENVIRONM RES INST,ALBUQUERQUE,NM. NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 99 TC 24 Z9 24 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1997 VL 105 SU 5 BP 1061 EP 1067 DI 10.2307/3433510 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA YH510 UT WOS:A1997YH51000011 PM 9400701 ER PT J AU Rahman, Q Mahmood, N Khan, SG Arif, JM Athar, M AF Rahman, Q Mahmood, N Khan, SG Arif, JM Athar, M TI Mechanism of asbestos-mediated DNA damage: Role of heme and heme proteins SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 6th International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles CY SEP 15-18, 1996 CL LAKE PLACID, NY DE asbestos DNA; heme; heme protein; heme peroxides ID CHROMOSOMAL CHANGES; MESOTHELIAL CELLS; DISEASES; OXIDANT; FIBERS AB Several observations, including studies from this laboratory, demonstrate that asbestos generates free radicals in the biological system that may play a role in the manifestation of asbestos-related cytotoxicity and carcinogenicity. It has also been demonstrated that iron associated with asbestos plays an important role in the asbestos-mediated generation of reactive oxygen species. Exposure to asbestos leads to degradation of heme proteins such as cytochrome P450-releasing heme in cytosol. Our simulation experiments in the presence of heme snow that such asbestos-released heme may increase lipid peroxidation and can cause DNA damage, Further, heme and horseradish peroxidase (HRP) can cause extensive DNA damage in the presence of asbestos and hydrogen peroxide/organic peroxide/hydroperoxides. HRP catalyzes oxidation reactions in a manner similar to that of prostaglandin H synthetase. Iron released from asbestos is only partially responsible for DNA damage. However, our studies indicate that DNA damage mediated by asbestos in vivo may be caused by a combination of effects such as the release and participation of iron, heme, and heme moiety of prostaglandin H synthetase in free radical generation from peroxides and hydroperoxides. C1 NIH,BETHESDA,MD 20892. UNIV KENTUCKY,DEPT PREVENT MED & ENVIRONM HLTH,LEXINGTON,KY 40506. HAMDARD UNIV,DEPT MED ELEMENTOL & TOXICOL,NEW DELHI,INDIA. RP Rahman, Q (reprint author), IND TOXICOL RES CTR,FIBER TOXICOL DIV,POST BOX 80,LUCKNOW 226001,UTTAR PRADESH,INDIA. NR 14 TC 10 Z9 11 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1997 VL 105 SU 5 BP 1109 EP 1112 DI 10.2307/3433517 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA YH510 UT WOS:A1997YH51000018 PM 9400708 ER PT J AU Kleinerman, RA Linet, MS Hatch, EE Wacholder, S Tarone, RE Severson, RK Kaune, WT Friedman, DR Haines, CM Muirhead, CR Boice, JD Robison, LL AF Kleinerman, RA Linet, MS Hatch, EE Wacholder, S Tarone, RE Severson, RK Kaune, WT Friedman, DR Haines, CM Muirhead, CR Boice, JD Robison, LL TI Magnetic field exposure assessment in a case control study of childhood leukemia SO EPIDEMIOLOGY LA English DT Article DE magnetic fields; childhood leukemia; case control study; exposure assessment; measurements; wire codes ID ELECTRICAL WIRING CONFIGURATIONS; POWER-FREQUENCY; CANCER; CHILDREN; RISK; LINES; CODES AB Epidemiologic evaluation of the relation between magnetic field exposures and cancer depends critically on study design, particularly the methods used for exposure assessment. We incorporated a complex magnetic field exposure assessment protocol into a large incident case-control study of childhood leukemia. We measured residential magnetic fields using a standard protocol in current and former homes of 638 cases and 620 controls and determined wire codes for 414 case-control pairs. We chose a time-weighted average of magnetic field measurements in each eligible home, weighted by the time the subject lived in each home as the main exposure metric for each subject. We found that 24-hour bedroom magnetic field measurements adequately characterize children's residential exposure and that measuring other rooms contributes only slightly to the estimate of average residential exposure to magnetic fields. Front door measured fields provide useful exposure information when interior measurements are missing. If feasible, measuring multiple homes in which the subject has resided is preferable to measuring a single home. A similar distribution of wire codes for controls agreeing or refusing to participate in our study implies that risk estimates derived from wire code data will not be influenced by response bias. C1 NCI,DIV CANC EPIDEMIOL & GENET,NIH,ROCKVILLE,MD. UNIV MINNESOTA,DIV PEDIAT EPIDEMIOL & CLIN RES,MINNEAPOLIS,MN. EM FACTORS,RICHLAND,WA. WESTAT CORP,ROCKVILLE,MD 20850. NATL RADIOL PROTECT BOARD,DIDCOT OX11 0RQ,OXON,ENGLAND. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [R01-CA48051, N01-CP-95608] NR 29 TC 35 Z9 35 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1997 VL 8 IS 5 BP 575 EP 583 DI 10.1097/00001648-199709000-00017 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XR463 UT WOS:A1997XR46300020 PM 9270962 ER PT J AU Hunter, D Caporaso, N AF Hunter, D Caporaso, N TI Informed consent in epidemiologic studies involving genetic markers SO EPIDEMIOLOGY LA English DT Article C1 CHANNING LABS,BOSTON,MA 02115. NCI,GENET EPIDEMIOL BRANCH,ROCKVILLE,MD. RP Hunter, D (reprint author), HARVARD UNIV,SCH PUBL HLTH,BRIGHAM & WOMENS HOSP,DEPT EPIDEMIOL,181 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 9 TC 15 Z9 15 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1997 VL 8 IS 5 BP 596 EP 599 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XR463 UT WOS:A1997XR46300024 PM 9270965 ER PT J AU Walther, W Stein, U Wendt, J Shoemaker, RH AF Walther, W Stein, U Wendt, J Shoemaker, RH TI Employment of the mdr1 promoter for a conditionally active retroviral vector system in cancer gene therapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NATL CANC INST,FREDERICK,MD. MAX DELBRUCK CTR MOL MED,BERLIN,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 376 EP 376 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83000372 ER PT J AU Daniele, B Secondulfo, M Pignata, S DeMartino, S deMagistris, L DeVivo, R Pergola, M DAgostino, L Monfardini, S Carratu, R AF Daniele, B Secondulfo, M Pignata, S DeMartino, S deMagistris, L DeVivo, R Pergola, M DAgostino, L Monfardini, S Carratu, R TI Effect of chemotherapy with 5-fluorouracil on intestinal permeability of patients with advanced colon cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,DIV MED ONCOL,BETHESDA,MD 20892. SECOND UNIV NAPLES,GI UNIT,NAPLES,ITALY. UNIV NAPLES FEDERICO II,GI UNIT,NAPLES,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 757 EP 757 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83000752 ER PT J AU Stein, U Walther, W Scheffer, GL Scheper, RJ Shoemaker, RH Schlag, PM AF Stein, U Walther, W Scheffer, GL Scheper, RJ Shoemaker, RH Schlag, PM TI Reversal of multidrug resistance by externally added or gene transduced cytokines: An alternative approach SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 MAX DELBRUCK CTR MOL MED,BERLIN,GERMANY. ROBERT ROSSLE KLIN,BERLIN,GERMANY. FREE UNIV AMSTERDAM HOSP,AMSTERDAM,NETHERLANDS. NATL CANC INST,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 776 EP 776 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83000771 ER PT J AU Fassina, G Aluigi, MG Cai, T Gentleman, S Noonan, DM Albini, A AF Fassina, G Aluigi, MG Cai, T Gentleman, S Noonan, DM Albini, A TI 8-Cl-cAMP induction of differentiation and apoptosis in Y-79 human retinoblastoma cell line SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 CNR,IST NAZL RIC CANC,DEPT EXPT ONCOL,GENOA,ITALY. CNR,CTR NEUROFISIOL CEREBRALE,GENOA,ITALY. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 815 EP 815 PG 2 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83000810 ER PT J AU Ebert, A Reinhold, J Stieler, J Pritze, W Salomon, DS Weitzel, H Schaller, G Brandt, R AF Ebert, A Reinhold, J Stieler, J Pritze, W Salomon, DS Weitzel, H Schaller, G Brandt, R TI Expression of cripto-1, a new ligand of the EGF superfamily, in gynecological carcinomas SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 FREE UNIV BERLIN,MED CTR BENJAMIN FRANKLIN,DEPT OB GYN,D-1000 BERLIN,GERMANY. NCI,LTBI,GROWTH FACTOR SECT,BETHESDA,MD 20892. CIBA GEIGY AG,DEPT CDD TECHNOL,CH-4002 BASEL,SWITZERLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 932 EP 932 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83000927 ER PT J AU Petersen, I Bujard, M Petersen, S Wolf, G Goeze, A Schwendel, A Cremer, T Ried, T Dietel, M AF Petersen, I Bujard, M Petersen, S Wolf, G Goeze, A Schwendel, A Cremer, T Ried, T Dietel, M TI Distinct patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 UNIV HOSP CHARITE,INST PATHOL,BERLIN,GERMANY. UNIV HEIDELBERG,INST HUMAN GENET,HEIDELBERG,GERMANY. NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 1027 EP 1027 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83001020 ER PT J AU Rusthoven, J Eisenhauer, E Butts, C Gregg, R Dancey, J Fisher, B Iglesias, J AF Rusthoven, J Eisenhauer, E Butts, C Gregg, R Dancey, J Fisher, B Iglesias, J TI Phase II trial of the multi-targeted antifolate LY231514 (MTA) as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,CANADA CLIN TRIALS GRP,KINGSTON,ON,CANADA. ELI LILLY & CO,INDIANAPOLIS,IN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 1045 EP 1045 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83001038 ER PT J AU Hochster, H Chachoua, A Sorich, J Wasserheit, C Taubes, B Friedberg, A Arbuck, S Speyer, J AF Hochster, H Chachoua, A Sorich, J Wasserheit, C Taubes, B Friedberg, A Arbuck, S Speyer, J TI Phase I Study of paclitaxel (P) combined with 14-day topotecan (T) continuous IV (CIV) infusion in previously treated and untreated patients (PTS) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NYU MED CTR,KAPLAN CANC CTR,NEW YORK,NY 10016. NCI,CTEP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 1131 EP 1131 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83001124 ER PT J AU Rivoltini, L Mazzocchi, A Squarcina, P Arienti, F Belli, F Castelli, C Marincola, FM Loftus, DJ Parmiani, G AF Rivoltini, L Mazzocchi, A Squarcina, P Arienti, F Belli, F Castelli, C Marincola, FM Loftus, DJ Parmiani, G TI T cell recognition of melanoma-derived antigens: Implication for peptide based immunotherapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NATL TUMOR INST,MILAN,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 1313 EP 1313 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83001306 ER PT J AU Haller, DG Sarosy, G Thurn, A Hubbard, SM AF Haller, DG Sarosy, G Thurn, A Hubbard, SM TI PDQ: A comprehensive cancer information database - The US experience SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1997 VL 33 SU 8 BP 1324 EP 1324 PG 1 WC Oncology SC Oncology GA XX830 UT WOS:A1997XX83001315 ER PT J AU Csako, G Rehak, NN Elin, RJ AF Csako, G Rehak, NN Elin, RJ TI Falsely high ionized magnesium results by an ion-selective electrode method in severe hypomagnesemia SO EUROPEAN JOURNAL OF CLINICAL CHEMISTRY AND CLINICAL BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 28-AUG 01, 1996 CL CHICAGO, IL SP Amer Assoc Clin Chem ID BLOOD-SERUM; INTERLEUKIN-2 IMMUNOTHERAPY; WHOLE-BLOOD; KONE ISE; MG2+; HEALTHY; CALCIUM; PLASMA; NOVA; HYPERMAGNESEMIA AB Changes in serum total and ionized magnesium (Mg and Mg2+) and calcium (Ca and Ca2+) were monitored in three patients who transiently developed severe (total Mg < 0.50 mmol/l) to profound hypomagnesemia (total Mg < 0.35 mmol/l) due to cisplatin or interleukin-2 therapies. Mg2+ and Ca2+ were measured with the Nova ion-selective electrodes at 37 degrees C and all results were normalized to pH 7.40. Independent of the etiology, the Mg2+ fraction (Mg2+/total Mg) increased as the concentration of the serum total Mg decreased in all three patients. When the total Mg was around or below 0.35 mmol/l the Mg2+ approached or exceeded total Mg, suggesting an error in the measurement of Mg2+. The findings were extended. by including a group of 31 additional patients whose serum total Mg, Mg2+, total Ca, and Ca2+ concentrations varied from abnormally low to above normal. The serum total and ionized concentrations strongly correlated for both Mg (r(2) = 0.88) and Ca (r(2) = 0.92). The Mg2+ fraction rapidly increased with a fall in the total Mg concentration (r(2) = 0.76) and total Mg/total Ca ratio (r(2) = 0.71). In fact, with decreasing total Mg concentrations or total Mg/total Ca ratios, the Mg2+ fraction progressively increased to 93-128% of the total, confirming an error in the Mg2+ determinations. The Ca2+ fraction showed a slight and insignificant decrease with falling total Ca concentrations and total Mg/total Ca ratios. The Mg2+ concentration was directly related (r(2) = 0.62), whereas the Ca2+ concentration showed a complex relationship to the total Mg/total Ca ratio. Whether this latter relationship represents a technical artifact or a true biological phenomenon requires further study. The apparent overestimation of Mg2+ at very low total Mg concentrations, and in the presence of a very low total Mg/total Ca ratio, could be due to improper chemometric correction of the Ca effect on the Mg electrode, nonlinearity, and inadequate calibration. Whatever the mechanism, the failure of this method to correctly measure very low serum Mg2+ concentrations in the sera of patients with severe hypomagnesemia, or likely in any patient with an unusually low total Mg/total Ca ratio, erodes its diagnostic usefulness. RP Csako, G (reprint author), NIH,CLIN CHEM SERV,DEPT CLIN PATHOL,WG MAGNUSON CLIN CTR,BLDG 10,RM 2C-407,BETHESDA,MD 20892, USA. NR 43 TC 11 Z9 11 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0939-4974 J9 EUR J CLIN CHEM CLIN JI Eur. J. Clin. Chem. Clin. Biochem. PD SEP PY 1997 VL 35 IS 9 BP 701 EP 709 PG 9 WC Biochemistry & Molecular Biology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Medical Laboratory Technology GA YD454 UT WOS:A1997YD45400008 PM 9352233 ER PT J AU Mostaccioli, S DeLaurenzi, V Terrinoni, A Richard, G Didona, B Cavalieri, R Melino, G AF Mostaccioli, S DeLaurenzi, V Terrinoni, A Richard, G Didona, B Cavalieri, R Melino, G TI White sponge nevus is caused by mutations in mucosal keratins SO EUROPEAN JOURNAL OF DERMATOLOGY LA English DT Article DE white sponge nevus; keratin; leukokeratoses; K4; K13 ID PACHYONYCHIA-CONGENITA; INTERMEDIATE FILAMENTS; DISEASE AB Cannon's white sponge nevus is a rare, autosomal dominant disorder affecting non-cornified, stratified, squamous epithelia. Clinically, it appears as ''spongy'' plaques on the oral mucosa. Recently, two distinct genetic defects on the 1A domain of keratins have been reported in one Italian and two Scottish families with white sponge nevus. The former defect is an in-frame deletion that results in the loss of an asparagine in keratin 4 (K4); while the latter family carries a single base pair mutation that leads to a leucine to proline substitution in keratin 13 (K13). Both defects result in abnormal K4/K13 heterodimer formation and irregular protofibrils. These findings extend the molecular defects described in intermediate keratin filaments, confirming the molecular role of the aggregation domains corresponding to genetic 'hot spots' for mutations. Furthermore, the identification of the molecular defects defines the correct target for new therapeutic approaches. C1 IST DERMOPAT IMMACOLATA,IRCCS,DIV 1,ROME,ITALY. IST DERMOPAT IMMACOLATA,IRCCS,BIOCHIM LAB,ROME,ITALY. NIAMSD,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. RI TERRINONI, Alessandro/J-1533-2012 OI TERRINONI, Alessandro/0000-0002-7442-2252 NR 29 TC 2 Z9 2 U1 0 U2 2 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1167-1122 J9 EUR J DERMATOL JI Eur. J. Dermatol. PD SEP PY 1997 VL 7 IS 6 BP 405 EP 408 PG 4 WC Dermatology SC Dermatology GA XX671 UT WOS:A1997XX67100002 ER PT J AU Felix, K Lin, S Janz, S AF Felix, K Lin, S Janz, S TI Elevated mutant frequencies in gene lacI in splenic lipopolysaccharide blasts after exposure to activated phagocytes in vitro SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B lymphocyte; lacI; mutagenicity; pristane ID TRANSGENIC MICE; MUTAGENESIS ASSAY; LYMPHOCYTES-B; NEUTROPHILS AB The interaction of B lymphocytes with phagocytes is critical for shaping the humoral immune response, as well as various aspects of normal and malignant B cell development, and has therefore been studied by immunologists in great detail. However, one potential outcome of this confrontation is often neglected, namely the mutagenicity of phagocytes to B lymphocytes. We are interested in phagocyte-induced B cell mutagenesis and have conducted a feasibility study on the utility of a transgenic reporter assay to evaluate mutant frequencies in B cells that have encountered phagocytes. An in vitro co-incubation system was designed in which splenic lipopolysaccharide (LPS) blasts carrying a phage lambda-derived lacI transgene were exposed to pristane-elicited peritoneal exudate cells (PEC). Mutant frequencies in LPS blasts were significantly increased (up to S-fold) when the cells were co-incubated with PEC that had been stimulated by phorbol myristate acetate to undergo an oxidative burst. The lacI-based transgenic mutation assay proved also useful for assessing mutagenicity in vivo, as demonstrated by the detection of elevated mutant frequencies in the spleen (3-fold) and the inflammatory granuloma (4.7-fold) obtained from pristane-treated mice. We propose to utilize the lacI-based transgenic mutagenesis assay as a tool to evaluate mutational levels during normal and aberrant B cell differentiation. C1 GSF MUNICH,INST KLIN MOL BIOL & TUMORGENET,MUNICH,GERMANY. RP Felix, K (reprint author), NCI,GENET LAB,DBS,NIH,BLDG 37,ROOM 2BO3,BETHESDA,MD 20892, USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 1997 VL 27 IS 9 BP 2160 EP 2164 DI 10.1002/eji.1830270907 PG 5 WC Immunology SC Immunology GA YA324 UT WOS:A1997YA32400006 PM 9341754 ER PT J AU Nilsson, G ForsbergNilsson, K Xiang, Z Hallbook, F Nilsson, K Metcalfe, DD AF Nilsson, G ForsbergNilsson, K Xiang, Z Hallbook, F Nilsson, K Metcalfe, DD TI Human mast cells express functional TrkA and are a source of nerve growth factor SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE mast cell; TrkA; nerve growth factor; nerve growth factor receptor; tyrosine kinase ID RAT SCIATIC-NERVE; MESSENGER-RNA; PROTOONCOGENE PRODUCT; NEUROTROPHIC FACTORS; SURVIVAL PROMOTION; MEDIATOR RELEASE; FACTOR RECEPTOR; B-LYMPHOCYTES; BONE-MARROW; KIT-LIGAND AB Mast cells are the principal effector cells in IgE-dependent hypersensitivity reactions. Despite reports that rodent mast cells proliferate in the presence of nerve growth factor (NGF), human mast cells reportedly do not respond to this factor. To determine if human mast cells express the NGF receptors, TrkA tyrosine receptor and the low affinity NGF receptor (LNGFR), we first analyzed the mRNA expression by RT-PCR of TrkA and LNGFR in a human mast cell line (HMC-1) and in human mast cells cultured in the presence of stem cell factor. Both HMC-1 and cultured human mast cells were found to express TrkA but not LNGFR. TrkA protein was demonstrated by Western blot analysis of HMC-1 lysates. Using flow cytometric analysis and mast cell tryptase as a mast cell marker, both HMC-1 cells and cultured human mast cells were shown to coexpress tryptase and TrkA. Treatment of mast cells with NGF resulted in phosphorylation of TrkA on tyrosine residues as detected by immunoblotting with an antiphosphotyrosine antibody. Furthermore, NGF induced the immediate early gene c-fos in HMC-1 cells. HMC-1 cells and cultured human mast cells were also found to express NGF mRNA, and conditioned medium from HMC-1 cells stimulated neurite outgrowth from chicken embryonic sensory ganglia in culture. This effect was blocked by anti-NGF. Thus, mast cells express functional TrkA and synthesize NGF, suggesting a mechanism by which NGF may act as an autocrine factor for human mast cells, and by which mast cells and nerves may interact. C1 NIAID,LAB ALLERG DIS,NIH,BETHESDA,MD 20892. NINCDS,MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV UPPSALA,DEPT DEV NEUROSCI,UPPSALA,SWEDEN. RP Nilsson, G (reprint author), UNIV UPPSALA,DEPT PATHOL,S-75185 UPPSALA,SWEDEN. OI Hallbook, Finn/0000-0001-7552-187X NR 59 TC 136 Z9 141 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 1997 VL 27 IS 9 BP 2295 EP 2301 DI 10.1002/eji.1830270925 PG 7 WC Immunology SC Immunology GA YA324 UT WOS:A1997YA32400024 PM 9341772 ER PT J AU Sommer, MA Tehovnik, EJ AF Sommer, MA Tehovnik, EJ TI Reversible inactivation of macaque frontal eye field SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE saccadic eye movements; fixations; frontal eye field; reversible inactivation; Macaca mulatta ID SUPERIOR COLLICULUS ABLATIONS; RHESUS-MONKEY; SACCADE INITIATION; FASTIGIAL NUCLEUS; NEURONAL-ACTIVITY; LOCAL FEEDBACK; BURST NEURONS; MOVEMENTS; LESIONS; MUSCIMOL AB The macaque frontal eye field (FEF) is involved in the generation of saccadic eye movements and fixations. To better understand the role of the FEF, we reversibly inactivated a portion of it while a monkey made saccades and fixations in response to visual stimuli. Lidocaine was infused into a FEF and neural inactivation was monitored with a nearby microelectrode. We used two saccadic tasks. In the delay task, a target was presented and then extinguished, but the monkey was not allowed to make a saccade to its location until a cue to move was given. In the step task, the monkey was allowed to look at a target as soon as it appeared. During FEF inactivation, monkeys were severely impaired at making saccades to locations of extinguished contralateral targets in the delay task. They were similarly impaired at making saccades to locations of contralateral targets in the step task if the target was flashed for less than or equal to 100 ms, such that it was gone before the saccade was initiated. Deficits included increases in saccadic latency, increases in saccadic error, and increases in the frequency of trials in which a saccade was not made. We varied the initial fixation location and found that the impairment specifically affected contraversive saccades rather than affecting all saccades made into head-centered contralateral space. Monkeys were impaired only slightly at making saccades to contralateral targets in the step task if the target duration was 1000 ms, such that the target was present during the saccade: latency increased, but increases in saccadic error were mild and increases in the frequency of trials in which a saccade was not made were insignificant. During FEF inactivation there usually was a direct correlation between the latency and the error of saccades made in response to contralateral targets. In the delay task, FEF inactivation increased the frequency of making premature saccades to ipsilateral targets. FEF inactivation had inconsistent and mild effects on saccadic peak velocity. FEF inactivation caused impairments in the ability to fixate lights steadily in contralateral space. FEF inactivation always caused an ipsiversive deviation of the eyes in darkness. In summary, our results suggest that the FEF plays major roles in (1) generating contraversive saccades to locations of extinguished or flashed targets, (2) maintaining contralateral fixations, and (3) suppressing inappropriate ipsiversive saccades. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. RP Sommer, MA (reprint author), NEI,SENSORIMOTOR RES LAB,NIH,BLDG 49,ROOM 2A50,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY-08502] NR 57 TC 129 Z9 130 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD SEP PY 1997 VL 116 IS 2 BP 229 EP 249 DI 10.1007/PL00005752 PG 21 WC Neurosciences SC Neurosciences & Neurology GA XX877 UT WOS:A1997XX87700004 PM 9348123 ER PT J AU Kohn, AF Floeter, MK Hallett, M AF Kohn, AF Floeter, MK Hallett, M TI Presynaptic inhibition compared with homosynaptic depression as an explanation for soleus H-reflex depression in humans SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE H-reflex depression; homosynaptic depression; presynaptic inhibition; spinal cord; human ID POST-ACTIVATION DEPRESSION; SPINAL-CORD; SYNAPTIC DEPRESSION; STRETCH REFLEX; IA AFFERENTS; MUSCLES; FIBERS; CAT AB The H-reflex is depressed for seconds if elicited following a single H-reflex or train of H-reflexes. Presynaptic inhibition from flexor afferents (tibialis anterior) onto soleus Ia afferents elicited by either single or trains of stimuli had no effect on the soleus H-reflex on a time scale of seconds. Postsynaptic inhibition was also excluded by magnetic stimulation tests that showed that the excitability of the motoneuron pool was not changed at latencies within a range of seconds. Homosynaptic depression localized at the presynaptic terminal seems to be the mechanism behind the H-reflex depression in humans. C1 NINCDS,HUMAN MOTOR CONTROL SECT,NIH,BETHESDA,MD. RI Kohn, Andre/N-4982-2016 OI Kohn, Andre/0000-0002-9770-3348 NR 29 TC 56 Z9 59 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD SEP PY 1997 VL 116 IS 2 BP 375 EP 380 DI 10.1007/PL00005765 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XX877 UT WOS:A1997XX87700017 PM 9348136 ER PT J AU Ye, JP Young, HA AF Ye, JP Young, HA TI Negative regulation of cytokine gene transcription SO FASEB JOURNAL LA English DT Review DE nuclear factor; DNA methylation; T cell ID NF-KAPPA-B; INTERFERON-GAMMA PROMOTER; TATA-BINDING PROTEIN; CBP-INDUCED STIMULATION; RNA-POLYMERASE-II; INTERLEUKIN-6 GENE; DNA-BINDING; NUCLEAR FACTOR; T-CELLS; TRANSGENIC MICE AB Cytokines are a class of soluble proteins that mediate signals throughout the immune system as well as between immune effector cells and other cell populations, This class of proteins includes interleukins, interferons, and chemokines, The expression of cytokines is tightly controlled in the producing cells, and one of the most important regulatory steps in this control is gene transcription, The transcription of most cytokine genes is silent until a producing cell is activated by extracellular stimuli, It is very common that transcription of these genes initiates immediately upon activation and shuts down quickly even in the continuous presence of the stimulating agent, Work performed over the past decade has revealed much about the molecular mechanism responsible for transcriptional regulation of these genes, Positive and negative transcription factors function in a concerted manner to regulate transcription of a specific cytokine at the promoter or intron region. We focus on recent progress in the field of transcriptional regulation of cytokine genes with an emphasis on the negative regulation of cytokine gene transcription. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,FREDERICK,MD 21702. RP Ye, JP (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284, USA. NR 99 TC 31 Z9 32 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1997 VL 11 IS 11 BP 825 EP 833 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA XT790 UT WOS:A1997XT79000001 PM 9285480 ER PT J AU Bolon, B Bucci, TJ Warbritton, AR Chen, JJ Mattison, DR Heindel, JJ AF Bolon, B Bucci, TJ Warbritton, AR Chen, JJ Mattison, DR Heindel, JJ TI Differential follicle counts as a screen for chemically induced ovarian toxicity in mice: Results from continuous breeding bioassays SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID SMOKING; REPRODUCTION; DESTRUCTION; STRAINS; FAILURE; OOCYTE; MOUSE; RATS; AGE AB Ovaries from National Toxicology Program Reproductive Assessment by Continuous Breeding (RACB) bioassays were used to directly compare differential ovarian follicle counts and reproductive performance for 15 chemicals, Ovaries of 10 animals per group from 16 studies in CD-1 mice and 1 study each in C3H and C57BL/6 mice were sectioned serially at 6 mu m. Counts of small, growing, and antral follicles were obtained in every 10th section, For all follicle types, younger mice had more follicles than older mice, and CD-1 mice had more follicles than age-matched animals from either inbred strain. The in-life portion of the RACB protocols demonstrated that 9 of 15 chemicals altered reproductive outcome in one or both sexes of mice, with six agents affecting females (R. E. Morrissey et al., 1989, Fundam. Appl. Toxicol. 13, 747-777), Three of six female toxicants [2,2-bis(boromoethyl)-1,3-propanediol, BPD; ethylene glycol monomethyl ether, EGME; methoxyacetic acid, MAA] significantly decreased counts of small and/or growing follicles by 33 to 92% in CD-1 mice; EGME also reduced follicle counts in the other strains. Follicle counts were decreased in progeny of animals treated with EGME or its active metabolite, MAA. For BPD, reductions in follicle numbers were proportional to dose. In CD-1 mice, female toxicants di-N-hexyl phthalate, propantheline bromide, and tricresyl phosphate reduced reproductive performance but not follicle numbers. Counts were not affected by toxicants for which the susceptible sex could not be determined (bisphenol A, ethylene glycol, oxalic acid). Altered follicle counts without apparent reproductive impairment occurred in CD-1 mice at lower doses of BPD but were not observed for nontoxic chemicals. These data suggest that differential follicle counts (1) are a quantifiable endpoint of ovarian injury in conventional bioassays, and (2) in some instances, may provide a more sensitive indicator of female reproductive toxicity than fertility. (C) 1997 Society of Toxicology. C1 NATL CTR TOXICOL RES, PATHOL ASSOCIATES INT, JEFFERSON, AR 72079 USA. NATL CTR TOXICOL RES, RISK ASSESSMENT DIV, JEFFERSON, AR 72079 USA. NIEHS, NATL TOXICOL PROGRAM, DEV & REPROD TOXICOL GRP, RES TRIANGLE PK, NC 27709 USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU PHS HHS [224-85-005] NR 36 TC 69 Z9 71 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD SEP PY 1997 VL 39 IS 1 BP 1 EP 10 DI 10.1006/faat.1997.2338 PG 10 WC Toxicology SC Toxicology GA YA718 UT WOS:A1997YA71800001 PM 9325022 ER PT J AU Debelenko, LV EmmertBuck, MR Zhuang, ZP Epshteyn, E Moskaluk, CA Jensen, RT Liotta, LA Lubensky, IA AF Debelenko, LV EmmertBuck, MR Zhuang, ZP Epshteyn, E Moskaluk, CA Jensen, RT Liotta, LA Lubensky, IA TI The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids SO GASTROENTEROLOGY LA English DT Article ID ZOLLINGER-ELLISON SYNDROME; PARATHYROID TUMORS; CHROMOSOME 11Q13; LINKAGE ANALYSIS; CELL CARCINOIDS; INTEGRATED MAP; ALLELIC LOSS; CLASSIFICATION; ASSOCIATION; DELETION AB Background & Aims: Both gastrin and genetic factors were suggested to underlie the pathogenesis of multiple gastric enterochromaffin-like (ECL) cell carcinoids, To assess the role of genetic alterations in carcinoid tumorigenesis, loss of heterozygosity (LOH) at the locus of the multiple endocrine neoplasia type 1 (MEN-1) gene was studied in gastric carcinoids of patients with MEN-1 and chronic atrophic type A gastritis (A-CAG), as well as in sporadically arising intestinal carcinoids, Methods: DNA extracted from archival tissue sections of 35 carcinoid tumors was assessed for LOH with eight polymorphic markers on chromosome 11q13. A combined tumor and family study was performed in 1 patient with MEN-1-Zollinger-Ellison syndrome (ZES), Results: LOH at 11q13 loci was detected in 15 of 20 (75%) MEN-1-ZES carcinoids, and each ECL-cell carcinoid with LOH showed deletion of the wildtype allele. Only 1 of 6 A-CAG carcinoids displayed LOH at the MEN-1 gene locus, and none of the 9 intestinal and rectal carcinoids showed 11q13 LOH, Conclusions: Gastric ECL-cell carcinoid is an independent tumor type of MEN-1 that shares a common developmental mechanism (via inactivation of the MEN-1 gene) with enteropancreatic and parathyroid MEN-1 tumors. Further analysis of sporadic and A-CAG carcinoids is needed to elucidate genetic factors involved in their tumorigenesis. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. UNIV VIRGINIA,DEPT PATHOL,CHARLOTTESVILLE,VA 22903. NIDDKD,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. NR 64 TC 111 Z9 113 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1997 VL 113 IS 3 BP 773 EP 781 DI 10.1016/S0016-5085(97)70171-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW960 UT WOS:A1997XW96000011 PM 9287968 ER PT J AU Park, JM Lee, JY Hatfield, DL Lee, BJ AF Park, JM Lee, JY Hatfield, DL Lee, BJ TI Differential mode of TBP utilization in transcription of the tRNA([Ser]Sec) gene and TATA-less class III genes SO GENE LA English DT Article DE selenocysteine; Xenopus laevis; RNA polymerase III; oligonucleotide competition ID RNA-POLYMERASE-III; BINDING PROTEIN; XENOPUS-LAEVIS; IN-VITRO; BOX; TFIIIB; INITIATION; MUTATIONS; ELEMENTS; PROMOTER AB The Xenopus laevis selenocysteine tRNA([Ser]Sec) gene utilizes the TATA box binding protein (TBP)for its transcription in a manner more like TATA-dependent class II genes than TATA-less class III tRNA genes, even though this gene is transcribed by RNA polymerase III (pol III). Addition of TBP increased in vitro transcription of the tRNA([Ser]Sec) gene and a RNA polymerase II- (Pol II-) dependent template, while it decreased TATA-independent tRNA(Met) gene transcription, in a dose-dependent manner. Addition of wild-type TBP, truncated TBP containing the highly conserved COOH-terminal domain or a mutant TBP defective in TATA-independent Pol III transcription to TBP-depleted extracts restored tRNA([Ser]Sec) transcription, while addition of a mutant TBP defective in pol II transcription did not. These studies provide evidence that common surfaces of TBP may be used in transcription from TATA-dependent promoters of the tRNA([Ser]Sec) gene and class II genes. Further, we show that distinct chromatographic fractions of TBP complexes are required for tRNA([Ser]Sec) gene transcription and TATA-less class III gene transcription. (C) 1997 Elsevier Science B.V. C1 SEOUL NATL UNIV,INST MOL BIOL & GENET,MOL GENET LAB,SEOUL 151742,SOUTH KOREA. NCI,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 25 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 1 PY 1997 VL 196 IS 1-2 BP 99 EP 103 DI 10.1016/S0378-1119(97)00211-4 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XV962 UT WOS:A1997XV96200013 PM 9322746 ER PT J AU Shakarian, AM Ellis, SL Mallinson, DJ Olafson, RW Dwyer, DM AF Shakarian, AM Ellis, SL Mallinson, DJ Olafson, RW Dwyer, DM TI Two tandemly arrayed genes encode the (histidine) secretory acid phosphatases of Leishmania donovani SO GENE LA English DT Article DE Leishmaniasis; phosphomonoesterase; trypanosomatid protozoan; kinetoplastid; human parasite ID PROMASTIGOTES; MECHANISM; SEQUENCE; PROTEINS; INVITRO; SITE AB Leishmania donovani promastigotes constitutively secrete a glycosylated and phosphorylated acid phosphatase activity. This secretory acid phosphatase (SAcP) was purified from L. donovani culture supernatants and amino-acid sequence was obtained from both the N-terminus and a tryptic peptide fragment derived from the isolated protein. A polymerase chain reaction (PCR)-based strategy, using degenerate oligo primers designed from the amino-acid sequence data, identified two single-copy, tandemly arrayed open reading frames (ORFs) capable of encoding the L. donovani SAcP (SAcP-1, 2052 bp and SAcP-2, 2124 bp). Both SAcP-1 and -2 were shown to be actively transcribed by L. donovani promastigotes by reverse transcription (RT) and PCR amplification. The deduced amino-acid sequences of SAcP-1 and SAcP-2 show high conservation to each other in four regions: a 23-amino-acid signal peptide; a catalytic domain containing several potential N-linked glycosylation sites; a Ser/Thr-rich repeat region containing multiple potential phosphorylation sites and a common C-terminus. Within the catalytic domain, the L. donovani SAcPs possess two conserved consensus sequences characteristic of histidine acid phosphatases (AcPs). Furthermore, antisera to native L. donovani SAcP immunoprecipitated in vitro transcription/translation products of both SAcP-1 and SAcP-2. Cumulatively, these data indicate that the acid phosphatase activity constitutively secreted by L. donovani promastigotes is composed of two (histidine) AcP isoforms that are encoded by SAcP-1 and SAcP-2, respectively. (C) 1997 Elsevier Science B.V. C1 NIAID,CELL BIOL SECT,PARASIT DIS LAB,DIV INTRAMURAL RES,NIH,BETHESDA,MD 20892. UNIV VICTORIA,DEPT BIOCHEM & MICROBIOL,VICTORIA,BC V8W 2Y2,CANADA. NR 29 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 1 PY 1997 VL 196 IS 1-2 BP 127 EP 137 DI 10.1016/S0378-1119(97)00218-7 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA XV962 UT WOS:A1997XV96200017 PM 9322750 ER PT J AU Muller, JR Mushinski, EB Williams, JA Hausner, PF AF Muller, JR Mushinski, EB Williams, JA Hausner, PF TI Immunoglobulin/Myc recombinations in murine Peyer's patch follicles SO GENES CHROMOSOMES & CANCER LA English DT Article ID C-MYC RECOMBINATIONS; CHROMOSOMAL TRANSLOCATIONS; PLASMACYTOMAS; TUMORS; BLOOD; CELLS; MICE AB Immunoglobulin heavy chain (Igh)/Myc recombinations are a hallmark of pristane-induced mouse plasmacytomas but are also frequently found in non-tumorous tissues. Here we describe for the first time a PCR-based technique for detecting fusions between Igh mu or Igh alpha and Myc in situ. lgh/Myc recombinations were found in transplanted and primary plasmacytomas. In addition, the gut-associated lymphoid tissues of plasmacytoma-free BALB/c mice were investigated for the presence of Igh/Myc fusions. Igh/Myc rearrangements were detected in Peyer's patch follicles and in the intestinal lamina propria both in normal mice and in mice shortly after pristane treatment. The sequence analysis showed that i) three to five different Igh/Myc hybrid sequences were present in individual follicles, ii) Igh/Myc recombinations can be subjected to additional switch recombinations as shown by related sequences in neighboring cells, and iii) cells harboring these rearrangements migrate into the adjacent lamina propria. The results indicate that Peyer's patches are a hyper-recombinogenic tissue. Myc recombination-positive cells are present in at least 100-fold more frequently than expected if recombinations were random, which suggests that this kind of trans-chromosomal rearrangement may be targeted. (C) 1997 Wiley-Liss, Inc.(dagger). RP Muller, JR (reprint author), NCI,GENET LAB,NIH,BLDG 37,ROOM 2B-09,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 20 TC 7 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 1997 VL 20 IS 1 BP 1 EP 8 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA XU170 UT WOS:A1997XU17000001 PM 9290947 ER PT J AU Sterneck, E Tessarollo, L Johnson, PF AF Sterneck, E Tessarollo, L Johnson, PF TI An essential role for C/EBP beta in female reproduction SO GENES & DEVELOPMENT LA English DT Article DE C/EBP beta knockout; granulosa cells; ovulation; corpus luteum; ovary; female reproduction ID ENHANCER-BINDING-PROTEIN; TRANSCRIPTION FACTOR; MYELOMONOCYTIC CELLS; LUTEINIZING-HORMONE; TARGETED DISRUPTION; GENE-EXPRESSION; NUCLEAR FACTOR; MESSENGER-RNA; MICE LACKING; RAT OVARY AB A large number of intercellular signaling molecules have been identified that orchestrate female reproductive physiology. However, with the exception of steroid hormone receptors, little information exists about the transcriptional regulators that mediate cellular responses to these signals. The transcription factor C/EBP beta (CCAAT/enhancer-binding protein beta) is expressed in ovaries and testes, as well as many other tissues of adult mice. Here we show that mice carrying a targeted deletion of the C/EBP beta gene exhibit reproductive defects. Although these animals develop normally and males are fertile, adult females are sterile. Transplantation of normal ovaries into mutant females restored fertility, thus localizing the primary reproductive defect to the ovary proper. In normal ovaries, C/EBP beta mRNA is specifically induced by luteinizing hormone (LH/hCG) in the granulosa layer of preovulatory antral follicles. C/EBP beta-deficient ovaries lack corpora lutea and fail to down-regulate expression of the prostaglandin endoperoxidase synthase 2 and P450 aromatase genes in response to gonadotropins. These findings demonstrate that C/EBP beta is essential for periovulatory granulosa cell differentiation in response to LH. C/EBP beta is thus established as a critical downstream target of G-protein-coupled LH receptor signaling and one of the first transcription factors, other than steroid hormone receptors, known to be required for ovarian follicle development in vivo. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT TRANSCRIPT REGULAT GRP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,ADV BIOSCI LABS INC,FREDERICK,MD 21702. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 48 TC 295 Z9 298 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 1997 VL 11 IS 17 BP 2153 EP 2162 DI 10.1101/gad.11.17.2153 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XV956 UT WOS:A1997XV95600001 PM 9303532 ER PT J AU Wilson, HR Kameyama, L Zhou, JG Guarneros, G Court, DL AF Wilson, HR Kameyama, L Zhou, JG Guarneros, G Court, DL TI Translational repression by a transcriptional elongation factor SO GENES & DEVELOPMENT LA English DT Article DE bacteriophage lambda; antitermination; N; RNA-binding proteins; long-distance regulation ID N-GENE-PRODUCT; RIBOSOMAL-PROTEIN OPERON; INTEGRATION HOST FACTOR; RNA-BINDING PROTEINS; SUBTILIS TRP OPERON; LAMBDA PL PROMOTER; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; PHAGE-LAMBDA; MESSENGER-RNA AB One of the classical positive regulators of gene expression is bacteriophage lambda N protein. N regulates the transcription of early phage genes by participating in the formation of a highly pro ces sive, terminator-resistant transcription complex and thereby stimulates the expression of genes lying downstream of transcriptional terminators. Also included in this antiterminating transcription complex are an RNA site (NUT) and host proteins (Nus). Here we demonstrate that N has an additional, hitherto unknown regulatory role, as a repressor of the translation of its own gene. N-dependent repression does not occur when NUT is deleted, demonstrating that N-mediated antitermination and translational repression both require the same cis-acting site in the RNA. In addition, we have identified one nut and several host mutations that eliminate antitermination and not translational repression, suggesting the independence of these two N-mediated mechanisms. finally, the position of nutL with respect to the gene whose expression is repressed is important. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL CONTROL & GENET SECT,FREDERICK,MD 21702. INST POLITECN NACL,CTR INVEST & ESTUDIOS AVANZADOS,DEPT GENET & MOL BIOL,MEXICO CITY 14,DF,MEXICO. NR 77 TC 27 Z9 30 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 1997 VL 11 IS 17 BP 2204 EP 2213 DI 10.1101/gad.11.17.2204 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XV956 UT WOS:A1997XV95600005 PM 9303536 ER PT J AU Rosenberg, M Hui, L Ma, JL Nusbaum, HC Clark, K Robinson, L Dziadzio, L Swain, PM Keith, T Hudson, TJ Biesecker, LG Flint, J AF Rosenberg, M Hui, L Ma, JL Nusbaum, HC Clark, K Robinson, L Dziadzio, L Swain, PM Keith, T Hudson, TJ Biesecker, LG Flint, J TI Characterization of short tandem repeats from thirty-one human telomeres SO GENOME RESEARCH LA English DT Letter ID CRYPTIC CHROMOSOMAL-ABNORMALITIES; GENETIC-LINKAGE MAP; HUMAN GENOME; MENTAL-RETARDATION; PHYSICAL ANALYSIS; DNA; POLYMORPHISM; REGION; KB; FRAGMENTS AB Completion of genetic and physical maps requires markers from the ends (telomeres) of every human chromosome. We have searched for short tandem repeats (microsatellites) in cosmid and P1 clones and generated 661 sequence-tagged sites (STS) from the terminal 300 kb of 31 human chromosome ends. PCR assays were successfully designed for 58 microsatellites and mapped both genetically and on radiation hybrids (RHs) to confirm their telomeric location. Sequence analysis revealed marked variation in sequence composition, consistent with the hypothesis that even very highly GC-rich chromosome bands (the T bands) are not homogenous. The STSs that we have generated will be a necessary resource For the construction of physical maps of these complex regions of the genome. C1 JOHN RADCLIFFE HOSP,INST MOL MED,OXFORD OX3 9DS,ENGLAND. NIH,NATL HUMAN GENOME RES INST,LAB GENET DIS RES,BETHESDA,MD 20892. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. GENOME THERAPEUT,WALTHAM,MA 02154. FU NHGRI NIH HHS [HG00098] NR 37 TC 36 Z9 36 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD SEP PY 1997 VL 7 IS 9 BP 917 EP 923 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XV957 UT WOS:A1997XV95700009 PM 9314497 ER PT J AU Shastry, BS Liu, XY Hejtmancik, JF Plager, DA Trese, MT AF Shastry, BS Liu, XY Hejtmancik, JF Plager, DA Trese, MT TI Evidence for genetic heterogeneity in X-linked familial exudative vitreoretinopathy SO GENOMICS LA English DT Article ID NORRIE DISEASE; MUTATION; LINKAGE C1 NEI,BETHESDA,MD 20892. INDIANA UNIV,DEPT OPHTHALMOL,INDIANAPOLIS,IN 46202. WILLIAM BEAUMONT HOSP,DEPT OPHTHALMOL,ROYAL OAK,MI 48073. RP Shastry, BS (reprint author), OAKLAND UNIV,EYE RES INST,ROCHESTER,MI 48309, USA. FU NEI NIH HHS [EY05230] NR 14 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1997 VL 44 IS 2 BP 247 EP 248 DI 10.1006/geno.1997.4863 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XY077 UT WOS:A1997XY07700014 PM 9299244 ER PT J AU Butler, RN Kupfer, C Faye, EE Guazzo, E AF Butler, RN Kupfer, C Faye, EE Guazzo, E TI Keeping an eye on vision: New tools to preserve sight and quality of life - A roundtable discussion .2. SO GERIATRICS LA English DT Editorial Material AB Research is pointing the way to new therapies for the eye diseases of aging. A gene that appears related to glaucoma has been identified, and a safe and effective inhibitor for aldose reductase is being sought for patients with diabetic retinopathy. Refinements in cataract surgery continue to improve the high success rate of this procedure. Physicians can educate their patients to participate in vision protection, through control of blood sugars, compliance with glaucoma medications, and the use of the Amsler grid by those at risk for macular degeneration. When vision cannot be corrected to the normal range, low vision rehabilitation offers magnification and new high-tech devices for optimizing independent patient function. C1 MT SINAI MED CTR, DEPT GERIATR & ADULT DEV, NEW YORK, NY USA. LIGHTHOUSE INC, MANHATTAN, KS USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. NEI, NIH, BETHESDA, MD 20892 USA. RP Butler, RN (reprint author), INT LONGEV CTR, NEW YORK, NY USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS INC PI DULUTH PA 131 W 1ST STREET, DULUTH, MN 55802 USA SN 0016-867X EI 1936-5764 J9 GERIATRICS JI Geriatrics PD SEP PY 1997 VL 52 IS 9 BP 48 EP + PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA XW961 UT WOS:A1997XW96100004 PM 9307572 ER PT J AU Vannucci, SJ Maher, F Simpson, IA AF Vannucci, SJ Maher, F Simpson, IA TI Glucose transporter proteins in brain: Delivery of glucose to neurons and glia SO GLIA LA English DT Review DE glucose transport; cerebral glucose utilization; neurons; glia ID DEVELOPING RAT-BRAIN; ELECTRON-MICROSCOPIC IMMUNOGOLD; CEREBELLAR GRANULE NEURONS; PRIMARY CULTURED NEURONS; CYTOCHALASIN-B BINDING; GENE-EXPRESSION; ALZHEIMERS-DISEASE; MESSENGER-RNA; FRUCTOSE TRANSPORTER; HYPOXIA-ISCHEMIA AB Glucose is the principle energy source for the mammalian brain. Delivery of glucose from the blood to the brain requires transport across the endothelial cells of the blood-brain barrier and into the neurons and glia. The facilitative glucose transporter proteins mediate these processes. The primary isoforms in brain are GLUT1, detected at high concentrations as a highly glycosylated form, (55 kDa) in blood-brain barrier, and also as a less glycosylated, 45 kDa form, present in parenchyma, predominantly glia; GLUTS in neurons; and GLUTS in microglia. The rest of the transporter family, GLUTs 2, 4, and 7, have also been detected in brain but at lower levels of expression and confined to more discrete regions. All of the transporters probably contribute to cerebral glucose utilization, as part of overall metabolism and metabolic interactions among cells. We discuss the properties, regulation, cell-specific location, and kinetic characteristics of the isoforms, their potential contributions to cerebral metabolism, and several experimental paradigms in which alterations in energetic demand and/or substrate supply affect glucose transporter expression. (C) 1997 Wiley-Liss, Inc. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT CELL & MOL PHYSIOL,HERSHEY,PA 17033. UNIV MELBOURNE,DEPT PATHOL,PARKVILLE,VIC 3052,AUSTRALIA. NIDDK,DB,NIH,BETHESDA,MD. RP Vannucci, SJ (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PEDIAT,POB 850,HERSHEY,PA 17033, USA. FU NICHD NIH HHS [R29 HD31521] NR 140 TC 353 Z9 367 U1 4 U2 30 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0894-1491 J9 GLIA JI Glia PD SEP PY 1997 VL 21 IS 1 BP 2 EP 21 DI 10.1002/(SICI)1098-1136(199709)21:1<2::AID-GLIA2>3.0.CO;2-C PG 20 WC Neurosciences SC Neurosciences & Neurology GA XU475 UT WOS:A1997XU47500002 PM 9298843 ER PT J AU Chow, WH Blaser, MJ Blot, WJ Gammon, MD Vaughan, TL Risch, HA PerezPerez, GI AF Chow, WH Blaser, MJ Blot, WJ Gammon, MD Vaughan, TL Risch, HA PerezPerez, GI TI H-pylori and CagA status in relation to risk of adenocarcinomas of esophagus and stomach by anatomic subsite SO GUT LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. COLUMBIA UNIV,NEW YORK,NY. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. YALE UNIV,NEW HAVEN,CT. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD SEP PY 1997 VL 41 SU 1 BP A33 EP A34 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW445 UT WOS:A1997XW44500126 ER PT J AU PerezPerez, GI Groves, F Zhang, L You, WC Fraumeni, JF Blaser, MJ AF PerezPerez, GI Groves, F Zhang, L You, WC Fraumeni, JF Blaser, MJ TI Relationship between CagA seroprevalence and gastric cancer rates in Chinese populations SO GUT LA English DT Meeting Abstract C1 VANDERBILT UNIV,SCH MED,NASHVILLE,TN. VET AFFAIRS MED CTR,NASHVILLE,TN 37212. BEIJING INST CANC RES,BEIJING,PEOPLES R CHINA. NCI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD SEP PY 1997 VL 41 SU 1 BP A49 EP A49 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW445 UT WOS:A1997XW44500186 ER PT J AU Omori, N Omori, M Evarts, RP Teramoto, T Miller, MJ Hoang, TN Thorgeirsson, SS AF Omori, N Omori, M Evarts, RP Teramoto, T Miller, MJ Hoang, TN Thorgeirsson, SS TI Partial cloning of rat CD34 cDNA and expression during stem cell-dependent liver regeneration in the adult rat SO HEPATOLOGY LA English DT Article ID SINUSOIDAL ENDOTHELIAL-CELLS; GROWTH-FACTOR-ALPHA; C-KIT; HEMATOPOIETIC PROGENITOR; HEPATIC DIFFERENTIATION; SIALOMUCIN CD34; MESSENGER-RNA; MURINE CD34; HEPATOCELLULAR-CARCINOMA; L-SELECTIN AB The sialomucin CD34 is expressed on human and mouse hematopoietic stem cells and is used as an important marker for isolating the hematopoietic stem/progenitor cells, The involvement of hepatic stem cells in liver regeneration under certain conditions in adult rats is now well supported. The objective of the present research was to explore the idea that CD34 might also be expressed on hepatic stem cell progeny, Polymerase chain reaction (PCR)-based cloning of rat CD34 was partially accomplished. During the hepatic stem cell activation (2-acetylaminofluorene/partial hepatectomy [AAF/PH] model), the CD34 transcripts were increased and reached the peak level between 9 and 12 days after partial hepatectomy when the progenitor cells (e.g., oval cells, early hepatocytes in basophilic foci, and intestinal type of cells) are most abundant, Both in situ hybridization and immunohistochemistry, using anti-mouse CD34 antibody, which recognizes the cytoplasmic domain, clearly showed the expression of CD34 on oval cells as well as on endothelial cells of large hepatic vessels, In addition, bile ductular epithelial (BDE) cells both in the AAF/PH model and in normal liver expressed CD34, suggesting a close relationship between BDE cells and the hepatic stem-cell compartment, Taken-together, the data indicate that CD34 would, similar to its role in the hematopoietic system, be an important probe for characterizing the cellular biology of the hepatic stem-cell compartment. C1 NCI,EXPT CARCINOGENESIS LAB,DBS,NIH,BETHESDA,MD 20892. NR 39 TC 117 Z9 120 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1997 VL 26 IS 3 BP 720 EP 727 DI 10.1002/hep.510260325 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XV952 UT WOS:A1997XV95200026 PM 9303503 ER PT J AU Alter, HJ ConryCantilena, C Melpolder, J Tan, D VanRaden, M Herion, D Lau, D Hoofnagle, JH AF Alter, HJ ConryCantilena, C Melpolder, J Tan, D VanRaden, M Herion, D Lau, D Hoofnagle, JH TI Hepatitis C in asymptomatic blood donors SO HEPATOLOGY LA English DT Article; Proceedings Paper CT National-Institute-of-Health Consensus Development Conference for the Management of Hepatitis C CY MAR 24-26, 1997 CL KENSINGTON, MD SP NIH, Off Med Applicat Res, NIAID, NHLBI, NIDA, Ctr Dis Control & Prevent ID CHRONIC LIVER-DISEASE; NON-A; TRANSFUSION AB Among 248 asymptomatic blood donors positive for antibody to hepatitis C virus (anti-HCV) enrolled in a long-term prospective study, 86% had chronic HCV infection and 14% appeared to have recovered as assessed by serial determinations of serum alanine aminotransferase (ALT) levels and HCV RNA by polymerase chain reaction. Established parenteral risk factors for HCV transmission were identified in 75% of donors. In addition, there was a strong independent association between HCV positivity and cocaine snorting, suggesting that shared snorting devices may be a covert route of parenteral transmission. Ear piercing in males was also significantly associated with transmission. There was no evidence for sexual spread, Although the majority of HCV carriers had both biochemical and histological evidence of chronic viral hepatitis, the extent of liver injury was generally mild. Among a larger population of 280 HCV RNA-positive donors, 17% had repeatedly normal ALT levels, 45% had levels that did not exceed twice, and only 22% had levels that exceeded five times the upper limit of the normal range. Among 81 patients who underwent liver biopsy, only 13% had evidence of severe hepatitis (8%) or cirrhosis (5%), despite a duration of infection that generally exceeded 15 years. No severe histological lesions were observed in blood donors with chronic HCV infection who had repeatedly normal ALT levels. In both donors and blood recipients, the frequency of severe morbidity or mortality related to HCV infection was less than 10% during the first two decades of infection. Further longterm studies are required to see if the progression to severe outcomes continues to accrue at this slow pace or whether it accelerates during subsequent decades. C1 NIAID,DIV MICROBIOL & INFECT DIS,NIH,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. RP Alter, HJ (reprint author), NIH,DEPT TRANSFUS MED,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 1C-711,BETHESDA,MD 20892, USA. NR 10 TC 61 Z9 67 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1997 VL 26 IS 3 SU 1 BP S29 EP S33 DI 10.1002/hep.510260705 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW273 UT WOS:A1997XW27300006 PM 9305660 ER PT J AU Everhart, JE Stolar, M Hoofnagle, JH AF Everhart, JE Stolar, M Hoofnagle, JH TI Management of hepatitis C: A national survey of gastroenterologists and hepatologists SO HEPATOLOGY LA English DT Article; Proceedings Paper CT National-Institute-of-Health Consensus Development Conference for the Management of Hepatitis C CY MAR 24-26, 1997 CL KENSINGTON, MD SP NIH, Off Med Applicat Res, NIAID, NHLBI, NIDA, Ctr Dis Control & Prevent AB A survey on the management of hepatitis C virus (HCV) infection was conducted by the American Digestive Health Foundation among United States physicians who are most familiar with the disease. The two-page survey was completed by 57% of a random sample of 2,500 members of the American Gastroenterological Association and the American Association for the Study of Liver Diseases. Analysis was limited to the 1,249 responses from physicians who spent at least 1 day per week in patient care. These physicians frequently managed patients with HCV, and nearly three quarters treated patients with interferon. To prevent transmission, the large majority of physicians recommended measures to avoid blood exposures, were uncertain or disagreed about the importance of sexual contact, and did not caution patients about casual contact. More than 70% of physicians told their patients to stop or minimize alcohol consumption. In the management of a patient with antibody to HCV but normal serum aminotransferase activities, 87% of physicians would have ordered a supplemental lest, and if HCV mere confirmed, 46% would have obtained a liver biopsy, but only 15% would have treated the patient with interferon. For a patient with chronic HCV infection and elevated serum aminotransferase activities, more than 90% of physicians mould have obtained a liver biopsy and approximately 60% would have treated with interferon. Physicians who are most familiar with the management of patients with HCV generally agreed with the recommendations of the Consensus Development Conference Panel regarding prevention of transmission, minimizing alcohol consumption, and managing patients with typical presentations, Controversies remain regarding some issues of general management, the value of molecular resting, and the need to treat certain patients with interferon. C1 AMER GASTROENTEROL ASSOC,BETHESDA,MD. RP Everhart, JE (reprint author), NIDDKD,EPIDEMIOL & CLIN TRIALS BRANCH,DIV DIGEST DIS & NUTR,NATCHER BLDG,ROOM 6AN-12J,BETHESDA,MD 20892, USA. NR 2 TC 26 Z9 26 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1997 VL 26 IS 3 SU 1 BP S78 EP S82 DI 10.1002/hep.510260714 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW273 UT WOS:A1997XW27300015 PM 9305669 ER PT J AU Hoofnagle, JH AF Hoofnagle, JH TI Hepatitis C: The clinical spectrum of disease SO HEPATOLOGY LA English DT Article; Proceedings Paper CT National-Institute-of-Health Consensus Development Conference for the Management of Hepatitis C CY MAR 24-26, 1997 CL KENSINGTON, MD SP NIH, Off Med Applicat Res, NIAID, NHLBI, NIDA, Ctr Dis Control & Prevent ID NON-B-HEPATITIS; NON-A-HEPATITIS; VIRUS-INFECTION; LIVER-DISEASE; BLOOD-DONORS; LONG-TERM; POSTTRANSFUSION HEPATITIS; HISTOLOGICAL FEATURES; VIRAL-HEPATITIS; UNITED-STATES AB Hepatitis C virus (HCV) accounts for approximately 20% of cases of acute hepatitis, 70% of chronic hepatitis, and 30% of end-stage liver disease in the United States. The acute infection has an incubation period of 7 weeks (range, 4-20 weeks) and is symptomatic and icteric in only one third of patients. Serum aminotransferase levels generally increase greater than 10-fold elevated and as symptoms and signs resolve decrease into the normal range. Antibody to HCV is usually but not always present at the time of onset of symptoms, HCV RNA appears in the serum early during the incubation period, increases in titer and peaks at the time of symptoms, and then disappears in resolving disease. Importantly, 85% of patients with acute HCV infection develop chronic infection. In these patients, HCV RNA remains present and in approximately two thirds of patients, aminotransferases remain elevated in the range of 1.5- to 10-fold the upper limit of normal. The course of chronic hepatitis C is variable, Probably fewer than 20% of patients have symptoms and they are usually intermittent, vague, and nonspecific, largely being malaise and easy fatiguability. A small percentage of patients develop extrahepatic manifestations of hepatitis C, including cryoglobulinemia and glomerulonephritis. It is estimated that 20% to 30% of patients with chronic hepatitis C develop cirrhosis, but the process is generally slow and insidious. Once cirrhosis develops, symptoms are more common and the signs of end-stage liver disease can appear with jaundice, weakness, wasting, and gastrointestinal bleeding. Patients with cirrhosis are also at risk for developing hepatocellular carcinoma. Thus, this important liver disease has protean manifestations but is often insidious and can lead to endstage liver disease despite the presence of few symptoms and signs of illness. RP Hoofnagle, JH (reprint author), NIDDKD,DIV DIGEST DIS & NUTR,NIH,BLDG 31,ROOM 9A23,BETHESDA,MD 20892, USA. NR 47 TC 270 Z9 274 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1997 VL 26 IS 3 SU 1 BP S15 EP S20 DI 10.1002/hep.510260703 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW273 UT WOS:A1997XW27300004 PM 9305658 ER PT J AU Purcell, R AF Purcell, R TI The hepatitis C virus: Overview SO HEPATOLOGY LA English DT Article; Proceedings Paper CT National-Institute-of-Health Consensus Development Conference for the Management of Hepatitis C CY MAR 24-26, 1997 CL KENSINGTON, MD SP NIH, Off Med Applicat Res, NIAID, NHLBI, NIDA, Ctr Dis Control & Prevent ID NON-B-HEPATITIS; POST-TRANSFUSION HEPATITIS; NON-A; GAMMA-GLOBULIN; ENVELOPE; GLYCOPROTEIN; ASSOCIATION; ANTIBODIES; PREVENTION; GENOTYPES AB Our knowledge of hepatitis C virus (HCV) dates only from 1975, when non-A, non-B hepatitis was first recognized. It was not until 1989 that the genome of the virus was first cloned and sequenced, and expressed viral antigens used to develop serological assays for screening and diagnosis. HCV is in a separate genus of the virus family Flaviviridae. It is a spherical enveloped virus of approximately 50 nm in diameter, Its genome is a single-stranded linear RNA molecule of positive sense and consists of a 5' noncoding region, a single large open reading frame, and a 3' noncoding region. The open reading frame encodes at least three structural and six nonstructural proteins. The genome is characterized by significant genetic heterogeneity, based on which HCV isolates can be classified into six major genotypes and more than 50 subtypes. Even individual isolates of HCV are genetically heterogeneous (quasispecies diversity), Genetic heterogeneity of HCV is greatest in the amino-terminal end of the second envelope protein (hypervariable region 1). This region map represent a neutralization epitope that is under selective pressure from the host's humoral immune response. Infection with HCV proceeds to chronicity in more than 80% of cases, and even recovery does not protect against subsequent re-exposure to the virus. The development of a broadly protective vaccine against HCV will therefore require a better understanding of the molecular biology and immune response to this virus. RP Purcell, R (reprint author), NIAID,HEPATITIS VIRUSES SECT,INFECT DIS LAB,NIH,BLDG 7,ROOM 202,BETHESDA,MD 20892, USA. NR 39 TC 85 Z9 88 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1997 VL 26 IS 3 SU 1 BP S11 EP S14 DI 10.1002/hep.510260702 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XW273 UT WOS:A1997XW27300003 PM 9305657 ER PT J AU Zaretsky, JZ Candotti, F Boerkoel, C Adams, EM Yewdell, JW Blaese, RM Plotz, PH AF Zaretsky, JZ Candotti, F Boerkoel, C Adams, EM Yewdell, JW Blaese, RM Plotz, PH TI Retroviral transfer of acid alpha-glucosidase cDNA to enzyme-deficient myoblasts results in phenotypic spread of the genotypic correction by both secretion and fusion SO HUMAN GENE THERAPY LA English DT Article ID GLYCOGENOSIS TYPE-II; MUCOPOLYSACCHARIDOSIS TYPE-VII; MEDIATED GENE-TRANSFER; SKELETAL-MUSCLE; LYSOSOMAL-ENZYMES; INTRACELLULAR-TRANSPORT; CULTURED FIBROBLASTS; SYSTEMIC DELIVERY; POMPE DISEASE; CELL-LINES AB Myoblasts have properties that make them suitable vehicles for gene replacement therapy, and lysosomal storage diseases are attractive targets for such therapy, Type II Glycogen Storage Disease, a deficiency of acid alpha-glucosidase (GAA), results in the abnormal accumulation of glycogen in skeletal and cardiac muscle lysosomes, The varied manifestations of the enzyme deficiency in affected patients are ultimately lethal, We used a retroviral vector carrying the cDNA encoding for GAA to replace the enzyme in deficient myoblasts and fibroblasts and analyzed the properties of the transduced cells, The transferred gene was efficiently expressed, and the de novo-synthesized enzyme reached lysosomes where it digested glycogen, In enzyme-deficient myoblasts after transduction, enzyme activity rose to more than 30-fold higher than in normal myoblasts and increased about five-fold more when the cells were allowed to differentiate into myotubes, The transduced cells secreted GAA that was endocytosed via the mannose-6-phosphate receptor into lysosomes of deficient cells and digested glycogen, Moreover, the transduced myoblasts were able to fuse with and provide enzyme for GAA-deficient fusion partners, Thus, the gene-corrected cells, which appear otherwise normal, may ultimately provide phenotypic correction to neighboring GAA-deficient cells by fusion and to distant cells by secretion and uptake mechanisms. C1 NIAMS,ARTHRITIS & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT CELL RES & IMMUNOL,RAMAT AVIV,ISRAEL. NCHGR,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 54 TC 27 Z9 28 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP 1 PY 1997 VL 8 IS 13 BP 1555 EP 1563 DI 10.1089/hum.1997.8.13-1555 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XX854 UT WOS:A1997XX85400003 PM 9322088 ER PT J AU Lavedan, CN Garrett, L Nussbaum, RL AF Lavedan, CN Garrett, L Nussbaum, RL TI Trinucleotide repeats (CGG)(22)TGG(CGG)(43)TGG(CGG)(21) from the fragile X gene remain stable in transgenic mice SO HUMAN GENETICS LA English DT Article ID DNA MISMATCH REPAIR; HUNTINGTONS-DISEASE; CAG REPEAT; CGG REPEAT; FOUNDER CHROMOSOMES; MYOTONIC-DYSTROPHY; CPG ISLAND; INSTABILITY; EXPANSION; METHYLATION AB Unstable premutation alleles in fragile X contain CGG repeats ranging from 34 to about 200. To study the mechanism of formation and the behavior of dynamic mutations, we constructed and cloned 88 trinucleotide repeats including 43 uninterrupted CGGs and injected them into mouse fertilized oocytes. We analyzed 342 transgenic animals obtained from 6 different founders after one to four generations, and found that the repeats remained stable regardless of the sex of the transmitting mouse. Therefore, we may need to consider factors other than trinucleotide repeat length alone to explain CGG instability and create an animal model. C1 NHGRI,LAB GENET DIS RES,NIH,BETHESDA,MD 20892. JOHNS HOPKINS BAYVIEW MED CTR,BALTIMORE,MD. NR 64 TC 28 Z9 29 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 1997 VL 100 IS 3-4 BP 407 EP 414 DI 10.1007/s004390050525 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA XQ407 UT WOS:A1997XQ40700018 PM 9272164 ER PT J AU Hayashi, T Fleming, MV StetlerStevenson, WG Liotta, LA Moss, J Ferrans, VJ Travis, WD AF Hayashi, T Fleming, MV StetlerStevenson, WG Liotta, LA Moss, J Ferrans, VJ Travis, WD TI Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM) SO HUMAN PATHOLOGY LA English DT Article DE matrix metalloproteinases; tissue inhibitors of metalloproteinases; lymphangioleiomyomatosis; immunohistochemistry, confocal microscopy ID INTERSTITIAL COLLAGENASE; TRANSBRONCHIAL BIOPSY; IV COLLAGENASE; ELASTIC FIBERS; CELL-LINES; LYMPHANGIOMYOMATOSIS; ANGIOMYOLIPOMA; MORPHOGENESIS; METASTASIS; EXPRESSION AB To evaluate the role of matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) in the pathogenesis of the structural damage and cystic lesions found in pulmonary lymphangioleiomyomatosis (LAM), immunohistochemical studies were made of the localization of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, HMB-45, and type TV collagen in sections of lung biopsy specimens from four patients with this disorder. These studies showed increased immunoreactivity compared with that in normal bronchiolar and vascular smooth muscle cells, of MMP-2 and, to a lesser extent, MMP-9 and MMP-1 in the LAM cells. MMP-2 was also localized in some elastic fibers and in the basement membranes of LAM cells and overlying epithelial cells. The basement membranes in both of these sites often showed colocalization of MMP-2 and type IV collagen. Some epithelial basement membranes showing this colocalization were disrupted. These changes were not accompanied by increased immunoreactivity for TIMPs. Taken together with previous observations showing structural damage to elastic fibers and collagen fibrils, and with the absence of demonstrable neutrophil or pancreatic types of elastase, these findings suggest that MMP-2 and MMP-9 (both of which can degrade elastin as well as collagens) are responsible for the connective tissue destruction and cyst formation in LAM. (C) 1997 by W.B. Saunders Company. C1 NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT PULM & MED PATHOL,WASHINGTON,DC 20306. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 20 TC 105 Z9 111 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1997 VL 28 IS 9 BP 1071 EP 1078 DI 10.1016/S0046-8177(97)90061-7 PG 8 WC Pathology SC Pathology GA XY090 UT WOS:A1997XY09000012 PM 9308732 ER PT J AU Peterson, JC Adler, S Burkart, JM Greene, T Hebert, LA Hunsicker, LG King, AJ Klahr, S Massry, SG Seifter, JL Kusek, JW Agodoa, LY Jones, CA Levey, AS Breyer, JA Faubert, P Rolin, HA Wang, SR AF Peterson, JC Adler, S Burkart, JM Greene, T Hebert, LA Hunsicker, LG King, AJ Klahr, S Massry, SG Seifter, JL Kusek, JW Agodoa, LY Jones, CA Levey, AS Breyer, JA Faubert, P Rolin, HA Wang, SR TI Effects of blood pressure control on progressive renal disease in blacks and whites SO HYPERTENSION LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Society-of-Nephrology CY NOV 14, 1993 CL BOSTON, MA SP Amer Soc Nephrol DE renal disease; blood pressure; renal function; proteinuria; race ID DIETARY-PROTEIN RESTRICTION; GLOMERULAR-FILTRATION RATE; FACTOR-INTERVENTION-TRIAL; DIABETES-MELLITUS; HYPERTENSION; INSUFFICIENCY; RACE AB African Americans (blacks) have a disproportionately high incidence of end-stage renal disease due to hypertension. The Modification of Diet in Renal Disease (MDRD) Study found that strict blood pressure control slowed the decline in glomerular filtration rate (GFR) only in the subgroup of patients with proteinuria. The present report compares the effects of blood pressure control in black and white MDRD Study participants. Fifty-three black and 495 white participants with baseline GFRs of 25 to 55 ml/min/1.73 m(2) were randomly assigned to a usual or low mean arterial pressure (MAP) goal of less than or equal to 107 or less than or equal to 92 mm HE, respectively. GFR decline was compared between randomized groups and correlated with the level of achieved blood pressure. The mean (+/-SE) GFR decline over 3 years in the low blood pressure group was 11.8+/-7.3 ml/min slower than in the usual blood pressure group among blacks (P=.11) compared with 0.3+/-1.3 ml!min slower among whites (P=.81) (P=.12 between blacks and whites). In both blacks and whites, higher baseline urine protein excretion was associated with a greater beneficial effect of the low MAP goal on GFR decline (P=.02 for both races). Combining both blood pressure groups and controlling for baseline characteristics, higher follow-up achieved MAP was associated with faster GFR decline in both blacks (P<.001) and whites (P=.002), with a sevenfold stronger relationship in blacks (P<.001). These secondary analyses support the prior recommendation for a lower than usual blood pressure goal (MAP less than or equal to 92 mm Hg) in black and white patients with proteinuria (>1 g/d). In addition, a lower level of blood pressure control may be even more important in blacks than in whites in slowing the progression of renal disease. C1 NIDDKD, NIH, BETHESDA, MD 20892 USA. NR 40 TC 0 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1997 VL 30 IS 3 BP 428 EP 435 PN 1 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY068 UT WOS:A1997XY06800020 ER PT J AU OConnor, DT Mahata, M Mahata, SK Taupenot, L Wu, HJ Yoo, SH Parmer, RJ AF OConnor, DT Mahata, M Mahata, SK Taupenot, L Wu, HJ Yoo, SH Parmer, RJ TI A novel, catecholamine release-inhibitory peptide from chromogranin A (CgA): Autocrine control of nicotinic cholinergic-stimulated exocytosis. SO HYPERTENSION LA English DT Meeting Abstract C1 NIDCD,NIH,BETHESDA,MD 20892. VET ADM MED CTR,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,CTR GENET MOL,SAN DIEGO,CA 92161. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1997 VL 30 IS 3 BP P114 EP P114 PN 1 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY068 UT WOS:A1997XY06800212 ER PT J AU Zeng, GY Clinton, BK Kirby, M Mostowski, H Quon, MJ AF Zeng, GY Clinton, BK Kirby, M Mostowski, H Quon, MJ TI Tyrosine kinase-deficient mutant insulin receptors overexpressed in vascular endothelial cells fail to mediate production of nitric oxide SO HYPERTENSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1997 VL 30 IS 3 BP P131 EP P131 PN 1 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XY068 UT WOS:A1997XY06800229 ER PT J AU Yoder, MC Hiatt, K Dutt, P Mukherjee, P Bodine, DM Orlic, D AF Yoder, MC Hiatt, K Dutt, P Mukherjee, P Bodine, DM Orlic, D TI Characterization of definitive lymphohematopoietic stem cells in the day 9 murine yolk sac SO IMMUNITY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; LONG-TERM REPOPULATION; COLONY-FORMING CELLS; IN-VIVO; MOUSE EMBRYO; C-KIT; SIALOMUCIN CD34; MESSENGER-RNA; EXPRESSION; VITRO AB The site of origin of lymphohematopoietic stem cells (HSC) that initiate definitive blood cell production in the murine fetal liver is controversial. Contrary to reports that the preliver yolk sac does not contain definitive HSC, we observed that CD34(+) day 9 yolk sac cells repopulated multiple blood cell lineages in newborn hosts for at least 1 year. Furthermore, 100 CD34(+)cKit(+) day 9 yolk sac or para-aortic splanchnopleura (P-Sp) cells, known to give rise to embryonic HSC, similarly repopulated hematopoiesis in recipient hosts, Surprisingly, 37-fold more CD34(+)c-Kit(+) cells reside in the day 9 yolk sac than in the P-Sp. In sum, definitive HSC are coexistent, but not equal in number, in the murine yolk sac and P-Sp prior to fetal liver colonization. C1 INDIANA UNIV,SCH MED,DEPT PEDIAT,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,INDIANAPOLIS,IN 46202. NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. RP Yoder, MC (reprint author), INDIANA UNIV,SCH MED,HERMAN B WELLS CTR PEDIAT RES,INDIANAPOLIS,IN 46202, USA. NR 47 TC 297 Z9 302 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 1997 VL 7 IS 3 BP 335 EP 344 DI 10.1016/S1074-7613(00)80355-6 PG 10 WC Immunology SC Immunology GA XY830 UT WOS:A1997XY83000003 PM 9324354 ER PT J AU Endres, R Luz, A Schulze, H Neubauer, H Futterer, A Holland, SM Wagner, H Pfeffer, K AF Endres, R Luz, A Schulze, H Neubauer, H Futterer, A Holland, SM Wagner, H Pfeffer, K TI Listeriosis in p47(phox-/-) and TRp55(-/-) mice: Protection despite absence of ROI and susceptibility despite presence of RNI SO IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA PRODUCTION; CELL-INDEPENDENT PATHWAY; NATURAL-KILLER-CELLS; IFN-GAMMA; MONOCYTOGENES INFECTION; MURINE LISTERIOSIS; NITRIC-OXIDE; MACROPHAGE ACTIVATION; TARGETED DISRUPTION AB The significance of host defense mechanisms in primary listeriosis in vivo is incompletely understood. Here, we show that tumor necrosis factor receptor p55(-/-) (TRp55(-/-)) mice are susceptible to Listeria monocytogenes infection in the presence of leukocyte recruitment, inflammatory cytokine production (including IFN gamma), nitric oxide synthesis, and oxidative burst formation. Mice deficient for oxidative burst (p47(phox-/-) mice) are relatively resistant to listeriosis. Despite activation of these antibacterial effector systems, TRp55(-/-) phagocytes in vivo are incapable of confining and eradicating L. monocytogenes inside phagolysosomes. Bone marrow chimeras reveal that for eradication of L. monocytogenes, TRp55 is crucially required only on cells from hematopoietic origin. Unexpectedly, prior to death, exocrine pancreatic cells undergo apoptosis in TRp55(-/-) mice. Collectively, these data demonstrate that in vivo, TRp55 initiates a protective, listericidal mechanism in phagocytes that differs from nitric oxide production and oxidative burst formation and that uncontrolled listeriosis results in necrotizing pancreatitis in TRp55(-/-) mice. C1 TECH UNIV MUNICH,INST MED MICROBIOL IMMUNOL & HYG,D-81675 MUNICH,GERMANY. GSF,NAT RES CTR ENVIRONM & HLTH,INST PATHOL,D-85758 OBERSCHLEISSHEIM,GERMANY. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. RI Neubauer, Hans/C-4467-2016 OI Neubauer, Hans/0000-0002-3467-4105 NR 57 TC 97 Z9 100 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 1997 VL 7 IS 3 BP 419 EP 432 DI 10.1016/S1074-7613(00)80363-5 PG 14 WC Immunology SC Immunology GA XY830 UT WOS:A1997XY83000011 PM 9324362 ER PT J AU Weinberger, DR Gallhofer, B AF Weinberger, DR Gallhofer, B TI Cognitive function in schizophrenia SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Xth World Congress of Psychiatry CY AUG 23-28, 1996 CL MADRID, SPAIN DE schizophrenia; cognitive function; risperidone; conventional neuroleptics; working executive memory ID MONOZYGOTIC TWINS DISCORDANT; CARD SORTING TEST; NEGATIVE SYNDROME SCALE; FRONTAL-LOBE LESIONS; PREFRONTAL CORTEX; IRRELEVANT INFORMATION; GUIDED BEHAVIOR; SMOOTH-PURSUIT; WORKING MEMORY; EYE TRACKING AB Impaired cognitive function in schizophrenia, once thought to be a secondary effect of the psychosis, is now seen as an enduring and core feature. It has many manifestations, but the most disruptive element is arguably a fundamental defect in the patient's ability to manipulate available information. The magnitude of the cognitive deficit in schizophrenia is considerable and remains relatively stable despite fluctuations in other symptoms. The degree of dysfunction also has a high predictive value for long-term disability. In recent years, more attention has been directed towards cognitive dysfunction in schizophrenia as a result of which assessment scales and diagnostic systems increasingly incorporate cognitive dysfunction as an independent domain. Good cognitive function depends upon the brain's ability to prioritize tasks and to switch from parallel processing to sequential processing when the processing load is excessive. This requires working executive memory. Neuroimaging and functional analyses suggest that such cognitive function relies upon unimpaired prefrontal activity. In addition, there is increasing evidence that antipsychotic drugs with 5-hydroxytryptamine (5-HT)(2A)-blocking activity produce better cognitive function in patients with schizophrenia than drugs with predominantly dopamine (D)(2)-blocking activity (conventional neuroleptics). The development of sophisticated, computer-delivered maze tasks has shown that newer antipsychotics, such as clozapine and risperidone, differ from conventional neuroleptics in their effects on cognitive function. The prospects, therefore, are that patients treated with drugs having 5-HT2A-blocking activity will have better cognitive function and will be better able to function in life's roles than will patients treated with conventional neuroleptics. C1 UNIV GIESSEN,SCH MED,CTR PSYCHIAT,GIESSEN,GERMANY. RP Weinberger, DR (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 89 TC 56 Z9 59 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 1997 VL 12 SU 4 BP S29 EP S36 DI 10.1097/00004850-199709004-00006 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA YA777 UT WOS:A1997YA77700006 PM 9352344 ER PT J AU Hwang, CP Lamb, ME AF Hwang, CP Lamb, ME TI Father involvement in Sweden: A longitudinal study of its stability and correlates SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article AB A total of 116 two-parent Swedish families were followed from the time their first-born children averaged 16 months until they were 8.5 years of age. Parents provided time-diary estimates of paternal participation and independent estimates of their relative responsibility and their children's preferences when the children were 16, 28, 40, 80, and 102 months of age. Children reported on their preferences and their parents' responsibilities in the last two phases. Analyses showed convergence between parents' and children's estimates of paternal involvement and parental preferences, underscoring the reliability of the data. Although poorly correlated with one another, relative and absolute measures of paternal involvement were modestly stable over time, with higher stability evident on reports of relative rather than absolute levels of involvement. C1 NATL INST CHILD HLTH & HUMAN DEV,SECT SOCIAL & EMOT DEV,BETHESDA,MD 20814. GOTHENBURG UNIV,S-41124 GOTHENBURG,SWEDEN. NR 17 TC 27 Z9 28 U1 1 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD SEP PY 1997 VL 21 IS 3 BP 621 EP 632 PG 12 WC Psychology, Developmental SC Psychology GA XZ422 UT WOS:A1997XZ42200010 ER PT J AU Tataranni, PA Monroe, MB Dueck, CA Traub, SA Nicolson, M Manore, MM Matt, KS Ravussin, E AF Tataranni, PA Monroe, MB Dueck, CA Traub, SA Nicolson, M Manore, MM Matt, KS Ravussin, E TI Adiposity, plasma leptin concentration and reproductive function in active and sedentary females SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE menstrual cycle; body composition; reproduction; energy balance ID OB GENE; FOOD-INTAKE; OBESE GENE; INSULIN; EXPRESSION; WEIGHT; WOMEN; HUMANS; CELLS; RNA AB OBJECTIVE: Circulating leptin has recently been proposed as the peripheral signal indicating the adequacy of nutritional status for reproductive function. To test whether low plasma leptin concentration for a given degree of adiposity is associated with menstrual dysfunction, we measured plasma leptin concentration and body composition in young premenopausal women with normal or abnormal reproductive function. DESIGN: Easting plasma leptin concentration (ELISA), body composition (dual energy X-ray absorptiometry) and menstrual status (menstrual history and hormonal profile) were assessed in 34 premenopausal women characterized by different levels of physical activity. RESULTS: Body fat content and plasma leptin concentration were both reduced in women with impaired reproductive function (amenorrheic < anovulatory < eumenorrheic women). However, after adjusting plasma leptin concentration for percentage body fat, there was no independent association between leptin and menstrual function. CONCLUSION: Menstrual abnormalities in young premenopausal women seem to occur as a consequence of the linear decline in adiposity and plasma leptin concentration observed in response to inadequate nutritional status. Levels of adiposity below 15% and plasma leptin concentration below 3 ng/ml are more likely to be associated with impaired reproductive function. C1 ARIZONA STATE UNIV,DEPT EXERCISE SCI & PHYS EDUC,TEMPE,AZ. AMGEN INC,THOUSAND OAKS,CA 91320. ARIZONA STATE UNIV,DEPT FAMILY RESOURCES & HUMAN DEV,TEMPE,AZ 85287. RP Tataranni, PA (reprint author), NIDDK,CLIN DIABET & NUTR CTR,NIH,4212 N 16TH ST,RM 541-A,PHOENIX,AZ 85016, USA. NR 24 TC 42 Z9 46 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 1997 VL 21 IS 9 BP 818 EP 821 DI 10.1038/sj.ijo.0800481 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA XU449 UT WOS:A1997XU44900013 PM 9376896 ER PT J AU vanWaes, C Surh, DM Chen, Z Carey, TE AF vanWaes, C Surh, DM Chen, Z Carey, TE TI Inhibition of integrin mediated cell adhesion of human head and neck squamous cell carcinoma to extracellular matrix laminin by monoclonal antibodies SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article; Proceedings Paper CT 4th International Conference on Head and Neck Cancer CY JUL 27-AUG 02, 1996 CL TORONTO, CANADA DE integrins; laminin; squamous cell carcinoma ID ALPHA-6-BETA-4 INTEGRIN; MELANOMA-CELLS; IV COLLAGEN; EXPRESSION; RECEPTOR; ALPHA-2-BETA-1; FIBRONECTIN; TUMOR; A9; ALPHA-3-BETA-1 AB We recently reported that three members of the integrin family of cell adhesion molecules, designated alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 4, are expressed at increased levels within the tumors and cell lines of patients with SCC. These three integrins have been reported to serve as receptors for laminin isoforms, and we also previously observed that laminins are secreted by SCC cell lines isolated from patients. In this study, the expression and localization of the three integrins and laminin in situ was evaluated in ten tumor specimens from patients with SCC by immunohistochemistry using integrin subunit-specific monoclonal antibodies. The ability of the antibodies to inhibit laminin attachment of a human squamous cell carcinoma line was determined by in vitro cell adhesion assay. Laminin and the three integrins were co-localized along the invasive border of the tumor parenchyma in 10/10 patient tumor specimens. Attachment of the UM-SCC-38 cell line to laminin was strongly inhibited by specific mAbs to alpha 2 and alpha 6 integrin subunits alone, or completely using a combination of alpha 2, alpha 3, and alpha 6 subunit specific mAbs. The co-localization of the three abnormally expressed integrins and laminin in patient tumor specimens indicates the potential for interaction of these receptors and ligand in vivo. The results of the cell adhesion assays using a patient SCC cell line that expresses the same repertoire of integrins confirms that SCC attach to laminin isoforms primarily through the alpha 2, alpha 3 and alpha 6 subunit-containing integrins. These findings provide a basis for undertaking experimental studies to obtain small molecule receptor antagonists to determine the role of these integrins in tumor formation, growth, invasion and metastasis in vivo. C1 UNIV MICHIGAN,CTR CANC,LAB HEAD & NECK CANC BIOL,DEPT OTOLARYNGOL HEAD & NECK SURG,ANN ARBOR,MI 48109. RP vanWaes, C (reprint author), NATL INST DEAFNESS & OTHER COMMUN DISORDERS,TUMOR BIOL SECT,HEAD & NECK SURG BRANCH,BLDG 10,BETHESDA,MD 20892, USA. OI Carey, Thomas/0000-0002-5202-7518 NR 36 TC 1 Z9 1 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1997 VL 11 IS 3 BP 457 EP 464 PG 8 WC Oncology SC Oncology GA XP910 UT WOS:A1997XP91000003 PM 21528232 ER PT J AU Venkatesh, H MezaCoria, C LopezCorella, E RidauraSanz, C OConor, G Luna, RR Bhatia, K Magrath, I AF Venkatesh, H MezaCoria, C LopezCorella, E RidauraSanz, C OConor, G Luna, RR Bhatia, K Magrath, I TI Expression of p53 in pediatric lymphomas from Mexico: Relation to histology and immunophenotype SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE immunohistochemistry; pediatric; lymphoma; p53 ID CELL LYMPHOMAS; MUTATIONS AB Eighty-five cases of pediatric non-Hodgkin's lymphomas (NHLs) from Mexico have been reviewed and classified according to histologic type and immunophenotype using a panel of markers which included CD20, CD45RO-(UCHLI), CD3 and Tdt. Twenty-five cases were classified as lymphoblastic lymphoma (LBL) of precursor cell origin and forty-nine cases as non-lymphoblastic lymphomas. Eleven cases could not be satisfactorily classified due to insufficient tissue or on technical grounds. All these lymphomas were subjected to immunohistochemistry (IHC) for detecting p53 expression. p53 was detectable in 7 (28%) lymphoblastic lymphomas, in 36 (73.4%) non-lymphoblastic lymphomas and in 4 (36.3%) of the lymphomas that could not be classified. Our results indicate that in contrast to adults with NHL and children with acute leukemia, p53 expression is relatively frequent in pediatric NHLs, although it is higher in lymphomas of B cell phenotype than in those of T cell type. C1 NCI,LBS,POB,NIH,BETHESDA,MD 20892. INST NACL PEDIAT,MEXICO CITY,DF,MEXICO. NR 17 TC 1 Z9 1 U1 1 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1997 VL 11 IS 3 BP 477 EP 480 PG 4 WC Oncology SC Oncology GA XP910 UT WOS:A1997XP91000006 PM 21528235 ER PT J AU Bisgaard, HC Mackay, AR Gomez, DE Ton, PT Thorgeirsson, SS Thorgeirsson, UP AF Bisgaard, HC Mackay, AR Gomez, DE Ton, PT Thorgeirsson, SS Thorgeirsson, UP TI Spontaneous metastasis of rat liver epithelial cells transformed with v-raf and v-raf/v-myc: Association with different phenotypic properties SO INVASION & METASTASIS LA English DT Article DE Raf; Myc; liver epithelial cells, rat ID C-MYC; HEPATOCELLULAR-CARCINOMA; TUMOR PROGRESSION; GENE-MUTATIONS; NUDE-MICE; EXPRESSION; ONCOGENE; METALLOPROTEINASE; LINEAGES; TISSUES AB Cloned v-raf, v-raf/v-myc, and spontaneously transformed rat liver epithelial (RLE) cell lines were examined for meastatic capability in nude mice, using the LacZ gene as a marker for quantitation of micrometastases, Six cloned lines (R3611-T lines) derived from nude mouse xenografts of the v-raf transformed R3611-3 cells displayed variable metastatic capabilities. Three of six subcutaneously inoculated R3611-TlacZ lines produced spontaneous lung metastasis in nude mice, One of the lines, R361l-T2lacZ was highly efficient at metastatic conversion and produced more lung colonies than a faster growing v-raf/v-myc-transformed RJ2-14lacZ line. The spontaneously transformed RLElacZ line (C4T) was nonmetastatic, although it produced larger subcutaneous tumors than the metastatic R3611-T2lacZ line. Metastatic conversion correlated with upregulation of urokinase-typo plasminogen activator receptor RNA expression and downregulation of plasminogen activator inhibitor-1, collagen alpha 1 (I), and cytokeratin 14 (K14) RNA expression. These findings indicate that proteolytic activities associated with plasminogen activation play a role in the metastatic development in this model, Decreased production of extracellular proteins and cytoskeletal changes associated with lack of K14 expression are also likely to have contributed to the metastatic conversion of the RLE transformants. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. Roskilde Univ, Dept Chem & Life Sci, Roskilde, Denmark. RP Thorgeirsson, UP (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, Bldg 37,Room 2D02, Bethesda, MD 20892 USA. EM thorgeiu@dc37a.nci.nih.gov OI Mackay, Andrew Reay/0000-0001-7096-3759; Gomez, Daniel E/0000-0002-8629-0787 NR 41 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-1789 J9 INVAS METAST JI Invasion Metastasis PD SEP-OCT PY 1997 VL 17 IS 5 BP 240 EP 250 PG 11 WC Oncology SC Oncology GA 159CY UT WOS:000078155300002 PM 9876218 ER PT J AU Feinstein, JA Epstein, FH Arai, AE Foo, TKF Hartley, MR Balaban, RS Wolff, SD AF Feinstein, JA Epstein, FH Arai, AE Foo, TKF Hartley, MR Balaban, RS Wolff, SD TI Using cardiac phase to order reconstruction [CAPTOR]: A method to improve diastolic images SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; heart; volume measurement; phase contrast; flow quantification; image reconstruction ID EJECTION FRACTION AB A method Is proposed to reconstruct multiphase images that accurately depicts the: entire cardiac cycle, A segmented, gradient-recalled-echo sequence (FASTCARD) was modified to acquire data continuously, Images were reconstructed retrospectively by selecting views from each heartbeat based on cardiac phase rather than the time elapsed from the QRS complex, Cardiac phase was calculated using a model that compensates for beat-to-beat heart rate changes, Images collected using cardiac phase to order reconstruction [CAPTOR] depict the entire cardiac cycle and lack the temporal gap that is characteristic of prospectively reconstructed sequences. Time-volume curves of the left ventricle capture the contribution of atrial contraction to end-diastolic volume (EDV). Transmitral phase-contrast now measurements shiny a second peak inflow (a wave) that is absent in the standard sequence, Because atrial contraction contributes to ventricular EDV, images using CAPTOR potentially may provide a more reliable measure of EDV, stroke volume, and ejection fraction than standard techniques. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 8 TC 41 Z9 41 U1 0 U2 1 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD SEP-OCT PY 1997 VL 7 IS 5 BP 794 EP 798 DI 10.1002/jmri.1880070505 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XW883 UT WOS:A1997XW88300004 PM 9307903 ER PT J AU Ryschon, TW Fowler, ND Wysong, RE Anthony, AR Balaban, RS AF Ryschon, TW Fowler, ND Wysong, RE Anthony, AR Balaban, RS TI Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE phosphorus 31 nuclear magnetic resonance; tibialis anterior; extensor digitorum longus; phosphocreatine; magnetic resonance imaging; adenosine 5'-triphosphate ID OXIDATIVE-PHOSPHORYLATION; KNEE EXTENSION; EXERCISE; CONTRACTION; DYNAMOMETER; ENERGETICS; TORQUE; MODEL; HEART; WORK AB The purpose of this study was to estimate the efficiency of ATP utilization for concentric, eccentric, and isometric muscle action in the human tibialis anterior and extensor digitorum longus in vivo. A dynamometer was used to quantitate muscle work, or tension, while simultaneous P-31-nuclear magnetic resonance data were collected to monitor ATP, phosphocreatine, inorganic phosphate, and pH. The relative efficiency of the actions was estimated in two ways: steady-state effects on high-energy phosphates and a direct comparison of ATP synthesis rates with work. In the steady state, the cytosolic free energy dropped to the lowest value with concentric activity, followed by eccentric and isometric action for comparative muscle tensions. Estimates of ATP synthesis rates revealed a mechanochemical efficiency [i.e., ATP production rate/work (both in J/s)] of 15.0 +/- 1.3% in concentric and 34.7 +/- 6.1% in eccentric activity. The estimated maximum ATP production rate was highest in concentric action, suggesting an activation of energy metabolism under these conditions. By using direct measures of metabolic strain and ATP turnover, these data demonstrate a decreasing metabolic efficiency in human muscle action from isometric, to eccentric, to concentric action. C1 NHLBI, LCE, NIH, BETHESDA, MD 20892 USA. NR 42 TC 93 Z9 94 U1 1 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 1997 VL 83 IS 3 BP 867 EP 874 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA XU622 UT WOS:A1997XU62200028 PM 9292475 ER PT J AU Fowler, MD Ryschon, TW Wysong, RE Combs, CA Balaban, RS AF Fowler, MD Ryschon, TW Wysong, RE Combs, CA Balaban, RS TI Normalized metabolic stress for P-31-MR spectroscopy studies of human skeletal muscle: MVC vs. muscle volume SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE maximal voluntary contraction; soleus; magnetic resonance imaging; 4 tesla; creatine phosphate; adenosine 5'-triphosphate; phosphorus-31 magnetic resonance spectroscopy ID MAGNETIC-RESONANCE SPECTROSCOPY; EXERCISE; MITOCHONDRIAL; INTENSITY; DEPLETION; FATIGUE; RATES; FORCE; AREA; MRS AB A critical requirement of submaximal exercise tests is the comparability of workload and associated metabolic stress between subjects. In this study, P-31-magnetic resonance spec troscopy was used to estimate metabolic strain in the soleus muscle during dynamic, submaximal plantar flexion in which target torque was 10 and 15% of a maximal voluntary contraction (MVC). In 10 healthy, normally active adults, (PCr + P-i)/PCr, where PCr is phosphocreatine, was highly correlated with power output normalized to the volume of muscle in the plantar flexor compartment (r = 0.89, P < 0.001). The same variable was also correlated, although less strongly (r = 0.78, P < 0.001), with power normalized to plantar flexor cross-sectional area. These findings suggest that comparable levels of metabolic strain can be obtained in subjects of different size when the power output, or stress, for dynamic plantar flexion is selected as a function of plantar flexor muscle volume. In contrast, selecting power output as a function of MVC resulted in a positive linear relationship between (PCr + P-i)/PCr and the torque produced, indicating that metabolic strain was increasing rather than achieving constancy as a function of MVC. These findings provide new insight into the design of dynamic muscle contraction protocols aimed at detecting metabolic differences between subjects of different body size but having similar blood flow capacity and mitochondrial volume per unit of muscle. C1 NHLBI,LAB CARDIAC ENERGET,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 30 TC 25 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 1997 VL 83 IS 3 BP 875 EP 883 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA XU622 UT WOS:A1997XU62200029 PM 9292476 ER PT J AU Edmunds, LH Mckinlay, S Anderson, JM Callahan, TH Chesebro, JH Geiser, EA Makanani, DM McIntire, LV Meeker, WQ Naughton, GK Panza, JA Schoen, FJ Didisheim, P AF Edmunds, LH Mckinlay, S Anderson, JM Callahan, TH Chesebro, JH Geiser, EA Makanani, DM McIntire, LV Meeker, WQ Naughton, GK Panza, JA Schoen, FJ Didisheim, P TI Directions for improvement of substitute heart valves: National Heart, Lung, and Blood Institute's Working Group report on Heart Valves SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article C1 NHLBI,DIV HEART & VASC DIS,BETHESDA,MD 20892. UNIV PENN,DEPT SURG,PHILADELPHIA,PA 19104. NEW ENGLAND RES INST,WATERTOWN,MA 02172. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. US FDA,DIV CARDIOVASC RESP & NEUROL DIS,ROCKVILLE,MD 20857. MT SINAI MED CTR,CARDIOL INST,NEW YORK,NY 10029. UNIV FLORIDA,CARDIOL SHANDS HOSP,GAINESVILLE,FL. CARBOMED,AUSTIN,TX. RICE UNIV,DEPT CHEM ENGN,HOUSTON,TX 77251. IOWA STATE UNIV,DEPT STAT,AMES,IA 50011. ADV TISSUE SCI INC,LA JOLLA,CA. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 23 Z9 23 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD FAL PY 1997 VL 38 IS 3 BP 263 EP 266 PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA XT742 UT WOS:A1997XT74200011 PM 9283972 ER PT J AU Kedar, PS Arden, K Foyle, M Pope, JH Zeichner, SL AF Kedar, PS Arden, K Foyle, M Pope, JH Zeichner, SL TI Umbilical cord blood mononuclear cell HIV-1 LTR binding activities SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HIV-1; LTR; umbilical cord blood; mononuclear cells; DNA binding; promoter; pathogenesis ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; LONG TERMINAL REPEAT; RNA POLYMERASE-II; T-CELLS; GENE-EXPRESSION; NUCLEAR FACTOR; LYMPHOCYTES-T; INFECTION; ENHANCER AB Vertically transmitted HIV disease constitutes a significant problem in pediatrics, In order to characterize some of the possible host factors involved in HIV replication in fetuses and newborns, we surveyed the HIV-1 LTR binding factors present in nuclear extracts from cord blood mononuclear cells. A series of electrophoretic mobility shift assays (EMSAs) showed that protein extracts from cord blood interacted with several regions of the HIV LTR, The most prominent binding activities involved the NF-kB sites, but other regions of the LTR also showed factor binding with the cord blood extracts, Some of these cord blood extract binding activities displayed qualitative differences when compared to adult peripheral blood mononuclear cell extracts in EMSA and UV cross-linking studies, Transient transfection experiments indicated that the NF-kB and Spl sequences were important for wild type levels of expression in cord blood cells, but that additional sequences 5' to the NF-kB sites also contributed activity. Thus, factors that interact with many of the well-known HIV LTR regulatory sites are present in cord blood cells. However, certain qualitative differences distinguished cord blood and adult peripheral blood binding activities and these may contribute to pathogenesis of HIV infection in neonates. C1 NCI,HIV & AIDS MALIGNANCY BRANCH,NIH,BETHESDA,MD 20892. ROYAL CHILDRENS HOSP,SIR ALBERT SAKZEWSKI VIRUS RES CTR,BRISBANE,QLD 4029,AUSTRALIA. RI Arden, Katherine/D-7970-2017 OI Arden, Katherine/0000-0003-3195-124X NR 38 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD SEP-OCT PY 1997 VL 4 IS 5 BP 217 EP 228 DI 10.1007/BF02253421 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA YE382 UT WOS:A1997YE38200003 ER PT J AU Neuveut, C Jin, DY Semmes, OJ Diella, F Callahan, R Jeang, KT AF Neuveut, C Jin, DY Semmes, OJ Diella, F Callahan, R Jeang, KT TI Divergent subcellular locations of HTLV-I Tax and Int-6: A contrast between in vitro protein-protein binding and intracellular protein colocalization SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HTLV; Tax; Int-6; transformation ID VIRUS TYPE-I; LOCALIZATION AB Protein-protein interactions define many important molecular and cellular processes in prokaryotic and eukaryotic biology. In trying to delineate the contact between two proteins, the yeast two-hybrid assay has emerged as a powerful technique. Complementing the yeast two-hybrid assay are in vitro techniques (e.g. GST-fusion-protein chromatography) that can also yield information on protein-protein associations. However, unambiguous functional significance to these interactions is best supported through a finding of colocalization of two proteins inside cells. In instances where two proteins interact in vitro but have divergent localizations within cells one needs to reconsider the biological importance of the former finding. Here, we present evidence for different subcellular locations of HTLV-I Tax and the Int-6 protein. We suggest a reexploration of the functional significance between Tax and Int-6 in cellular transformation. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 9 TC 11 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD SEP-OCT PY 1997 VL 4 IS 5 BP 229 EP 234 DI 10.1007/BF02253422 PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA YE382 UT WOS:A1997YE38200004 ER PT J AU Kuznetsov, SA Krebsbach, PH Satomura, K Kerr, J Riminucci, M Benayahu, D Robey, PG AF Kuznetsov, SA Krebsbach, PH Satomura, K Kerr, J Riminucci, M Benayahu, D Robey, PG TI Single-colony derived strains of human marrow stromal fibroblasts form bone after transplantation in vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID CLONAL CELL-LINES; CFU-F; HEMATOPOIETIC MICROENVIRONMENT; GROWTH-FACTOR; STEM-CELLS; CULTURES; INVITRO; DIFFERENTIATION; SUPPORT; IDENTIFICATION AB Populations of marrow stromal fibroblasts (MSFs) can differentiate into functional osteoblasts and form bone in vivo, It is not known, however, what proportion of MSP precursor cells, colony forming units-fibroblast (CFU-Fs), have osteogenic potential, In the present study, analysis of bone formation in vivo by single-colony derived strains of human marrow stromal fibroblasts (HMSFs) has been performed for the first time, Each strain originated from an individual CFU-F and underwent four passages in vitro prior to subcutaneous implantation into immunodeficient mice within vehicles containing hydroxyapatite-tricalcium phosphate ceramic, Multicolony derived HMSF strains were also transplanted to serve as positive controls, After 8 weeks, abundant bone formation was found in the transplants of all multicolony derived HMSF strains, whereas 20 out of 34 (58.8%) single-colony derived strains fi om four donors formed bone, Immunostaining with antibody directed against human osteonectin and in situ hybridization for human-specific alu sequences demonstrated that cells forming new bone were of human origin and were vital for at least 45 weeks post-transplantation. Both the incidence of bone-forming colonies and the extent of bone formation by single-colony derived HMSF strains were increased by cultivation with dexamethasone and ascorbic acid phosphate, Other factors, including type of transplantation vehicle, morphology, size, and structure of the original HMSF colonies showed no obvious correlation with the incidence or extent of bone formation, Hematopoietic tissue within the newly formed bone was developed in the transplants exhibiting exuberant bone formation, These results provide evidence that individual human CFU-Fs have osteogenic potential and yet differ from each other with respect to their osteogenic capacity. C1 NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. RP Kuznetsov, SA (reprint author), NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BLDG 30,ROOM 106,30 CONVENT DR MSC 4320,BETHESDA,MD 20892, USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 46 TC 484 Z9 504 U1 1 U2 13 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1997 VL 12 IS 9 BP 1335 EP 1347 DI 10.1359/jbmr.1997.12.9.1335 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT349 UT WOS:A1997XT34900004 PM 9286749 ER PT J AU Xing, L Franzoso, G Siebenlist, U Boyce, BF AF Xing, L Franzoso, G Siebenlist, U Boyce, BF TI Expression of the p50 and p52 subunits of NF-kappa B transcription factor is required for osteoclast formation, but not survival SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1997 VL 12 IS 9 BP O1 EP O1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT349 UT WOS:A1997XT34900026 ER PT J AU Fuller, K Chambers, TJ Leonard, EJ AF Fuller, K Chambers, TJ Leonard, EJ TI The effect of macrophage stimulating protein on the behavior of osteoclasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 ST GEORGE HOSP,SCH MED,DEPT HISTOPATHOL,LONDON SW17 0RE,ENGLAND. NCI,IMMUNOBIOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1997 VL 12 IS 9 BP P39 EP P39 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XT349 UT WOS:A1997XT34900080 ER PT J AU Lillibridge, CD OConnell, BC AF Lillibridge, CD OConnell, BC TI In human salivary gland cells, overexpression of E2F1 overcomes an interferon-gamma- and tumor necrosis factor-alpha-induced growth arrest but does not result in complete mitosis SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; S-PHASE; SJOGRENS-SYNDROME; EXPRESSION; DNA; SUPPRESSION; INDUCTION; APOPTOSIS; PROTEIN; LEADS AB Increased levels of cytokines in the salivary glands have been associated with the loss of secretory cells and reduced salivary function. It has been demonstrated that interferon-gamma(IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) treatment of a human submandibular gland (HSG) cell line causes growth arrest in the G(0)/G(1) phase of the cell cycle, followed by apoptosis. To stimulate DNA synthesis and reverse this growth arrest, we used an adenovirus vector to overexpress the transcription factor E2F1 in HSG cells. Initially, cells were synchronized by a double thymidine block and then infected with recombinant adenovirus (AdE2F1) expressing E2F1. Cells were harvested at intervals and analyzed by flow cytometry. Greater than 50% of synchronized cells infected with AdE2F1 were in S phase by 18 hours postinfection (hpi) compared to 12% of uninfected cells. Similarly, AdE2F1-infection of HSG cells arrested by IFN-gamma and TNF-alpha treatment caused a fivefold increase in S-phase cells by 48 hpi. However, by 72 hpi, AdE2F1-infected cells showed increases in the subdiploid cell population. Forty-one percent of AdE2F1-infected cells labeled positive by TUNEL, compared to fewer than 6% for controls. Additionally, AdE2F1-infected cells (84 hpi) had low forward-angle and high side scatter light characteristics, similar to apoptotic lymphocytes. These results suggest that E2F1 accumulation in growth-arrested salivary grand cells can stimulate DNA synthesis and overcome a G(0)/G(1) block in the cell cycle. However, E2F1 overexpression did not lead to complete mitosis in HSG cells but, rather, diverted cells into an apoptotic pathway. (C) 1997 Wiley-Liss, Inc.(dagger). C1 NIDR,GENE TRANSFER UNIT,NIH,BETHESDA,MD 20892. OI O'Connell, Brian/0000-0003-4529-7664 NR 21 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1997 VL 172 IS 3 BP 343 EP 350 DI 10.1002/(SICI)1097-4652(199709)172:3<343::AID-JCP8>3.0.CO;2-O PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XT775 UT WOS:A1997XT77500008 PM 9284954 ER PT J AU Endres, CJ Kolachana, BS Saunders, RC Su, T Weinberger, D Breier, A Eckelman, WC Carson, RE AF Endres, CJ Kolachana, BS Saunders, RC Su, T Weinberger, D Breier, A Eckelman, WC Carson, RE TI Kinetic modeling of [C-11]raclopride: Combined PET-microdialysis studies SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE raclopride; positron emission tomography; microdialysis; compartmental models; D-2 receptors ID POSITRON EMISSION TOMOGRAPHY; IN-VIVO MICRODIALYSIS; CEREBRAL BLOOD-FLOW; DOPAMINE-RECEPTORS; C-11 RACLOPRIDE; QUANTITATIVE MICRODIALYSIS; ENDOGENOUS DOPAMINE; NONHUMAN-PRIMATES; BASAL GANGLIA; BINDING AB The in vivo binding of D-2 receptor ligands can be affected by agents that alter the concentration of endogenous dopamine. To define a more explicit relation between dopamine and D-2 receptor binding, the conventional compartment model for reversible ligands has been extended to account for a time-varying dopamine pulse. This model was tested with [C-11]raclopride positron emission tomography and dopamine microdialysis data that were acquired simultaneously in rhesus monkeys. The microdialysis data were incorporated into the model assuming a proportional relation to synaptic dopamine. Positron emission tomography studies used a bolus-plus infusion tracer delivery with amphetamine given at 40 minutes to induce dopamine release. The extended model described the entire striatal time-activity curve, including the decrease in radioactivity concentration after an amphetamine-induced dopamine pulse. Based on these results, simulation studies were performed using the extended model. The simulation studies showed that the percent decrease in specific binding after amphetamine measured with the bolus-plus-infusion protocol correlates well with the integral of the postamphetamine dopamine pulse. This suggests that changes in specific binding observed in studies in humans can be interpreted as being linearly proportional to the integral of the amphetamine-induced dopamine pulse. C1 NIH,CTR CLIN,PET DEPT,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 34 TC 129 Z9 130 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1997 VL 17 IS 9 BP 932 EP 942 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA XX163 UT WOS:A1997XX16300002 PM 9307606 ER PT J AU Kornyshev, AA Leikin, S AF Kornyshev, AA Leikin, S TI Theory of interaction between helical molecules SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DNA DOUBLE HELICES; HYDRATION FORCES; ELECTROSTATIC INTERACTION; COLLAGEN; WATER; CONFORMATION; XANTHAN; TENDON AB This work builds a basis for understanding electrostatic and solvation forces between various types of helical molecules by explicitly incorporating the helical structure and symmetries into the theory. We derive exact expressions for interaction between molecules with cylindrical inner cores and arbitrary distribution of discrete surface charges and analyze forces between single-stranded, double-stranded, and multistranded helices. For example, we demonstrate that the traditional approximation by a homogeneously charged rod becomes inappropriate when even less than a third of the strand charge on a single-stranded helix is neutralized by countercharges (adsorbed or intrinsic to the helix by their nature). The traditionally expected force is then complemented by helix-specific interactions. These helix-specific forces allow commensurate helices (with the ratio of pitches equal to a rational number) to recognize each other at a distance and self-assemble into an aggregate. Under certain conditions, these forces may induce a spontaneous symmetry loss, e.g., two DNA-type double helices rotate around their long axes to a separation-dependent angle when the molecules come closer than a critical interaxial separation. In general, while a longer-range helix-specific attraction induces the self-assembly, a shorter-range helix-specific repulsion prevents the tight molecular contact creating a force balance responsible for a nonzero surface separation in equilibrium. The decay rates and the amplitudes of the attraction and of the repulsion depend on the helical pitch and on the number and relative disposition of the helical strands. The theory of these forces allows us to explain a number of puzzling features of interactions measured between biological helices, including DNA, collagen, and four-stranded guanosine macromolecules. (C) 1997 American Institute of Physics. C1 NIH, DIV COMP RES & TECHNOL, STRUCT BIOL LAB, BETHESDA, MD 20892 USA. FORSCHUNGSZENTRUM JULICH, FORSCHUNGSZENTRUM, INST ENERGIEVERFAHRENSTECH, D-52425 JULICH, GERMANY. RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 55 TC 125 Z9 126 U1 4 U2 18 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 1 PY 1997 VL 107 IS 9 BP 3656 EP 3674 DI 10.1063/1.475320 PG 19 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA XU115 UT WOS:A1997XU11500034 ER PT J AU BenNaim, A AF BenNaim, A TI Statistical potentials extracted from protein structures: Are these meaningful potentials? SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article AB We present an inventory of factors that determine the stability of proteins. It is shown that the (true) potential of mean force between pairs of amino acid residues does not belong to this inventory. Therefore, such quantities are not needed for either estimating the stability of a protein or for predicting its structure. It is also shown that the so-called ''statistical potential'' as derived from the data bank of protein structures is neither the potential nor the potential of mean force for pairs of amino-acid residues. A critical examination of the nonadditivity of the many body potential of the mean force is also presented. (C) 1997 American Institute of Physics. C1 HEBREW UNIV JERUSALEM,DEPT PHYS CHEM,IL-91904 JERUSALEM,ISRAEL. RP BenNaim, A (reprint author), NIH,MATH BIOL LAB,BETHESDA,MD 20892, USA. NR 15 TC 107 Z9 111 U1 0 U2 10 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 1 PY 1997 VL 107 IS 9 BP 3698 EP 3706 DI 10.1063/1.474725 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA XU115 UT WOS:A1997XU11500038 ER PT J AU Maller, A Hyland, K Milstien, S Biaggioni, I Butler, IJ AF Maller, A Hyland, K Milstien, S Biaggioni, I Butler, IJ TI Aromatic L-amino acid decarboxylase deficiency: Clinical features, diagnosis, and treatment of a second family SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID DIHYDROPTERIDINE REDUCTASE DEFICIENCY; PERFORMANCE LIQUID-CHROMATOGRAPHY; CEREBROSPINAL-FLUID; TETRAHYDROBIOPTERIN; HYPERPHENYLALANINEMIA; PTERINS; PHENYLKETONURIA; PURIFICATION; BIOSYNTHESIS; PARKINSONISM AB Aromatic L-amino acid decarboxylase deficiency is an inborn error of metabolism that leads to combined serotonin and catecholamine deficiency, first described by Hyland et al in 1990. The clinical features, biochemical findings, and treatment of the second family with this condition are reported. Our male patient presented with developmental delay, extreme hypotonia, oculogyric crises, and irritability. The diagnosis of this inborn error of biogenic amine metabolism was accomplished by determining low concentrations of homovanillic, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenyl-ethyleneglycol in cerebrospinal fluid with normal biopterin metabolism and increased L-dopa, in plasma, cerebrospinal fluid, and urine. Greatly reduced activity of aromatic L-amino acid decarboxylase in plasma confirmed this diagnosis. Combined treatment with pyridoxine, tranylcypromine, and bromocriptine produced some clinical improvement. C1 UNIV TEXAS,HLTH SCI CTR,SCH MED,DEPT NEUROL,HOUSTON,TX 77225. BAYLOR UNIV,MED CTR,INST METAB DIS,DALLAS,TX. UNIV TEXAS,SW MED CTR,DEPT NEUROL,DALLAS,TX 75235. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. VANDERBILT UNIV,CLIN RES CTR,NASHVILLE,TN. FU NCRR NIH HHS [RR02558] NR 41 TC 31 Z9 31 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 1997 VL 12 IS 6 BP 349 EP 354 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA XX811 UT WOS:A1997XX81100002 PM 9309516 ER PT J AU Nesbitt, EH Temeck, BK Williams, KS AF Nesbitt, EH Temeck, BK Williams, KS TI Bilateral lung collapse in an asthmatic patient during thoracotomy SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE asthma; equipment and supplies, endobronchial tube, double-lumen; lung, pulmonary collapse ID MUCUS AB Bilateral sequential pulmonary atelectasis occurred during median sternotomy for metastasis resection in a 19-year-old woman with asthma. Collapse was secondary to mucus plugging and resolved with mechanical ventilation, suctioning, and treatment for bronchospasm. (C) 1997 by Elsevier Science Inc. RP Nesbitt, EH (reprint author), NIH,DEPT ANESTHESIOL,THORAC SURG ONCOL SECT,10 CTR DR,MSC 1512,BLDG 10,ROOM 2C624,BETHESDA,MD 20814, USA. NR 6 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 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 1997 VL 9 IS 6 BP 499 EP 500 DI 10.1016/S0952-8180(97)00108-6 PG 2 WC Anesthesiology SC Anesthesiology GA XT096 UT WOS:A1997XT09600015 PM 9278840 ER PT J AU Reincke, M Mora, P Beuschlein, F Arlt, W Chrousos, GP Allolio, B AF Reincke, M Mora, P Beuschlein, F Arlt, W Chrousos, GP Allolio, B TI Deletion of the adrenocorticotropin receptor gene in human adrenocortical tumors: Implications for tumorigenesis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ONCOGENIC MUTATIONS; NO EVIDENCE; CHROMOSOME-18; NEOPLASMS; HORMONE; ILLNESS; ADENOMA; REGION AB Constitutive activating mutations of G protein-coupled receptors, such as that of TSH, have been implicated in the tumorigenesis of human endocrine neoplasms, such as thyroid adenomas. In a previous study we reported that constitutive activating point mutations of the ACTH receptor (ACTH-R) gene, a member of the G protein-coupled receptor superfamily, were not present in hormone-secreting and nonsecretory adrenocortical neoplasms. In this study, we investigated whether allelic loss of the ACTH-R gene is present in sporadic adrenal tumors. We identified a PstI polymorphism in the promoter region 3 kilobases upstream of the coding region of the ACTH-R gene. The rate of heterozygosity for this polymorphism in 99 unrelated Caucasian individuals was 53.5%. Using this polymorphism, we analyzed loss of heterozygosity (LOH) of the ACTH-R gene in 20 informative cases with beni,sn and malignant adrenocortical tumors. Of 16 patients with benign lesions, LOH was present in 1 oncocytic nonfunctional adenoma, but not in 15 hyperfunctioning adenomas. Of 4 informative patients with adrenocortical carcinomas, LOH was present in 2 cases. Both patients had advanced tumor stages and showed a more rapid course than carcinoma patients without LOH. Analysis of the flanking region of the ACTH-R using the polymorphic microsatellite marker D18S37 and D18S40 showed that this deletion was confined to the ACTH-R gene. Northern blot experiments demonstrated reduced expression of ACTH-R messenger ribonucleic acid in the tumors with LOH of the ACTH-R gene, suggesting functional significance of this finding at the transcriptional level. We conclude that LOH of the ACTH-R gene is possibly involved in adrenal tumorigenesis, contributing to cellular dedifferentiation in adenomas and carcinomas. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Reincke, M (reprint author), UNIV WURZBURG, MED KLIN, DEPT INTERNAL MED, JOSEF SCHNEIDER STR 2, D-97080 WURZBURG, GERMANY. RI Arlt, Wiebke/B-6310-2009 OI Arlt, Wiebke/0000-0001-5106-9719 NR 26 TC 86 Z9 87 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1997 VL 82 IS 9 BP 3054 EP 3058 DI 10.1210/jc.82.9.3054 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XU362 UT WOS:A1997XU36200051 PM 9284742 ER PT J AU Janik, JE Curti, BD Considine, RV Rager, HC Powers, GC Alvord, WG Smith, JW Gause, BL Kopp, WC AF Janik, JE Curti, BD Considine, RV Rager, HC Powers, GC Alvord, WG Smith, JW Gause, BL Kopp, WC TI Interleukin 1 alpha increases serum leptin concentrations in humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PITUITARY-ADRENAL AXIS; OBESE GENE; NEUROPEPTIDE-Y; BODY-WEIGHT; OB PROTEIN; EXPRESSION; MOUSE; MICE AB Leptin, the protein product of the ob gene, regulates appetite and body weight in animals. Endotoxin and cytokines, induced by endotoxin, interleukin (IL) 1 and tumor necrosis factor, increase expression of leptin in mice and hamsters. We measured serum leptin concentrations in patients with cancer before and after administration of recombinant human IL-1 alpha. Fourteen patients received IL-1 alpha at one of three dose levels (0.03, 0.1, or 0.3 mu g/kg.day) for 5 days. Serum leptin concentrations increased in all but two patients within 24 h after the first dose. The increase in leptin was correlated directly with IL-1 alpha dose (P = 0.0030). Despite continued administration of IL-1 alpha, serum leptin concentrations returned to pretreatment levels by day 5 of therapy. An increase in serum leptin concentrations may be one mechanism by which anorexia is induced by IL-1 alpha. However, tachyphylaxis of the leptin response suggests that other mechanisms also are involved. C1 INDIANA UNIV, SCH MED, INDIANAPOLIS, IN 46202 USA. PROVIDENCE MED CTR, EARLE CHILES RES INST, PORTLAND, OR 97213 USA. NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, DATA MANAGEMENT SERV INC, FREDERICK, MD 21702 USA. RP Janik, JE (reprint author), NCI, MED BRANCH,DIV CLIN SCI,NIH,BLDG 10, ROOM 12N226, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 29 TC 172 Z9 178 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1997 VL 82 IS 9 BP 3084 EP 3086 DI 10.1210/jc.82.9.3084 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XU362 UT WOS:A1997XU36200058 PM 9284748 ER PT J AU Schechter, AN AF Schechter, AN TI No therapy? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material RP Schechter, AN (reprint author), NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892, USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 10 TC 5 Z9 5 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 1 PY 1997 VL 100 IS 5 BP 955 EP 956 DI 10.1172/JCI119646 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XV753 UT WOS:A1997XV75300002 PM 9303925 ER PT J AU Cope, JU Hildesheim, A Schiffman, MH Manos, MM Lorincz, AT Burk, RD Glass, AG Greer, C Buckland, J Helgesen, K Scott, DR Sherman, ME Kurman, RJ Liaw, KL AF Cope, JU Hildesheim, A Schiffman, MH Manos, MM Lorincz, AT Burk, RD Glass, AG Greer, C Buckland, J Helgesen, K Scott, DR Sherman, ME Kurman, RJ Liaw, KL TI Comparison of the hybrid capture tube test and PCR for detection of human papillomavirus DNA in cervical specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; INFECTION; RISK; DIAGNOSIS; CANCER; CELLS; HYBRIDIZATION; POPULATION; COLOMBIA; SPAIN AB The strong association of human papillomavirus (HPV) and cervical cancer makes it important to study NPV detection methods that may play a role In cervical cancer screening. We compared two DNA methods that are commonly used for HPV research in the United States: the MY09/MY11 L1 consensus primer PCR-based test and the first-generation Hybrid Capture tube method (HCT). Laboratory assays by each method were performed with 596 cervicovaginal specimens collected from participants in a large cohort study conducted in Portland, Oreg, Included were 499 specimens from women whose cytology was normal and 97 specimens from women with squamous intraepithelial lesions (SILs). The overall HPV DNA positivity for known types was 22.5% by PCR compared to 13.6% by BCT. When the analysis nas restricted to the 14 HPV types detectable by both methods, the sensitivity of HCT, with PCR used as the standard for HPV status, was higher for specimens from women with concurrent SILs (81.0%) than for specimens from women with normal cytology (46.7%), Among specimens testing positive by both methods, 97.2% of the time the two methods agreed on whether specimens were positive for cancer-associated HPV types. Both of these HPV test methods provide information that supplements the information provided by the Pap smear. The PCR method has higher analytic sensitivity than RCT in detecting HPV, but HCT magi be helpful in identifying women with concurrent SILs. C1 DIGENE CORP,SILVER SPRING,MD. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. KAISER PERMANENTE NO CALIF,OAKLAND,CA. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. ALBERT EINSTEIN COLL MED,NEW YORK,NY. KAISER PERMANENTE,PORTLAND,OR. CHIRON CORP,EMERYVILLE,CA 94608. RP Cope, JU (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EPN RM 439,BETHESDA,MD 20892, USA. NR 29 TC 72 Z9 75 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1997 VL 35 IS 9 BP 2262 EP 2265 PG 4 WC Microbiology SC Microbiology GA XR237 UT WOS:A1997XR23700013 PM 9276398 ER PT J AU Arens, M Meyer, W Brambilla, D Bremer, J Fiscus, S Griffith, B Hammer, S Hodinka, R Kabat, W YenLieberman, B Myers, L Reichelderfer, P AF Arens, M Meyer, W Brambilla, D Bremer, J Fiscus, S Griffith, B Hammer, S Hodinka, R Kabat, W YenLieberman, B Myers, L Reichelderfer, P TI Stabilities of free and complexed human immunodeficiency virus p24 antigens during short-and long-term storage SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IMMUNE-COMPLEXES; ZIDOVUDINE AZT; INFECTION; DISSOCIATION; CHILDREN AB By the standard p24 assay there was a 25 to 27% decrease in free p24 antigen in serum after storage at 4 degrees C over 14 days but no loss at -70 degrees C. There was no loss at either temperature by the immune complex dissociation (ICD) procedure. Furthermore, there was no significant loss of detectable p24 in serum by either the ICD or the standard p24 assay after 700 days of storage at -70 degrees C. C1 CORNING CLIN LABS,BALTIMORE,MD 21227. NEW ENGLAND RES INST,WATERTOWN,MA 02172. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV N CAROLINA,DEPT MICROBIOL & IMMUNOL,CHAPEL HILL,NC 27599. YALE UNIV,SCH MED,DEPT LAB MED,NEW HAVEN,CT 06510. VA CONNECTICUT HEALTHCARE SYST,VIROL REFERENCE LAB,W HAVEN,CT 06516. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,MED CTR,BOSTON,MA 02215. CHILDRENS HOSP,VIROL LAB,PHILADELPHIA,PA 19104. NORTHWESTERN UNIV,CHILDRENS MEM HOSP,SCH MED,INFECT DIS LAB,CHICAGO,IL 60614. CLEVELAND CLIN FDN,DEPT CLIN PATHOL,CLEVELAND,OH 44195. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIAID,DIV AIDS,BETHESDA,MD 20892. RP Arens, M (reprint author), WASHINGTON UNIV,SCH MED,DEPT PEDIAT,1 CHILDRENS PL,ST LOUIS,MO 63110, USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1997 VL 35 IS 9 BP 2413 EP 2416 PG 4 WC Microbiology SC Microbiology GA XR237 UT WOS:A1997XR23700043 PM 9276428 ER PT J AU Leibenluft, E FeldmanNaim, S Turner, EH Wehr, TA Rosenthal, NE AF Leibenluft, E FeldmanNaim, S Turner, EH Wehr, TA Rosenthal, NE TI Effects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CIRCADIAN-RHYTHMS; LIGHT; SLEEP; SUPERSENSITIVITY; SUPPRESSION; PEOPLE; MOOD AB Background: The ready availability of exogenous melatonin means that its use in patients with mood disorders is probably not uncommon. Nonetheless, few controlled trials of exogenous melatonin in these patients have been conducted. Method: Five patients with rapid-cycling DSM-III-R bipolar disorder were treated with melatonin 10 mg q.d. at 10:00 p.m. for 12 weeks. Melatonin was added to a stable regimen of medication and administered in a double-blind, placebo-controlled fashion. Results: Melatonin administration had no positive effects. One patient developed a free-running (unentrained) sleep-wake cycle after melatonin withdrawal. In addition, in both this and a second patient, there is evidence that the administration of exogenous melatonin may have suppressed the secretion of endogenous melatonin. Conclusion: The administration of melatonin had no significant effects on mood or sleep. However, melatonin withdrawal delayed sleep onset time and may have had some mild mood-elevating effects. RP Leibenluft, E (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,10-4S-239,10 CTR DR,MSC 1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 29 TC 27 Z9 29 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1997 VL 58 IS 9 BP 383 EP 388 DI 10.4088/JCP.v58n0902 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA XY690 UT WOS:A1997XY69000002 PM 9378688 ER PT J AU Bavelier, D Corina, D Jezzard, P Padmanabhan, S Clark, VP Karni, A Prinster, A Braun, A Lalwani, A Rauschecker, JP Turner, R Neville, H AF Bavelier, D Corina, D Jezzard, P Padmanabhan, S Clark, VP Karni, A Prinster, A Braun, A Lalwani, A Rauschecker, JP Turner, R Neville, H TI Sentence reading: A functional MRI study at 4 tesla SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; HUMAN EXTRASTRIATE CORTEX; MEDIAL TEMPORAL-LOBE; HUMAN-BRAIN; CORTICAL LOCALIZATION; FIELD POTENTIALS; WORKING MEMORY; LANGUAGE; ACTIVATION AB In this study changes in blood oxygenation and volume were monitored while monolingual right-handed subjects read English sentences. Our results confirm the role of the left peri-sylvian cortex in language processing. Interestingly, individual subject analyses reveal a pattern of activation characterized by several small,limited patches rather than a fen large, anatomically well-circumscribed centers. Between-subject analyses confirm a lateralized pattern of activation and reveal active classical language areas including Broca's area, Wernicke's area, and the angular gyrus. In addition they point to areas only more recently considered as language-relevant including. the anterior portion of the superior temporal sulcus. This area has not been reliably observed in imaging studies of isolated word processing. This raises the hypothesis that activation in this area is dependent on processes specific to sentence reading. C1 UNIV WASHINGTON, SEATTLE, WA 98195 USA. NIMH, NIH, ROCKVILLE, MD USA. UNIV OREGON, EUGENE, OR 97403 USA. UNIV MILAN, INB, CNR, INST HS RAFFAELE, MILAN, ITALY. NIDCD, NIH, BETHESDA, MD USA. EPSTEIN LABS, SAN FRANCISCO, CA USA. RI Turner, Robert/C-1820-2008; Rauschecker, Josef/A-4120-2013; Prinster, Anna/B-8414-2015; Clark, Vincent/B-3343-2010; OI Prinster, Anna/0000-0003-2706-3071; Clark, Vincent/0000-0002-9151-2102; Jezzard, Peter/0000-0001-7912-2251 NR 95 TC 130 Z9 133 U1 8 U2 16 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 1997 VL 9 IS 5 BP 664 EP 686 DI 10.1162/jocn.1997.9.5.664 PG 23 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA YA932 UT WOS:A1997YA93200006 PM 23965123 ER PT J AU Petralia, RS Wang, YX Mayat, E Wenthold, RJ AF Petralia, RS Wang, YX Mayat, E Wenthold, RJ TI Glutamate receptor subunit 2-selective antibody shows a differential distribution of calcium-impermeable AMPA receptors among populations of neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE glutamate receptors; hippocampus; cochlear nucleus; cerebellum; spinal cord ID RAT CEREBRAL-CORTEX; MESSENGER-RNAS; SPINAL-CORD; CA2+ PERMEABILITY; NMDA RECEPTORS; IMMUNOCYTOCHEMICAL LOCALIZATION; ULTRASTRUCTURAL-LOCALIZATION; IMMUNOGOLD LOCALIZATION; HIPPOCAMPAL-NEURONS; EXPRESSION PATTERNS AB alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors are the major excitatory neurotransmitter receptors of the central nervous system. AMPA receptor complexes that contain the AMPA-type glutamate receptor subunit 2 (GluR2) are responsible for the low calcium permeability typical of most AMPA receptors, and the absence of GluR2 may be a key factor in neurotoxicity. A polyclonal antibody was produced to a 16 amino acid peptide near the C-terminus of GluR2 and was affinity-purified in a three-step procedure. The antibody did not recognize other AMPA subunits in transfected cells with the use of either Western blots or immunocytochemistry. This highly specific GluR2 antibody was used to provide a specific morphological study of GluR2 protein distribution in neurons and synapses of the rat. GluR2 is prevalent in most principal neurons throughout the telencephalon. Neurons with few or no GluR2 subunits include two major types: 1) some populations of interneurons of the telencephalon and of some other areas and 2) many populations of principal neurons in the brainstem and spinal cord. Immunofluorescence showed that GluR2 immunolabeling was widespread, including in dendrites and puncta, in the hippocampus and neocortex. Where they were present, GluR2 subunits colocalized with other AMPA receptor subunits in individual neurons. Electron microscopy of the hippocampus showed GluR2-bearing, calcium-impermeable AMPA receptors postsynaptic to dendrite synapses of forebrain principal neurons. In addition, electron microscopy of the neocortex showed significant staining in postsynaptic profiles. Electron microscopy of the cerebellum revealed the presence of GluR2 subunits in the postsynaptic profiles of many parallel fiber/Purkinje cell spine synapses, whereas electron microscopy of the spinal cord showed substantial staining in the postsynaptic profiles of dorsal horn synapses, but not in ventral horn synapses. Both ultrastructural and immunofluorescence data showed that calcium-impermeable AMPA receptors are wide spread in dendrite arborizations. (C) 1997 Wiley-Liss, Inc.dagger. RP Petralia, RS (reprint author), NIDCD,NEUROCHEM LAB,NIH,36-5D08,36 CONVENT DR,MSC 4162,BETHESDA,MD 20892, USA. NR 67 TC 159 Z9 160 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 1 PY 1997 VL 385 IS 3 BP 456 EP 476 DI 10.1002/(SICI)1096-9861(19970901)385:3<456::AID-CNE9>3.0.CO;2-2 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA XU675 UT WOS:A1997XU67500009 PM 9300771 ER PT J AU Pires, A Coon, SL Hadfield, MG AF Pires, A Coon, SL Hadfield, MG TI Catecholamines and dihydroxyphenylalanine in metamorphosing larvae of the nudibranch Phestilla sibogae Bergh (Gastropoda: Opisthobranchia) SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE mollusca; opisthobranchia; high-performance liquid chromatography; catecholamines; metamorphosis ID CENTRAL PATTERN GENERATOR; NERVOUS-SYSTEM; CRASSOSTREA-GIGAS; PACIFIC OYSTER; SEROTONIN-LIKE; IMMUNOREACTIVE NEURONS; LIQUID-CHROMATOGRAPHY; LYMNAEA-STAGNALIS; ACTINOTROCH LARVA; MOTOR OUTPUT AB The content of catecholamines and dihydroxyphenylalanine in larvae of the nudibranch Phestilla sibogae was analyzed by high-performance liquid chromatography with electrochemical detection. Dihydroxyphenylalanine, norepinephrine and dopamine were identified in larvae of all ages examined (5 through 12 days post-fertilization). Dihydroxyphenylalanine could be accurately quantified only in larvae of ages 8 through 12 days, when its average concentration increased from 0.62 to 6.71 x 10(-2) pmol mu g protein(-1). Between ages 5 and 12 days dopamine rose from 0.081 to 0.616 pmol mu g protein(-1), and norepinephrine from 0.45 to 2.17 x 10 pmol mu g protein(-1). Dihydroxyphenylalanine, dopamine and norepinephrine were also measured at different stages of metamorphic progress in 10- to 12-day larvae. Dihydroxyphenylalanine increased by a factor of 2.4 between the onset and completion of metamorphosis, but levels of dopamine and norepinephrine remained stable. One millimolar alpha-methyl-DL-m-tyrosine, an inhibitor of catecholamine synthesis, inhibited natural metamorphosis and depleted endogenous norepinephrine and especially dopamine, respectively, to 75% and 35% of control values. The existence of unexpectedly high levels of catecholamines in metamorphically competent larvae, and the association of catecholamine depletion with inhibition of metamorphosis, indicate that these compounds may participate in the control of gastropod development. C1 UNIV HAWAII,PACIFIC BIOMED RES CTR,KEWALO MARINE LAB,HONOLULU,HI 96813. NICHHD,SECT NEUROENDOCRINOL,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 57 TC 35 Z9 35 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A-Sens. Neural Behav. Physiol. PD SEP PY 1997 VL 181 IS 3 BP 187 EP 194 DI 10.1007/s003590050105 PG 8 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA XU873 UT WOS:A1997XU87300001 PM 9309865 ER PT J AU Agarwala, R Batzoglou, S Dancik, V Decatur, SE Hannenhalli, S Farach, M Muthukrishnan, S Skiena, S AF Agarwala, R Batzoglou, S Dancik, V Decatur, SE Hannenhalli, S Farach, M Muthukrishnan, S Skiena, S TI Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article AB We consider the problem of determining the three-dimensional folding of a protein given its one-dimensional amino acid sequence, We use the HP model for protein folding proposed by Dill (1985), which models protein as a chain of amino acid residues that are either hydrophobic or polar, and hydrophobic interactions are the dominant initial driving force for the protein folding, Hart and Istrail (1996a) gave approximation algorithms for folding proteins on the cubic lattice under the HP model, In this paper, we examine the choice of a lattice by considering its algorithmic and geometric implications and argue that the triangular lattice is a more reasonable choice, We present a set of folding rules for a triangular lattice and analyze the approximation ratio they achieve, In addition, we introduce a generalization of the HP model to account for residues having different levels of hydrophobicity. After describing the biological foundation for this generalization, we show that in the new model we are able to achieve similar constant factor approximation guarantees on the triangular lattice as were achieved in the standard HP model, While the structures derived from our folding rules are probably still far from biological reality, we hope that having a set of folding rules with different properties will yield more interesting folds when combined. C1 MIT,COMP SCI LAB,CAMBRIDGE,MA 02139. MIT,DEPT MATH,CAMBRIDGE,MA 02139. UNIV SO CALIF,DEPT MATH,LOS ANGELES,CA 90089. RUTGERS STATE UNIV,DEPT COMP SCI,PISCATAWAY,NJ 08855. AT&T BELL LABS,LUCENT TECHNOL,INFORMAT SCI CTR,MURRAY HILL,NJ 07974. SUNY STONY BROOK,DEPT COMP SCI,STONY BROOK,NY 11794. RP Agarwala, R (reprint author), NATL HUMAN GENOME RES INST,NIH,BLDG 38A,ROOM 616,BETHESDA,MD 20892, USA. FU NHGRI NIH HHS [1R01 HG00987]; NIGMS NIH HHS [GM 36230] NR 18 TC 38 Z9 38 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD FAL PY 1997 VL 4 IS 3 BP 275 EP 296 DI 10.1089/cmb.1997.4.275 PG 22 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA XR809 UT WOS:A1997XR80900006 PM 9278060 ER PT J AU Choyke, PL Walther, MM Glenn, GM Wagner, JR Venzon, DJ Lubensky, IA Zbar, B Linehan, WM AF Choyke, PL Walther, MM Glenn, GM Wagner, JR Venzon, DJ Lubensky, IA Zbar, B Linehan, WM TI Imaging features of hereditary papillary renal cancers SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE kidneys, neoplasms; diseases, hereditary; ultrasound; computed tomography; contrast media; magnetic resonance imaging ID CELL-CARCINOMA; MASSES AB Purpose: Our goal was to describe the imaging features of hereditary papillary renal cancer syndrome (HPRC), a new familial cancer syndrome. Method: Members of seven kindreds with HPRC comprising 78 individuals were screened with contrast-enhanced CT and abdominal US. MRI was performed in three patients. Enhancement values and doubling times of solid masses were determined from CT scans. Results: Seventeen of 78 (22%) patients were affected. The HPRCs demonstrated lower enhancement (mean change in enhancement = 31 HU) than a comparable group of clear cell tumors (mean change in enhancement = 67 HU; p = 0.00001). The median tumor doubling time on serial CT was 18 months. The HPRCs were relatively hypovascular, enhanced uniformly, and grew slowly. Therefore, careful measurements of the region of interest should be obtained before and after intravenous administration of contrast medium. Though US detected only 45% of the lesions visualized on CT, it was useful in determining if lesions were cystic. Contrast-enhanced MRI demonstrated similar characteristics to contrast-enhanced CT. Conclusion: The tumors of patients with HPRC pose some diagnostic difficulties because they can be missed by US, are small, and enhance poorly on CT. CT is preferable to US as a screening tool because of its higher sensitivity in detecting small lesions, and when contrast media cannot be administered, MR is a suitable alternative to CT. C1 NATL CANC INST,UROL ONCOL BRANCH,DIV CLIN SCI,BETHESDA,MD. NATL CANC INST,GENET EPIDEMIOL BRANCH,BETHESDA,MD. NATL CANC INST,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD. NATL CANC INST,DEPT PATHOL,BETHESDA,MD. NATL CANC INST,IMMUNOBIOL SECT,BETHESDA,MD. RP Choyke, PL (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT RADIOL,BLDG 10,RM 1C660,10 CTR DR,MSC 1182,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 9 TC 37 Z9 38 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1997 VL 21 IS 5 BP 737 EP 741 DI 10.1097/00004728-199709000-00014 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XT931 UT WOS:A1997XT93100015 PM 9294565 ER PT J AU Ostuni, JL Santha, AKS Mattay, VS Weinberger, DR Levin, RL Frank, JA AF Ostuni, JL Santha, AKS Mattay, VS Weinberger, DR Levin, RL Frank, JA TI Analysis of interpolation effects in the reslicing of functional MR images SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE image registration; magnetic resonance imaging, functional; magnetic resonance imaging, physics; echo planar imaging ID AUTOMATED ALGORITHM; REGISTRATION AB Purpose: Typically, the final step in volume registration is the reslicing of the volume of interest. The purpose of this work is to examine the effects of this reslicing on functional MRI (fMRI) data using different interpolation methods. Method: Functional whale-brain echo planar imaging (EPI) volumes were resliced using six different interpolation methods: trilinear, tricubic splines, and a 3D sine function using a rectangular and a Hanning window, both with half-window lengths of 3 and 4 voxels. Results: Interpolation by tricubic spline and 3D sine using a Hanning window had comparable errors, although tricubic spline interpolation was computationally the fastest. Interpolation by trilinear and 3D sine using a rectangular window had relatively large errors, although the speed of trilinear makes it desirable for some applications. Conclusion: Interpolations using all of the tested methods adversely affected the fMRT data, although these effects differed for each method. C1 NIH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. RP Ostuni, JL (reprint author), NIH,LAB DIAGNOST RADIOL RES,BLDG 10,RM B1N256,10 CTR DR MSC 1074,BETHESDA,MD 20892, USA. NR 12 TC 37 Z9 38 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1997 VL 21 IS 5 BP 803 EP 810 DI 10.1097/00004728-199709000-00029 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XT931 UT WOS:A1997XT93100030 PM 9294580 ER PT J AU Gulson, BL Jameson, CW Gillings, BR AF Gulson, BL Jameson, CW Gillings, BR TI Stable lead isotopes in teeth as indicators of past domicile - A potential new tool in forensic science? SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; human identification; teeth; lead isotope ratios; missing persons; country of origin ID BLOOD LEAD; EXPOSURE; CHILDREN; RATIOS; BONE AB A pilot study using stable lead isotope analyses has shown that permanent and deciduous teeth from Eastern and Southern European subjects have completely different lead isotopic compositions to those of Australian subjects. There are statistically significant differences between groups of teeth from subjects from the former Soviet Union (CIS), the former Yugoslavia, United Kingdom, and Lebanon. The isotopic analyses confirm the stability of lead in enamel but suggest that there is exchange of European lead with Australian lead in dentine amounting to about 1% per year. The isotopic differences in, and exchange of, European lead and Australian lead offer an exciting and powerful tool for forensic identification. C1 CSIRO,EM,N RYDE,NSW 2113,AUSTRALIA. NIEHS,RES TRIANGLE PK,NC 27709. UNIV SYDNEY,WESTMEAD HOSP,FAC DENT,WESTMEAD,NSW 2145,AUSTRALIA. RP Gulson, BL (reprint author), MACQUARIE UNIV,GRAD SCH ENVIRONM,SYDNEY,NSW 2109,AUSTRALIA. FU NIEHS NIH HHS [N01-ES-05292] NR 23 TC 43 Z9 43 U1 0 U2 5 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 1997 VL 42 IS 5 BP 787 EP 791 PG 5 WC Medicine, Legal SC Legal Medicine GA XW332 UT WOS:A1997XW33200003 PM 9304823 ER PT J AU Jenkins, AJ Goldberger, BA AF Jenkins, AJ Goldberger, BA TI Identification of unique cocaine metabolites and smoking by-products in postmortem blood and urine specimens SO JOURNAL OF FORENSIC SCIENCES LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Academy-of-Forensic-Sciences CY FEB, 1993 CL BOSTON, MA SP Amer Acad Forens Sci DE forensic science; forensic toxicology; postmortem; cocaine; cocaine metabolites; smoking; anhydroecgonine methyl ester; cocaethylene ID CHROMATOGRAPHY-MASS-SPECTROMETRY; GAS-CHROMATOGRAPHY; COCAETHYLENE AB Toxicological investigation of suspected cocaine-related deaths routinely involves the identification of cocaine (COG) and its metabolites including benzoylecgonine (BE) and ecgonine methyl ester (EME) in postmortem specimens. We utilized solid-phase extraction followed by gas chromatography/mass spectrometry for the qualitative and quantitative analysis of cocaine and eight cocaine-related analytes. These analytes included anhydroecgonine methyl ester (AEME), a unique product formed during cocaine smoking, and cocaethylene (CE), formed by transesterification of cocaine in the presence of ethanol. Thirteen pairs of postmortem heart blood and urine specimens were analyzed from cases of death due to acute cocaine intoxication, multiple drug intoxication, or other non-dug related causes. COG, EME, and BE were detected in all specimens. The range of concentrations in blood were: COG, 23-2088 ng/mL; BE, 215-9195 ng/mL; and EME, 220-7275 ng/mL. AEME was identified in 2 blood and 10 urine specimens, and CE was identified in 1 blood specimen and 4 urine specimens. The identification of AEME in the specimens indicated that ''crack'' cocaine had been smoked, and the presence of CE indicated coadministration of cocaine and ethanol. The presence of these unique cocaine analytes in postmortem specimens provides valuable information regarding the cause and manner of death. C1 NIDA,STATE MARYLAND & INTRAMURAL RES PROGRAM,BALTIMORE,MD. OFF CHIEF MED EXAMINER,BALTIMORE,MD. UNIV FLORIDA,COLL MED,DEPT PATHOL IMMUNOL & LAB MED,GAINESVILLE,FL. NR 11 TC 25 Z9 27 U1 2 U2 7 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 1997 VL 42 IS 5 BP 824 EP 827 PG 4 WC Medicine, Legal SC Legal Medicine GA XW332 UT WOS:A1997XW33200010 PM 9304829 ER PT J AU Wang, ZH Christensen, N Schiller, JT Dillner, J AF Wang, ZH Christensen, N Schiller, JT Dillner, J TI A monoclonal antibody against intact human papillomavirus type 16 capsids blocks the serological reactivity of most human sera SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; LINKED-IMMUNOSORBENT-ASSAY; INCIDENT CERVICAL-CANCER; INFECTION; EPITOPES; CARCINOMA; NEOPLASIA; RISK; L1 AB A type-specific and neutralizing mouse MAb (V5) against human papillomavirus (HPV)type 16 capsids was found to block the serological reactivity of human sera with the corresponding capsids. Out of 352 human serum samples tested for the presence of IgG against HPV-16, more than 75% of reactive sera were completely blocked by the V5 antibody. Type-specific MAbs against HPV-6, -18 and -33 were also found to block serological reactivity with capsids of the corresponding HPV types for the majority of reactive human sera. The results suggest that most antibodies in human sera that are reactive with intact HPV capsids recognize the same or closely related major antigenic determinant(s). C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. MILTON S HERSHEY MED CTR,DEPT PATHOL MICROBIOL & IMMUNOL,HERSHEY,PA 17033. NATL CANC INST,CELLULAR ONCOL LAB,BETHESDA,MD. NR 23 TC 70 Z9 73 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 1997 VL 78 BP 2209 EP 2215 PN 9 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA XT710 UT WOS:A1997XT71000011 PM 9292008 ER PT J AU McKenzie, LM Cooper, DW AF McKenzie, LM Cooper, DW TI Hybridization between tammar wallaby (Macropus eugenii) populations from Western and South Australia SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT Interspecies Hybrids in Mammals Symposium / Australasian Gene Mapping Workshop CY NOV 30-DEC 01, 1995 CL DUNEDIN, NEW ZEALAND SP New Zealand Genet Soc ID LINKAGE AB Populations of tammar wallabies (Macropus eugenii) occur in southwest Western Australia and on five Australian offshore islands, four in Western Australia and one in South Australia. The South Australia and Western Australia populations have probably been isolated from each other for 50,000-100,000 years. Studies have shown that there are morphological and genetic differences between these populations. Attempts at mating individuals from Garden Island (Western Australia) with individuals from Kangaroo Island (South Australia) indicate that while the two populations can hybridize in captivity and F-1 hybrids of both sexes are fertile, a barrier to successful reproduction between these two populations is in the initial stages of development. C1 MACQUARIE UNIV,COOPERAT RES CTR CONSERVAT & MANAGEMENT MARSUPIAL,SYDNEY,NSW 2109,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP McKenzie, LM (reprint author), MACQUARIE UNIV,SCH BIOL SCI,SYDNEY,NSW 2109,AUSTRALIA. NR 14 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0022-1503 J9 J HERED JI J. Hered. PD SEP-OCT PY 1997 VL 88 IS 5 BP 398 EP 400 PG 3 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA XZ133 UT WOS:A1997XZ13300012 PM 9378916 ER PT J AU OBrien, SJ Cevario, SJ Martenson, JS Thompson, MA Nash, WG Chang, E Graves, JAM Spencer, JA Cho, KW Tsujimoto, H Lyons, LA AF OBrien, SJ Cevario, SJ Martenson, JS Thompson, MA Nash, WG Chang, E Graves, JAM Spencer, JA Cho, KW Tsujimoto, H Lyons, LA TI Comparative gene mapping in the domestic cat (Felis catus) SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT Interspecies Hybrids in Mammals Symposium / Australasian Gene Mapping Workshop CY NOV 30-DEC 01, 1995 CL DUNEDIN, NEW ZEALAND SP New Zealand Genet Soc ID LINKAGE MAP; MOLECULAR-CLONING; BOVINE GENOME; LOCI; MAMMALS AB The genetic map of the domestic cat has been developed as a model for studying both feline analogues of human genetic disease and comparative genome organization of mammals. We present here the results of syntenic mapping of 35 genes based upon concordant occurrence of feline gene homologues with feline chromosomes and previously mapped loci in a panel of 41 rodent x cat somatic cell hybrids, These somatic cell hybrids retain rodent chromosomes and segregate feline chromosomes, but in different combinations in each hybrid cell line, Thirty-three of the 35 new locus assignments extend and reaffirm conserved chromosome segment homologies between the human and cat genomes previously recognized by comparative mapping and zoo-FISH. These results demonstrate the extensive syntenic conservation between the human and feline genomes and extend the feline gene map to include 105 assigned loci. C1 H&W CYTOGENET SERV INC,LOVETTSVILLE,VA. GEORGETOWN UNIV,LOMBARDI CANC CTR,WASHINGTON,DC. LA TROBE UNIV,DEPT GENET & HUMAN VARIAT,BUNDOORA,VIC 3083,AUSTRALIA. UNIV TOKYO,DEPT VET INTERNAL MED,TOKYO,JAPAN. RP OBrien, SJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB GENOM DIVERS,FREDERICK,MD 21702, USA. RI Graves, Jennifer/A-1387-2008 NR 41 TC 37 Z9 38 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0022-1503 J9 J HERED JI J. Hered. PD SEP-OCT PY 1997 VL 88 IS 5 BP 408 EP 414 PG 7 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA XZ133 UT WOS:A1997XZ13300014 PM 9378918 ER PT J AU Zipp, F Martin, R Lichtenfels, R Roth, W Dichgans, J Krammer, PH Weller, M AF Zipp, F Martin, R Lichtenfels, R Roth, W Dichgans, J Krammer, PH Weller, M TI Human autoreactive and foreign antigen-specific T cells resist apoptosis induced by soluble recombinant CD95 ligand SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; TUMOR-NECROSIS-FACTOR; HUMAN FAS LIGAND; ANTIBODY-MEDIATED APOPTOSIS; HUMAN-MALIGNANT GLIOMA; MULTIPLE-SCLEROSIS; PERIPHERAL-BLOOD; GENE-TRANSFER; DEATH; LYMPHOCYTES AB Mature T cells are susceptible to activation-induced cell death in the periphery, Activation-induced cell death is thought to involve CD95/CD95 ligand interactions in vivo. Here we report that stimulated, CD45RO(+) human T cell lines specific for myelin basic protein or tetanus toroid from multiple sclerosis patients and healthy individuals resist apoptosis induced by soluble recombinant CD95 ligand in vitro, In contrast, the same CD95 ligand effectively kills Jurkat T lymphoma and human malignant glioma cells, The resistance of the T cell lines is not due to a lack of CD95 expression at the cell surface and is not overcome by coexposure to CD95 ligand and inhibitors of RNA or protein synthesis, The expression level of BCL-2 is lower in Jurkat than in Ag-specific T cells, After exposure to soluble CD95 ligand, Jurkat T cells, but not Ag-specific T cells, exhibit loss of BCL-2 and BCL-X expression whereas BAX expression is not affected, Surprisingly, Ag-specific T cells are rather sensitive to CD95 ligand expressed at the cell surface of N2A neuroblastoma cells, Accessory molecules expressed by the CD95 ligand-expressing effector cell are dispensable for apoptosis since the T cells are equally sensitive to agonistic APO-1 Ab, Further studies are required to determine whether resistance to soluble CD95 ligand-mediated apoptosis is a possible escape mechanism for T cells from peripheral deletion that may have relevance for autoimmune disorders. C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. GERMAN CANC RES CTR,D-6900 HEIDELBERG,GERMANY. RP Zipp, F (reprint author), UNIV TUBINGEN,DEPT NEUROL,HOPPE SEYLER STR 3,D-72076 TUBINGEN,GERMANY. RI Zipp, Frauke/C-9968-2015 OI Zipp, Frauke/0000-0002-1231-1928 NR 63 TC 63 Z9 64 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1997 VL 159 IS 5 BP 2108 EP 2115 PG 8 WC Immunology SC Immunology GA XR802 UT WOS:A1997XR80200007 PM 9278296 ER PT J AU Chen, HJ Paul, WE AF Chen, HJ Paul, WE TI Cultured NK1.1(+)CD4(+) T cells produce large amounts of IL-4 and IFN-gamma upon activation by anti-CD3 or CD1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULES; ANTIGEN RECEPTOR; TRANSGENIC MICE; CD4+; THYMOCYTES; INTERLEUKIN-4; EXPRESSION; COMPLEX; FAMILY; NK1.1+ AB NK1.1(+)CD4(+) T cells produce more IL-4 and IFN-gamma in response to stimulation with anti-CD3 than conventional CD4(+) T cells that have been primed to be, respectively, Th2 or Th1 cells, Furthermore, NK1.1(+)CD4(+) T cells produce IL-4 even if cultured in the absence of IL-4, whereas conventional CD4(+) T cells require IL-4 to develop into IL-4 producers, The IFN-gamma-producing capacity of NK1.1(+)CD4(+) T cells is enhanced by IL-12. In addition, NK1.1(+)CD4(+) T cells produce substantial amounts of IL-3, IL-5, and IL-10 upon anti-CD3 stimulation, NK1.1(+)CD4(+) T cells can be stimulated to produce IL-4 by culture with L cells expressing CD1 (L-CD1), but primary IL-4 production was rather slow and weak, Restimulation of L-CD1-activated NK1.1(+)CD4(+) T cells with L-CD1 gave rise to a much stronger and more rapid response, yielding IL-l production comparable with anti-CD3 activation of cells initially primed with anti-CDS. L-CD1 stimulation of L-CD1-primed cells resulted in far less IFN-gamma than that elicited by anti-CDS from cells that had been primed with anti-CD3, but such production is substantially increased by adding IL-12 to the culture, The differing patterns of cytokine production by NK1.1(+)CD4(+) T cells suggest that these cells may have complex effects on the priming of conventional T cells and may not simply drive such cells to the acquisition of a Th2 phenotype. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 48 TC 229 Z9 233 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1997 VL 159 IS 5 BP 2240 EP 2249 PG 10 WC Immunology SC Immunology GA XR802 UT WOS:A1997XR80200023 PM 9278312 ER PT J AU Kitazawa, H Muegge, K Badolato, R Wang, JM Fogler, WE Ferris, DK Lee, CK Candeias, S Smith, MR Oppenheim, JJ Durum, SK AF Kitazawa, H Muegge, K Badolato, R Wang, JM Fogler, WE Ferris, DK Lee, CK Candeias, S Smith, MR Oppenheim, JJ Durum, SK TI IL-7 activates alpha(4)beta(1) integrin in murine thymocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID THYMIC STROMAL CELLS; INTERLEUKIN-7 RECEPTOR; T-CELLS; EXPRESSION; PHOSPHORYLATION; ADHESION; KINASES; GROWTH; STAGE AB IL-7, a cytokine produced by thymic epithelium, was shown to induce adhesion of murine thymocytes to gelatin-coated membranes. A major binding component of gelatin was identified as fibronectin, IL-7-induced adhesion was observed for all of the major thymocyte subsets, including double-negative, double-positive, and single-positive cells, and specific IL-7R were verified on each subset. Fibronectin binding was mediated via alpha(4) beta(1) integrin (VLA-4), which is expressed at high levels on thymocytes. VLA-4 surface expression was not increased following IL-7 treatment, but was shown to undergo rapid tyrosine phosphorylation on the beta(1) subunit. This tyrosine phosphorylation was blocked by genistein, which also blocked IL-7-induced adhesion. IL-7 was detected on the extracellular matrix of the thymus, suggesting that it could promote matrix association through an integrin pathway. C1 NCI,MOL IMMUNOREGULAT LAB,FREDERICK CANC RES FACIL,NIH,FREDERICK,MD 21702. NCI,SCI APPLICAT INT CORP,NIH,FREDERICK,MD 21702. NCI,EXPT IMMUNOL LAB,NIH,FREDERICK,MD 21702. RI Badolato, Raffaele/A-8081-2010; Kitazawa, Haruki/C-1256-2011 OI Badolato, Raffaele/0000-0001-7375-5410; NR 25 TC 37 Z9 37 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1997 VL 159 IS 5 BP 2259 EP 2264 PG 6 WC Immunology SC Immunology GA XR802 UT WOS:A1997XR80200025 PM 9278314 ER PT J AU Jankovic, D Caspar, P Zweig, M GarciaMoll, M Showalter, SD Vogel, FR Sher, A AF Jankovic, D Caspar, P Zweig, M GarciaMoll, M Showalter, SD Vogel, FR Sher, A TI Adsorption to aluminum hydroxide promotes the activity of IL-12 as an adjuvant for antibody as well as type 1 cytokine responses to HIV-1 gp120 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; IN-VIVO; PROTECTIVE IMMUNITY; TOXOPLASMA-GONDII; LEISHMANIA-MAJOR; INTERLEUKIN-12; ANTIGEN; EXPRESSION; INFECTION; CELLS AB A series of protocols were tested to examine the adjuvant effects of IL-12 on humoral and type 1 cytokine responses elicited in mice by recombinant gp120 envelope protein from HIV-1. This Ag fails to induce detectable Ab responses when administered s.c. alone, but stimulates low Ab levels when combined with aluminum hydroxide (alum), Moreover, when i.p. injected rIL-12 was included in the immunization, no increase in Ab production was observed, Importantly, optimal gp120 Ab responses were achieved by immunizing mice s.c. with gp120 and rlL-12 simultaneously coadsorbed to alum, These animals displayed a highly polarized, type 1 cytokine profile, with the emergence of anti-gp120 Ig belonging to the lgG2 and lgG3 isotypes, In addition, a major increase occurred in Ab of the IgG1 subclass. The superior adjuvant activity of alum-adsorbed IL-12 compared with that of the free cytokine correlated with the prolonged detection of IFN-gamma in the sera of animals immunized using the former procedure, In related experiments, in vitro neutralization of IL-12 was shown to inhibit IFN-gamma production by spleen cells from mice immunized with gp120 plus alum, but not by splenocytes from mice primed in the presence of IL-12, suggesting that the latter protocol induces a stable type 1 phenotype. These studies demonstrate that presentation of IL-12 on alum enhances its immunomodulatory effects and establish a protocol for the use of the cytokine as an adjuvant for simultaneously promoting both humoral Ab and type 1 cytokine responses. C1 NIAID,VACCINE & PREVENT RES PROGRAM,DIV AIDS,NIH,BETHESDA,MD 20892. BIOMOL TECHNOL INC,FREDERICK,MD 21703. RP Jankovic, D (reprint author), NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,NIH,9000 ROCKVILLE PIKE,BLDG 4-126,BETHESDA,MD 20892, USA. NR 41 TC 81 Z9 82 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1997 VL 159 IS 5 BP 2409 EP 2417 PG 9 WC Immunology SC Immunology GA XR802 UT WOS:A1997XR80200043 PM 9278332 ER PT J AU McCarthy, JB Vachhani, BV Wahl, SM Finbloom, DS Feldman, GM AF McCarthy, JB Vachhani, BV Wahl, SM Finbloom, DS Feldman, GM TI Human monocyte binding to fibronectin enhances IFN-gamma-induced early signaling events SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE PHOSPHORYLATION; CENTRIFUGAL ELUTRIATION CCE; MONONUCLEAR CELL SUBSETS; TRANSCRIPTION FACTOR; EXTRACELLULAR-MATRIX; INTERFERON ACTIVATION; ADHESION MOLECULES; ENRICHED FRACTIONS; INVITRO ACTIVATION; GENE-EXPRESSION AB Leukocyte integrins are fundamentally important in modulating adhesion to extracellular matrix components and to other cells, This integrin-mediated adhesion controls leukocyte arrest and extravasation during the onset of inflammatory responses, Moreover, integrin-ligand interactions trigger signaling pathways that may influence leukocyte phenotype and function at sites of inflammation, In the current studies, we evaluated the combinatorial effects of monocyte adhesion and IFN-gamma on intracellular signaling pathways, IFN-gamma triggers a well-defined signal transduction pathway, which although not directly stimulated by monocyte adherence to fibronectin or arginine-glycine-aspartate (RGD)-coated substrata, was enhanced significantly in these matrix-adherent cells, Compared with monocytes in suspension or adherent on plastic surfaces, monocytes adherent to fibronectin or RGD exhibited a greater than threefold increase in steady state levels of IFN-gamma-induced mRNA for the high affinity Fc gamma RI receptor, By electrophoretic mobility shift assays, this increase in mRNA was associated with a 5- to 10-fold increase in the STAT1-containing DNA-binding complex that binds to Fc gamma RI promoter elements, Furthermore, the tyrosine phosphorylation of STAT1 and the tyrosine kinases JAK1 and JAK2 was enhanced significantly in RGD-adherent monocytes compared with control cells, These results suggest a novel mechanism by which integrin-mediated cell adhesion can modulate the magnitude of cytokine-induced signal transduction pathways, thereby amplifying cellular events leading to monocyte activation and inflammation. C1 US FDA,CBER,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. NR 56 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1997 VL 159 IS 5 BP 2424 EP 2430 PG 7 WC Immunology SC Immunology GA XR802 UT WOS:A1997XR80200045 PM 9278334 ER PT J AU Chen, YM Yang, WK WhangPeng, J Tsai, WY Hung, YM Yang, DM Lin, WC Perng, RP Ting, CC AF Chen, YM Yang, WK WhangPeng, J Tsai, WY Hung, YM Yang, DM Lin, WC Perng, RP Ting, CC TI Restoration of the immunocompetence by IL-2 activation and TCR-CD3 engagement of the in vivo anergized tumor-specific CTL from lung cancer patients SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE lung cancer; pleural effusion; T-cell anergy; tumor immunity ID CD4(+) T-CELLS; CLONAL ANERGY; IN-VIVO; IMMUNOSUPPRESSION; COSTIMULATION; LYMPHOCYTES; TOLERANCE; MECHANISM AB The present study investigates the nature of the immunosuppressed state of the lymphocytes obtained from the malignant pleural effusion (effusion associated lymphocytes, EAL) of lung cancer patients. The immunocompetence of EAL from 13 patients was assessed by determining their T-helper cell phenotype, proliferative response to alpha CD3-activation, and their cytolytic activity against three tumor targets: the autologous tumor, Daudi, and K562. Flow cytometry analysis showed that the lymphocytes in EAL were predominantly T cells with <1% natural killer cells. The T-helper cell phenotype was found to be predominantly of Th2 type, but could be readily converted to Th1 type by culturing the EAL in vitro, and this conversion was augmented by interleukin-2 (IL-2) or IL-2 plus alpha CD3. To test the cytolytic activity of EAL, it was found that after 6-day culturing, the EAL remained in an immunosuppressed state so that they failed to kill any of the three tumor targets. Stimulation with IL-2 partially restored the immunocompetence of EAL. Further engagement of TCR-CD3 by alpha CD3 fully restored the cytolytic activity of the EAL to kill the autologous tumor target but not Daudi or K562 tumor cells, and thus seemed to be tumor specific. The specificity was further confirmed by testing the activating EAL and normal donor peripheral blood lymphocytes against a variety of tumor targets and control targets. Furthermore, the killing by EAL against the autologous tumor targets seemed to be major histocompatibility complex-restricted and was inhibited by anti-human leukocyte antigen class I antibody. The EAL from lung cancer patients also showed much reduced responsiveness to the alpha CD3 stimulation to induce proliferation, and addition of IL-2 restored the responsiveness. These results suggest that, through close contact with tumor cells, anergy of cytotoxic T lymphocytes (CTLs) was induced in vivo at a localized site. IL-2 stimulation and TCR-CD3 engagement could reverse the anergic state and restored the full competence of CTLs in EAL to mediate the specific anti-tumor killing against the autologous tumor. Proper manipulation of EAL may prove useful as a source of anti-tumor effectors for cancer adoptive immunotherapy. C1 NCI,LAB IMMUNE CELL BIOL,NIH,BETHESDA,MD 20892. VET GEN HOSP,CHEST DEPT,TAIPEI,TAIWAN. NATL HLTH RES INST,CANC CLIN RES CTR,TAIPEI,TAIWAN. NATL YANG MING UNIV,SCH MED,TAIPEI 112,TAIWAN. RI Lin, Wen-chang/B-3100-2011 OI Lin, Wen-chang/0000-0003-0194-1745 NR 26 TC 31 Z9 32 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 1997 VL 20 IS 5 BP 354 EP 364 DI 10.1097/00002371-199709000-00004 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA XY969 UT WOS:A1997XY96900004 PM 9336742 ER PT J AU Moriuchi, H Moriuchi, M Sun, CCJ Trucksis, M AF Moriuchi, H Moriuchi, M Sun, CCJ Trucksis, M TI Disseminated cutaneous zoster and aseptic meningitis in a previously healthy patient SO JOURNAL OF INFECTION LA English DT Article ID CEREBROSPINAL-FLUID; HERPES-ZOSTER; INFECTION; LYMPHOMA; VIRUS AB A previously healthy, 37-year-old immunocompetent man presented with disseminated cutaneous tester and aseptic meningitis, Varicella tester virus DNA was recovered from the cerebrospinal fluid (CSF) by the polymerase chain reaction. Cytological evaluation of the CSF revealed 'reactive, highly atypical lymphocytosis'. The patient fully recovered after treatment with aciclovir. C1 UNIV MARYLAND,SCH MED,DEPT INTERNAL MED,DIV GEOG MED,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. RP Moriuchi, H (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,RM 6A11,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 5 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0163-4453 J9 J INFECTION JI J. Infect. PD SEP PY 1997 VL 35 IS 2 BP 183 EP 185 DI 10.1016/S0163-4453(97)91842-9 PG 3 WC Infectious Diseases SC Infectious Diseases GA YA168 UT WOS:A1997YA16800017 PM 9354356 ER PT J AU Krause, RM Dimmock, NJ Morens, DM AF Krause, RM Dimmock, NJ Morens, DM TI Summary of antibody workshop: The role of humoral immunity in the treatment and prevention of emerging and extant infectious diseases SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; PASSIVE-IMMUNIZATION; TYPE-1 GP120; CD4 BINDING; SYNERGISTIC NEUTRALIZATION; ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; CD4-BINDING SITE; HIV-1 INFECTION AB In the era before antibiotics, human diseases were commonly treated with immune animal and human sera, often with life-saving results. With the advent of emerging infectious diseases, many of which cannot be adequately treated or prevented, attempts to develop antibody treatments have taken on new importance. The role of humoral immunity in treatment and prevention was the focus of discussion at a 1996 workshop. The cellular and molecular mechanisms of neutralization were examined in detail. It was noted that success in passive immunity has frequently been the key element in devising a successful strategy to develop a vaccine for active immunization. The workshop concluded on a cautious note of optimism that antibody-based treatment and prevention for diseases such as human immunodeficiency virus infection, Ebola fever, and others of clinical and public health importance deserve further development and clinical trial. C1 UNIV WARWICK, DEPT BIOL SCI, COVENTRY CV4 7AL, W MIDLANDS, ENGLAND. UNIV HAWAII, PACIFIC BIOMED RES CTR, HONOLULU, HI 96822 USA. UNIV HAWAII, SCH PUBL HLTH, HONOLULU, HI USA. UNIV HAWAII, SCH MED, HONOLULU, HI 96822 USA. RP Krause, RM (reprint author), NIH, FOGARTY INT CTR, BLDG 16, ROOM 202B, 16 CTR DR, BETHESDA, MD 20892 USA. NR 72 TC 42 Z9 43 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1997 VL 176 IS 3 BP 549 EP 559 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT819 UT WOS:A1997XT81900002 PM 9291299 ER PT J AU Thomas, DL Nakatsuji, Y Shih, JW Alter, HJ Nelson, KE Astemborski, JA Lyles, CM Vlahov, D AF Thomas, DL Nakatsuji, Y Shih, JW Alter, HJ Nelson, KE Astemborski, JA Lyles, CM Vlahov, D TI Persistence and clinical significance of hepatitis G virus infections in injecting drug users SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Antibody Workshop - The Role of Humoral Immunity in the Treatment and Prevention of Emerging and Extant Infectious Diseases CY JUN 02-04, 1996 CL WASHINGTON, DC SP Fogarty Int Ctr, NIH, NIAID, NICHD, NCI, US FDA ID NON-B-HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; UNITED-STATES-ARMY; CHRONIC NON-A; C VIRUS; 1942 EPIDEMIC; BLOOD-DONORS; FOLLOW-UP; ASSOCIATION AB To assess the persistence of hepatitis G virus (HGV) infection and its association with liver disease, HGV RNA was assessed in the most recent serum sample for 246 long-term injecting drug users (IDUs) and in prior specimens for those found HGV RNA-positive. HGV RNA was detected at the most recent visit in 38 (15.4%). For 31 (82%), HGV RNA was also found at all prior visits occurring a median of 6.1 years earlier. HGV-positive IDUs were younger and had fewer years of drug use, suggesting that HGV RNA had previously been cleared. Serial samples from 29 short-term IDUs were then assessed. HGV RNA was detected in 9 (31%) of 29 short-term IDUs, and 5 (56%) of the 9 HGV infections cleared. No differences were detected in serum levels of liver-related enzymes among HGV RNA-positive and -negative participants (P > .20). HGV infection is not associated with hepatic inflammation. HGV clearance occurs after many acute infections but uncommonly in persons who remain RNA-positive years after exposure. C1 JOHNS HOPKINS MED SCH,DIV INFECT DIS,BALTIMORE,MD. JOHNS HOPKINS SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. FU NIDA NIH HHS [DA-23201, DA-08004, DA-04334] NR 26 TC 34 Z9 34 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1997 VL 176 IS 3 BP 586 EP 592 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT819 UT WOS:A1997XT81900006 PM 9291303 ER PT J AU Stewart, DR Morris, TS Purcell, RH Emerson, SU AF Stewart, DR Morris, TS Purcell, RH Emerson, SU TI Detection of antibodies to the nonstructural 3C proteinase of hepatitis A virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Antibody Workshop - The Role of Humoral Immunity in the Treatment and Prevention of Emerging and Extant Infectious Diseases CY JUN 02-04, 1996 CL WASHINGTON, DC SP Fogarty Int Ctr, NIH, NIAID, NICHD, NCI, US FDA ID A VIRUS; VIRAL-HEPATITIS; INFECTION; CLEAVAGE AB Hepatitis A virus (HAV) infection can stimulate the production of antibodies to structural and nonstructural proteins of the virus. However, vaccination with an inactivated vaccine produces antibodies exclusively to the structural proteins. Current diagnostic assays, such as the Abbott HAVAB test, used to determine exposure to HAV detect antibodies only to the structural proteins and as a result are not able to distinguish between a natural infection and vaccination with an inactivated virus. Therefore, an ELISA was developed that is specific for antibodies to the nonstructural protein 3C of HAV and thus serves to document the occurrence of viral replication. Antibodies to the proteinase were not detected by this assay in serum from HAVAB-seropositive primates that were immunized with inactivated HAV. However, antibodies to the proteinase were detected in the serum of all primates experimentally infected with virulent HAV and in the serum of naturally infected humans. C1 NIAID,HEPATITIS VIRUSES SECT,INFECT DIS LAB,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-050569, AO-45180] NR 15 TC 11 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1997 VL 176 IS 3 BP 593 EP 601 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT819 UT WOS:A1997XT81900007 PM 9291304 ER PT J AU Blauvelt, A Sei, S Cook, PM Schulz, TF Jeang, KT AF Blauvelt, A Sei, S Cook, PM Schulz, TF Jeang, KT TI Human herpesvirus 8 infection occurs following adolescence in the United States SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; DNA-SEQUENCES; ANTIBODIES; SEMEN AB Most recent evidence suggests that human herpesvirus 8 (HHV-8) infection is restricted to persons with Kaposi's sarcoma (KS) or to persons who may subsequently develop KS. To accurately determine the prevalence of infection in the United States, children and adults with AIDS were examined for evidence of HHV-8 infection to see whether HHV-8 (like other herpesviruses) would be readily detected in immunosuppressed persons. By use of nested polymerase chain reaction, DNA specific for HHV-8, Epstein-Barr virus, and cytomegalovirus was detected in blood leukocytes from 0, 26 (51%), and 9 (18%), respectively, of 51 children. Similarly, HHV-8-specific antibodies were not detected in analyses of sera from the children. By contrast, HHV-8 DNA was detected in 9 (27%) of 33 adult AIDS patients without KS. These findings suggest that the pattern of transmission of HHV-8 in the United States differs from that of other herpesviruses in that primary infection occurs predominantly in adults. C1 NCI, HIV & AIDS MALIGNANCY BRANCH, BETHESDA, MD 20892 USA. NIAID, MOL MICROBIOL LAB, NIH, BETHESDA, MD 20892 USA. UNIV LIVERPOOL, DEPT MED MICROBIOL & GENITOURINARY MED, LIVERPOOL L69 3BX, MERSEYSIDE, ENGLAND. RP Blauvelt, A (reprint author), NCI, DERMATOL BRANCH, BLDG 10, ROOM 12N238, 10 CTR DR MSC 1908, BETHESDA, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 15 TC 59 Z9 63 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1997 VL 176 IS 3 BP 771 EP 774 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT819 UT WOS:A1997XT81900033 PM 9291330 ER PT J AU Torpy, DJ Chrousos, GP AF Torpy, DJ Chrousos, GP TI Stress and critical illness: The integrated immune hypothalamic-pituitary-adrenal axis response SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; INSULIN-INDUCED HYPOGLYCEMIA; HORMONE GENE-EXPRESSION; SUSCEPTIBLE LEWIS RATS; GLUCOCORTICOID RECEPTOR; ARGININE VASOPRESSIN; PARAVENTRICULAR NUCLEUS; RHEUMATOID-ARTHRITIS; MESSENGER-RNA; SUBSTANCE-P AB Critical illness leads to a coordinated reaction that is categorized as the stress response; activation of the hypothalamic pituitary-adrenal (HPA) axis and the sympathetic nervous system leads to metabolic and cardiovascular changes that are generally directed toward maintenance of homeostasis. The HPA axis and the sympathetic nervous system are linked via reciprocally activating brainstem pathways. The immune system acts via cytokines, which are hormones, to activate the HPA axis. Glucocorticoid secretion suppresses immune activity, thus completing an immune-HPA feedback loop. Restraint of immune activity may be a major function of glucocorticoids during stress, thus averting the potential for immune-mediated damage to healthy tissues. Cortisol also acts to produce adaptive metabolic, cardiovascular, and cognitive changes. Activation of the stress system is also associated with inhibition of thyroid, gonadal, and growth axes through neuroendocrine and peripheral mechanisms; such effects can be seen as directed toward conservation of energy. There is growing evidence that hyperfunction and hypofunction of the integrated stress system may lead to a variety of previously unexplained disorders. Recently, a more detailed understanding of the stress system combined with astute clinical observation of critically ill patients has led to promising new avenues for therapeutic investigation. RP Torpy, DJ (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 10N262,BETHESDA,MD 20892, USA. NR 145 TC 5 Z9 5 U1 1 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0885-0666 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD SEP-OCT PY 1997 VL 12 IS 5 BP 225 EP 238 PG 14 WC Critical Care Medicine SC General & Internal Medicine GA XX279 UT WOS:A1997XX27900003 ER PT J AU Jakob, T Udey, MC AF Jakob, T Udey, MC TI Mediators that mobilize Langerhans cells (LC) in vivo regulate E-cadherin (E-cad) mRNA, E-cad surface expression and E-cad-mediated adhesion in LC-like dendritic cells in vitro. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1997 VL 109 IS 3 BP 404 EP 404 PG 1 WC Dermatology SC Dermatology GA XT103 UT WOS:A1997XT10300028 ER PT J AU Haase, C Budinger, L Merk, HF Yee, C Borradori, L Yancey, K Hertl, M AF Haase, C Budinger, L Merk, HF Yee, C Borradori, L Yancey, K Hertl, M TI Detection of autoantibodies against the extracellular domain of BPAG2 (BP180) in the majority of bullous and gestational pemphigoid sera by ELISA. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 RHEIN WESTFAL TH AACHEN,DEPT DERMATOL,D-5100 AACHEN,GERMANY. NIH,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1997 VL 109 IS 3 BP 405 EP 405 PG 1 WC Dermatology SC Dermatology GA XT103 UT WOS:A1997XT10300035 ER PT J AU Kirnbauer, R Armstrong, A Haderer, P Christensen, N Lowy, D Schiller, J Roden, R AF Kirnbauer, R Armstrong, A Haderer, P Christensen, N Lowy, D Schiller, J Roden, R TI Characterization of a human papillomavirus (HPV) type 16 variant-dependent neutralizing epitope. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,LAB VIRAL ONCOL,DIAID,DEPT DERMATOL,A-1010 VIENNA,AUSTRIA. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1997 VL 109 IS 3 BP 414 EP 414 PG 1 WC Dermatology SC Dermatology GA XT103 UT WOS:A1997XT10300087 ER PT J AU Pfutzner, W Hengge, U Ye, X Jakob, T Jensen, T Vogel, J AF Pfutzner, W Hengge, U Ye, X Jakob, T Jensen, T Vogel, J TI Optimization of retroviral mediated gene transfer to primary keratinocytes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. UNIV ESSEN GESAMTHSCH,DEPT DERMATOL,ESSEN,GERMANY. NCHGR,CLIN GENE THERAPY BRANCH,BETHESDA,MD. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1997 VL 109 IS 3 BP 424 EP 424 PG 1 WC Dermatology SC Dermatology GA XT103 UT WOS:A1997XT10300149 ER PT J AU Hengge, UR Schiffer, D Podsakoff, G Kurzmann, G Goos, M Vogel, JC AF Hengge, UR Schiffer, D Podsakoff, G Kurzmann, G Goos, M Vogel, JC TI Adeno-associated virus (AAV) efficiently expresses trangenes in epidermis in vivo: Comparison with naked plasmid DNA. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 AVIGEN,ALAMEDA,CA. UNIV ESSEN GESAMTHSCH,DEPT DERMATOL,D-4300 ESSEN 1,GERMANY. NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1997 VL 109 IS 3 BP 427 EP 427 PG 1 WC Dermatology SC Dermatology GA XT103 UT WOS:A1997XT10300168 ER PT J AU Boni, R Matt, D Burg, G Tronnier, M Zhuang, Z AF Boni, R Matt, D Burg, G Tronnier, M Zhuang, Z TI UV induced acute histologic changes in melanocytic nevi and allelic loss SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV ZURICH HOSP,DEPT DERMATOL,CH-8091 ZURICH,SWITZERLAND. UNIV LUBECK,DEPT DERMATOL,D-2400 LUBECK,GERMANY. NATL CANC INST HLTH,DEPT PATHOL,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1997 VL 109 IS 3 BP 439 EP 439 PG 1 WC Dermatology SC Dermatology GA XT103 UT WOS:A1997XT10300235 ER PT J AU Domachowske, JB Rosenberg, HF AF Domachowske, JB Rosenberg, HF TI Eosinophils inhibit retroviral transduction of human target cells by a ribonuclease-dependent mechanism SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE granule proteins; RNA viruses; beta-galactosidase ID RESPIRATORY SYNCYTIAL VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CATIONIC PROTEIN; SCHISTOSOMA-MANSONI; TRICHINELLA-SPIRALIS; MOLECULAR-CLONING; GENE FAMILY; NEUROTOXIN; INFECTION; RESISTANCE AB Human eosinophils contain a number of granule proteins for which specific physiological roles remain unclear. The combined ribonucleolytic and membrane disruptive properties of the eosinophil-derived neurotoxin and eosinophil cationic protein, respectively, suggest the possibility that eosinophils might participate in host defense against enveloped single-stranded RNA viruses. To test this hypothesis, stocks of a replication-defective retrovirus encoding the reporter gene beta-galactosidase were pretreated with isolated human eosinophils, then used to transduce human erythroleukemia (K-562) target cells. Histochemical staining for beta-galactosidase activity was used to detect and quantitate the transduced cells. Co-incubation of retrovirus with eosinophils (0.4 x 10(6)/mL) before target cell transduction resulted in a marked decrease in transduction efficiency corresponding to an similar to 20-fold dilution of viral stock (P < 0.01), an effect that was directly proportional to the concentration of eosinophils, and that was reversed in the presence of ribonuclease inhibitor. Reverse transcriptase-polymerase chain reaction analysis demonstrated loss of the retroviral RNA genome as a result of eosinophil, pretreatment, indicating that eosinophils are capable of mediating direct ribonucleolytic destruction of the isolated retroviral particles. Our results demonstrate that eosinophils function as effective anti-retroviral agents in vitro via the actions of their secreted ribonucleases, and suggest that eosinophils may represent an unrecognized arm of host defense against enveloped single-stranded RNA viral pathogens. C1 NIAID,LHD,NIH,BETHESDA,MD 20892. NR 45 TC 30 Z9 30 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1997 VL 62 IS 3 BP 363 EP 368 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA XV690 UT WOS:A1997XV69000010 PM 9307075 ER PT J AU Snell, JC Chernyshev, O Gilbert, DL Colton, CA AF Snell, JC Chernyshev, O Gilbert, DL Colton, CA TI Polyribonucleotides induce nitric oxide production by human monocyte-derived macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE nitrite; virus; species specificity; interferon ID INTERFERON-GAMMA; HUMAN MONOCYTES/MACROPHAGES; PERITONEAL-MACROPHAGES; MYCOBACTERIUM-AVIUM; MOUSE MACROPHAGES; SYNTHASE GENE; MESSENGER-RNA; IFN-GAMMA; NO NO; EXPRESSION AB Cytokine-mediated activation of inducible nitric oxide synthase (iNOS) in monocytes or macrophages is species specific. In contrast to rat or mouse, human macrophages do not produce measurable levels of nitric oxide (NO) when induced by inflammatory mediators. Exposure to noncytokine mediators such as tumor cells or viruses, however, has recently been shown to activate human iNOS. NO production in response to these mediators is much lower than that seen for rat or mouse cells and often requires several days of stimulation. We have found that the synthetic, double-stranded polyribonucleotide polyinosinic-polycytidilic acid (Poly I:C), commonly used to mimic viral exposure, activated iNOS in human monocyte-derived macrophages (MDM). The production of NO, measured by nitrite accumulation, was detected after 24 h of stimulation with Poly I:C. The single-stranded polyribonucleotide Poly I, but not Poly C, also increased NO production. Nitrite production was enhanced when the MDM were primed (pretreated) with gamma or alpha interferon or other immune mediators such as IL-4 and was reduced by the iNOS inhibitor, N-methyl-L-arginine (L-NMMA). The use of Poly I:C to initiate NO production in human macrophages provides a useful tool to study the differences between the commonly used animal models and human cells and may provide insight into the pathophysiological significance of these differences. C1 GEORGETOWN UNIV,MED CTR,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. NINCDS,UNIT REACT OXYGEN SPECIES,BIOPHYS SECT,NIH,BETHESDA,MD 20892. NR 30 TC 32 Z9 33 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1997 VL 62 IS 3 BP 369 EP 373 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA XV690 UT WOS:A1997XV69000011 PM 9307076 ER PT J AU Ortaldo, JR Mason, LH Gregorio, TA Stoll, J WinklerPickett, RT AF Ortaldo, JR Mason, LH Gregorio, TA Stoll, J WinklerPickett, RT TI The Ly-49 family: Regulation of cytokine production in murine NK cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE tumor necrosis factor alpha; interferon-gamma; granulocyte-macrophage colony-stimulating factor; flow cytometry analysis; natural killer; Ly49 ID NATURAL-KILLER-CELLS; MULTIGENE FAMILY; INHIBITORY RECEPTOR; MEMBRANE-PROTEINS; BONE-MARROW; ANTIGEN; RECOGNITION; RESISTANCE; MOLECULES; SUBSETS AB Most proteins encoded by members of the Ly-49 gene family are class I-recognizing receptors on murine natural killer (NK) cells. Class I recognition by Ly-49 receptors usually results in inhibition of Nh cell Iysis of target cells. However, Nh cells function not only in a lytic capacity, but also can mediate cytokine production. In this report we have demonstrated the ability of Ly-49A and Ly-49G2 to inhibit production of cytokines by NK cells by showing that specific antibodies against these gene products stimulate cytokine production. Murine NK cells were cultured in the presence of P815 (H2-D-d), and supernatants were analyzed for the production of interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Nh cell populations were sorted for Ly-49A(+) or Ly-49G(+) subsets, and these subsets were analyzed for their ability to alter cytokine induction by target cell interaction. In the presence of target cells expressing the appropriate class I molecules, Ly-49A and 62 were found to inhibit cytokine induction by Nh cells. Examination of mRNA for IFN-gamma and GM-CSF indicated that Ly-49 receptors increased mRNA levels of Nh cells. These results demonstrate that class I binding of these Nh receptors can inhibit production of important physiological cytokines, in addition to the regulation of cytotoxic activity. RP Ortaldo, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,BLDG 560,RM 31-93,FREDERICK,MD 21702, USA. NR 27 TC 20 Z9 21 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1997 VL 62 IS 3 BP 381 EP 388 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA XV690 UT WOS:A1997XV69000013 PM 9307078 ER PT J AU Dugi, KA Vaisman, BL Sakai, N Knapper, CL Meyn, SM Brewer, HB SantamarinaFojo, S AF Dugi, KA Vaisman, BL Sakai, N Knapper, CL Meyn, SM Brewer, HB SantamarinaFojo, S TI Adenovirus-mediated expression of hepatic lipase in LCAT transgenic mice SO JOURNAL OF LIPID RESEARCH LA English DT Article DE adenoviridae; apolipoproteins A; apolipoproteins E; lecithin acyltransferase; lipoproteins HDL/metabolism ID HIGH-DENSITY-LIPOPROTEINS; LECITHIN-CHOLESTEROL ACYLTRANSFERASE; APOLIPOPROTEIN-A-I; ESTER TRANSFER PROTEIN; FISH-EYE DISEASE; TRIGLYCERIDE LIPASE; MAMMALIAN-CELLS; PLASMA-LIPOPROTEINS; FIREFLY LUCIFERASE; PARTICLE SURFACE AB In order to evaluate the coordinate role that hepatic lipase (HL) and lecithin: Cholesterol acyltransferase (LCAT) play in modulating HDL particle heterogeneity and function in vivo we utilized recombinant adenovirus to express HL in control and LCAT transgenic mice. Adenovirus-mediated expression of human HL in control (n = 4, LCAT activity = 42 +/- 1 nmol/ml per h) and LCAT-tg mice (n = 4, LCAT activity = 3566 +/- 93 nmol/ml per h) resulted in post heparin HL activities of 24358 +/- 6080 and 27266 +/- 7985 nmol/ml per min, respectively. Overexpression of HL led to significant reductions in total cholesterol, phospholipids, and HDL cholesterol in both LCAT-tg (62, 62, and 63%, P < 0.05) and control mice (68, 63, and 78%, P < 0.01) as well as to the formation of more homogenous HDL. However, compared to control animals, the reductions in the plasma concentrations of HDL-cholesterol and apoA-I were less in LCAT-tg mice (HDL-cholesterol: -62 +/- 15% vs. -78 +/- 15%, P = 0.18; apoA-I: -36 +/- 7% vs. -76 +/- 8%, P < 0.0005). Gel filtration analysis revealed that in LCAT-tg mice the apoE-rich HDL1 was preferentially reduced by expression of HL in vivo. Compared to control mice the reduction in the apoA-I/A-II HDL in transgenic mice was significantly less indicating that a subset of HDL in LCAT transgenic mice are resistant to the action of HL. These combined data support a role for both HL and LCAT in modulating HDL heterogeneity and function, properties which may ultimately affect the ability of LCAT transgenic mouse HDL to function in the process of reverse cholesterol transport. RP Dugi, KA (reprint author), NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892, USA. NR 58 TC 26 Z9 30 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 1997 VL 38 IS 9 BP 1822 EP 1832 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XY767 UT WOS:A1997XY76700011 PM 9323591 ER PT J AU Woodward, E Rose, S Schmidt, L Affara, NA Maher, ER AF Woodward, E Rose, S Schmidt, L Affara, NA Maher, ER TI Mutation analysis of the MET proto-oncogene and the von Hippel-Lindau (VHL) tumour suppressor gene in familial renal cell carcinoma. SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1TN,ENGLAND. BIRMINGHAM WOMENS HOSP,REG MOL GENET LAB,BIRMINGHAM B15 2TG,W MIDLANDS,ENGLAND. NCI,IMMUNOBIOL LAB,BETHESDA,MD 20892. UNIV BIRMINGHAM,DEPT PAEDIAT & CHILD HLTH,DIV MED GENET,BIRMINGHAM B15 2TG,W MIDLANDS,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 1997 VL 34 SU 1 BP 247 EP 247 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA XX125 UT WOS:A1997XX12500101 ER PT J AU Cai, T Tagle, DA Xia, X Yu, P He, XX Li, LY Xia, JH AF Cai, T Tagle, DA Xia, X Yu, P He, XX Li, LY Xia, JH TI A novel case of unilateral blepharophimosis syndrome and mental retardation associated with de novo trisomy for chromosome 3q SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE blepharophimosis; ptosis; mental retardation; 3q26-qter trisomy ID EPICANTHUS-INVERSUS SYNDROME; SYNDROME BPES; INTERSTITIAL DELETION; SHORT ARM; CERULOPLASMIN GENE; HYPOPLASTIC TEETH; EYE MORPHOGENESIS; DROSOPHILA-HAIRY; OVARIAN FAILURE; PROBE POOL AB We have evaluated a 3 2/12 year old girl who presented with unilateral blepharophimosis, ptosis of the eyelid, and mental retardation. Additional dysmorphic features include microcephaly, high, narrow forehead, short stubby fingers, and adduction of the right first toe. Cytogenetic analysis showed an unbalanced karyotype consisting of 46,XX,add(7)(q+) that was de novo in origin. Fluorescence in situ hybridisation (FISH) using microdissected library probe pools from chromosomes 1, 2, 3, 7, and 3q26-qter showed that the additional material on 7q was derived from the distal end of the long arm of chromosome 3. Our results indicate that the patient had an unbalanced translocation, 46,XX,der(7)t(3;7) (q26-qter;q+) which resulted in trisomy for distal 3q. All currently reported cases of BPES (blepharophimosis-ptosis-epicanthus inversus syndrome) with associated cytogenetic abnormalities show interstitial deletions or balanced translocations involving 3q22-q23 or 3p25.3. Our patient shares similar features to BPES, except for the unilateral ptosis and absence of epicanthus inversus. It is possible that our patient has a contiguous gene defect including at least one locus for a type of blepharophimosis, further suggesting that multiple loci exist for eyelid development. C1 HUNAN MED UNIV,NATL KEY LAB MED GENET,CHANGSHA,PEOPLES R CHINA. NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NR 63 TC 7 Z9 9 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 1997 VL 34 IS 9 BP 772 EP 776 DI 10.1136/jmg.34.9.772 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XW800 UT WOS:A1997XW80000015 PM 9321768 ER PT J AU Green, E Maliszewska, C Kuzmin, I Latif, F Maher, ER AF Green, E Maliszewska, C Kuzmin, I Latif, F Maher, ER TI Molecular delineation of the 3p-syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 UNIV BIRMINGHAM,DEPT PAEDIAT & CHILD HLTH,DIV MED GENET,BIRMINGHAM B15 2TG,W MIDLANDS,ENGLAND. BIRMINGHAM WOMENS HOSP,DEPT CYTOGENET,BIRMINGHAM B15 2TG,W MIDLANDS,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 1997 VL 34 SU 1 BP SP34 EP SP34 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA XX125 UT WOS:A1997XX12500032 ER PT J AU SingerLahat, D Rojas, E Felder, CC AF SingerLahat, D Rojas, E Felder, CC TI A9 fibroblasts transfected with the m3 muscarinic receptor clone express a Ca2+ channel activated by carbachol, GTP and GDP SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE Ca2+ channel; receptor; carbachol; acetylcholine; voltage-independent Ca2+ channel; cation channel ID INTRACELLULAR CALCIUM STORES; HUMAN-PLATELETS; ACETYLCHOLINE-RECEPTORS; EXTRACELLULAR ATP; CELLS; INFLUX; ENTRY AB Muscarinic m3 receptor-mediated changes in cytosolic Ca2+ concentration ([Ca2+](1)) occur by activation of Ca2+ release channels present in the endoplasmic reticulum membrane and Ca2+ entry pathways across the plasma membrane. In this report we demonstrate the coupling of m3 muscarinic receptors to the activation of a voltage-insensitive, cation-selective channel of low conductance (3.2 +/- 0.6 pS; 25 mM Ca2+ as charge carrier) in a fibroblast cell line expressing m3 muscarinic receptor clone (A9m3 cells). Carbachol (CCh)-induced activation of the cation-selective channel occurred both in whole cell and excised membrane patches (CCh on the external side), suggesting that the underlying mechanism involves receptor-channel coupling independent of intracellular messengers. in excised inside-out membrane patches from nonstimulated A9m3 cells GTP (10 mu M) and GDP (10 mu M) activated cation-selective channels with conductances of approximately 4.3 and 3.3 pS, (25 mM Ca2+ as charge carrier) respectively. In contrast, ATP (10 mu M), UTP (10 mu M) or CTP (10 mu M) failed to activate the channel. Taken together, these results suggest that carbachol and guanine nucleotides regulate the activation of a cation channel that conducts calcium. C1 NIMH,LAB CELLULAR & MOL REGULAT,BETHESDA,MD 20892. NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. NR 28 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP 1 PY 1997 VL 159 IS 1 BP 21 EP 28 DI 10.1007/s002329900265 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA XV199 UT WOS:A1997XV19900002 PM 9309207 ER PT J AU Safi, J Gloe, TR Riccioni, T Kovesdi, I Capogrossi, MC AF Safi, J Gloe, TR Riccioni, T Kovesdi, I Capogrossi, MC TI Gene therapy with angiogenic factors: A new potential approach to the treatment of ischemic diseases SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Review DE gene therapy; angiogenesis; ischemia; FGF; VEGF; heparin; adenovirus; retrovirus; liposomes; DNA ID FIBROBLAST GROWTH-FACTOR; VECTOR INDUCES ANGIOGENESIS; HUMAN ENDOTHELIAL-CELLS; COLLATERAL BLOOD-FLOW; SMOOTH-MUSCLE CELLS; IN-VIVO; RECOMBINANT ADENOVIRUSES; RABBIT MODEL; MOLECULAR MECHANISMS; ANTIGEN PRESENTATION C1 IRCCS, IST DERMOPAT IMMACOLATA, LAB PATOL VASC, I-00167 ROME, ITALY. GENVEC INC, ROCKVILLE, MD USA. NIA, GENE THERAPY UNIT, LAB CARDIOVASC SURG, NIHON UNIV, BALTIMORE, MD 21224 USA. NR 128 TC 20 Z9 22 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 SEP PY 1997 VL 29 IS 9 BP 2311 EP 2325 DI 10.1006/jmcc.1997.0459 PG 15 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA XX809 UT WOS:A1997XX80900001 PM 9299355 ER PT J AU Herman, EH Zhang, J Hasinoff, BB Clark, JR Ferrans, VJ AF Herman, EH Zhang, J Hasinoff, BB Clark, JR Ferrans, VJ TI Comparison of the structural changes induced by doxorubicin and mitoxantrone in the heart, kidney and intestine and characterization of the Fe(III) mitoxantrone complex SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE doxorubicin; mitoxantrone; cardiac toxicity; renal toxicity; apoptosis; iron-mitoxantrone complex ID AGENT ICRF-187 (+)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE; SPONTANEOUSLY HYPERTENSIVE RATS; FREE-RADICAL FORMATION; PROGRAMMED CELL-DEATH; ANTITUMOR AGENTS; HYDROGEN-PEROXIDE; HYDROXYL RADICALS; DNA; HYDROLYSIS; ADRIAMYCIN AB Histologic, nick end labeling for apoptosis and electron microscopic studies were made of the heart, kidney and small intestine in spontaneously hypertensive rats (SHR) treated for 12 weeks with doxorubicin (1 mg/kg/week), mitoxantrone (0.5 or 0.25 mg/kg/week) or saline (controls). Semiquantitative scoring showed that the severity of the cardiac lesions produced by doxorubicin was comparable to that resulting from 0.5 mg/kg mitoxantrone, but greater than that induced by 0.25 mg/kg mitoxantrone (to which it is therapeutically equivalent). The nephropathy and the intestinal toxicity produced by doxorubicin were also more severe than those resulting from either dose of mitoxantrone. Apoptosis of cardiac myocytes was not induced by either drug, but involved cardiac dendritic cells in SHR given doxorubicin. Apoptosis in renal tubular epithelium was comparable in SHR given doxorubicin and the higher dose of mitoxantrone. Doxorubicin induced more frequent apoptosis in intestinal epithelium than did the higher dose of mitoxantrone. We also show that mitoxantrone and iron(III) form a strong 2:1 complex, in which the drug may be acting as a tridentate ligand. This complex, like the iron(III)-doxorubicin complex, may be capable of redox cycling and producing reactive oxygen intermediates (ROI) that damage tissue. Decreased formation of ROI by mitoxantrone may account for its reduced cardiotoxicity compared to that of doxorubicin. (C) 1997 Academic Press Limited. C1 UNIV MANITOBA, FAC PHARM, WINNIPEG, MB R3T 2N2, CANADA. NHLBI, NIH, PATHOL SECT, BETHESDA, MD 20892 USA. RP Herman, EH (reprint author), US FDA, CTR DRUG EVALUAT & RES, DIV RES & TESTING HFD 910, 8301 MUIRKIRK RD, LAUREL, MD 20708 USA. NR 51 TC 48 Z9 50 U1 0 U2 1 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 SEP PY 1997 VL 29 IS 9 BP 2415 EP 2430 DI 10.1006/jmcc.1997.0477 PG 16 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA XX809 UT WOS:A1997XX80900011 PM 9299365 ER PT J AU Shen, LY Figurov, A Lu, B AF Shen, LY Figurov, A Lu, B TI Recent progress in studies of neurotropic factors and their clinical implications SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE brain-derived neurotrophic factor; trk receptor; long-term potentiation; glia-derived neurotrophic factor; c-ret tyrosine kinase; dopaminergic neurons; kidney organogenesis; enteric nervous system; gene knockout; Hirschsprung's disease ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; MIDBRAIN DOPAMINERGIC-NEURONS; MESSENGER-RNA EXPRESSION; MICE LACKING GDNF; CULTURED HIPPOCAMPAL-NEURONS; C-RET PROTOONCOGENE; POSTNATAL RAT-BRAIN; TYROSINE KINASE; SYNAPTIC TRANSMISSION AB Neurotrophic factors are endogenous soluble proteins that regulate long-term survival and differentia tion of neurons of the peripheral and central nervous systems. These factors play an important role in the structural integrity of the nervous system, and therefore are good candidates as therapeutic agents for neurodegenerative diseases. However, recent studies have revealed some unexpected, novel roles of neurotrophic factors, Of particular significance is the discovery of the new functions of brain-derived neurotrophic factor (BDNF) and glia-derived neurotrophic factor (GDNF), Physiological experiments indicate that BDNF may serve as regulatory factors for synaptic transmission as well as for learning and memory. Gene targeting studies demonstrate that GDNF may be essential for development of the enteric nervous system (ENS) and kidney organogenesis. These results not only provide new insights into our understanding of the function of neurotrophic factors but may also have significant implications in the therapeutic usages of neurotrophic factors. C1 NICHD,LAB MAMMALIAN GENE & DEV,NIH,BETHESDA,MD 20205. NICHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20205. RI Lu, Bai/A-4018-2012 NR 90 TC 29 Z9 32 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD SEP PY 1997 VL 75 IS 9 BP 637 EP 644 DI 10.1007/s001090050147 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA XV494 UT WOS:A1997XV49400005 PM 9351702 ER PT J AU Hinnebusch, BJ AF Hinnebusch, BJ TI Bubonic plague: a molecular genetic case history of the emergence of an infectious disease SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE Yersinia pestis; Yersinia pseudotuberculosis; bubonic plague; emerging infectious disease; evolution of virulence ID YERSINIA-PSEUDOTUBERCULOSIS; PESTIS; ENTEROCOLITICA; PATHOGENESIS; TRANSMISSION; VIRULENCE; INVASION; LOCUS; CELLS; PATHOGENICITY AB Yersinia pestis, the bacterial agent of bubonic plague, is transmitted primarily by fleas and has been responsible for devastating epidemics throughout history. Y. pseudotuberculosis is a food-and water-borne pathogen that causes a much more benign enteric disease in humans, Despite these profoundly different pathogenesis strategies, the two bacteria are very closely related phylogenetically. Thus, identifying the specific genetic differences between them should provide an instructive case study in the evolution of microbial pathogenicity. Some key pathogenesis-related genes of Y. pestis and Y. pseudotuberculosis that have been described to date are compared in this review. Factors that potentiate plague transmission as well as disease are discussed, since dependence on the blood-sucking flea for transmission likely fueled the selection of virulent Y. pestis strains able to produce a high-density bacteremia, Retracing the evolutionary steps between these two Yersinia species may ultimately furnish a historical model for the sudden emergence of new human disease agents. RP Hinnebusch, BJ (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 55 TC 41 Z9 42 U1 3 U2 13 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD SEP PY 1997 VL 75 IS 9 BP 645 EP 652 DI 10.1007/s001090050148 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA XV494 UT WOS:A1997XV49400006 PM 9351703 ER PT J AU Lin, YM Anderson, H Flavin, MT Pai, YHS MataGreenwood, E Pengsuparp, T Pezzuto, JM Schinazi, RF Hughes, SH Chen, FC AF Lin, YM Anderson, H Flavin, MT Pai, YHS MataGreenwood, E Pengsuparp, T Pezzuto, JM Schinazi, RF Hughes, SH Chen, FC TI In vitro anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; LIPID-PEROXIDATION; PHENOLIC-COMPOUNDS; FLAVONOIDS; INHIBITORS; AIDS; 3'-AZIDO-3'-DEOXYTHYMIDINE; RETROVIRUS; KOLA AB Eleven biflavonoids, including amentoflavone (1), agathisflavone (2), robustaflavone (3), hinokiflavone (4), volkensiflavone (5), morelloflavone (7), rhusflavanone (9), succedaneaflavanone (10), GB-1a (11), GB-1a 7 ''-O-beta-glucoside (13), and GB-2a (14) isolated from Rhus succedanea and Garcinia multifilora, as well as their methyl ethers, volkensiflavone hexamethyl ether (6), morelloflavone heptamethyl ether (8), and GB-1a hexamethyl ether (12), were evaluated for their anti-HIV-1 RT activity. The results indicated that compounds 3 and 4 demonstrated similar activity against HIV-1 reverse transcriptase (RT), with IC50 values of 65 mu M. Compounds 1, 2, 7, 11, and 14 were moderately active against HIV-1 RT, with IC50 values of 119 mu M, 100 mu M, 116 mu M, 236 mu M, and 170 mu M, respectively. Morelloflavone (7) also demonstrated significant antiviral activity against HIV-1 (strain LAV-1) in phytohemagglutinin-stimulated primary human peripheral blood mononuclear cells at an EC50 value of 6.9 mu M and a selectivity index value of approximately 10. The other biflavonoids were either weakly active, inactive, or not selective against HIV-1 in human lymphocytes. C1 UNIV ILLINOIS,DEPT MED CHEM & PHARMACOGNOSY,CHICAGO,IL 60612. VET AFFAIRS MED CTR,GEORGIA VA RES CTR AIDS & HIV INFECT,DECATUR,GA 30033. EMORY UNIV,SCH MED,DECATUR,GA 30033. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. TAMKANG UNIV,DEPT CHEM,TAIPEI,TAIWAN. RP Lin, YM (reprint author), MEDICHEM RES INC,12305 S NEW AVE,LEMONT,IL 60439, USA. RI Schinazi, Raymond/B-6777-2017 FU PHS HHS [N01-A1-05078] NR 45 TC 136 Z9 147 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP PY 1997 VL 60 IS 9 BP 884 EP 888 DI 10.1021/np9700275 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA XY520 UT WOS:A1997XY52000004 PM 9322359 ER PT J AU Moody, EJ Knauer, C Granja, R Strakhova, M Skolnick, P AF Moody, EJ Knauer, C Granja, R Strakhova, M Skolnick, P TI Distinct loci mediate the direct and indirect actions of the anesthetic etomidate at GABA(A) receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE etomidate; anesthetics; GABA(A) receptors; chloride currents; flunitrazepam ID SINGLE AMINO-ACID; RAT-BRAIN; BENZODIAZEPINE RECEPTORS; SUBUNIT COMPOSITION; A RECEPTORS; BINDING; POTENTIATION; MECHANISMS; GLUTAMATE; COMPLEX AB Most general anesthetics produce two distinct actions at GABA(A) receptors. Thus, these drugs augment GABA-gated chloride currents (referred to as an indirect action) and, at higher concentrations, elicit chloride currents in the absence of GABA (referred to as a direct action). Because a beta subunit appears to be required for the direct action of intravenous anesthetics in recombinant GABA(A) receptors, site-directed mutagenesis of the beta 3 subunit was performed to identify amino acid residues that are critical for this action. In HEK293 cells expressing a prototypical GABA(A) receptor composed of alpha 1 beta 3 gamma 2 subunits, mutation of amino acid 290 from Asn to Ser dramatically reduced both etomidate-induced chloride currents and its ability to stimulate [H-3]flunitrazepam binding. By contrast, the ability of etomidate to augment GABA-gated chloride currents and GABA-enhanced [H-3]flunitrazepam binding was retained. The demonstration that the direct, but not the indirect, actions of etomidate are dependent an beta 3(Asn(290)) indicates that the dual actions of this intravenous anesthetic at GABA(A) receptors are mediated via distinct loci. RP Moody, EJ (reprint author), NIDDK,NIH,NEUROSCI LAB,BLDG 8,RM 111,BETHESDA,MD 20892, USA. NR 29 TC 34 Z9 34 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1997 VL 69 IS 3 BP 1310 EP 1313 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XR467 UT WOS:A1997XR46700048 PM 9282957 ER PT J AU Smith, SB McClung, J Wiggert, BN Nir, I AF Smith, SB McClung, J Wiggert, BN Nir, I TI Delayed rhodopsin regeneration and altered distribution of interphotoreceptor retinoid binding protein (IRBP) in the mi(vit)/mi(vit) (vitiligo) mouse SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID PIGMENT-EPITHELIUM; MUTANT MICE; C57BL/6-MI(VIT)/MI(VIT) MOUSE; DETACHED RETINA; VITAMIN-A; DEGENERATION; PHOTORECEPTORS; TRANSPORT; MATRIX; MODEL AB Rhodopsin regeneration requires attachment between the retinal pigment epithelium (RPE) and rod outer segments; however, in experimentally induced retinal detachment, rhodopsin regeneration can be restored partially upon addition of IRBP (interphotoreceptor retinoid binding protein). The mi(vit)/mi(vit) (vitiligo) mutant mouse, a model of slowly progressing photoreceptor cell degeneration, has a marked elevation of IRBP at 4 weeks as well as progressive detachment of the retina. The purpose of this study was to determine whether this mutant is capable of regenerating rhodopsin within a few hours following an intense light bleach. Rhodopsin regeneration was determined spectrophotometrically in mice after an intense one hour light bleach followed by 0, 1, 2, 4 or 24 h of dark recovery. IRBP was localized immunohistochemically in fixed frozen tissue at the light microscopic level and in LR Gold embedded tissue at the ultrastructural level. Rhodopsin regeneration experiments indicated that rhodopsin levels following 0, 1, 2 and 4 h dark-recovery were significantly less in mi(vit)/mi(vit) mutants compared with controls. Immunohistochemical detection of IRBP indicated an altered distribution of the protein in the mutant mice compared with controls. There was accumulation in the region of the inner segments in mutant retinas rather than distribution only to the RPE/OS apical regions as in controls. The data suggest that regeneration of rhodopsin is reduced by 4 weeks postnatally in the mi(vit)/mi(vit) mouse. There is partial detachment of the retina at this age; and IRBP, thought to be essential for proper functioning of the visual cycle, is aberrantly distributed in this mutant. C1 MED COLL GEORGIA,DEPT OPHTHALMOL,AUGUSTA,GA 30912. NEI,RETINAL CELL & MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. RP Smith, SB (reprint author), MED COLL GEORGIA,DEPT ANAT & CELLULAR BIOL,AUGUSTA,GA 30912, USA. FU NEI NIH HHS [EY09682, EY10286] NR 33 TC 8 Z9 8 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD SEP PY 1997 VL 26 IS 9 BP 605 EP 613 DI 10.1023/A:1018589609622 PG 9 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA YA166 UT WOS:A1997YA16600002 PM 9352446 ER PT J AU Lopez, FJ Moretto, M Merchenthaler, I NegroVilar, A AF Lopez, FJ Moretto, M Merchenthaler, I NegroVilar, A TI Nitric oxide is involved in the genesis of pulsatile LHRH secretion from immortalized LHRH neurons SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE nitric oxide; LHRH; LHRH pulses; GT1-7 cells ID HORMONE-RELEASING HORMONE; EXCITATORY AMINO-ACIDS; HYPOTHALAMIC NEURONS; L-ARGININE; CELL-LINE; NERVOUS-SYSTEM; GNRH NEURONS; GT1-1; NEUROPEPTIDE; STIMULATION AB Neuronal networks controlling endocrine events present synchronous activity which is required for maintaining physiological functions, including reproduction, Although pulsatile hormone secretion is of paramount importance, the mechanism(s) by which secretory episodes are generated remain largely unknown, Nitric oxide (NO) has become the prototype of a new family of signaling molecules in the body. Nitric oxide diffuses from the source cell and controls activity of neighboring neurons as well as itself as a retrograde messenger, Cells of the luteinizing hormone-releasing hormone (LHRH) neuronal network, the key component in the control of reproduction, are scattered and loosely arranged in the anterior hypothalamus. A diffusible neurotransmitter could provide a means for establishing synchronous activation of the LHRH neuronal network leading to physiologically-relevant pulsatile LHRH secretion. In this study, we demonstrate that immortalized LHRH-producing neurons (GT1-7 cells) express NO synthase (NOS) mRNA and protein, Furthermore, GT1-7 cells are NADPH-diaphorase-positive (a marker of NOS activity) and the histochemical reaction can be abolished by treatment with a competitive NOS blocker, The presence of citrulline in these cells provides further evidence for the biological activity of NOS, These observations indicate that an active NO synthesizing machinery is present in immortalized LHRH neurons, In addition, we show that LHRH secretion is enhanced by NO in a cGMP-dependent manner, Since pulsatile LHRH secretion from immortalized LHRH neurons in vitro is abolished by NOS blockers and NO scavengers, it appears that NO is a unique neurotransmitter that is necessary to set LHRH neurons in phase to establish synchronized pulsatile LHRH secretion. C1 NIEHS, MOL & INTEGRAT NEUROSCI LAB, REPROD NEUROENDOCRINOL SECT, RES TRIANGLE PK, NC 27709 USA. NIEHS, MOL & INTEGRAT NEUROSCI LAB, FUNCT MORPHOL SECT, RES TRIANGLE PK, NC 27709 USA. NR 39 TC 31 Z9 34 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD SEP PY 1997 VL 9 IS 9 BP 647 EP 654 DI 10.1046/j.1365-2826.1997.t01-1-00618.x PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA XY968 UT WOS:A1997XY96800001 PM 9355031 ER PT J AU RabadanDiehl, C Makara, G Kiss, A Zelena, D Aguilera, G AF RabadanDiehl, C Makara, G Kiss, A Zelena, D Aguilera, G TI Regulation of pituitary corticotropin releasing hormone (CRH) receptor mRNA and CRH binding during adrenalectomy: Role of glucocorticoids and hypothalamic factors SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE HPA axis; corticotropin releasing hormone receptor; vasopressin; PVN lesions; proopiomelanocortin (POMC); glucocorticoids ID MESSENGER-RIBONUCLEIC-ACID; RAT ANTERIOR-PITUITARY; MEDIAN-EMINENCE; ADRENOCORTICOTROPIN SECRETION; VASOPRESSIN; STRESS; EXPRESSION; BRAIN; DESENSITIZATION; RESPONSES AB The role of glucocorticoids and hypothalamic factors on CRH receptor expression in the pituitary were studied by analysis of the effects of adrenalectomy and suppression of CRH and VP secretion by hypothalamic lesions in the rat, Consistent with previous in situ hybridization studies, Northern blots showed that pituitary CRH receptor mRNA decreased only transiently after adrenalectomy, falling to 51% of the control levels after 18 h, and returning to control values after 6 days (112%). The early decrease was prevented by dexamethasone injection, 100 mu g, s.c. The role of increased levels of CRH and VP in the pituitary portal circulation on the transient decrease in CRH receptor mRNA levels after adrenalectomy were studied by in situ hybridization in rats subjected to PVN lesions or median eminence deafferentation by hypothalamic anterolateral cuts (ALC). PVN lesion (12 days) or ALC (8 days) resulted in undetectable irCRH and VP in the external zone of the median eminence and had no effect on basal levels of pituitary POMC mRNA, CRH binding and CRH receptor mRNA, In sham lesioned rats, adrenalectomy for 18 h or 4 days caused the expected increases in pituitary POMC hnRNA and mRNA, and decreases in CRH binding. CRH-R mRNA levels decreased by about 50% after 18 h adrenalectomy but returned to basal by 4 days, PVN lesion or ALC fully prevented the fall in CRH binding after 18 h or 4 days adrenalectomy and the increase in POMC mRNA after 4 days adrenalectomy, whereas only attenuated the decrease in CRH receptor mRNA and increase in POMC mRNA levels after 18 h adrenalectomy. Administration of a CRH antagonist did not affect CRH receptor mRNA and POMC hnRNA and mRNA indicating that residual CRH in the median eminence after hypothalamic surgery is not responsible for the effect of adrenalectomy, These studies confirm previous in situ hybridization studies showing that adrenalectomy causes transient decreases in pituitary CRH receptor mRNA levels. The data indicate that while increases in hypothalamic CRH secretion following glucocorticoid withdrawal mediate pituitary CRH receptor binding loss and the increase in POMC expression after long-term adrenalectomy, CRH only partially accounts for the early changes in CRH receptor mRNA and POMC mRNA. C1 NICHHD,SECT ENDOCRINE PHYSIOL,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. HUNGARIAN ACAD SCI,INST EXPT MED,BUDAPEST,HUNGARY. RI Makara, Gabor/H-8397-2013 OI Makara, Gabor/0000-0001-9220-0373 NR 39 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD SEP PY 1997 VL 9 IS 9 BP 689 EP 697 DI 10.1046/j.1365-2826.1997.00626.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA XY968 UT WOS:A1997XY96800006 PM 9355036 ER PT J AU Millar, DB Mazorow, DL Hough, C AF Millar, DB Mazorow, DL Hough, C TI The K channel blocker, tetraethylammonium, displaces beta-endorphin and naloxone from T-cell binding sites SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE beta-endorphin; K channel; channel blocker; opioid receptor; neuroimmunomodulation; naloxone; T-cell ID HUMAN LYMPHOCYTES-T; POTASSIUM CHANNELS; EXPRESSION; RECEPTORS; CHARYBDOTOXIN AB Beta-endorphin and naloxone bind to Jurkat cell membrane preparations and can mutually displace each Ether from membrane binding sites. Tetraethylammonium ion, a potassium channel blocker, competitively displaces beta-endorphin and naloxone from membrane binding sites. Mitogen stimulated calcium ion flux is inhibited by tetraethyl ammonium and this inhibition is relieved by naloxone. With data derived from whole cell calcium ion flux studies, we accurately calculated the competitive displacement of beta-endorphin and naloxone from membrane preparations by tetraethylammonium thus showing that the action of these agents on potassium channels does not require second messengers. Using the resuspension induced ion flux technique, we find that beta-endorphin competes against naloxone for binding to Jurkat cells and naloxone competes against charybdotoxin, a potassium channel inhibitor, which like tetraethylammonium, is known to bind to the outer vestibule of the channel. Patch clamp electrophysiological studies show that beta-endorphin and naloxone exert complex actions on potassium channels in the presence or absence of mitogens. We conclude that one molecule of beta-endorphin or naloxone, but not both at the same time, bind to an area near the charybdotoxin/tetraethylammonium binding locus of Jurkat potassium channels. (C) 1997 Elsevier Science B.V. C1 NIDDK,PHYS BIOCHEM LAB,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,MOL NEUROBIOL SECT,BETHESDA,MD 20892. RP Millar, DB (reprint author), NEW IDEAS CO,1716 MARK LANE,ROCKVILLE,MD 20852, USA. NR 35 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 1997 VL 78 IS 1-2 BP 8 EP 18 DI 10.1016/S0165-5728(97)00078-7 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA XV851 UT WOS:A1997XV85100002 PM 9307224 ER PT J AU LovettRacke, AE Martin, R McFarland, HF Racke, MK Utz, U AF LovettRacke, AE Martin, R McFarland, HF Racke, MK Utz, U TI Longitudinal study of myelin basic protein-specific T-cell receptors during the course of multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; myelin basic protein; T-cell receptor; complementarity-determining region 3; magnetic resonance imaging ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BETA GENE USAGE; V-BETA; FINE SPECIFICITY; CLONAL EXPANSION; PEPTIDE; DIVERSITY; DISEASE; ALPHA AB This study analyzed the stability of the myelin basic protein (MBP)-specific T-cell receptor (TCR) repertoire during the course of multiple sclerosis (MS) in three patients who were monitored for three years by gadolinium-enhanced magnetic resonance imaging. Bulk-culture T-cell lines (TCLs) were generated from 3-4 time points for each patient, including times of active and quiescent disease. TCR analysis of these TCLs indicated that both the V alpha and V beta usage was similar over time for each patient. Sequencing of TCRs demonstrated conserved complementarity-determining region 3 (CDR3) sequences within TCLs that expressed the same V alpha segment over time, although the J alpha usage was different for each TCR. This indicates that the population of MBP-reactive T-cells is changing during the course of MS, but that host and/or environmental factors may be selecting T-cells with particular MHC/peptide binding domains. (C) 1997 Elsevier Science B.V. C1 WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. CLIN RES INST MONTREAL,IMMUNOL LAB,MONTREAL,PQ H2W 1R7,CANADA. RP LovettRacke, AE (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,BLDG 10,ROOM 5B-16,BETHESDA,MD 20892, USA. RI Lovett-Racke, Amy/E-3545-2011 NR 44 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 1997 VL 78 IS 1-2 BP 162 EP 171 DI 10.1016/S0165-5728(97)00097-0 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA XV851 UT WOS:A1997XV85100019 PM 9307241 ER PT J AU Heckmann, JG Lang, CJG Petruch, F Druschky, A Erb, C Brown, P Neundorfer, B AF Heckmann, JG Lang, CJG Petruch, F Druschky, A Erb, C Brown, P Neundorfer, B TI Transmission of Creutzfeldt-Jakob disease via a corneal transplant SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE Creutzfeldt-Jakob disease; corneal graft; iatrogenic transmission ID HUMAN SPONGIFORM ENCEPHALOPATHY AB A 45 year old woman is reported who initially presented with a cerebellar syndrome, severe ataxia, and dysarthria. She rapidly deteriorated to coma vigile with bilateral myoclonic jerks, flexion rigidity, and immobility necessitating complete nursing. Her EEG showed generalised slow activity and periodic biphasic and triphasic waves. The CSF concentration of neuron specific enolase was very high. Consequently the diagnosis of Creutzfeldt-Jakob disease was established. Eight months later she died of respiratory complications. Thirty years earlier the patient had undergone corneal transplantation for keratoconus. Review of the organ donor's hospital records showed that death was caused by intercurrent pneumonia subsequent to subacute spongiform encephalopathy confirmed by necropsy. In view of two previous case reports in the literature it is presumed that the cadaveric cornea was the source of transmission of Creutzfeldt-Jakob disease in this patient. C1 BEZIRKSKRANKENHAUS,DEPT NEUROL,ANSBACH,GERMANY. UNIV TUBINGEN,DEPT OPHTHALMOL,D-72074 TUBINGEN,GERMANY. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. RP Heckmann, JG (reprint author), UNIV ERLANGEN NURNBERG,DEPT NEUROL,SCHWABACHANLAGE 6,D-91054 ERLANGEN,GERMANY. NR 5 TC 74 Z9 74 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD SEP PY 1997 VL 63 IS 3 BP 388 EP 390 DI 10.1136/jnnp.63.3.388 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA XW807 UT WOS:A1997XW80700025 PM 9328261 ER PT J AU daCunha, A Mintz, M Eiden, LE Sharer, LR AF daCunha, A Mintz, M Eiden, LE Sharer, LR TI A neuronal and neuroanatomical correlate of HIV-1 encephalopathy relative to HIV-1 encephalitis in HIV-1-infected children SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE AIDS; children; encephalitis; encephalopathy; mRNA; SIV; somatostatin ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY-SYNDROME; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; TUMOR-NECROSIS-FACTOR; PROGRESSIVE ENCEPHALOPATHY; CEREBRAL-CORTEX; MESSENGER-RNA; HUMAN-BRAIN; NEUROLOGIC MANIFESTATIONS AB Progressive central nervous system dysfunction analogous to the AIDS dementia complex (ADC) seen in adults (HIV-1-associated progressive encephalopathy or HIV-1 encephalopathy) commonly occurs in HIV-1-infected children. The cause appears to be directly or indirectly related to HIV-1, rather than to other opportunistic pathogens. The exact mechanism(s) by which the virus affects brain function is not known. To determine whether the virus might modify brain function via an alteration in cortical neurons, we examined peptide neurotransmitter expression in the frontal cortex of HIV-1-infected cases with clinical HIV-1 encephalopathy relative to pathologic HIV-1 encephalitis. In situ hybridization was used to determine the level of peptide neurotransmitter expression of somatostatin in the frontal cortex of cases with and without HIV-1 encephalopathy and/or HIV-1 encephalitis. A 2-fold higher number of preprosomatostatin mRNA-positive interneurons was present in layer IV of cases with HIV-1 encephalitis compared with cases without HIV-1 encephalitis. In cases with PE, this neuronal alteration was 4- to 5-fold higher than in cases without PE, and was present in subcortical white matter in addition to layer IV. In cases having both PE and HIV-1 encephalitis, and in cases with HIV-1 encephalitis alone, these neuronal alterations in layer TV and/or subcortical white matter related to disseminated microglial nodules, even when these potentially viral-infected cells were negative for HIV-1 p24 antigen, a marker of productive viral infection. An alteration in preprosomatostatin mRNA-expressing cells occurring with HIV-1 encephalitis may be at least one mechanism that contributes to HIV-1 encephalopathy. When compared with other cortical laminae, layer IV receives most of its synaptic input from the mediodorsal nucleus of the thalamus. Neurons in the subcortical white matter project to the thalamus. The thalamus has been shown to have high amounts of viral antigen and increased metabolic activity in patients with AIDS. An alteration in preprosomatostatin mRNA-expressing cells may play a role in HIV-1 encephalopathy. C1 NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DIV PEDIAT NEUROL,CAMDEN,NJ 08103. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT LAB MED & PATHOL,DIV NEUROPATHOL,NEWARK,NJ 07103. OI Eiden, Lee/0000-0001-7524-944X FU NINDS NIH HHS [P01NS 31492] NR 74 TC 12 Z9 12 U1 1 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 1997 VL 56 IS 9 BP 974 EP 987 PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XV470 UT WOS:A1997XV47000003 PM 9291939 ER PT J AU Umeno, MM Goldberg, ME AF Umeno, MM Goldberg, ME TI Spatial processing in the monkey frontal eye field .1. Predictive visual responses SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SACCADE-RELATED ACTIVITY; NIGRA PARS RETICULATA; SUPERIOR COLLICULUS; OCULOMOTOR FUNCTIONS; SUBSTANTIA NIGRA; PARIETAL CORTEX; NEURONS; MOVEMENTS; REPRESENTATION; ENHANCEMENT AB Neurons in the lateral intraparietal area and intermediate layers of the superior colliculus show predictive visual responses. They respond before an impending saccade to a stimulus that will be brought into their receptive field by that saccade. In these experiments we sought to establish whether the monkey frontal eye field had a similar predictive response. We recorded from 100 presaccadic frontal eye field neurons (32 visual cells, 48 visuomovement cells, and 20 movement cells) with the use of the classification criteria of Bruce and Goldberg. We studied each cell in a continuous stimulus task, where the monkey made a saccade that brought a recently appearing stimulus into its receptive field. The latency of response in the continuous stimulus task varied from 52 ms before the saccade to 272 ms after the saccade. We classified cells as having predictive visual responses if their latency in the continuous stimulus task was less than the latency of their visual ON response to a stimulus in their receptive or movement field as described in a visual fixation task. Thirty-four percent (11 of 32) of the visual cells, 31% (15 of 48) of the visuomovement cells, and no (0 of 20) movement cells showed a predictive visual response. The cells with predictive responses never responded to the stimulus when the monkey did not make the saccade that would bring that stimulus into the receptive field, and never discharged in association with that saccade unless it brought a stimulus into the receptive field. The response in the continuous stimulus task was almost always weaker than the visual ON response to a stimulus flashed in the receptive field. Because cells with visual responses but not cells with movement activity alone showed the effect, we conclude that the predictive visual response is a property of the visual processing in the frontal eye field, i.e., a response to the stimulus in the future receptive field. It is not dependent on the actual planning or execution of a saccade to that stimulus. We suggest that the predictive visual mechanism is one in which the brain dynamically calculates the spatial location of objects in terms of desired displacement. This enables the oculomotor system to perform in a spatially accurate manner when there is a dissonance between the retinal location of a target and the saccade necessary to acquire that target. This mechanism does not require an explicit calculation of target position in some supraretinal coordinate system. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT NEUROL,WASHINGTON,DC 20007. AMERICAN UNIV,DEPT PHYS,WASHINGTON,DC 20016. NR 41 TC 268 Z9 269 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1997 VL 78 IS 3 BP 1373 EP 1383 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XY503 UT WOS:A1997XY50300017 PM 9310428 ER PT J AU Kreiss, DS Mastropietro, CW Rawji, SS Walters, JR AF Kreiss, DS Mastropietro, CW Rawji, SS Walters, JR TI The response of subthalamic nucleus neurons to dopamine receptor stimulation in a rodent model of Parkinson's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE L-3,4-dihydroxyphenylalanine; apomorphine; 6-hydroxydopamine; (+/-)-1-phenyl-2 3,4,5-tetrahydro-(1H)-3-benzazepine-7,; 8-diol; quinpirole; haloperidol; dopamine; D1 receptor; D2 receptor; subthalamic nucleus; Parkinson's disease; basal ganglia; electrophysiology; burst analysis; firing pattern ID GLOBUS-PALLIDUS NEURONS; GENE-EXPRESSION; GLUTAMATE-DECARBOXYLASE; HORSERADISH-PEROXIDASE; NIGROSTRIATAL LESIONS; GLUCOSE-UTILIZATION; CEREBRAL-CORTEX; MESSENGER-RNAS; FIRING PATTERN; RAT AB Overactivity in the subthalamic nucleus (STN) is believed to contribute to the pathophysiology of Parkinson's disease, It is hypothesized that dopamine receptor agonists reduce neuronal output from the STN. The present study tests this hypothesis by using in vivo extracellular single unit recording techniques to measure neuronal activity in the STN of rats with 6-hydroxydopamine-induced lesions of the nigrostriatal pathway (a model of Parkinson's disease), As predicted, firing rates of STN neurons in lesioned rats were tonically elevated under basal conditions and were decreased by the nonselective dopamine receptor agonists apomorphine and L-3,4-dihydroxyphenylalanine (L-DOPA), STN firing rates were also decreased by the D2 receptor agonist quinpirole when administered after the D1 receptor agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393). Results of the present study challenge the prediction that dopaminergic agonists reduce STN activity predominantly through actions at striatal dopamine D2 receptors. Firing rates of STN neurons were not altered by selective stimulation of D2 receptors and were increased by selective stimulation of D1 receptors. Moreover, there was a striking difference between the responses of the STN to D1/D2 receptor stimulation in the lesioned and intact rat; apomorphine inhibited STN firing in the lesioned rat and increased STN firing in the intact rat. These findings support the premise that therapeutic efficacy in the treatment of Parkinson's disease is associated with a decrease in the activity of the STN, but challenge assumptions about the roles of D1 and D2 receptors in the regulation of neuronal activity of the STN in both the intact and dopamine-depleted states. C1 NINCDS,NIH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NR 71 TC 135 Z9 138 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 1997 VL 17 IS 17 BP 6807 EP 6819 PG 13 WC Neurosciences SC Neurosciences & Neurology GA XT283 UT WOS:A1997XT28300031 PM 9254691 ER PT J AU Mason, RB Nieman, LK Doppman, JL Oldfield, EH AF Mason, RB Nieman, LK Doppman, JL Oldfield, EH TI Selective excision of adenomas originating in or extending into the pituitary stalk with preservation of pituitary function SO JOURNAL OF NEUROSURGERY LA English DT Article DE pituitary adenoma; Cushing's disease; pituitary stalk ID CUSHINGS-SYNDROME; TRANSSPHENOIDAL SURGERY; DIFFERENTIAL-DIAGNOSIS; DISEASE; ADOLESCENTS; MANAGEMENT; CHILDREN; TUMOR AB When the surgeon identifies an adenoma within the gland and selectively excises it, endocrine-active pituitary tumors are usually cured and pituitary function is preserved. Occasionally ectopic adenomas arise primarily in the pituitary stalk or arise superiorly in the midportion of the anterior lobe and extend upward within the stalk. To determine if these tumors can be selectively excised with preservation of pituitary function, the authors examined the outcome of selective adenomectomy in 10 patients with Cushing's disease with an ectopic adenoma originating in, and confined to, the stalk (four microadenomas) or an adenoma extending superiorly through the diaphragma sella and into the stalk (five microadenomas and one macroadenoma) from an operative series of 516 patients with Cushing's disease. To reach the adenoma transsphenoidally in these patients, the diaphragma sella was incised anteroposteriorly in the midline to the anterior edge of the stalk, the suprasellar cistern was entered and the adenoma was selectively excised using care to limit injury to the infundibulum. After selective adenomectomy, Cushing's disease remitted in all patients. All patients were hypocortisolemic immediately after surgery and required hydrocortisone for up to 21 months. Apart from the adrenal axis, pituitary function was normal in five patients in the immediate postoperative period, including two patients with tumors confined to the stalk and three patients with preoperative hypothyroidism (one patient) and/or hypogonadism (three patients). Three others with transient postoperative hypothyroidism (one patient) or diabetes insipidus (two patients) had normal pituitary function within 7 months of surgery. One patient with hypothyroidism and one with hypogonadism before surgery had panhypopituitarism postoperatively. A patient with a microadenoma located high in the stalk next to the optic chiasm had bitemporal hemianopsia postoperatively. These results demonstrate the feasibility of achieving curative transsphenoidal resection and preservation of pituitary function in cases of pituitary adenomas that are confined to the pituitary stalk or tumors that extend superiorly within the stalk from an intrasellar origin. C1 NINCDS, SURG NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIH, DEPT DIAGNOST RADIOL, CTR CLIN, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT NEUROSURG, BETHESDA, MD 20889 USA. NR 28 TC 109 Z9 118 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 1997 VL 87 IS 3 BP 343 EP 351 DI 10.3171/jns.1997.87.3.0343 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XT611 UT WOS:A1997XT61100001 PM 9285597 ER PT J AU Kuze, K Sunamoto, M Komatsu, T Iehara, N Takeoka, H Yamada, Y Kita, T Doi, T AF Kuze, K Sunamoto, M Komatsu, T Iehara, N Takeoka, H Yamada, Y Kita, T Doi, T TI A novel transcription factor is correlated with both glomerular proliferation and sclerosis in the rat renal ablation model SO JOURNAL OF PATHOLOGY LA English DT Article ID REPLICATION FACTOR-C; DIFFERENTIATION-SPECIFIC ELEMENT; DNA-BINDING PROTEIN; GROWTH FACTOR-I; LARGE SUBUNIT; ANGIOTENSINOGEN GENE; CELL-PROLIFERATION; ESCHERICHIA-COLI; MESSENGER-RNA; HELA-CELLS AB Glomerular accumulation of the extracellular matrix (ECM) with subsequent sclerosis is a common finding in most progressive, renal diseases, Recently MSW (Mouse South Western) protein was cloned by its ability to bind the bidirectional promoter of the collagen IV genes, This protein was also reported as the large subunit of the DNA replication complex A1, as well as the promoter binding protein of corticotropin-releasing hormone and the angiotensinogen gene, To investigate the mechanism of accumulation of the ECM as it relates to glomerular cellular events, the expression of MSW protein was studied in the remnant kidney model, Progressive expression of MSW protein was found in the glomerular sclerotic lesion at week 4 and at later time points after renal ablation, The expression of proliferating cell nuclear antigen (PCNA) and type IV collagen was also correlated,vith the expression of MSW protein by immunofluorescence. RNA dot blot analysis also showed that the expression of MSW mRNA was increased at week 7 in association with the augmented expression of type TV collagen, These results, taken together, suggest that MSW protein plays an important role in the regulation of type TV collagen gene expression in vivo and may contribute to glomerular cell proliferation and the development of glomerulosclerosis. (C) 1997 by John Whey & Sons, Ltd. C1 KYOTO UNIV,FAC MED,DIV ARTIFICIAL KIDNEYS,SAKYO KU,KYOTO 606,JAPAN. KYOTO NATL HOSP,DIV CARDIOL,FUSHIMI KU,KYOTO 612,JAPAN. KYOTO UNIV,DEPT GERIATR MED,DIV CLIN BIOREGULATORY SCI,SAKYO KU,KYOTO 606,JAPAN. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 38 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PD SEP PY 1997 VL 183 IS 1 BP 16 EP 23 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA XR714 UT WOS:A1997XR71400004 PM 9370942 ER PT J AU Lehrnbecher, T Foster, C Vazquez, N Mackall, CL Chanock, SJ AF Lehrnbecher, T Foster, C Vazquez, N Mackall, CL Chanock, SJ TI Therapy-induced alterations in host defense in children receiving therapy for cancer SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; PNEUMOCYSTIS-CARINII PNEUMONIA; NATURAL-KILLER-CELLS; ATTENUATED VARICELLA VACCINE; ACUTE LYMPHOCYTIC-LEUKEMIA; BLOOD MONONUCLEAR-CELLS; TUMOR-NECROSIS-FACTOR; HUMAN POLYMORPHONUCLEAR LEUKOCYTES C1 NCI,PEDIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. UNIV WURZBURG,DEPT PEDIAT,WURZBURG,GERMANY. NR 288 TC 69 Z9 70 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD SEP-OCT PY 1997 VL 19 IS 5 BP 399 EP 417 DI 10.1097/00043426-199709000-00001 PG 19 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA XZ493 UT WOS:A1997XZ49300001 PM 9329461 ER PT J AU Bleyer, WA Tejeda, HA Murphy, SB Brawley, OW Smith, MA Ungerleider, RS AF Bleyer, WA Tejeda, HA Murphy, SB Brawley, OW Smith, MA Ungerleider, RS TI Equal participation of minority patients in US National Pediatric Cancer Clinical Trials SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the American-Society-of-Pediatric-Hematology/Oncology CY SEP 29-30, 1995 CL ALEXANDRIA, VA SP Amer Soc Pediat Hematol Oncol DE minorities; pediatric cancer trials ID UNITED-STATES; SURVIVAL; PLACE AB Purpose: To determine the ethnic/racial distribution of patients entered in national pediatric cancer clinical trials relative to the patient population served. Methods: The ethnic/racial distribution of 29,134 patients <20 years of age entered in clinical trials conducted by the Children's Cancer Group (CCG) and Pediatric Oncology Group (FOG) between January 1, 1991 and June 30, 1994 were compared with the expected distribution of patients of the same age in the United States. The latter was predicted from the 1989 to 1991 crude incidence data of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program applied to the 1990 United States census. Results: Of the patients on CCG and FOG trials, 11.6% were reported to be Hispanic, 10.4% were African-American, and 4.7% were other racial groups. The expected values were 9.1%, 10.7%, and 4.3%, respectively. Representation of minority patients was equal or greater than expected for 24 of 27 subgroups analyzed. Conclusions: In the United States, minority children with cancer are proportionately represented on clinical trials of the two national pediatric cancer cooperative groups. They and their families are provided with an equal opportunity to access clinical cancer trials and the potential benefits of cancer research. C1 PEDIAT ONCOL GRP,CHICAGO,IL. NCI,EARLY DETECT & COMMUNITY ONCOL PROGRAM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,CANC TREATMENT EVALUAT PROGRAM,DIV CANC TREATMENT DIAG & CTR,BETHESDA,MD 20892. RP Bleyer, WA (reprint author), CHILDRENS CANC GRP,POB 60012,ARCADIA,CA 91066, USA. FU NCI NIH HHS [CA 30969, CA13539] NR 17 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD SEP-OCT PY 1997 VL 19 IS 5 BP 423 EP 427 DI 10.1097/00043426-199709000-00003 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA XZ493 UT WOS:A1997XZ49300003 PM 9329463 ER PT J AU Salbe, AD Fontvieille, AM Harper, IT Ravussin, E AF Salbe, AD Fontvieille, AM Harper, IT Ravussin, E TI Low levels of physical activity in 5-year-old children SO JOURNAL OF PEDIATRICS LA English DT Article ID NUTRITION EXAMINATION SURVEYS; TOTAL-ENERGY EXPENDITURE; DOUBLY LABELED WATER; CAUCASIAN CHILDREN; NATIONAL-HEALTH; BODY FATNESS; PIMA-INDIANS; OBESITY; OVERWEIGHT; ADOLESCENTS AB As the prevalence of obesity in Western societies has increased to disturbing levels, interest in the role of physical inactivity in promoting this trend has increased. We assessed physical activity energy expenditure (AEE) in 127 5-year-old children, 43 of whom were white children and 84 Pima Indian children; the latter group represents a population with an extremely high prevalence of obesity. Total energy expenditure (TEE) and resting metabolic rate (RMR) were measured by the doubly labeled water method and indirect calorimetry, respectively. From these measured values, different indexes of physical activity were calculated, including AEE = TEE - (RMR + 0.1 x TEE) and physical activity level (PAL = TEE/RMR). By the age of 5 years, Pima Indian children were significantly heavier (23.0 +/- 5.3 kg vs 19.1 +/- 2.6 kg) and fatter (30 +/- 7% vs 21 +/- 5% body fat) than white children (p < 0.0001), whereas TEE (5996 +/- 1005 kJ/day vs 5690 +/- 760 kJ/day) and RMR (4431 +/- 625 kJ/day vs 4236 +/- 534 kJ/day) were similar in the 2 groups in both absolute values and after adjustment for fat-free mass, fat mass, and sex. Both white and Pima Indian children had physical activity levels 20% to 30% lower (PAL = 1.35 +/- 0.13) than currently recommended by the World Health Organization (1.7 to 2.0). However, the different calculated indexes of physical activity were comparable in the two racial groups. Differences in TEE or AEE are unlikely to explain the obesity seen in Pima Indian children at a later age, suggesting that excess food intake is likely to play a major role in the cause of obesity in this obesity-prone population. However, both white and Pima Indian children have surprisingly low levels of physical activity, a condition that portends poorly for the prevention of obesity in adulthood. RP Salbe, AD (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, NIH, 4212 N 16TH ST, PHOENIX, AZ 85016 USA. NR 45 TC 35 Z9 36 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1997 VL 131 IS 3 BP 423 EP 429 DI 10.1016/S0022-3476(97)80069-8 PG 7 WC Pediatrics SC Pediatrics GA XZ765 UT WOS:A1997XZ76500020 PM 9329420 ER PT J AU Guo, NH Krutzsch, HC Inman, JK Shannon, CS Roberts, DD AF Guo, NH Krutzsch, HC Inman, JK Shannon, CS Roberts, DD TI Antiproliferative and antitumor activities of D-reverse peptides derived from the second type-1 repeat of thrombospondin-1 SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE thrombospondin-1; endothelial cells; adhesion; heparin-binding; transforming growth factor beta; tumor growth inhibitors; D-reverse peptides ID ENDOTHELIAL-CELL PROLIFERATION; BREAST-CARCINOMA; HEPARIN-BINDING; I REPEATS; TUMOR-GROWTH; ANGIOGENESIS; ADHESION; EXPRESSION; DOMAIN; METASTASIS AB The extracellular matrix glycoprotein thrombospondin-1 (TSP1) inhibits angiogenesis, endothelial cell growth, motility and adhesion. Peptides from the type I repeats of TSP1 mimic the adhesive and growth inhibitory activities of the intact protein and specifically interact with heparin and transforming growth factor-beta (TGF beta). To define the structural basis for the antiangiogenic activities of these peptides, we prepared analogs of the TSP1 peptide KRFKQDGGWSHWSPWSSC. L-forward, L-reverse, and D-reverse (retro-inverso) analogs displayed identical activities for binding to heparin, demonstrating a lack of stereospecificity for heparin binding. The L-reverse and D-reverse peptides, however, had somewhat decreased abilities to activate latent TGF beta. Conjugation of the forward peptides through a C-terminal thioether and the reverse peptides through an N-terminal thioether to polysucrose abolished the adhesive activity of the peptides and enhanced their antiproliferative activities for endothelial and breast carcinoma cells stimulated by fibroblast growth factor-2. Their antiproliferative activities were independent of latent TGF beta activation, because substitution of an Ala residue for the essential Phe residue in the TSP1 type-1 repeat peptide increased their potency for inhibiting TSP1 binding to heparin and for inhibiting endothelial cell proliferation, Although the conjugated peptides were inactive in vivo, an unconjugated retro-inverso analog of the native TSP peptide inhibited breast tumor growth in a mouse xenograft model. Thus, these TSP-derived peptide analogs antagonize endothelial growth through their heparin-binding activity rather than through activation of latent TGF beta or increasing cell adhesion. These stable analogs may therefore be useful as therapeutic inhibitors of angiogenesis stimulated by fibroblast growth factor-2. (C) Munksgaard 1997. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008; OI Roberts, David/0000-0002-2481-2981; `, Caitlin/0000-0002-1680-421X NR 46 TC 63 Z9 66 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD SEP PY 1997 VL 50 IS 3 BP 210 EP 221 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU354 UT WOS:A1997XU35400008 PM 9309585 ER PT J AU Pilkonis, PA Blehar, MC Prien, RF AF Pilkonis, PA Blehar, MC Prien, RF TI Introduction to the special feature: Research directions for the personality disorders .1. SO JOURNAL OF PERSONALITY DISORDERS LA English DT Editorial Material C1 NIMH,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,BETHESDA,MD 20892. NIMH,CLIN TREATMENT RES BRANCH,BETHESDA,MD 20892. RP Pilkonis, PA (reprint author), UNIV PITTSBURGH,SCH MED,WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,3811 OHARA ST,PITTSBURGH,PA 15213, USA. NR 2 TC 5 Z9 5 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD FAL PY 1997 VL 11 IS 3 BP 201 EP 204 PG 4 WC Psychiatry SC Psychiatry GA YB381 UT WOS:A1997YB38100001 PM 9348485 ER PT J AU Joseph, RE Tsai, WJ Tsao, LI Su, TP Cone, EJ AF Joseph, RE Tsai, WJ Tsao, LI Su, TP Cone, EJ TI In vitro characterization of cocaine binding sites in human hair SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Review ID TESTING HUMAN-HAIR; POLYACRYLAMIDE-GEL-ELECTROPHORESIS; CHROMATOGRAPHY MASS-SPECTROMETRY; MUSCARINIC RECEPTOR SUBTYPES; SODIUM DODECYL-SULFATE; ECGONINE METHYL-ESTER; IN-VITRO; RAT HAIR; BENZODIAZEPINE RECEPTORS; DOPAMINE TRANSPORTER AB In vitro studies were performed to characterize [H-3]cocaine binding to dark and light ethnic hair types. In vitro binding to hair was selective, was reversible and increased linearly with increasing hair concentration. Scatchard analyses revealed high-affinity (6-112 nM) and low-affinity (906-4433 nM) binding in hair. Competition studies demonstrated that the potencies of 3 beta-(4-bromophenyl)tropane-2 beta-carboxylic acid methyl ester, and 5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo l[2,1-alpha]isoindole-5-ol and 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane were similar to or less than that of (-)-cocaine. The potency of (-)-cocaine was 10-fold greater than that of (+)-cocaine at inhibiting radioligand specific binding to hair. Multivariate analysis indicated that significantly greater nonspecific and specific radioligand binding occurred in dark hair than in light hair. Multivariate analysis also demonstrated a significant ethnicity x sex effect on specific and nonspecific binding to hair. Greater radioligand binding occurred in male Africoid hair than in female Africoid hair and in all Caucasoid hair types. Melanin was considered the most likely binding site for cocaine in hair. Typically, the concentration of melanin is much greater in dark than in light hair. Scatchard analysis indicated that dark hair had a 5- to 43-fold greater binding capacity than light hair. Differences in radioligand binding between hair types appeared to be due to differences in the density of binding sites formed by melanin in hair. C1 NIDA,ADDICT RES CTR,CHEM & DRUG METAB SECT,CLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,NEUROCHEM UNIT,MOL PHARMACOL SECT,NEUROSCI BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,BALTIMORE,MD 21224. NR 122 TC 33 Z9 34 U1 3 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1997 VL 282 IS 3 BP 1228 EP 1241 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XX354 UT WOS:A1997XX35400013 PM 9316830 ER PT J AU Stachlewitz, RF Arteel, GE Raleigh, JA Connor, HD Mason, RP Thurman, RG AF Stachlewitz, RF Arteel, GE Raleigh, JA Connor, HD Mason, RP Thurman, RG TI Development and characterization of a new model of tacrine-induced hepatotoxicity: Role of the sympathetic nervous system and hypoxia-reoxygenation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PERFUSED-RAT-LIVER; ALZHEIMERS-DISEASE; TETRAHYDROAMINOACRIDINE; HYDROCHLORIDE; MICROCIRCULATION; METABOLITES; BINDING; INVIVO; NERVES; INJURY AB Tacrine is an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease. Unfortunately, reversible hepatotoxicity in about 30% of patients at therapeutic doses limits clinical use. The purpose of this study was to develop and characterize a model of tacrine hepatotoxicity to begin to understand the mechanisms of injury. Rats were given tacrine (10-50 mg/kg, intragatrically) and killed 24 hr later. An increase in serum aspartate aminotransferase was observed up to 35 mg/kg and histology revealed pericentral necrosis and fatty changes, Aspartate aminotransferase was increased from 12 to 24 hr and returned to control values by 32 hr. Livers were perfused in a nonrecirculating system to measure oxygen uptake and trypan blue was infused at the end of each experiment to evaluate tissue perfusion. Time for trypan blue to distribute evenly throughout the liver 3 hr after tacrine treatment was significantly increased (6.9 +/- 1.3 min) compared to controls (1.0 +/- 0.3 min) reflecting decreased tissue perfusion. Tacrine also significantly increased the binding of a hypoxia marker, pimonidazole, in pericentral regions almost 3-fold, and increased portal pressure in vivo significantly. It is hypothesized that tacrine, by inhibiting acetylcholine breakdown in the celiac ganglion, increases sympathetic activity in the liver leading to vascular constriction, hypoxia and liver injury. To test this hypothesis, the hepatic nerve was severed and animals were allowed to recover before tacrine treatment. This procedure significantly reduced serum aspartate aminotransferase, time of dye distribution, pimonidazole binding and portal pressure. Furthermore, a free radical adduct was detected with spin trapping and electron spin resonance spectroscopy 8 hr after tacrine treatment, providing evidence for reoxygenation. When catechin (100 mg/kg, i.p.), a free radical scavenger, was given before tacrine, injury was decreased by about 45%. Furthermore, feeding 5% arginine in the diet significantly reduced portal pressure and time of dye distribution. These data are consistent with the hypothesis that tacrine hepatotoxicity is a hypoxia-reoxygenation injury mediated through the sympathetic nervous system. C1 UNIV N CAROLINA,DEPT PHARMACOL,CB 7365,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT RADIAT ONCOL,CHAPEL HILL,NC 27599. NIEHS,MOL BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [ES-04325]; NIGMS NIH HHS [GM-07040-2] NR 46 TC 20 Z9 21 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1997 VL 282 IS 3 BP 1591 EP 1599 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XX354 UT WOS:A1997XX35400059 PM 9316876 ER PT J AU Sautter, FJ McDermott, BE Cornwell, J Wilson, AF Johnson, J Vasterling, JJ AF Sautter, FJ McDermott, BE Cornwell, J Wilson, AF Johnson, J Vasterling, JJ TI Neuropsychological deficits in probands from multiply-affected schizophrenic families SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID RISK; VULNERABILITY; INDICATORS; RELATIVES; HISTORY; HETEROGENEITY; DIAGNOSIS; GENETICS; CHILDREN AB This study was designed to determine if schizophrenics from families with more than one psychotic relative show more severe neuropsychological deficits than schizophrenics with only one psychotic relative, non-familial schizophrenics, and a group of matched normal controls. Eighty one schizophrenic-spectrum patients were divided into three groups on the basis of the presence of psychotic disorder among first-and second-degree relatives. The three groups of schizophrenics and the normal controls were compared for differences on a brief neuropsychological testing battery. The four groups showed significant multivariate differences. Patients from multiply-affected families showed significantly greater neuropsychological dysfunction on measures of abstract concept formation, visuomotor-coordination, and attention than patients from families that had only one psychotic relative. Schizophrenics from low-density families showed more severe deficits in fine motor-control than non-familial schizophrenics. These data suggest that abnormalities in those frontal systems that are likely to mediate fine motor control and abstract concept formation may be related to the degree of familial loading for psychotic disorder. (C) 1997 Elsevier Science Ltd. C1 NIH,NATL CTR HUMAN GENOME RES,BALTIMORE,MD 21224. VET AFFAIRS MED CTR,PSYCHIAT SERV 116B,NEW ORLEANS,LA 70146. RP Sautter, FJ (reprint author), TULANE UNIV,SCH MED,DEPT PSYCHIAT & NEUROL,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. RI Wilson, Alexander/C-2320-2009 FU NIMH NIH HHS [MH-46530] NR 40 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD SEP-OCT PY 1997 VL 31 IS 5 BP 497 EP 508 DI 10.1016/S0022-3956(97)00024-1 PG 12 WC Psychiatry SC Psychiatry GA YD301 UT WOS:A1997YD30100001 PM 9368192 ER PT J AU Denicoff, KD SmithJackson, EE Disney, ER Suddath, RL Leverich, GS Post, RM AF Denicoff, KD SmithJackson, EE Disney, ER Suddath, RL Leverich, GS Post, RM TI Preliminary evidence of the reliability and validity of the prospective life-chart methodology (LCM-p) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID FOLLOW-UP; AFFECTIVE-DISORDERS; AFFECTIVE-ILLNESS; SCALE; MANIA AB This article describes the use of the NIMH prospective life-charting methodology (NIMH LCM-p) in the context of a formal double-blind, clinical trial and provides preliminary evidence of its reliability and validity. Subjects included in this report were 30 outpatients with bipolar I and II disorder who completed the first 2 years of a long-term maintenance study: I year on carbamazepine or lithium and a crossover to the other in the second year. The LCM-p follows the same types of guidelines and principles utilized in the previously described retrospective life-chart process, allowing for continuity of illness assessment prior and subsequent to study entry. In the LCM-p, daily ratings of severity of mood symptoms based on the degree of associated functional incapacity, provide a more detailed topography of manic and depressive fluctuations. Inter-rater reliability was examined by comparing the severity of daily LCM-p ratings assigned by two raters. In order to assess the validity, we correlated the LCM-p ratings with well-standardized scares, including Hamilton and Beck Depression Ratings, Young Mania Ratings and the Global Assessment Scale (GAS). The Kappa scores for inter-rater reliability demonstrated significant and satisfactory strength of agreement with no fall off over 14 days prior to the rating interview. Strong correlations were found: (1) between the LCM-p average severity for depression rating and the mean Hamilton Depression Rating(r=0.86,p<.001), and the Beck Depression Inventory (r=0.73, p<.001); 2) between the LCM-p average severity for mania rating and the Young Mania Rating Scale (r=0.61, p<.001); and (3) between the LCM-p average severity and the GAS (r=-0.81, p<.001). These preliminary data suggest the reliability and validity of the NIMH-LCM-p in assessing manic and depressive episode severity. It also provides a useful continuous daily measure of affective illness-related symptom fluctuations that allows for detailed prospective assessment of frequency and pattern of illness, treatment response, and continuity with retrospective life chart assessments. Published by Elsevier Science Ltd. RP Denicoff, KD (reprint author), NIMH,BIOL PSYCHIAT BRANCH,SECT PSYCHOBIOL,BLDG 10,ROOM 3N212,10 CTR DR MSC 1272,BETHESDA,MD 20892, USA. NR 32 TC 81 Z9 81 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD SEP-OCT PY 1997 VL 31 IS 5 BP 593 EP 603 DI 10.1016/S0022-3956(96)00027-1 PG 11 WC Psychiatry SC Psychiatry GA YD301 UT WOS:A1997YD30100009 PM 9368200 ER PT J AU Grant, BF AF Grant, BF TI Prevalence and correlates of alcohol use and DSM-IV alcohol dependence in the United States: Results of the National Longitudinal Alcohol Epidemiologic Survey SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID COMORBIDITY-SURVEY AB Objective: The purpose of this study was to present updated estimates of the prevalence of, and to examine the correlates of, alcohol use and DSM-IV alcohol dependence in a representative sample of the U.S. population. Method: This study was based on the National institute on Alcohol Abuse and Alcoholism's National Longitudinal Alcohol Epidemiologic Survey (NLAES), a representative sample (N = 42,862) of the United States population aged 18 years and older. Results: The prevalence of lifetime alcohol use was 66.0%, with 44.4% of the respondents reporting alcohol use during the past 12 months. Lifetime and 12-month prevalences of alcohol dependence were estimated at 13.3% and 4.4%, respectively. Men were significantly more likely than women to use alcohol, and alcohol use and dependence were much more common among cohorts born after Prohibition and after World War II, Members of the youngest cohorts, between the ages of 18 and 24 years at the time of the interview, were more likely to use drugs, to become dependent and to persist in dependence compared to the older cohorts. In addition, the conditional probability of dependence among users was greatest in Cohort 1 (born between 1968 and 1974) after early adolescence compared to Cohort 2 (born between 1958 and 1967), despite the finding that the probability of lifetime use was lower in Cohort 1 compared to Cohort 2. The sociodemographic correlates of first use, onset of dependence and persistence of dependence varied as a function of the stage of progression. Conclusions: Implications of these findings are discussed in terms of changes over time in drinking patterns, dependence liability and vulnerability among recent alcohol users. RP Grant, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 21 TC 320 Z9 326 U1 1 U2 8 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 1997 VL 58 IS 5 BP 464 EP 473 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA XR235 UT WOS:A1997XR23500003 PM 9273910 ER PT J AU Weinberg, NZ AF Weinberg, NZ TI Cognitive and behavioral deficits associated with parental alcohol use SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE children of alcoholics; fetal alcohol syndrome; learning problems; behavior problems; children; adolescents ID PRENATAL ALCOHOL; CHILDHOOD PSYCHOPATHOLOGY; INHERITED PREDISPOSITION; SUBSTANCE-ABUSE; EXPOSURE; CHILDREN; RISK; AGE; HYPERACTIVITY; EPIDEMIOLOGY AB Objective: To review and synthesize the scientific literature on cognitive and behavioral deficits associated with parental alcohol use and to highlight areas for future attention. Method: Studies of children of alcoholic parents (generally fathers) and of children prenatally exposed to alcohol were reviewed, focusing on cognitive and behavioral findings. Relevant animal studies were also reviewed. Results: Large numbers of children may be affected by parental alcohol use. Prenatal alcohol exposure is frequently associated with specific cognitive and behavioral deficits. Children of alcoholic fathers also can present with difficulties in learning, language, and temperament. Similarities in the deficits of these two groups were noted. Conclusions: The problems associated with parental alcohol use merit much more clinical and research attention. Current clinical approaches often fail to recognize the diagnostic and therapeutic significance of this history, and subgroups of alcohol-affected children may confound research studies of other problems. Subtle deficits in learning, language, and self-regulation may be the most developmentally devastating and the least likely to be identified and addressed effectively. This is an important area in which to combine behavior genetic and environmental approaches to understanding development. C1 JOHNS HOPKINS MED INST,DIV CHILD PSYCHIAT,BALTIMORE,MD 21205. NIDA,DIV EPIDEMIOL & PREVENT RES,ROCKVILLE,MD. NR 73 TC 67 Z9 69 U1 1 U2 11 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1997 VL 36 IS 9 BP 1177 EP 1186 DI 10.1097/00004583-199709000-00009 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA XT950 UT WOS:A1997XT95000010 PM 9291718 ER PT J AU Shiota, T Jones, M Aida, S Tsujino, H Yamada, I Delabays, A Pandian, NG Sahn, DJ AF Shiota, T Jones, M Aida, S Tsujino, H Yamada, I Delabays, A Pandian, NG Sahn, DJ TI Calculation of aortic regurgitant volume by a new digital Doppler color flow mapping method: An animal study with quantified chronic aortic regurgitation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VENTRICULAR OUTFLOW TRACT; MITRAL REGURGITATION; ORIFICE AREA; ECHOCARDIOGRAPHIC METHOD; VELOCITY DISTRIBUTIONS; CARDIAC-OUTPUT; SAMPLING SITE; BLOOD-FLOW; INSUFFICIENCY; ACCELERATION AB Objectives. The aim of the present study was to quantitate aortic regurgitant volume and regurgitant fraction in a chronic animal model with surgically created aortic regurgitation using a new semiautomated color Doppler flow calculation method. Background. The conventional noninvasive methods for evaluating the severity of aortic regurgitation have not been accepted widely nor compared with truly quantitative reference standards, Methods. Eight to 20 weeks after aortic regurgitation was surgically induced in six sheep, a total of 22 hemodynamic states were studied, Electromagnetic how probes and meters provided reference flow data, Epicardial color Doppler echocardiographic studies were pet-formed to image left ventricular outflow tract forward and aortic regurgitant blood flows, The new method digitally integrated spatial and temporal color flow velocity data for left ventricular outflow tract forward flow and ascending aortic regurgitant flow, The pulsed Doppler method using the velocity-time integral was also used to obtain regurgitant volumes and regurgitant fractions. Results. Regurgitant volumes and regurgitant fractions by the new method agreed well with those obtained electromagnetically, whereas the pulsed Doppler method overestimated these reference data (mean [+/- SD] difference 0.23 +/- 2.9 ml vs, 11 +/- 5.8 ml, p < 0.0001 for regurgitant volume; mean difference 1.2 +/- 7.6% vs. 19 +/- 13%, p < 0.0001 for regurgitant fraction). Conclusions. This animal study, using strictly quantified aortic regurgitant volumes, demonstrated that the digital color Doppler method provides accurate aortic regurgitant volumes and regurgitant fractions without cumbersome measurements. (C) 1997 by the American College of Cardiology. C1 NHLBI,LAB ANIM MED & SURG,NIH,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. TOSHIBA CO LTD,TOKYO,JAPAN. TUFTS UNIV,NEW ENGLAND MED CTR,NONINVAS CARDIAC LAB,BOSTON,MA 02111. FU NHLBI NIH HHS [HL-43287] NR 46 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1997 VL 30 IS 3 BP 834 EP 842 DI 10.1016/S0735-1097(97)00210-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XT436 UT WOS:A1997XT43600035 PM 9283548 ER PT J AU Slavkin, HC AF Slavkin, HC TI Nutrients and micronutrients: Progress in science-based understanding SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material ID FOLIC-ACID RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 1997 VL 128 IS 9 BP 1306 EP 1313 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XV194 UT WOS:A1997XV19400022 PM 9297954 ER PT J AU Harnack, L Block, G Subar, A Lane, S Brand, R AF Harnack, L Block, G Subar, A Lane, S Brand, R TI Association of cancer prevention-related nutrition knowledge, beliefs, and attitudes to cancer prevention dietary behavior SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; HEALTH INTERVIEW SURVEY; NHANES-II SURVEY; LOW-FAT DIET; QUANTITATIVE DATA; VEGETABLE CONSUMPTION; NUTRIENT SOURCES; AMERICAN DIET; WOMEN; VALIDATION AB Objective To examine the relationship of cancer prevention-related nutrition knowledge, beliefs, and attitudes to cancer prevention dietary behavior. Subjects/setting Noninstitutionalized US adults aged 18 years and older. Methods Data collected in the 1992 National Health Interview Survey Cancer Epidemiology Supplement were analyzed. The supplement included questions to ascertain knowledge, beliefs, and attitudes and a food frequency questionnaire to ascertain nutrient intake. Statistics Multivariate linear regression modeling was conducted to assess the hypothesized relationships. Results After adjustment for relevant covariates (age, sex, education, total energy, perceived barriers to eating a more healthful diet), knowledge and belief constructs were predictive of dietary behavior. Specifically, fat, fiber, and fruit and vegetable intakes more closely approximated dietary recommendations for persons with more cancer-prevention knowledge. The strength of the associations between these constructs and dietary behavior varied in some cases according to level of education and perceived barriers to eating a healthful diet. Of the perceived barriers to eating a healthful diet, perceived ease of eating a healthful diet was most strongly and consistently predictive of intake. Conclusions Research findings challenge dietetics practitioners to design diet-and health-promotion programs and activities that not only educate the public about the importance of diet to health, but also address barriers to dietary change. C1 UNIV CALIF BERKELEY,PUBL HLTH NUTR PROGRAM,BERKELEY,CA 94720. UNIV CALIF BERKELEY,DIV PUBL HLTH BIOL & EPIDEMIOL,BERKELEY,CA 94720. UNIV CALIF BERKELEY,DIV BIOSTAT & INFORMAT SCI,BERKELEY,CA 94720. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RI Block, Gladys/E-3304-2010 NR 44 TC 80 Z9 82 U1 0 U2 11 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 1997 VL 97 IS 9 BP 957 EP 965 DI 10.1016/S0002-8223(97)00231-9 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XU116 UT WOS:A1997XU11600005 PM 9284871 ER PT J AU Nebeling, LC AF Nebeling, LC TI Practice points: Translating research into practice - Breaking down the barriers to healthful eating SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article RP Nebeling, LC (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 1997 VL 97 IS 9 BP 965 EP 965 DI 10.1016/S0002-8223(97)00232-0 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XU116 UT WOS:A1997XU11600006 ER PT J AU Nebeling, LC Forman, MR Graubard, BI Snyder, RA AF Nebeling, LC Forman, MR Graubard, BI Snyder, RA TI Changes in carotenoid intake in the United States: The 1987 and 1992 National Health Interview Surveys SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID BASE-LINE; FRUIT; CONSUMPTION; VEGETABLES; CANCER AB Objectives To assess the changes in carotenoid intake between 1987 and 1992 among US adults by sociodemographic characteristics and high-risk groups for chronic disease; and to identify the dietary sources of specific carotenoid intake. Design A food frequency questionnaire (FFQ) was collected from a representative sample of respondents to the 1987 and 1992 National Health Interview Surveys throughout two calendar quarters. Black and white adults, 18 to 69 years old, participated in 1987 (n=8,161) and 1992 (n=8,341). Method FFQ data were matched and linked to the US Department of Agriculture-National Cancer Institute carotenoid food composition database for analysis. Statistical analysis Mean differences in carotenoid intake over time were compared by sociodemographic characteristics and region of the country, after adjustment for sampling weights in a multiple linear regression model. Results Mean intake of the carotenoid lutein declined among white women (18%), among adults aged 40 to 69 years (16%), among persons with 9 to 12 years of education (11%), among nondrinkers (18%), among drinkers of 1 to 6 alcoholic drinks/week (7%), among smokers (former smokers by 11%, current smokers by 7%, and never smokers by 9%), among income groups (<$20,000 by 7%, greater than or equal to$20,000 by 9%), and residents in the south and northeast Coy 13% each, respectively). Mean intake of the carotenoid lycopene increased among white men (9%), among adults aged 18 to 39 years and aged 40 to 69 years (by 5% and 6%, respectively), among those with 13 years of education or more (12.5%), among alcohol drinkers Coy 10% and 7% for 1 to 6 vs 7 or more drinks/week, respectively), among former and current smokers (by 6% each), among those with incomes greater than or equal to$20,000 (8%), and among residents in the west (16%) and midwest (5%). AU differences described were statistically significant (P<.01). Application The decline in lutein intake (from dark green leafy vegetables), particularly in white women, may have public health implications as a result of the recognized inverse association between carotenoid intake and disease risk. C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Nebeling, LC (reprint author), NCI,EPN 211,6130 EXECUT BLVD,MSC 7326,BETHESDA,MD 20892, USA. NR 30 TC 47 Z9 48 U1 0 U2 5 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 1997 VL 97 IS 9 BP 991 EP 996 DI 10.1016/S0002-8223(97)00239-3 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XU116 UT WOS:A1997XU11600012 PM 9284877 ER PT J AU Wang, MC Crawford, PB Bachrach, LK AF Wang, MC Crawford, PB Bachrach, LK TI Intakes of nutrients and foods relevant to bone health in ethnically diverse youths SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID LACTOSE-INTOLERANCE; CALCIUM INTAKE; NHANES-II; DIET; AMERICANS C1 STANFORD UNIV,SCH MED,DEPT PEDIAT,DIV PEDIAT ENDOCRINOL,STANFORD,CA 94305. UNIV CALIF BERKELEY,SCH PUBL HLTH,NHLBI,GROWTH & HLTH STUDY,BERKELEY,CA 94720. RP Wang, MC (reprint author), SAN JOSE STATE UNIV,DEPT NUTR & FOOD SCI,1 WASHINGTON SQ,SAN JOSE,CA 95192, USA. FU NIDDK NIH HHS [DK45226, DK09003] NR 23 TC 7 Z9 7 U1 0 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 1997 VL 97 IS 9 BP 1010 EP 1013 DI 10.1016/S0002-8223(97)00243-5 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XU116 UT WOS:A1997XU11600016 PM 9284881 ER PT J AU Warner, HR Hodes, RJ Pocinki, K AF Warner, HR Hodes, RJ Pocinki, K TI What does cell death have to do with aging? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE GENE; C-ELEGANS; RHEUMATOID-ARTHRITIS; IN-VIVO; LYMPHOPROLIFERATIVE SYNDROME; CAENORHABDITIS-ELEGANS; MYOCARDIAL-INFARCTION; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE C1 NIA, PUBL INFORMAT OFF, NIH, BETHESDA, MD 20892 USA. NR 104 TC 85 Z9 93 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP 1140 EP 1146 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300019 PM 9288026 ER PT J AU Ryan, SD Simonsick, EM Fried, LP AF Ryan, SD Simonsick, EM Fried, LP TI Opportunities for prevention among older disabled women. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21218. NIA,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP A18 EP A18 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300051 ER PT J AU Leveille, S Wagner, E Davis, C AF Leveille, S Wagner, E Davis, C TI Innovations in disability prevention with frail older adults: Partnerships between managed care and a neighborhood senior center SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. GRP HLTH COOPERAT PUGET SOUND,SEATTLE,WA 98121. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP P82 EP P82 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300155 ER PT J AU Studenski, S Wallace, D Belt, J Duncan, P Rooney, E AF Studenski, S Wallace, D Belt, J Duncan, P Rooney, E TI Efficient use of performance measures in the clinical setting SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP P2 EP P2 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300075 ER PT J AU Walston, J Sorkin, J Muller, D Silver, K Laheri, A Valdes, F Tran, K Harper, M Beamer, B Elahi, D Shuldiner, AR AF Walston, J Sorkin, J Muller, D Silver, K Laheri, A Valdes, F Tran, K Harper, M Beamer, B Elahi, D Shuldiner, AR TI The TRP64ARG beta-3-adrenergic receptor variant is not associated with the insulin resistance syndrome in participants of the Baltimore longitudinal study on aging (BLSA). SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21224. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1997 VL 45 IS 9 BP P209 EP P209 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XU233 UT WOS:A1997XU23300282 ER PT J AU Yergey, AL Yergey, AK AF Yergey, AL Yergey, AK TI Preparative scale mass spectrometry: A brief history of the calutron SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article AB Calutrons were developed in the laboratory of E. O. Lawrence at the University of California at Berkeley. They were a modification of the cyclotrons he had invented and used in his Noble Prize winning investigations of the atomic nucleus. At the time their construction was undertaken, calutrons represented the only certain means of preparing enriched uranium isotopes for the construction of a fission bomb. The effort was successful enough that every atom of the 42 kg of U-235 used in the first uranium bomb had passed through at least one stage of calutron separation. At peak production, the first stage separators, alpha tanks, yielded an aggregate 258-g/d U-235 enriched to about 10 at. % from its natural abundance level of 0.72 at. %. The second stage separators, beta tanks, used the 10 at. % material as feedstock and produced a total 204-g/d U-235 enriched to at least 80 at. %. The latter, weapons grade, material was used in fission bombs. Under typical operating conditions, each alpha tank operated at a uranium beam intensity at the collectors of approximately 20 mA and each beta tank at a beam intensity of approximately 215 mA at the collectors. Bulk separation of isotopes for bomb production ceased in 1945. Since that time calutrons have been used to separate stable isotopes, but on a more Limited scale than wartime weapons production. Stable isotope separations since 1960 have taken place using one modified beta tank. (C) 1997 American Society for Mass Spectrometry. C1 NICHHD,BETHESDA,MD 20892. W VIRGINIA UNIV,DEPT HIST,MORGANTOWN,WV 26506. NR 17 TC 22 Z9 22 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD SEP PY 1997 VL 8 IS 9 BP 943 EP 953 DI 10.1016/S1044-0305(97)00123-2 PG 11 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA XT643 UT WOS:A1997XT64300001 ER EF